Tissue penetration device

Information

  • Patent Grant
  • 9248267
  • Patent Number
    9,248,267
  • Date Filed
    Thursday, July 18, 2013
    11 years ago
  • Date Issued
    Tuesday, February 2, 2016
    8 years ago
Abstract
A tissue penetration device and method of using same. The tissue penetration device may optionally include sampling and analyzing functions, which may be integrated. An embodiment provides control of a lancet used for sampling blood. Electric field coils or solenoids may drive the lancet using electromagnetic force. Advancement and retraction of a lancet may be controlled by a feedback loop monitoring the position and velocity of the lancet embodiments of the lancet driver can be configured to follow a predetermined tissue lancing profile. Embodiments of the invention include a lancet and method for using a lancet to maintain the patency of the wound tract once the lancet has cut into the skin.
Description
BACKGROUND

Lancing devices are known in the medical health-care products industry for piercing the skin to produce blood for analysis. Biochemical analysis of blood samples is a diagnostic tool for determining clinical information. Many point-of-care tests are performed using whole blood, the most common being monitoring diabetic blood glucose level. Other uses for this method include the analysis of oxygen and coagulation based on Prothrombin time measurement. Typically, a drop of blood for this type of analysis is obtained by making a small incision in the fingertip, creating a small wound, which generates a small blood droplet on the surface of the skin.


Early methods of lancing included piercing or slicing the skin with a needle or razor. Current methods utilize lancing devices that contain a multitude of spring, cam and mass actuators to drive the lancet. These include cantilever springs, diaphragms, coil springs, as well as gravity plumbs used to drive the lancet. Typically, the device is pre-cocked or the user cocks the device. The device is held against the skin and the user, or pressure from the users skin, mechanically triggers the ballistic launch of the lancet. The forward movement and depth of skin penetration of the lancet is determined by a mechanical stop and/or dampening, as well as a spring or cam to retract the lancet. Such devices have the possibility of multiple strikes due to recoil, in addition to vibratory stimulation of the skin as the driver impacts the end of the launcher stop, and only allow for rough control for skin thickness variation. Different skin thickness may yield different results in terms of pain perception, blood yield and success rate of obtaining blood between different users of the lancing device.


Success rate generally encompasses the probability of producing a blood sample with one lancing action, which is sufficient in volume to perform the desired analytical test. The blood may appear spontaneously at the surface of the skin, or may be “milked” from the wound. Milking generally involves pressing the side of the digit, or in proximity of the wound to express the blood to the surface. The blood droplet produced by the lancing action must reach the surface of the skin to be viable for testing. For a one-step lance and blood sample acquisition method, spontaneous blood droplet formation is requisite. Then it is possible to interface the test strip with the lancing process for metabolite testing.


When using existing methods, blood often flows from the cut blood vessels but is then trapped below the surface of the skin, forming a hematoma. In other instances, a wound is created, but no blood flows from the wound. In either case, the lancing process cannot be combined with the sample acquisition and testing step. Spontaneous blood droplet generation with current mechanical launching system varies between launcher types but on average it is about 50% of lancet strikes, which would be spontaneous. Otherwise milking is required to yield blood. Mechanical launchers are unlikely to provide the means for integrated sample acquisition and testing if one out of every two strikes does not yield a spontaneous blood sample.


Many diabetic patients (insulin dependent) are required to self-test for blood glucose levels five to six times daily. Reducing the number of steps required for testing would increase compliance with testing regimes. A one-step testing procedure where test strips are integrated with lancing and sample generation would achieve a simplified testing regimen. Improved compliance is directly correlated with long-term management of the complications arising from diabetes including retinopathies, neuropathies, renal failure and peripheral vascular degeneration resulting from large variations in glucose levels in the blood. Tight control of plasma glucose through frequent testing is therefore mandatory for disease management.


Another problem frequently encountered by patients who must use lancing equipment to obtain and analyze blood samples is the amount of manual dexterity and hand-eye coordination required to properly operate the lancing and sample testing equipment due to retinopathies and neuropathies particularly, severe in elderly diabetic patients. For those patients, operating existing lancet and sample testing equipment can be a challenge. Once a blood droplet is created, that droplet must then be guided into a receiving channel of a small test strip or the like. If the sample placement on the strip is unsuccessful, repetition of the entire procedure including re-lancing the skin to obtain a new blood droplet is necessary.


What is needed is a device, which can reliably, repeatedly and painlessly generate spontaneous blood samples. In addition, a method for performing analytical testing on a sample that does not require a high degree of manual dexterity or hand-eye coordination is required. Integrating sample generation (lancing) with sample testing (sample to test strip) will result in a simple one-step testing procedure resulting in better disease management through increased compliance with self testing regimes.


SUMMARY

Advantages can be achieved by use of a tissue penetration device that has user definable control of parameters such as lancet displacement, velocity of incision, retraction, acceleration, and tissue dwell time. A device having features of the invention can compensate for long-term changes in skin physiology, nerve function, and peripheral vascular perfusion such as occurs in diabetes, as well as diurnal variation in skin tensile properties. Alternatively, a device having features of the invention can compensate for skin differences between widely differing populations such as pediatric and geriatric patients, in addition to reducing the pain associated with lancing.


An embodiment of the invention is directed to a lancing device, which controls the advancement and retraction of a lancet by monitoring the position of the lancet in conjunction with a velocity control system in the form of a feedback loop. The feedback loop can modulate the lancet driver to follow a predetermined velocity versus position profile. The advancement and retraction profiles of the lancet through the skin govern the pain, success and spontaneous generation of the blood sample. Such a tissue penetration device can be combined with a sampling module, or sampling module cartridge, that contains a plurality of sampling modules. By integrating the tissue penetration function with the sample acquisition, and, (optionally), sample analysis, user convenience can be greatly enhanced as well as other advantages.


In another embodiment of the invention, a tissue penetration device includes a tissue penetration element coupled to a controllable driver. The controllable driver may include a magnetic source that produces a controllable magnetic field in a magnetically active region adjacent the magnetic source. A magnetic member disposed at least partially in the magnetically active region is coupled to the tissue penetration element. A position sensor is configured to measure the position of the tissue penetration element. The tissue penetration element can be a lancet.


In yet another embodiment of the invention, a controllable driver includes a magnetic source that produces a controllable magnetic field in a magnetically active region adjacent the magnetic source. A magnetic member is disposed at least partially in the magnetically active region and configured to be coupled to a lancet. A position sensor is configured to measure the position of the magnetic member. A processor is electrically coupled to the magnetic source and configured to control the magnitude of the magnetic field by controlling the amount of time the magnetic source is on in the magnetically active region based on feedback from the position sensor.


Another embodiment of the invention is directed to a tissue penetration device that includes a flat coil controllable driver having a magnetic source that produces a first magnetic field in a first magnetically active region and a second magnetic field in a second magnetically active region. A flat coil is secured to a translation substrate and has a leading segment disposed at least partially within the first magnetically active region and a trailing segment disposed at least partially within the second magnetically active region. A tissue penetration element is configured to penetrate tissue and mechanically coupled to the translation substrate. A position sensor is configured to measure the position of the tissue penetration element.


In yet another embodiment, the magnetically active regions are constructed from collections (2 or more) of solenoid coils, allowing coils to be energized such that the “slug” is always at least half (or ⅔, ¾, etc.) within the active portion of the solenoid, ensuring that the force exerted is always near optimal.


In an alternative embodiment, a tissue penetration device includes a controllable driver that has a magnetic source that produces a magnetic field in a magnetically active region. A cylindrical coil is secured to a translation substrate and disposed at least partially within the magnetically active region. A tissue penetration element configured to penetrate tissue is mechanically coupled to the translation substrate. A position sensor is configured to measure the position of the tissue penetration element directly or indirectly.


In an embodiment of a method of lancing for obtaining a sample of blood from a patient, a tissue penetration device for obtaining a blood sample from a patient is provided. The tissue penetration device has a magnetic source that produces a controllable magnetic field in a magnetically active region adjacent the magnetic source. A magnetic member is disposed at least partially in the magnetically active region and a tissue penetration element is coupled to the magnetic member. Next, the tissue penetration device is disposed adjacent tissue of the patient. The magnetic source is then activated to produce a magnetic field in the magnetically active region generating a magnetic force between the magnetic field and the magnetic member and driving the tissue penetration element into the patient's tissue.


In some embodiments, the magnetic field produced by the magnetic source is reversed after the tissue penetration element has entered the patient's tissue, reversing the force on the tissue penetration element and withdrawing the tissue penetration element from the patient's tissue. In addition, in other embodiments of the method, the magnitude of the magnetic force on the magnetic member during penetration of the patient's tissue by the tissue penetration element is greater than the magnitude of the magnetic force on the magnetic member during withdrawal of the tissue penetration element from the patient's tissue. In this way, the tissue penetration element may be withdrawn at a lower velocity from the patient's tissue than a velocity of the tissue penetration element during penetration of the patient's tissue.


Advantages can be achieved in a tissue penetration device for blood sampling by integrating a lancing and blood sample collection procedure so that the device can capture and transport the capillary blood from the wound created by the lancet or other tissue penetration element to a desired analytical area, such as a strip for analyzing glucose. This can be done in embodiments of the invention by integrating the lancet, sample flow channel and reservoir into a disposable sampling module, which can be inserted into a tissue penetration sampling device with instrumentation for analyzing the blood sample.


In the use of an embodiment of the invention, a finger is placed over an ergonomically contoured sampling area and pressure is applied with the finger so that a sensor will activate a driver, which will, in turn, lance the finger and allow the blood sample to be collected in the sample flow channel and transported to the reservoir for analysis in a single step from the patient's perspective.


Once a sample has been obtained and transported to a reservoir, advantages can be achieved by using devices and methods for easily measuring the zero or start-time of an assay and applying such a technology to kinetic assays. In addition, advantages can be achieved by using devices and methods that accurately detect successful sample introduction into a sampling module, to detect sample arrival at any predefined point or local environment in a sample flow channel, to detect sample arrival at a particular sensor or array of sensors, or to perform similar functions for fluids that are not samples containing the analyte to be measured, e.g., subsequent reagents or wash fluids. Embodiments of the invention generally relate to a method for using a thermal sensor to detect the presence or arrival of a fluid. Embodiments of the invention use the signal obtained from a thermal sensor to define the zero or start time of an assay for which knowing the rate of reaction is important or useful.


In some embodiments, a first signal from the thermal sensor is read prior to arrival of the fluid, a second signal is read as the fluid arrives, and the first signal and the second signal are related to provide an indicator that the fluid has arrived. In another embodiment, the method comprises determining the temperature of the local environment at the thermal sensor before the fluid arrives, determining the temperature of the local environment at the thermal sensor as the fluid arrives, and calculating the thermal differential, which may be used to indicate the arrival of the fluid.


Other embodiments of the invention can allow acquisition of the blood sample seamlessly, that is, without substantial contamination from ambient air, such that the blood sample may be analyzed accurately for gaseous components such as oxygen and carbon dioxide. Sampled blood can be acquired and transported to an analysis or storage device without substantial contamination by ambient air.


In one embodiment, a surface treatment of a support material is used on the target tissue to engender a difference in wetting ability. In another embodiment, an active pumping device is used in addition to capillary forces for drawing the blood into the sample reservoir and for dispensing blood from the reservoir to additional sites. Another embodiment includes the use of a device which compensates for an inadequate sample volume in the first sample reservoir by isolating the first sample reservoir and triggering a second lancing and acquisition step to fill a second “back-up” sample reservoir. Any of these three embodiments can be used alone, or in any combination of the other two embodiments.


User convenience as well as other advantages can be achieved with the use of a sampling cartridge containing a plurality of sampling modules capable of being used multiple times and obtaining multiple analytical readings before being discarded. Simplified actuation, lancing, sample acquisition, testing, and readout, can all be provided in a handheld apparatus capable of multiple uses on one sampling module cartridge. A sampling cartridge embodiment contains many individual sampling modules, each of which allows the collection and testing of a sample of blood. This allows the sampling cartridge to be used numerous times before exchange with a new cartridge and disposal of the used cartridge becomes necessary, thus reducing the need to dispose of used materials after each test. The sampling cartridge embodiment also retains used sampling materials safely, thereby reducing the problem of handling biohazardous materials.


In yet another embodiment, the sampling module can be configured to contain a hypodermic (patent) needle, and drug delivery chamber. Inherent in the position control mechanism of the electronic actuator is the ability to precisely define the position in space, allowing finite placement of a hypodermic syringe in the skin for injection of drugs, vaccines or the like. The reservoir for the drug or vaccine to be injected is the polymeric needle support module. Drug delivery can be discrete or continuous depending on the need.


A sampling cartridge embodiment provides for a simplified blood sampling and analysis process by having fewer components requiring assembly by the user and reducing the frequency that the components must be assembled for testing. A single sampling module combines the lancet and sample reservoir with analytical region, reducing the task of assembly by the user. The sampling cartridge combines a plurality of such sampling modules in a unit package that fits cassette-like into a reader device. This multi-use sampling cartridge need only be removed and replaced after all of the sampling modules are used, further reducing the task of assembly, disassembly, and disposal by the user. In one possible configuration, a separate apparatus provides a driver. In other embodiments the driver is included in the analyzer device or is integrated directly on the sampling module.


In a method, a series of blood samples may be collected and tested using a single disposable sampling cartridge which is designed to couple to an analyzer that can include a processor configured to interpret raw data from analyzed region. The sampling cartridge has a plurality of sampling modules, each sampling module adapted to be used for a single blood sampling cycle. The method starts with coupling of the sampling cartridge and analyzer and then initiating a blood sampling cycle. Upon completion of the blood sampling cycle, the sampling cartridge is advanced to bring a fresh, unused sampling module online, ready to perform another blood sampling cycle. After a series of blood sampling cycles has been performed, the sampling cartridge is decoupled from the analyzer and discarded, leaving the analyzer ready to be coupled with a new sampling cartridge.


In accordance with some embodiments of the invention, a method for lancing uses a lancet, a helix, or an elastomer to maintain the patency of the wound tract once the lancet has cut into the skin. If penetration takes place, and an appropriate number of blood vessels are cut, blood is allowed to flow up through the wound tract and onto the surface of the skin because the lancet, the helix, or the elastomer coats or braces the wound tract, keeping it open and patent. Coating or bracing is defined generally as keeping the wound open so that the blood can reach the surface of the finger. The term flow control can include any means for bracing the wound tract created by the lancet.





BRIEF DESCRIPTION OF THE DRAWINGS


FIGS. 1-3 are graphs of lancet velocity versus position for embodiments of spring driven, cam driven, and controllable force drivers.



FIG. 4 illustrates an embodiment of a controllable force driver in the form of a flat electric lancet driver that has a solenoid-type configuration.



FIG. 5 illustrates an embodiment of a controllable force driver in the form of a cylindrical electric lancet driver using a coiled solenoid-type configuration.



FIG. 6 illustrates a displacement over time profile of a lancet driven by a harmonic spring/mass system.



FIG. 7 illustrates the velocity over time profile of a lancet driver by a harmonic spring/mass system.



FIG. 8 illustrates a displacement over time profile of an embodiment of a controllable force driver.



FIG. 9 illustrates a velocity over time profile of an embodiment of a controllable force driver.



FIG. 10 illustrates the lancet needle partially retracted, after severing blood vessels; blood is shown following the needle in the wound tract.



FIG. 11 illustrates blood following the lancet needle to the skin surface, maintaining an open wound tract.



FIG. 12 is a diagrammatic view illustrating a controlled feed-back loop.



FIG. 13 is a graph of force vs. time during the advancement and retraction of a lancet showing some characteristic phases of a lancing cycle.



FIG. 14 illustrates a lancet tip showing features, which can affect lancing pain, blood volume, and success rate.



FIG. 15 illustrates an embodiment of a lancet tip.



FIG. 16 is a graph showing displacement of a lancet over time.



FIG. 17 is a graph showing an embodiment of a velocity profile, which includes the velocity of a lancet over time including reduced velocity during retraction of the lancet.



FIG. 18 illustrates the tip of an embodiment of a lancet before, during and after the creation of an incision braced with a helix.



FIG. 19 illustrates a finger wound tract braced with an elastomer embodiment.



FIG. 20 is a perspective view of a tissue penetration device having features of the invention.



FIG. 21 is an elevation view in partial longitudinal section of the tissue penetration device of FIG. 20.



FIG. 22 is an elevation view in partial section of an alternative embodiment.



FIG. 23 is a transverse cross sectional view of the tissue penetration device of FIG. 21 taken along lines 23-23 of FIG. 21.



FIG. 24 is a transverse cross sectional view of the tissue penetration device of FIG. 21 taken along lines 24-24 of FIG. 21.



FIG. 25 is a transverse cross sectional view of the tissue penetration device of FIG. 21 taken along lines 25-25 of FIG. 21.



FIG. 26 is a transverse cross sectional view of the tissue penetration device of FIG. 21 taken along lines 26-26 of FIG. 21.



FIG. 27 is a side view of the drive coupler of the tissue penetration device of FIG.



FIG. 28 is a front view of the drive coupler of the tissue penetration device of FIG. 21 with the lancet not shown for purposes of illustration.



FIGS. 29A-29C show a flowchart illustrating a lancet control method.



FIG. 30 is a diagrammatic view of a patient's finger and a lancet tip moving toward the skin of the finger.



FIG. 31 is a diagrammatic view of a patient's finger and the lancet tip making contact with the skin of a patient's finger.



FIG. 32 is a diagrammatic view of the lancet tip depressing the skin of a patient's finger.



FIG. 33 is a diagrammatic view of the lancet tip further depressing the skin of a patient's finger.



FIG. 34 is a diagrammatic view of the lancet tip penetrating the skin of a patient's finger.



FIG. 35 is a diagrammatic view of the lancet tip penetrating the skin of a patient's finger to a desired depth.



FIG. 36 is a diagrammatic view of the lancet tip withdrawing from the skin of a patient's finger.



FIGS. 37-41 illustrate a method of tissue penetration that may measure elastic recoil of the skin.



FIG. 42 is a graphical representation of position and velocity vs. time for a lancing cycle.



FIG. 43 illustrates a sectional view of the layers of skin with a lancet disposed therein.



FIG. 44 is a graphical representation of velocity vs. position of a lancing cycle.



FIG. 45 is a graphical representation of velocity vs. time of a lancing cycle.



FIG. 46 is an elevation view in partial longitudinal section of an alternative embodiment of a driver coil pack and position sensor.



FIG. 47 is a perspective view of a flat coil driver having features of the invention.



FIG. 48 is an exploded view of the flat coil driver of FIG. 47.



FIG. 49 is an elevational view in partial longitudinal section of a tapered driver coil pack having features of the invention.



FIG. 50 is a transverse cross sectional view of the tapered coil driver pack of FIG. 49 taken along lines 50-50 in FIG. 49.



FIG. 51 shows an embodiment of a sampling module which houses a lancet and sample reservoir.



FIG. 52 shows a housing that includes a driver and a chamber where the module shown in FIG. 51 can be loaded.



FIG. 53 shows a tissue penetrating sampling device with the module loaded into the housing.



FIG. 54 shows an alternate embodiment of a lancet configuration.



FIG. 55 illustrates an embodiment of a sample input port, sample reservoir and ergonomically contoured finger contact area.



FIG. 56 illustrates the tissue penetration sampling device during a lancing event.



FIG. 57 illustrates a thermal sample sensor having a sample detection element near a surface over which a fluid may flow and an alternative position for a sampled detection element that would be exposed to a fluid flowing across the surface.



FIG. 58 shows a configuration of a thermal sample sensor with a sample detection element that includes a separate heating element.



FIG. 59 depicts three thermal sample detectors such as that shown in FIG. 58 with sample detection elements located near each other alongside a surface.



FIG. 60 illustrates thermal sample sensors positioned relative to a channel having an analysis site.



FIG. 61 shows thermal sample sensors with sample detection analyzers positioned relative to analysis sites arranged in an array on a surface.



FIG. 62 schematically illustrates a sampling module device including several possible configurations of thermal sample sensors including sample detection elements positioned relative to sample flow channels and analytical regions.



FIG. 63 illustrates a tissue penetration sampling device having features of the invention.



FIG. 64 is a top view in partial section of a sampling module of the tissue penetration sampling device of FIG. 63.



FIG. 65 is a cross sectional view through line 65-65 of the sampling module shown in FIG. 64.



FIG. 66 schematically depicts a sectional view of an alternative embodiment of the sampling module.



FIG. 67 depicts a portion of the sampling module surrounding a sampling port.



FIGS. 68-70 show in sectional view one implementation of a spring powered lancet driver in three different positions during use of the lancet driver.



FIG. 71 illustrates an embodiment of a tissue penetration sampling device having features of the invention.



FIG. 72 shows a top surface of a cartridge that includes multiple sampling modules.



FIG. 73 shows in partial section a sampling module of the sampling cartridge positioned in a reader device.



FIG. 74 is a perspective view in partial section of a tissue penetration sampling device with a cartridge of sampling modules.



FIG. 75 is a front view in partial section of the tissue penetration sampling device of FIG. 56.



FIG. 76 is a top view of the tissue penetration sampling device of FIG. 75.



FIG. 77 is a perspective view of a section of a sampling module belt having a plurality of sampling modules connected in series by a sheet of flexible polymer.



FIG. 78 is a perspective view of a single sampling module of the sampling module belt of FIG. 59.



FIG. 79 is a bottom view of a section of the flexible polymer sheet of the sampling module of FIG. 78 illustrating the flexible conductors and contact points deposited on the bottom surface of the flexible polymer sheet.



FIG. 80 is a perspective view of the body portion of the sampling module of FIG. 77 without the flexible polymer cover sheet or lancet.



FIG. 81 is an enlarged portion of the body portion of the sampling module of FIG. 80 illustrating the input port, sample flow channel, analytical region, lancet channel and lancet guides of the sampling module.



FIG. 82 is an enlarged elevational view of a portion of an alternative embodiment of a sampling module having a plurality of small volume analytical regions.



FIG. 83 is a perspective view of a body portion of a lancet module that can house and guide a lancet without sampling or analytical functions.



FIG. 84 is an elevational view of a drive coupler having a T-slot configured to accept a drive head of a lancet.



FIG. 85 is an elevational view of the drive coupler of FIG. 84 from the side and illustrating the guide ramps of the drive coupler.



FIG. 86 is a perspective view of the drive coupler of FIG. 84 with a lancet being loaded into the T-slot of the drive coupler.



FIG. 87 is a perspective view of the drive coupler of FIG. 86 with the drive head of the lancet completely loaded into the T-slot of the drive coupler.



FIG. 88 is a perspective view of a sampling module belt disposed within the T-slot of the drive coupler with a drive head of a lancet of one of the sampling modules loaded within the T-slot of the drive coupler.



FIG. 89 is a perspective view of a sampling module cartridge with the sampling modules arranged in a ring configuration.



FIG. 90 is a perspective view of a sampling module cartridge with the plurality of sampling modules arranged in a block matrix with lancet drive heads configured to mate with a drive coupler having adhesive coupling.



FIG. 91 is a side view of an alternative embodiment of a drive coupler having a lateral slot configured to accept the L-shaped drive head of the lancet that is disposed within a lancet module and shown with the L-shaped drive head loaded in the lateral slot.



FIG. 92 is an exploded view of the drive coupler, lancet with L-shaped drive head and lancet module of FIG. 91.



FIG. 93 is a perspective view of the front of a lancet cartridge coupled to the distal end of a controlled electromagnetic driver.



FIG. 94 is an elevational front view of the lancet cartridge of FIG. 93.



FIG. 95 is a top view of the lancet cartridge of FIG. 93.



FIG. 96 is a perspective view of the lancet cartridge of FIG. 93 with a portion of the cartridge body and lancet receptacle not shown for purposes of illustration of the internal mechanism.



FIGS. 97-101 illustrate an embodiment of an agent injection device.



FIGS. 102-106 illustrate an embodiment of a cartridge for use in sampling having a sampling cartridge body and a lancet cartridge body.





DETAILED DESCRIPTION

Variations in skin thickness including the stratum corneum and hydration of the epidermis can yield different results between different users with existing tissue penetration devices, such as lancing devices wherein the tissue penetrating element of the tissue penetration device is a lancet. Many current devices rely on adjustable mechanical stops or damping, to control the lancet's depth of penetration.


Displacement velocity profiles for both spring driven and cam driven tissue penetration devices are shown in FIGS. 1 and 2, respectively. Velocity is plotted against displacement X of the lancet. FIG. 1 represents a displacement/velocity profile typical of spring driven devices. The lancet exit velocity increases until the lancet hits the surface of the skin 10. Because of the tensile characteristics of the skin, it will bend or deform until the lancet tip cuts the surface 20, the lancet will then penetrate the skin until it reaches a full stop 30. At this point displacement is maximal and reaches a limit of penetration and the lancet stops. Mechanical stops absorb excess energy from the driver and transfer it to the lancet. The energy stored in the spring can cause recoil resulting in multiple piercing as seen by the coiled profile in FIG. 1. This results in unnecessary pain from the additional tissue penetration as well as from transferring vibratory energy into the skin and exciting nerve endings. Retraction of the lancet then occurs and the lancet exits the skin 40 to return into the housing. Velocity cannot be controlled in any meaningful way for this type of spring-powered driver.



FIG. 2 shows a displacement/velocity profile for a cam driven driver, which is similar to that of FIG. 1, but because the return path is specified in the cam configuration, there is no possibility of multiple tissue penetrations from one actuation. Cam based drivers can offer some level of control of lancet velocity vs. displacement, but not enough to achieve many desirable displacement/velocity profiles.


Advantages are achieved by utilizing a controllable force driver to drive a lancet, such as a driver, powered by electromagnetic energy. A controllable driver can achieve a desired velocity versus position profile, such as that shown in FIG. 3. Embodiments of the present invention allow for the ability to accurately control depth of penetration, to control lancet penetration and withdrawal velocity, and therefore reduce the pain perceived when cutting into the skin. Embodiments of the invention include a controllable driver that can be used with a feedback loop with a position sensor to control the power delivered to the lancet, which can optimize the velocity and displacement profile to compensate for variations in skin thickness


Pain reduction can be achieved by using a rapid lancet cutting speed, which is facilitated by the use of a lightweight lancet. The rapid cutting minimizes the shock waves produced when the lancet strikes the skin in addition to compressing the skin for efficient cutting. If a controllable driver is used, the need for a mechanical stop can be eliminated. Due to the very light mass of the lancet and lack of a mechanical stop, there is little or no vibrational energy transferred to the finger during cutting.


The lancing devices such as those whose velocity versus position profiles are shown in FIGS. 1 and 2 typically yield 50% spontaneous blood. In addition, some lancing events are unsuccessful and yield no blood, even on milking the finger. A spontaneous blood droplet generation is dependent on reaching the blood capillaries and venuoles, which yield the blood sample. It is therefore an issue of correct depth of penetration of the cutting device. Due to variations in skin thickness and hydration, some types of skin will deform more before cutting starts, and hence the actual depth of penetration will be less, resulting in less capillaries and venuoles cut. A controllable force driver can control the depth of penetration of a lancet and hence improve the spontaneity of blood yield. Furthermore, the use of a controllable force driver can allow for slow retraction of the lancet (slower than the cutting velocity) resulting in improved success rate due to the would channel remaining open for the free passage of blood to the surface of the skin.


Spontaneous blood yield occurs when blood from the cut vessels flow up the wound tract to the surface of the skin, where it can be collected and tested. Tissue elasticity parameters may force the wound tract to close behind the retracting lancet preventing the blood from reaching the surface. If however, the lancet were to be withdrawn slowly from the wound tract, thus keeping the wound open, blood could flow up the patent channel behind the tip of the lancet as it is being withdrawn (ref. FIGS. 10 and 11). Hence the ability to control the lancet speed into and out of the wound allows the device to compensate for changes in skin thickness and variations in skin hydration and thereby achieves spontaneous blood yield with maximum success rate while minimizing pain.


An electromagnetic driver can be coupled directly to the lancet minimizing the mass of the lancet and allowing the driver to bring the lancet to a stop at a predetermined depth without the use of a mechanical stop. Alternatively, if a mechanical stop is required for positive positioning, the energy transferred to the stop can be minimized. The electromagnetic driver allows programmable control over the velocity vs. position profile of the entire lancing process including timing the start of the lancet, tracking the lancet position, measuring the lancet velocity, controlling the distal stop acceleration, and controlling the skin penetration depth.


Referring to FIG. 4, an embodiment of a tissue penetration device is shown. The tissue penetration device includes a controllable force driver in the form of an electromagnetic driver, which can be used to drive a lancet. The term Lancet, as used herein, generally includes any sharp or blunt member, preferably having a relatively low mass, used to puncture the skin for the purpose of cutting blood vessels and allowing blood to flow to the surface of the skin. The term Electromagnetic driver, as used herein, generally includes any device that moves or drives a tissue penetrating element, such as a lancet under an electrically or magnetically induced force. FIG. 4 is a partially exploded view of an embodiment of an electromagnetic driver. The top half of the driver is shown assembled. The bottom half of the driver is shown exploded for illustrative purposes.



FIG. 4 shows the inner insulating housing 22 separated from the stationary housing or PC board 20, and the lancet 24 and flag 26 assembly separated from the inner insulating housing 22 for illustrative purposes. In addition, only four rivets 18 are shown as attached to the inner insulating housing 22 and separated from the PC board 20. In an embodiment, each coil drive field core in the PC board located in the PC Board 20 and 30 is connected to the inner insulating housing 22 and 32 with rivets.


The electromagnetic driver has a moving part comprising a lancet assembly with a lancet 24 and a magnetically permeable flag 26 attached at the proximal or drive end and a stationary part comprising a stationary housing assembly with electric field coils arranged so that they produce a balanced field at the flag to reduce or eliminate any net lateral force on the flag. The electric field coils are generally one or more metal coils, which generate a magnetic field when electric current passes through the coil. The iron flag is a flat or enlarged piece of magnetic material, which increases the surface area of the lancet assembly to enhance the magnetic forces generated between the proximal end of the lancet and a magnetic field produced by the field coils. The combined mass of the lancet and the iron flag can be minimized to facilitate rapid acceleration for introduction into the skin of a patient, to reduce the impact when the lancet stops in the skin, and to facilitate prompt velocity profile changes throughout the sampling cycle.


The stationary housing assembly consists of a PC board 20, a lower inner insulating housing 22, an upper inner insulating housing 32, an upper PC board 30, and rivets 18 assembled into a single unit. The lower and upper inner insulating housing 22 and 32 are relieved to form a slot so that lancet assembly can be slid into the driver assembly from the side perpendicular to the direction of the lancet's advancement and retraction. This allows the disposal of the lancet assembly and reuse of the stationary housing assembly with another lancet assembly while avoiding accidental lancet launches during replacement.


The electric field coils in the upper and lower stationary housing 20 and 30 are fabricated in a multi-layer printed circuit (PC) board. They may also be conventionally wound wire coils. A Teflon® material, or other low friction insulating material is used to construct the lower and upper inner insulating housing 22 and 32. Each insulating housing is mounted on the PC board to provide electrical insulation and physical protection, as well as to provide a low-friction guide for the lancet. The lower and upper inner insulating housing 22 and 32 provide a reference surface with a small gap so that the lancet assembly 24 and 26 can align with the drive field coils in the PC board for good magnetic coupling.


Rivets 18 connect the lower inner insulating housing 22 to the lower stationary housing 20 and are made of magnetically permeable material such as ferrite or steel, which serves to concentrate the magnetic field. This mirrors the construction of the upper inner insulating housing 32 and upper stationary housing 30. These rivets form the poles of the electric field coils. The PC board is fabricated with multiple layers of coils or with multiple boards. Each layer supports spiral traces around a central hole. Alternate layers spiral from the center outwards or from the edges inward. In this way each layer connects via simple feed-through holes, and the current always travels in the same direction, summing the ampere-turns.


The PC boards within the lower and upper stationary housings 20 and 30 are connected to the lower and upper inner insulating housings 22 and 32 with the rivets 18. The lower and upper inner insulating housings 22 and 32 expose the rivet heads on opposite ends of the slot where the lancet assembly 24 and 26 travels. The magnetic field lines from each rivet create magnetic poles at the rivet heads. An iron bar on the opposite side of the PC board within each of the lower and upper stationary housing 20 and 30 completes the magnetic circuit by connecting the rivets. Any fastener made of magnetically permeable material such as iron or steel can be used In place of the rivets. A single component made of magnetically permeable material and formed in a horseshoe shape can be used in place of the rivet/screw and iron bar assembly. In operation, the magnetically permeable flag 26 attached to the lancet 24 is divided into slits and bars 34. The slit patterns are staggered so that coils can drive the flag 26 in two, three or more phases.


Both lower and upper PC boards 20 and 30 contain drive coils so that there is a symmetrical magnetic field above and below the flag 26. When the pair of PC boards is turned on, a magnetic field is established around the bars between the slits of the magnetically permeable iron on the flag 26. The bars of the flag experience a force that tends to move the magnetically permeable material to a position minimizing the number and length of magnetic field lines and conducting the magnetic field lines between the magnetic poles.


When a bar of the flag 26 is centered between the rivets 18 of a magnetic pole, there is no net force on the flag, and any disturbing force is resisted by imbalance in the field. This embodiment of the device operates on a principle similar to that of a solenoid. Solenoids cannot push by repelling iron; they can only pull by attracting the iron into a minimum energy position. The slits 34 on one side of the flag 26 are offset with respect to the other side by approximately one half of the pitch of the poles. By alternately activating the coils on each side of the PC board, the lancet assembly can be moved with respect to the stationary housing assembly. The direction of travel is established by selectively energizing the coils adjacent the metal flag on the lancet assembly. Alternatively, a three phase, three-pole design or a shading coil that is offset by one-quarter pitch establishes the direction of travel. The lower and upper PC boards 20 and 30 shown in FIG. 4 contain electric field coils, which drive the lancet assembly and the circuitry for controlling the entire electromagnetic driver.


The embodiment described above generally uses the principles of a magnetic attraction drive, similar to commonly available circular stepper motors (Hurst Manufacturing BA Series motor, or “Electrical Engineering Handbook” Second edition p 1472-1474, 1997). These references are hereby incorporated by reference. Other embodiments can include a linear induction drive that uses a changing magnetic field to induce electric currents in the lancet assembly. These induced currents produce a secondary magnetic field that repels the primary field and applies a net force on the lancet assembly. The linear induction drive uses an electrical drive control that sweeps a magnetic field from pole to pole, propelling the lancet before it. Varying the rate of the sweep and the magnitude of the field by altering the driving voltage and frequency controls the force applied to the lancet assembly and its velocity.


The arrangement of the coils and rivets to concentrate the magnetic flux also applies to the induction design creating a growing magnetic field as the electric current in the field switches on. This growing magnetic field creates an opposing electric current in the conductive flag. In a linear induction motor the flag is electrically conductive, and its magnetic properties are unimportant. Copper or aluminum are materials that can be used for the conductive flags. Copper is generally used because of its good electrical conductivity. The opposing electrical field produces an opposing magnetic field that repels the field of the coils. By phasing the power of the coils, a moving field can be generated which pushes the flag along just below the synchronous speed of the coils. By controlling the rate of sweep, and by generating multiple sweeps, the flag can be moved at a desired speed.



FIG. 5 shows another embodiment of a solenoid type electromagnetic driver that is capable of driving an iron core or slug mounted to the lancet assembly using a direct current (DC) power supply. The electromagnetic driver includes a driver coil pack that is divided into three separate coils along the path of the lancet, two end coils and a middle coil. Direct current is alternated to the coils to advance and retract the lancet. Although the driver coil pack is shown with three coils, any suitable number of coils may be used, for example, 4, 5, 6, 7 or more coils may be used.


The stationary iron housing 40 contains the driver coil pack with a first coil 52 is flanked by iron spacers 50 which concentrate the magnetic flux at the inner diameter creating magnetic poles. The inner insulating housing 48 isolates the lancet 42 and iron core 46 from the coils and provides a smooth, low friction guide surface. The lancet guide 44 further centers the lancet 42 and iron core 46. The lancet 42 is protracted and retracted by alternating the current between the first coil 52, the middle coil, and the third coil to attract the iron core 46. Reversing the coil sequence and attracting the core and lancet back into the housing retracts the lancet. The lancet guide 44 also serves as a stop for the iron core 46 mounted to the lancet 42.


As discussed above, tissue penetration devices which employ spring or cam driving methods have a symmetrical or nearly symmetrical actuation displacement and velocity profiles on the advancement and retraction of the lancet as shown in FIGS. 6 and 7. In most of the available lancet devices, once the launch is initiated, the stored energy determines the velocity profile until the energy is dissipated. Controlling impact, retraction velocity, and dwell time of the lancet within the tissue can be useful in order to achieve a high success rate while accommodating variations in skin properties and minimize pain. Advantages can be achieved by taking into account that tissue dwell time is related to the amount of skin deformation as the lancet tries to puncture the surface of the skin and variance in skin deformation from patient to patient based on skin hydration.


The ability to control velocity and depth of penetration can be achieved by use of a controllable force driver where feedback is an integral part of driver control. Such drivers can control either metal or polymeric lancets or any other type of tissue penetration element. The dynamic control of such a driver is illustrated in FIG. 8 which illustrates an embodiment of a controlled displacement profile and FIG. 9 which illustrates an embodiment of a the controlled velocity profile. These are compared to FIGS. 6 and 7, which illustrate embodiments of displacement and velocity profiles, respectively, of a harmonic spring/mass powered driver.


Reduced pain can be achieved by using impact velocities of greater than 2 m/s entry of a tissue penetrating element, such as a lancet, into tissue.


Retraction of the lancet at a low velocity following the sectioning of the venuole/capillary mesh allows the blood to flood the wound tract and flow freely to the surface, thus using the lancet to keep the channel open during retraction as shown in FIGS. 10 and 11. Low-velocity retraction of the lancet near the wound flap prevents the wound flap from sealing off the channel. Thus, the ability to slow the lancet retraction directly contributes to increasing the success rate of obtaining blood. Increasing the sampling success rate to near 100% can be important to the combination of sampling and acquisition into an integrated sampling module such as an integrated glucose-sampling module, which incorporates a glucose test strip.


Referring again to FIG. 5, the lancet and lancet driver are configured so that feedback control is based on lancet displacement, velocity, or acceleration. The feedback control information relating to the actual lancet path is returned to a processor such as that illustrated in FIG. 12 that regulates the energy to the driver, thereby precisely controlling the lancet throughout its advancement and retraction. The driver may be driven by electric current, which includes direct current and alternating current.


In FIG. 5, the electromagnetic driver shown is capable of driving an iron core or slug mounted to the lancet assembly using a direct current (DC) power supply and is also capable of determining the position of the iron core by measuring magnetic coupling between the core and the coils. The coils can be used in pairs to draw the iron core into the driver coil pack. As one of the coils is switched on, the corresponding induced current in the adjacent coil can be monitored. The strength of this induced current is related to the degree of magnetic coupling provided by the iron core, and can be used to infer the position of the core and hence, the relative position of the lancet.


After a period of time, the drive voltage can be turned off, allowing the coils to relax, and then the cycle is repeated. The degree of magnetic coupling between the coils is converted electronically to a proportional DC voltage that is supplied to an analog-to-digital converter. The digitized position signal is then processed and compared to a desired “nominal” position by a central processing unit (CPU). The CPU to set the level and/or length of the next power pulse to the solenoid coils uses error between the actual and nominal positions.


In another embodiment, the driver coil pack has three coils consisting of a central driving coil flanked by balanced detection coils built into the driver assembly so that they surround an actuation or magnetically active region with the region centered on the middle coil at mid-stroke. When a current pulse is applied to the central coil, voltages are induced in the adjacent sense coils. If the sense coils are connected together so that their induced voltages oppose each other, the resulting signal will be positive for deflection from mid-stroke in one direction, negative in the other direction, and zero at mid-stroke. This measuring technique is commonly used in Linear Variable Differential Transformers (LVDT). Lancet position is determined by measuring the electrical balance between the two sensing coils.


In another embodiment, a feedback loop can use a commercially available LED/photo transducer module such as the OPB703 manufactured by Optek Technology, Inc., 1215 W. Crosby Road, Carrollton, Tex., 75006 to determine the distance from the fixed module on the stationary housing to a reflective surface or target mounted on the lancet assembly. The LED acts as a light emitter to send light beams to the reflective surface, which in turn reflects the light back to the photo transducer, which acts as a light sensor. Distances over the range of 4 mm or so are determined by measuring the intensity of the reflected light by the photo transducer. In another embodiment, a feedback loop can use a magnetically permeable region on the lancet shaft itself as the core of a Linear Variable Differential Transformer (LVDT).


A permeable region created by selectively annealing a portion of the lancet shaft, or by including a component in the lancet assembly, such as ferrite, with sufficient magnetic permeability to allow coupling between adjacent sensing coils. Coil size, number of windings, drive current, signal amplification, and air gap to the permeable region are specified in the design process. In another embodiment, the feedback control supplies a piezoelectric driver, superimposing a high frequency oscillation on the basic displacement profile. The piezoelectric driver provides improved cutting efficiency and reduces pain by allowing the lancet to “saw” its way into the tissue or to destroy cells with cavitation energy generated by the high frequency of vibration of the advancing edge of the lancet. The drive power to the piezoelectric driver is monitored for an impedance shift as the device interacts with the target tissue. The resulting force measurement, coupled with the known mass of the lancet is used to determine lancet acceleration, velocity, and position.



FIG. 12 illustrates the operation of a feedback loop using a processor. The processor 60 stores profiles 62 in non-volatile memory. A user inputs information 64 about the desired circumstances or parameters for a lancing event. The processor 60 selects a driver profile 62 from a set of alternative driver profiles that have been preprogrammed in the processor 60 based on typical or desired tissue penetration device performance determined through testing at the factory or as programmed in by the operator. The processor 60 may customize by either scaling or modifying the profile based on additional user input information 64. Once the processor has chosen and customized the profile, the processor 60 is ready to modulate the power from the power supply 66 to the lancet driver 68 through an amplifier 70. The processor 60 measures the location of the lancet 72 using a position sensing mechanism 74 through an analog to digital converter 76. Examples of position sensing mechanisms have been described in the embodiments above. The processor 60 calculates the movement of the lancet by comparing the actual profile of the lancet to the predetermined profile. The processor 60 modulates the power to the lancet driver 68 through a signal generator 78, which controls the amplifier 70 so that the actual profile of the lancet does not exceed the predetermined profile by more than a preset error limit. The error limit is the accuracy in the control of the lancet.


After the lancing event, the processor 60 can allow the user to rank the results of the lancing event. The processor 60 stores these results and constructs a database 80 for the individual user. Using the database 80, the processor 60 calculates the profile traits such as degree of painlessness, success rate, and blood volume for various profiles 62 depending on user input information 64 to optimize the profile to the individual user for subsequent lancing cycles. These profile traits depend on the characteristic phases of lancet advancement and retraction. The processor 60 uses these calculations to optimize profiles 62 for each user. In addition to user input information 64, an internal clock allows storage in the database 80 of information such as the time of day to generate a time stamp for the lancing event and the time between lancing events to anticipate the user's diurnal needs. The database stores information and statistics for each user and each profile that particular user uses.


In addition to varying the profiles, the processor 60 can be used to calculate the appropriate lancet diameter and geometry necessary to realize the blood volume required by the user. For example, if the user requires a 1-5 micro liter volume of blood, the processor selects a 200 micron diameter lancet to achieve these results. For each class of lancet, both diameter and lancet tip geometry, is stored in the processor to correspond with upper and lower limits of attainable blood volume based on the predetermined displacement and velocity profiles.


The lancing device is capable of prompting the user for information at the beginning and the end of the lancing event to more adequately suit the user. The goal is to either change to a different profile or modify an existing profile. Once the profile is set, the force driving the lancet is varied during advancement and retraction to follow the profile. The method of lancing using the lancing device comprises selecting a profile, lancing according to the selected profile, determining lancing profile traits for each characteristic phase of the lancing cycle, and optimizing profile traits for subsequent lancing events.



FIG. 13 shows an embodiment of the characteristic phases of lancet advancement and retraction on a graph of force versus time illustrating the force exerted by the lancet driver on the lancet to achieve the desired displacement and velocity profile. The characteristic phases are the lancet introduction phase A-C where the lancet is longitudinally advanced into the skin, the lancet rest phase D where the lancet terminates its longitudinal movement reaching its maximum depth and becoming relatively stationary, and the lancet retraction phase E-G where the lancet is longitudinally retracted out of the skin. The duration of the lancet retraction phase E-G is longer than the duration of the lancet introduction phase A-C, which in turn is longer than the duration of the lancet rest phase D.


The introduction phase further comprises a lancet launch phase prior to A when the lancet is longitudinally moving through air toward the skin, a tissue contact phase at the beginning of A when the distal end of the lancet makes initial contact with the skin, a tissue deformation phase A when the skin bends depending on its elastic properties which are related to hydration and thickness, a tissue lancing phase which comprises when the lancet hits the inflection point on the skin and begins to cut the skin B and the lancet continues cutting the skin C. The lancet rest phase D is the limit of the penetration of the lancet into the skin. Pain is reduced by minimizing the duration of the lancet introduction phase A-C so that there is a fast incision to a certain penetration depth regardless of the duration of the deformation phase A and inflection point cutting B which will vary from user to user. Success rate is increased by measuring the exact depth of penetration from inflection point B to the limit of penetration in the lancet rest phase D. This measurement allows the lancet to always, or at least reliably, hit the capillary beds which are a known distance underneath the surface of the skin.


The lancet retraction phase further comprises a primary retraction phase E when the skin pushes the lancet out of the wound tract, a secondary retraction phase F when the lancet starts to become dislodged and pulls in the opposite direction of the skin, and lancet exit phase G when the lancet becomes free of the skin. Primary retraction is the result of exerting a decreasing force to pull the lancet out of the skin as the lancet pulls away from the finger. Secondary retraction is the result of exerting a force in the opposite direction to dislodge the lancet. Control is necessary to keep the wound tract open as blood flows up the wound tract. Blood volume is increased by using a uniform velocity to retract the lancet during the lancet retraction phase E-G regardless of the force required for the primary retraction phase E or secondary retraction phase F, either of which may vary from user to user depending on the properties of the user's skin.



FIG. 14 shows a standard industry lancet for glucose testing which has a three-facet geometry. Taking a rod of diameter 114 and grinding 8 degrees to the plane of the primary axis to create the primary facet 110 produces the lancet 116. The secondary facets 112 are then created by rotating the shaft of the needle 15 degrees, and then rolling over 12 degrees to the plane of the primary facet. Other possible geometry's require altering the lancet's production parameters such as shaft diameter, angles, and translation distance.



FIG. 15 illustrates facet and tip geometry 120 and 122, diameter 124, and depth 126 which are significant factors in reducing pain, blood volume and success rate. It is known that additional cutting by the lancet is achieved by increasing the shear percentage or ratio of the primary to secondary facets, which when combined with reducing the lancet's diameter reduces skin tear and penetration force and gives the perception of less pain. Overall success rate of blood yield, however, also depends on a variety of factors, including the existence of facets, facet geometry, and skin anatomy.



FIG. 16 shows another embodiment of displacement versus time profile of a lancet for a controlled lancet retraction. FIG. 17 shows the velocity vs. time profile of the lancet for the controlled retraction of FIG. 16. The lancet driver controls lancet displacement and velocity at several steps in the lancing cycle, including when the lancet cuts the blood vessels to allow blood to pool 130, and as the lancet retracts, regulating the retraction rate to allow the blood to flood the wound tract while keeping the wound flap from sealing the channel 132 to permit blood to exit the wound.


In addition to slow retraction of a tissue-penetrating element in order to hold the wound open to allow blood to escape to the skin surface, other methods are contemplated. FIG. 18 shows the use of an embodiment of the invention, which includes a retractable coil on the lancet tip. A coiled helix or tube 140 is attached externally to lancet 116 with the freedom to slide such that when the lancet penetrates the skin 150, the helix or tube 140 follows the trajectory of the lancet 116. The helix begins the lancing cycle coiled around the facets and shaft of the lancet 144. As the lancet penetrates the skin, the helix braces the wound tract around the lancet 146. As the lancet retracts, the helix remains to brace open the wound tract, keeping the wound tract from collapsing and keeping the surface skin flap from closing 148. This allows blood 152 to pool and flow up the channel to the surface of the skin. The helix is then retracted as the lancet pulls the helix to the point where the helix is decompressed to the point where the diameter of the helix becomes less than the diameter of the wound tract and becomes dislodged from the skin.


The tube or helix 140 is made of wire or metal of the type commonly used in angioplasty stents such as stainless steel, nickel titanium alloy or the like. Alternatively the tube or helix 140 or a ring can be made of a biodegradable material, which braces the wound tract by becoming lodged in the skin. Biodegradation is completed within seconds or minutes of insertion, allowing adequate time for blood to pool and flow up the wound tract. Biodegradation is activated by heat, moisture, or pH from the skin.


Alternatively, the wound could be held open by coating the lancet with a powder or other granular substance. The powder coats the wound tract and keeps it open when the lancet is withdrawn. The powder or other granular substance can be a coarse bed of microspheres or capsules which hold the channel open while allowing blood to flow through the porous interstices.


In another embodiment the wound can be held open using a two-part needle, the outer part in the shape of a “U” and the inner part filling the “U.” After creating the wound the inner needle is withdrawn leaving an open channel, rather like the plugs that are commonly used for withdrawing sap from maple trees.



FIG. 19 shows a further embodiment of a method and device for facilitating blood flow utilizing an elastomer to coat the wound. This method uses an elastomer 154, such as silicon rubber, to coat or brace the wound tract 156 by covering and stretching the surface of the finger 158. The elastomer 154 is applied to the finger 158 prior to lancing. After a short delay, the lancet (not shown) then penetrates the elastomer 154 and the skin on the surface of the finger 158 as is seen in 160. Blood is allowed to pool and rise to the surface while the elastomer 154 braces the wound tract 156 as is seen in 162 and 164. Other known mechanisms for increasing the success rate of blood yield after lancing can include creating a vacuum, suctioning the wound, applying an adhesive strip, vibration while cutting, or initiating a second lance if the first is unsuccessful.



FIG. 20 illustrates an embodiment of a tissue penetration device, more specifically, a lancing device 180 that includes a controllable driver 179 coupled to a tissue penetration element. The lancing device 180 has a proximal end 181 and a distal end 182. At the distal end 182 is the tissue penetration element in the form of a lancet 183, which is coupled to an elongate coupler shaft 184 by a drive coupler 185. The elongate coupler shaft 184 has a proximal end 186 and a distal end 187. A driver coil pack 188 is disposed about the elongate coupler shaft 184 proximal of the lancet 183. A position sensor 191 is disposed about a proximal portion 192 of the elongate coupler shaft 184 and an electrical conductor 194 electrically couples a processor 193 to the position sensor 191. The elongate coupler shaft 184 driven by the driver coil pack 188 controlled by the position sensor 191 and processor 193 form the controllable driver, specifically, a controllable electromagnetic driver.


Referring to FIG. 21, the lancing device 180 can be seen in more detail, in partial longitudinal section. The lancet 183 has a proximal end 195 and a distal end 196 with a sharpened point at the distal end 196 of the lancet 183 and a drive head 198 disposed at the proximal end 195 of the lancet 183. A lancet shaft 201 is disposed between the drive head 198 and the sharpened point 197. The lancet shaft 201 may be comprised of stainless steel, or any other suitable material or alloy and have a transverse dimension of about 0.1 to about 0.4 mm. The lancet shaft may have a length of about 3 mm to about 50 mm, specifically, about 15 mm to about 20 mm. The drive head 198 of the lancet 183 is an enlarged portion having a transverse dimension greater than a transverse dimension of the lancet shaft 201 distal of the drive head 198. This configuration allows the drive head 198 to be mechanically captured by the drive coupler 185. The drive head 198 may have a transverse dimension of about 0.5 to about 2 mm.


A magnetic member 202 is secured to the elongate coupler shaft 184 proximal of the drive coupler 185 on a distal portion 203 of the elongate coupler shaft 184. The magnetic member 202 is a substantially cylindrical piece of magnetic material having an axial lumen 204 extending the length of the magnetic member 202. The magnetic member 202 has an outer transverse dimension that allows the magnetic member 202 to slide easily within an axial lumen 205 of a low friction, possibly lubricious, polymer guide tube 205′ disposed within the driver coil pack 188. The magnetic member 202 may have an outer transverse dimension of about 1.0 to about 5.0 mm, specifically, about 2.3 to about 2.5 mm. The magnetic member 202 may have a length of about 3.0 to about 5.0 mm, specifically, about 4.7 to about 4.9 mm. The magnetic member 202 can be made from a variety of magnetic materials including ferrous metals such as ferrous steel, iron, ferrite, or the like. The magnetic member 202 may be secured to the distal portion 203 of the elongate coupler shaft 184 by a variety of methods including adhesive or epoxy bonding, welding, crimping or any other suitable method.


Proximal of the magnetic member 202, an optical encoder flag 206 is secured to the elongate coupler shaft 184. The optical encoder flag 206 is configured to move within a slot 207 in the position sensor 191. The slot 207 of the position sensor 191 is formed between a first body portion 208 and a second body portion 209 of the position sensor 191. The slot 207 may have separation width of about 1.5 to about 2.0 mm. The optical encoder flag 206 can have a length of about 14 to about 18 mm, a width of about 3 to about 5 mm and a thickness of about 0.04 to about 0.06 mm.


The optical encoder flag 206 interacts with various optical beams generated by LEDs disposed on or in the position sensor body portions 208 and 209 in a predetermined manner. The interaction of the optical beams generated by the LEDs of the position sensor 191 generates a signal that indicates the longitudinal position of the optical flag 206 relative to the position sensor 191 with a substantially high degree of resolution. The resolution of the position sensor 191 may be about 200 to about 400 cycles per inch, specifically, about 350 to about 370 cycles per inch. The position sensor 191 may have a speed response time (position/time resolution) of 0 to about 120,000 Hz, where one dark and light stripe of the flag constitutes one Hertz, or cycle per second. The position of the optical encoder flag 206 relative to the magnetic member 202, driver coil pack 188 and position sensor 191 is such that the optical encoder 191 can provide precise positional information about the lancet 183 over the entire length of the lancet's power stroke.


An optical encoder that is suitable for the position sensor 191 is a linear optical incremental encoder, model HEDS 9200, manufactured by Agilent Technologies. The model HEDS 9200 may have a length of about 20 to about 30 mm, a width of about 8 to about 12 mm, and a height of about 9 to about 11 mm. Although the position sensor 191 illustrated is a linear optical incremental encoder, other suitable position sensor embodiments could be used, provided they posses the requisite positional resolution and time response. The HEDS 9200 is a two channel device where the channels are 90 degrees out of phase with each other. This results in a resolution of four times the basic cycle of the flag. These quadrature outputs make it possible for the processor to determine the direction of lancet travel. Other suitable position sensors include capacitive encoders, analog reflective sensors, such as the reflective position sensor discussed above, and the like.


A coupler shaft guide 211 is disposed towards the proximal end 181 of the lancing device 180. The guide 211 has a guide lumen 212 disposed in the guide 211 to slidingly accept the proximal portion 192 of the elongate coupler shaft 184. The guide 211 keeps the elongate coupler shaft 184 centered horizontally and vertically in the slot 202 of the optical encoder 191.


The driver coil pack 188, position sensor 191 and coupler shaft guide 211 are all secured to a base 213. The base 213 is longitudinally coextensive with the driver coil pack 188, position sensor 191 and coupler shaft guide 211. The base 213 can take the form of a rectangular piece of metal or polymer, or may be a more elaborate housing with recesses, which are configured to accept the various components of the lancing device 180.


As discussed above, the magnetic member 202 is configured to slide within an axial lumen 205 of the driver coil pack 188. The driver coil pack 188 includes a most distal first coil 214, a second coil 215, which is axially disposed between the first coil 214 and a third coil 216, and a proximal-most fourth coil 217. Each of the first coil 214, second coil 215, third coil 216 and fourth coil 217 has an axial lumen. The axial lumens of the first through fourth coils are configured to be coaxial with the axial lumens of the other coils and together form the axial lumen 205 of the driver coil pack 188 as a whole. Axially adjacent each of the coils 214-217 is a magnetic disk or washer 218 that augments completion of the magnetic circuit of the coils 214-217 during a lancing cycle of the device 180. The magnetic washers 218 of the embodiment of FIG. 21 are made of ferrous steel but could be made of any other suitable magnetic material, such as iron or ferrite. The outer shell 189 of the driver coil pack 188 is also made of iron or steel to complete the magnetic path around the coils and between the washers 218. The magnetic washers 218 have an outer diameter commensurate with an outer diameter of the driver coil pack 188 of about 4.0 to about 8.0 mm. The magnetic washers 218 have an axial thickness of about 0.05, to about 0.4 mm, specifically, about 0.15 to about 0.25 mm.


Wrapping or winding an elongate electrical conductor 221 about an axial lumen until a sufficient number of windings have been achieved forms the coils 214-217. The elongate electrical conductor 221 is generally an insulated solid copper wire with a small outer transverse dimension of about 0.06 mm to about 0.88 mm, specifically, about 0.3 mm to about 0.5 mm. In one embodiment, 32 gauge copper wire is used for the coils 214-217. The number of windings for each of the coils 214-217 of the driver pack 188 may vary with the size of the coil, but for some embodiments each coil 214-217 may have about 30 to about 80 turns, specifically, about 50 to about 60 turns. Each coil 214-217 can have an axial length of about 1.0 to about 3.0 mm, specifically, about 1.8 to about 2.0 mm. Each coil 214-217 can have an outer transverse dimension or diameter of about 4.0, to about 2.0 mm, specifically, about 9.0 to about 12.0 mm. The axial lumen 205 can have a transverse dimension of about 1.0 to about 3.0 mm.


It may be advantageous in some driver coil 188 embodiments to replace one or more of the coils with permanent magnets, which produce a magnetic field similar to that of the coils when the coils are activated. In particular, it may be desirable in some embodiments to replace the second coil 215, the third coil 216 or both with permanent magnets. In addition, it may be advantageous to position a permanent magnet at or near the proximal end of the coil driver pack in order to provide fixed magnet zeroing function for the magnetic member (Adams magnetic Products 23A0002 flexible magnet material (800) 747-7543).



FIGS. 20 and 21 show a permanent bar magnet 219 disposed on the proximal end of the driver coil pack 188. As shown in FIG. 21, the bar magnet 219 is arranged so as to have one end disposed adjacent the travel path of the magnetic member 202 and has a polarity configured so as to attract the magnetic member 202 in a centered position with respect to the bar magnet 219. Note that the polymer guide tube 205′ can be configured to extend proximally to insulate the inward radial surface of the bar magnet 219 from an outer surface of the magnetic member 202. This arrangement allows the magnetic member 219 and thus the elongate coupler shaft 184 to be attracted to and held in a zero point or rest position without the consumption of electrical energy from the power supply 225.


Having a fixed zero or start point for the elongate coupler shaft 184 and lancet 183 can be critical to properly controlling the depth of penetration of the lancet 183 as well as other lancing parameters. This can be because some methods of depth penetration control for a controllable driver measure the acceleration and displacement of the elongate coupler shaft 184 and lancet 183 from a known start position. If the distance of the lancet tip 196 from the target tissue is known, acceleration and displacement of the lancet is known and the start position of the lancet is know, the time and position of tissue contact and depth of penetration can be determined by the processor 193.


Any number of configurations for a magnetic bar 219 can be used for the purposes discussed above. In particular, a second permanent bar magnet (not shown) could be added to the proximal end of the driver coil pack 188 with the magnetic fields of the two bar magnets configured to complement each other. In addition, a disc magnet 219′ could be used as illustrated in FIG. 22. Disc magnet 219′ is shown disposed at the proximal end of the driver coiled pack 188 with a polymer non-magnetic disc 219″ disposed between the proximal-most coil 217 and disc magnet 219′ and positions disc magnet 219′ away from the proximal end of the proximal-most coil 217. The polymer non-magnetic disc spacer 219″ is used so that the magnetic member 202 can be centered in a zero or start position slightly proximal of the proximal-most coil 217 of the driver coil pack 188. This allows the magnetic member to be attracted by the proximal-most coil 217 at the initiation of the lancing cycle instead of being passive in the forward drive portion of the lancing cycle.


An inner lumen of the polymer non-magnetic disc 219″ can be configured to allow the magnetic member 202 to pass axially there through while an inner lumen of the disc magnet 219′ can be configured to allow the elongate coupler shaft 184 to pass through but not large enough for the magnetic member 202 to pass through. This results in the magnetic member 202 being attracted to the disc magnet 219′ and coming to rest with the proximal surface of the magnetic member 202 against a distal surface of the disc magnet 219′. This arrangement provides for a positive and repeatable stop for the magnetic member, and hence the lancet. A similar configuration could also be used for the bar magnet 219 discussed above.


Typically, when the electrical current in the coils 214-217 of the driver coil pack 188 is off, a magnetic member 202 made of soft iron is attracted to the bar magnet 219 or disc magnet 219′. The magnetic field of the driver coil pack 188 and the bar magnet 219 or disc magnet 219′, or any other suitable magnet, can be configured such that when the electrical current in the coils 214-217 is turned on, the leakage magnetic field from the coils 214-217 has the same polarity as the bar magnet 219 or disc magnet 219′. This results in a magnetic force that repels the magnetic member 202 from the bar magnet 219 or disc magnet 219′ and attracts the magnetic member 202 to the activated coils 214-217. For this configuration, the bar magnet 219 or disc magnet thus act to facilitate acceleration of the magnetic member 202 as opposed to working against the acceleration.


Electrical conductors 222 couple the driver coil pack 188 with the processor 193 which can be configured or programmed to control the current flow in the coils 214-217 of the driver coil pack 188 based on position feedback from the position sensor 191, which is coupled to the processor 193 by electrical conductors 194. A power source 225 is electrically coupled to the processor 193 and provides electrical power to operate the processor 193 and power the coil driver pack 188. The power source 225 may be one or more batteries that provide direct current power to the 193 processor.



FIG. 23 shows a transverse cross sectional view of drive coupler 185 in more detail. The drive head 198 of the lancet 183 is disposed within the drive coupler 185 with a first retaining rail 226 and second retaining rail 227 capturing the drive head 198 while allowing the drive head 198 to be inserted laterally into the drive coupler 185 and retracted laterally with minimal mechanical resistance. The drive coupler 185 may optionally be configured to include snap ridges 228 which allow the drive head 198 to be laterally inserted and retracted, but keep the drive head 198 from falling out of the drive coupler 185 unless a predetermined amount of externally applied lateral force is applied to the drive head 198 of the lancet 183 towards the lateral opening 231 of the drive coupler 185. FIG. 27 shows an enlarged side view into the coupler opening 231 of the drive coupler 185 showing the snap ridges 228 disposed in the lateral opening 231 and the retaining rails 226 and 227. FIG. 28 shows an enlarged front view of the drive coupler 185. The drive coupler 185 can be made from an alloy such as stainless steel, titanium or aluminum, but may also be made from a suitable polymer such as ABS, PVC, polycarbonate plastic or the like. The drive coupler may be open on both sides allowing the drive head and lancet to pass through.


Referring to FIG. 24, the magnetic member 202 is disposed about and secured to the elongate coupler shaft 184. The magnetic member 202 is disposed within the axial lumen 232 of the fourth coil 217. The driver coil pack 188 is secured to the base 213. In FIG. 25 the position sensor 191 is secured to the base 213 with the first body portion 208 of the position sensor 191 disposed opposite the second body portion 209 of the position sensor 191 with the first and second body portions 208 and 209 of the position sensor 191 separated by the gap or slot 207. The elongate coupler shaft 184 is slidably disposed within the gap 207 between the first and second body portions 208 and 209 of the position sensor 191. The optical encoder flag 206 is secured to the elongate coupler shaft 184 and disposed between the first body portion 208 and second body portion 209 of the position sensor 191. Referring to FIG. 26, the proximal portion 192 of the elongate coupler shaft 184 is disposed within the guide lumen 212 of the coupler shaft guide 211. The guide lumen 212 of the coupler shaft guide 211 may be lined with a low friction material such as Teflon® or the like to reduce friction of the elongate coupler shaft 184 during the power stroke of the lancing device 180.


Referring to FIGS. 29A-29C, a flow diagram is shown that describes the operations performed by the processor 193 in controlling the lancet 183 of the lancing device 180 discussed above during an operating cycle. FIGS. 30-36 illustrate the interaction of the lancet 183 and skin 233 of the patient's finger 234 during an operation cycle of the lancet device 183. The processor 193 operates under control of programming steps that are stored in an associated memory. When the programming steps are executed, the processor 193 performs operations as described herein. Thus, the programming steps implement the functionality of the operations described with respect to the flow diagram of FIG. 29. The processor 193 can receive the programming steps from a program product stored in recordable media, including a direct access program product storage device such as a hard drive or flash ROM, a removable program product storage device such as a floppy disk, or in any other manner known to those of skill in the art. The processor 193 can also download the programming steps through a network connection or serial connection.


In the first operation, represented by the flow diagram box numbered 245 in FIG. 29A, the processor 193 initializes values that it stores in memory relating to control of the lancet, such as variables that it uses to keep track of the controllable driver 179 during movement. For example, the processor may set a clock value to zero and a lancet position value to zero or to some other initial value. The processor 193 may also cause power to be removed from the coil pack 188 for a period of time, such as for about 10 ms, to allow any residual flux to dissipate from the coils.


In the initialization operation, the processor 193 also causes the lancet to assume an initial stationary position. When in the initial stationary position, the lancet 183 is typically fully retracted such that the magnetic member 202 is positioned substantially adjacent the fourth coil 217 of the driver coil pack 188, shown in FIG. 21 above. The processor 193 can move the lancet 183 to the initial stationary position by pulsing an electrical current to the fourth coil 217 to thereby attract the magnetic member 202 on the lancet 183 to the fourth coil 217. Alternatively, the magnetic member can be positioned in the initial stationary position by virtue of a permanent magnet, such as bar magnet 219, disc magnet 219′ or any other suitable magnet as discussed above with regard to the tissue penetration device illustrated in FIGS. 20 and 21.


In the next operation, represented by the flow diagram box numbered 247, the processor 193 energizes one or more of the coils in the coil pack 188. This should cause the lancet 183 to begin to move (i.e., achieve a non-zero speed) toward the skin target 233. The processor 193 then determines whether or not the lancet is indeed moving, as represented by the decision box numbered 249. The processor 193 can determine whether the lancet 183 is moving by monitoring the position of the lancet 183 to determine whether the position changes over time. The processor 193 can monitor the position of the lancet 183 by keeping track of the position of the optical encoder flag 206 secured to the elongate coupler shaft 184 wherein the encoder 191 produces a signal coupled to the processor 193 that indicates the spatial position of the lancet 183.


If the processor 193 determines (via timeout without motion events) that the lancet 183 is not moving (a “No” result from the decision box 249), then the process proceeds to the operation represented by the flow diagram box numbered 253, where the processor deems that an error condition is present. This means that some error in the system is causing the lancet 183 not to move. The error may be mechanical, electrical, or software related. For example, the lancet 183 may be stuck in the stationary position because something is impeding its movement.


If the processor 193 determines that the lancet 183 is indeed moving (a “Yes” result from the decision box numbered 249), then the process proceeds to the operation represented by the flow diagram box numbered 257. In this operation, the processor 193 causes the lancet 183 to continue to accelerate and launch toward the skin target 233, as indicated by the arrow 235 in FIG. 30. The processor 193 can achieve acceleration of the lancet 183 by sending an electrical current to an appropriate coil 214-217 such that the coil 214-217 exerts an attractive magnetic launching force on the magnetic member 202 and causes the magnetic member 202 and the lancet 183 coupled thereto to move in a desired direction. For example, the processor 193 can cause an electrical current to be sent to the third coil 216 so that the third coil 216 attracts the magnetic member 202 and causes the magnetic member 202 to move from a position adjacent the fourth coil 217 toward the third coil 216. The processor preferably determines which coil 214-217 should be used to attract the magnetic member 202 based on the position of the magnetic member 202 relative to the coils 214-217. In this manner, the processor 193 provides a controlled force to the lancet that controls the movement of the lancet.


During this operation, the processor 193 periodically or continually monitors the position and/or velocity of the lancet 183. In keeping track of the velocity and position of the lancet 183 as the lancet 183 moves towards the patient's skin 233 or other tissue, the processor 193 also monitors and adjusts the electrical current to the coils 214-217. In some embodiments, the processor 193 applies current to an appropriate coil 214-217 such that the lancet 183 continues to move according to a desired direction and acceleration. In the instant case, the processor 193 applies current to the appropriate coil 214-217 that will cause the lancet 183 to continue to move in the direction of the patient's skin 233 or other tissue to be penetrated.


The processor 193 may successively transition the current between coils 214-217 so that as the magnetic member 202 moves past a particular coil 214-217, the processor 193 then shuts off current to that coil 214-217 and then applies current to another coil 214-217 that will attract the magnetic member 202 and cause the magnetic member 202 to continue to move in the desired direction. In transitioning current between the coils 214-217, the processor 193 can take into account various factors, including the speed of the lancet 183, the position of the lancet 183 relative to the coils 214-217, the number of coils 214-217, and the level of current to be applied to the coils 214-217 to achieve a desired speed or acceleration.


In the next operation, the processor 193 determines whether the cutting or distal end tip 196 of the lancet 183 has contacted the patient's skin 233, as shown in FIG. 31 and as represented by the decision box numbered 265 in FIG. 29B. The processor 193 may determine whether the lancet 183 has made contact with the target tissue 233 by a variety of methods, including some that rely on parameters which are measured prior to initiation of a lancing cycle and other methods that are adaptable to use during a lancing cycle without any predetermined parameters.


In one embodiment, the processor 193 determines that the skin has been contacted when the end tip 196 of the lancet 183 has moved a predetermined distance with respect to its initial position. If the distance from the tip 961 of the lancet 183 to the target tissue 233 is known prior to initiation of lancet 183 movement, the initial position of the lancet 183 is fixed and known, and the movement and position of the lancet 183 can be accurately measured during a lancing cycle, then the position and time of lancet contact can be determined.


This method requires an accurate measurement of the distance between the lancet tip 196 and the patient's skin 233 when the lancet 183 is in the zero time or initial position. This can be accomplished in a number of ways. One way is to control all of the mechanical parameters that influence the distance from the lancet tip 196 to the patient's tissue or a surface of the lancing device 180 that will contact the patient's skin 233. This could include the start position of the magnetic member 202, magnetic path tolerance, magnetic member 202 dimensions, driver coil pack 188 location within the lancing device 180 as a whole, length of the elongate coupling shaft 184, placement of the magnetic member 202 on the elongate coupling shaft 184, length of the lancet 183 etc.


If all these parameters, as well as others can be suitably controlled in manufacturing with a tolerance stack-up that is acceptable, then the distance from the lancet tip 196 to the target tissue 233 can be determined at the time of manufacture of the lancing device 180. The distance could then be programmed into the memory of the processor 193. If an adjustable feature is added to the lancing device 180, such as an adjustable length elongate coupling shaft 184, this can accommodate variations in all of the parameters noted above, except length of the lancet 183. An electronic alternative to this mechanical approach would be to calibrate a stored memory contact point into the memory of the processor 193 during manufacture based on the mechanical parameters described above.


In another embodiment, moving the lancet tip 196 to the target tissue 233 very slowly and gently touching the skin 233 prior to actuation can accomplish the distance from the lancet tip 196 to the tissue 233. The position sensor can accurately measure the distance from the initialization point to the point of contact, where the resistance to advancement of the lancet 183 stops the lancet movement. The lancet 183 is then retracted to the initialization point having measured the distance to the target tissue 233 without creating any discomfort to the user.


In another embodiment, the processor 193 may use software to determine whether the lancet 183 has made contact with the patient's skin 233 by measuring for a sudden reduction in velocity of the lancet 183 due to friction or resistance imposed on the lancet 183 by the patient's skin 233. The optical encoder 191 measures displacement of the lancet 183. The position output data provides input to the interrupt input of the processor 193. The processor 193 also has a timer capable of measuring the time between interrupts. The distance between interrupts is known for the optical encoder 191, so the velocity of the lancet 183 can be calculated by dividing the distance between interrupts by the time between the interrupts.


This method requires that velocity losses to the lancet 183 and elongate coupler 184 assembly due to friction are known to an acceptable level so that these velocity losses and resulting deceleration can be accounted for when establishing a deceleration threshold above which contact between lancet tip 196 and target tissue 233 will be presumed. This same concept can be implemented in many ways. For example, rather than monitoring the velocity of the lancet 183, if the processor 193 is controlling the lancet driver in order to maintain a fixed velocity, the power to the driver 188 could be monitored. If an amount of power above a predetermined threshold is required in order to maintain a constant velocity, then contact between the tip of the lancet 196 and the skin 233 could be presumed.


In yet another embodiment, the processor 193 determines skin 233 contact by the lancet 183 by detection of an acoustic signal produced by the tip 196 of the lancet 183 as it strikes the patient's skin 233. Detection of the acoustic signal can be measured by an acoustic detector 236 placed in contact with the patient's skin 233 adjacent a lancet penetration site 237, as shown in FIG. 31. Suitable acoustic detectors 236 include piezo electric transducers, microphones and the like. The acoustic detector 236 transmits an electrical signal generated by the acoustic signal to the processor 193 via electrical conductors 238. In another embodiment, contact of the lancet 183 with the patient's skin 233 can be determined by measurement of electrical continuity in a circuit that includes the lancet 183, the patient's finger 234 and an electrical contact pad 240 that is disposed on the patient's skin 233 adjacent the contact site 237 of the lancet 183, as shown in FIG. 31. In this embodiment, as soon as the lancet 183 contacts the patient's skin 233, the circuit 239 is completed and current flows through the circuit 239. Completion of the circuit 239 can then be detected by the processor 193 to confirm skin 233 contact by the lancet 183.


If the lancet 183 has not contacted the target skin 233, then the process proceeds to a timeout operation, as represented by the decision box numbered 267 in FIG. 29B. In the timeout operation, the processor 193 waits a predetermined time period. If the timeout period has not yet elapsed (a “No” outcome from the decision box 267), then the processor continues to monitor whether the lancet has contacted the target skin 233. The processor 193 preferably continues to monitor the position and speed of the lancet 183, as well as the electrical current to the appropriate coil 214-217 to maintain the desired lancet 183 movement.


If the timeout period elapses without the lancet 183 contacting the skin (a “Yes” output from the decision box 267), then it is deemed that the lancet 183 will not contact the skin and the process proceeds to a withdraw phase, where the lancet is withdrawn away from the skin 233, as discussed more fully below. The lancet 183 may not have contacted the target skin 233 for a variety of reasons, such as if the patient removed the skin 233 from the lancing device or if something obstructed the lancet 183 prior to it contacting the skin.


The processor 193 may also proceed to the withdraw phase prior to skin contact for other reasons. For example, at some point after initiation of movement of the lancet 183, the processor 193 may determine that the forward acceleration of the lancet 183 towards the patient's skin 233 should be stopped or that current to all coils 214-217 should be shut down. This can occur, for example, if it is determined that the lancet 183 has achieved sufficient forward velocity, but has not yet contacted the skin 233. In one embodiment, the average penetration velocity of the lancet 183 from the point of contact with the skin to the point of maximum penetration may be about 2.0 to about 10.0 m/s, specifically, about 3.8 to about 4.2 m/s. In another embodiment, the average penetration velocity of the lancet may be from about 2 to about 8 meters per second, specifically, about 2 to about 4 m/s.


The processor 193 can also proceed to the withdraw phase if it is determined that the lancet 183 has fully extended to the end of the power stroke of the operation cycle of lancing procedure. In other words, the process may proceed to withdraw phase when an axial center 241 of the magnetic member 202 has moved distal of an axial center 242 of the first coil 214 as show in FIG. 21. In this situation, any continued power to any of the coils 214-217 of the driver coil pack 188 serves to decelerate the magnetic member 202 and thus the lancet 183. In this regard, the processor 193 considers the length of the lancet 183 (which can be stored in memory) the position of the lancet 183 relative to the magnetic member 202, as well as the distance that the lancet 183 has traveled.


With reference again to the decision box 265 in FIG. 29B, if the processor 193 determines that the lancet 183 has contacted the skin 233 (a “Yes” outcome from the decision box 265), then the processor 193 can adjust the speed of the lancet 183 or the power delivered to the lancet 183 for skin penetration to overcome any frictional forces on the lancet 183 in order to maintain a desired penetration velocity of the lancet. The flow diagram box numbered 267 represents this.


As the velocity of the lancet 183 is maintained after contact with the skin 233, the distal tip 196 of the lancet 183 will first begin to depress or tent the contacted skin 237 and the skin 233 adjacent the lancet 183 to form a tented portion 243 as shown in FIG. 32 and further shown in FIG. 33. As the lancet 183 continues to move in a distal direction or be driven in a distal direction against the patient's skin 233, the lancet 183 will eventually begin to penetrate the skin 233, as shown in FIG. 34. Once penetration of the skin 233 begins, the static force at the distal tip 196 of the lancet 183 from the skin 233 will become a dynamic cutting force, which is generally less than the static tip force. As a result in the reduction of force on the distal tip 196 of the lancet 183 upon initiation of cutting, the tented portion 243 of the skin 233 adjacent the distal tip 196 of the lancet 183 which had been depressed as shown in FIGS. 32 and 24 will spring back as shown in FIG. 34.


In the next operation, represented by the decision box numbered 271 in FIG. 29B, the processor 193 determines whether the distal end 196 of the lancet 183 has reached a brake depth. The brake depth is the skin penetration depth for which the processor 193 determines that deceleration of the lancet 183 is to be initiated in order to achieve a desired final penetration depth 244 of the lancet 183 as show in FIG. 35. The brake depth may be pre-determined and programmed into the processor's memory, or the processor 193 may dynamically determine the brake depth during the actuation. The amount of penetration of the lancet 183 in the skin 233 of the patient may be measured during the operation cycle of the lancet device 180. In addition, as discussed above, the penetration depth necessary for successfully obtaining a useable sample can depend on the amount of tenting of the skin 233 during the lancing cycle. The amount of tenting of the patient's skin 233 can in turn depend on the tissue characteristics of the patient such as elasticity, hydration etc. A method for determining these characteristics is discussed below with regard to skin 233 tenting measurements during the lancing cycle and illustrated in FIGS. 37-41.


Penetration measurement can be carried out by a variety of methods that are not dependent on measurement of tenting of the patient's skin. In one embodiment, the penetration depth of the lancet 183 in the patient's skin 233 is measured by monitoring the amount of capacitance between the lancet 183 and the patient's skin 233. In this embodiment, a circuit includes the lancet 183, the patient's finger 234, the processor 193 and electrical conductors connecting these elements. As the lancet 183 penetrates the patient's skin 233, the greater the amount of penetration, the greater the surface contact area between the lancet 183 and the patient's skin 233. As the contact area increases, so does the capacitance between the skin 233 and the lancet 183. The increased capacitance can be easily measured by the processor 193 using methods known in the art and penetration depth can then be correlated to the amount of capacitance. The same method can be used by measuring the electrical resistance between the lancet 183 and the patient's skin.


If the brake depth has not yet been reached, then a “No” results from the decision box 271 and the process proceeds to the timeout operation represented by the flow diagram box numbered 273. In the timeout operation, the processor 193 waits a predetermined time period. If the timeout period has not yet elapsed (a “No” outcome from the decision box 273), then the processor continues to monitor whether the brake depth has been reached. If the timeout period elapses without the lancet 183 achieving the brake depth (a “Yes” output from the decision box 273), then the processor 193 deems that the lancet 183 will not reach the brake depth and the process proceeds to the withdraw phase, which is discussed more fully below. This may occur, for example, if the lancet 183 is stuck at a certain depth.


With reference again to the decision box numbered 271 in FIG. 29B, if the lancet does reach the brake depth (a “Yes” result), then the process proceeds to the operation represented by the flow diagram box numbered 275. In this operation, the processor 193 causes a braking force to be applied to the lancet to thereby reduce the speed of the lancet 183 to achieve a desired amount of final skin penetration depth 244, as shown in FIG. 26. Note that FIGS. 32 and 33 illustrate the lancet making contact with the patient's skin and deforming or depressing the skin prior to any substantial penetration of the skin. The speed of the lancet 183 is preferably reduced to a value below a desired threshold and is ultimately reduced to zero. The processor 193 can reduce the speed of the lancet 183 by causing a current to be sent to a 214-217 coil that will exert an attractive braking force on the magnetic member 202 in a proximal direction away from the patient's tissue or skin 233, as indicated by the arrow 290 in FIG. 36. Such a negative force reduces the forward or distally oriented speed of the lancet 183. The processor 193 can determine which coil 214-217 to energize based upon the position of the magnetic member 202 with respect to the coils 214-217 of the driver coil pack 188, as indicated by the position sensor 191.


In the next operation, the process proceeds to the withdraw phase, as represented by the flow diagram box numbered 277. The withdraw phase begins with the operation represented by the flow diagram box numbered 279 in FIG. 29C. Here, the processor 193 allows the lancet 183 to settle at a position of maximum skin penetration 244, as shown in FIG. 35. In this regard, the processor 193 waits until any motion in the lancet 183 (due to vibration from impact and spring energy stored in the skin, etc.) has stopped by monitoring changes in position of the lancet 183. The processor 193 preferably waits until several milliseconds (ms), such as on the order of about 8 ms, have passed with no changes in position of the lancet 183. This is an indication that movement of the lancet 183 has ceased entirely. In some embodiments, the lancet may be allowed to settle for about 1 to about 2000 milliseconds, specifically, about 50 to about 200 milliseconds. For other embodiments, the settling time may be about 1 to about 200 milliseconds.


It is at this stage of the lancing cycle that a software method can be used to measure the amount of tenting of the patient's skin 233 and thus determine the skin 233 characteristics such as elasticity, hydration and others. Referring to FIGS. 37-41, a lancet 183 is illustrated in various phases of a lancing cycle with target tissue 233. FIG. 37 shows tip 196 of lancet 183 making initial contact with the skin 233 at the point of initial impact.



FIG. 38 illustrates an enlarged view of the lancet 183 making initial contact with the tissue 233 shown in FIG. 37. In FIG. 39, the lancet tip 196 has depressed or tented the skin 233 prior to penetration over a distance of X, as indicated by the arrow labeled X in FIG. 39. In FIG. 40, the lancet 183 has reached the full length of the cutting power stroke and is at maximum displacement. In this position, the lancet tip 196 has penetrated the tissue 233 a distance of Y, as indicated by the arrow labeled Yin FIG. 39. As can be seen from comparing FIG. 38 with FIG. 40, the lancet tip 196 was displaced a total distance of X plus Y from the time initial contact with the skin 233 was made to the time the lancet tip 196 reached its maximum extension as shown in FIG. 40. However, the lancet tip 196 has only penetrated the skin 233 a distance Y because of the tenting phenomenon.


At the end of the power stroke of the lancet 183, as discussed above with regard to FIG. 26 and box 279 of FIG. 29C, the processor 193 allows the lancet to settle for about 8 msec. It is during this settling time that the skin 233 rebounds or relaxes back to approximately its original configuration prior to contact by the lancet 183 as shown in FIG. 41. The lancet tip 196 is still buried in the skin to a depth of Y, as shown in FIG. 41, however the elastic recoil of the tissue has displaced the lancet rearward or retrograde to the point of inelastic tenting that is indicated by the arrows Z in FIG. 41. During the rearward displacement of the lancet 183 due to the elastic tenting of the tissue 233, the processor reads and stores the position data generated by the position sensor 191 and thus measures the amount of elastic tenting, which is the difference between X and Z.


The tenting process and retrograde motion of the lancet 183 during the lancing cycle is illustrated graphically in FIG. 42 which shows both a velocity versus time graph and a position versus time graph of a lancet tip 196 during a lancing cycle that includes elastic and inelastic tenting. In FIG. 42, from point 0 to point A, the lancet 183 is being accelerated from the initialization position or zero position. From point A to point B, the lancet is in ballistic or coasting mode, with no additional power being delivered. At point B, the lancet tip 196 contacts the tissue 233 and begins to tent the skin 233 until it reaches a displacement C. As the lancet tip 196 approaches maximum displacement, braking force is applied to the lancet 183 until the lancet comes to a stop at point D. The lancet 183 then recoils in a retrograde direction during the settling phase of the lancing cycle indicated between D and E. Note that the magnitude of inelastic tenting indicated in FIG. 42 is exaggerated for purposes of illustration.


The amount of inelastic tenting indicated by Z tends to be fairly consistent and small compared to the magnitude of the elastic tenting. Generally, the amount of inelastic tenting Z can be about 120 to about 140 microns. As the magnitude of the inelastic tenting has a fairly constant value and is small compared to the magnitude of the elastic tenting for most patients and skin types, the value for the total amount of tenting for the penetration stroke of the lancet 183 is effectively equal to the rearward displacement of the lancet during the settling phase as measured by the processor 193 plus a predetermined value for the inelastic recoil, such as 130 microns. Inelastic recoil for some embodiments can be about 100 to about 200 microns. The ability to measure the magnitude of skin 233 tenting for a patient is important to controlling the depth of penetration of the lancet tip 196 as the skin is generally known to vary in elasticity and other parameters due to age, time of day, level of hydration, gender and pathological state.


This value for total tenting for the lancing cycle can then be used to determine the various characteristics of the patient's skin 233. Once a body of tenting data is obtained for a given patient, this data can be analyzed in order to predict the total lancet displacement, from the point of skin contact, necessary for a successful lancing procedure. This enables the tissue penetration device to achieve a high success rate and minimize pain for the user. A rolling average table can be used to collect and store the tenting data for a patient with a pointer to the last entry in the table. When a new entry is input, it can replace the entry at the pointer and the pointer advances to the next value. When an average is desired, all the values are added and the sum divided by the total number of entries by the processor 193. Similar techniques involving exponential decay (multiply by 0.95, add 0.05 times current value, etc.) are also possible.


With regard to tenting of skin 233 generally, some typical values relating to penetration depth are now discussed. FIG. 43 shows a cross sectional view of the layers of the skin 233. In order to reliably obtain a useable sample of blood from the skin 233, it is desirable to have the lancet tip 196 reach the venuolar plexus of the skin. The stratum corneum is typically about 0.1 to about 0.6 mm thick and the distance from the top of the dermis to the venuole plexus can be from about 0.3 to about 1.4 mm. Elastic tenting can have a magnitude of up to about 2 mm or so, specifically, about 0.2 to about 2.0 mm, with an average magnitude of about 1 mm. This means that the amount of lancet displacement necessary to overcome the tenting can have a magnitude greater than the thickness of skin necessary to penetrate in order to reach the venuolar plexus. The total lancet displacement from point of initial skin contact may have an average value of about 1.7 to about 2.1 mm. In some embodiments, penetration depth and maximum penetration depth may be about 0.5 mm to about 5 mm, specifically, about 1 mm to about 3 mm. In some embodiments, a maximum penetration depth of about 0.5 to about 3 mm is useful.


Referring back to FIG. 29C, in the next operation, represented by the flow diagram box numbered 280 in FIG. 29C, the processor 193 causes a withdraw force to be exerted on the lancet 183 to retract the lancet 183 from the skin 233, as shown by arrow 290 in FIG. 36 The processor 193 sends a current to an appropriate coil 214-217 so that the coil 214-217 exerts an attractive distally oriented force on the magnetic member 202, which should cause the lancet 183 to move backward in the desired direction. In some embodiments, the lancet 183 is withdrawn with less force and a lower speed than the force and speed during the penetration portion of the operation cycle. Withdrawal speed of the lancet in some embodiments can be about 0.004 to about 0.5 m/s, specifically, about 0.006 to about 0.01 m/s. In other embodiments, useful withdrawal velocities can be about 0.001 to about 0.02 meters per second, specifically, about 0.001 to about 0.01 meters per second. For embodiments that use a relatively slow withdrawal velocity compared to the penetration velocity, the withdrawal velocity may up to about 0.02 meters per second. For such embodiments, a ratio of the average penetration velocity relative to the average withdrawal velocity can be about 100 to about 1000. In embodiments where a relatively slow withdrawal velocity is not important, a withdrawal velocity of about 2 to about 10 meters per second may be used.


In the next operation, the processor 193 determines whether the lancet 183 is moving in the desired backward direction as a result of the force applied, as represented by the decision box numbered 281. If the processor 193 determines that the lancet 183 is not moving (a “No” result from the decision box 281), then the processor 193 continues to cause a force to be exerted on the lancet 183, as represented by the flow diagram box numbered 282. The processor 193 may cause a stronger force to be exerted on the lancet 183 or may just continue to apply the same amount of force. The processor then again determines whether the lancet is moving, as represented by the decision box numbered 283. If movement is still not detected (a “No” result from the decision box numbered 283), the processor 193 determines that an error condition is present, as represented by the flow diagram box numbered 284. In such a situation, the processor preferably de-energizes the coils to remove force from the lancet, as the lack of movement may be an indication that the lancet is stuck in the skin of the patient and, therefore, that it may be undesirable to continue to attempt pull the lancet out of the skin.


With reference again to the decision boxes numbered 281 and 283 in FIG. 29C, if the processor 193 determines that the lancet is indeed moving in the desired backward direction away from the skin 233, then the process proceeds to the operation represented by the flow diagram box numbered 285. In this operation, the backward movement of the lancet 183 continues until the lancet distal end has been completely withdrawn from the patient's skin 233. As discussed above, in some embodiments the lancet 183 is withdrawn with less force and a lower speed than the force and speed during the penetration portion of the operation cycle. The relatively slow withdrawal of the lancet 183 may allow the blood from the capillaries of the patient accessed by the lancet 183 to follow the lancet 183 during withdrawal and reach the skin surface to reliably produce a usable blood sample. The process then ends.


Controlling the lancet motion over the operating cycle of the lancet 183 as discussed above allows a wide variety of lancet velocity profiles to be generated by the lancing device 180. In particular, any of the lancet velocity profiles discussed above with regard to other embodiments can be achieved with the processor 193, position sensor 191 and driver coil pack 188 of the lancing device 180.


Another example of an embodiment of a velocity profile for a lancet can be seen in FIGS. 44 and 45, which illustrates a lancet profile with a fast entry velocity and a slow withdrawal velocity. FIG. 44 illustrates an embodiment of a lancing profile showing velocity of the lancet versus position. The lancing profile starts at zero time and position and shows acceleration of the lancet towards the tissue from the electromagnetic force generated from the electromagnetic driver. At point A, the power is shut off and the lancet 183 begins to coast until it reaches the skin 233 indicated by B at which point, the velocity begins to decrease. At point C, the lancet 183 has reached maximum displacement and settles momentarily, typically for a time of about 8 milliseconds.


A retrograde withdrawal force is then imposed on the lancet by the controllable driver, which is controlled by the processor to maintain a withdrawal velocity of no more than about 0.006 to about 0.01 meters/second. The same cycle is illustrated in the velocity versus time plot of FIG. 45 where the lancet is accelerated from the start point to point A. The lancet 183 coasts from A to B where the lancet tip 196 contacts tissue 233. The lancet tip 196 then penetrates the tissue and slows with braking force eventually applied as the maximum penetration depth is approached. The lancet is stopped and settling between C and D. At D, the withdrawal phase begins and the lancet 183 is slowly withdrawn until it returns to the initialization point shown by E in FIG. 45. Note that retrograde recoil from elastic and inelastic tenting was not shown in the lancing profiles of FIGS. 44 and 45 for purpose of illustration and clarity.


In another embodiment, the withdrawal phase may use a dual speed profile, with the slow 0.006 to 0.01 meter per second speed used until the lancet is withdrawn past the contact point with the tissue, then a faster speed of 0.01 to 1 meters per second may be used to shorten the complete cycle.


Referring to FIG. 46, another embodiment of a lancing device including a controllable driver 294 with a driver coil pack 295, position sensor and lancet 183 are shown. The lancet 297 has a proximal end 298 and a distal end 299 with a sharpened point at the distal end 299 of the lancet 297. A magnetic member 301 disposed about and secured to a proximal end portion 302 of the lancet 297 with a lancet shaft 303 being disposed between the magnetic member 301 and the sharpened point 299. The lancet shaft 303 may be comprised of stainless steel, or any other suitable material or alloy. The lancet shaft 303 may have a length of about 3 mm to about 50 mm specifically, about 5 mm to about 15 mm.


The magnetic member 301 is configured to slide within an axial lumen 304 of the driver coil pack 295. The driver coil pack 295 includes a most distal first coil 305, a second coil 306, which is axially disposed between the first coil 305 and a third coil 307, and a proximal-most fourth coil 308. Each of the first coil 305, second coil 306, third coil 307 and fourth coil 308 has an axial lumen. The axial lumens of the first through fourth coils 305-308 are configured to be coaxial with the axial lumens of the other coils and together form the axial lumen 309 of the driver coil pack 295 as a whole. Axially adjacent each of the coils 305-308 is a magnetic disk or washer 310 that augments completion of the magnetic circuit of the coils 305-308 during a lancing cycle of the driven coil pack 295. The magnetic washers 310 of the embodiment of FIG. 46 are made of ferrous steel but could be made of any other suitable magnetic material, such as iron or ferrite. The magnetic washers 310 have an outer diameter commensurate with an outer diameter of the driver coil pack 295 of about 4.0 to about 8.0 mm. The magnetic washers 310 have an axial thickness of about 0.05, to about 0.4 mm, specifically, about 0.15 to about 0.25 mm. The outer shell 294 of the coil pack is also made of iron or steel to complete the magnetic path around the coils and between the washers 310.


Wrapping or winding an elongate electrical conductor 311 about the axial lumen 309 until a sufficient number of windings have been achieved forms the coils 305-308. The elongate electrical conductor 311 is generally an insulated solid copper wire. The particular materials, dimensions number of coil windings etc. of the coils 305-308, washers 310 and other components of the driver coil pack 295 can be the same or similar to the materials, dimensions number of coil windings etc. of the driver coil pack 188 discussed above.


Electrical conductors 312 couple the driver coil pack 295 with a processor 313 which can be configured or programmed to control the current flow in the coils 305-308 of the driver coil pack 295 based on position feedback from the position sensor 296, which is coupled to the processor 313 by electrical conductors 315. A power source 316 is electrically coupled to the processor 313 and provides electrical power to operate the processor 313 and power the driver coil pack 295. The power source 316 may be one or more batteries (not shown) that provide direct current power to the processor 313 as discussed above.


The position sensor 296 is an analog reflecting light sensor that has a light source and light receiver in the form of a photo transducer 317 disposed within a housing 318 with the housing 318 secured in fixed spatial relation to the driver coil pack 295. A reflective member 319 is disposed on or secured to a proximal end 320 of the magnetic member 301. The processor 313 determines the position of the lancet 299 by first emitting light from the light source of the photo transducer 317 towards the reflective member 319 with a predetermined solid angle of emission. Then, the light receiver of the photo transducer 317 measures the intensity of light reflected from the reflective member 319 and electrical conductors 315 transmit the signal generated therefrom to the processor 313.


By calibrating the intensity of reflected light from the reflective member 319 for various positions of the lancet 297 during the operating cycle of the driver coil pack 295, the position of the lancet 297 can thereafter be determined by measuring the intensity of reflected light at any given moment. In one embodiment, the sensor 296 uses a commercially available LED/photo transducer module such as the OPB703 manufactured by Optek Technology, Inc., 1215 W. Crosby Road, Carrollton, Tex., 75006. This method of analog reflective measurement for position sensing can be used for any of the embodiments of lancet actuators discussed herein. In addition, any of the lancet actuators or drivers that include coils may use one or more of the coils to determine the position of the lancet 297 by using a magnetically permeable region on the lancet shaft 303 or magnetic member 301 itself as the core of a Linear Variable Differential Transformer (LVDT).


Referring to FIGS. 47 and 48, a flat coil lancet driver 325 is illustrated which has a main body housing 326 and a rotating frame 327. The rotating frame 327 pivots about an axle 328 disposed between a base 329, a top body portion 330 of the main body housing 326 and disposed in a pivot guide 331 of the rotating frame 327. An actuator arm 332 of the rotating frame 327 extends radially from the pivot guide 331 and has a linkage receiving opening 333 disposed at an outward end 334 of the actuator arm 332. A first end 335 of a coupler linkage 336 is coupled to the linkage receiving opening 333 of the actuator arm 332 and can rotate within the linkage receiving opening 333. A second end 337 of the coupler linkage 336 is disposed within an opening at a proximal end 338 of a coupler translation member 341. This configuration allows circumferential forces imposed upon the actuator arm 332 to be transferred into linear forces on a drive coupler 342 secured to a distal end 343 of the coupler translation member 341. The materials and dimensions of the drive coupler 342 can be the same or similar to the materials and dimensions of the drive coupler 342 discussed above.


Opposite the actuator arm 332 of the rotating frame 327, a translation substrate in the form of a coil arm 344 extends radially from the pivot guide 331 of the rotating frame 327. The coil arm 344 is substantially triangular in shape. A flat coil 345 is disposed on and secured to the coil arm 344. The flat coil 345 has leading segment 346 and a trailing segment 347, both of which extend substantially orthogonal to the direction of motion of the segments 346 and 347 when the rotating frame 327 is rotating about the pivot guide 331. The leading segment 346 is disposed within a first magnetically active region 348 generated by a first upper permanent magnet 349 secured to an upper magnet base 351 and a first lower permanent magnet 352 secured to a lower magnet base 353. The trailing segment 347 is disposed within a second magnetically active region 354 generated by a second upper permanent magnet 355 secured to the upper magnet base 351 and a second lower permanent magnet secured to the lower magnet base 353.


The magnetic field lines or circuit of the first upper and lower permanent magnets 349, 352, 355 and 356 can be directed upward from the first lower permanent magnet 352 to the first upper permanent magnet 349 or downward in an opposite direction. The magnetic field lines from the second permanent magnets 355 and 356 are also directed up or down, and will have a direction opposite to that of the first upper and lower permanent magnets 349 and 352. This configuration produces rotational force on the coil arm 344 about the pivot guide 331 with the direction of the force determined by the direction of current flow in the flat coil 345.


A position sensor 357 includes an optical encoder disk section 358 is secured to the rotating frame 327 which rotates with the rotating frame 327 and is read by an optical encoder 359 which is secured to the base 329. The position sensor 357 determines the rotational position of the rotating frame 327 and sends the position information to a processor 360 which can have features which are the same or similar to the features of the processor 193 discussed above via electrical leads 361. Electrical conductor leads 363 of the flat coil 345 are also electrically coupled to the processor 360.


As electrical current is passed through the leading segment 346 and trailing segment 347 of the flat coil 345, the rotational forces imposed on the segments 346 and 347 are transferred to the rotating frame 327 to the actuator arm 332, through the coupler linkage 336 and coupler translation member 341 and eventually to the drive coupler 342. In use, a lancet (not shown) is secured into the drive coupler 342, and the flat coil lancet actuator 325 activated. The electrical current in the flat coil 345 determines the forces generated on the drive coupler 342, and hence, a lancet secured to the coupler 342. The processor 360 controls the electrical current in the flat coil 345 based on the position and velocity of the lancet as measured by the position sensor 357 information sent to the processor 360. The processor 360 is able to control the velocity of a lancet in a manner similar to the processor 193 discussed above and can generate any of the desired lancet velocity profiles discussed above, in addition to others.



FIGS. 49 and 50 depict yet another embodiment of a controlled driver 369 having a driver coil pack 370 for a tissue penetration device. The driver coil pack 370 has a proximal end 371, a distal end 372 and an axial lumen 373 extending from the proximal end 371 to the distal end 372. An inner coil 374 is disposed about the axial lumen 373 and has a tapered configuration with increasing wraps per inch of an elongate conductor 375 in a distal direction. The inner coil 374 extends from the proximal end 371 of the coil driver pack 370 to the distal end 372 of the driver coil pack 370 with a major outer diameter or transverse dimension of about 1 to about 25 mm, specifically about 1 to about 12 mm.


The outer diameter or transverse dimension of the inner coil 374 at the proximal end 371 of the driver coil pack 370 is approximately equal to the diameter of the axial lumen 373 at the proximal end 371 of the coil pack 370. That is, the inner coil 374 tapers to a reduce outer diameter proximally until there are few or no wraps of elongate electrical conductor 375 at the proximal end 371 of the driver coil pack 370. The tapered configuration of the inner coil 374 produces an axial magnetic field gradient within the axial lumen 373 of the driver coil pack 370 when the inner coil 374 is activated with electrical current flowing through the elongate electrical conductor 375 of the inner coil 374.


The axial magnetic field gradient produces a driving force for a magnetic member 376 disposed within the axial lumen 373 that drives the magnetic member 376 towards the distal end 372 of the driver coil pack 370 when the inner coil 374 is activated. The driving force on the magnetic member produced by the inner coil 374 is a smooth continuous force, which can produce a smooth and continuous acceleration of the magnetic member 376 and lancet 377 secured thereto. In some embodiments, the ratio of the increase in outer diameter versus axial displacement along the inner coil 374 in a distal direction can be from about 1 to about 0.08, specifically, about 1 to about 0.08.


An outer coil 378 is disposed on and longitudinally coextensive with the inner coil 374. The outer coil 378 can have the same or similar dimensions and construction as the inner coil 374, except that the outer coil 378 tapers proximally to an increased diameter or transverse dimension. The greater wraps per inch of elongate electrical conductor 379 in a proximal direction for the outer coil 378 produces a magnetic field gradient that drives the magnetic member 376 in a proximal direction when the outer coil 378 is activated with electrical current. This produces a braking or reversing effect on the magnetic member 376 during an operational cycle of the lancet 377 and driver coil pack 370. The elongate electrical conductors 375 and 379 of the inner coil 374 and outer coil 378 are coupled to a processor 381, which is coupled to an electrical power source 382. The processor 381 can have properties similar to the other processors discussed above and can control the velocity profile of the magnetic member 376 and lancet 377 to produce any of the velocity profiles above as well as others. The driver coil pack 370 can be used as a substitute for the coil driver pack discussed above, with other components of the lancing device 180 being the same or similar.


Embodiments of driver or actuator mechanisms having been described, we now discuss embodiments of devices which can house lancets, collect samples of fluids, analyze the samples or any combination of these functions. These front-end devices may be integrated with actuators, such as those discussed above, or any other suitable driver or controllable driver.


Generally, most known methods of blood sampling require several steps. First, a measurement session is set up by gathering various articles such as lancets, lancet drivers, test strips, analyzing instrument, etc. Second, the patient must assemble the paraphernalia by loading a sterile lancet, loading a test strip, and arming the lancet driver. Third, the patient must place a finger against the lancet driver and using the other hand to activate the driver. Fourth, the patient must put down the lancet driver and place the bleeding finger against a test strip, (which may or may not have been loaded into an analyzing instrument). The patient must insure blood has been loaded onto the test strip and the analyzing instrument has been calibrated prior to such loading. Finally, the patient must dispose of all the blood-contaminated paraphernalia including the lancet. As such, integrating the lancing and sample collection features of a tissue penetration sampling device can achieve advantages with regard to patient convenience.



FIG. 51 shows a disposable sampling module 410, which houses the lancet 412. The lancet 412 has a head on a proximal end 416 which connects to the driver 438 and a distal end 414, which lances the skin. The distal end 414 is disposed within the conduit 418. The proximal end 416 extends into the cavity 420. The sample reservoir 422 has a narrow input port 424 on the ergonomically contoured surface 426, which is adjacent to the distal end 414 of the lancet 412. The term ergonomically contoured, as used herein, generally means shaped to snugly fit a finger or other body portion to be lanced or otherwise tested placed on the surface. The sampling module 410 is capable of transporting the blood sample from the sample reservoir 422 through small passages (not shown), to an analytical region 428. The analytical region 428 can include chemical, physical, optical, electrical or other means of analyzing the blood sample. The lancet, sample flow channel, sample reservoir and analytical region are integrated into the sampling module 410 in a single packaged unit.



FIG. 52 shows the chamber 430 in the housing 410′ where the sampling module 410 is loaded. The sampling module 410 is loaded on a socket 432 suspended with springs 434 and sits in slot 436. A driver 438 is attached to the socket 432. The driver 438 has a proximal end 440 and a distal end 442. The driver 438 can be either a controllable driver or non-controllable driver any mechanical, such as spring or cam driven, or electrical, such as electromagnetically or electronically driven, means for advancing, stopping, and retracting the lancet. There is a clearance 444 between the distal end 442 of the driver 438 and the sensor 446, which is attached to the chamber 430. The socket 432 also contains an analyzer 448, which is a system for analyzing blood. The analyzer 448 corresponds to the analytical region 428 on the module 410 when it is loaded into the socket 432.



FIG. 53 shows a tissue penetration sampling device 411 with the sampling module 410 loaded into the socket 432 of housing 410′. The analytical region 428 and analyzer 448 overlap. The driver 438 fits into the cavity 420. The proximal end 440 of the driver 438 abuts the distal end 416 of the lancet 412. The patient's finger 450 sits on the ergonomically contoured surface 426.



FIG. 54 shows a drawing of an alternate lancet configuration where the lancet 412 and driver 438 are oriented to lance the side of the finger 450 as it sits on the ergonomically contoured surface 426.



FIG. 55 illustrates the orifice 452 and ergonomically contoured surface 426. The conduit 418 has an orifice 452, which opens on a blood well 454. The sample input port 424 of the reservoir 422 also opens on the blood well 454. The diameter of the sample input port 424 is significantly greater than the diameter of the orifice 452, which is substantially the same diameter as the diameter of the lancet 412. After the lancet is retracted, the blood flowing from the finger 450 will collect in the blood well 454. The lancet 412 will have been retracted into the orifice 452 effectively blocking the passage of blood down the orifice 452. The blood will flow from the blood well 454 through the sample input port 424 into the reservoir 422.



FIG. 56 shows a drawing of the lancing event. The patient applies pressure by pushing down with the finger 450 on the ergonomically contoured surface 426. This applies downward pressure on the sampling module 410, which is loaded into the socket 432. As the socket 432 is pushed downward it compresses the springs 434. The sensor 446 makes contact with the distal end 442 of the driver 438 and thereby electrically detects the presence of the finger on the ergonomically contoured surface. The sensor can be a piezoelectric device, which detects this pressure and sends a signal to circuit 456, which actuates the driver 438 and advances and then retracts the lancet 412 lancing the finger 450. In another embodiment, the sensor 446 is an electric contact, which closes a circuit when it contacts the driver 438 activating the driver 438 to advance and retract the lancet 412 lancing the finger 450.


An embodiment of a method of sampling includes a reduced number of steps that must be taken by a patient to obtain a sample and analysis of the sample. First, the patient loads a sampling module 410 with an embedded sterile lancet into the housing device 410′. Second, the patient initiates a lancing cycle by turning on the power to the device or by placing the finger to be lanced on the ergonomically contoured surface 426 and pressing down. Initiation of the sensor makes the sensor operational and gives control to activate the launcher.


The sensor is unprompted when the lancet is retracted after its lancing cycle to avoid unintended multiple lancing events. The lancing cycle consists of arming, advancing, stopping and retracting the lancet, and collecting the blood sample in the reservoir. The cycle is complete once the blood sample has been collected in the reservoir. Third, the patient presses down on the sampling module, which forces the driver 38 to make contact with the sensor, and activates the driver 438. The lancet then pierces the skin and the reservoir collects the blood sample.


The patient is then optionally informed to remove the finger by an audible signal such as a buzzer or a beeper, and/or a visual signal such as an LED or a display screen. The patient can then dispose of all the contaminated parts by removing the sampling module 410 and disposing of it. In another embodiment, multiple sampling modules 410 may be loaded into the housing 410′ in the form of a cartridge (not shown). The patient can be informed by the tissue penetration sampling device 411 as to when to dispose of the entire cartridge after the analysis is complete.


In order to properly analyze a sample in the analytical region 428 of the sampling module 410, it may be desirable or necessary to determine whether a fluid sample is present in a given portion of the sample flow channel, sample reservoir or analytical area. A variety of devices and methods for determining the presence of a fluid in a region are discussed below.


In FIG. 57, a thermal sensor 500 embedded in a substrate 502 adjacent to a surface 504 over which a fluid may flow. The surface may be, for example, a wall of a channel through which fluid may flow or a surface of a planar device over which fluid may flow. The thermal sensor 500 is in electrical communication with a signal-conditioning element 506, which may be embedded in the substrate 502 or may be remotely located. The signal-conditioning element 506 receives the signal from the thermal sensor 500 and modifies it by means such as amplifying it and filtering it to reduce noise. FIG. 57 also depicts a thermal sensor 508 located at an alternate location on the surface where it is directly exposed to the fluid flow.



FIG. 58 shows a configuration of a thermal sensor 500 adjacent to a separate heating element 510. The thermal sensor 500 and the heating element 510 are embedded in a substrate 502 adjacent to a surface 504 over which a fluid may flow. In an alternate embodiment, one or more additional thermal sensors may be adjacent the heating element and may provide for increased signal sensitivity. The thermal sensor 500 is in electrical communication with a signal-conditioning element 506, which may be embedded in the substrate 502 or may be remotely located.


The signal-conditioning element 506 receives the signal from the thermal sensor 500 and modifies it by means such as amplifying it and filtering it to reduce noise. The heating element 510 is in electrical communication with a power supply and control element 512, which may be embedded in the substrate 502 or may be remotely located. The power supply and control element 512 provides a controlled source of voltage and current to the heating element 510.



FIG. 59 depicts a configuration of thermal sensors 500 having three thermal sensor/heating element pairs (500/510), or detector elements, (with associated signal conditioning elements 506 and power supply and control elements 512 as described in FIG. 58) embedded in a substrate 502 near each other alongside a surface 504. The figure depicts the thermal sensors 500 arranged in a linear fashion parallel to the surface 504, but any operable configuration may be used. In alternate embodiments, fewer than three or more than three thermal sensor/heating element pairs (500/510) may be used to indicate the arrival of fluid flowing across a surface 504. In other embodiments, self-heating thermal sensors are used, eliminating the separate heating elements.


Embodiments of the present invention provide a simple and accurate methodology for detecting the arrival of a fluid at a defined location. Such detection can be particularly useful to define the zero- or start-time of a timing cycle for measuring rate-based reactions. This can be used in biochemical assays to detect a variety of analytes present in a variety of types of biological specimens or fluids and for rate-based reactions such as enzymatic reactions. Examples of relevant fluids include, blood, serum, plasma, urine, cerebral spinal fluid, saliva, enzymatic substances and other related substances and fluids that are well known in the analytical and biomedical art. The reaction chemistry for particular assays to analyze biomolecular fluids is generally well known, and selection of the particular assay used will depend on the biological fluid of interest.


Assays that are relevant to embodiments of the present invention include those that result in the measurement of individual analytes or enzymes, e.g., glucose, lactate, creatinine kinase, etc, as well as those that measure a characteristic of the total sample, for example, clotting time (coagulation) or complement-dependent lysis. Other embodiments for this invention provide for sensing of sample addition to a test article or arrival of the sample at a particular location within that article.


Referring now to FIG. 60, a substrate 502 defines a channel 520 having an interior surface 522 over which fluid may flow. An analysis site 524 is located within the channel 520 where fluid flowing in the channel 520 may contact the analysis site 524. In various embodiments, the analysis site 524 may alternatively be upon the interior surface 522, recessed into the substrate 502, or essentially flush with the interior surface 522. FIG. 60, depicts several possible locations for thermal sensors relative the substrate, the channel, and the analysis site; also, other locations may be useful and will depend upon the design of the device, as will be apparent to those of skill in art.


In use, thermal sensors may be omitted from one or more of the locations depicted in FIG. 60, depending on the intended design. A recess in the analysis site 524 may provide the location for a thermal sensor 526, as may the perimeter of the analysis site provide the location for a thermal sensor 528. One or more thermal sensors 530, 532, 534 may be located on the upstream side of the analysis site 524 (as fluid flows from right to left in FIG. 60), or one or more thermal sensors 536, 538, 540 may be located on the downstream side of the analysis site 524.


The thermal sensor may be embedded in the substrate near the surface, as thermal sensor 542 is depicted. In various other embodiments, the thermal sensor(s) may be located upon the interior surface, recessed into the interior surface, or essentially flush with the interior surface. Each thermal sensor may also be associated with a signal conditioning element, heating element, and power supply and control elements, as described above, and a single signal conditioning element, heating element, or power supply and control element may be associated with more than one thermal sensor.



FIG. 61 shows possible positions for thermal sensors relative to analysis sites 524 arranged in an array on a surface 556. A recess in the analysis site 524 may provide the location for a thermal sensor 544, as may the perimeter of the analysis site provide the location for a thermal sensor 546. The edge of the surface surrounding the array of analysis sites may provide the position for one or more thermal sensors 548. Thermal sensors may be positioned between analysis sites in a particular row 550 or column 552 of the array, or may be arranged on the diagonal 554.


In various embodiments, the thermal sensor(s) may be may be embedded in the substrate near the surface or may be located upon the surface, recessed into the surface, or essentially flush with the surface. Each thermal sensor may also be associated with a signal conditioning elements, heating elements, and power supply and control elements, as described above, and a single signal conditioning element, heating element, or power supply and control element may be associated with more than one thermal sensor.


The use of small thermal sensors can be useful in miniaturized systems, such as microfluidic devices, which perform biomolecular analyses on very small fluid samples. Such analyses generally include passing a biomolecular fluid through, over, or adjacent to an analysis site and result in information about the biomolecular fluid being obtained through the use of reagents and/or test circuits and/or components associated with the analysis site.



FIG. 62 depicts several possible configurations of thermal sensors relative to channels and analysis sites. The device schematically depicted in FIG. 62 may be, e.g., a microfluidic device for analyzing a small volume of a sample fluid, e.g. a biomolecular fluid. The device has a sample reservoir 560 for holding a quantity of a sample fluid. The sample fluid is introduced to the sample reservoir 560 via a sample inlet port 562 in fluid communication with the sample reservoir 560. A thermal sensor 564 is located in or near the sample inlet port 562. A primary channel 566 originates at the sample reservoir 560 and terminates at an outflow reservoir 568.


One or more supplemental reservoirs 570 are optionally present and are in fluid communication with the primary channel 566 via one or more supplemental channels 572, which lead from the supplemental reservoir 570 to the primary channel 566. The supplemental reservoir 570 functions to hold fluids necessary for the operation of the assay, such as reagent solutions, wash solutions, developer solutions, fixative solutions, et cetera. In the primary channel 566 at a predetermined distance from the sample reservoir 560, an array of analysis sites 574 is present.


Thermal sensors are located directly upstream (as fluid flows from right to left in the figure) from the array 576 and directly downstream from the array 578. Thermal sensors are also located in the primary channel adjacent to where the primary channel originates at the sample reservoir 580 and adjacent to where the primary channel terminates at the outflow reservoir 582. The supplemental channel provides the location for another thermal sensor 584.


When the device is in operation, the thermal sensor 564 located in or near the sample inlet port 562 is used to indicate the arrival of the sample fluid, e.g. the biomolecular fluid, in the local environment of the thermal sensor, as described herein, and thus provides confirmation that the sample fluid has successfully been introduced into the device. The thermal sensor 580 located in the primary channel 566 adjacent to where the primary channel 566 originates at the sample reservoir 560 produces a signal indicating that sample fluid has started to flow from the sample reservoir 560 into the primary channel 566. The thermal sensors 576 in the primary channel 566 just upstream from the array of analysis sites 574 may be used to indicate that the fluid sample is approaching the array 574. Similarly, the thermal sensors 578 in the primary channel 566 just downstream from the array of analysis sites 574 may be used to indicate that the fluid sample has advanced beyond the array 574 and has thus contacted each analysis site.


The thermal sensor 584 in the supplemental channel 572 provides confirmation that the fluid contained within the supplemental reservoir 570 has commenced to flow therefrom. The thermal sensor 582 in the primary channel 566 adjacent to where the primary channel 566 terminates at the outflow reservoir 568 indicates when sample fluid arrives near the outflow reservoir 568, which may then indicate that sufficient sample fluid has passed over the array of analysis sites 574 and that the analysis at the analysis sites is completed.


Embodiments of the invention provide for the use of a thermal sensor to detect the arrival of the fluid sample at a determined region, such as an analysis site, in the local environment of the thermal sensor near the thermal sensor. A variety of thermal sensors may be used. Thermistors are thermally-sensitive resistors whose prime function is to detect a predictable and precise change in electrical resistance when subjected to a corresponding change in temperature Negative Temperature Coefficient (NTC) thermistors exhibit a decrease in electrical resistance when subjected to an increase in temperature and Positive Temperature Coefficient (PTC) thermistors exhibit an increase in electrical resistance when subjected to an increase in temperature.


A variety of thermistors have been manufactured for over the counter use and application. Thermistors are capable of operating over the temperature range of −100 degrees to over 600 degrees Fahrenheit. Because of their flexibility, thermistors are useful for application to micro-fluidics and temperature measurement and control.


A change in temperature results in a corresponding change in the electrical resistance of the thermistor. This temperature change results from either an external transfer of heat via conduction or radiation from the sample or surrounding environment to the thermistor, or as an internal application of heat due to electrical power dissipation within the device. When a thermistor is operated in “self-heating” mode, the power dissipated in the device is sufficient to raise its temperature above the temperature of the local environment, which in turn more easily detects thermal changes in the conductivity of the local environment.


Thermistors are frequently used in “self heating” mode in applications such as fluid level detection, airflow detection and thermal conductivity materials characterization. This mode is particularly useful in fluid sensing, since a self-heating conductivity sensor dissipates significantly more heat in a fluid or in a moving air stream than it does in still air.


Embodiments of the invention may be designed such that the thermal sensor is exposed directly to the sample. However, it may also be embedded in the material of the device, e.g., in the wall of a channel meant to transport the sample. The thermal sensor may be covered with a thin coating of polymer or other protective material.


Embodiments of the device need to establish a baseline or threshold value of a monitored parameter such as temperature. Ideally this is established during the setup process. Once fluid movement has been initiated, the device continuously monitors for a significant change thereafter. The change level designated as “significant” is designed as a compromise between noise rejection and adequate sensitivity. The actual definition of the “zero- or start-time” may also include an algorithm determined from the time history of the data, i.e., it can be defined ranging from the exact instant that a simple threshold is crossed, to a complex mathematical function based upon a time sequence of data.


In use, a signal is read from a thermal sensor in the absence of the sample or fluid. The fluid sample is then introduced. The sample flows to or past the site of interest in the local environment of the thermal sensor, and the thermal sensor registers the arrival of the sample. The site of interest may include an analysis site for conducting, e.g., an enzymatic assay. Measuring the arrival of fluid at the site of interest thus indicates the zero- or start-time of the reaction to be performed. For detection of fluid presence, these sites may be any of a variety of desired locations along the fluidic pathway. Embodiments of the invention are particularly well suited to a microfluidic cartridge or platform, which provide the user with an assurance that a fluid sample has been introduced and has flowed to the appropriate locations in the platform.


A rate-based assay must measure both an initiation time, and some number of later time points, one of which is the end-point of the assay. Therefore, baseline or threshold value can be established, and then continuously monitored for a significant change thereafter; one such change is the arrival of the fluid sample that initiates the enzyme reaction. Baseline values are frequently established during the device setup process. The threshold is designed as a compromise between noise rejection and adequate sensitivity. The defined zero- or “start-time” can be defined ranging from the exact instant that a simple threshold is crossed, to the value algorithmically determined using a filter based on a time sequence of data.


Embodiments of the invention accomplish this in a variety of ways. In one embodiment, an initial temperature measurement is made at a thermal sensor without the sample present. The arrival of a sample changes causes the thermal sensor to register a new value. These values are then compared.


Another embodiment measures the change in thermal properties (such as thermal conductivity or thermal capacity) in the local environment of a thermal sensor caused by the arrival of a fluid sample. In general this is the operating principle of a class of devices known as “thermal conductivity sensors” or “heat flux sensors”. At least two hardware implementations have been used and are described above. One implementation utilizes a thermal sensor in a “self-heating mode.” In “self-heating mode,” a self-heating thermal sensor may utilize a positive temperature coefficient thermistor placed in or near the flow channel, e.g. located in the wall of the flow channel.


An electrical current is run through the thermistor, causing the average temperature of the thermistor to rise above that of the surrounding environment. The temperature can be determined from the electrical resistance, since it is temperature dependent. When fluid flows through the channel, it changes the local thermal conductivity near the thermistor (usually to become higher) and this causes a change in the average temperature of the thermistor. It also changes the thermal capacity, which modifies the thermal dynamic response. These changes give rise to a signal, which can be detected electronically by well-known means, and the arrival of the fluid can thereby be inferred.


A second hardware implementation requires a separate heating element in or near the flow channel, plus a thermal sensor arrangement in close proximity. Passing a current through the element provides heat to the local environment and establishes a local temperature detected by the thermocouple device. This temperature or its dynamic response is altered by the arrival of the fluid or blood in or near the local environment, similar to the previously described implementation, and the event is detected electronically.


The heating element can be operated in a controlled input mode, which may include controlling one or more of the following parameters—applied current, voltage or power—in a prescribed manner. When operating in controlled input mode, fluctuations of the temperature of the thermal sensor are monitored in order to detect the arrival of the fluid.


Alternatively, the heating element can be operated in such a fashion as to control the temperature of the thermal sensor in a prescribed manner. In this mode of operation, the resulting fluctuations in one or more of the input parameters to the heating element (applied current, voltage, and power) can be monitored in order to detect the arrival of the fluid.


In either of the above-described operating modes, the prescribed parameter can be held to a constant value or sequence of values that are held constant during specific phases of operation of the device. The prescribed parameter can also varied as a known function or waveform in time.


The change in the monitored parameters caused by the arrival of the fluid can be calculated in any of a number of ways, using methods well known in the art of signal processing. The signal processing methods allow the relation of the signal received prior to arrival of the fluid with the signal received upon arrival of the fluid to indicate that the fluid has arrived. For example, and after suitable signal filtering is applied, changes in the monitored value or the rate of change of the value of the signal can be monitored to detect the arrival of the fluid. Additionally, the arrival of fluid will cause a dynamic change in the thermodynamic properties of the local environment, such as thermal conductivity or thermal capacity. When the input parameter is a time varying function this change of thermodynamic properties will cause a phase shift of the measured parameter relative to the controlled parameter. This phase shift can be monitored to detect the arrival of the fluid.


It should also be noted that sensitivity to thermal noise and operating power levels could be reduced in these either of these modes of operation by a suitable choice of time-varying waveforms for the prescribed parameter, together with appropriate and well-known signal processing methods applied to the monitored parameters. However, these potential benefits may come at the cost of slower response time.


Referring to FIG. 63, an alternative embodiment of a tissue penetration sampling device is shown which incorporates disposable sampling module 590, a lancet driver 591, and an optional module cartridge 592 are shown. The optional module cartridge comprises a case body 593 having a storage cavity 594 for storing sampling modules 590. A cover to this cavity has been left out for clarity. The cartridge further comprises a chamber 595 for holding the lancet driver 591. The lancet driver has a preload adjustment knob 596, by which the trigger point of the lancet driver may be adjusted. This insures a reproducible tension on the surface of the skin for better control of the depth of penetration and blood yield. In one embodiment, the sampling module 590 is removably attached to the lancet driver 591, as shown, so that the sampling module 590 is disposable and the lancet driver 591 is reusable. In an alternative embodiment, the sampling module and lancet driver are contained within a single combined housing, and the combination sample acquisition module/lancet driver is disposable. The sampling module 590 includes a sampling site 597, preferably having a concave depression 598, or cradle, that can be ergonomically designed to conform to the shape of a user's finger or other anatomical feature (not shown).


The sampling site further includes an opening 599 located in the concave depression. The lancet driver 591 is used to fire a lancet contained within and guided by the sampling module 590 to create an incision on the user's finger when the finger is placed on the sampling site 597. In one embodiment, the sampling site forms a substantially airtight seal at the opening when the skin is firmly pressed against the sampling site; the sampling site may additionally have a soft, compressible material surrounding the opening to further limit contamination of the blood sample by ambient air. “Substantially airtight” in this context means that only a negligible amount of ambient air may leak past the seal under ordinary operating conditions, the substantially airtight seal allowing the blood to be collected seamlessly.


Referring to FIGS. 64 and 65, the lancet 600 is protected in the integrated housing 601 that provides a cradle 602 for positioning the user's finger or other body part, a sampling port 603 within the cradle 602, and a sample reservoir 603′ for collecting the resulting blood sample. The lancet 600 is a shaft with a distal end 604 sharpened to produce the incision with minimal pain. The lancet 600 further has an enlarged proximal end 605 opposite the distal end. Similar lancets are commonly known in the art.


Rather than being limited to a shaft having a sharp end, the lancet may have a variety of configurations known in the art, with suitable modifications being made to the system to accommodate such other lancet configurations, such configurations having a sharp instrument that exits the sampling port to create a wound from which a blood sample may be obtained.


In the figures, the lancet 600 is slidably disposed within a lancet guide 606 in the housing 601, and movement of the lancet 600 within the lancet guide 606 is closely controlled to reduce lateral motion of the lancet, thereby reducing the pain of the lance stick. The sample acquisition module also includes a return stop 613, which retains the lancet within the sample acquisition module. The sampling module has an attachment site 615 for attachment to the lancet driver.


The sampling module further includes a depth selector allowing the user to select one of several penetration depth settings. The depth selector is shown as a multi-position thumbwheel 607 having a graduated surface. By rotating the thumbwheel 607, the user selects which part of the graduated surface contacts the enlarged proximal end 605 of the lancet to limit the movement of the lancet 600 within the lancet guide 606.


The thumbwheel is maintained in the selected position by a retainer 608 having a protruding, rounded surface which engages at least one of several depressions 609 (e.g. dimples, grooves, or slots) in the thumbwheel 607. The depressions 609 are spatially aligned to correspond with the graduated slope of the thumbwheel 607, so that, when the thumbwheel 607 is turned, the depth setting is selected and maintained by the retainer 608 engaging the depression 609 corresponding to the particular depth setting selected.


In alternate embodiments, the retainer may be located on the depth selector and the depressions corresponding to the depth setting located on the housing such that retainer may functionally engage the depressions. Other similar arrangements for maintaining components in alignment are known in the art and may be used. In further alternate embodiments, the depth selector may take the form of a wedge having a graduated slope, which contacts the enlarged proximal end of the lancet, with the wedge being retained by a groove in the housing.


The sample reservoir 603′ includes an elongate, rounded chamber 610 within the housing 601 of the sample acquisition module. The chamber 610 has a flat or slightly spherical shape, with at least one side of the chamber 610 being formed by a smooth polymer, preferably absent of sharp corners. The sample reservoir 603′ also includes a sample input port 611 to the chamber 610, which is in fluid communication with the sampling port 603, and a vent 612 exiting the chamber.


A cover (not shown), preferably of clear material such as plastic, positions the lancet 600 and closes the chamber 603′, forming an opposing side of the chamber 603′. In embodiments where the cover is clear, the cover may serve as a testing means whereby the sample may be analyzed in the reservoir via optical sensing techniques operating through the cover. A clear cover will also aid in determining by inspection when the sample reservoir is full of the blood sample.



FIG. 66 shows a portion of the sampling module illustrating an alternate embodiment of the sample reservoir. The sample reservoir has a chamber 616 having a sample input port 617 joining the chamber 616 to a blood transport capillary channel 618; the chamber 616 also has a vent 619. The chamber has a first side 620 that has a flat or slightly spherical shape absent of sharp corners and is formed by a smooth polymer. An elastomeric diaphragm 621 is attached to the perimeter of the chamber 616 and preferably is capable of closely fitting to the first side of the chamber 620.


To control direction of blood flow, the sample reservoir is provided with a first check valve 622 located at the entrance 617 of the sample reservoir and a second check valve 623 leading to an exit channel 624 located at the vent 619. Alternately, a single check valve (at the location 622) may be present controlling both flow into the chamber 616 via the blood transport capillary channel 618 and flow out of the chamber 616 into an optional alternate exit channel 625. The sample reservoir has a duct 626 connecting to a source of variable pressure facilitating movement of the diaphragm 621.


When the diaphragm 621 is flexed away from the first side of the chamber 620 (low pressure supplied from the source via duct 626), the first check valve 622 is open and the second check valve 623 is closed, aspiration of the blood sample into the sample reservoir follows. When the diaphragm 621 is flexed in the direction of the first side of the chamber 620 (high pressure supplied from the source via duct 626) with the first check valve 622 closed and the second check valve 623 open, the blood is forced out of the chamber 616. The direction of movement and actuation speed of the diaphragm 621 can be controlled by the pressure source, and therefore the flow of the sample can be accelerated or decelerated. This feature allows not only reduced damage to the blood cells but also for the control of the speed by which the chamber 616 is filled.


While control of the diaphragm 621 via pneumatic means is described in this embodiment, mechanical means may alternately be used. Essentially, this micro diaphragm pump fulfills the aspiration, storage, and delivery functions. The diaphragm 621 may be used essentially as a pump to facilitate transfer of the blood to reach all areas required. Such required areas might be simple sample storage areas further downstream for assaying or for exposing the blood to a chemical sensor or other testing means. Delivery of the blood may be to sites within the sampling module or to sites outside the sampling module, i.e. a separate analysis device.


In an alternate embodiment, a chemical sensor or other testing means is located within the sampling module, and the blood is delivered to the chemical sensor or other testing means via a blood transfer channel in fluid communication with the sample reservoir. The components of the sampling module may be injection molded and the diaphragm may be fused or insertion molded as an integral component.



FIG. 67 depicts a portion of the disposable sampling module surrounding the sampling port 627, including a portion of the sampling site cradle surface 628. The housing of the sampling module includes a primary sample flow channel 629 that is a capillary channel connecting the sample input port to the sample reservoir. The primary sample flow channel 629 includes a primary channel lumenal surface 630 and a primary channel entrance 631, the primary channel entrance 631 opening into the sample input port 627. The sampling module may optionally include a supplemental sample flow channel 632 that is also a capillary channel having a supplemental channel lumenal surface 633 and a supplemental channel entrance 634, the supplemental channel entrance 634 opening into the sample input port 627.


The primary sample flow channel 629 has a greater cross-sectional area than the supplemental sample flow channel 632, preferably by at least a factor of two. Thus, the supplemental sample flow channel 632 draws fluid faster than the primary sample flow channel 629. When the first droplet of blood is received into the sample input port 627, the majority of this droplet is drawn through the supplemental sample flow channel 632. However, as the blood continues to flow from the incision into the sample input port 627, most of this blood is drawn through the primary sample flow channel 629, since the supplemental sample flow channel 632 is of limited capacity and is filled or mostly filled with the first blood droplet. This dual capillary channel configuration is particularly useful in testing where there is a concern with contamination of the sample, e.g. with debris from the lancet strike or (particularly in the case of blood gas testing) with air.


In order to improve blood droplet flow, some priming or wicking of the surface with blood is at times necessary to begin the capillary flow process. Portions of the surfaces of the sample input port 627 and the primary and supplemental (if present) sample flow channels 629, 632 are treated to render those surfaces hydrophilic. The surface modification may be achieved using mechanical, chemical, corona, or plasma treatment. Examples of such coatings and methods are marketed by AST Products (Billerica, Mass.) and Spire Corporation (Bedford, Mass.).


However, a complete blanket treatment of the surface could prove detrimental by causing blood to indiscriminately flow all over the surface and not preferentially through the capillary channel(s). This ultimately will result in losses of blood fluid. The particular surfaces which receive the treatment are selected to improve flow of blood from an incised finger on the sampling site cradle surface 628 through the sample input port 627 and at least one of the sample flow channels 629, 632 to the sample reservoir. Thus, the treatment process should be masked off and limited only to the selected surfaces. The masking process of selectively modifying the sampling surface from hydrophobic to hydrophilic may be done with mechanical masking techniques such as with metal shielding, deposited dielectric or conductive films, or electrical shielding means.


In some embodiments, the treated surfaces are limited to one or more of the following: the surface of the sampling port which lies between the sampling site cradle surface and the primary and supplemental sample flow channel, the surface immediately adjacent to the entrances to the primary and/or supplemental sample flow channels 631, 634 (both within the sample input port and within the sample flow channel), and the lumenal surface of the primary and/or supplemental sample flow channels 630, 633.


Upon exiting the incision blood preferentially moves through the sample input port 627 into the supplementary sample flow channel 632 (if present) and into the primary sample flow channel 629 to the sample reservoir, resulting in efficient capture of the blood. Alternatively, the substrate material may be selected to be hydrophilic or hydrophobic, and a portion of the surface of the substrate material may be treated for the opposite characteristic.


In an embodiment, FIG. 67 a membrane 635 at the base of the sample input port 627 is positioned between the retracted sharpened distal end of the lancet 636 and the entrance to the sample flow channels 631, 634. The membrane 635 facilitates the blood sample flow through the sample flow channels 629, 632 by restricting the blood from flowing into the area 636 surrounding the distal end of the lancet 637. The blood thus flows preferentially into the sample reservoir. In an embodiment, the membrane 635 is treated to have a hydrophobic characteristic. In another embodiment, the membrane 635 is made of polymer-based film 638 that has been coated with a silicone-based gel 639.


For example, the membrane structure may comprise a polymer-based film 638 composed of polyethylene terephthalate, such as the film sold under the trademark MYLAR. The membrane structure may further comprise a thin coating of a silicone-based gel 639 such as the gel sold under the trademark SYLGARD on at least one surface of the film. The usefulness of such a film is its ability to reseal after the lancet has penetrated it without physically affecting the lancet's cutting tip and edges. The MYLAR film provides structural stability while the thin SYLGARD silicone laminate is flexible enough to retain its form and close over the hole made in the MYLAR film. Other similar materials fulfilling the structural stability and flexibility roles may be used in the manufacture of the membrane in this embodiment.


The membrane 635 operates to allow the sharpened distal end of the lancet 637 to pierce the membrane as the sharpened distal end of the lancet 637 travels into and through the sample input port 627. In an embodiment, the silicone-based gel 639 of the membrane 635 automatically seals the cut caused by the piercing lancet. Therefore, after an incision is made on a finger of a user, the blood from the incision is prevented from flowing through the membrane 635, which aids the blood to travel through the primary sample flow channel 629 to accumulate within the sample reservoir. Thus the film prevents any blood from flowing into the lancet device assembly, and blood contamination and loss into the lancet device mechanism cavity are prevented. Even without the resealing layer 639, the hydrophobic membrane 635 deters the flow of blood across the membrane 635, resulting in improved flow through the primary sample flow channel 629 and reduced or eliminated flow through the pierced membrane 635.



FIGS. 68-70 illustrate one implementation of a lancet driver 640 at three different points during the use of the lancet driver. In this description of the lancet driver, proximal indicates a position relatively close to the site of attachment of the sampling module; conversely, distal indicates a position relatively far from the site of attachment of the sampling module. The lancet driver has a driver handle body 641 defining a cylindrical well 642 within which is a preload spring 643. Proximal to the preload spring 643 is a driver sleeve 644, which closely fits within and is slidably disposed within the well 642. The driver sleeve 644 defines a cylindrical driver chamber 645 within which is an actuator spring 646. Proximal to the actuator spring 646 is a plunger sleeve 647, which closely fits within and is slidably disposed within the driver sleeve 644.


The driver handle body 641 has a distal end 648 defining a threaded passage 649 into which a preload screw 650 fits. The preload screw defines a counterbore 651. The preload screw 650 has a distal end 652 attached to a preload adjustment knob 653 and a proximal end 654 defining an aperture 655. The driver sleeve 644 has a distal end 656 attached to a catch fitting 657. The catch fitting 657 defines a catch hole 658. The driver sleeve 644 has a proximal end 659 with a sloped ring feature 660 circling the interior surface of the driver sleeve's proximal end 659.


The lancet driver includes a plunger stem 660 having a proximal end 661 and a distal end 662. At its distal end 662, an enlarged plunger head 663 terminates the plunger stem 660. At its proximal end 661, the plunger stem 660 is fixed to the plunger tip 667 by adhesively bonding, welding, crimping, or threading into a hole 665 in the plunger tip 667. A plunger hook 665 is located on the plunger stem 660 between the plunger head 663 and the plunger tip 667. The plunger head 663 is slidably disposed within the counterbore 651 defined by the preload screw 650. The plunger stem 660 extends from the plunger head 663, through the aperture 655 defined by the proximal end 654 of the preload screw, thence through the hole 658 in the catch fitting 657, to the joint 664 in the plunger tip 667. For assembly purposes, the plunger base joint 664 may be incorporated into the plunger sleeve 647, and the plunger stem 660 attached to the plunger base 664 by crimping, swaging, gluing, welding, or some other means. Note that the lancet driver 640 could be replaced with any of the controlled electromagnetic drivers discussed above.


The operation of the tissue penetration sampling device may be described as follows, with reference to FIGS. 63-70. In operation, a fresh sampling module 590 is removed from the storage cavity 594 and adjusted for the desired depth setting using the multi-position thumbwheel 607. The sampling module 590 is then placed onto the end of the lancet driver 591. The preload setting may be checked, but will not change from cycle to cycle once the preferred setting is found; if necessary, the preload setting may be adjusted using the preload adjustment knob 596.


The combined sampling module and lancet driver assembly is then pressed against the user's finger (or other selected anatomical feature) in a smooth motion until the preset trigger point is reached. The trigger point corresponds to the amount of preload force that needs to be overcome to actuate the driver to drive the lancet towards the skin. The preload screw allows the preload setting to be adjusted by the user such that a consistent, preset (by the user) amount of preload force is applied to the sampling site 597 each time a lancing is performed.


When the motion to press the assembly against the user's finger is begun (see FIG. 68), the plunger hook 665 engages catch fitting 657, holding the actuator spring 646 in a cocked position while the force against the finger builds as the driver sleeve 644 continues to compress the preload spring 643. Eventually (see FIG. 69) the sloped back of the plunger hook 665 slides into the hole 655 in the proximal end of the preload screw 654 and disengages from the catch fitting 657. The plunger sleeve 647 is free to move in a proximal direction once the plunger hook 665 releases, and the plunger sleeve 647 is accelerated by the actuator spring 646 until the plunger tip 667 strikes the enlarged proximal end of the lancet 212.


Upon striking the enlarged proximal end of the lancet 605, the plunger tip 667 of the actuated lancet driver reversibly engages the enlarged proximal end of the lancet 605. This may be accomplished by mechanical means, e.g. a fitting attached to the plunger tip 667 that detachably engages a complementary fitting on the enlarged proximal end of the lancet 605, or the enlarged proximal end of the lancet 605 may be coated with an adhesive that adheres to the plunger tip 667 of the actuated lancet driver. Upon being engaged by the plunger tip 667, the lancet 600 slides within the lancet guide 606 with the sharpened distal end of the lancet 604 emerging from the housing 601 through the sampling port 603 to create the incision in the user's finger.


At approximately the point where the plunger tip 667 contacts the enlarged proximal end of the lancet 605, the actuator spring 646 is at its relaxed position, and the plunger tip 667 is traveling at its maximum velocity. During the extension stroke, the actuator spring 646 is being extended and is slowing the plunger tip 667 and lancet 600. The end of stroke occurs (see FIG. 70) when the enlarged proximal end of the lancet 605 strikes the multi-position thumbwheel 607.


The direction of movement of the lancet 600 is then reversed and the extended actuator spring then quickly retracts the sharpened distal end of the lancet 604 back through the sampling port 603. At the end of the return stroke, the lancet 600 is stripped from the plunger tip 667 by the return stop 613. The adhesive adheres to the return stop 613 retaining the lancet in a safe position.


As blood seeps from the wound, it fills the sample input port 603 and is drawn by capillary action into the sample reservoir 603′. In this embodiment, there is no reduced pressure or vacuum at the wound, i.e. the wound is at ambient air pressure, although embodiments which draw the blood sample by suction, e.g. supplied by a syringe or pump, may be used. The vent 612 allows the capillary action to proceed until the entire chamber is filled, and provides a transfer port for analysis of the blood by other instrumentation. The finger is held against the sample acquisition module until a complete sample is observed in the sample reservoir.


As the sampling module 600 is removed from the lancet driver 591, a latch 614 that is part of the return stop 613 structure engages a sloped ring feature 660 inside the lancet driver 591. As the lancet driver 591 is removed from the sampling module 600, the latch forces the return stop 613 to rotate toward the lancet 600, bending it to lock it in a safe position, and preventing reuse.


As the sampling module 600 is removed from the lancet driver 591, the driver sleeve 644 is forced to slide in the driver handle body 641 by energy stored in the preload spring 643. The driver sleeve 644, plunger sleeve 647, and actuator spring 646 move outward together until the plunger head 663 on the plunger stem 660 contacts the bottom of the counterbore 651 at the proximal end of the preload screw 654. The preload spring 643 continues to move the driver sleeve 644 outward compressing the actuator spring 646 until the plunger hook 665 passes through the hole 658 in the catch fitting 657. Eventually the two springs reach equilibrium and the plunger sleeve 647 comes to rest in a cocked position.


After the sampling module 600 is removed from the lancet driver 591, it may be placed in a separate analysis device to obtain blood chemistry readings. In a preferred embodiment, the integrated housing 601 or sample reservoir 603′ of the sampling module 600 contains at least one biosensor, which is powered by and/or read by the separate analysis device. In another embodiment, the analysis device performs an optical analysis of the blood sample directly through the clear plastic cover of the sampling module. Alternatively, the blood sample may be transferred from the sampling module into an analysis device for distribution to various analysis processes.


Alternate embodiments of the invention offer improved success rates for sampling, which reduces the needless sacrifice of a sample storage reservoir or an analysis module due to inadequate volume fill. Alternate embodiments allow automatic verification that sufficient blood has been collected before signaling the user (e.g. by a signal light or an audible beep) that it is okay to remove the skin from the sampling site. In such alternate embodiments, one or more additional lancet(s) (denoted backup lancets) and/or lancet driver(s) (denoted backup lancet drivers) and/or sample reservoir(s) (denoted backup sample reservoirs) are present with the “primary” sampling module.


In one such preferred embodiment, following detection of inadequate blood sample volume (e.g., by light or electronic methods), a backup sampling cycle is initiated automatically. The “backup sampling cycle” includes disconnecting the primary sample reservoir via a simple valving system, bringing the backup components online, lancing of the skin, collection of the blood, and movement of the blood to the backup sample reservoir.


Blood flows into the backup sample reservoir until the required volume is obtained. The cycle repeats itself, if necessary, until the correct volume is obtained. Only then is the sample reservoir made available as a source of sampled blood for use in measurements or for other applications. The series of reservoirs and/or lancets and/or lancet drivers may easily be manufactured in the same housing and be transparent to the user.


In one embodiment, up to three sample reservoirs (the primary plus two backup) are present in a single sample acquisition module, each connected via a capillary channel/valving system to one or more sampling ports. Another embodiment has four sample reservoirs (the primary plus three backup) present in a single sample acquisition module, each connected via a capillary channel/valving system to one or more sampling ports. With three or four sample reservoirs, at least an 80% sampling success rate can be achieved for some embodiments.


Another embodiment includes a miniaturized version of the tissue penetration sampling device. Several of the miniature lancets may be located in a single sampling site, with corresponding sample flow channels to transfer blood to one or more reservoirs. The sample flow channels may optionally have valves for controlling flow of blood. The device may also include one or more sensors, such as the thermal sensors discussed above, for detecting the presence of blood, e.g. to determine if a sufficient quantity of blood has been obtained. In such an embodiment, the disposable sampling module, the lancet driver, and the optional module cartridge will have dimensions no larger than about 150 mm long, 60 mm wide, and 25 mm thick.


In other embodiments, the size of the tissue penetration sampling device including the disposable sampling module, the lancet driver, and the optional cartridge will have dimensions no larger than about 100 mm long, about 50 mm wide, and about 20 mm thick, and in still other embodiments no larger than about 70 mm long, about 30 mm wide, and about 10 mm thick. The size of the tissue penetration sampling device including the disposable sampling module, the lancet driver, and the optional cartridge will generally be at least about 10 mm long, about 5 mm wide, and about 2 mm thick.


In another miniature embodiment, the dimensions of the lancet driver without the cartridge or sampling module are no larger than about 80 mm long, 10 mm wide, and 10 mm thick, or specifically no larger than about 50 mm long, 7 mm wide, and 7 mm thick, or even more specifically no larger than about 15 mm long, 5 mm wide, and 3 mm thick; dimensions of the lancet driver without the cartridge or sampling module are generally at least about 1 mm long, 0.1 mm wide, and 0.1 mm thick, or specifically at least about 2 mm long, 0.2 mm wide, and 0.2 mm thick, or more specifically at least about 4 mm long, 0.4 mm wide, and 0.4 mm thick.


In yet another miniature embodiment, dimensions of the miniature sampling module without the lancet driver or cartridge are no larger than about 15 mm long, about 10 mm wide, and about 10 mm thick, or no larger than about 10 mm long, about 7 mm wide, and about 7 mm thick, or no larger than about 5 mm long, about 3 mm wide, and about 2 mm thick; dimensions of the miniature sampling module without the lancet driver or cartridge are generally at least about 1 mm long, 0.1 mm wide, and 0.1 mm thick, specifically at least about 2 mm long, 0.2 mm wide, and 0.2 mm thick, or more specifically at least about 4 mm long, 0.4 mm wide, and 0.4 mm thick.


In another embodiment, the miniaturized sampling module and the lancet driver form a single unit having a shared housing, and the combined sample acquisition module/lancet driver unit is disposable. Such a combined unit is no larger than about 80 mm long, about 30 mm wide, and about 10 mm thick, specifically no larger than about 50 mm long, about 20 mm wide, and about 5 mm thick, more specifically, no larger than about 20 mm long, about 5 mm wide, and about 3 mm thick; the combined unit is generally at least about 2 mm long, about 0.3 mm wide, and about 0.2 mm thick, specifically at least about 4 mm long, 0.6 mm wide, and 0.4 mm thick, more specifically, at least about 8 mm long, 1 mm wide, and 0.8 mm thick.


Referring to FIG. 71, another embodiment of a tissue penetration sampling device is shown, incorporating a disposable sampling module 608 cartridge and analyzer device 669 is shown. The analyzer device 669 includes a deck 670 having a lid 671 attached to the deck by hinges along the rear edge of the system 672. A readout display 673 on the lid 671 functions to give the user information about the status of the analyzer device 669 and/or the sampling module cartridge 668, or to give readout of a blood test. The analyzer device 669 has several function buttons 674 for controlling function of the analyzer device 669 or for inputting information into the reader device 669. Alternatively, the reader device may have a touch-sensitive screen, an optical scanner, or other input means known in the art.


An analyzer device with an optical scanner may be particularly useful in a clinical setting, where patient information may be recorded using scan codes on patients' wristbands or files. The analyzer reader device may have a memory, enabling the analyzer device to store results of many recent tests. The analyzer device may also have a clock and calendar function, enabling the results of tests stored in the memory to be time and date-stamped. A computer interface 675 enables records in memory to be exported to a computer. The analyzer device 669 has a chamber located between the deck 670 and the lid 671, which closely accommodates a sampling module cartridge 668. Raising the lid 671, allowing a sampling module cartridge 668 to be inserted or removed, accesses the chamber.



FIG. 72 is an illustration showing some of the features of an embodiment of a sampling module cartridge. The sampling module cartridge 668 has a housing having an orientation sensitive contact interface for mating with a complementary surface on the analyzer device. The contact interface functions to align the sampling module cartridge with the analyzer device, and also allows the analyzer device to rotate the sampling module cartridge in preparation for a new sampling event. The contact interface may take the form of cogs or grooves formed in the housing, which mate with complementary cogs, or grooves in the chamber of the analyzer device.


The sampling module cartridge has a plurality of sampling sites 678 on the housing, which are shown as slightly concave depressions near the perimeter of the sampling module cartridge 668. Each sampling site defines an opening 679 contiguous with a sample input port entering the sampling module. In an alternate embodiment, the sampling sites and sample input ports are located on the edge of the sampling module cartridge. Optical windows 680 allow transmission of light into the sampling module cartridge for the purpose of optically reading test results. Alternatively, sensor connection points allow transmission of test results to the analyzer device via electrical contact. Access ports 681, if present, allow transmission of force or pressure into the sampling module cartridge from the analyzer device. The access ports may be useful in conjunction with running a calibration test or combining reagents with sampled blood or other bodily fluids.


The described features are arranged around the sampling module cartridge, and the sampling module cartridge is radially partitioned into many sampling modules, each sampling module having the components necessary to perform a single blood sampling and testing event. A plurality of sampling modules are present on a sampling module cartridge, generally at least ten sampling modules are present on a single disposable sampling module cartridge; at least about 20, or more on some embodiments, and at least about 34 sampling modules are present on one embodiment, allowing the sampling module cartridge to be maintained in the analyzer device for about a week before replacing with a new sampling module cartridge (assuming five sampling and testing events per day for seven days). With increasing miniaturization, up to about 100, or more preferably up to about 150, sampling modules may be included on a single sampling module cartridge, allowing up to a month between replacements with new sampling module cartridges. It may be necessary for sampling sites to be located in several concentric rings around the sampling module cartridge or otherwise packed onto the housing surface to allow the higher number of sampling modules on a single sampling module cartridge.


In other embodiments, the sampling module cartridge may be any other shape which may conveniently be inserted into a analyzer device and which are designed to contain multiple sampling modules, e.g. a square, rectangular, oval, or polygonal shape. Each sampling module is miniaturized, being generally less than about 6.0 cm long by about 1.0 cm wide by about 1.0 cm thick, so that thirty five more or less wedge-shaped sampling modules can fit around a disk having a radius of about 6.0 cm. In some embodiments, the sampling modules can be much smaller, e.g. less than about 3.0 cm long by about 0.5 cm wide by about 0.5 cm thick.



FIG. 73 depicts, in a highly schematic way, a single sampling module, positioned within the analyzer device. Of course, it will occur to the person of ordinary skill in the art that the various recited components may be physically arranged in various configurations to yield a functional system. FIG. 73 depicts some components, which might only be present in alternate embodiments and are not necessarily all present in any single embodiment. The sampling module has a sample input port 682, which is contiguous with an opening 683 defined by a sampling site 684 on the cartridge housing 685. A lancet 686 having a lancet tip 687 adjacent to the sample input port 682 is operably maintained within the housing such that the lancet 686 can move to extend the lancet tip 687 through the sample input port 682 to outside of the sampling module cartridge.


The lancet 686 also has a lancet head 688 opposite the lancet tip. The lancet 686 driven to move by a lancet driver 689, which is schematically depicted as a coil around the lancet 686. The lancet driver 689 optionally is included in the sampling module cartridge as pictured or alternatively is external to the sampling module cartridge. The sampling module may further include a driver port 690 defined by the housing adjacent to the lancet head 688—the driver port 690 allows an external lancet driver 691 access to the lancet 686.


In embodiments where the lancet driver 689 is in the sampling module cartridge, it may be necessary to have a driver connection point 694 upon the housing accessible to the analyzer device. The driver connection point 694 may be a means of triggering the lancet driver 689 or of supplying motive force to the lancet driver 689, e.g. an electrical current to an electromechanical lancet driver. Note that any of the drivers discussed above, including controllable drivers, electromechanical drivers, etc., can be substituted for the lancet driver 689 shown.


In one embodiment a pierceable membrane 692 is present between the lancet tip 687 and the sample input port 682, sealing the lancet 686 from any outside contact prior to use. A second membrane 693 may be present adjacent to the lancet head 688 sealing the driver port 690. The pierceable membrane 692 and the second membrane 693 function to isolate the lancet 686 within the lancet chamber to maintain sterility of the lancet 686 prior to use. During use the lancet tip 687 and the external lancet driver 691 pierce the pierceable membrane 692 and the second membrane 693, if present respectively.


A sample flow channel 695 leads from the sample input port 682 to an analytical region 696. The analytical region 696 is associated with a sample sensor capable of being read by the analyzer device. If the sample sensor is optical in nature, the sample sensor may include optically transparent windows 697 in the housing above and below the analytical region 696, allowing a light source in the analyzer device to pass light 698 through the analytical region. An optical sensor 698′, e.g. a CMOS array, is present in the analyzer device for sensing the light 699 that has passed through the analytical region 696 and generating a signal to be analyzed by the analyzer device.


In a separate embodiment, only one optically transparent window is present, and the opposing side of the analytical region is silvered or otherwise reflectively coated to reflect light back through the analytical region and out the window to be analyzed by the analyzer device. In an alternate embodiment, the sensor is electrochemical 700, e.g. an enzyme electrode, and includes a means of transmitting an electric current from the sampling module cartridge to the analyzer device, e.g. an electrical contact 701, or plurality of electrical contacts 701, on the housing accessible to the analyzer device.


In one embodiment, the pierceable membrane 692 may be made of polymer-based film that has been coated with a silicone-based gel. For example, the membrane structure may comprise a polymer-based film composed of polyethylene terephthalate, such as the film sold under the trademark MYLAR®. The membrane structure may further comprise a thin coating of a silicone-based gel such as the gel sold under the trademark SYLGARD® on at least one surface of the film.


The usefulness of such a film is its ability to reseal after the lancet tip has penetrated it without physically affecting the lancet's cutting tip and edges. The MYLAR® film provides structural stability while the thin SYLGARD® silicone laminate is flexible enough to retain its form and close over the hole made in the MYLAR® film. Other similar materials fulfilling the structural stability and flexibility roles may be used in the manufacture of the pierceable membrane in this embodiment.


The pierceable membrane 692 operates to allow the lancet tip 687 to pierce the pierceable membrane 692 as the lancet tip 687 travels into and through the sampling port 682. In the described embodiment, the silicone-based gel of the membrane 692 automatically seals the cut caused by the lancet tip 687. Therefore, after an incision is made on a finger of a user and the lancet tip 687 is retracted back through the pierceable membrane 692, the blood from the incision is prevented from flowing through the pierceable membrane 692, which aids the blood to travel through the sample flow channel 695 to accumulate within the analytical region 696.


Thus the pierceable membrane 692 prevents blood from flowing into the lancet device assembly, and blood contamination and loss into the lancet device mechanism cavity are prevented. In yet another embodiment, used sample input ports are automatically sealed off before going to the next sample acquisition cycle by a simple button mechanism. A similar mechanism seals off a sample input port should sampling be unsuccessful.


In an alternate embodiment, a calibrant supply reservoir 702 is also present in each sampling module. The calibrant supply reservoir 702 is filled with a calibrant solution and is in fluid communication with a calibration chamber 703. The calibration chamber 703 provides a source of a known signal from the sampling module cartridge to be used to validate and quantify the test conducted in the analytical region 696. As such, the configuration of the calibration chamber 703 closely resembles the analytical region 696.


During use, the calibrant solution is forced from the calibrant supply reservoir 702 into the calibration chamber 703. The figure depicts a stylized plunger 704 above the calibrant supply reservoir 702 ready to squeeze the calibrant supply reservoir 702. In practice, a variety of methods of transporting small quantities of fluid are known in the art and can be implemented on the sampling module cartridge. The calibration chamber 703 is associated with a calibrant testing means.



FIG. 73 shows two alternate calibrant testing means—optical windows 697 and an electrochemical sensor 676. In cases where the sampling module is designed to perform several different tests on the blood, both optical and electrochemical testing means may be present. The optical windows 697 allow passage of light 677 from the analyzer device through the calibration chamber 703, whereupon the light 703′ leaving the calibration chamber 703 passes onto an optical sensor 698′ to result in a signal in the analyzer device.


The electrochemical sensor 676 is capable of generating a signal that is communicated to the analyzer device via, e.g. an electrical contact 704′, which is accessible to a contact probe 702′ on the analyzer device that can be extended to contact the electrical contact 704′. The calibrant solution may be any solution, which, in combination with the calibrant testing means, will provide a suitable signal, which will serve as calibration measurement to the analyzer device. Suitable calibrant solutions are known in the art, e.g. glucose solutions of known concentration. The calibration measurement is used to adjust the results obtained from sample sensor from the analytical region 696.


To maintain small size in some sampling module cartridge embodiments, allowing small quantities of sampled blood to be sufficient, each component of the sampling module must be small, particularly the sample flow channel and the analytical region. The sample flow channel can be less than about 0.5 mm in diameter, specifically less than about 0.3 mm in diameter, more specifically less than about 0.2 mm in diameter, and even more specifically less than about 0.1 mm in diameter.


The sample flow channel may generally be at least about 50 micrometers in diameter. The dimensions of the analytical region may be less than about 1 mm by about 1 mm by about 1 mm, specifically less than about 0.6 mm by about 0.6 mm by about 0.4 mm, more specifically less than about 0.4 mm by 0.4 mm by 0.2 mm, and even more specifically less than about 0.2 mm by about 0.2 mm by about 0.1 mm. The analytical region can generally be at least about 100 micrometers by 100 micrometers by 50 micrometers.


The sampling module cartridge is able to return a valid testing result with less than about 5 microliters of blood taken from the skin of a patient, specifically less than about 1 microliter, more specifically less than about 0.4 microliters, and even more specifically less than about 0.2 microliters. Generally, at least 0.05 microliters of blood is drawn for a sample.


The cartridge housing may be made in a plurality of distinct pieces, which are then assembled to provide the completed housing. The distinct pieces may be manufactured from a wide range of substrate materials. Suitable materials for forming the described apparatus include, but are not limited to, polymeric materials, ceramics (including aluminum oxide and the like), glass, metals, composites, and laminates thereof. Polymeric materials are particularly preferred herein and will typically be organic polymers that are homopolymers or copolymers, naturally occurring or synthetic, crosslinked or uncrosslinked.


It is contemplated that the various components and devices described herein, such as sampling module cartridges, sampling modules, housings, etc., may be made from a variety of materials, including materials such as the following: polycarbonates; polyesters, including poly (ethylene terephthalate) and poly(butylene terephthalate); polyamides, (such as nylons); polyethers, including polyformaldehyde and poly (phenylene sulfide); polyimides, such as that manufactured under the trademarks KAPTON (DuPont, Wilmington, Del.) and UPILEX (Ube Industries, Ltd., Japan); polyolefin compounds, including ABS polymers, Kel-F copolymers, poly(methyl methacrylate), poly(styrene-butadiene) copolymers, poly(tetrafluoroethylene), poly(ethylenevinyl acetate) copolymers, poly(N-vinylcarbazole) and polystyrene.


The various components and devices described herein may also be fabricated from a “composite,” i.e., a composition comprised of unlike materials. The composite may be a block composite, e.g., an A-B-A block composite, an A-B—C block composite, or the like. Alternatively, the composite may be a heterogeneous combination of materials, i.e., in which the materials are distinct from separate phases, or a homogeneous combination of unlike materials. A laminate composite with several different bonded layers of identical or different materials can also be used.


Other preferred composite substrates include polymer laminates, polymer-metal laminates, e.g., polymer coated with copper, a ceramic-in-metal or a polymer-in-metal composite. One composite material is a polyimide laminate formed from a first layer of polyimide such as KAPTON polyimide, available from DuPont (Wilmington, Del.), that has been co-extruded with a second, thin layer of a thermal adhesive form of polyimide known as KJ®, also available from DuPont (Wilmington, Del.).


Any suitable fabrication method for the various components and devices described herein can be used, including, but not limited to, molding and casting techniques, embossing methods, surface machining techniques, bulk machining techniques, and stamping methods. Further, injection-molding techniques well known in the art may be useful in shaping the materials used to produce sample modules and other components.


For some embodiments, the first time a new sampling module cartridge 668 is used, the user removes any outer packaging material from the sampling module cartridge 668 and opens the lid 671 of the analyzer device 669, exposing the chamber. The sampling module cartridge 668 is slipped into the chamber and the lid 671 closed. The patient's skin is positioned upon the sampling site 678 and the integrated process of lancing the skin, collecting the blood sample, and testing the blood sample is initiated, e.g. by pressing a function button 674 to cause the lancet driver to be triggered. The patient's skin is maintained in position upon the sampling site 678, adjacent the sample input port 682, until an adequate volume of blood has been collected, whereupon the system may emit a signal (e.g. an audible beep) that the patient's skin may be lifted from the sampling site 678.


When the testing of the sample is complete, the analyzer device 669 automatically reads the results from the sampling module cartridge 668 and reports the results on the readout display 673. The analyzer device 669 may also store the result in memory for later downloading to a computer system. The sampling module cartridge 668 may then automatically be advanced to bring the next sampling module inline for the next use. Each successive time the system is used (optionally until the sampling module cartridge 668 is used up), the patient's skin may be placed upon the sampling site 678 of the (already installed) sampling module cartridge 668, thus simplifying the process of blood sampling and testing.


A method of providing more convenient blood sampling, wherein a series of blood samples may be collected and tested using a single disposable sampling module cartridge which is designed to couple to an analyzer device is described. Embodiments of the sampling module cartridge include a plurality of sampling modules. Each sampling module can be adapted to perform a single blood sampling cycle and is functionally arranged within the sampling module cartridge to allow a new sampling module to be brought online after a blood sampling cycle is completed.


Each blood sampling cycle may include lancing of a patient's skin, collection of a blood sample, and testing of the blood sample. The blood sampling cycle may also include reading of information about the blood sample by the analyzer device, display and/or storage of test results by the analyzer device, and/or automatically advancing the sampling module cartridge to bring a new sampling module online and ready for the next blood sampling cycle to begin.


A method embodiment starts with coupling of the sampling module cartridge and analyzer device and then initiating a blood sampling cycle. Upon completion of the blood sampling cycle, the sampling module cartridge is advanced to bring a fresh, unused sampling module online, ready to perform another blood sampling cycle. Generally, at least ten sampling modules are present, allowing the sampling module cartridge to be advanced nine times after the initial blood sampling cycle.


In some embodiments, more sampling modules are present and the sampling module cartridge may be advanced about 19 times, and about 34 times in some embodiments, allowing about 19 or about 34 blood sampling cycles, respectively, after the initial blood sampling cycle. After a series of blood sampling cycles has been performed and substantially all (i.e. more than about 80%) of the sampling modules have been used, the sampling module cartridge is decoupled from the analyzer device and discarded, leaving the analyzer device ready to be coupled with a new sampling module cartridge.


Referring to FIGS. 74-76, a tissue penetration sampling device 180 is shown with the controllable driver 179 of FIG. 20 coupled to a sampling module cartridge 705 and disposed within a driver housing 706. A ratchet drive mechanism 707 is secured to the driver housing 706, coupled to the sampling module cartridge 705 and configured to advance a sampling module belt 708 within the sampling module cartridge 705 so as to allow sequential use of each sampling module 709 in the sampling module belt 708. The ratchet drive mechanism 707 has a drive wheel 711 configured to engage the sampling modules 709 of the sampling module belt 708. The drive wheel 711 is coupled to an actuation lever 712 that advances the drive wheel 711 in increments of the width of a single sampling module 709. A T-slot drive coupler 713 is secured to the elongated coupler shaft 184.


A sampling module 709 is loaded and ready for use with the drive head 198 of the lancet 183 of the sampling module 709 loaded in the T-slot 714 of the drive coupler 713. A sampling site 715 is disposed at the distal end 716 of the sampling module 709 disposed about a lancet exit port 717. The distal end 716 of the sampling module 709 is exposed in a module window 718, which is an opening in a cartridge cover 721 of the sampling module cartridge 705. This allows the distal end 716 of the sampling module 709 loaded for use to be exposed to avoid contamination of the cartridge cover 721 with blood from the lancing process.


A reader module 722 is disposed over a distal portion of the sampling module 709 that is loaded in the drive coupler 713 for use and has two contact brushes 724 that are configured to align and make electrical contact with sensor contacts 725 of the sampling module 709 as shown in FIG. 77. With electrical contact between the sensor contacts 725 and contact brushes 724, the processor 193 of the controllable driver 179 can read a signal from an analytical region 726 of the sampling module 709 after a lancing cycle is complete and a blood sample enters the analytical region 726 of the sampling module 709. The contact brushes 724 can have any suitable configuration that will allow the sampling module belt 708 to pass laterally beneath the contact brushes 724 and reliably make electrical contact with the sampling module 709 loaded in the drive coupler 713 and ready for use. A spring loaded conductive ball bearing is one example of a contact brush 724 that could be used. A resilient conductive strip shaped to press against the inside surface of the flexible polymer sheet 727 along the sensor contact region 728 of the sampling module 709 is another embodiment of a contact brush 724.


The sampling module cartridge 705 has a supply canister 729 and a receptacle canister 730. The unused sampling modules of the sampling module belt 708 are disposed within the supply canister 729 and the sampling modules of the sampling module belt 708 that have been used are advanced serially after use into the receptacle canister 730.



FIG. 77 is a perspective view of a section of the sampling module belt 708 shown in the sampling module cartridge 705 in FIG. 74. The sampling module belt 708 has a plurality of sampling modules 709 connected in series by a sheet of flexible polymer 727. The sampling module belt 708 shown in FIG. 77 is formed from a plurality of sampling module body portions 731 that are disposed laterally adjacent each other and connected and sealed by a single sheet of flexible polymer 727. The flexible polymer sheet 727 can optionally have sensor contacts 725, flexible electrical conductors 732, sample sensors 733 or any combination of these elements formed on the inside surface 734 of the flexible polymer sheet 727. These electrical, optical or chemical elements can be formed by a variety of methods including vapor deposition and the like.


The proximal portion 735 of the flexible polymer sheet 727 has been folded over on itself in order to expose the sensor contacts 725 to the outside surface of the sampling module 709. This makes electrical contact between the contact brushes 724 of the reader module 722 and the sensor contacts 725 easier to establish as the sampling modules 709 are advanced and loaded into position with the drive coupler 713 of the controllable driver 179 ready for use. The flexible polymer sheet 727 can be secured to the sampling module body portion 731 by adhesive bonding, solvent bonding, ultrasonic thermal bonding or any other suitable method.



FIG. 78 shows a perspective view of a single sampling module 709 of the sampling module belt 708 of FIG. 77 during the assembly phase of the sampling module 709. The proximal portion 735 of the flexible polymer sheet 727 is being folded over on itself as shown in order to expose the sensor contacts 725 on the inside surface of the flexible polymer sheet 727. FIG. 79 is a bottom view of a section of the flexible polymer sheet 727 of the sampling module 709 of FIG. 78 illustrating the sensor contacts 725, flexible conductors 732 and sample sensors 733 deposited on the bottom surface of the flexible polymer sheet 727.


A lancet 183 is shown disposed within the lancet channel 736 of the sampling module 709 of FIG. 78 as well as within the lancet channels 736 of the sampling modules 709 of the sampling module belt 708 of FIG. 77. The lancet 183 has a tip 196 and a shaft portion 201 and a drive head 198. The shaft portion 201 of the lancet slides within the lancet channel 736 of the sampling module 709 and the drive head 198 of the lancet 183 has clearance to move in a proximal and distal direction within the drive head slot 737 of the sampling module 709. Disposed adjacent the drive head slot 737 and at least partially forming the drive head slot are a first protective strut 737′ and a second protective strut 737″ that are elongated and extend substantially parallel to the lancet 183.


In one lancet 183 embodiment, the drive head 198 of the lancet 183 can have a width of about 0.9 to about 1.1 mm. The thickness of the drive head 198 of the lancet 183 can be about 0.4 to about 0.6 mm. The drive head slot 714 of the sampling module 709 should have a width that allows the drive head 198 to move freely within the drive head slot 714. The shaft portion 201 of the lancet 183 can have a transverse dimension of about 50 μm to about 1000 μm. Typically, the shaft portion 201 of the lancet 183 has a round transverse cross section, however, other configurations are contemplated.


The sampling module body portions 731 and the sheet of flexible polymer 727 can both be made of polymethylmethacrylate (PMMA), or any other suitable polymer, such as those discussed above. The dimensions of a typical sampling module body portion 731 can be about 14 to about 18 mm in length, about 4 to about 5 mm in width, and about 1.5 to about 2.5 mm in thickness. In other embodiments, the length of the sample module body portion can be about 0.5 to about 2.0 inch and the transverse dimension can be about 0.1 to about 0.5 inch. The thickness of the flexible polymer sheet 727 can be about 100 to about 150 microns. The distance between adjacent sampling modules 709 in the sampling module belt 708 can vary from about 0.1 mm to about 0.3 mm, and in some embodiments, from about 0.2 to about 0.6.



FIGS. 80 and 81 show a perspective view of the body portion 731 of the sampling module 709 of FIG. 77 without the flexible polymer cover sheet 727 or lancet 183 shown for purposes of illustration. FIG. 81 is an enlarged view of a portion of the body portion 731 of the sampling module 709 of FIG. 80 illustrating the sampling site 715, sample input cavity 715′, sample input port 741, sample flow channel 742, analytical region 743, control chamber 744, vent 762, lancet channel 736, lancet channel stopping structures 747 and 748 and lancet guides 749-751 of the sampling module 709.


The lancet channel 736 has a proximal end 752 and a distal end 753 and includes a series of lancet bearing guide portions 749-751 and sample flow stopping structures 747-748. The lancet guides 749-751 may be configured to fit closely with the shaft of the lancet 183 and confine the lancet 183 to substantially axial movement. At the distal end 753 of the lancet channel 736 the distal-most lancet guide portion 749 is disposed adjacent the sample input port 741 and includes at its distal-most extremity, the lancet exit port 754 which is disposed adjacent the sample input cavity 715′. The sample input cavity can have a transverse dimension, depth or both, of about 2 to 5 times the transverse dimension of the lancet 183, or about 0.2 to about 2 mm, specifically, about 0.4 to about 1.5 mm, and more specifically, about 0.5 to about 1.0 mm. The distal-most lancet guide 749 can have inner transverse dimensions of about 300 to about 350 microns in width and about 300 to about 350 microns in depth. Proximal of the distal-most lancet guide portion 749 is a distal sample flow stop 747 that includes a chamber adjacent the distal-most lancet 749. The chamber has a transverse dimension that is significantly larger than the transverse dimension of the distal-most lancet guide 749. The chamber can have a width of about 600 to about 800 microns, and a depth of about 400 to about 600 microns and a length of about 2000 to about 2200 microns. The rapid transition of transverse dimension and cross sectional area between the distal-most lancet bearing guide 749 and the distal sample flow stop 747 interrupts the capillary action that draws a fluid sample through the sample input cavity 715′ and into the lancet channel 736.


A center lancet bearing guide 750 is disposed proximal of the distal lancet channel stop 747 and can have dimensions similar to those of the distal-most lancet bearing guide 749. Proximal of the center lancet guide 750 is a proximal lancet channel stop 748 with a chamber. The dimensions of the proximal lancet channel stop can be the same or similar to those of the distal lancet channel stop 747. The proximal lancet channel stop 748 can have a width of about 600 to about 800 microns, and a depth of about 400 to about 600 microns and a length of about 2800 to about 3000 microns. Proximal of the proximal lancet channel stop 748 is a proximal lancet guide 751. The proximal lancet guide 751 can dimensions similar to those of the other lancet guide 749 and 750 portions with inner transverse dimensions of about 300 to about 350 microns in width and about 300 to about 350 microns in depth. Typically, the transverse dimension of the lancet guides 749-751 are about 10 percent larger than the transverse dimension of the shaft portion 201 of the lancet 183 that the lancet guides 749-751 are configured to guide.


A proximal fracturable seal (not shown) can be positioned between the proximal lancet guide 751 and the shaft portion 201 of the lancet 183 that seals the chamber of the proximal lancet channel stop 748 from the outside environment. The fracturable seal seals the chamber of the proximal lancet channel stop 748 and other interior portions of the sample chamber from the outside environment when the sampling module 709 is stored for use. The fracturable seal remains intact until the lancet 183 is driven distally during a lancet cycle at which point the seal is broken and the sterile interior portion of the sample chamber is exposed and ready to accept input of a liquid sample, such as a sample of blood. A distal fracturable seal (not shown) can be disposed between the lancet 183 and the distal-most lancet guide 749 of the sampling module 709 to seal the distal end 753 of the lancet channel 736 and sample input port 741 to maintain sterility of the interior portion of the sampling module 709 until the lancet 183 is driven forward during a lancing cycle.


Adjacent the lancet exit port 754 within the sample input cavity 715′ is the sample input port 741 that is configured to accept a fluid sample that emanates into the sample input cavity 715′ from target tissue 233 at a lancing site after a lancing cycle. The dimensions of the sample input port 741 can a depth of about 60 to about 70 microns, a width of about 400 to about 600 microns. The sample input cavity can have a transverse dimension of about 2 to about 5 times the transverse dimension of the lancet 183, or about 400 to about 1000 microns. The sample input cavity serves to accept a fluid sample as it emanates from lanced tissue and direct the fluid sample to the sample input port 741 and thereafter the sample flow channel 742. The sample flow channel 742 is disposed between and in fluid communication with the sample input port 741 and the analytical region 743. The transverse dimensions of the sample flow channel 742 can be the same as the transverse dimensions of the sample input port 741 with a depth of about 60 to about 70 microns, a width of about 400 to about 600 microns. The length of the sample flow channel 742 can be about 900 to about 1100 microns. Thus, in use, target tissue is disposed on the sampling site 715 and a lancing cycle initiated. Once the target tissue 233 has been lanced and the sample begins to flow therefrom, the sample enters the sample input cavity 715′ and then the sample input port 741. The sample input cavity 715′ may be sized and configured to facilitate sampling success by applying pressure to a perimeter of target tissue 233 before, during and after the lancing cycle and hold the wound track open after the lancing cycle to allow blood or other fluid to flow from the wound track and into the sample input cavity 715′. From the sample input port 741, the sample in then drawn by capillary or other forces through the sample flow channel 742 and into the analytical region 743 and ultimately into the control chamber 744. The control chamber 744 may be used to provide indirect confirmation of a complete fill of the analytical region 743 by a sample fluid. If a fluid sample has been detected in the control chamber 744, this confirms that the sample has completely filled the analytical region 743. Thus, sample detectors may be positioned within the control chamber 744 to confirm filling of the analytical region 743.


The analytical region 743 is disposed between and in fluid communication with the sample flow channel 742 and the control chamber 744. The analytical region 743 can have a depth of about 60 to about 70 microns, a width of about 900 to about 1100 microns and a length of about 5 to about 6 mm. A typical volume for the analytical region 743 can be about 380 to about 400 nanoliters. The control chamber 744 is disposed adjacent to and proximal of the analytical region 743 and can have a transverse dimension or diameter of about 900 to about 1100 microns and a depth of about 60 to about 70 microns.


The control chamber 744 is vented to the chamber of the proximal lancet channel stop 748 by a vent that is disposed between and in fluid communication with the control chamber 744 and the chamber of the proximal lancet channel stop 748. Vent 762 can have transverse dimensions that are the same or similar to those of the sample flow channel 742 disposed between the analytical region 743 and the sample input port 741. Any of the interior surfaces of the sample input port 741, sample flow channels 742 and 762, analytical region 743, vents 745 or control chamber 744 can be coated with a coating that promotes capillary action. A hydrophilic coating such as a detergent is an example of such a coating.


The analytical region 743 accommodates a blood sample that travels by capillary action from the sampling site 715 through the sample input cavity 715′ and into the sample input port 741, through the sample flow channel 742 and into the analytical region 743. The blood can then travel into the control chamber 744. The control chamber 744 and analytical region 743 are both vented by the vent 762 that allows gases to escape and prevents bubble formation and entrapment of a sample in the analytical region 743 and control chamber 744. Note that, in addition to capillary action, flow of a blood sample into the analytical region 743 can be facilitated or accomplished by application of vacuum, mechanical pumping or any other suitable method.


Once a blood sample is disposed within the analytical region 743, analytical testing can be performed on the sample with the results transmitted to the processor 193 by electrical conductors 732, optically or by any other suitable method or means. In some embodiments, it may be desirable to confirm that the blood sample has filled the analytical region 743 and that an appropriate amount of sample is present in the chamber in order to carry out the analysis on the sample.


Confirmation of sample arrival in either the analytical region 743 or the control chamber 744 can be achieved visually, through the flexible polymer sheet 727 which can be transparent. However, it may be desirable in some embodiments to use a very small amount of blood sample in order to reduce the pain and discomfort to the patient during the lancing cycle. For sampling module 709 embodiments such as described here, having the sample input cavity 715′ and sample input port 741 adjacent the lancet exit port 754 allows the blood sample to be collected from the patient's skin 233 without the need for moving the sampling module 709 between the lancing cycle and the sample collection process. As such, the user does not need to be able to see the sample in order to have it transferred into the sampling module 709. Because of this, the position of the sample input cavity 715′ and the sample input port 741 adjacent the lancet exit port 754 allows a very small amount of sample to be reliably obtained and tested.


Samples on the order of tens of nanoliters, such as about 10 to about 50 nanoliters can be reliably collected and tested with a sampling module 709. This size of blood sample is too small to see and reliably verify visually. Therefore, it is necessary to have another method to confirm the presence of the blood sample in the analytical region 743. Sample sensors 733, such as the thermal sample sensors discussed above can positioned in the analytical region 743 or control chamber 744 to confirm the arrival of an appropriate amount of blood sample.


In addition, optical methods, such as spectroscopic analysis of the contents of the analytical region 743 or control chamber 744 could be used to confirm arrival of the blood sample. Other methods such as electrical detection could also be used and these same detection methods can also be disposed anywhere along the sample flow path through the sampling module 709 to confirm the position or progress of the sample (or samples) as it moves along the flow path as indicated by the arrows 763 in FIG. 81. The detection methods described above can also be useful for analytical methods requiring an accurate start time.


The requirement for having an accurate start time for an analytical method can in turn require rapid filling of an analytical region 743 because many analytical processes begin once the blood sample enters the analytical region 743. If the analytical region 743 takes too long to fill, the portion of the blood sample that first enters the analytical region 743 will have been tested for a longer time that the last portion of the sample to enter the analytical region 743 which can result in inaccurate results. Therefore, it may be desirable in these circumstances to have the blood sample flow first to a reservoir, filling the reservoir, and then have the sample rapidly flow all at once from the reservoir into the analytical region 743.


In one embodiment of the sampling module 709, the analytical region 743 can have a transverse cross section that is substantially greater than a transverse cross section of the control chamber 744. The change in transverse cross section can be accomplished by restrictions in the lateral transverse dimension of the control chamber 744 versus the analytical region 743, by step decreases in the depth of the control chamber 744, or any other suitable method. Such a step between the analytical region 743 and the control chamber 744 is shown in FIG. 81. In such an embodiment, the analytical region 743 can behave as a sample reservoir and the control chamber 744 as an analytical region that requires rapid or nearly instantaneous filling in order to have a consistent analysis start time. The analytical region 743 fills by a flow of sample from the sample flow channel 742 until the analytical region is full and the sample reaches the step decrease in chamber depth at the boundary with the control chamber 744. Once the sample reaches the step decrease in cross sectional area of the control chamber 744, the sample then rapidly fills the control chamber 744 by virtue of the enhanced capillary action of the reduced cross sectional area of the control chamber 744. The rapid filling of the control chamber allows any analytical process initiated by the presence of sample to be carried out in the control chamber 744 with a reliable start time for the analytical process for the entire sample of the control chamber 744.


Filling by capillary force is passive. It can also be useful for some types of analytical testing to discard the first portion of a sample that enters the sampling module 709, such as the case where there may be interstitial fluid contamination of the first portion of the sample. Such a contaminated portion of a sample can be discarded by having a blind channel or reservoir that draws the sample by capillary action into a side sample flow channel (not shown) until the side sample flow channel or reservoir in fluid communication therewith, is full. The remainder of the sample can then proceed to a sample flow channel adjacent the blind sample flow channel to the analytical region 743.


For some types of analytical testing, it may be advantageous to have multiple analytical regions 743 in a single sampling module 709. In this way multiple iterations of the same type of analysis could be performed in order to derive some statistical information, e.g. averages, variation or confirmation of a given test or multiple tests measuring various different parameters could be performed in different analytical regions 743 in the same sampling module 709 filled with a blood sample from a single lancing cycle.



FIG. 82 is an enlarged elevational view of a portion of an alternative embodiment of a sampling module 766 having a plurality of small volume analytical regions 767. The small volume analytical regions 767 can have dimensions of about 40 to about 60 microns in width in both directions and a depth that yields a volume for each analytical region 767 of about 1 nanoliter to about 100 nanoliters, specifically about 10 nanoliters to about 50 nanoliters. The array of small volume analytical regions 767 can be filled by capillary action through a sample flow channel 768 that branches at a first branch point 769, a second branch point 770 and a third branch point 771. Each small volume analytical region 767 can be used to perform a like analytical test or a variety of different tests can be performed in the various analytical regions 767.


For some analytical tests, the analytical regions 767 must have maintain a very accurate volume, as some of the analytical tests that can be performed on a blood sample are volume dependent. Some analytical testing methods detect glucose levels by measuring the rate or kinetic of glucose consumption. Blood volume required for these tests is on the order of about 1 to about 3 microliters. The kinetic analysis is not sensitive to variations in the volume of the blood sample as it depends on the concentration of glucose in the relatively large volume sample with the concentration of glucose remaining essentially constant throughout the analysis. Because this type of analysis dynamically consumes glucose during the testing, it is not suitable for use with small samples, e.g. samples on the order of tens of nanoliters where the consumption of glucose would alter the concentration of glucose.


Another analytical method uses coulomb metric measurement of glucose concentration. This method is accurate if the sample volume is less than about 1 microliter and the volume of the analytical region is precisely controlled. The accuracy and the speed of the method is dependent on the small and precisely known volume of the analytical region 767 because the rate of the analysis is volume dependent and large volumes slow the reaction time and negatively impact the accuracy of the measurement.


Another analytical method uses an optical fluorescence decay measurement that allows very small sample volumes to be analyzed. This method also requires that the volume of the analytical region 767 be precisely controlled. The small volume analytical regions 767 discussed above can meet the criteria of maintaining small accurately controlled volumes when the small volume analytical regions 767 are formed using precision manufacturing techniques. Accurately formed small volume analytical regions 767 can be formed in materials such as PMMA by methods such as molding and stamping. Machining and etching, either by chemical or laser processes can also be used. Vapor deposition and lithography can also be used to achieve the desired results.


The sampling modules 709 and 766 discussed above all are directed to embodiments that both house the lancet 183 and have the ability to collect and analyze a sample. In some embodiments of a sampling module, the lancet 183 may be housed and a sample collected in a sample reservoir without any analytical function. In such an embodiment, the analysis of the sample in the sample reservoir may be carried out by transferring the sample from the reservoir to a separate analyzer. In addition, some modules only serve to house a lancet 183 without any sample acquisition capability at all. The body portion 774 of such a lancet module 775 is shown in FIG. 83. The lancet module 775 has an outer structure similar to that of the sampling modules 709 and 766 discussed above, and can be made from the same or similar materials.


A flexible polymer sheet 727 (not shown) can be used to cover the face of the lancet module 775 and contain the lancet 183 in a lancet channel 776 that extends longitudinally in the lancet module body portion 774. The flexible sheet of polymer 727 can be from the same material and have the same dimensions as the flexible polymer sheet 727 discussed above. Note that the proximal portion of the flexible polymer sheet 727 need not be folded over on itself because there are no sensor contacts 725 to expose. The flexible polymer sheet 727 in such a lancet module 775 serves only to confine the lancet 183 in the lancet channel 776. The lancet module 775 can be configured in a lancet module belt, similar to the sampling module belt 708 discussed above with the flexible polymer sheet 727 acting as the belt. A drive head slot 777 is dispose proximal of the lancet channel 776.


With regard to the tissue penetration sampling device 180 of FIG. 74, use of the device 180 begins with the loading of a sampling module cartridge 705 into the controllable driver housing 706 so as to couple the cartridge 705 to the controllable driver housing 706 and engage the sampling module belt 708 with the ratchet drive 707 and drive coupler 713 of the controllable driver 179. The drive coupler 713 can have a T-slot configuration such as shown in FIGS. 84 and 85. The distal end of the elongate coupler shaft 184 is secured to the drive coupler 713 which has a main body portion 779, a first and second guide ramp 780 and 781 and a T-slot 714 disposed within the main body portion 779. The T-slot 714 is configured to accept the drive head 198 of the lancet 183. After the sampling module cartridge 705 is loaded into the controllable driver housing 706, the sampling module belt 708 is advanced laterally until the drive head 198 of a lancet 183 of one of the sampling modules 709 is fed into the drive coupler 713 as shown in FIGS. 86-88. FIGS. 86-88 also illustrate a lancet crimp device 783 that bends the shaft portion 201 of a used lancet 183 that is adjacent to the drive coupler 713. This prevents the used lancet 183 from moving out through the module body 731 and being reused.


As the sampling modules 709 of the sampling module belt 708 are used sequentially, they are advanced laterally one at a time into the receptacle canister 730 where they are stored until the entire sampling module belt 708 is consumed. The receptacle canister 730 can then be properly disposed of in accordance with proper techniques for disposal of blood-contaminated waste. The sampling module cartridge 705 allows the user to perform multiple testing operations conveniently without being unnecessarily exposed to blood waste products and need only dispose of one cartridge after many uses instead of having to dispose of a contaminated lancet 183 or module 709 after each use.



FIGS. 89 and 90 illustrate alternative embodiments of sampling module cartridges. FIG. 89 shows a sampling module cartridge 784 in a carousel configuration with adjacent sampling modules 785 connected rigidly and with sensor contacts 786 from the analytical regions of the various sampling modules 785 disposed near an inner radius 787 of the carousel. The sampling modules 785 of the sampling module cartridge 784 are advanced through a drive coupler 713 but in a circular as opposed to a linear fashion.



FIG. 90 illustrates a block of sampling modules 788 in a four by eight matrix. The drive head 198 of the lancets 183 of the sampling modules 789 shown in FIG. 90 are engaged and driven using a different method from that of the drive coupler 713 discussed above. The drive heads 198 of the lancets 183 have an adhesive coating 790 that mates with and secures to the drive coupler 791 of the lancet driver 179, which can be any of the drivers, including controllable drivers, discussed above.


The distal end 792 of the drive coupler 791 contacts and sticks to the adhesive 790 of proximal surface of the drive head 198 of the lancet 183 during the beginning of the lancet cycle. The driver coupler 791 pushes the lancet 183 into the target tissue 237 to a desired depth of penetration and stops. The drive coupler 791 then retracts the lancet 183 from the tissue 233 using the adhesive contact between the proximal surface of the drive head 198 of the lancet 183 and distal end surface of the drive coupler 791, which is shaped to mate with the proximal surface.


At the top of the retraction stroke, a pair of hooked members 793 which are secured to the sampling module 789 engage the proximal surface of the drive head 198 and prevent any further retrograde motion by the drive head 198 and lancet 183. As a result, the drive coupler 791 breaks the adhesive bond with the drive head 198 and can then be advanced by an indexing operation to the next sampling module 789 to be used.



FIG. 91 is a side view of an alternative embodiment of a drive coupler 796 having a lateral slot 797 configured to accept the L-shaped drive head 798 of the lancet 799 that is disposed within a lancet module 800 and shown with the L-shaped drive head 798 loaded in the lateral slot 797. FIG. 92 is an exploded view of the drive coupler 796, lancet 799 with L-shaped drive head 798 and lancet module 800 of FIG. 91. This type of drive coupler 796 and drive head 798 arrangements could be substituted for the configuration discussed above with regard to FIGS. 84-88. The L-shaped embodiment of the drive head 798 may be a less expensive option for producing a coupling arrangement that allows serial advancement of a sampling module belt or lancet module belt through the drive coupler 796 of a lancet driver, such as a controllable lancet driver 179.


For some embodiments of multiple lancing devices 180, it may be desirable to have a high capacity-lancing device that does not require a lancet module 775 in order to house the lancets 183 stored in a cartridge. Eliminating the lancet modules 775 from a multiple lancet device 180 allows for a higher capacity cartridge because the volume of the cartridge is not taken up with the bulk of multiple modules 775. FIGS. 93-96 illustrate a high capacity lancet cartridge coupled to a belt advance mechanism 804. The belt advance mechanism 804 is secured to a controlled driver 179 housing which contains a controlled electromagnetic driver.


The lancet cartridge 803 has a supply canister 805 and a receptacle canister 806. A lancet belt 807 is disposed within the supply canister 805. The lancet belt 807 contains multiple sterile lancets 183 with the shaft portion 201 of the lancets 183 disposed between the adhesive surface 808 of a first carrier tape 809 and the adhesive surface 810 of a second carrier tape 811 with the adhesive surfaces 808 and 810 pressed together around the shaft portion 201 of the lancets 183 to hold them securely in the lancet belt 807. The lancets 183 have drive heads 198 which are configured to be laterally engaged with a drive coupler 713, which is secured to an elongate coupler shaft 184 of the controllable driver 179.


The belt advance mechanism 804 includes a first cog roller 814 and a second cog roller 815 that have synchronized rotational motion and are advanced in unison in an incremental indexed motion. The indexed motion of the first and second cog rollers 814 and 815 advances the lancet belt 807 in units of distance equal to the distance between the lancets 183 disposed in the lancet belt 807. The belt advance mechanism 804 also includes a first take-up roller 816 and a second take-up roller 817 that are configured to take up slack in the first and second carrier tapes 809 and 811 respectively.


When a lancet belt cartridge 803 is loaded in the belt advance mechanism 804, a lead portion 818 of the first carrier tape 809 is disposed between a first cog roller 814 and a second cog roller 815 of the belt advance mechanism 804. The lead portion 818 of the first carrier tape 809 wraps around the outer surface 819 of the first turning roller 827, and again engages roller 814 with the cogs 820 of the first cog roller 814 engaged with mating holes 821 in the first carrier tape 809. The lead portion 818 of the first carrier tape 809 is then secured to a first take-up roller 816. A lead portion 822 of the second carrier tape 811 is also disposed between the first cog roller 814 and second cog roller 815 and is wrapped around an outer surface 823 of the second turning roller 828, and again engages roller 815 with the cogs 826′ of the second cog roller 815 engaged in with mating holes 825 of the second carrier tape 811. The lead portion 822 of the second carrier tape 811 is thereafter secured to a second take-up roller 817.


As the first and second cog rollers 814 and 815 are advanced, the turning rollers 827 and 828 peel the first and second carrier tapes 809 and 811 apart and expose a lancet 183. The added length or slack of the portions of the first and second carrier tapes 809 and 811 produced from the advancement of the first and second cog rollers 814 and 815 is taken up by the first and second take-up rollers 816 and 817. As a lancet 183 is peeled out of the first and second carrier tapes 809 and 811, the exposed lancet 183 is captured by a lancet guide wheel 826′ of the belt advance mechanism 804, shown in FIG. 96, which is synchronized with the first and second cog rollers 814 and 815. The lancet guide wheel 826′ then advances the lancet 183 laterally until the drive head 198 of the lancet 183 is loaded into the drive coupler 713 of the controllable driver 179. The controllable driver 179 can then be activated driving the lancet 183 into the target tissue 233 and retracted to complete the lancing cycle.


Once the lancing cycle is complete, the belt advance mechanism 804 can once again be activated which rotates the lancet guide wheel 826 and advances the used lancet 183 laterally and into the receptacle canister 806. At the same time, a new unused lancet 183 is loaded into the drive coupler 713 and readied for the next lancing cycle. This repeating sequential use of the multiple lancing device 180 continues until all lancets 183 in the lancet belt 807 have been used and disposed of in the receptacle canister 806. After the last lancet 183 has been consumed, the lancet belt cartridge 803 can then be removed and disposed of without exposing the user to any blood contaminated materials. The belt advance mechanism 804 can be activated by a variety of methods, including a motorized drive or a manually operated thumbwheel which is coupled to the first and second cog rollers 814 and 815 and lancet guide wheel 826.


Although discussion of the devices described herein has been directed primarily to substantially painless methods and devices for access to capillary blood of a patient, there are many other uses for the devices and methods. For example, the tissue penetration devices discussed herein could be used for substantially painless delivery of small amounts of drugs, or other bioactive agents such as gene therapy agents, vectors, radioactive sources etc. As such, it is contemplated that the tissue penetration devices and lancet devices discussed herein could be used to delivery agents to positions within a patient's body as well as taking materials from a patient's body such as blood, lymph fluid, spinal fluid and the like. Drugs delivered may include analgesics that would further reduce the pain perceived by the patient upon penetration of the patient's body tissue, as well as anticoagulants that may facilitate the successful acquisition of a blood sample upon penetration of the patient's tissue.


Referring to FIGS. 97-101, a device for injecting a drug or other useful material into the tissue of a patient is illustrated. The ability to localize an injection or vaccine to a specific site within a tissue, layers of tissue or organ within the body can be important. For example, epithelial tumors can be treated by injection of antigens, cytokine, or colony stimulating factor by hypodermic needle or high-pressure injection sufficient for the antigen to enter at least the epidermis or the dermis of a patient. Often, the efficacy of a drug or combination drug therapy depends on targeted delivery to localized areas thus affecting treatment outcome.


The ability to accurately deliver drugs or vaccinations to a specific depth within the skin or tissue layer may avoid wastage of expensive drug therapies therefore impacting cost effectiveness of a particular treatment. In addition, the ability to deliver a drug or other agent to a precise depth can be a clear advantage where the outcome of treatment depends on precise localized drug delivery (such as with the treatment of intralesional immunotherapy). Also, rapid insertion velocity of a hypodermic needle to a precise predetermined depth in a patient's skin is expected to reduce pain of insertion of the needle into the skin. Rapid insertion and penetration depth of a hypodermic needle, or any other suitable elongated delivery device suitable for penetrating tissue, can be accurately controlled by virtue of a position feedback loop of a controllable driver coupled to the hypodermic needle.



FIG. 97 illustrates 901 distal end 901 of a hypodermic needle 902 being driven into layers of skin tissue 903 by an electromagnetic controllable driver 904. The electromagnetic controllable driver 904 of FIG. 79 can have any suitable configuration, such as the configuration of electromagnetic controllable drivers discussed above. The layers of skin 903 being penetrated include the stratum corneum 905, the stratum lucidum 906, the stratum granulosum 907, the stratum spinosum 908, the stratum basale 909 and the dermis 911. The thickness of the stratum corneum 905 is typically about 300 micrometers in thickness. The portion of the epidermis excluding the stratum corneum 905 includes the stratum lucidum 906, stratum granulosum 907, and stratum basale can be about 200 micrometers in thickness. The dermis can be about 1000 micrometers in thickness. In FIG. 97, an outlet port 912 of the hypodermic needle 902 is shown disposed approximately in the stratum spinosum 908 layer of the skin 903 injecting an agent 913 into the stratum spinosum 908.



FIGS. 98-101 illustrate an agent injection module 915 including an injection member 916, that includes a collapsible canister 917 and the hypodermic needle 902, that may be driven or actuated by a controllable driver, such as any of the controllable drivers discussed above, to drive the hypodermic needle into the skin 903 for injection of drugs, vaccines or the like. The agent injection module 915 has a reservoir, which can be in the form of the collapsible canister 917 having a main chamber 918, such as shown in FIG. 98, for the drug or vaccine 913 to be injected. A cassette of a plurality of agent injection modules 915 (not shown) may provide a series of metered doses for long-term medication needs. Such a cassette may be configured similarly to the module cassettes discussed above. Agent injection modules 915 and needles 902 may be disposable, avoiding biohazard concerns from unspent drug or used hypodermic needles 902. The geometry of the cutting facets 921 of the hypodermic needle shown in FIG. 79, may be the same or similar to the geometry of the cutting facets of the lancet 183 discussed above.


Inherent in the position and velocity control system of some embodiments of a controllable driver is the ability to precisely determine the position or penetration depth of the hypodermic needle 902 relative to the controllable driver or layers of target tissue or skin 903 being penetrated. For embodiments of controllable drivers that use optical encoders for position sensors, such as an Agilent HEDS 9200 series, and using a four edge detection algorithm, it is possible to achieve an in plane spatial resolution of +/−17 μm in depth. If a total tissue penetration stroke is about 3 mm in length, such as might be used for intradermal or subcutaneous injection, a total of 88 position points can be resolved along the penetration stroke. A spatial resolution this fine allows precise placement of a distal tip 901 or outlet port 912 of the hypodermic needle 902 with respect to the layers of the skin 903 during delivery of the agent or drug 913. In some embodiments, a displacement accuracy of better than about 200 microns can be achieved, in others a displacement accuracy of better than about 40 microns can be achieved.


The agent injection module 915 includes the injection member 916 which includes the hypodermic needle 902 and drug reservoir or collapsible canister 917, which may couple to an elongated coupler shaft 184 via a drive coupler 185 as shown. The hypodermic needle 902 can be driven to a desired penetration depth, and then the drug or other agent 913, such as a vaccine, is passed into an inlet port 922 of the needle 902 through a central lumen 923 of the hypodermic needle 902 as shown by arrow 924, shown in FIG. 98, and out of the outlet port 912 at the distal end 901 of the hypodermic needle 902, shown in FIG. 97.


Drug or agent delivery can occur at the point of maximum penetration, or following retraction of the hypodermic needle 902. In some embodiments, it may be desirable to deliver the drug or agent 913 during insertion of the hypodermic needle 902. Drug or agent delivery can continue as the hypodermic needle 902 is being withdrawn (this is commonly the practice during anesthesia in dental work). Alternatively drug delivery can occur while the needle 902 is stationary during any part of the retraction phase.


The hollow hypodermic needle 902 is fitted with the collapsible canister 917 containing a drug or other agent 913 to be dispensed. The walls 928 of this collapsible canister 917 can be made of a soft resilient material such as plastic, rubber, or any other suitable material. A distal plate 925 is disposed at the distal end 926 of the collapsible canister is fixed securely to the shaft 927 of the hypodermic needle proximal of the distal tip 901 of the hypodermic needle 902. The distal plate 925 is sealed and secured to the shaft 927 of the hypodermic needle 902 to prevent leakage of the medication 913 from the collapsible canister 917.


A proximal plate 931 disposed at a proximal end 932 of the collapsible canister 917 is slidingly fitted to a proximal portion 933 of the shaft 927 of the hypodermic needle 902 with a sliding seal 934. The sliding seal 934 prevents leakage of the agent or medication 913 between the seal 934 and an outside surface of the shaft 927 of the hypodermic needle 902. The sliding seal allows the proximal plate 931 of the collapsible canister 917 to slide axially along the needle 902 relative to the distal plate 925 of the collapsible canister 917. A drug dose may be loaded into the main chamber 918 of the collapsible canister 917 during manufacture, and the entire assembly protected during shipping and storage by packaging and guide fins 935 surrounding the drive head slot 936 of the agent injection module 915.


An injection cycle may begin when the agent injection module 915 is loaded into a ratchet advance mechanism (not shown), and registered at a drive position with a drive head 937 of the hypodermic needle 902 engaged in the drive coupler 185. The position of the hypodermic needle 902 and collapsible canister 917 in this ready position is shown in FIG. 99.


Once the drive head 937 of the agent injection module 915 is loaded into the driver coupler 185, the controllable driver can then be used to launch the injection member 916 including the hypodermic needle 902 and collapsible canister 917 towards and into the patient's tissue 903 at a high velocity to a pre-determined depth into the patient's skin or other organ. The velocity of the injection member 916 at the point of contact with the patient's skin 903 or other tissue can be up to about 10 meters per second for some embodiments, specifically, about 2 to about 5 m/s. In some embodiments, the velocity of the injection member 916 may be about 2 to about 10 m/s at the point of contact with the patient's skin 903. As the collapsible canister 917 moves with the hypodermic needle 902, the proximal plate 931 of the collapsible canister 917 passes between two latch springs 938 of module body 939 that snap in behind the proximal plate 931 when the collapsible canister 917 reaches the end of the penetration stroke, as shown in FIG. 100.


The controllable driver then reverses, applies force in the opposite retrograde direction and begins to slowly (relative to the velocity of the penetration stroke) retract the hypodermic needle 902. The hypodermic needle 902 slides through the sliding seal 934 of the collapsible canister 917 while carrying the distal plate 925 of the collapsible canister with it in a proximal direction relative to the proximal plate 931 of the collapsible canister 917. This relative motion between the distal plate 925 of the collapsible canister 917 and the proximal plate 931 of the collapsible canister 917 causes the volume of the main chamber 918 to decrease. The decreasing volume of the main chamber 918 forces the drug or other agent 913 disposed within the main chamber 918 of the collapsible canister 917 out of the main chamber 918 into the inlet port 922 in the shaft 927 of the hypodermic needle 902. The inlet port 922 of the hypodermic needle 902 is disposed within an in fluid communication with the main chamber 918 of the collapsible canister 917 as shown in FIG. 80. The drug or agent then passes through the central lumen 923 of the hollow shaft 927 of the hypodermic needle 902 and is then dispensed from the output port 912 at the distal end 901 of the hypodermic needle 902 into the target tissue 903. The rate of perfusion of the drug or other agent 913 may be determined by an inside diameter or transverse dimension of the collapsible canister 917. The rate of perfusion may also be determined by the viscosity of the drug or agent 913 being delivered, the transverse dimension or diameter of the central lumen 923, the input port 922, or the output port 912 of the hypodermic needle 902, as well as other parameters.


During the proximal retrograde retraction stroke of the hypodermic needle 902, drug delivery continues until the main chamber 918 of the collapsible canister 917 is fully collapsed as shown in FIG. 101. At this point, the drive coupler 185 may continue to be retracted until the drive head 937 of the hypodermic needle 902 breaks free or the distal seal 941 between the distal plate 925 of the chamber and the hypodermic needle 902 fails, allowing the drive coupler 185 to return to a starting position. The distal tip 901 of the hypodermic needle 902 can be driven to a precise penetration depth within the tissue 903 of the patient using any of the methods or devices discussed above with regard to achieving a desired penetration depth using a controllable driver or any other suitable driver.


In another embodiment, the agent injection module 915 is loaded into a ratchet advance mechanism that includes an adjustable or movable distal stage or surface (not shown) that positions the agent injection 915 module relative to a skin contact point or surface 942. In this way, an agent delivery module 915 having a penetration stroke of predetermined fixed length, such as shown in FIGS. 99-101, reaches a pre-settable penetration depth. The movable stage remains stationary during a drug delivery cycle. In a variation of this embodiment, the moveable stage motion may be coordinated with a withdrawal of the hypodermic needle 902 to further control the depth of drug delivery.


In another embodiment, the latch springs 938 shown in the agent injection module 915 of FIGS. 99-101 may be molded with a number of ratchet teeth (not shown) that engage the proximal end 932 of the collapsible canister 917 as it passes by on the penetration stroke. If the predetermined depth of penetration is less than the full stroke, the intermediate teeth retain the proximal end 932 of the collapsible canister 917 during the withdrawal stroke in order to collapse the main chamber 918 of the collapsible canister 917 and dispense the drug or agent 913 as discussed above.


In yet another embodiment, drive fingers (not shown) are secured to an actuation mechanism (not shown) and replace the latch springs 938. The actuation mechanism is driven electronically in conjunction with the controllable driver by a processor or controller, such as the processor 60 discussed above, to control the rate and amount of drug delivered anywhere in the actuation cycle. This embodiment allows the delivery of medication during the actuation cycle as well as the retraction cycle.


Inherent in the position and velocity control system of a controllable driver is the ability to precisely define the position in space of the hypodermic needle 902, allowing finite placement of the hypodermic needle in the skin 903 for injection of drugs, vaccines or the like. Drug delivery can be discrete or continuous depending on the need.



FIGS. 102-106 illustrate an embodiment of a cartridge 945 that may be used for sampling that has both a lancet cartridge body 946 and an sampling cartridge body 947. The sampling cartridge body 947 includes a plurality of sampling module portions 948 that are disposed radially from a longitudinal axis 949 of the sampling cartridge body 947. The lancet cartridge body 946 includes a plurality of lancet module portions 950 that have a lancet channel 951 with a lancet 183 slidably disposed therein. The lancet module portions 950 are disposed radially from a longitudinal axis 952 of the lancet cartridge body 946.


The sampling cartridge body 947 and lancet cartridge body 946 are disposed adjacent each other in an operative configuration such that each lancet module portion 950 can be readily aligned in a functional arrangement with each sampling module portion 948. In the embodiment shown in FIGS. 102-106, the sampling cartridge body 947 is rotatable with respect to the lancet cartridge body 946 in order to align any lancet channel 951 and corresponding lancet 183 of the lancet cartridge body 946 with any of the lancet channels 953 of the sampling module portions 948 of the sampling cartridge body 947. The operative configuration of the relative location and rotatable coupling of the sampling cartridge body 947 and lancet cartridge body 946 allow ready alignment of lancet channels 951 and 953 in order to achieve a functional arrangement of a particular lancet module portion 950 and sampling module portion 948. For the embodiment shown, the relative motion used to align the particular lancet module portions 950 and sampling module portions 948 is confined to a single degree of freedom via relative rotation.


The ability of the cartridge 945 to align the various sampling module 948 portions and lancet module portions 950 allows the user to use a single lancet 183 of a particular lancet module portion 950 with multiple sampling module portions 948 of the sampling cartridge body 947. In addition, multiple different lancets 183 of lancet module portions 950 could be used to obtain a sample in a single sampling module portion 948 of the sampling cartridge body 947 if a fresh unused lancet 183 is required or desired for each lancing action and previous lancing cycles have been unsuccessful in obtaining a usable sample.



FIG. 102 shows an exploded view in perspective of the cartridge 945, which has a proximal end portion 954 and a distal end portion 955. The lancet cartridge body 946 is disposed at the proximal end portion 954 of the cartridge 945 and has a plurality of lancet module portions 950, such as the lancet module portion 950 shown in FIG. 103. Each lancet module portion 950 has a lancet channel 951 with a lancet 183 slidably disposed within the lancet channel 951. The lancet channels 951 are substantially parallel to the longitudinal axis 952 of the lancet cartridge body 946. The lancets 183 shown have a drive head 198, shaft portion 201 and sharpened tip 196. The drive head 198 of the lancets are configured to couple to a drive coupler (not shown), such as the drive coupler 185 discussed above.


The lancets 183 are free to slide in the respective lancet channels 951 and are nominally disposed with the sharpened tip 196 withdrawn into the lancet channel 951 to protect the tip 196 and allow relative rotational motion between the lancet cartridge body 946 and the sampling cartridge body 947 as shown by arrow 956 and arrow 957 in FIG. 102. The radial center of each lancet channel 951 is disposed a fixed, known radial distance from the longitudinal axis 952 of the lancet cartridge body 946 and a longitudinal axis 958 of the cartridge 945. By disposing each lancet channel 951 a fixed known radial distance from the longitudinal axes 952 and 958 of the lancet cartridge body 946 and cartridge 945, the lancet channels 951 can then be readily and repeatably aligned in a functional arrangement with lancet channels 953 of the sampling cartridge body 947. The lancet cartridge body 946 rotates about a removable pivot shaft 959 which has a longitudinal axis 960 that is coaxial with the longitudinal axes 952 and 950 of the lancet cartridge body 946 and cartridge 945.


The sampling cartridge body 947 is disposed at the distal end portion 955 of the cartridge and has a plurality of sampling module portions 948 disposed radially about the longitudinal axis 949 of the sampling cartridge body 947. The longitudinal axis 949 of the sampling cartridge body 947 is coaxial with the longitudinal axes 952, 958 and 960 of the lancet cartridge body 946, cartridge 945 and pivot shaft 959. The sampling cartridge body 947 may also rotate about the pivot shaft 959. In order to achieve precise relative motion between the lancet cartridge body 946 and the sampling cartridge body 947, one or both of the cartridge bodies 946 and 947 must be rotatable about the pivot shaft 959, however, it is not necessary for both to be rotatable about the pivot shaft 959, that is, one of the cartridge bodies 946 and 947 may be secured, permanently or removably, to the pivot shaft 959.


The sampling cartridge body 947 includes a base 961 and a cover sheet 962 that covers a proximal surface 963 of the base forming a fluid tight seal. Each sampling module portion 948 of the sampling cartridge body 947, such as the sampling module portion 948 shown in FIG. 104 (without the cover sheet for clarity of illustration), has a sample reservoir 964 and a lancet channel 953. The sample reservoir 964 has a vent 965 at an outward radial end that allows the sample reservoir 964 to readily fill with a fluid sample. The sample reservoir 964 is in fluid communication with the respective lancet channel 953 which extends substantially parallel to the longitudinal axis 949 of the sampling cartridge body 947. The lancet channel 953 is disposed at the inward radial end of the sample reservoir 964.


The lancet channels 953 of the sample cartridge body 947 allow passage of the lancet 183 and also function as a sample flow channel 966 extending from an inlet port 967 of the lancet channel 953, shown in FIG. 106, to the sample reservoir 964. Note that a proximal surface 968 of the cover sheet 962 is spatially separated from a distal surface 969 of the lancet cartridge body 946 at the lancet channel site in order to prevent any fluid sample from being drawn by capillary action into the lancet channels 951 of the lancet cartridge body 946. The spatial separation of the proximal surface 968 of the cover sheet 962 from the distal surface 969 of the lancet cartridge body 946 is achieved with a boss 970 between the two surfaces 968 and 969 that is formed into the distal surface 969 of the lancet cartridge body as shown in FIG. 105.


The sample reservoirs 964 of the sampling cartridge body 947 may include any of the sample detection sensors, testing sensors, sensor contacts or the like discussed above with regard to other sampling module embodiments. The cover sheet 962 may be formed of PMMA and have conductors, sensors or sensor contacts formed on a surface thereof. It may also be desirable to have the cover sheet 962 made from a transparent or translucent material in order to use optical sensing or testing methods for samples obtained in the sample reservoirs. In the embodiment shown, the outer radial location of at least a portion of the sample reservoirs 964 of the sampling cartridge body 967 is beyond an outer radial dimension of the lancet cartridge body 946. Thus, an optical detector or sensor 971, such as shown in FIG. 105, can detect or test a sample disposed within a sample reservoir 964 by transmitting an optical signal through the cover sheet 962 and receiving an optical signal from the sample.


The cartridge bodies 946 and 947 may have features, dimensions or materials that are the same as, or similar to, features, dimensions or materials of the sampling cartridges and lancet cartridges, or any components thereof, discussed above. The module portions 948 and 950 may also have features, dimensions or materials that are the same as, or similar to, features, dimensions or materials of the lancet or sampling modules, or any components thereof, discussed above. In addition, the cartridge 945 can be coupled to, or positioned adjacent any of the drivers discussed above, or any other suitable driver, in an operative configuration whereby the lancets of the lancet cartridge body can be selectively driven in a lancing cycle. Although the embodiment shown in FIGS. 102-106 allows for alignment of various sampling module portions 948 and lancet module portions 950 with relative rotational movement, other embodiments that function similarly are also contemplated. For example, lancet module portions, sampling module portions or both, could be arranged in a two dimensional array with relative x-y motion being used to align the module portions in a functional arrangement. Such relative x-y motion could be accomplished with position sensors and servo motors in such an alternative embodiment order to achieve the alignment.


Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the appended claims.

Claims
  • 1. A penetrating member system for injecting a medicament to a body part, comprising: a housing;a penetrating member positioned in the housing, the penetrating member including a widened portion and a tip;a medicament injection source configured to be coupled to the penetrating membera deformable member sealing the housing;wherein, during a medicament injection movement of the penetrating member, the tip pierces the deformable member to produce an opening in the deformable member, the widened portion contacting the deformable member during the injection movement and enlarging the opening; anda cover sheet with a proximal surface with a spatial separation from a distal surface of a lancet cartridge body at a penetrating member channel site, the spatial separation of the proximal surface of the cover sheet from a distal surface of the lancet cartridge body being between the two surfaces that is formed into the distal surface of the lancet cartridge body,the deformable member configured to reseal after the penetrating member tip has penetrated it while injection medicament from the medicament injection source; wherein, during the injection movement, the portion of the deformable member pierced by the tip becomes flared.
  • 2. The penetrating member system of claim 1, wherein after the injection movement, the tip retracts into the housing and the opening substantially maintains its shape after the retraction.
  • 3. The penetrating member system of claim 1, wherein during the injection movement, the deformable member remains substantially intact.
  • 4. The penetrating member system of claim 1, wherein the widened portion is a substantially conical shape.
  • 5. The penetrating member system of claim 4, wherein a radius of the widened portion increases in a direction along the penetrating member away from the tip.
  • 6. The penetrating member system of claim 1, wherein the widened portion is positioned adjacent to the tip.
  • 7. The penetrating member system of claim 1, wherein the penetrating member defines a needle having the tip and the widened portion, the needle being at least partially surrounded by a penetrating member body.
  • 8. The penetrating member system of claim 1, wherein the housing includes a first end and a second end, the first end including the deformable member and the second end having a second film.
  • 9. The penetrating member system of claim 8, wherein the second film is configured to be pierced by an actuator and the penetrating member is adapted to be driven by the actuator during the injection movement to move the tip toward the deformable member.
  • 10. The penetrating member system of claim 1, wherein during the injection movement, the widened portion enlarges the opening to a size that is substantially larger than the size of the tip.
RELATED APPLICATIONS

This application is a divisional of U.S. Ser. No. 12/335,808 filed Dec. 16, 2008, which is a continuation of U.S. Ser. No. 11/244,311 filed Oct. 4, 2005, and Ser. No. 10/558,976 filed May 28, 2004. Said Ser. No. 11/244,311 is also related to and claims priority from U.S. 60/298,055 filed Jun. 12, 2001; U.S. Ser. No. 60/298,126 filed Jun. 12, 2001; U.S. Ser. No. 60/297,861 filed Jun. 12, 2001; U.S. Ser. No. 60/298,001 filed Jun. 12, 2001, U.S. Ser. No. 60/298,056 filed Jun. 12, 2001; U.S. Ser. No. 60/297,864 filed Jun. 12, 2001; U.S. Ser. No. 60/297,860 filed Jun. 12, 2001. Said Ser. No. 11/244,311 is also related to U.S. Ser. No. 10/558,976 filed May 28, 2004; all U.S. patent applications stated above being hereby fully incorporated by reference herein. This application is also related to U.S. Patent Application Ser. No. 60/375,304, and U.S. Ser. No. 10/127,201 now U.S. Pat. No. 7,041,068 both of which are hereby incorporated by reference in their entirety.

US Referenced Citations (2924)
Number Name Date Kind
55620 Capewell Jun 1866 A
1135465 Pollock Apr 1915 A
1733847 Wilmot Oct 1929 A
2258857 McCann Oct 1941 A
2628319 Vang Feb 1953 A
2714890 Vang Aug 1955 A
2763935 Whaley et al. Sep 1956 A
2801633 Ehrlich Aug 1957 A
2880876 Dujardin Apr 1959 A
3030959 Grunert Apr 1962 A
3046987 Ehrlich Jul 1962 A
3063451 Kowalk Nov 1962 A
3086288 Balamuth et al. Apr 1963 A
3090384 Baldwin et al. May 1963 A
3208452 Stern Sep 1965 A
3358689 Higgins Dec 1967 A
3412729 Smith, Jr. Nov 1968 A
3424154 Kinsley Jan 1969 A
3448307 Duris Jun 1969 A
3494358 Fehlis et al. Feb 1970 A
3607097 Auphan et al. Sep 1971 A
3620209 Kravitz Nov 1971 A
3626929 Sanz et al. Dec 1971 A
3628026 Cronin Dec 1971 A
3665672 Speelman May 1972 A
3673475 Britton, Jr. Jun 1972 A
3703174 Smith Nov 1972 A
3712292 Zentmeyer, Jr. Jan 1973 A
3712293 Mielke, Jr. Jan 1973 A
3734812 Yazawa May 1973 A
3742954 Strickland Jul 1973 A
3780960 Tokuno et al. Dec 1973 A
3832776 Sawyer Sep 1974 A
3836148 Manning Sep 1974 A
3851543 Krom Dec 1974 A
3853010 Christen et al. Dec 1974 A
3924818 Pfeifle Dec 1975 A
3938526 Anderson et al. Feb 1976 A
3971365 Smith Jul 1976 A
4057394 Genshaw Nov 1977 A
4077406 Sandhage et al. Mar 1978 A
4109655 Chacornac Aug 1978 A
4139011 Benoit et al. Feb 1979 A
4154228 Feldstein et al. May 1979 A
4168130 Barth et al. Sep 1979 A
4184486 Papa Jan 1980 A
4190420 Covington et al. Feb 1980 A
4191193 Seo Mar 1980 A
4193690 Levenson et al. Mar 1980 A
4203446 Hofert et al. May 1980 A
4207870 Eldridge Jun 1980 A
4223674 Fluent et al. Sep 1980 A
4224949 Scott et al. Sep 1980 A
4240439 Abe et al. Dec 1980 A
4254083 Columbus Mar 1981 A
4258001 Pierce et al. Mar 1981 A
4259653 McGonigal Mar 1981 A
4299230 Kubota Nov 1981 A
4301412 Hill et al. Nov 1981 A
4321397 Nix et al. Mar 1982 A
4338174 Tamura Jul 1982 A
4350762 De Luca et al. Sep 1982 A
4356826 Kubota Nov 1982 A
4360016 Sarrine Nov 1982 A
4388922 Telang Jun 1983 A
4392933 Nakamura et al. Jul 1983 A
4394512 Batz Jul 1983 A
4397556 Muller Aug 1983 A
4407008 Schmidt et al. Sep 1983 A
4411266 Cosman Oct 1983 A
4414975 Ryder et al. Nov 1983 A
4418037 Katsuyama et al. Nov 1983 A
4420564 Tsuji et al. Dec 1983 A
4425039 Grant Jan 1984 A
4426884 Polchaninoff Jan 1984 A
4440301 Intengan Apr 1984 A
4442836 Meinecke et al. Apr 1984 A
4442972 Sahay et al. Apr 1984 A
4449529 Burns et al. May 1984 A
4462405 Ehrlich Jul 1984 A
4469110 Slama Sep 1984 A
4490139 Huizenga et al. Dec 1984 A
4517978 Levin et al. May 1985 A
4518384 Tarello et al. May 1985 A
4523994 Shono et al. Jun 1985 A
4525164 Loeb et al. Jun 1985 A
4535769 Burns Aug 1985 A
4535773 Yoon Aug 1985 A
4537197 Hulka Aug 1985 A
4539988 Shirley et al. Sep 1985 A
4545382 Higgins et al. Oct 1985 A
4553541 Burns Nov 1985 A
4561445 Berke et al. Dec 1985 A
4577630 Nitzsche et al. Mar 1986 A
4580564 Andersen Apr 1986 A
4580565 Cornell et al. Apr 1986 A
4586819 Tochigi et al. May 1986 A
4586926 Osborne May 1986 A
4590411 Kelly May 1986 A
4600014 Beraha Jul 1986 A
4603209 Tsien et al. Jul 1986 A
4608997 Conway Sep 1986 A
4615340 Cronenberg et al. Oct 1986 A
4616649 Burns Oct 1986 A
4622974 Coleman et al. Nov 1986 A
4624253 Burns Nov 1986 A
4627445 Garcia et al. Dec 1986 A
4637393 Ray Jan 1987 A
4637403 Garcia et al. Jan 1987 A
4643189 Mintz Feb 1987 A
4648408 Hutcheson et al. Mar 1987 A
4648714 Benner et al. Mar 1987 A
4653511 Goch et al. Mar 1987 A
4653513 Dombrowski Mar 1987 A
4655225 Dahne et al. Apr 1987 A
4661768 Carusillo Apr 1987 A
4666438 Raulerson May 1987 A
4676244 Enstrom Jun 1987 A
4677979 Burns Jul 1987 A
4678277 Delhaye et al. Jul 1987 A
4682892 Chawla Jul 1987 A
4695273 Brown Sep 1987 A
4702594 Grant Oct 1987 A
4711245 Higgins et al. Dec 1987 A
4712460 Allen et al. Dec 1987 A
4712548 Enstrom Dec 1987 A
4714462 DiDomenico Dec 1987 A
4715374 Maggio Dec 1987 A
4731330 Hill et al. Mar 1988 A
4731726 Allen, III Mar 1988 A
4734360 Phillips Mar 1988 A
4735203 Ryder et al. Apr 1988 A
4737458 Batz et al. Apr 1988 A
4750489 Berkman et al. Jun 1988 A
4753776 Hillman et al. Jun 1988 A
4756884 Hillman et al. Jul 1988 A
4757022 Shults et al. Jul 1988 A
4758323 Davis et al. Jul 1988 A
4774192 Terminiello et al. Sep 1988 A
4784486 Van Wagenen et al. Nov 1988 A
4787398 Garcia et al. Nov 1988 A
4790979 Terminiello et al. Dec 1988 A
4797283 Allen et al. Jan 1989 A
4814661 Ratzlaff et al. Mar 1989 A
4817603 Turner et al. Apr 1989 A
4818493 Coville et al. Apr 1989 A
4820010 Scifres et al. Apr 1989 A
4823806 Bajada Apr 1989 A
RE32922 Levin et al. May 1989 E
4825711 Jensen et al. May 1989 A
4827763 Bourland et al. May 1989 A
4829011 Gibbons May 1989 A
4840893 Hill et al. Jun 1989 A
4844095 Chiodo et al. Jul 1989 A
4845392 Mumbower Jul 1989 A
4850973 Jordan et al. Jul 1989 A
4868129 Gibbons et al. Sep 1989 A
4869249 Crossman et al. Sep 1989 A
4869265 McEwen Sep 1989 A
4873993 Meserol et al. Oct 1989 A
4877026 de Laforcade Oct 1989 A
4883055 Merrick Nov 1989 A
4883068 Dechow Nov 1989 A
4886499 Cirelli et al. Dec 1989 A
4889529 Haindl Dec 1989 A
4892097 Ranalletta et al. Jan 1990 A
4895147 Bodicky et al. Jan 1990 A
4895156 Schulze Jan 1990 A
4900666 Phillips Feb 1990 A
4920977 Haynes May 1990 A
4924879 O'Brien May 1990 A
4935346 Phillips et al. Jun 1990 A
4938218 Goodman et al. Jul 1990 A
4940468 Petillo Jul 1990 A
4944304 Nishina Jul 1990 A
4946795 Gibbons et al. Aug 1990 A
4948961 Hillman et al. Aug 1990 A
4952373 Sugarman et al. Aug 1990 A
4953552 DeMarzo Sep 1990 A
4953976 Adler-Golden et al. Sep 1990 A
4963498 Hillman et al. Oct 1990 A
4966581 Landau Oct 1990 A
4966646 Zdeblick Oct 1990 A
4975581 Robinson et al. Dec 1990 A
4976724 Nieto et al. Dec 1990 A
4977910 Miyahara et al. Dec 1990 A
4983178 Schnell Jan 1991 A
4984085 Landowski Jan 1991 A
4990154 Brown et al. Feb 1991 A
4995402 Smith et al. Feb 1991 A
4999582 Parks et al. Mar 1991 A
5001054 Wagner Mar 1991 A
5001873 Rufin Mar 1991 A
5004923 Hillman et al. Apr 1991 A
5010772 Bourland et al. Apr 1991 A
5010774 Kikuo et al. Apr 1991 A
5014718 Mitchen May 1991 A
5019974 Beckers May 1991 A
5026388 Ingalz Jun 1991 A
D318331 Phillips et al. Jul 1991 S
5028142 Ostoich et al. Jul 1991 A
5029583 Meserol et al. Jul 1991 A
5035704 Lambert et al. Jul 1991 A
5039617 McDonald et al. Aug 1991 A
5043143 Shaw et al. Aug 1991 A
5046496 Betts et al. Sep 1991 A
5047044 Smith et al. Sep 1991 A
5049373 Ballou Sep 1991 A
5049487 Phillips et al. Sep 1991 A
5054487 Clarke Oct 1991 A
5054499 Swierczek Oct 1991 A
5057082 Burchette, Jr. Oct 1991 A
5057277 Mauze et al. Oct 1991 A
5059394 Phillips et al. Oct 1991 A
5059789 Salcudean Oct 1991 A
5060174 Gross Oct 1991 A
5062898 McDermott et al. Nov 1991 A
5064411 Gordon, III Nov 1991 A
5070874 Barnes et al. Dec 1991 A
5070886 Mitchen et al. Dec 1991 A
5073500 Saito et al. Dec 1991 A
5074872 Brown et al. Dec 1991 A
5077017 Gorin et al. Dec 1991 A
5077199 Basagni et al. Dec 1991 A
5080865 Leiner et al. Jan 1992 A
5086229 Rosenthal et al. Feb 1992 A
5092842 Bechtold et al. Mar 1992 A
5094943 Siedel et al. Mar 1992 A
5096669 Lauks et al. Mar 1992 A
5097810 Fishman et al. Mar 1992 A
5100427 Crossman et al. Mar 1992 A
5100428 Mumford Mar 1992 A
5104380 Holman et al. Apr 1992 A
5104382 Brinkerhoff et al. Apr 1992 A
5104813 Besemer et al. Apr 1992 A
5107764 Gasparrini Apr 1992 A
5108889 Smith et al. Apr 1992 A
5132801 Yamano Jul 1992 A
5133730 Biro et al. Jul 1992 A
5135719 Hillman et al. Aug 1992 A
5140161 Hillman et al. Aug 1992 A
5144139 Hillman et al. Sep 1992 A
5145565 Kater et al. Sep 1992 A
5146091 Knudson Sep 1992 A
5152296 Simons Oct 1992 A
5152775 Ruppert Oct 1992 A
5153671 Miles Oct 1992 A
5156611 Haynes et al. Oct 1992 A
5162525 Masilamani et al. Nov 1992 A
5163442 Ono Nov 1992 A
5164598 Hillman et al. Nov 1992 A
5167619 Wuchinich Dec 1992 A
5170364 Gross et al. Dec 1992 A
5174726 Findlay Dec 1992 A
D332490 Brown et al. Jan 1993 S
5178142 Harjunmaa et al. Jan 1993 A
5179005 Phillips et al. Jan 1993 A
5181910 Scanlon Jan 1993 A
5181914 Zook Jan 1993 A
5183042 Harjunmaa et al. Feb 1993 A
5188118 Terwilliger Feb 1993 A
5189751 Giuliani et al. Mar 1993 A
5194391 Nauze et al. Mar 1993 A
5196025 Ranalletta et al. Mar 1993 A
5201324 Swierczek Apr 1993 A
5208163 Charlton et al. May 1993 A
5209028 McDermott et al. May 1993 A
5211652 Derbyshire May 1993 A
5212879 Biro et al. May 1993 A
5215587 McConnellogue et al. Jun 1993 A
5216597 Beckers Jun 1993 A
5217476 Wishinsky Jun 1993 A
5217480 Haber et al. Jun 1993 A
5218966 Yamasawa Jun 1993 A
5222504 Solomon Jun 1993 A
5228972 Osaka et al. Jul 1993 A
5231993 Haber et al. Aug 1993 A
5241969 Carson et al. Sep 1993 A
5247932 Chung et al. Sep 1993 A
5249583 Mallaby Oct 1993 A
5250066 Lambert Oct 1993 A
5251126 Kahn et al. Oct 1993 A
5253656 Rincoe et al. Oct 1993 A
5256998 Becker et al. Oct 1993 A
5266359 Spielvogel Nov 1993 A
D342573 Cerola Dec 1993 S
5267974 Lambert Dec 1993 A
5277181 Mendelson et al. Jan 1994 A
5279294 Anderson et al. Jan 1994 A
5279791 Aldrich et al. Jan 1994 A
5282822 Macors et al. Feb 1994 A
5294261 McDermott et al. Mar 1994 A
5296378 Sakata et al. Mar 1994 A
5300779 Hillman et al. Apr 1994 A
5304192 Crouse Apr 1994 A
5304193 Zhadanov Apr 1994 A
5304347 Mann et al. Apr 1994 A
5304468 Phillips et al. Apr 1994 A
5306623 Kiser et al. Apr 1994 A
5307263 Brown Apr 1994 A
5312590 Gunasingham May 1994 A
5314441 Cusack et al. May 1994 A
5314442 Morita May 1994 A
5315793 Peterson et al. May 1994 A
5316012 Siegal May 1994 A
5318583 Rabenau et al. Jun 1994 A
5318584 Lange et al. Jun 1994 A
5320607 Ishibashi Jun 1994 A
5320808 Holen et al. Jun 1994 A
5324302 Crouse Jun 1994 A
5324303 Strong et al. Jun 1994 A
5330634 Wong et al. Jul 1994 A
5341206 Pittaro et al. Aug 1994 A
5342382 Brinkerhoff et al. Aug 1994 A
5344703 Kovar et al. Sep 1994 A
5350392 Purcell et al. Sep 1994 A
5352351 White et al. Oct 1994 A
5354287 Wacks Oct 1994 A
5356420 Czernecki et al. Oct 1994 A
5360410 Wacks Nov 1994 A
5365699 Armstrong et al. Nov 1994 A
5366469 Steg et al. Nov 1994 A
5366470 Ramel Nov 1994 A
5368047 Suzuki et al. Nov 1994 A
5370509 Golding et al. Dec 1994 A
5371687 Holmes, II et al. Dec 1994 A
5372135 Mendelson et al. Dec 1994 A
5375397 Ferrand et al. Dec 1994 A
5383885 Bland Jan 1995 A
5390450 Goenka Feb 1995 A
5395339 Talonn et al. Mar 1995 A
5395387 Burns Mar 1995 A
5397334 Schenk et al. Mar 1995 A
5402798 Swierczek et al. Apr 1995 A
5405283 Goenka Apr 1995 A
5405510 Betts et al. Apr 1995 A
5405511 White et al. Apr 1995 A
5409664 Allen Apr 1995 A
5410474 Fox Apr 1995 A
5415169 Siczek et al. May 1995 A
5418142 Kiser et al. May 1995 A
5423847 Strong et al. Jun 1995 A
5424545 Block et al. Jun 1995 A
5426032 Phillips et al. Jun 1995 A
5438271 White et al. Aug 1995 A
D362719 Kaplan Sep 1995 S
5453360 Yu Sep 1995 A
5454828 Schraga Oct 1995 A
5456875 Lambert Oct 1995 A
5459325 Hueton et al. Oct 1995 A
5460182 Goodman et al. Oct 1995 A
5462533 Daugherty Oct 1995 A
5464418 Schraga Nov 1995 A
5465722 Fort et al. Nov 1995 A
5471102 Becker et al. Nov 1995 A
5472427 Rammler Dec 1995 A
5474084 Cunniff Dec 1995 A
5476474 Davis et al. Dec 1995 A
5480387 Gabriel et al. Jan 1996 A
5487748 Marshall et al. Jan 1996 A
D367109 Ryner et al. Feb 1996 S
5490505 Diab et al. Feb 1996 A
5496274 Graves et al. Mar 1996 A
5496453 Uenoyama et al. Mar 1996 A
5498542 Corey et al. Mar 1996 A
5501836 Myerson Mar 1996 A
5501893 Laermer et al. Mar 1996 A
5507288 Bocker et al. Apr 1996 A
5507629 Jarvik Apr 1996 A
5508171 Walling et al. Apr 1996 A
5509410 Hill et al. Apr 1996 A
5510266 Bonner et al. Apr 1996 A
5512159 Yoshioka et al. Apr 1996 A
5514152 Smith May 1996 A
5515170 Matzinger et al. May 1996 A
5518006 Mawhirt et al. May 1996 A
D371198 Savage et al. Jun 1996 S
5524636 Sarvazyan et al. Jun 1996 A
5525511 D'Costa Jun 1996 A
5525518 Lundsgaard et al. Jun 1996 A
5526120 Jina et al. Jun 1996 A
5527333 Nikkels et al. Jun 1996 A
5527334 Kanner et al. Jun 1996 A
5529074 Greenfield Jun 1996 A
5540676 Freiberg Jul 1996 A
5540709 Ramel Jul 1996 A
5543326 Heller et al. Aug 1996 A
5545174 Schenk et al. Aug 1996 A
5545291 Smith et al. Aug 1996 A
5547702 Gleisner Aug 1996 A
D373419 Muramatsu et al. Sep 1996 S
5554153 Costello et al. Sep 1996 A
5554166 Lange et al. Sep 1996 A
5558834 Chu et al. Sep 1996 A
5562384 Alvite et al. Oct 1996 A
5562696 Nobles et al. Oct 1996 A
5563031 Yu Oct 1996 A
5563042 Phillips et al. Oct 1996 A
5569286 Peckham et al. Oct 1996 A
5569287 Tezuka et al. Oct 1996 A
5571132 Mawhirt et al. Nov 1996 A
5575284 Athan et al. Nov 1996 A
5575403 Charlton et al. Nov 1996 A
5575895 Ikeda et al. Nov 1996 A
5582697 Ikeda et al. Dec 1996 A
5584846 Mawhirt et al. Dec 1996 A
5591139 Lin et al. Jan 1997 A
5593852 Heller et al. Jan 1997 A
5599501 Carey et al. Feb 1997 A
5605837 Karimi et al. Feb 1997 A
D378612 Clark et al. Mar 1997 S
5608006 Myerson Mar 1997 A
5609749 Yamauchi et al. Mar 1997 A
5611809 Marshall et al. Mar 1997 A
5611810 Arnold et al. Mar 1997 A
5613978 Harding Mar 1997 A
5616135 Thorne et al. Apr 1997 A
5617851 Lipkovker Apr 1997 A
5618297 Hart et al. Apr 1997 A
5620579 Genshaw et al. Apr 1997 A
5620863 Tomasco et al. Apr 1997 A
5624458 Lipscher Apr 1997 A
5624459 Kortenbach et al. Apr 1997 A
5624537 Turner et al. Apr 1997 A
D379516 Rutter May 1997 S
5628764 Schraga May 1997 A
5628765 Morita May 1997 A
5628890 Carter et al. May 1997 A
5628961 Davis et al. May 1997 A
5630828 Mawhirt et al. May 1997 A
5630986 Charlton et al. May 1997 A
5632410 Moulton et al. May 1997 A
5640954 Pfeiffer et al. Jun 1997 A
D381591 Rice et al. Jul 1997 S
5643306 Schraga Jul 1997 A
5643308 Markman Jul 1997 A
5645555 Davis et al. Jul 1997 A
5647851 Pokras Jul 1997 A
5650062 Ikeda et al. Jul 1997 A
5653863 Genshaw et al. Aug 1997 A
5657760 Ying et al. Aug 1997 A
5658444 Black et al. Aug 1997 A
5660791 Brenneman et al. Aug 1997 A
D383550 Larson et al. Sep 1997 S
5662127 De Vaughn Sep 1997 A
5662672 Pambianchi et al. Sep 1997 A
5666966 Horie et al. Sep 1997 A
5676143 Simonsen et al. Oct 1997 A
5678306 Bozeman, Jr. et al. Oct 1997 A
5680858 Hansen et al. Oct 1997 A
5680872 Sesekura et al. Oct 1997 A
5682233 Brinda Oct 1997 A
5682884 Hill et al. Nov 1997 A
5683562 Schaffar et al. Nov 1997 A
5691898 Rosenberg et al. Nov 1997 A
5692514 Bowman Dec 1997 A
5695947 Guo et al. Dec 1997 A
5700695 Yassinzadeh et al. Dec 1997 A
5705045 Park et al. Jan 1998 A
5707384 Kim Jan 1998 A
5708247 McAleer et al. Jan 1998 A
5709668 Wacks Jan 1998 A
5709699 Warner Jan 1998 A
5710011 Forrow et al. Jan 1998 A
5714123 Sohrab Feb 1998 A
5714390 Hallowitz et al. Feb 1998 A
5719034 Kiser et al. Feb 1998 A
5720862 Hamamoto et al. Feb 1998 A
5720924 Eikmeier et al. Feb 1998 A
D392391 Douglas et al. Mar 1998 S
D392740 Yung et al. Mar 1998 S
5723284 Ye Mar 1998 A
5727548 Hill et al. Mar 1998 A
5729905 Mathiasmeier et al. Mar 1998 A
5730753 Morita Mar 1998 A
5733085 Shida et al. Mar 1998 A
5733300 Pambianchi et al. Mar 1998 A
D393716 Brenneman et al. Apr 1998 S
D393717 Brenneman et al. Apr 1998 S
5735868 Lee Apr 1998 A
5736103 Pugh Apr 1998 A
5738244 Charlton et al. Apr 1998 A
5741228 Lambrecht et al. Apr 1998 A
5741634 Nozoe et al. Apr 1998 A
RE35803 Lange et al. May 1998 E
5746217 Erickson et al. May 1998 A
5746761 Turchin May 1998 A
5746898 Preidel May 1998 A
5753429 Pugh May 1998 A
5753452 Smith May 1998 A
5755228 Wilson et al. May 1998 A
5755733 Morita May 1998 A
5758643 Wong et al. Jun 1998 A
5759364 Charlton et al. Jun 1998 A
5762770 Pritchard et al. Jun 1998 A
5770086 Indriksons et al. Jun 1998 A
5770369 Meade et al. Jun 1998 A
5772586 Heinonen et al. Jun 1998 A
5772677 Mawhirt et al. Jun 1998 A
5773270 D'Orazio et al. Jun 1998 A
5776157 Thorne et al. Jul 1998 A
5776719 Douglas et al. Jul 1998 A
5779365 Takaki Jul 1998 A
5780304 Matzinger et al. Jul 1998 A
5782770 Mooradian et al. Jul 1998 A
5782852 Foggia et al. Jul 1998 A
5788651 Weilandt Aug 1998 A
5788652 Rahn Aug 1998 A
5789255 Yu Aug 1998 A
5794219 Brown Aug 1998 A
5795725 Buechler et al. Aug 1998 A
5795774 Matsumoto et al. Aug 1998 A
5797940 Mawhirt et al. Aug 1998 A
5797942 Schraga Aug 1998 A
5798030 Raguse et al. Aug 1998 A
5798031 Charlton et al. Aug 1998 A
5800781 Gavin et al. Sep 1998 A
5801057 Smart et al. Sep 1998 A
5807375 Gross et al. Sep 1998 A
5810199 Charlton et al. Sep 1998 A
D399566 Sohrab et al. Oct 1998 S
5820551 Hill et al. Oct 1998 A
5822715 Worthington et al. Oct 1998 A
5823973 Racchini et al. Oct 1998 A
5824491 Priest et al. Oct 1998 A
5827181 Dias et al. Oct 1998 A
5828943 Brown Oct 1998 A
5829589 Nguyen et al. Nov 1998 A
5830219 Bird et al. Nov 1998 A
5832448 Brown Nov 1998 A
5840020 Heinonen et al. Nov 1998 A
5840171 Birch et al. Nov 1998 A
5843691 Douglas et al. Dec 1998 A
5843692 Phillips et al. Dec 1998 A
5846216 Gonzales et al. Dec 1998 A
5846486 Pugh Dec 1998 A
5846490 Yokota et al. Dec 1998 A
5849174 Sanghera et al. Dec 1998 A
5853373 Griffith et al. Dec 1998 A
5854074 Charlton et al. Dec 1998 A
D403975 Douglas et al. Jan 1999 S
5855377 Murphy Jan 1999 A
5855801 Lin et al. Jan 1999 A
5856174 Lipshutz et al. Jan 1999 A
5856195 Charlton et al. Jan 1999 A
5857967 Frid et al. Jan 1999 A
5857983 Douglas et al. Jan 1999 A
5858804 Zanzucchi et al. Jan 1999 A
5860922 Gordon et al. Jan 1999 A
5863800 Eikmeier et al. Jan 1999 A
5866353 Berneth et al. Feb 1999 A
5868135 Kaufman et al. Feb 1999 A
5869972 Birch et al. Feb 1999 A
5871494 Simons et al. Feb 1999 A
5872713 Douglas et al. Feb 1999 A
5873856 Hjertman et al. Feb 1999 A
5873887 King et al. Feb 1999 A
5876351 Rohde Mar 1999 A
5876957 Douglas et al. Mar 1999 A
5879163 Brown et al. Mar 1999 A
5879310 Sopp et al. Mar 1999 A
5879311 Duchon et al. Mar 1999 A
5879373 Roper et al. Mar 1999 A
5880829 Kauhaniemi et al. Mar 1999 A
5882494 Van Antwerp Mar 1999 A
5885211 Eppstein et al. Mar 1999 A
5886056 Hershkowitz et al. Mar 1999 A
5887133 Brown et al. Mar 1999 A
5890128 Diaz et al. Mar 1999 A
RE36191 Solomon Apr 1999 E
5891053 Sesekura Apr 1999 A
5892569 Van de Velde Apr 1999 A
5893848 Negus et al. Apr 1999 A
5893870 Talen et al. Apr 1999 A
5897493 Brown Apr 1999 A
5897569 Kellogg et al. Apr 1999 A
5899855 Brown May 1999 A
5899915 Saadat May 1999 A
5900130 Benvegnu et al. May 1999 A
5902731 Ouyang et al. May 1999 A
5906921 Ikeda et al. May 1999 A
D411619 Duchon Jun 1999 S
5908416 Costello et al. Jun 1999 A
5911937 Hekal Jun 1999 A
5912134 Shartle Jun 1999 A
5913310 Brown Jun 1999 A
5916156 Hildenbrand et al. Jun 1999 A
5916229 Evans Jun 1999 A
5916230 Brenneman et al. Jun 1999 A
5918603 Brown Jul 1999 A
5919711 Boyd et al. Jul 1999 A
5921963 Erez et al. Jul 1999 A
5922188 Ikeda et al. Jul 1999 A
5922530 Yu Jul 1999 A
5922591 Anderson et al. Jul 1999 A
RE36268 Szuminsky et al. Aug 1999 E
5931794 Pitesky Aug 1999 A
5933136 Brown Aug 1999 A
5935075 Casscells et al. Aug 1999 A
5938635 Kuhle Aug 1999 A
5938679 Freeman et al. Aug 1999 A
5940153 Castaneda et al. Aug 1999 A
5942102 Hodges et al. Aug 1999 A
5942189 Wolfbeis et al. Aug 1999 A
5947957 Morris Sep 1999 A
5951300 Brown Sep 1999 A
5951492 Douglas et al. Sep 1999 A
5951493 Douglas et al. Sep 1999 A
5951582 Thorne et al. Sep 1999 A
5951836 McAleer et al. Sep 1999 A
5954738 LeVaughn et al. Sep 1999 A
5956501 Brown Sep 1999 A
5957846 Chiang et al. Sep 1999 A
5958199 Miyamoto et al. Sep 1999 A
5959098 Goldberg et al. Sep 1999 A
5960403 Brown Sep 1999 A
5961451 Reber et al. Oct 1999 A
5964718 Duchon et al. Oct 1999 A
5965380 Heller et al. Oct 1999 A
5968063 Chu et al. Oct 1999 A
5968760 Phillips et al. Oct 1999 A
5968836 Matzinger et al. Oct 1999 A
5971941 Simons et al. Oct 1999 A
5972199 Heller et al. Oct 1999 A
5972294 Smith et al. Oct 1999 A
5972715 Celentano et al. Oct 1999 A
5974124 Schlueter, Jr. et al. Oct 1999 A
5976085 Kimball et al. Nov 1999 A
5983193 Heinonen et al. Nov 1999 A
5985116 Ikeda et al. Nov 1999 A
5985559 Brown Nov 1999 A
5986754 Harding Nov 1999 A
5993400 Rincoe et al. Nov 1999 A
5993434 Dev et al. Nov 1999 A
D417504 Love et al. Dec 1999 S
5997476 Brown Dec 1999 A
5997509 Rosengart et al. Dec 1999 A
5997561 Bocker et al. Dec 1999 A
5997817 Crismore et al. Dec 1999 A
5997818 Hacker et al. Dec 1999 A
6001067 Shults et al. Dec 1999 A
6007497 Huitema Dec 1999 A
D418602 Prokop et al. Jan 2000 S
6014577 Henning et al. Jan 2000 A
6015392 Douglas et al. Jan 2000 A
6018289 Sekura et al. Jan 2000 A
6020110 Williams et al. Feb 2000 A
6022324 Skinner Feb 2000 A
6022366 Schraga Feb 2000 A
6022748 Charych et al. Feb 2000 A
6023629 Tamada Feb 2000 A
6023686 Brown Feb 2000 A
6027459 Shain et al. Feb 2000 A
6030399 Ignotz et al. Feb 2000 A
6030827 Davis et al. Feb 2000 A
6030967 Marui et al. Feb 2000 A
6032059 Henning et al. Feb 2000 A
6032119 Brown et al. Feb 2000 A
6033421 Theiss et al. Mar 2000 A
6033866 Guo et al. Mar 2000 A
6036924 Simons et al. Mar 2000 A
6037178 Leiner et al. Mar 2000 A
6041253 Kost et al. Mar 2000 A
6045567 Taylor et al. Apr 2000 A
6046055 Wolfbeis et al. Apr 2000 A
6048352 Douglas et al. Apr 2000 A
D424696 Ray et al. May 2000 S
6056701 Duchon et al. May 2000 A
6059815 Lee et al. May 2000 A
6060327 Keen May 2000 A
6061128 Zweig et al. May 2000 A
6063039 Cunningham et al. May 2000 A
6066103 Duchon et al. May 2000 A
6066243 Anderson et al. May 2000 A
6066296 Brady et al. May 2000 A
6067463 Jeng et al. May 2000 A
6068615 Brown et al. May 2000 A
D426638 Ray et al. Jun 2000 S
6070761 Bloom et al. Jun 2000 A
6071249 Cunningham et al. Jun 2000 A
6071250 Douglas et al. Jun 2000 A
6071251 Cunningham et al. Jun 2000 A
6071294 Simons et al. Jun 2000 A
6071391 Gotoh et al. Jun 2000 A
6074360 Haar et al. Jun 2000 A
6077408 Miyamoto et al. Jun 2000 A
6080106 Lloyd et al. Jun 2000 A
6080172 Fujiwara et al. Jun 2000 A
D428150 Ruf et al. Jul 2000 S
6083196 Trautman et al. Jul 2000 A
6083710 Heller et al. Jul 2000 A
6084660 Shartle Jul 2000 A
6085576 Sunshine et al. Jul 2000 A
6086544 Hibner et al. Jul 2000 A
6086545 Roe et al. Jul 2000 A
6086562 Jacobsen et al. Jul 2000 A
6090078 Erskine Jul 2000 A
6091975 Daddona et al. Jul 2000 A
6093146 Filangeri Jul 2000 A
6093156 Cunningham et al. Jul 2000 A
D428993 Lubs Aug 2000 S
6099484 Douglas et al. Aug 2000 A
6099802 Pugh Aug 2000 A
6100107 Lei et al. Aug 2000 A
6101478 Brown Aug 2000 A
6102933 Lee et al. Aug 2000 A
6103033 Say et al. Aug 2000 A
6103509 Sode Aug 2000 A
6104940 Watanabe et al. Aug 2000 A
6106751 Talbot et al. Aug 2000 A
6107083 Collins et al. Aug 2000 A
6113578 Brown Sep 2000 A
6117115 Hill et al. Sep 2000 A
6117630 Reber et al. Sep 2000 A
6118126 Zanzucchi Sep 2000 A
6119033 Spigelman et al. Sep 2000 A
6120462 Hibner et al. Sep 2000 A
6120676 Heller et al. Sep 2000 A
6121009 Heller et al. Sep 2000 A
6122536 Sun et al. Sep 2000 A
6126804 Andresen Oct 2000 A
6126899 Woudenberg et al. Oct 2000 A
6129823 Hughes et al. Oct 2000 A
6132449 Lum et al. Oct 2000 A
6133837 Riley Oct 2000 A
6134461 Say et al. Oct 2000 A
6136013 Marshall et al. Oct 2000 A
6139562 Mauze et al. Oct 2000 A
6143164 Heller et al. Nov 2000 A
6144837 Quy Nov 2000 A
6144976 Silva et al. Nov 2000 A
6149203 Hanlon Nov 2000 A
6151586 Brown Nov 2000 A
6152875 Hakamata Nov 2000 A
6152942 Brenneman et al. Nov 2000 A
6153069 Pottgen et al. Nov 2000 A
RE36991 Yamamoto et al. Dec 2000 E
6155267 Nelson Dec 2000 A
6155992 Henning et al. Dec 2000 A
6156051 Schraga Dec 2000 A
6157442 Raskas Dec 2000 A
6159147 Lichter et al. Dec 2000 A
6159424 Kauhaniemi et al. Dec 2000 A
6161095 Brown Dec 2000 A
6162397 Jurik et al. Dec 2000 A
6162611 Heller et al. Dec 2000 A
6167362 Brown et al. Dec 2000 A
6167386 Brown Dec 2000 A
6168563 Brown Jan 2001 B1
6168957 Matzinger et al. Jan 2001 B1
6171325 Mauze et al. Jan 2001 B1
6172743 Kley et al. Jan 2001 B1
6175752 Say et al. Jan 2001 B1
6176847 Humphreys, Jr. et al. Jan 2001 B1
6176865 Mauze et al. Jan 2001 B1
6177000 Peterson Jan 2001 B1
6177931 Alexander et al. Jan 2001 B1
6183489 Douglas et al. Feb 2001 B1
6186145 Brown Feb 2001 B1
6190612 Berger et al. Feb 2001 B1
6191852 Paffhausen et al. Feb 2001 B1
6192891 Gravel et al. Feb 2001 B1
6193673 Viola et al. Feb 2001 B1
6193873 Ohara et al. Feb 2001 B1
6194900 Freeman et al. Feb 2001 B1
6197040 LeVaughn et al. Mar 2001 B1
6197257 Raskas Mar 2001 B1
6200289 Hochman et al. Mar 2001 B1
6200773 Ouyang et al. Mar 2001 B1
6203504 Latterell et al. Mar 2001 B1
6206841 Cunningham et al. Mar 2001 B1
6210133 Aboul-Hosn et al. Apr 2001 B1
6210272 Brown Apr 2001 B1
6210369 Wilmot et al. Apr 2001 B1
6210420 Mauze et al. Apr 2001 B1
6210421 Bocker et al. Apr 2001 B1
6212417 Ikeda et al. Apr 2001 B1
6214626 Meller et al. Apr 2001 B1
6214804 Felgner et al. Apr 2001 B1
6218571 Zheng et al. Apr 2001 B1
6219574 Cormier et al. Apr 2001 B1
6221023 Matsuba et al. Apr 2001 B1
6221238 Grundig et al. Apr 2001 B1
6224617 Saadat et al. May 2001 B1
6225078 Ikeda et al. May 2001 B1
6228100 Schraga May 2001 B1
6230051 Cormier et al. May 2001 B1
6230501 Bailey, Sr. et al. May 2001 B1
6231531 Lum et al. May 2001 B1
6233471 Berner et al. May 2001 B1
6233539 Brown May 2001 B1
6234772 Wampler et al. May 2001 B1
6240393 Brown May 2001 B1
D444235 Roberts et al. Jun 2001 S
6241862 McAleer et al. Jun 2001 B1
6242207 Douglas et al. Jun 2001 B1
6245060 Loomis et al. Jun 2001 B1
6245215 Douglas et al. Jun 2001 B1
6246992 Brown Jun 2001 B1
6248065 Brown Jun 2001 B1
6251083 Yum et al. Jun 2001 B1
6251121 Saadat Jun 2001 B1
6251260 Heller et al. Jun 2001 B1
6251344 Goldstein Jun 2001 B1
D444557 Levaughn et al. Jul 2001 S
6254831 Barnard et al. Jul 2001 B1
6256533 Yuzhakov et al. Jul 2001 B1
6258111 Ross et al. Jul 2001 B1
6258229 Winarta et al. Jul 2001 B1
6258254 Miyamoto et al. Jul 2001 B1
6261241 Burbank et al. Jul 2001 B1
6261245 Kawai et al. Jul 2001 B1
6261519 Harding et al. Jul 2001 B1
6264635 Wampler et al. Jul 2001 B1
6268161 Han et al. Jul 2001 B1
6268162 Phillips et al. Jul 2001 B1
6269314 Iitawaki et al. Jul 2001 B1
6270455 Brown Aug 2001 B1
6270637 Crismore et al. Aug 2001 B1
6272359 Kivela et al. Aug 2001 B1
6272364 Kurnik Aug 2001 B1
6275717 Gross et al. Aug 2001 B1
6280254 Wu et al. Aug 2001 B1
6281006 Heller et al. Aug 2001 B1
6283926 Cunningham et al. Sep 2001 B1
6283982 Levaughn et al. Sep 2001 B1
6284478 Heller et al. Sep 2001 B1
6285448 Kuenstner Sep 2001 B1
6289254 Shimizu et al. Sep 2001 B1
6290683 Erez et al. Sep 2001 B1
6294897 Champlin Sep 2001 B1
6295506 Heinonen et al. Sep 2001 B1
6299578 Kurnik et al. Oct 2001 B1
6299596 Ding Oct 2001 B1
6299757 Feldman et al. Oct 2001 B1
6302844 Walker et al. Oct 2001 B1
6302855 Lav et al. Oct 2001 B1
6305804 Rice et al. Oct 2001 B1
6306104 Cunningham et al. Oct 2001 B1
6306152 Verdonk et al. Oct 2001 B1
6306347 Mason et al. Oct 2001 B1
6309351 Kurnik et al. Oct 2001 B1
6309370 Haim et al. Oct 2001 B1
6309535 Williams et al. Oct 2001 B1
6312612 Sherman et al. Nov 2001 B1
6315738 Nishikawa et al. Nov 2001 B1
6318970 Backhouse Nov 2001 B1
6319210 Douglas et al. Nov 2001 B1
6322574 Lloyd et al. Nov 2001 B1
6322808 Trautman et al. Nov 2001 B1
6322963 Bauer Nov 2001 B1
6329161 Heller et al. Dec 2001 B1
6330426 Brown et al. Dec 2001 B2
6331163 Kaplan Dec 2001 B1
6332871 Douglas et al. Dec 2001 B1
6334363 Testud et al. Jan 2002 B1
6334778 Brown Jan 2002 B1
6334856 Allen et al. Jan 2002 B1
6335203 Patel et al. Jan 2002 B1
6336900 Alleckson et al. Jan 2002 B1
6338790 Feldman et al. Jan 2002 B1
6346120 Yamazaki et al. Feb 2002 B1
6349229 Watanabe et al. Feb 2002 B1
6350273 Minagawa et al. Feb 2002 B1
6350451 Horn et al. Feb 2002 B1
6352514 Douglas et al. Mar 2002 B1
6352523 Brown et al. Mar 2002 B1
6353753 Flock et al. Mar 2002 B1
6358196 Rayman Mar 2002 B1
6364889 Kheiri et al. Apr 2002 B1
6364890 Lum et al. Apr 2002 B1
6368273 Brown Apr 2002 B1
6375469 Brown Apr 2002 B1
6375626 Allen et al. Apr 2002 B1
6375627 Mauze et al. Apr 2002 B1
6379301 Worthington et al. Apr 2002 B1
6379317 Kintzig et al. Apr 2002 B1
6379324 Gartstein et al. Apr 2002 B1
6379969 Mauze et al. Apr 2002 B1
6381577 Brown Apr 2002 B1
D456910 Clark et al. May 2002 S
6387709 Mason et al. May 2002 B1
6391005 Lum et al. May 2002 B1
6395227 Kiser et al. May 2002 B1
6398522 Skill Jun 2002 B2
6398562 Butler et al. Jun 2002 B1
6399394 Dahm et al. Jun 2002 B1
6402701 Kaplan et al. Jun 2002 B1
6402704 McMorrow Jun 2002 B1
6409740 Kuhr et al. Jun 2002 B1
6413410 Hodges et al. Jul 2002 B1
6413411 Pottgen et al. Jul 2002 B1
6415821 Kamholz et al. Jul 2002 B2
6419661 Kuhr et al. Jul 2002 B1
6420128 Ouyang et al. Jul 2002 B1
6421633 Heinonen et al. Jul 2002 B1
6423014 Churchill et al. Jul 2002 B1
6428664 Bhullar et al. Aug 2002 B1
6436055 Roe Aug 2002 B1
6436256 Williams et al. Aug 2002 B1
6436721 Kuo et al. Aug 2002 B1
6440645 Yon-Hin et al. Aug 2002 B1
6444115 Hodges et al. Sep 2002 B1
6447119 Stewart et al. Sep 2002 B1
6447265 Antaki et al. Sep 2002 B1
6451040 Purcell Sep 2002 B1
6453810 Rossmeisl et al. Sep 2002 B1
6458258 Taniike et al. Oct 2002 B2
6461496 Feldman et al. Oct 2002 B1
6462162 Van Antwerp et al. Oct 2002 B2
6464649 Duchon et al. Oct 2002 B1
6471903 Sherman et al. Oct 2002 B2
6472220 Simons et al. Oct 2002 B1
6475360 Hodges et al. Nov 2002 B1
6475372 Ohara et al. Nov 2002 B1
6475436 Schabbach et al. Nov 2002 B1
6475750 Han et al. Nov 2002 B1
6477394 Rice et al. Nov 2002 B2
6477424 Thompson et al. Nov 2002 B1
6484046 Say et al. Nov 2002 B1
6485439 Roe et al. Nov 2002 B1
6485461 Mason et al. Nov 2002 B1
6485923 Yani et al. Nov 2002 B1
6488827 Shartle Dec 2002 B1
6488872 Beebe et al. Dec 2002 B1
6488891 Mason et al. Dec 2002 B2
6489133 Phillips et al. Dec 2002 B2
6491709 Sharma et al. Dec 2002 B2
6491870 Patel et al. Dec 2002 B2
6494830 Wessel Dec 2002 B1
6497845 Sacherer Dec 2002 B1
6501404 Walker Dec 2002 B2
6501976 Sohrab Dec 2002 B1
6503209 Hakky et al. Jan 2003 B2
6503210 Hirao et al. Jan 2003 B1
6503231 Prausnitz et al. Jan 2003 B1
6503381 Gotoh et al. Jan 2003 B1
6506165 Sweeney Jan 2003 B1
6506168 Fathallah et al. Jan 2003 B1
6506575 Knappe et al. Jan 2003 B1
6508785 Eppstein Jan 2003 B1
6512986 Harmon Jan 2003 B1
6514270 Schraga Feb 2003 B1
6514460 Fendrock Feb 2003 B1
6519241 Theimer Feb 2003 B1
6520326 McIvor et al. Feb 2003 B2
6521110 Hodges et al. Feb 2003 B1
6521182 Shartle et al. Feb 2003 B1
6527521 Noda Mar 2003 B2
6527716 Eppstein Mar 2003 B1
6527778 Athanasiou et al. Mar 2003 B2
6529377 Nelson et al. Mar 2003 B1
6530892 Kelly Mar 2003 B1
6530937 Schraga Mar 2003 B1
6531322 Jurik et al. Mar 2003 B1
6533949 Yeshurun et al. Mar 2003 B1
6537207 Rice et al. Mar 2003 B1
6537242 Palmer Mar 2003 B1
6537264 Cormier et al. Mar 2003 B1
6537292 Lee Mar 2003 B1
6540672 Simonsen et al. Apr 2003 B1
6540675 Aceti et al. Apr 2003 B2
6540762 Bertling Apr 2003 B1
6540891 Stewart et al. Apr 2003 B1
6541266 Modzelewski et al. Apr 2003 B2
6547954 Ikeda et al. Apr 2003 B2
6549796 Sohrab Apr 2003 B2
6551494 Heller et al. Apr 2003 B1
6553244 Lesho et al. Apr 2003 B2
6554381 Locher et al. Apr 2003 B2
6555061 Leong et al. Apr 2003 B1
D475136 Taniguchi May 2003 S
6558320 Causey, III et al. May 2003 B1
6558361 Yeshurun May 2003 B1
6558402 Chelak et al. May 2003 B1
6558528 Matzinger May 2003 B1
6560471 Heller et al. May 2003 B1
6561978 Conn et al. May 2003 B1
6561989 Whitson May 2003 B2
6562210 Bhullar et al. May 2003 B1
6565509 Say et al. May 2003 B1
6565808 Hudak et al. May 2003 B2
6569157 Shain et al. May 2003 B1
6571651 Hodges Jun 2003 B1
6572566 Effenhauser Jun 2003 B2
6572822 Jurik et al. Jun 2003 B2
6574490 Abbink et al. Jun 2003 B2
6575905 Knobbe et al. Jun 2003 B2
6576101 Heller et al. Jun 2003 B1
6576117 Iketaki et al. Jun 2003 B1
6576416 Haviland et al. Jun 2003 B2
6579690 Bonnecaze et al. Jun 2003 B1
6582573 Douglas et al. Jun 2003 B2
6584338 Van Muiswinkel Jun 2003 B1
D477670 Jurik et al. Jul 2003 S
6586199 Ouyang et al. Jul 2003 B2
6587705 Kim et al. Jul 2003 B1
6589260 Schmelzeisen-Redeker et al. Jul 2003 B1
6589261 Abulhaj et al. Jul 2003 B1
6591124 Sherman et al. Jul 2003 B2
6591125 Buse et al. Jul 2003 B1
6592744 Hodges et al. Jul 2003 B1
6592745 Feldman et al. Jul 2003 B1
6595919 Berner et al. Jul 2003 B2
6599281 Struys et al. Jul 2003 B1
6599407 Taniike et al. Jul 2003 B2
6599693 Webb Jul 2003 B1
6599769 Kondo et al. Jul 2003 B2
6601534 Hebrank Aug 2003 B2
6602205 Erickson et al. Aug 2003 B1
6602268 Kuhr et al. Aug 2003 B2
6602678 Kwon et al. Aug 2003 B2
6604050 Trippel et al. Aug 2003 B2
6607362 Lum Aug 2003 B2
6607494 Fowler Aug 2003 B1
6607658 Heller et al. Aug 2003 B1
6612111 Hodges et al. Sep 2003 B1
6616616 Fritz et al. Sep 2003 B2
6616819 Liamos et al. Sep 2003 B1
6618934 Feldman et al. Sep 2003 B1
6620112 Klitmose Sep 2003 B2
6620310 Ohara et al. Sep 2003 B1
6623501 Heller et al. Sep 2003 B2
6626851 Hirao et al. Sep 2003 B2
6632349 Hodges et al. Oct 2003 B1
6635222 Kent Oct 2003 B2
6638415 Hodges et al. Oct 2003 B1
6638772 Douglas et al. Oct 2003 B1
6641533 Causey, III et al. Nov 2003 B2
6645142 Braig et al. Nov 2003 B2
6645219 Roe Nov 2003 B2
6645368 Beaty et al. Nov 2003 B1
6649416 Kauer et al. Nov 2003 B1
6650915 Routt et al. Nov 2003 B2
6652720 Mansouri et al. Nov 2003 B1
6652734 Hodges et al. Nov 2003 B1
6652814 House et al. Nov 2003 B1
D484600 Kaar et al. Dec 2003 S
6656428 Clark et al. Dec 2003 B1
6656697 Ouyang et al. Dec 2003 B1
6656702 Yugawa et al. Dec 2003 B1
6659966 Essenpreis Dec 2003 B2
6660018 Lum et al. Dec 2003 B2
6662439 Bhullar Dec 2003 B1
6669669 Flaherty et al. Dec 2003 B2
6671527 Petersson et al. Dec 2003 B2
D484980 Hartwein et al. Jan 2004 S
6673617 Patel Jan 2004 B2
6676995 Dick et al. Jan 2004 B2
6679841 Bojan et al. Jan 2004 B2
6679852 Schmeizeisen-Redeker et al. Jan 2004 B1
6682933 Patel et al. Jan 2004 B2
6689411 Dick et al. Feb 2004 B2
6706000 Perez et al. Mar 2004 B2
6706049 Moerman Mar 2004 B2
6706159 Moerman et al. Mar 2004 B2
6706232 Hasegawa et al. Mar 2004 B2
6709692 Sudor Mar 2004 B2
6713660 Roe et al. Mar 2004 B1
6716577 Yu et al. Apr 2004 B1
6719887 Hasegawa et al. Apr 2004 B2
6719923 Stiene et al. Apr 2004 B2
6721586 Kiser et al. Apr 2004 B2
6723046 Lichtenstein et al. Apr 2004 B2
6723111 Abulhaj et al. Apr 2004 B2
6723371 Chih-hui Apr 2004 B2
6723500 Yu Apr 2004 B2
6726818 Cui et al. Apr 2004 B2
6729546 Roustaei May 2004 B2
6730494 Toranto et al. May 2004 B1
6731966 Spigelman et al. May 2004 B1
6733493 Gruzdev et al. May 2004 B2
6736777 Kim et al. May 2004 B2
6738654 Sohrab May 2004 B2
6740215 Nakaminami et al. May 2004 B1
6743211 Prausnitz et al. Jun 2004 B1
6743597 Guo et al. Jun 2004 B1
6743635 Neel et al. Jun 2004 B2
6746872 Zheng et al. Jun 2004 B2
6749618 Levaughn et al. Jun 2004 B2
6749740 Liamos et al. Jun 2004 B2
6749792 Olson Jun 2004 B2
6749887 Dick et al. Jun 2004 B1
6751491 Lew et al. Jun 2004 B2
6752817 Flora et al. Jun 2004 B2
6753187 Cizdziel et al. Jun 2004 B2
6759190 Lin et al. Jul 2004 B2
6764496 Schraga Jul 2004 B2
6764581 Forrow et al. Jul 2004 B1
6767441 Cai et al. Jul 2004 B1
6773671 Lewis et al. Aug 2004 B1
6776888 Yamamoto et al. Aug 2004 B2
6780645 Hayter et al. Aug 2004 B2
6780647 Fujiwara et al. Aug 2004 B2
6783502 Orloff et al. Aug 2004 B2
6783537 Kuhr et al. Aug 2004 B1
6784274 Van Antwerp et al. Aug 2004 B2
6786874 Grace et al. Sep 2004 B2
6787013 Chang et al. Sep 2004 B2
6787109 Haar et al. Sep 2004 B2
6790327 Ikeda et al. Sep 2004 B2
6790599 Madou Sep 2004 B1
6792791 Sato et al. Sep 2004 B2
6793632 Sohrab Sep 2004 B2
6793633 Douglas et al. Sep 2004 B2
6793802 Lee et al. Sep 2004 B2
6797150 Kermani et al. Sep 2004 B2
6800488 Khan et al. Oct 2004 B2
6801041 Karinka et al. Oct 2004 B2
6801804 Miller et al. Oct 2004 B2
6802199 Hilgers et al. Oct 2004 B2
6802811 Slepian Oct 2004 B1
6802957 Jung et al. Oct 2004 B2
6805780 Ryu et al. Oct 2004 B1
6808499 Churchill et al. Oct 2004 B1
6808908 Yao et al. Oct 2004 B2
6808937 Ligler et al. Oct 2004 B2
6809807 Erickson et al. Oct 2004 B1
6811406 Grube Nov 2004 B2
6811557 Schraga Nov 2004 B2
6811659 Vachon et al. Nov 2004 B2
6811753 Hirao et al. Nov 2004 B2
6811792 Roser et al. Nov 2004 B2
6812031 Carlsson Nov 2004 B1
6814843 Bhullar et al. Nov 2004 B1
6814844 Bhullar et al. Nov 2004 B2
6814845 Wilson et al. Nov 2004 B2
6815186 Clark, Jr. Nov 2004 B2
6816742 Kim et al. Nov 2004 B2
6818180 Douglas et al. Nov 2004 B2
6821483 Phillips et al. Nov 2004 B2
6823750 Hodges Nov 2004 B2
6825047 Woudenberg et al. Nov 2004 B1
6827250 Uhland et al. Dec 2004 B2
6827829 Kawanaka et al. Dec 2004 B2
6829507 Lidman et al. Dec 2004 B1
6830551 Uchigaki et al. Dec 2004 B1
6830668 Musho et al. Dec 2004 B2
6830669 Miyazaki et al. Dec 2004 B2
6830934 Harding et al. Dec 2004 B1
6833540 MacKenzie et al. Dec 2004 B2
6835184 Sage et al. Dec 2004 B1
6835553 Han et al. Dec 2004 B2
6835570 Patel Dec 2004 B2
6837858 Cunningham et al. Jan 2005 B2
6837976 Cai et al. Jan 2005 B2
6837988 Leong et al. Jan 2005 B2
6840912 Kloepfer et al. Jan 2005 B2
6841052 Musho et al. Jan 2005 B2
6843254 Tapper Jan 2005 B2
6843902 Penner et al. Jan 2005 B1
6847451 Pugh Jan 2005 B2
6849052 Uchigaki et al. Feb 2005 B2
6849168 Crumly et al. Feb 2005 B2
6849216 Rappin et al. Feb 2005 B2
6849456 Patel et al. Feb 2005 B2
6850790 Berner et al. Feb 2005 B2
6852119 Abulhaj et al. Feb 2005 B1
6852212 Maxwell et al. Feb 2005 B2
6852500 Hoss et al. Feb 2005 B1
6853854 Proniewicz et al. Feb 2005 B1
6855243 Khan Feb 2005 B2
6856125 Kermani Feb 2005 B2
6856928 Harmon Feb 2005 B2
6858015 List Feb 2005 B2
6858401 Phillips et al. Feb 2005 B2
6859738 Bush et al. Feb 2005 B2
6862466 Ackerman Mar 2005 B2
6862534 Sterling et al. Mar 2005 B2
6863800 Karinka et al. Mar 2005 B2
6863801 Hodges et al. Mar 2005 B2
6865408 Abbink et al. Mar 2005 B1
6866641 Marshall Mar 2005 B2
6866675 Perez et al. Mar 2005 B2
6866758 Bhullar et al. Mar 2005 B2
6866822 House et al. Mar 2005 B1
6869418 Marano-Ford Mar 2005 B2
6872200 Mann et al. Mar 2005 B2
6872297 Mansouri et al. Mar 2005 B2
6872298 Kermani Mar 2005 B2
6872299 Kermani et al. Mar 2005 B2
6872358 Hagen et al. Mar 2005 B2
6875208 Santini, Jr. et al. Apr 2005 B2
6875223 Argauer Apr 2005 B2
6875327 Miyazaki et al. Apr 2005 B1
6875613 Shartle et al. Apr 2005 B2
6878120 Roe et al. Apr 2005 B2
6878251 Hodges et al. Apr 2005 B2
6878255 Wang et al. Apr 2005 B1
6878262 Taniike et al. Apr 2005 B2
6880968 Haar Apr 2005 B1
6881203 Delmore et al. Apr 2005 B2
6881322 Tokunaga et al. Apr 2005 B2
6881378 Zimmer et al. Apr 2005 B1
6881541 Petersen et al. Apr 2005 B2
6881550 Phillips et al. Apr 2005 B2
6881551 Heller et al. Apr 2005 B2
6881578 Otake Apr 2005 B2
6882940 Potts et al. Apr 2005 B2
6884592 Matzinger et al. Apr 2005 B2
6885196 Taniike et al. Apr 2005 B2
6885883 Parris et al. Apr 2005 B2
6887202 Currie et al. May 2005 B2
6887239 Elstrom et al. May 2005 B2
6887253 Schraga May 2005 B2
6887426 Phillips et al. May 2005 B2
6887709 Leong May 2005 B2
6889069 Routt et al. May 2005 B2
6890319 Crocker May 2005 B1
6890421 Ohara et al. May 2005 B2
6890484 Bautista et al. May 2005 B2
6891936 Kai et al. May 2005 B2
6892085 McIvor et al. May 2005 B2
6893396 Schulze et al. May 2005 B2
6893545 Gotoh et al. May 2005 B2
6893552 Wang et al. May 2005 B1
6895263 Shin et al. May 2005 B2
6895264 Rice et al. May 2005 B2
6895265 Silver May 2005 B2
6896793 Erdosy et al. May 2005 B2
6897788 Khair et al. May 2005 B2
6902905 Burson et al. Jun 2005 B2
6904301 Raskas Jun 2005 B2
6905733 Russell et al. Jun 2005 B2
6908008 Pugh Jun 2005 B2
6908535 Rankin et al. Jun 2005 B2
6908591 MacPhee et al. Jun 2005 B2
6908593 Shartle Jun 2005 B1
6911130 Brenneman et al. Jun 2005 B2
6911131 Miyazaki et al. Jun 2005 B2
6911621 Bhullar et al. Jun 2005 B2
6911937 Sparrow et al. Jun 2005 B1
6913210 Baasch et al. Jul 2005 B2
6913668 Matzinger Jul 2005 B2
6916410 Katsuki et al. Jul 2005 B2
6918874 Hatch et al. Jul 2005 B1
6918901 Theeuwes et al. Jul 2005 B1
6918918 Schraga Jul 2005 B1
6922576 Raskas Jul 2005 B2
6922578 Eppstein et al. Jul 2005 B2
6923764 Aceti et al. Aug 2005 B2
6923894 Huang et al. Aug 2005 B2
6923936 Swanson et al. Aug 2005 B2
6924093 Haviland et al. Aug 2005 B2
6925317 Samuels et al. Aug 2005 B1
6925393 Kalatz et al. Aug 2005 B1
6929631 Brugger et al. Aug 2005 B1
6929649 Pugh Aug 2005 B2
6929650 Fukuzawa et al. Aug 2005 B2
6931327 Goode, Jr. et al. Aug 2005 B2
6931328 Braig et al. Aug 2005 B2
RE38803 Rodgers, Jr. Sep 2005 E
6939310 Matzinger et al. Sep 2005 B2
6939312 Hodges et al. Sep 2005 B2
6939450 Karinka et al. Sep 2005 B2
6939685 Ouyang et al. Sep 2005 B2
6940591 Sopp et al. Sep 2005 B2
6942518 Liamos et al. Sep 2005 B2
6942769 Cheng et al. Sep 2005 B2
6942770 Cai et al. Sep 2005 B2
6944486 Braig et al. Sep 2005 B2
6945943 Pugh Sep 2005 B2
6946067 Hodges et al. Sep 2005 B2
6946098 Miekka et al. Sep 2005 B2
6946299 Neel et al. Sep 2005 B2
6949111 Schraga Sep 2005 B2
6949221 Kiser et al. Sep 2005 B2
6951631 Catt et al. Oct 2005 B1
6951728 Qian et al. Oct 2005 B2
6952603 Gerber et al. Oct 2005 B2
6952604 DeNuzzio et al. Oct 2005 B2
6953693 Neel et al. Oct 2005 B2
6954662 Freger et al. Oct 2005 B2
6958072 Schraga Oct 2005 B2
6958129 Galen et al. Oct 2005 B2
6958809 Sterling et al. Oct 2005 B2
6959211 Rule et al. Oct 2005 B2
6959247 Neel et al. Oct 2005 B2
6960287 Charlton Nov 2005 B2
6960289 Hodges et al. Nov 2005 B2
6960323 Guo et al. Nov 2005 B2
6964871 Bell et al. Nov 2005 B2
6965791 Hitchcock et al. Nov 2005 B1
6966880 Boecker et al. Nov 2005 B2
6966977 Hasegawa et al. Nov 2005 B2
6967105 Nomura et al. Nov 2005 B2
6968375 Brown Nov 2005 B1
6969359 Duchon et al. Nov 2005 B2
6969450 Taniike et al. Nov 2005 B2
6969451 Shin et al. Nov 2005 B2
6973706 Say et al. Dec 2005 B2
6975893 Say et al. Dec 2005 B2
6977032 Hasegawa et al. Dec 2005 B2
6977722 Wohlstadter et al. Dec 2005 B2
6979544 Keen Dec 2005 B2
6979571 Modzelewski et al. Dec 2005 B2
6982027 Yagi Jan 2006 B2
6982431 Modlin et al. Jan 2006 B2
6983176 Gardner et al. Jan 2006 B2
6983177 Rule et al. Jan 2006 B2
6984307 Zweig Jan 2006 B2
6986777 Kim Jan 2006 B2
6986869 Tuohy et al. Jan 2006 B2
6988996 Roe et al. Jan 2006 B2
6989243 Yani et al. Jan 2006 B2
6989891 Braig et al. Jan 2006 B2
6990365 Parker et al. Jan 2006 B1
6990366 Say et al. Jan 2006 B2
6990367 Kiser et al. Jan 2006 B2
6990849 Bohm et al. Jan 2006 B2
6991918 Keith Jan 2006 B2
6991940 Carroll et al. Jan 2006 B2
6994825 Haviland et al. Feb 2006 B2
6997317 Catelli Feb 2006 B2
6997343 May et al. Feb 2006 B2
6997344 Brown et al. Feb 2006 B2
6997936 Marshall Feb 2006 B2
6998247 Monfre et al. Feb 2006 B2
6998248 Yani et al. Feb 2006 B2
6999810 Berner et al. Feb 2006 B2
7001343 Erickson et al. Feb 2006 B2
7001344 Freeman et al. Feb 2006 B2
7003337 Harjunmaa et al. Feb 2006 B2
7003340 Say et al. Feb 2006 B2
7003341 Say et al. Feb 2006 B2
7004928 Aceti et al. Feb 2006 B2
7005048 Watanabe et al. Feb 2006 B1
7005273 Heller Feb 2006 B2
7005459 Hekal Feb 2006 B2
7005857 Stiene et al. Feb 2006 B2
7006857 Braig et al. Feb 2006 B2
7006858 Silver et al. Feb 2006 B2
7008384 Tapper Mar 2006 B2
7010432 Kermani Mar 2006 B2
7011630 Desai et al. Mar 2006 B2
7011954 Ouyang et al. Mar 2006 B2
7014615 Erickson et al. Mar 2006 B2
7015262 Leong Mar 2006 B2
7016713 Gardner et al. Mar 2006 B2
7018568 Tierney Mar 2006 B2
7018848 Douglas et al. Mar 2006 B2
7022217 Hodges et al. Apr 2006 B2
7022218 Taniike et al. Apr 2006 B2
7022286 Lemke et al. Apr 2006 B2
7024236 Ford et al. Apr 2006 B2
7024248 Penner et al. Apr 2006 B2
7024399 Sumner, II et al. Apr 2006 B2
7025425 Kovatchev et al. Apr 2006 B2
7025774 Freeman et al. Apr 2006 B2
7027848 Robinson et al. Apr 2006 B2
7029444 Shin et al. Apr 2006 B2
7033322 Silver Apr 2006 B2
7033371 Alden et al. Apr 2006 B2
7039560 Kawatahara et al. May 2006 B2
7041057 Faupel et al. May 2006 B1
7041063 Abreu May 2006 B2
7041068 Freeman et al. May 2006 B2
7041210 Hodges et al. May 2006 B2
7041254 Haviland et al. May 2006 B2
7041468 Drucker et al. May 2006 B2
7043287 Khalil et al. May 2006 B1
7043821 Hodges May 2006 B2
7044911 Drinan et al. May 2006 B2
7045046 Chambers et al. May 2006 B2
7045054 Buck et al. May 2006 B1
7045097 Kovacs May 2006 B2
7045310 Buck, Jr. et al. May 2006 B2
7045361 Heiss et al. May 2006 B2
7047070 Wilkinson et al. May 2006 B2
7047795 Sato May 2006 B2
7049087 Jenny et al. May 2006 B2
7049130 Carroll et al. May 2006 B2
7050843 Shartle et al. May 2006 B2
7051495 Lang et al. May 2006 B2
7052268 Powell et al. May 2006 B2
7052591 Gao et al. May 2006 B2
7052652 Zanzucchi et al. May 2006 B2
7052864 Durkop et al. May 2006 B2
7054682 Young et al. May 2006 B2
7054759 Fukunaga et al. May 2006 B2
D522656 Orr et al. Jun 2006 S
D523555 Loerwald et al. Jun 2006 S
7056425 Hasegawa et al. Jun 2006 B2
7056495 Roser et al. Jun 2006 B2
7058437 Buse et al. Jun 2006 B2
7059352 Bohm Jun 2006 B2
7060059 Keith et al. Jun 2006 B2
7060168 Taniike et al. Jun 2006 B2
7060192 Yuzhakov et al. Jun 2006 B2
7061593 Braig et al. Jun 2006 B2
7063234 Giraud Jun 2006 B2
7063774 Bhullar et al. Jun 2006 B2
7063775 Yamaoka Jun 2006 B2
7063776 Huang Jun 2006 B2
7066884 Custer et al. Jun 2006 B2
7066885 Erickson et al. Jun 2006 B2
7070564 Matzinger et al. Jul 2006 B2
7070680 Bae et al. Jul 2006 B2
7073246 Bhullar et al. Jul 2006 B2
7074307 Simpson et al. Jul 2006 B2
7074308 Mao et al. Jul 2006 B2
7077328 Krishnaswamy et al. Jul 2006 B2
7077828 Kuhr et al. Jul 2006 B2
7078480 Nagel et al. Jul 2006 B2
7079252 Debreczeny et al. Jul 2006 B1
7081188 Cho Jul 2006 B1
7083712 Morita et al. Aug 2006 B2
7086277 Tess et al. Aug 2006 B2
7087149 Muguruma et al. Aug 2006 B1
7090764 Iyengar et al. Aug 2006 B2
7096053 Loeb et al. Aug 2006 B2
7096124 Sterling et al. Aug 2006 B2
7097631 Trautman et al. Aug 2006 B2
7098038 Fukuoka et al. Aug 2006 B2
7103578 Beck et al. Sep 2006 B2
7105006 Shraga Sep 2006 B2
7107253 Sumner, II et al. Sep 2006 B1
7108680 Rohr et al. Sep 2006 B2
7108778 Simpson et al. Sep 2006 B2
7109271 Liu et al. Sep 2006 B2
7110112 Uchida et al. Sep 2006 B2
7110803 Shults et al. Sep 2006 B2
7112265 McAleer et al. Sep 2006 B1
7112451 Takahashi et al. Sep 2006 B2
7113172 Hohl et al. Sep 2006 B2
7115362 Douglas et al. Oct 2006 B2
7118351 Effenhauser et al. Oct 2006 B2
7118667 Lee Oct 2006 B2
7118668 Edelbrock et al. Oct 2006 B1
7118916 Matzinger Oct 2006 B2
7118919 Yatscoff et al. Oct 2006 B2
7120483 Russell et al. Oct 2006 B2
7122102 Wogoman Oct 2006 B2
7122110 Deng et al. Oct 2006 B2
7122111 Tokunaga et al. Oct 2006 B2
7125481 Musho et al. Oct 2006 B2
7129038 Gopalan et al. Oct 2006 B2
RE39390 Hasegawa et al. Nov 2006 E
D531725 Loerwald et al. Nov 2006 S
7131342 Hodges Nov 2006 B2
7131984 Sato et al. Nov 2006 B2
7132041 Deng et al. Nov 2006 B2
7133710 Acosta et al. Nov 2006 B2
7134550 Groth Nov 2006 B2
7134999 Brauker et al. Nov 2006 B2
7135100 Lau et al. Nov 2006 B1
7137957 Erickson et al. Nov 2006 B2
7138041 Su et al. Nov 2006 B2
7138089 Aitken et al. Nov 2006 B2
7141034 Eppstein et al. Nov 2006 B2
7141058 Briggs et al. Nov 2006 B2
7144404 Whitson et al. Dec 2006 B2
7144485 Hsu et al. Dec 2006 B2
7144495 Teodorczyk et al. Dec 2006 B2
7144496 Meserol et al. Dec 2006 B2
7144709 Ouyang et al. Dec 2006 B2
7147825 Matsuda et al. Dec 2006 B2
7150755 Levaughn et al. Dec 2006 B2
7150975 Tamada et al. Dec 2006 B2
7150995 Xie et al. Dec 2006 B2
7153696 Fukuoka et al. Dec 2006 B2
7155371 Kawatahara et al. Dec 2006 B2
7156117 Bohm Jan 2007 B2
7156810 Cho et al. Jan 2007 B2
7157723 Colvin et al. Jan 2007 B2
7160251 Neel et al. Jan 2007 B2
7160313 Galloway et al. Jan 2007 B2
7160678 Kayyem et al. Jan 2007 B1
7162289 Shah et al. Jan 2007 B2
7163616 Vreeke et al. Jan 2007 B2
7166074 Reghabi et al. Jan 2007 B2
7166208 Zweig Jan 2007 B2
7167734 Khalil et al. Jan 2007 B2
7167735 Uchida et al. Jan 2007 B2
7167818 Brown Jan 2007 B2
7169116 Day et al. Jan 2007 B2
7169117 Allen Jan 2007 B2
7169289 Schulein et al. Jan 2007 B2
7169600 Hoss et al. Jan 2007 B2
7172728 Otake Feb 2007 B2
7174199 Berner et al. Feb 2007 B2
7175641 Schraga Feb 2007 B1
7175642 Briggs et al. Feb 2007 B2
7179233 Chang Feb 2007 B2
7182910 Allen et al. Feb 2007 B2
7183068 Burson et al. Feb 2007 B2
7183102 Monfre et al. Feb 2007 B2
7188034 Staib et al. Mar 2007 B2
7189576 Fukuoka et al. Mar 2007 B2
7190988 Say et al. Mar 2007 B2
7192405 DeNuzzio et al. Mar 2007 B2
7192450 Brauker et al. Mar 2007 B2
7195704 Kermani et al. Mar 2007 B2
7198606 Boecker et al. Apr 2007 B2
7199594 Kermani Apr 2007 B2
7202854 Hohl et al. Apr 2007 B2
7206620 Erickson et al. Apr 2007 B2
7206623 Blank et al. Apr 2007 B2
D542681 Young May 2007 S
7211052 Roe May 2007 B2
7211096 Kuhr et al May 2007 B2
7212925 Genshaw May 2007 B2
7213720 Giraud May 2007 B2
7215982 Oshima et al. May 2007 B2
7215983 Cho et al. May 2007 B2
7223248 Erickson et al. May 2007 B2
7225008 Ward et al. May 2007 B1
D543878 Castillo et al. Jun 2007 S
D545438 Huang et al. Jun 2007 S
7225535 Feldman et al. Jun 2007 B2
7226414 Ballerstadt et al. Jun 2007 B2
7226461 Boecker et al. Jun 2007 B2
7226978 Tapsak et al. Jun 2007 B2
7227156 Colvin, Jr. et al. Jun 2007 B2
7228159 Petersson et al. Jun 2007 B2
7228162 Ward et al. Jun 2007 B2
7228163 Ackerman Jun 2007 B2
7229458 Boecker et al. Jun 2007 B2
7232451 Boecker et al. Jun 2007 B2
7232510 Miyazaki et al. Jun 2007 B2
7233816 Blank et al. Jun 2007 B2
7235056 Duchon et al. Jun 2007 B2
7235170 Watanabe et al. Jun 2007 B2
7235378 Yonehara Jun 2007 B2
7236812 Ballerstadt et al. Jun 2007 B1
7236814 Shioi et al. Jun 2007 B2
D545705 Voege Jul 2007 S
D546216 Bolognesi et al. Jul 2007 S
D546218 Grasso et al. Jul 2007 S
7238192 List et al. Jul 2007 B2
7238534 Zimmer Jul 2007 B1
7241265 Cummings et al. Jul 2007 B2
7244264 Roe et al. Jul 2007 B2
7244265 Freeman et al. Jul 2007 B2
7244266 Garthe et al. Jul 2007 B2
7247138 Reghabi et al. Jul 2007 B2
7247144 Douglas et al. Jul 2007 B2
7250037 Shermer et al. Jul 2007 B2
7250056 Hamamoto Jul 2007 B2
7250095 Black et al. Jul 2007 B2
7250105 Davies et al. Jul 2007 B1
7251513 Kondoh et al. Jul 2007 B2
7251514 Cho et al. Jul 2007 B2
7251515 Cho et al. Jul 2007 B2
7251516 Walker et al. Jul 2007 B2
7251517 Cho et al. Jul 2007 B2
7251518 Herrmann Jul 2007 B2
7252804 Miyashita et al. Aug 2007 B2
7254426 Cho et al. Aug 2007 B2
7254427 Cho et al. Aug 2007 B2
7254428 Cho et al. Aug 2007 B2
7254429 Schurman et al. Aug 2007 B2
7254430 Cho et al. Aug 2007 B2
7254432 Fine Aug 2007 B2
7258673 Racchini et al. Aug 2007 B2
7258693 Freeman et al. Aug 2007 B2
7262061 Petrich et al. Aug 2007 B2
7264139 Brickwood et al. Sep 2007 B2
7264627 Perez Sep 2007 B2
7266400 Fine et al. Sep 2007 B2
7267665 Steil et al. Sep 2007 B2
7267750 Watanabe et al. Sep 2007 B2
7270247 Charlton Sep 2007 B2
7271912 Sterling et al. Sep 2007 B2
7273484 Thoes et al. Sep 2007 B2
7276027 Haar et al. Oct 2007 B2
7276029 Goode, Jr. et al. Oct 2007 B2
7276146 Wilsey Oct 2007 B2
7276147 Wilsey Oct 2007 B2
7276380 Fukuyama Oct 2007 B2
7277740 Rohleder et al. Oct 2007 B2
7278983 Ireland et al. Oct 2007 B2
7279130 Brown Oct 2007 B2
7282058 Levin et al. Oct 2007 B2
7287318 Bhullar et al. Oct 2007 B2
7288073 Effenhauser et al. Oct 2007 B2
7288102 Griffin et al. Oct 2007 B2
7288174 Cui et al. Oct 2007 B2
7289836 Colvin, Jr. Oct 2007 B2
7291117 Boecker et al. Nov 2007 B2
7291159 Schmelzeisen-Redeker et al. Nov 2007 B2
7291256 Teodorczyk et al. Nov 2007 B2
7291497 Holmes et al. Nov 2007 B2
7294246 Gundel et al. Nov 2007 B2
7295867 Berner et al. Nov 2007 B2
7297122 Boecker et al. Nov 2007 B2
7297151 Boecker et al. Nov 2007 B2
7297152 Fukuzawa et al. Nov 2007 B2
7297241 Kontschieder et al. Nov 2007 B2
7297248 Bae et al. Nov 2007 B2
7297627 Shah et al. Nov 2007 B2
7299079 Rebec et al. Nov 2007 B2
7299080 Acosta et al. Nov 2007 B2
7299081 Mace et al. Nov 2007 B2
7299082 Feldman et al. Nov 2007 B2
7300402 Iliff Nov 2007 B2
7301629 Bambot et al. Nov 2007 B2
7303573 D'Agostino Dec 2007 B2
7303726 McAllister et al. Dec 2007 B2
7303922 Jeng et al. Dec 2007 B2
7305896 Howell et al. Dec 2007 B2
7306560 Iliff Dec 2007 B2
7308164 Banks Dec 2007 B1
7308292 Colvin et al. Dec 2007 B2
7310542 Jeon et al. Dec 2007 B2
7310543 Smart et al. Dec 2007 B2
7310544 Brister et al. Dec 2007 B2
7311718 Schraga Dec 2007 B2
7311812 Forrow et al. Dec 2007 B2
7312042 Petyt et al. Dec 2007 B1
7313425 Finarov et al. Dec 2007 B2
7314453 Kuo Jan 2008 B2
7315752 Kraemer et al. Jan 2008 B2
7316700 Alden et al. Jan 2008 B2
7316766 Chen et al. Jan 2008 B2
7316929 Purcell Jan 2008 B2
7317938 Lorenz et al. Jan 2008 B2
7317939 Fine et al. Jan 2008 B2
7322942 Roe Jan 2008 B2
7322996 Taylor et al. Jan 2008 B2
7322997 Shi Jan 2008 B2
7322998 Kuhr et al. Jan 2008 B2
7323098 Miyashita et al. Jan 2008 B2
7323141 Kirchhevel et al. Jan 2008 B2
7323315 Marfurt Jan 2008 B2
7324012 Mann et al. Jan 2008 B2
7328052 Samsoondar et al. Feb 2008 B2
7331931 Freeman et al. Feb 2008 B2
7335292 Hodges et al. Feb 2008 B2
7335294 Heller et al. Feb 2008 B2
7337918 Fowler et al. Mar 2008 B2
7338639 Burke et al. Mar 2008 B2
7343188 Sohrab Mar 2008 B2
7344499 Prausnitz et al. Mar 2008 B1
7344500 Talbot et al. Mar 2008 B2
7344507 Briggs et al. Mar 2008 B2
7344626 Harding et al. Mar 2008 B2
7347925 Hsieh Mar 2008 B2
7347926 Morita et al. Mar 2008 B2
7347973 Douglas et al. Mar 2008 B2
RE40198 Buck, Jr. et al. Apr 2008 E
7351213 Wong et al. Apr 2008 B2
7351323 Iketaki et al. Apr 2008 B2
7351375 Noda et al. Apr 2008 B2
7351770 Liu et al. Apr 2008 B2
7357808 Kennedy Apr 2008 B2
7357851 Reid et al. Apr 2008 B2
7361182 Fukuda et al. Apr 2008 B2
7361307 Shartle et al. Apr 2008 B2
7371247 Boecker et al. May 2008 B2
7372277 Diamond et al. May 2008 B2
7374544 Freeman et al. May 2008 B2
7374546 Roe et al. May 2008 B2
7378007 Moerman et al. May 2008 B2
7378720 Fu et al. May 2008 B2
7402616 Rodgers et al. Jul 2008 B2
7404815 Kollias et al. Jul 2008 B2
7410468 Freeman et al. Aug 2008 B2
7429630 Liu et al. Sep 2008 B2
7431814 Hodges et al. Oct 2008 B2
7431820 Hodges Oct 2008 B2
7438694 Boozer et al. Oct 2008 B2
D579652 Lim et al. Nov 2008 S
D579653 Lim et al. Nov 2008 S
7458956 Adams Dec 2008 B1
7462265 Leach et al. Dec 2008 B2
7465380 Rodgers et al. Dec 2008 B2
7468125 Kraft et al. Dec 2008 B2
D585314 Schvetz Jan 2009 S
7473264 Allen Jan 2009 B2
7474390 Robinson et al. Jan 2009 B2
7474391 Baskeyfield et al. Jan 2009 B2
7481776 Boecker et al. Jan 2009 B2
7481818 Allen et al. Jan 2009 B2
D586465 Faulkner et al. Feb 2009 S
D586466 Smith et al. Feb 2009 S
D586678 Schvetz Feb 2009 S
D586916 Faulkner et al. Feb 2009 S
7485128 Boecker et al. Feb 2009 B2
7491178 Boecker et al. Feb 2009 B2
7498132 Yu et al. Mar 2009 B2
7501052 Iyengar et al. Mar 2009 B2
7501093 Demelo et al. Mar 2009 B2
7521019 Polak et al. Apr 2009 B2
7524293 Freeman et al. Apr 2009 B2
7537571 Freeman et al. May 2009 B2
7547287 Boecker et al. Jun 2009 B2
7548772 Shartle et al. Jun 2009 B2
7553511 Hleong Jun 2009 B2
7563232 Freeman et al. Jul 2009 B2
D598126 Alvarez-Icaza et al. Aug 2009 S
7572356 Rodgers et al. Aug 2009 B2
7575558 Boecker et al. Aug 2009 B2
D600349 Bell et al. Sep 2009 S
D600812 Lei Sep 2009 S
D600813 Bell et al. Sep 2009 S
D601255 Schvetz Sep 2009 S
D601258 Bell et al. Sep 2009 S
7582063 Wurster et al. Sep 2009 B2
7582099 Freeman et al. Sep 2009 B2
7586590 Baskeyfield et al. Sep 2009 B2
7588670 Rodgers et al. Sep 2009 B2
7589828 Robinson et al. Sep 2009 B2
7592151 Liu et al. Sep 2009 B2
7593097 Robinson et al. Sep 2009 B2
7604592 Freeman et al. Oct 2009 B2
7604722 Hodges et al. Oct 2009 B2
7608175 Hodges et al. Oct 2009 B2
7618522 Davies Nov 2009 B2
7645263 Angel et al. Jan 2010 B2
7648468 Boecker et al. Jan 2010 B2
7648469 Boecker et al. Jan 2010 B2
7653492 Davies et al. Jan 2010 B2
7654127 Krulevitch et al. Feb 2010 B2
7655119 Davies Feb 2010 B2
7665303 Bohm et al. Feb 2010 B2
7666287 Zhao et al. Feb 2010 B2
D611151 Lei Mar 2010 S
D611372 Salter et al. Mar 2010 S
D611489 Bell et al. Mar 2010 S
D611853 Salter et al. Mar 2010 S
D612274 Heidemann et al. Mar 2010 S
D612275 Salter et al. Mar 2010 S
D612279 Heidemann et al. Mar 2010 S
7674232 Boecker et al. Mar 2010 B2
7682318 Alden et al. Mar 2010 B2
7713214 Freeman et al. May 2010 B2
7833172 Hein et al. Nov 2010 B2
7879058 Ikeda Feb 2011 B2
7901365 Freeman et al. Mar 2011 B2
7976778 Drucker et al. Jul 2011 B2
8062235 Planman et al. Nov 2011 B2
8079960 Briggs et al. Dec 2011 B2
8162968 Boozer et al. Apr 2012 B2
8197421 Freeman et al. Jun 2012 B2
8206319 Freeman et al. Jun 2012 B2
8231548 Hoenes Jul 2012 B2
8251922 List et al. Aug 2012 B2
8491500 Briggs et al. Jul 2013 B2
20010011157 Latterell et al. Aug 2001 A1
20010016682 Berner et al. Aug 2001 A1
20010017269 Heller et al. Aug 2001 A1
20010018353 Ishigaki Aug 2001 A1
20010027328 Lum et al. Oct 2001 A1
20010031931 Cunningham et al. Oct 2001 A1
20010037072 Virtanen Nov 2001 A1
20010037355 Britt Nov 2001 A1
20010042004 Taub Nov 2001 A1
20010045355 Gephart et al. Nov 2001 A1
20010054319 Heller et al. Dec 2001 A1
20020002326 Causey et al. Jan 2002 A1
20020002344 Douglas et al. Jan 2002 A1
20020004196 Whitson Jan 2002 A1
20020016568 Lebel et al. Feb 2002 A1
20020016606 Moerman Feb 2002 A1
20020016923 Knaus et al. Feb 2002 A1
20020019606 Lebel et al. Feb 2002 A1
20020019747 Ware et al. Feb 2002 A1
20020019748 Brown Feb 2002 A1
20020020646 Groth et al. Feb 2002 A1
20020025469 Heller Feb 2002 A1
20020029058 Levaughn et al. Mar 2002 A1
20020040208 Flaherty et al. Apr 2002 A1
20020040230 Kuhr et al. Apr 2002 A1
20020042090 Heller et al. Apr 2002 A1
20020042594 Lum et al. Apr 2002 A1
20020044890 Black Apr 2002 A1
20020052618 Haar et al. May 2002 A1
20020053523 Liamos et al. May 2002 A1
20020057993 Maisey et al. May 2002 A1
20020058902 Kollias et al. May 2002 A1
20020076349 Aitken et al. Jun 2002 A1
20020078091 Vu et al. Jun 2002 A1
20020081559 Brown et al. Jun 2002 A1
20020081588 De Lumley-woodyear et al. Jun 2002 A1
20020082543 Park et al. Jun 2002 A1
20020084196 Liamos et al. Jul 2002 A1
20020087056 Aceti et al. Jul 2002 A1
20020092612 Davies et al. Jul 2002 A1
20020099308 Bojan et al. Jul 2002 A1
20020103499 Perez et al. Aug 2002 A1
20020109600 Mault et al. Aug 2002 A1
20020111634 Stoianovici et al. Aug 2002 A1
20020120216 Fritz et al. Aug 2002 A1
20020120261 Morris et al. Aug 2002 A1
20020123335 Luna et al. Sep 2002 A1
20020130042 Moerman et al. Sep 2002 A1
20020133377 Brown Sep 2002 A1
20020136667 Subramanian et al. Sep 2002 A1
20020136863 Subramanian et al. Sep 2002 A1
20020137998 Smart et al. Sep 2002 A1
20020138040 Flora et al. Sep 2002 A1
20020148739 Liamos et al. Oct 2002 A2
20020156355 Gough Oct 2002 A1
20020160520 Orloff et al. Oct 2002 A1
20020161289 Hopkins et al. Oct 2002 A1
20020168290 Yuzhakov et al. Nov 2002 A1
20020169393 Cunningham et al. Nov 2002 A1
20020169394 Eppstein et al. Nov 2002 A1
20020176984 Smart et al. Nov 2002 A1
20020177761 Orloff et al. Nov 2002 A1
20020177763 Burns et al. Nov 2002 A1
20020188224 Roe et al. Dec 2002 A1
20030014010 Carpenter et al. Jan 2003 A1
20030018282 Effenhauser et al. Jan 2003 A1
20030018300 Duchon et al. Jan 2003 A1
20030028125 Yuzhakov et al. Feb 2003 A1
20030028126 List Feb 2003 A1
20030032077 Itoh et al. Feb 2003 A1
20030038047 Sleva et al. Feb 2003 A1
20030050537 Wessel Mar 2003 A1
20030050573 Kuhr et al. Mar 2003 A1
20030050656 Schraga Mar 2003 A1
20030057391 Krulevitch et al. Mar 2003 A1
20030060730 Perez Mar 2003 A1
20030069509 Matzinger et al. Apr 2003 A1
20030069753 Brown Apr 2003 A1
20030072647 Lum Apr 2003 A1
20030073089 Mauze et al. Apr 2003 A1
20030073229 Greenstein et al. Apr 2003 A1
20030073931 Boecker et al. Apr 2003 A1
20030083685 Freeman et al. May 2003 A1
20030083686 Freeman et al. May 2003 A1
20030088160 Halleck et al. May 2003 A1
20030088191 Freeman et al. May 2003 A1
20030089730 May et al. May 2003 A1
20030092982 Eppstein May 2003 A1
20030093010 Essenpreis May 2003 A1
20030100040 Bonnecaze et al. May 2003 A1
20030106810 Douglas et al. Jun 2003 A1
20030109777 Kloepfer et al. Jun 2003 A1
20030109860 Black Jun 2003 A1
20030111357 Black Jun 2003 A1
20030113827 Burkoth Jun 2003 A1
20030116447 Surridge et al. Jun 2003 A1
20030120297 Beyerlein Jun 2003 A1
20030135333 Aceti et al. Jul 2003 A1
20030136189 Lauman et al. Jul 2003 A1
20030139653 Manser et al. Jul 2003 A1
20030143113 Yuzhakov et al. Jul 2003 A2
20030144608 Kojima et al. Jul 2003 A1
20030144609 Kennedy Jul 2003 A1
20030146110 Karinka et al. Aug 2003 A1
20030149348 Raskas Aug 2003 A1
20030149377 Erickson et al. Aug 2003 A1
20030150745 Teodorczyk et al. Aug 2003 A1
20030153900 Aceti et al. Aug 2003 A1
20030159944 Pottgen et al. Aug 2003 A1
20030163351 Brown et al. Aug 2003 A1
20030178322 Iyengar et al. Sep 2003 A1
20030191376 Samuels et al. Oct 2003 A1
20030191415 Moerman et al. Oct 2003 A1
20030195435 Williams Oct 2003 A1
20030195540 Moerman Oct 2003 A1
20030199744 Buse et al. Oct 2003 A1
20030199789 Boecker et al. Oct 2003 A1
20030199790 Boecker et al. Oct 2003 A1
20030199791 Boecker et al. Oct 2003 A1
20030199891 Argauer Oct 2003 A1
20030199893 Boecker et al. Oct 2003 A1
20030199894 Boecker et al. Oct 2003 A1
20030199895 Boecker et al. Oct 2003 A1
20030199896 Boecker et al. Oct 2003 A1
20030199897 Boecker et al. Oct 2003 A1
20030199898 Boecker et al. Oct 2003 A1
20030199899 Boecker et al. Oct 2003 A1
20030199900 Boecker et al. Oct 2003 A1
20030199901 Boecker et al. Oct 2003 A1
20030199902 Boecker et al. Oct 2003 A1
20030199903 Boecker et al. Oct 2003 A1
20030199904 Boecker et al. Oct 2003 A1
20030199905 Boecker et al. Oct 2003 A1
20030199906 Boecker et al. Oct 2003 A1
20030199907 Boecker et al. Oct 2003 A1
20030199908 Boecker et al. Oct 2003 A1
20030199909 Boecker et al. Oct 2003 A1
20030199910 Boecker et al. Oct 2003 A1
20030199911 Boecker et al. Oct 2003 A1
20030199912 Pugh Oct 2003 A1
20030201194 Heller et al. Oct 2003 A1
20030203352 Haviland et al. Oct 2003 A1
20030206828 Bell Nov 2003 A1
20030208140 Pugh Nov 2003 A1
20030210811 Dubowsky et al. Nov 2003 A1
20030211619 Olson et al. Nov 2003 A1
20030212344 Yuzhakov et al. Nov 2003 A1
20030212345 McAllister et al. Nov 2003 A1
20030212346 Yuzhakov et al. Nov 2003 A1
20030212347 Sohrab Nov 2003 A1
20030212379 Bylund et al. Nov 2003 A1
20030212423 Pugh et al. Nov 2003 A1
20030212424 Briggs et al. Nov 2003 A1
20030212579 Brown et al. Nov 2003 A1
20030216767 List et al. Nov 2003 A1
20030217918 Davies et al. Nov 2003 A1
20030220552 Reghabi et al. Nov 2003 A1
20030220663 Fletcher et al. Nov 2003 A1
20030223906 McAllister et al. Dec 2003 A1
20030225317 Schell Dec 2003 A1
20030225429 Garthe et al. Dec 2003 A1
20030225430 Schraga Dec 2003 A1
20030228637 Wang Dec 2003 A1
20030229514 Brown Dec 2003 A2
20030232370 Trifiro Dec 2003 A1
20030233055 Erickson et al. Dec 2003 A1
20030233112 Alden et al. Dec 2003 A1
20030233113 Alden et al. Dec 2003 A1
20040007585 Griffith et al. Jan 2004 A1
20040009100 Simons et al. Jan 2004 A1
20040010279 Freeman et al. Jan 2004 A1
20040015064 Parsons Jan 2004 A1
20040019250 Catelli Jan 2004 A1
20040019259 Brown et al. Jan 2004 A1
20040026243 Davies et al. Feb 2004 A1
20040026244 Hodges et al. Feb 2004 A1
20040030353 Schmelzeisen-Redeker et al. Feb 2004 A1
20040031682 Wilsey Feb 2004 A1
20040034318 Fritz et al. Feb 2004 A1
20040038045 Smart et al. Feb 2004 A1
20040039303 Wurster et al. Feb 2004 A1
20040039342 Eppstein et al. Feb 2004 A1
20040039407 Schraga Feb 2004 A1
20040039408 Abulhaj et al. Feb 2004 A1
20040049219 Briggs et al. Mar 2004 A1
20040049220 Boecker et al. Mar 2004 A1
20040050694 Yang et al. Mar 2004 A1
20040054267 Feldman et al. Mar 2004 A1
20040055898 Heller et al. Mar 2004 A1
20040059256 Perez Mar 2004 A1
20040060818 Feldman et al. Apr 2004 A1
20040061841 Black et al. Apr 2004 A1
20040064068 DeNuzzio et al. Apr 2004 A1
20040065669 Giraud et al. Apr 2004 A1
20040068093 Merrigan et al. Apr 2004 A1
20040068283 Fukuzawa et al. Apr 2004 A1
20040069657 Hodges et al. Apr 2004 A1
20040087990 Boecker et al. May 2004 A1
20040092842 Boecker et al. May 2004 A1
20040092994 Briggs et al. May 2004 A1
20040092995 Boecker et al. May 2004 A1
20040096991 Zhang May 2004 A1
20040098009 Boecker et al. May 2004 A1
20040098010 Davison et al. May 2004 A1
20040102803 Boecker et al. May 2004 A1
20040106855 Brown Jun 2004 A1
20040106858 Say et al. Jun 2004 A1
20040106859 Say et al. Jun 2004 A1
20040106860 Say et al. Jun 2004 A1
20040106904 Gonnelli et al. Jun 2004 A1
20040106941 Roe et al. Jun 2004 A1
20040107116 Brown Jun 2004 A1
20040115754 Chang Jun 2004 A1
20040115831 Meathrel et al. Jun 2004 A1
20040116780 Brown Jun 2004 A1
20040116829 Raney et al. Jun 2004 A1
20040117207 Brown Jun 2004 A1
20040117208 Brown Jun 2004 A1
20040117209 Brown Jun 2004 A1
20040117210 Brown Jun 2004 A1
20040122339 Roe Jun 2004 A1
20040127818 Roe et al. Jul 2004 A1
20040127819 Roe Jul 2004 A1
20040127928 Whitson et al. Jul 2004 A1
20040127929 Roe Jul 2004 A1
20040132167 Rule et al. Jul 2004 A1
20040133125 Miyashita et al. Jul 2004 A1
20040133127 Roe et al. Jul 2004 A1
20040137640 Hirao et al. Jul 2004 A1
20040138541 Ward et al. Jul 2004 A1
20040138588 Saikley et al. Jul 2004 A1
20040138688 Giraud Jul 2004 A1
20040146958 Bae et al. Jul 2004 A1
20040154932 Deng et al. Aug 2004 A1
20040157017 Mauze et al. Aug 2004 A1
20040157149 Hofmann Aug 2004 A1
20040157319 Keen Aug 2004 A1
20040157338 Burke et al. Aug 2004 A1
20040157339 Burke et al. Aug 2004 A1
20040158137 Eppstein et al. Aug 2004 A1
20040158271 Hamamoto Aug 2004 A1
20040161737 Yang et al. Aug 2004 A1
20040162473 Sohrab Aug 2004 A1
20040162474 Kiser et al. Aug 2004 A1
20040162506 Duchon et al. Aug 2004 A1
20040162573 Kheiri Aug 2004 A1
20040167383 Kim et al. Aug 2004 A1
20040171057 Mauze et al. Sep 2004 A1
20040171968 Katsuki et al. Sep 2004 A1
20040172000 Roe et al. Sep 2004 A1
20040173472 Jung et al. Sep 2004 A1
20040173488 Griffin et al. Sep 2004 A1
20040176705 Stevens et al. Sep 2004 A1
20040176732 Frazier et al. Sep 2004 A1
20040178066 Miyazaki et al. Sep 2004 A1
20040178067 Miyazaki et al. Sep 2004 A1
20040178216 Brickwood et al. Sep 2004 A1
20040180379 Van Duyne et al. Sep 2004 A1
20040182703 Bell et al. Sep 2004 A1
20040185568 Matsumoto Sep 2004 A1
20040186359 Beaudoin et al. Sep 2004 A1
20040186394 Roe et al. Sep 2004 A1
20040186500 Koike et al. Sep 2004 A1
20040193201 Kim Sep 2004 A1
20040193377 Brown Sep 2004 A1
20040194302 Bhullar et al. Oct 2004 A1
20040197231 Katsuki et al. Oct 2004 A1
20040197821 Bauer Oct 2004 A1
20040199062 Petersson et al. Oct 2004 A1
20040199409 Brown Oct 2004 A1
20040200720 Musho et al. Oct 2004 A1
20040200721 Bhullar et al. Oct 2004 A1
20040202576 Aceti et al. Oct 2004 A1
20040204662 Perez et al. Oct 2004 A1
20040206625 Bhullar et al. Oct 2004 A1
20040206636 Hodges et al. Oct 2004 A1
20040206658 Hammerstedt et al. Oct 2004 A1
20040209307 Valkirs et al. Oct 2004 A1
20040209350 Sakata Oct 2004 A1
20040209354 Mathies et al. Oct 2004 A1
20040210279 Gruzdev et al. Oct 2004 A1
20040211666 Pamidi et al. Oct 2004 A1
20040214253 Paek et al. Oct 2004 A1
20040215224 Sakata et al. Oct 2004 A1
20040215225 Nakayama Oct 2004 A1
20040216516 Sato Nov 2004 A1
20040217019 Cai et al. Nov 2004 A1
20040219500 Brown et al. Nov 2004 A1
20040219535 Bell et al. Nov 2004 A1
20040220456 Eppstein Nov 2004 A1
20040220495 Cahir et al. Nov 2004 A1
20040220564 Ho et al. Nov 2004 A1
20040220603 Rutynowski et al. Nov 2004 A1
20040222092 Musho et al. Nov 2004 A1
20040224369 Cai et al. Nov 2004 A1
20040225230 Liamos et al. Nov 2004 A1
20040225311 Levaughn et al. Nov 2004 A1
20040225312 Orloff et al. Nov 2004 A1
20040230216 Levaughn et al. Nov 2004 A1
20040231983 Shen et al. Nov 2004 A1
20040231984 Lauks et al. Nov 2004 A1
20040232009 Okuda et al. Nov 2004 A1
20040236250 Hodges et al. Nov 2004 A1
20040236251 Roe et al. Nov 2004 A1
20040236268 Mitragotri et al. Nov 2004 A1
20040236362 Shraga Nov 2004 A1
20040238357 Bhullar et al. Dec 2004 A1
20040238358 Forrow et al. Dec 2004 A1
20040238359 Ikeda et al. Dec 2004 A1
20040241746 Adlassnig et al. Dec 2004 A1
20040242977 Dosmann Dec 2004 A1
20040243164 D'Agostino Dec 2004 A1
20040243165 Koike et al. Dec 2004 A1
20040245101 Willner et al. Dec 2004 A1
20040248282 Sobha M. et al. Dec 2004 A1
20040248312 Vreeke et al. Dec 2004 A1
20040249254 Racchini et al. Dec 2004 A1
20040249310 Shartle et al. Dec 2004 A1
20040249311 Haar et al. Dec 2004 A1
20040249405 Watanabe et al. Dec 2004 A1
20040249406 Griffin et al. Dec 2004 A1
20040251131 Ueno et al. Dec 2004 A1
20040253634 Wang Dec 2004 A1
20040254434 Goodnow et al. Dec 2004 A1
20040254599 Lipoma et al. Dec 2004 A1
20040256228 Huang Dec 2004 A1
20040256248 Burke et al. Dec 2004 A1
20040256685 Chou et al. Dec 2004 A1
20040258564 Charlton Dec 2004 A1
20040260204 Boecker et al. Dec 2004 A1
20040260324 Fukuzawa et al. Dec 2004 A1
20040260325 Kuhr et al. Dec 2004 A1
20040260326 Lipoma et al. Dec 2004 A1
20040260511 Burke et al. Dec 2004 A1
20040267105 Monfre et al. Dec 2004 A1
20040267121 Sarvazyan et al. Dec 2004 A1
20040267160 Perez Dec 2004 A9
20040267299 Kuriger Dec 2004 A1
20040267300 Mace Dec 2004 A1
20050000806 Hsieh Jan 2005 A1
20050000807 Wang et al. Jan 2005 A1
20050000808 Cui et al. Jan 2005 A1
20050003470 Nelson et al. Jan 2005 A1
20050004437 Kaufmann et al. Jan 2005 A1
20050004494 Perez et al. Jan 2005 A1
20050008537 Mosoiu et al. Jan 2005 A1
20050008851 Ezoe et al. Jan 2005 A1
20050009191 Swenson et al. Jan 2005 A1
20050010090 Acosta et al. Jan 2005 A1
20050010093 Ford et al. Jan 2005 A1
20050010134 Douglas et al. Jan 2005 A1
20050010137 Hodges et al. Jan 2005 A1
20050010198 Marchitto et al. Jan 2005 A1
20050011759 Moerman et al. Jan 2005 A1
20050013731 Burke et al. Jan 2005 A1
20050014997 Ruchti et al. Jan 2005 A1
20050015020 LeVaughn et al. Jan 2005 A1
20050016844 Burke et al. Jan 2005 A1
20050019212 Bhullar et al. Jan 2005 A1
20050019219 Oshiman et al. Jan 2005 A1
20050019805 Groll Jan 2005 A1
20050019945 Groll et al. Jan 2005 A1
20050019953 Groll Jan 2005 A1
20050021066 Kuhr et al. Jan 2005 A1
20050027181 Goode et al. Feb 2005 A1
20050027211 Kuhr et al. Feb 2005 A1
20050027562 Brown Feb 2005 A1
20050033340 Lipoma et al. Feb 2005 A1
20050033341 Vreeke et al. Feb 2005 A1
20050034983 Chambers et al. Feb 2005 A1
20050036020 Li et al. Feb 2005 A1
20050036146 Braig et al. Feb 2005 A1
20050036906 Nakahara et al. Feb 2005 A1
20050036909 Erickson et al. Feb 2005 A1
20050037482 Braig et al. Feb 2005 A1
20050038329 Morris et al. Feb 2005 A1
20050038330 Jansen et al. Feb 2005 A1
20050038463 Davar Feb 2005 A1
20050038464 Shraga Feb 2005 A1
20050038465 Shraga Feb 2005 A1
20050038674 Braig et al. Feb 2005 A1
20050042766 Ohman et al. Feb 2005 A1
20050043894 Fernandez Feb 2005 A1
20050043965 Heller et al. Feb 2005 A1
20050045476 Neel et al. Mar 2005 A1
20050049472 Manda et al. Mar 2005 A1
20050049473 Desai et al. Mar 2005 A1
20050050859 Coppeta et al. Mar 2005 A1
20050054082 Pachl et al. Mar 2005 A1
20050054908 Blank et al. Mar 2005 A1
20050059872 Shartle et al. Mar 2005 A1
20050059895 Brown Mar 2005 A1
20050060194 Brown Mar 2005 A1
20050061668 Brenneman et al. Mar 2005 A1
20050064528 Kwon et al. Mar 2005 A1
20050067280 Reid et al. Mar 2005 A1
20050067737 Rappin et al. Mar 2005 A1
20050070771 Rule et al. Mar 2005 A1
20050070819 Poux et al. Mar 2005 A1
20050070945 Schraga Mar 2005 A1
20050072670 Hasegawa et al. Apr 2005 A1
20050077176 Hodges et al. Apr 2005 A1
20050077584 Uhland et al. Apr 2005 A1
20050079542 Cullen Apr 2005 A1
20050080652 Brown Apr 2005 A1
20050085839 Allen et al. Apr 2005 A1
20050085840 Yi et al. Apr 2005 A1
20050086083 Brown Apr 2005 A1
20050090754 Wolff et al. Apr 2005 A1
20050090850 Thoes et al. Apr 2005 A1
20050096520 Maekawa et al. May 2005 A1
20050096565 Chang May 2005 A1
20050096586 Trautman et al. May 2005 A1
20050096587 Santini et al. May 2005 A1
20050096686 Allen May 2005 A1
20050098431 Hodges et al. May 2005 A1
20050098432 Gundel May 2005 A1
20050098433 Gundel May 2005 A1
20050098434 Gundel et al. May 2005 A1
20050100880 Chang May 2005 A1
20050101841 Kaylor et al. May 2005 A9
20050101979 Alden et al. May 2005 A1
20050101980 Alden et al. May 2005 A1
20050101981 Alden et al. May 2005 A1
20050103624 Bhullar et al. May 2005 A1
20050106713 Phan et al. May 2005 A1
20050109637 Iyengar et al. May 2005 A1
20050112712 Ouyang et al. May 2005 A1
20050112782 Buechler May 2005 A1
20050113658 Jacobson et al. May 2005 A1
20050113717 Matzinger et al. May 2005 A1
20050114062 Davies et al. May 2005 A1
20050114154 Wolkowicz et al. May 2005 A1
20050114444 Brown et al. May 2005 A1
20050118056 Swanson et al. Jun 2005 A1
20050118062 Otake Jun 2005 A1
20050119681 Marshall et al. Jun 2005 A1
20050123443 Fujiwara et al. Jun 2005 A1
20050124869 Hefti et al. Jun 2005 A1
20050125017 Kudrna et al. Jun 2005 A1
20050125018 Galloway et al. Jun 2005 A1
20050125019 Kudrna et al. Jun 2005 A1
20050126929 Mansouri et al. Jun 2005 A1
20050130248 Willner et al. Jun 2005 A1
20050130249 Parris et al. Jun 2005 A1
20050130292 Ahn et al. Jun 2005 A1
20050131286 Parker et al. Jun 2005 A1
20050131441 Iio et al. Jun 2005 A1
20050133368 Davies et al. Jun 2005 A1
20050136471 Bhullar et al. Jun 2005 A1
20050136501 Kuriger Jun 2005 A1
20050136529 Yang et al. Jun 2005 A1
20050136550 Yang et al. Jun 2005 A1
20050137531 Prausnitz et al. Jun 2005 A1
20050137536 Gonnelli Jun 2005 A1
20050140659 Hohl et al. Jun 2005 A1
20050143675 Neel et al. Jun 2005 A1
20050143713 Delmore et al. Jun 2005 A1
20050143771 Stout et al. Jun 2005 A1
20050145490 Shinno et al. Jul 2005 A1
20050145491 Amano et al. Jul 2005 A1
20050145520 Ilo et al. Jul 2005 A1
20050149088 Fukuda et al. Jul 2005 A1
20050149089 Trissel et al. Jul 2005 A1
20050149090 Morita et al. Jul 2005 A1
20050150762 Butters et al. Jul 2005 A1
20050150763 Butters et al. Jul 2005 A1
20050154277 Tang et al. Jul 2005 A1
20050154374 Hunter et al. Jul 2005 A1
20050154410 Conway et al. Jul 2005 A1
20050154616 Iliff Jul 2005 A1
20050158850 Kubo et al. Jul 2005 A1
20050159656 Hockersmith et al. Jul 2005 A1
20050159768 Boehm et al. Jul 2005 A1
20050164322 Heller et al. Jul 2005 A1
20050164329 Wallace-Davis et al. Jul 2005 A1
20050165285 Iliff Jul 2005 A1
20050165393 Eppstein Jul 2005 A1
20050165622 Neel et al. Jul 2005 A1
20050169810 Hagen et al. Aug 2005 A1
20050169961 Hunter et al. Aug 2005 A1
20050170448 Burson et al. Aug 2005 A1
20050171567 DeHart Aug 2005 A1
20050172021 Brown Aug 2005 A1
20050172022 Brown Aug 2005 A1
20050173245 Feldman et al. Aug 2005 A1
20050173246 Hodges et al. Aug 2005 A1
20050175509 Nakaminami et al. Aug 2005 A1
20050176084 Burkoth Aug 2005 A1
20050176133 Miyashita et al. Aug 2005 A1
20050176153 O'hara et al. Aug 2005 A1
20050177071 Nakayama et al. Aug 2005 A1
20050177201 Freeman Aug 2005 A1
20050177398 Watanabe et al. Aug 2005 A1
20050178218 Montagu Aug 2005 A1
20050181010 Hunter et al. Aug 2005 A1
20050181497 Saito et al. Aug 2005 A1
20050182307 Currie et al. Aug 2005 A1
20050187439 Blank et al. Aug 2005 A1
20050187442 Cho et al. Aug 2005 A1
20050187444 Hubner et al. Aug 2005 A1
20050192488 Bryenton et al. Sep 2005 A1
20050196821 Monfre et al. Sep 2005 A1
20050197666 Raney Sep 2005 A1
20050201897 Zimmer et al. Sep 2005 A1
20050202567 Zanzucchi et al. Sep 2005 A1
20050203358 Monfre et al. Sep 2005 A1
20050203364 Monfre et al. Sep 2005 A1
20050204939 Krejci Sep 2005 A1
20050205136 Freeman Sep 2005 A1
20050205422 Moser et al. Sep 2005 A1
20050205816 Hayenga et al. Sep 2005 A1
20050209515 Hockersmith et al. Sep 2005 A1
20050209564 Bonner et al. Sep 2005 A1
20050209625 Chan Sep 2005 A1
20050211571 Schulein et al. Sep 2005 A1
20050211572 Buck et al. Sep 2005 A1
20050214881 Azarnia et al. Sep 2005 A1
20050214892 Kovatchev et al. Sep 2005 A1
20050215871 Feldman et al. Sep 2005 A1
20050215872 Berner et al. Sep 2005 A1
20050215923 Wiegel Sep 2005 A1
20050215925 Chan Sep 2005 A1
20050216046 Yeoh et al. Sep 2005 A1
20050218024 Lang et al. Oct 2005 A1
20050221276 Rozakis et al. Oct 2005 A1
20050221470 Matsumoto et al. Oct 2005 A1
20050222599 Czernecki et al. Oct 2005 A1
20050227372 Khan Oct 2005 A1
20050228242 Kawamura et al. Oct 2005 A1
20050228883 Brown Oct 2005 A1
20050230252 Tsai et al. Oct 2005 A1
20050230253 Marquant Oct 2005 A1
20050232813 Karmali Oct 2005 A1
20050232815 Ruhl et al. Oct 2005 A1
20050234368 Wong et al. Oct 2005 A1
20050234486 Allen et al. Oct 2005 A1
20050234487 Shi Oct 2005 A1
20050234488 Allen Oct 2005 A1
20050234489 Allen Oct 2005 A1
20050234490 Allen et al. Oct 2005 A1
20050234491 Allen et al. Oct 2005 A1
20050234492 Tsai et al. Oct 2005 A1
20050234494 Conway et al. Oct 2005 A1
20050234495 Schraga Oct 2005 A1
20050235060 Brown Oct 2005 A1
20050239154 Feldman et al. Oct 2005 A1
20050239156 Drucker et al. Oct 2005 A1
20050239194 Takahashi et al. Oct 2005 A1
20050240090 Ruchti et al. Oct 2005 A1
20050240119 Draudt et al. Oct 2005 A1
20050240207 Marshall Oct 2005 A1
20050240778 Saito Oct 2005 A1
20050245798 Yamaguchi et al. Nov 2005 A1
20050245843 Day et al. Nov 2005 A1
20050245844 Mace et al. Nov 2005 A1
20050245845 Roe et al. Nov 2005 A1
20050245846 Casey Nov 2005 A1
20050245954 Roe et al. Nov 2005 A1
20050245955 Schraga Nov 2005 A1
20050256534 Alden et al. Nov 2005 A1
20050258035 Harding et al. Nov 2005 A1
20050258036 Harding Nov 2005 A1
20050258050 Harding Nov 2005 A1
20050265094 Harding et al. Dec 2005 A1
20050276133 Harding et al. Dec 2005 A1
20050278945 Feldman et al. Dec 2005 A1
20050279631 Celentano Dec 2005 A1
20050279647 Beaty Dec 2005 A1
20050283094 Thym et al. Dec 2005 A1
20050284110 Lang et al. Dec 2005 A1
20050284757 Allen Dec 2005 A1
20050287620 Heller et al. Dec 2005 A1
20050288637 Kuhr et al. Dec 2005 A1
20050288698 Matsumoto Dec 2005 A1
20050288699 Schraga Dec 2005 A1
20060000549 Lang et al. Jan 2006 A1
20060003398 Heller et al. Jan 2006 A1
20060004270 Bedard et al. Jan 2006 A1
20060004271 Peyser et al. Jan 2006 A1
20060004272 Shah et al. Jan 2006 A1
20060006574 Lang et al. Jan 2006 A1
20060008389 Sacherer et al. Jan 2006 A1
20060015129 Shahrokni et al. Jan 2006 A1
20060016698 Lee et al. Jan 2006 A1
20060020228 Fowler et al. Jan 2006 A1
20060024774 Zocchi Feb 2006 A1
20060025662 Buse et al. Feb 2006 A1
20060029979 Bai et al. Feb 2006 A1
20060029991 Hagino et al. Feb 2006 A1
20060030028 Nakaminami et al. Feb 2006 A1
20060030050 Milne et al. Feb 2006 A1
20060030761 Raskas Feb 2006 A1
20060030788 Wong et al. Feb 2006 A1
20060034728 Kloepfer et al. Feb 2006 A1
20060037859 Hodges et al. Feb 2006 A1
20060040333 Zocchi Feb 2006 A1
20060047220 Sakata et al. Mar 2006 A1
20060047294 Mori Mar 2006 A1
20060052723 Roe Mar 2006 A1
20060052724 Roe Mar 2006 A1
20060052809 Karbowniczek et al. Mar 2006 A1
20060052810 Freeman et al. Mar 2006 A1
20060058827 Sakata Mar 2006 A1
20060058828 Shi Mar 2006 A1
20060062852 Holmes Mar 2006 A1
20060063988 Schurman et al. Mar 2006 A1
20060064035 Wang et al. Mar 2006 A1
20060079739 Chen Wang et al. Apr 2006 A1
20060079810 Patel et al. Apr 2006 A1
20060079811 Roe et al. Apr 2006 A1
20060079920 Schraga Apr 2006 A1
20060081469 Lee Apr 2006 A1
20060085020 Freeman et al. Apr 2006 A1
20060085137 Bartkowiak et al. Apr 2006 A1
20060086624 Tapsak et al. Apr 2006 A1
20060088945 Douglas et al. Apr 2006 A1
20060089566 DeHart Apr 2006 A1
20060091006 Wang et al. May 2006 A1
20060094944 Chuang May 2006 A1
20060094947 Kovatchev et al. May 2006 A1
20060094985 Aceti et al. May 2006 A1
20060094986 Neel et al. May 2006 A1
20060095061 Trautman et al. May 2006 A1
20060096859 Lau et al. May 2006 A1
20060099107 Yamamoto May 2006 A1
20060099703 Choi et al. May 2006 A1
20060100542 Wong et al. May 2006 A9
20060100543 Raney et al. May 2006 A1
20060100654 Fukuda et al. May 2006 A1
20060100655 Leong et al. May 2006 A1
20060100656 Olson et al. May 2006 A1
20060106373 Cahir et al. May 2006 A1
20060108236 Kasielke et al. May 2006 A1
20060113187 Deng et al. Jun 2006 A1
20060115857 Keen Jun 2006 A1
20060116562 Acosta et al. Jun 2006 A1
20060116704 Ashby et al. Jun 2006 A1
20060116705 Schraga Jun 2006 A1
20060119362 Kermani Jun 2006 A1
20060121547 McIntire Jun 2006 A1
20060121625 Clemens et al. Jun 2006 A1
20060121759 Kasai Jun 2006 A1
20060122099 Aoki Jun 2006 A1
20060122536 Haar et al. Jun 2006 A1
20060129065 Matsumoto et al. Jun 2006 A1
20060129172 Crossman et al. Jun 2006 A1
20060129173 Wilkinson Jun 2006 A1
20060134713 Rylatt et al. Jun 2006 A1
20060140457 Simshauser Jun 2006 A1
20060144704 Ghesquiere et al. Jul 2006 A1
20060151323 Cho Jul 2006 A1
20060155215 Cha et al. Jul 2006 A1
20060155316 Perez et al. Jul 2006 A1
20060155317 List Jul 2006 A1
20060156796 Burke et al. Jul 2006 A1
20060157362 Schraga Jul 2006 A1
20060160100 Gao et al. Jul 2006 A1
20060161078 Schraga Jul 2006 A1
20060161194 Freeman et al. Jul 2006 A1
20060163061 Hodges et al. Jul 2006 A1
20060166302 Clarke et al. Jul 2006 A1
20060167382 Deshmukh Jul 2006 A1
20060169599 Feldman et al. Aug 2006 A1
20060173254 Acosta et al. Aug 2006 A1
20060173255 Acosta et al. Aug 2006 A1
20060173379 Rasch-Menges et al. Aug 2006 A1
20060173380 Hoenes et al. Aug 2006 A1
20060173478 Schraga Aug 2006 A1
20060175216 Freeman et al. Aug 2006 A1
20060178573 Kermani et al. Aug 2006 A1
20060178599 Faupel et al. Aug 2006 A1
20060178600 Kennedy et al. Aug 2006 A1
20060178686 Schraga Aug 2006 A1
20060178687 Freeman et al. Aug 2006 A1
20060178688 Freeman et al. Aug 2006 A1
20060178689 Freeman et al. Aug 2006 A1
20060178690 Freeman et al. Aug 2006 A1
20060183871 Ward et al. Aug 2006 A1
20060183983 Acosta et al. Aug 2006 A1
20060184065 Deshmukh et al. Aug 2006 A1
20060184101 Srinivasan et al. Aug 2006 A1
20060188395 Taniike et al. Aug 2006 A1
20060189895 Neel et al. Aug 2006 A1
20060191787 Wang et al. Aug 2006 A1
20060195023 Acosta et al. Aug 2006 A1
20060195047 Freeman et al. Aug 2006 A1
20060195128 Alden et al. Aug 2006 A1
20060195129 Freeman et al. Aug 2006 A1
20060195130 Freeman et al. Aug 2006 A1
20060195131 Freeman et al. Aug 2006 A1
20060195132 Freeman et al. Aug 2006 A1
20060195133 Freeman et al. Aug 2006 A1
20060196031 Hoenes et al. Sep 2006 A1
20060196795 Windus-Smith et al. Sep 2006 A1
20060200044 Freeman et al. Sep 2006 A1
20060200045 Roe Sep 2006 A1
20060200046 Windus-Smith et al. Sep 2006 A1
20060200981 Bhullar et al. Sep 2006 A1
20060200982 Bhullar et al. Sep 2006 A1
20060201804 Chambers et al. Sep 2006 A1
20060204399 Freeman et al. Sep 2006 A1
20060205029 Heller Sep 2006 A1
20060205060 Kim et al. Sep 2006 A1
20060206135 Uehata et al. Sep 2006 A1
20060211127 Iwaki et al. Sep 2006 A1
20060211927 Acosta et al. Sep 2006 A1
20060211931 Blank et al. Sep 2006 A1
20060219551 Edelbrock et al. Oct 2006 A1
20060222566 Brauker et al. Oct 2006 A1
20060222567 Kloepfer et al. Oct 2006 A1
20060224171 Sakata et al. Oct 2006 A1
20060224172 LeVaughn et al. Oct 2006 A1
20060229532 Wong et al. Oct 2006 A1
20060229533 Hoenes et al. Oct 2006 A1
20060229651 Marshall et al. Oct 2006 A1
20060229652 Iio et al. Oct 2006 A1
20060231396 Yamaoka Oct 2006 A1
20060231418 Harding et al. Oct 2006 A1
20060231421 Diamond et al. Oct 2006 A1
20060231423 Harding et al. Oct 2006 A1
20060231425 Harding et al. Oct 2006 A1
20060231442 Windus-Smith et al. Oct 2006 A1
20060232278 Diamond et al. Oct 2006 A1
20060232528 Harding et al. Oct 2006 A1
20060233666 Vu et al. Oct 2006 A1
20060234263 Light Oct 2006 A1
20060234369 Sih Oct 2006 A1
20060235284 Lee Oct 2006 A1
20060235454 LeVaughn et al. Oct 2006 A1
20060241517 Fowler et al. Oct 2006 A1
20060241666 Briggs et al. Oct 2006 A1
20060241667 Freeman Oct 2006 A1
20060241668 Schraga Oct 2006 A1
20060241669 Stout et al. Oct 2006 A1
20060247154 Palmieri et al. Nov 2006 A1
20060247554 Roe Nov 2006 A1
20060247555 Harttig Nov 2006 A1
20060247670 LeVaughn et al. Nov 2006 A1
20060247671 LeVaughn Nov 2006 A1
20060254932 Hodges et al. Nov 2006 A1
20060259057 Kim et al. Nov 2006 A1
20060259058 Schiff et al. Nov 2006 A1
20060259060 Whitson et al. Nov 2006 A1
20060264718 Ruchti et al. Nov 2006 A1
20060264996 LeVaughn et al. Nov 2006 A1
20060264997 Colonna et al. Nov 2006 A1
20060266644 Pugh et al. Nov 2006 A1
20060266765 Pugh Nov 2006 A1
20060271083 Boecker et al. Nov 2006 A1
20060271084 Schraga Nov 2006 A1
20060276724 Freeman et al. Dec 2006 A1
20060277048 Kintzig et al. Dec 2006 A1
20060278545 Henning Dec 2006 A1
20060279431 Bakarania et al. Dec 2006 A1
20060281187 Emery et al. Dec 2006 A1
20060282109 Jansen et al. Dec 2006 A1
20060286620 Werner et al. Dec 2006 A1
20060287664 Grage, Jr. et al. Dec 2006 A1
20060293577 Morrison et al. Dec 2006 A1
20070004989 Dhillon Jan 2007 A1
20070004990 Kistner et al. Jan 2007 A1
20070007183 Schulat et al. Jan 2007 A1
20070009381 Schulat et al. Jan 2007 A1
20070010839 Galloway et al. Jan 2007 A1
20070010841 Teo et al. Jan 2007 A1
20070015978 Kanayama et al. Jan 2007 A1
20070016079 Freeman et al. Jan 2007 A1
20070016103 Calasso et al. Jan 2007 A1
20070016104 Jansen et al. Jan 2007 A1
20070016239 Sato et al. Jan 2007 A1
20070017805 Hodges et al. Jan 2007 A1
20070027370 Brauker et al. Feb 2007 A1
20070027427 Trautman et al. Feb 2007 A1
20070032812 Loerwald et al. Feb 2007 A1
20070032813 Flynn et al. Feb 2007 A1
20070038149 Calasso et al. Feb 2007 A1
20070038235 Freeman et al. Feb 2007 A1
20070043305 Boecker et al. Feb 2007 A1
20070043386 Freeman et al. Feb 2007 A1
20070049901 Wu et al. Mar 2007 A1
20070049959 Feaster et al. Mar 2007 A1
20070055174 Freeman et al. Mar 2007 A1
20070055297 Fukuzawa et al. Mar 2007 A1
20070055298 Uehata et al. Mar 2007 A1
20070060842 Alvarez-Icaza et al. Mar 2007 A1
20070060843 Alvarez-Icaza et al. Mar 2007 A1
20070060844 Alvarez-Icaza et al. Mar 2007 A1
20070060845 Perez Mar 2007 A1
20070061393 Moore Mar 2007 A1
20070062250 Krulevitch et al. Mar 2007 A1
20070062251 Anex Mar 2007 A1
20070062315 Hodges Mar 2007 A1
20070064516 Briggs et al. Mar 2007 A1
20070066939 Krulevitch et al. Mar 2007 A1
20070066940 Karunaratne et al. Mar 2007 A1
20070068807 Feldman et al. Mar 2007 A1
20070073188 Freeman et al. Mar 2007 A1
20070073189 Freeman et al. Mar 2007 A1
20070074977 Guo et al. Apr 2007 A1
20070078358 Escutia et al. Apr 2007 A1
20070078360 Matsumoto et al. Apr 2007 A1
20070078474 Kim Apr 2007 A1
20070080093 Boozer et al. Apr 2007 A1
20070083130 Thomson et al. Apr 2007 A1
20070083131 Escutia et al. Apr 2007 A1
20070083222 Schraga Apr 2007 A1
20070083335 Moerman Apr 2007 A1
20070084749 Demelo et al. Apr 2007 A1
20070088377 LeVaughn et al. Apr 2007 A1
20070092923 Chang Apr 2007 A1
20070093728 Douglas et al. Apr 2007 A1
20070093752 Zhao et al. Apr 2007 A1
20070093753 Krulevitch et al. Apr 2007 A1
20070093863 Pugh Apr 2007 A1
20070093864 Pugh Apr 2007 A1
20070095178 Schraga May 2007 A1
20070100255 Boecker et al. May 2007 A1
20070100256 Sansom May 2007 A1
20070100364 Sansom May 2007 A1
20070102312 Cha et al. May 2007 A1
20070106178 Roe et al. May 2007 A1
20070108048 Wang et al. May 2007 A1
20070112281 Olson May 2007 A1
20070112367 Olson May 2007 A1
20070118051 Korner et al. May 2007 A1
20070119710 Goldberger et al. May 2007 A1
20070123801 Goldberger et al. May 2007 A1
20070123802 Freeman May 2007 A1
20070123803 Fujiwara et al. May 2007 A1
20070129618 Goldberger et al. Jun 2007 A1
20070129650 Freeman et al. Jun 2007 A1
20070131565 Fujiwara et al. Jun 2007 A1
20070135828 Rutynowski Jun 2007 A1
20070142747 Boecker et al. Jun 2007 A1
20070142748 Deshmukh et al. Jun 2007 A1
20070142776 Kovelman et al. Jun 2007 A9
20070142854 Schraga Jun 2007 A1
20070144235 Werner et al. Jun 2007 A1
20070149875 Ouyang et al. Jun 2007 A1
20070149897 Ghesquiere et al. Jun 2007 A1
20070161960 Chen et al. Jul 2007 A1
20070162064 Starnes Jul 2007 A1
20070162065 Li et al. Jul 2007 A1
20070167869 Roe Jul 2007 A1
20070167870 Freeman et al. Jul 2007 A1
20070167871 Freeman et al. Jul 2007 A1
20070167872 Freeman et al. Jul 2007 A1
20070167873 Freeman et al. Jul 2007 A1
20070167874 Freeman et al. Jul 2007 A1
20070167875 Freeman et al. Jul 2007 A1
20070173739 Chan Jul 2007 A1
20070173740 Chan et al. Jul 2007 A1
20070173741 Deshmukh et al. Jul 2007 A1
20070173742 Freeman et al. Jul 2007 A1
20070173743 Freeman et al. Jul 2007 A1
20070173874 Uschold et al. Jul 2007 A1
20070173875 Uschold Jul 2007 A1
20070173876 Aylett et al. Jul 2007 A1
20070176120 Schwind et al. Aug 2007 A1
20070179356 Wessel Aug 2007 A1
20070179404 Escutia et al. Aug 2007 A1
20070179405 Emery et al. Aug 2007 A1
20070179406 DeNuzzio et al. Aug 2007 A1
20070182051 Harttig Aug 2007 A1
20070185412 Boecker et al. Aug 2007 A1
20070185515 Stout Aug 2007 A1
20070185516 Schosnig et al. Aug 2007 A1
20070191702 Yodfat et al. Aug 2007 A1
20070191737 Freeman et al. Aug 2007 A1
20070191738 Raney et al. Aug 2007 A1
20070191739 Roe Aug 2007 A1
20070193019 Feldman et al. Aug 2007 A1
20070193882 Dai et al. Aug 2007 A1
20070196240 Boozer et al. Aug 2007 A1
20070196242 Boozer et al. Aug 2007 A1
20070203514 Flaherty et al. Aug 2007 A1
20070203903 Attaran Rezaei et al. Aug 2007 A1
20070205103 Hodges et al. Sep 2007 A1
20070207498 Palmieri et al. Sep 2007 A1
20070213601 Freeman et al. Sep 2007 A1
20070213637 Boozer et al. Sep 2007 A1
20070213682 Haar et al. Sep 2007 A1
20070213756 Freeman et al. Sep 2007 A1
20070218543 Flaherty et al. Sep 2007 A1
20070219346 Trifiro Sep 2007 A1
20070219432 Thompson Sep 2007 A1
20070219436 Takase et al. Sep 2007 A1
20070219462 Briggs et al. Sep 2007 A1
20070219463 Briggs et al. Sep 2007 A1
20070219572 Deck et al. Sep 2007 A1
20070219573 Freeman et al. Sep 2007 A1
20070219574 Freeman et al. Sep 2007 A1
20070225741 Ikeda Sep 2007 A1
20070225742 Abe et al. Sep 2007 A1
20070227907 Shah et al. Oct 2007 A1
20070227911 Wang et al. Oct 2007 A1
20070227912 Chatelier et al. Oct 2007 A1
20070229085 Kawai Oct 2007 A1
20070232872 Prough et al. Oct 2007 A1
20070232956 Harman et al. Oct 2007 A1
20070233013 Schoenberg Oct 2007 A1
20070233166 Stout Oct 2007 A1
20070233167 Weiss et al. Oct 2007 A1
20070233395 Neel et al. Oct 2007 A1
20070235329 Harding et al. Oct 2007 A1
20070235347 Chatelier et al. Oct 2007 A1
20070239068 Rasch-Menges et al. Oct 2007 A1
20070239188 Boozer et al. Oct 2007 A1
20070239189 Freeman et al. Oct 2007 A1
20070239190 Alden et al. Oct 2007 A1
20070240984 Popovich et al. Oct 2007 A1
20070240986 Reymond et al. Oct 2007 A1
20070244380 Say et al. Oct 2007 A1
20070244412 Lav et al. Oct 2007 A1
20070244498 Steg Oct 2007 A1
20070244499 Briggs et al. Oct 2007 A1
20070249921 Groll et al. Oct 2007 A1
20070249962 Alden et al. Oct 2007 A1
20070249963 Alden et al. Oct 2007 A1
20070250099 Flora et al. Oct 2007 A1
20070251836 Hsu Nov 2007 A1
20070254359 Rezania et al. Nov 2007 A1
20070255141 Esenaliev et al. Nov 2007 A1
20070255178 Alvarez-Icaza et al. Nov 2007 A1
20070255179 Alvarez-Icaza et al. Nov 2007 A1
20070255180 Alvarez-Icaza et al. Nov 2007 A1
20070255181 Alvarez-Icaza et al. Nov 2007 A1
20070255300 Vanhiel et al. Nov 2007 A1
20070255301 Freeman et al. Nov 2007 A1
20070255302 Koeppel et al. Nov 2007 A1
20070260271 Freeman et al. Nov 2007 A1
20070260272 Weiss et al. Nov 2007 A1
20070264721 Buck Nov 2007 A1
20070265511 Renouf Nov 2007 A1
20070265532 Maynard et al. Nov 2007 A1
20070265654 Iio et al. Nov 2007 A1
20070273901 Baskeyfield et al. Nov 2007 A1
20070273903 Baskeyfield et al. Nov 2007 A1
20070273904 Robinson et al. Nov 2007 A1
20070273928 Robinson et al. Nov 2007 A1
20070276197 Harmon Nov 2007 A1
20070276211 Mir et al. Nov 2007 A1
20070276290 Boecker et al. Nov 2007 A1
20070276425 Kim et al. Nov 2007 A1
20070276621 Davies et al. Nov 2007 A1
20070278097 Bhullar et al. Dec 2007 A1
20070282186 Gilmore Dec 2007 A1
20070282362 Berg et al. Dec 2007 A1
20070288047 Thoes et al. Dec 2007 A1
20070293743 Monfre et al. Dec 2007 A1
20070293744 Monfre et al. Dec 2007 A1
20070293790 Bainczyk et al. Dec 2007 A1
20070293882 Harttig et al. Dec 2007 A1
20070293883 Horie Dec 2007 A1
20070295616 Harding et al. Dec 2007 A1
20080004651 Nicholls et al. Jan 2008 A1
20080007141 Deck Jan 2008 A1
20080009767 Effenhauser et al. Jan 2008 A1
20080009768 Sohrab Jan 2008 A1
20080009892 Freeman et al. Jan 2008 A1
20080009893 LeVaughn Jan 2008 A1
20080015425 Douglas et al. Jan 2008 A1
20080015623 Deck Jan 2008 A1
20080017522 Heller et al. Jan 2008 A1
20080019870 Newman et al. Jan 2008 A1
20080021291 Zocchi Jan 2008 A1
20080021293 Schurman et al. Jan 2008 A1
20080021295 Wang et al. Jan 2008 A1
20080021296 Creaven Jan 2008 A1
20080021346 Haar et al. Jan 2008 A1
20080021490 Briggs et al. Jan 2008 A1
20080021491 Freeman et al. Jan 2008 A1
20080021492 Freeman et al. Jan 2008 A1
20080021493 Levaughn et al. Jan 2008 A1
20080021494 Schmelzeisen-Redeker et al. Jan 2008 A1
20080027385 Freeman et al. Jan 2008 A1
20080031778 Kramer Feb 2008 A1
20080033268 Stafford Feb 2008 A1
20080033318 Mace et al. Feb 2008 A1
20080033319 Kloepfer et al. Feb 2008 A1
20080033468 Lathrop et al. Feb 2008 A1
20080033469 Winheim et al. Feb 2008 A1
20080034834 Schell Feb 2008 A1
20080034835 Schell Feb 2008 A1
20080039885 Purcell Feb 2008 A1
20080039886 Shi Feb 2008 A1
20080039887 Conway et al. Feb 2008 A1
20080040919 Griss et al. Feb 2008 A1
20080045825 Melker et al. Feb 2008 A1
20080045992 Schraga Feb 2008 A1
20080047764 Lee et al. Feb 2008 A1
20080053201 Roesicke et al. Mar 2008 A1
20080057484 Miyata et al. Mar 2008 A1
20080058624 Smart et al. Mar 2008 A1
20080058626 Miyata et al. Mar 2008 A1
20080058631 Draudt et al. Mar 2008 A1
20080058847 Abe et al. Mar 2008 A1
20080058848 Griffin et al. Mar 2008 A1
20080058849 Conway et al. Mar 2008 A1
20080060424 Babic et al. Mar 2008 A1
20080064986 Kraemer et al. Mar 2008 A1
20080064987 Escutia et al. Mar 2008 A1
20080065130 Patel et al. Mar 2008 A1
20080065131 List Mar 2008 A1
20080065132 Trissel et al. Mar 2008 A1
20080065133 Kennedy Mar 2008 A1
20080065134 Conway et al. Mar 2008 A1
20080073224 Diamond et al. Mar 2008 A1
20080077048 Escutia et al. Mar 2008 A1
20080077167 Flynn et al. Mar 2008 A1
20080077168 Nicholls et al. Mar 2008 A1
20080081969 Feldman et al. Apr 2008 A1
20080081976 Hodges et al. Apr 2008 A1
20080082023 Deck et al. Apr 2008 A1
20080082116 Lathrop et al. Apr 2008 A1
20080082117 Ruf Apr 2008 A1
20080086042 Brister et al. Apr 2008 A1
20080086044 Brister et al. Apr 2008 A1
20080086273 Shults et al. Apr 2008 A1
20080093227 Diamond et al. Apr 2008 A1
20080093228 Diamond et al. Apr 2008 A1
20080093230 Diamond et al. Apr 2008 A1
20080094804 Reynolds et al. Apr 2008 A1
20080097171 Smart et al. Apr 2008 A1
20080097241 Maltezos et al. Apr 2008 A1
20080097503 Creaven Apr 2008 A1
20080098802 Burke et al. May 2008 A1
20080103396 Johnson et al. May 2008 A1
20080103415 Roe et al. May 2008 A1
20080103517 Takemoto et al. May 2008 A1
20080105024 Creaven et al. May 2008 A1
20080105568 Wu May 2008 A1
20080108130 Nakaminami et al. May 2008 A1
20080108942 Brister et al. May 2008 A1
20080109024 Berkovitch et al. May 2008 A1
20080109025 Yang et al. May 2008 A1
20080109259 Thompson et al. May 2008 A1
20080112268 Ronnekleiv et al. May 2008 A1
20080112279 Nakagaki May 2008 A1
20080114227 Haar et al. May 2008 A1
20080114228 McCluskey et al. May 2008 A1
20080118400 Neel et al. May 2008 A1
20080119703 Brister et al. May 2008 A1
20080119704 Brister et al. May 2008 A1
20080119706 Brister et al. May 2008 A1
20080119761 Boecker et al. May 2008 A1
20080119883 Conway et al. May 2008 A1
20080119884 Flora et al. May 2008 A1
20080121533 Hodges et al. May 2008 A1
20080125800 List May 2008 A1
20080125801 List May 2008 A1
20080134806 Capriccio et al. Jun 2008 A1
20080134810 Neel et al. Jun 2008 A1
20080135559 Byrd Jun 2008 A1
20080140105 Zhong et al. Jun 2008 A1
20080144022 Schulat et al. Jun 2008 A1
20080146899 Ruchti et al. Jun 2008 A1
20080146966 Levaughn et al. Jun 2008 A1
20080147108 Kennedy Jun 2008 A1
20080149268 Zhao et al. Jun 2008 A1
20080149599 Bohm et al. Jun 2008 A1
20080152507 Bohm Jun 2008 A1
20080154187 Krulevitch et al. Jun 2008 A1
20080154513 Kovatchev et al. Jun 2008 A1
20080159913 Jung et al. Jul 2008 A1
20080161664 Mastrototaro et al. Jul 2008 A1
20080161724 Roe Jul 2008 A1
20080161725 Wong et al. Jul 2008 A1
20080166269 Jansen Jul 2008 A1
20080167578 Bryer et al. Jul 2008 A1
20080167673 Zhong et al. Jul 2008 A1
20080188771 Boecker et al. Aug 2008 A1
20080194987 Boecker Aug 2008 A1
20080194989 Briggs et al. Aug 2008 A1
20080200782 Planman et al. Aug 2008 A1
20080208026 Noujaim et al. Aug 2008 A1
20080208079 Hein et al. Aug 2008 A1
20080210574 Boecker Sep 2008 A1
20080214909 Fuerst et al. Sep 2008 A1
20080214917 Boecker Sep 2008 A1
20080214919 Harmon et al. Sep 2008 A1
20080214956 Briggs et al. Sep 2008 A1
20080228212 List Sep 2008 A1
20080249435 Haar et al. Oct 2008 A1
20080249554 Freeman et al. Oct 2008 A1
20080255598 LeVaughn et al. Oct 2008 A1
20080262387 List et al. Oct 2008 A1
20080262388 List et al. Oct 2008 A1
20080267822 List et al. Oct 2008 A1
20080269723 Mastrototaro et al. Oct 2008 A1
20080269791 Hoenes et al. Oct 2008 A1
20080275365 Guthrie et al. Nov 2008 A1
20080275384 Mastrototaro Nov 2008 A1
20080277291 Heller et al. Nov 2008 A1
20080277292 Heller et al. Nov 2008 A1
20080277293 Heller et al. Nov 2008 A1
20080277294 Heller et al. Nov 2008 A1
20080286149 Roe et al. Nov 2008 A1
20080294068 Briggs et al. Nov 2008 A1
20080300614 Freeman et al. Dec 2008 A1
20080318193 Alvarez-Icaza Dec 2008 A1
20080319284 Alvarez-Icaza Dec 2008 A1
20080319291 Freeman et al. Dec 2008 A1
20090005664 Freeman et al. Jan 2009 A1
20090020438 Hodges Jan 2009 A1
20090024009 Freeman et al. Jan 2009 A1
20090026075 Harding et al. Jan 2009 A1
20090026091 Harding et al. Jan 2009 A1
20090027040 Kermani et al. Jan 2009 A1
20090029479 Docherty et al. Jan 2009 A1
20090030441 Kudrna et al. Jan 2009 A1
20090043177 Milledge et al. Feb 2009 A1
20090043183 Kermani et al. Feb 2009 A1
20090048536 Freeman et al. Feb 2009 A1
20090054813 Freeman et al. Feb 2009 A1
20090057146 Teodorczyk et al. Mar 2009 A1
20090069716 Freeman et al. Mar 2009 A1
20090076415 Moerman Mar 2009 A1
20090084687 Chatelier et al. Apr 2009 A1
20090099477 Hoenes et al. Apr 2009 A1
20090105572 Malecha Apr 2009 A1
20090105573 Malecha Apr 2009 A1
20090112123 Freeman et al. Apr 2009 A1
20090112155 Zhao et al. Apr 2009 A1
20090112180 Krulevitch et al. Apr 2009 A1
20090112185 Krulevitch et al. Apr 2009 A1
20090112247 Freeman et al. Apr 2009 A1
20090118752 Perez et al. May 2009 A1
20090119760 Hung et al. May 2009 A1
20090124932 Freeman et al. May 2009 A1
20090131829 Freeman et al. May 2009 A1
20090131830 Freeman et al. May 2009 A1
20090131964 Freeman et al. May 2009 A1
20090131965 Freeman et al. May 2009 A1
20090137930 Freeman et al. May 2009 A1
20090138032 Freeman et al. May 2009 A1
20090139300 Pugh et al. Jun 2009 A1
20090177117 Amano et al. Jul 2009 A1
20090184004 Chatelier et al. Jul 2009 A1
20090187351 Orr et al. Jul 2009 A1
20090192410 Freeman et al. Jul 2009 A1
20090192411 Freeman Jul 2009 A1
20090196580 Freeman Aug 2009 A1
20090204025 Marsot et al. Aug 2009 A1
20090216100 Ebner et al. Aug 2009 A1
20090237262 Smith et al. Sep 2009 A1
20090240127 Ray Sep 2009 A1
20090247838 Cummings et al. Oct 2009 A1
20090247982 Krulevitch et al. Oct 2009 A1
20090259146 Freeman et al. Oct 2009 A1
20090270765 Ghesquiere et al. Oct 2009 A1
20090280551 Cardosi et al. Nov 2009 A1
20090281457 Faulkner et al. Nov 2009 A1
20090281458 Faulkner et al. Nov 2009 A1
20090281459 Faulkner et al. Nov 2009 A1
20090301899 Hodges et al. Dec 2009 A1
20090302872 Haggett et al. Dec 2009 A1
20090302873 Haggett et al. Dec 2009 A1
20090322630 Friman et al. Dec 2009 A1
20090325307 Haggett et al. Dec 2009 A1
20100016700 Sieh et al. Jan 2010 A1
20100018878 Davies Jan 2010 A1
20100030110 Choi et al. Feb 2010 A1
20100041084 Stephens et al. Feb 2010 A1
20100113981 Oki et al. May 2010 A1
20100145377 Lai et al. Jun 2010 A1
20100198107 Groll et al. Aug 2010 A1
20100210970 Horikawa et al. Aug 2010 A1
20100256525 List et al. Oct 2010 A1
20100274273 Schraga et al. Oct 2010 A1
20100292611 Lum et al. Nov 2010 A1
20100324452 Freeman et al. Dec 2010 A1
20110041449 Espinosa Feb 2011 A1
20110077478 Freeman et al. Mar 2011 A1
20110077553 Alroy Mar 2011 A1
20110098541 Freeman et al. Apr 2011 A1
20110178429 Jacobs Jul 2011 A1
20110184448 Brown et al. Jul 2011 A1
20120149999 Freeman et al. Jun 2012 A1
20120184876 Freeman et al. Jul 2012 A1
20120232425 Freeman et al. Sep 2012 A1
20120271197 Castle et al. Oct 2012 A1
20120296233 Freeman Nov 2012 A9
20130261500 Jacobs Oct 2013 A1
Foreign Referenced Citations (360)
Number Date Country
1946340 Apr 2007 CN
2206674 Aug 1972 DE
3538313 Apr 1986 DE
4212315 Oct 1993 DE
4320347 Dec 1994 DE
4344452 Jun 1995 DE
4420232 Dec 1995 DE
29800611 Jun 1998 DE
19819407 Nov 1999 DE
20009475 Sep 2000 DE
29824204 Sep 2000 DE
10032042 Jan 2002 DE
10057832 Feb 2002 DE
10053974 May 2002 DE
10142232 Mar 2003 DE
10208575 Aug 2003 DE
10208575 Aug 2003 DE
10245721 Dec 2003 DE
10361560 Jul 2005 DE
0112498 Jul 1984 EP
136362 Apr 1985 EP
137975 Apr 1985 EP
160768 Nov 1985 EP
170375 Feb 1986 EP
199484 Oct 1986 EP
254246 Jan 1988 EP
289269 Nov 1988 EP
0317847 May 1989 EP
320109 Jun 1989 EP
351891 Jan 1990 EP
359831 Mar 1990 EP
364208 Apr 1990 EP
368474 May 1990 EP
374355 Jun 1990 EP
406304 Jan 1991 EP
415388 Mar 1991 EP
415393 Mar 1991 EP
429076 May 1991 EP
0449147 Oct 1991 EP
449525 Oct 1991 EP
453283 Oct 1991 EP
461601 Dec 1991 EP
470649 Feb 1992 EP
471986 Feb 1992 EP
505475 Sep 1992 EP
505494 Sep 1992 EP
505504 Sep 1992 EP
530994 Mar 1993 EP
537761 Apr 1993 EP
552223 Jul 1993 EP
560336 Sep 1993 EP
562370 Sep 1993 EP
593096 Apr 1994 EP
0630609 Dec 1994 EP
636879 Feb 1995 EP
654659 May 1995 EP
0662367 Jul 1995 EP
685737 Dec 1995 EP
730037 Sep 1996 EP
735363 Oct 1996 EP
736607 Oct 1996 EP
759553 Feb 1997 EP
777123 Jun 1997 EP
795601 Sep 1997 EP
795748 Sep 1997 EP
817809 Jan 1998 EP
823239 Feb 1998 EP
847447 Jun 1998 EP
851224 Jul 1998 EP
856586 Aug 1998 EP
872728 Oct 1998 EP
874984 Nov 1998 EP
878708 Nov 1998 EP
894869 Feb 1999 EP
898936 Mar 1999 EP
901018 Mar 1999 EP
937249 Aug 1999 EP
938493 Sep 1999 EP
951939 Oct 1999 EP
964059 Dec 1999 EP
964060 Dec 1999 EP
969097 Jan 2000 EP
985376 Mar 2000 EP
1021950 Jul 2000 EP
1074832 Feb 2001 EP
1093854 Apr 2001 EP
1114995 Jul 2001 EP
1157660 Nov 2001 EP
1174083 Jan 2002 EP
1337182 Aug 2003 EP
1374770 Feb 2004 EP
1401233 Apr 2004 EP
1404232 Apr 2004 EP
1486766 Dec 2004 EP
1492457 Jan 2005 EP
1502614 Feb 2005 EP
1643908 Apr 2006 EP
1779780 May 2007 EP
1790288 May 2007 EP
1881322 Jan 2008 EP
1921992 May 2008 EP
2039294 Mar 2009 EP
2119396 Nov 2009 EP
2130493 Dec 2009 EP
2555432 May 1985 FR
2622457 May 1989 FR
1558111 Dec 1979 GB
2168815 Jun 1986 GB
2331936 Jun 1999 GB
2335860 Oct 1999 GB
2335990 Oct 1999 GB
04-194660 Jul 1992 JP
19920194660 Jul 1992 JP
10-104906 Jan 1998 JP
2000-116768 Apr 2000 JP
2009082631 Apr 2009 JP
WO-8001389 Jul 1980 WO
WO-8504089 Sep 1985 WO
WO-8605966 Oct 1986 WO
WO-8607632 Dec 1986 WO
WO-8908713 Sep 1989 WO
WO-9109139 Jun 1991 WO
WO-9109316 Jun 1991 WO
WO-9109373 Jun 1991 WO
WO-9203099 Mar 1992 WO
WO-9206971 Apr 1992 WO
WO-9207263 Apr 1992 WO
WO-9207468 May 1992 WO
WO-9300044 Jan 1993 WO
WO-9302720 Feb 1993 WO
WO-9306979 Apr 1993 WO
WO-9309723 May 1993 WO
WO-9312726 Jul 1993 WO
WO-9325898 Dec 1993 WO
WO-9427140 Nov 1994 WO
WO-9429703 Dec 1994 WO
WO-9429704 Dec 1994 WO
WO-9429731 Dec 1994 WO
WO-9500662 Jan 1995 WO
WO-9506240 Mar 1995 WO
WO-9510223 Apr 1995 WO
WO-9512583 May 1995 WO
WO-9522597 Aug 1995 WO
WO-9614799 May 1996 WO
WO-9630431 Oct 1996 WO
WO-9637148 Nov 1996 WO
WO-9702359 Jan 1997 WO
WO-9702487 Jan 1997 WO
WO-9711883 Apr 1997 WO
WO-9718464 May 1997 WO
WO-9728741 Aug 1997 WO
WO-9730344 Aug 1997 WO
WO-9742882 Nov 1997 WO
WO-9742888 Nov 1997 WO
WO-9745720 Dec 1997 WO
WO-9803431 Jan 1998 WO
WO-9814436 Apr 1998 WO
WO-9819159 May 1998 WO
WO-9819609 May 1998 WO
WO-9820332 May 1998 WO
WO-9820348 May 1998 WO
WO-9820867 May 1998 WO
WO-9824366 Jun 1998 WO
WO-9824373 Jun 1998 WO
WO-9835225 Aug 1998 WO
WO-9845276 Oct 1998 WO
WO-9903584 Jan 1999 WO
WO-9905966 Feb 1999 WO
WO-9907295 Feb 1999 WO
WO-9907431 Feb 1999 WO
WO-9913100 Mar 1999 WO
WO-9918532 Apr 1999 WO
WO-9919507 Apr 1999 WO
WO-9919717 Apr 1999 WO
WO-9917854 Apr 1999 WO
WO-9927483 Jun 1999 WO
WO-9927852 Jun 1999 WO
WO-9962576 Dec 1999 WO
WO-9964508 Dec 1999 WO
WO-0006024 Feb 2000 WO
WO-0009184 Feb 2000 WO
WO-0011578 Mar 2000 WO
WO-0015103 Mar 2000 WO
WO-0017799 Mar 2000 WO
WO-0017800 Mar 2000 WO
WO-0018293 Apr 2000 WO
WO-0019346 Apr 2000 WO
WO-0020626 Apr 2000 WO
WO-0029577 May 2000 WO
WO-0030186 May 2000 WO
WO-0032097 Jun 2000 WO
WO-0032098 Jun 2000 WO
WO-0033236 Jun 2000 WO
WO-0039914 Jul 2000 WO
WO-0042422 Jul 2000 WO
WO-0044084 Jul 2000 WO
WO-0046854 Aug 2000 WO
WO-0050771 Aug 2000 WO
WO-0055915 Sep 2000 WO
WO-0060340 Oct 2000 WO
WO-0067245 Oct 2000 WO
WO-0067245 Nov 2000 WO
WO-0067268 Nov 2000 WO
WO-0072452 Nov 2000 WO
WO-0100090 Jan 2001 WO
WO-0115807 Mar 2001 WO
WO-0116578 Mar 2001 WO
WO-0123885 Apr 2001 WO
WO-0125775 Apr 2001 WO
WO-0126813 Apr 2001 WO
WO-0129037 Apr 2001 WO
WO-0133216 May 2001 WO
WO-0134029 May 2001 WO
WO-0136955 May 2001 WO
WO-0137174 May 2001 WO
WO-0140788 Jun 2001 WO
WO-0145014 Jun 2001 WO
WO-0157510 Aug 2001 WO
WO-0163271 Aug 2001 WO
WO-0164105 Sep 2001 WO
WO-0169505 Sep 2001 WO
WO-0166010 Sep 2001 WO
WO-0172220 Oct 2001 WO
WO-0172225 Oct 2001 WO
WO-0173124 Oct 2001 WO
WO-0173395 Oct 2001 WO
WO-0175433 Oct 2001 WO
WO-0189691 Nov 2001 WO
WO-0191634 Dec 2001 WO
WO-0195806 Dec 2001 WO
WO-0200101 Jan 2002 WO
WO-0202796 Jan 2002 WO
WO-0208750 Jan 2002 WO
WO-0208753 Jan 2002 WO
WO-0208950 Jan 2002 WO
WO-0218940 Mar 2002 WO
WO-0221317 Mar 2002 WO
WO-0225551 Mar 2002 WO
WO-0232559 Apr 2002 WO
WO-0241227 May 2002 WO
WO-0241779 May 2002 WO
WO-0244948 Jun 2002 WO
WO-0249507 Jun 2002 WO
WO-02056769 Jul 2002 WO
WO-02059734 Aug 2002 WO
WO-02069791 Sep 2002 WO
WO-02077638 Oct 2002 WO
WO-02099308 Dec 2002 WO
WO-02100251 Dec 2002 WO
WO-02100252 Dec 2002 WO
WO-02100253 Dec 2002 WO
WO-02100254 Dec 2002 WO
WO-02100460 Dec 2002 WO
WO-02100461 Dec 2002 WO
WO-02101343 Dec 2002 WO
WO-02101359 Dec 2002 WO
WO-03000321 Jan 2003 WO
WO-03023389 Mar 2003 WO
WO-03039369 May 2003 WO
WO-03042691 May 2003 WO
WO-03045557 Jun 2003 WO
WO-03046542 Jun 2003 WO
WO-03049609 Jun 2003 WO
WO-03050534 Jun 2003 WO
WO-03066128 Aug 2003 WO
WO-03070099 Aug 2003 WO
WO-03071940 Sep 2003 WO
WO-03082091 Oct 2003 WO
WO-03088824 Oct 2003 WO
WO-03088834 Oct 2003 WO
WO-03088835 Oct 2003 WO
WO-03088851 Oct 2003 WO
WO-03094752 Nov 2003 WO
WO-03101297 Dec 2003 WO
WO-2004003147 Jan 2004 WO
WO-2004008130 Jan 2004 WO
WO-2004022133 Mar 2004 WO
WO-2004017964 Mar 2004 WO
WO-2004026130 Apr 2004 WO
WO-2004040285 May 2004 WO
WO-2004040287 May 2004 WO
WO-2004040948 May 2004 WO
WO-2004041082 May 2004 WO
WO-2004045375 Jun 2004 WO
WO-2004054455 Jul 2004 WO
WO-2004060174 Jul 2004 WO
WO-2004060446 Jul 2004 WO
WO-2004065545 Aug 2004 WO
WO-2004091693 Oct 2004 WO
WO-2004098405 Nov 2004 WO
WO-2004107964 Dec 2004 WO
WO-2004107975 Dec 2004 WO
WO-2004112602 Dec 2004 WO
WO-2004112612 Dec 2004 WO
WO-2004103147 Dec 2004 WO
WO-2005001418 Jan 2005 WO
WO-2005006939 Jan 2005 WO
WO-2005011774 Feb 2005 WO
WO-2005013824 Feb 2005 WO
WO-2005016125 Feb 2005 WO
WO-2005018425 Mar 2005 WO
WO-2005018430 Mar 2005 WO
WO-2005018454 Mar 2005 WO
WO 2005018709 Mar 2005 WO
WO-2005018710 Mar 2005 WO
WO-2005018711 Mar 2005 WO
WO-2005022143 Mar 2005 WO
WO-2005023088 Mar 2005 WO
WO-2005033659 Apr 2005 WO
WO-2005034720 Apr 2005 WO
WO-2005034721 Apr 2005 WO
WO-2005034741 Apr 2005 WO
WO-2005034778 Apr 2005 WO
WO-2005035017 Apr 2005 WO
WO-2005037095 Apr 2005 WO
WO-20005035018 Apr 2005 WO
WO-2005045414 May 2005 WO
WO-2005046477 May 2005 WO
WO-2005065399 Jul 2005 WO
WO-2005065414 Jul 2005 WO
WO-2005065415 Jul 2005 WO
WO-2005072604 Aug 2005 WO
WO-2005084546 Sep 2005 WO
WO-2005084557 Sep 2005 WO
WO-2005104948 Nov 2005 WO
WO-2005114185 Dec 2005 WO
WO-2005116622 Dec 2005 WO
WO-2005119234 Dec 2005 WO
WO-2005120197 Dec 2005 WO
WO-2005120199 Dec 2005 WO
WO-2005121759 Dec 2005 WO
WO-2005123680 Dec 2005 WO
WO-2006001797 Jan 2006 WO
WO-2006001973 Jan 2006 WO
WO-2006005545 Jan 2006 WO
WO-2006011062 Feb 2006 WO
WO-2006-013045 Feb 2006 WO
WO-2006015615 Feb 2006 WO
WO-2006027702 Mar 2006 WO
WO-2006031920 Mar 2006 WO
WO-2006032391 Mar 2006 WO
WO-2006037646 Apr 2006 WO
WO-2006051342 May 2006 WO
WO-2006072004 Jul 2006 WO
WO-2006105146 Oct 2006 WO
WO-2006116441 Nov 2006 WO
WO-2006120365 Nov 2006 WO
WO-2007010087 Jan 2007 WO
WO-2007025635 Mar 2007 WO
WO-2007044834 Apr 2007 WO
WO-2007054335 May 2007 WO
WO-2007070719 Jun 2007 WO
WO-2007084367 Jul 2007 WO
WO-2007088905 Aug 2007 WO
WO-2007106470 Sep 2007 WO
WO-2007119900 Oct 2007 WO
WO-2008085052 Jul 2008 WO
WO-2008112268 Sep 2008 WO
WO-2008112279 Sep 2008 WO
WO-2010109461 Sep 2010 WO
Related Publications (1)
Number Date Country
20130303984 A1 Nov 2013 US
Divisions (1)
Number Date Country
Parent 12335808 Dec 2008 US
Child 13945131 US
Continuations (2)
Number Date Country
Parent 11244311 Oct 2005 US
Child 12335808 US
Parent 10558976 Nov 2006 US
Child 11244311 US