Method and apparatus using optical techniques to measure analyte levels

Information

  • Patent Grant
  • 9034639
  • Patent Number
    9,034,639
  • Date Filed
    Tuesday, June 26, 2012
    12 years ago
  • Date Issued
    Tuesday, May 19, 2015
    9 years ago
Abstract
A device is provided for use with a tissue penetrating system and/or a metering device for measuring analyte levels. The device comprises a cartridge and a plurality of analyte detecting members mounted on the cartridge. The cartridge may have a radial disc shape. The cartridge may also be sized to fit within the metering device. The analyte detecting members may be optical system using fluorescence lifetime to determine analyte levels. In one embodiment, the device may also include a fluid spreader positioned over at least a portion of the analyte detecting member to urge fluid toward one of the detecting members. A plurality of analyte detecting members may be used. Each analyte detecting member may be a low volume device.
Description
BACKGROUND OF THE INVENTION

Lancing devices are known in the medical health-care products industry for piercing the skin to produce blood for analysis. 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. The device may be held against the skin and mechanically triggered to ballistically launch the lancet. Unfortunately, the pain associated with each lancing event using known technology discourages patients from testing. In addition to vibratory stimulation of the skin as the driver impacts the end of a launcher stop, known spring based devices have the possibility of firing lancets that harmonically oscillate against the patient tissue, causing multiple strikes due to recoil. This recoil and multiple strikes of the lancet is one major impediment to patient compliance with a structured glucose monitoring regime.


Another impediment to patient compliance is the lack of spontaneous blood flow generated by known lancing technology. In addition to the pain as discussed above, a patient may need more than one lancing event to obtain a blood sample since spontaneous blood generation is unreliable using known lancing technology. Thus the pain is multiplied by the number of attempts required by a patient to successfully generate spontaneous blood flow. 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. Known devices poorly account for these skin thickness variations.


A still further impediment to improved compliance with glucose monitoring are the many steps and inconvenience associated with each lancing event. Many diabetic patients that are insulin dependent may need to self-test for blood glucose levels five to six times daily. The large number of steps required in traditional methods of glucose testing, ranging from lancing, to milking of blood, applying blood to a test strip, and getting the measurements from the test strip, discourages many diabetic patients from testing their blood glucose levels as often as recommended. Older patients and those with deteriorating motor skills encounter difficulty loading lancets into launcher devices, transferring blood onto a test strip, or inserting thin test strips into slots on glucose measurement meters. Additionally, the wound channel left on the patient by known systems may also be of a size that discourages those who are active with their hands or who are worried about healing of those wound channels from testing their glucose levels. Still further, the inconvenience of having to carry around a large number of individual test strips encumbers the users of conventional test equipment.


SUMMARY OF THE INVENTION

The present invention provides solutions for at least some of the drawbacks discussed above. Specifically, some embodiments of the present invention provide a multiple lancet solution to measuring analyte levels in the body. The invention may use a high density design, with regards to the number of penetrating members in a cartridge or number of analyte detecting members on a cartridge. The present invention may provide optical techniques for measuring analyte levels. The present invention may provide manufacturing techniques for such optical analyte detecting members. At least some of these and other objectives described herein will be met by embodiments of the present invention.


In one embodiment, a device is provided for use with a metering device or tissue penetrating device for measuring analyte levels. The device comprises a cartridge and a plurality of analyte detecting members mounted on the cartridge. The cartridge may have a radial disc shape. The cartridge may also be sized to fit within the metering device. The analyte detecting members may be optical system using fluorescence lifetime to determine analyte levels. In one embodiment, the device may also include a fluid spreader positioned over at least a portion of the analyte detecting member to urge fluid toward one of the detecting members. A plurality of analyte detecting members may be used. Each analyte detecting member may be a low volume device.


A further understanding of the nature and advantages of the invention will become apparent by reference to the remaining portions of the specification and drawings.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 is a perspective view illustrating a system, according to an embodiment for use in piercing skin to obtain a blood sample;



FIG. 2 is a plan view of a portion of a replaceable penetrating member cartridge forming part of the system;



FIG. 3 is a cross-sectional end view on 3-3 in FIG. 2;



FIG. 4 is a cross-sectional end view on 4-4 in FIG. 2;



FIG. 5 is a perspective view of an apparatus forming part of the system and used for manipulating components of the cartridge, illustrating pivoting of a penetrating member accelerator in a downward direction;



FIG. 6A is a view similar to FIG. 5, illustrating how the cartridge is rotated or advanced;



FIG. 6B is a cross-sectional side view illustrating how the penetrating member accelerator allows for the cartridge to be advanced;



FIGS. 7A and 7B are views similar to FIGS. 6A and 6B, respectively, illustrating pivoting of the penetrating member accelerator in an opposite direction to engage with a select one of the penetrating members in the cartridge;



FIGS. 8A and 8B are views similar to FIGS. 7A and 7B, respectively, illustrating how the penetrating member accelerator moves the selected penetrating member to pierce skin;



FIGS. 9A and 9B are views similar to FIGS. 8A and 8B, respectively, illustrating how the penetrating member accelerator returns the penetrating member to its original position;



FIG. 10 is a block diagram illustrating functional components of the apparatus; and



FIG. 11 is an end view illustrating a cartridge according to an optional embodiment that allows for better adhesion of sterilization barriers.



FIG. 12 is a cross-sectional view of an embodiment having features of the invention.



FIG. 13 is a cross-sectional view of an embodiment having features of the invention in operation.



FIG. 14 is a cross-sectional view illustrating a low-friction coating applied to one penetrating member contact surface.



FIG. 15 is a cross-sectional view illustrating a coating applied to one penetrating member contact surface which increases friction and improves the microscopic contact area between the penetrating member and the penetrating member contact surface.



FIG. 16 illustrates a portion of a penetrating member cartridge having an annular configuration with a plurality of radially oriented penetrating member slots and a distal edge of a drive member disposed in one of the penetrating member slots.



FIG. 17 is an elevational view in partial longitudinal section of a coated penetrating member in contact with a coated penetrating member contact surface.



FIG. 18 illustrates an embodiment of a lancing device having features of the invention.



FIG. 19 is a perspective view of a portion of a penetrating member cartridge base plate having a plurality of penetrating member slots and drive member guide slots disposed radially inward of and aligned with the penetrating member slots.



FIGS. 20-22 illustrate a penetrating member cartridge in section, a drive member, a penetrating member and the tip of a patient's finger during three sequential phases of a lancing cycle.



FIG. 23 illustrates an embodiment of a penetrating member cartridge having features of the invention.



FIG. 24 is an exploded view of a portion of the penetrating member cartridge of FIG. 12.



FIGS. 25 and 26 illustrate a multiple layer sterility barrier disposed over a penetrating member slot being penetrated by the distal end of a penetrating member during a lancing cycle.



FIGS. 27 and 28 illustrate an embodiment of a drive member coupled to a driver wherein the drive member includes a cutting member having a sharpened edge which is configured to cut through a sterility barrier of a penetrating member slot during a lancing cycle in order for the drive member to make contact with the penetrating member.



FIGS. 29 and 30 illustrate an embodiment of a penetrating member slot in longitudinal section having a ramped portion disposed at a distal end of the penetrating member slot and a drive member with a cutting edge at a distal end thereof for cutting through a sterility barrier during a lancing cycle.



FIGS. 31-34 illustrate drive member slots in a penetrating member cartridge wherein at least a portion of the drive member slots have a tapered opening which is larger in transverse dimension at the top of the drive member slot than at the bottom of the drive member slot.



FIGS. 35-37 illustrate an embodiment of a penetrating member cartridge and penetrating member drive member wherein the penetrating member drive member has a contoured jaws configured to grip a penetrating member shaft.



FIGS. 38 and 39 show a portion of a lancing device having a lid that can be opened to expose a penetrating member cartridge cavity for removal of a used penetrating member cartridge and insertion of a new penetrating member cartridge.



FIGS. 40 and 41 illustrate a penetrating member cartridge that has penetrating member slots on both sides.



FIGS. 42-44 illustrate end and perspective views of a penetrating member cartridge having a plurality of penetrating member slots formed from a corrugated surface of the penetrating member cartridge.



FIGS. 45-48 illustrate embodiments of a penetrating member and drive member wherein the penetrating member has a slotted shaft and the drive member has a protuberance configured to mate with the slot in the penetrating member shaft.



FIG. 49 is a perspective view of a cartridge according to the present invention.



FIGS. 50 and 51 show close-ups of outer peripheries various cartridges.



FIG. 52 is a perspective view of an underside of a cartridge.



FIG. 53A shows a top down view of a cartridge and the punch and pusher devices.



FIG. 53B is a perspective view of one embodiment of a punch plate.



FIGS. 54A-54G show a sequence of motion for the punch plate, the cartridge, and the cartridge pusher.



FIGS. 55A-55B show cross-sections of the system according to the present invention.



FIG. 56A shows a perspective view of the system according to the present invention.



FIGS. 56B-56D are cut-away views showing mechanisms within the present invention.



FIGS. 57-65B show optional embodiments according to the present invention.



FIG. 66-68 shows a still further embodiment of a cartridge according to the present invention.



FIGS. 69A-69L show the sequence of motions associated with an optional embodiment of a cartridge according to the present invention.



FIG. 70-72 show views of a sample modules used with still further embodiments of a cartridge according to the present invention.



FIG. 73 shows a cartridge with a sterility barrier and an analyte detecting member layer.



FIG. 74-78 show still further embodiments of analyte detecting members coupled to a cartridge.



FIGS. 79-84 show optional configurations for a cartridge for use with the present invention.



FIG. 85 shows a see-through view of one embodiment of a system according to the present invention.



FIG. 86 is a schematic of an optional embodiment of a system according to the present invention.



FIGS. 87A-87B show still further embodiments of cartridges according to the present invention.



FIG. 88 shows a cartridge having an array of analyte detecting members.



FIGS. 89-90 show embodiments of illumination systems for use with the present invention.



FIGS. 91-96 show further embodiments using optical methods for analyte detection.



FIG. 97 shows a perspective view of one embodiment of the present invention.



FIG. 98 shows one embodiment of optics according to the present invention.



FIG. 99 shows one embodiment of pixel and storage configurations.



FIG. 100 is a graph showing fluorescence lifetime intensity.



FIGS. 101 through 104 show various embodiments of optics according to the present invention.



FIG. 105 shows one embodiment of a well with microbeads.



FIG. 106 through 107B show various configurations of wells and channels.



FIGS. 108 and 109 show configurations of penetrating members and wells.



FIG. 110 shows a still further configuration of optics according to the present invention.



FIG. 111 shows a disc-shaped cartridge with wells and attachable separators.



FIG. 112 shows a disc-shaped cartridge with a plurality of wells.



FIGS. 113-116 show methods for manufacturing cartridges with wells.



FIG. 117 shows one embodiment of the present invention using a separate cartridge for penetrating members and analyte detecting members.





DESCRIPTION OF THE SPECIFIC EMBODIMENTS

The present invention provides a multiple analyte detecting member solution for body fluid sampling. Specifically, some embodiments of the present invention provide a multiple analyte detecting member and multiple lancet solution to measuring analyte levels in the body. The invention may use a high density design. It may use lancets of smaller size, such as but not limited to diameter or length, than known lancets. The device may be used for multiple lancing events without having to remove a disposable from the device. The invention may provide improved sensing capabilities. At least some of these and other objectives described herein will be met by embodiments of the present invention.


It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the invention, as claimed. It may be noted that, as used in the specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a material” may include mixtures of materials, reference to “a chamber” may include multiple chambers, and the like. References cited herein are hereby incorporated by reference in their entirety, except to the extent that they conflict with teachings explicitly set forth in this specification.


In this specification and in the claims which follow, reference will be made to a number of terms which shall be defined to have the following meanings:


“Optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. For example, if a device optionally contains a feature for analyzing a blood sample, this means that the analysis feature may or may not be present, and, thus, the description includes structures wherein a device possesses the analysis feature and structures wherein the analysis feature is not present.


“Analyte detecting member” refers to any use, singly or in combination, of chemical test reagents and methods, electrical test circuits and methods, physical test components and methods, optical test components and methods, and biological test reagents and methods to yield information about a blood sample. Some of these methods are well known in the art and may be based on teachings of, e.g. Tietz Textbook of Clinical Chemistry, 3d Ed., Sec. V, pp. 776-78 (Burtis & Ashwood, Eds., W.B. Saunders Company, Philadelphia, 1999); U.S. Pat. No. 5,997,817 to Chrismore et al. (Dec. 7, 1999); U.S. Pat. No. 5,059,394 to Phillips et al. (Oct. 22, 1991); U.S. Pat. No. 5,001,054 to Wagner et al. (Mar. 19, 1991); and U.S. Pat. No. 4,392,933 to Nakamura et al. (Jul. 12, 1983), the teachings of which are hereby incorporated by reference, as well as others. Analyte detecting member may include tests in the sample test chamber that test electrochemical properties of the blood, or they may include optical means for sensing optical properties of the blood (e.g. oxygen saturation level), or they may include biochemical reagents (e.g. antibodies) to sense properties (e.g. presence of antigens) of the blood. The analyte detecting member may comprise biosensing or reagent material that will react with an analyte in blood (e.g. glucose) or other body fluid so that an appropriate signal correlating with the presence of the analyte is generated and can be read by the reader apparatus. By way of example and not limitation, analyte detecting member may be “associated with”, “mounted within”, or “coupled to” a chamber or other structure when the analyte detecting member participates in the function of providing an appropriate signal about the blood sample to the reader device. Analyte detecting member may also include nanowire analyte detecting members as described herein. Analyte detecting member may use any, singly or in combination, potentiometric, coulometric, or other method useful for detection of analyte levels.



FIGS. 1-11 of the accompanying drawings illustrates one embodiment of a system 10 for piercing tissue to obtain a blood sample. The system 10 may include a replaceable cartridge 12 and an apparatus 14 for removably receiving the cartridge 12 and for manipulating components of the cartridge 12.


Referring jointly to FIGS. 1 and 2, the cartridge 12 may include a plurality of penetrating members 18. The cartridge 12 may be in the form of a circular disc and has an outer circular surface 20 and an opening forming an inner circular surface 22. A plurality of grooves 24 are formed in a planar surface 26 of the cartridge 12. Each groove 24 is elongated and extends radially out from a center point of the cartridge 12. Each groove 24 is formed through the outer circular surface 20. Although not shown, it should be understood that the grooves 24 are formed over the entire circumference of the planar surface 26. As shown in FIGS. 3 and 4, each groove 24 is relatively narrow closer to the center point of the cartridge 12 and slightly wider further from the center point. These grooves 24 may be molded into the cartridge 12, machined into the cartridge, forged, pressed, or formed using other methods useful in the manufacture of medical devices.


In the present embodiment, each penetrating member 18 has an elongated body 26 and a sharpened distal end 27 having a sharp tip 30. The penetrating member 18 may have a circular cross-section with a diameter in this embodiment of about 0.315 mm. All outer surfaces of the penetrating member 18 may have the same coefficient of friction. The penetrating member may be, but is not necessarily, a bare lancet. The lancet is “bare”, in the sense that no raised formations or molded parts are formed thereon that are complementarily engageable with another structure. Traditional lancets include large plastic molded parts that are used to facilitate engagement. Unfortunately, such attachments add size and cost. In the most basic sense, a bare lancet or bare penetrating member is an elongate wire having sharpened end. If it is of sufficiently small diameter, the tip may be penetrating without having to be sharpened. A bare lancet may be bent and still be considered a bare lancet. The bare lancet in one embodiment may be made of one material.


In the present embodiment, each penetrating member 18 is located in a respective one of the grooves 24. The penetrating members 18 have their sharpened distal ends 27 pointed radially out from the center point of the cartridge 12. A proximal end of each penetrating member 15 may engage in an interference fit with opposing sides of a respective groove 24 as shown in FIG. 3. Other embodiments of the cartridge 12 may not use such an interference fit. As a nonlimiting example, they may use a fracturable adhesive to releasably secure the penetrating member 18 to the cartridge 12. As shown in FIG. 4, more distal portions of the penetrating member 18 are not engaged with the opposing sides of the groove 24 due to the larger spacing between the sides.


The cartridge 12 may further include a sterilization barrier 28 attached to the upper surface 26. The sterilization barrier 28 is located over the penetrating members 18 and serves to insulate the penetrating members 18 from external contaminants. The sterilization barrier 28 is made of a material that can easily be broken when an edge of a device applies a force thereto. The sterilization barrier 28 alone or in combination with other barriers may be used to create a sterile environment about at least the tip of the penetrating member prior to lancing or actuation. The sterilization barrier 28 may be made of a variety of materials such as but not limited to metallic foil, aluminum foil, paper, polymeric material, or laminates combining any of the above. Other details of the sterilization barrier are detailed herein.


In the present embodiment, the apparatus 14 may include a housing 30, an initiator button 32, a penetrating member movement subassembly 34, a cartridge advance subassembly 36, batteries 38, a capacitor 40, a microprocessor controller 42, and switches 44. The housing 30 may have a lower portion 46 and a lid 48. The lid 48 is secured to the lower portion 46 with a hinge 50. The lower portion 46 may have a recess 52. A circular opening 54 in the lower portion 46 defines an outer boundary of the recess 52 and a level platform 56 of the lower portion 46 defines a base of the recess 52.


In use, the lid 48 of the present embodiment is pivoted into a position as shown in FIG. 1. The cartridge 12 is flipped over and positioned in the recess 52. The planar surface 26 rests against the level platform 56 and the circular opening 54 contacts the outer circular surface 20 to prevent movement of the cartridge 12 in a plane thereof. The lid 48 is then pivoted in a direction 60 and closes the cartridge 12.


Referring to the embodiment shown in FIG. 5, the penetrating member movement subassembly 34 includes a lever 62, a penetrating member accelerator 64, a linear actuator 66, and a spring 68. Other suitable actuators including but not limited to rotary actuators are described in commonly assigned, copending U.S. patent application Ser. No. 10/127,395 filed Apr. 19, 2002. The lever 62 may be pivotably secured to the lower portion 46. The button 32 is located in an accessible position external of the lower portion 46 and is connected by a shaft 70 through the lower portion 46 to one end of the lever 62. The penetrating member accelerator 64 is mounted to an opposing end of the lever 62. A user depresses the button 32 in an upward direction 66 so that the shaft 70 pivots the end of the lever 62 to which it is connected in an upward direction. The opposing end of the lever pivots in a downward direction 66. The spring 46 is positioned between the button 32 and the base 40 and compresses when the button 32 is depressed to create a force that tends to move the button 32 down and pivot the penetrating member accelerator upward in a direction opposite to the direction 64.


Referring to FIGS. 6A and 6B in this particular embodiment, the movement of the button into the position shown in FIG. 5 also causes contact between a terminal 74 on the shaft 20 with a terminal 70 secured to the lower portion 46. Contact between the terminals 74 and 76 indicates that the button 32 has been fully depressed. With the button 32 depressed, the cartridge 12 can be rotated without interference by the penetrating member actuator 64. To this effect, the cartridge advancer subsystem 36 includes a pinion gear 80 and a stepper motor 82. The stepper motor 82 is secured to the lower portion 46. The pinion gear 80 is secured to the stepper motor 82 and is rotated by the stepper motor 82. Teeth on the pinion gear 80 engage with teeth on the inner circular surface 22 of the cartridge 12. Rotation of the pinion gear 80 causes rotation of the cartridge 12 about the center point thereof. Each time that the terminals 74 and 76 make contact, the stepper motor 82 is operated to rotate the cartridge 12 through a discrete angle equal to an angular spacing from a centerline of one of the penetrating members 18 to a centerline of an adjacent penetrating member. A select penetrating member 18 is so moved over the penetrating member accelerator 64, as shown in FIG. 6B. Subsequent depressions of the button 32 will cause rotation of subsequent adjacent penetrating members 18 into a position over the penetrating member accelerator 64.


The user then releases pressure from the button, as shown in FIG. 7A. The force created by the spring 68 or other resilient member moves the button 32 in a downward direction 76. The shaft 70 is pivotably secured to the lever 62 so that the shaft 70 moves the end of the lever 62 to which it is connected down. The opposite end of the lever 62 pivots the penetrating member accelerator 64 upward in a direction 80. As shown in FIG. 7B, an edge 82 of the penetrating member accelerator 64 breaks through a portion of the sterilization barrier 28 and comes in to physical contact with a lower side surface of the penetrating member 18.


Referring to FIG. 8A, the linear actuator 66 includes separate advancing coils 86A and retracting coils 86B, and a magnetizable slug 90 within the coils 86A and 86B. The coils 86A and 86B are secured to the lower portion of 46, and the slug 90 can move within the coils 86A and 88B. Once the penetrating member accelerator 64 is located in the position shown in FIGS. 7A and 7B, electric current is provided to the advancing coils 86 only. The current in the advancing coils 86 creates a force in a direction 88 on the slug 90 according to conventional principles relating to electromagnetics.


A bearing 91 is secured to the lever and the penetrating member accelerator 64 has a slot 92 over the bearing 91. The slot 92 allows for the movement of the penetrating member accelerator 64 in the direction 88 relative to the lever 62, so that the force created on the slug moves the penetrating member accelerator 64 in the direction 88.


The spring 68 is not entirely relaxed, so that the spring 68, through the lever 62, biases the penetrating member accelerator 64 against the lower side surface of the penetrating member 18 with a force F1. The penetrating member 18 rests against a base 88 of the cartridge 12. An equal and opposing force F2 is created by the base 88 on an upper side surface of the penetrating member 18.


The edge 82 of the penetrating member accelerator 64 has a much higher coefficient of friction than the base 88 of the cartridge 12. The higher coefficient of friction of the edge contributes to a relatively high friction force F3 on the lower side surface of the penetrating member 18. The relatively low coefficient of friction of the base 88 creates a relatively small friction force F4 on the upper side surface of the penetrating member 18. A difference between the force F3 and F4 is a resultant force that accelerates the penetrating member in the direction 88 relative to the cartridge 12. The penetrating member is moved out of the interference fit illustrated in FIG. 3. The bare penetrating member 18 is moved without the need for any engagement formations on the penetrating member. Current devices, in contrast, often make use a plastic body molded onto each penetrating member to aid in manipulating the penetrating members. Movement of the penetrating member 18 moves the sharpened end thereof through an opening 90 in aside of the lower portion 46. The sharp end 30 of the penetrating member 18 is thereby moved from a retracted and safe position within the lower portion 46 into a position wherein it extends out of the opening 90. Accelerated, high-speed movement of the penetrating member is used so that the sharp tip 30 penetrates skin of a person. A blood sample can then be taken from the person, typically for diabetic analysis.


Reference is now made to FIGS. 9A and 9B. After the penetrating member is accelerated (for example, but not limitation, less than 0.25 seconds thereafter), the current to the accelerating coils 86A is turned off and the current is provided to the retracting coils 86B. The slug 90 moves in an opposite direction 92 together with the penetrating member accelerator 64. The penetrating member accelerator 64 then returns the used penetrating member into its original position, i.e., the same as shown in FIG. 7B.


Subsequent depression of the button as shown in FIG. 5 will then cause one repetition of the process described, but with an adjacent sterile penetrating member. Subsequent sterile penetrating members can so be used until all the penetrating members have been used, i.e., after one complete revolution of the cartridge 12. In this embodiment, a second revolution of the cartridge 12 is disallowed to prevent the use of penetrating members that have been used in a previous revolution and have become contaminated. The user can continue to use the apparatus 14 is by opening the lid 48 as shown in FIG. 1, removing the used cartridge 12, and replacing the used cartridge with another cartridge. A detector (not shown) detects whenever a cartridge is removed and replaced with another cartridge. Such a detector may be but is not limited to an optical sensor, an electrical contact sensor, a bar code reader, or the like.



FIG. 10 illustrates the manner in which the electrical components may be functionally interconnected for the present embodiment. The battery 38 provides power to the capacitor 40 and the controller 42. The terminal 76 is connected to the controller 42 so that the controller recognizes when the button 32 is depressed. The capacitor to provide power (electric potential and current) individually through the switches (such as but not limited to field-effect transistors) to the advancing coils 86A, retracting coils 86B and the stepper motor 82. The switches 44A, B, and C are all under the control of the controller 42. A memory 100 is connected to the controller. A set of instructions is stored in the memory 100 and is readable by the controller 42. Further functioning of the controller 42 in combination with the terminal 76 and the switches 44A, B, and C should be evident from the foregoing description.



FIG. 11 illustrates a configuration for another embodiment of a cartridge having penetrating members. The cartridge 112 has a corrugated configuration and a plurality of penetrating members 118 in grooves 124 formed in opposing sides of the cartridge 112. Sterilization barriers 126 and 128 are attached over the penetrating members 118 at the top and the penetrating members 118 at the bottom, respectively. Such an arrangement provides large surfaces for attachment of the sterilization barriers 126 and 128. All the penetrating members 118 on the one side are used first, whereafter the cartridge 112 is turned over and the penetrating members 118 on the other side are used. Additional aspects of such a cartridge are also discussed in FIGS. 42-44.


Referring now to FIGS. 12-13, a friction based method of coupling with and driving bare lancets or bare penetrating members will be described in further detail. Any embodiment of the present invention disclosed herein may be adapted to use these methods. As seen in FIG. 12, surface 201 is physically in contact with penetrating member 202. Surface 203 is also physically in contact with penetrating member 202. In the present embodiment of the invention, surface 201 is stainless steel, penetrating member 202 is stainless steel, and surface 203 is polytetrafluoroethylene-coated stainless steel.



FIG. 13 illustrates one embodiment of the friction based coupling in use. Normal force 206 may be applied vertically to surface 201, pressing it against penetrating member 202. Penetrating member 202 is thereby pressed against surface 203. Normal force 206 is transmitted through surface 201 and penetrating member 202 to also act between penetrating member 202 and surface 203. Surface 203 is held rigid or stationary with respect to a target of the lancet. Using the classical static friction model, the maximum frictional force between surface 201 and penetrating member 202 is equal to the friction coefficient between surface 201 and penetrating member 202 multiplied by the normal force between surface 201 and penetrating member 202. In this embodiment, the maximum frictional force between surface 203 and penetrating member 202 is equal to the coefficient of friction between the surface 203 and the penetrating member 202 multiplied by the normal force between the surface 203 and the penetrating member 202. Because friction coefficient between surface 203 and penetrating member 202 is less than friction coefficient between surface 201 and penetrating member 202, the interface between surface 201 and penetrating member 202 can develop a higher maximum static friction force than can the interface between surface 203 and penetrating member 202.


Driving force as indicated by arrow 207 is applied to surface 201 perpendicular to normal force 206. The sum of the forces acting horizontally on surface 201 is the sum of driving force 207 and the friction force developed at the interface of surface 201 and penetrating member 202, which acts in opposition to driving force 207. Since the coefficient of friction between surface 203 and penetrating member 202 is less than the coefficient of friction between surface 201 and penetrating member 202, penetrating member 202 and surface 201 will remain stationary with respect to each other and can be considered to behave as one piece when driving force 207 just exceeds the maximum frictional force that can be supported by the interface between surface 203 and penetrating member 202. Surface 201 and penetrating member 202 can be considered one piece because the coefficient of friction between surface 201 and penetrating member 202 is high enough to prevent relative motion between the two.


In one embodiment, the coefficient of friction between surface 201 and penetrating member 202 is approximately 0.8 corresponding to the coefficient of friction between two surfaces of stainless steel, while the coefficient of friction between surface 203 and penetrating member 202 is approximately 0.04, corresponding to the coefficient of friction between a surface of stainless steel and one of polytetrafluoroethylene. Normal force 206 has a value of 202 Newtons. Using these values, the maximum frictional force that the interface between surface 201 and penetrating member 202 can support is 1.6 Newtons, while the maximum frictional force that the interface between surface 203 and penetrating member 202 can support is 0.08 Newtons. If driving force 207 exceeds 0.08 Newtons, surface 201 and penetrating member 202 will begin to accelerate together with respect to surface 203. Likewise, if driving force 207 exceeds 1.6 Newtons and penetrating member 202 encounters a rigid barrier, surface 201 would move relative to penetrating member 202.


Another condition, for example, for surface 201 to move relative to penetrating member 202 would be in the case of extreme acceleration. In an embodiment, penetrating member 202 has a mass of 8.24×10−6 kg. An acceleration of 194,174 m/s2 of penetrating member 202 would therefore be required to exceed the frictional force between penetrating member 202 and surface 201, corresponding to approximately 19,800 g's. Without being bound to any particular embodiment or theory of operation, other methods of applying friction base coupling may also be used. For example, the penetrating member 202 may be engaged by a coupler using a interference fit to create the frictional engagement with the member.



FIG. 14 illustrates a polytetrafluoroethylene coating on stainless steel surface 203 in detail. It should be understood that the surface 203 may be coated with other materials such as but not limited to Telfon®, silicon, polymer or glass. The coating may cover all of the penetrating member, only the proximal portions, only the distal portions, only the tip, only some other portion, or some combination of some or all of the above. FIG. 15 illustrates a doping of lead applied to surface 201, which conforms to penetrating member 202 microscopically when pressed against it. Both of these embodiments and other coated embodiments of a penetrating member may be used with the actuation methods described herein.


The shapes and configurations of surface 201 and surface 102 could be some form other than shown in FIGS. 12-15. For example, surface 201 could be the surface of a wheel, which when rotated causes penetrating member 202 to advance or retract relative to surface 203. Surface 201 could be coated with another conformable material besides lead, such as but not limited to a plastic. It could also be coated with particles, such as but not limited to diamond dust, or given a surface texture to enhance the friction coefficient of surface 201 with penetrating member 202. Surface 202 could be made of or coated with diamond, fluorinated ethylene propylene, perfluoroalkoxy, a copolymer of ethylene and tetrafluoroethylene, a copolymer of ethylene and chlorotrifluoroethylene, or any other material with a coefficient of friction with penetrating member 202 lower than that of the material used for surface 201.


Referring to FIG. 16, a portion of a base plate 210 of an embodiment of a penetrating member cartridge is shown with a plurality of penetrating member slots 212 disposed in a radial direction cut into a top surface 214 of the base plate. A drive member 216 is shown with a distal edge 218 disposed within one of the penetrating member slots 212 of the base plate 210. The distal edge 218 of the drive member 216 is configured to slide within the penetrating member slots 212 with a minimum of friction but with a close fit to minimize lateral movement during a lancing cycle.



FIG. 17 shows a distal portion 220 of a coated penetrating member 222 in partial longitudinal section. The coated penetrating member 222 has a core portion 224, a coating 226 and a tapered distal end portion 228. A portion of a coated drive member 230 is shown having a coating 234 with penetrating member contact surface 236. The penetrating member contact surface 236 forms an interface 238 with an outer surface 240 of the coated penetrating member 222. The interface 238 has a characteristic friction coefficient that will depend in part on the choice of materials for the penetrating member coating 226 and the drive member coating 234. If silver is used as the penetrating member and drive member coating 226 and 236, this yields a friction coefficient of about 1.3 to about 1.5. Other materials can be used for coatings 226 and 236 to achieve the desired friction coefficient. For example, gold, platinum, stainless steel and other materials may be used for coatings 226 and 236. It may be desirable to use combinations of different materials for coatings 226 and 236. For example, an embodiment may include silver for a penetrating member coating 226 and gold for a drive member coating. Some embodiments of the interface 238 can have friction coefficients of about 1.15 to about 5.0, specifically, about 1.3 to about 2.0.


Embodiments of the penetrating member 222 can have an outer transverse dimension or diameter of about 200 to about 400 microns, specifically, about 275 to about 325 microns. Embodiments of penetrating member 222 can have a length of about 10 to about 30 millimeters, specifically, about 15 to about 25 millimeters. Penetrating member 222 can be made from any suitable high strength alloy such as but not limited to stainless steel or the like.



FIG. 18 is a perspective view of a lancing device 242 having features of the invention. A penetrating member cartridge 244 is disposed about a driver 246 that is coupled to a drive member 248 by a coupler rod 250. The penetrating member cartridge 244 has a plurality of penetrating member slots 252 disposed in a radial configuration in a top surface 254 a base plate 256 of the penetrating member cartridge 244. The distal ends 253 of the penetrating member slots 252 are disposed at an outer surface 260 of the base plate 256. A fracturable sterility barrier 258, shown partially cut away, is disposed on the top surface 254 of base plate 256 over the plurality of penetrating member slots 252. The sterility barrier 258 is also disposed over the outer surface 260 of the base plate 256 in order to seal the penetrating member slots from contamination prior to a lancing cycle. A distal portion of a penetrating member 262 is shown extending radially from the penetrating member cartridge 244 in the direction of a patient's finger 264.



FIG. 19 illustrates a portion of the base plate 256 used with the lancing device 242 in more detail and without sterility barrier 258 in place (for ease of illustration). The base plate 256 includes a plurality of penetrating member slots 252 which are in radial alignment with corresponding drive member slots 266. The drive member slots 266 have an optional tapered input configuration that may facilitate alignment of the drive member 248 during downward movement into the drive member slot 266 and penetrating member slot 252. Penetrating member slots 252 are sized and configured to accept a penetrating member 262 disposed therein and allow axial movement of the penetrating member 262 within the penetrating member slots 252 without substantial lateral movement.


Referring again to FIG. 18, in use, the present embodiment of penetrating member cartridge 242 is placed in an operational configuration with the driver 246. A lancing cycle is initiated and the drive member 248 is brought down through the sterility barrier 258 and into a penetrating member slot 252. A penetrating member contact surface of the drive member then makes contact with an outside surface of the penetrating member 262 and is driven distally toward the patient's finger 264 as described above with regard to the embodiment discussed in FIG. 20. The friction coefficient between the penetrating member contact surface of the drive member 248 and the penetrating member 262 is greater than the friction coefficient between the penetrating member 262 and an interior surface of the penetrating member slots 252. As such, the drive member 248 is able to drive the penetrating member 262 distally through the sterility barrier 258 and into the patient's finger 264 without any relative movement or substantial relative movement between the drive member 248 and the penetrating member 262.


Referring to FIGS. 20-22, a lancing cycle sequence is shown for a lancing device 242 with another embodiment of a penetrating member cartridge 244 as shown in FIGS. 23 and 24. The base plate 256 of the penetrating member cartridge 242 shown in FIGS. 23 and 24 has a plurality of penetrating member slots 252 with top openings 268 that do not extend radially to the outer surface 260 of the base plate 256. In this way, the penetrating member slots 252 can be sealed with a first sterility barrier 270 disposed on the top surface 254 of the base plate 256 and a second sterility barrier 272 disposed on the outer surface 260 of the base plate 256. Penetrating member outlet ports 274 are disposed at the distal ends of the penetrating member slots 252.


Referring again to FIG. 20, the penetrating member 262 is shown in the proximally retracted starting position within the penetrating member slot 252. The outer surface of the penetrating member 276 is in contact with the penetrating member contact surface 278 of the drive member 248. The friction coefficient between the penetrating member contact surface 278 of the drive member 248 and the outer surface 276 of the penetrating member 262 is greater than the friction coefficient between the penetrating member 262 and an interior surface 280 of the penetrating member slots 252. A distal drive force as indicated by arrow 282 in FIG. 10 is then applied via the drive coupler 250 to the drive member 248 and the penetrating member is driven out of the penetrating member outlet port 274 and into the patient's finger 264. A proximal retraction force, as indicated by arrow 284 in FIG. 22, is then applied to the drive member 248 and the penetrating member 262 is withdrawn from the patient's finger 264 and back into the penetrating member slot 252.



FIGS. 25 and 26 illustrate an embodiment of a multiple layer sterility barrier 258 in the process of being penetrated by a penetrating member 62. It should be understood that this barrier 258 may be adapted for use with any embodiment of the present invention. The sterility barrier 258 shown in FIGS. 25 and 26 is a two layer sterility barrier 258 that facilitates maintaining sterility of the penetrating member 262 as it passes through and exits the sterility barrier 258. In FIG. 25, the distal end 286 of the penetrating member 262 is applying an axial force in a distal direction against an inside surface 288 of a first layer 290 of the sterility barrier 258, so as to deform the first layer 290 of the sterility barrier 258. The deformation 291 of the first layer 290 in turn applies a distorting force to the second layer 292 of the sterility barrier 258. The second layer of the sterility barrier is configured to have a lower tensile strength that the first layer 290. As such, the second layer 292 fails prior to the first layer 290 due to the strain imposed on the first layer 290 by the distal end 286 of the penetrating member 262, as shown in FIG. 26. After the second layer 292 fails, it then retracts from the deformed portion 291 of the first layer 290 as shown by arrows 294 in FIG. 26. As long as the inside surface 288 and outside surface 296 of the first layer 290 are sterile prior to failure of the second layer 292, the penetrating member 262 will remain sterile as it passes through the first layer 290 once the first layer eventually fails. Such a multiple layer sterility barrier 258 can be used for any of the embodiments discussed herein. The multiple layer sterility barrier 258 can also include three or more layers.


Referring to FIGS. 27 and 28, an embodiment of a drive member 300 coupled to a driver 302 wherein the drive member 300 includes a cutting member 304 having a sharpened edge 306 which is configured to cut through a sterility barrier 258 of a penetrating member slot 252 during a lancing cycle in order for the drive member 300 to make contact with a penetrating member. An optional lock pin 308 on the cutting member 304 can be configured to engage the top surface 310 of the base plate in order to prevent distal movement of the cutting member 304 with the drive member 300 during a lancing cycle.



FIGS. 29 and 30 illustrate an embodiment of a penetrating member slot 316 in longitudinal section having a ramped portion 318 disposed at a distal end 320 of the penetrating member slot. A drive member 322 is shown partially disposed within the penetrating member slot 316. The drive member 322 has a cutting edge 324 at a distal end 326 thereof for cutting through a sterility barrier 328 during a lancing cycle. FIG. 30 illustrates the cutting edge 324 cutting through the sterility barrier 328 during a lancing cycle with the cut sterility barrier 328 peeling away from the cutting edge 324.



FIGS. 31-34 illustrate drive member slots in a base plate 330 of a penetrating member cartridge wherein at least a portion of the drive member slots have a tapered opening which is larger in transverse dimension at a top surface of the base plate than at the bottom of the drive member slot. FIG. 31 illustrates a base plate 330 with a penetrating member slot 332 that is tapered at the input 334 at the top surface 336 of the base plate 330 along the entire length of the penetrating member slot 332. In such a configuration, the penetrating member slot and drive member slot (not shown) would be in communication and continuous along the entire length of the slot 332. As an optional alternative, a base plate 338 as shown in FIGS. 32 and 33 can have a drive member slot 340 that is axially separated from the corresponding penetrating member slot 342. With this configuration, the drive member slot 340 can have a tapered configuration and the penetrating member slot 342 can have a straight walled configuration. In addition, this configuration can be used for corrugated embodiments of base plates 346 as shown in FIG. 34. In FIG. 34, a drive member 348 is disposed within a drive member slot 350. A penetrating member contact surface 352 is disposed on the drive member 348. The contact surface 352 has a tapered configuration that will facilitate lateral alignment of the drive member 348 with the drive member slot 350.



FIGS. 35-37 illustrate an embodiment of a penetrating member cartridge 360 and drive member 362 wherein the drive member 362 has contoured jaws 364 configured to grip a penetrating member shaft 366. In FIG. 35, the drive member 362 and penetrating member shaft 366 are shown in transverse cross section with the contoured jaws 364 disposed about the penetrating member shaft 366. A pivot point 368 is disposed between the contoured jaws 364 and a tapered compression slot 370 in the drive member 362. A compression wedge 372 is shown disposed within the tapered compression slot 370. Insertion of the compression wedge 372 into the compression slot 370 as indicated by arrow 374, forces the contoured jaws 364 to close about and grip the penetrating member shaft 366 as indicated by arrows 376.



FIG. 36 shows the drive member 362 in position about a penetrating member shaft 366 in a penetrating member slot 378 in the penetrating member cartridge 360. The drive member can be actuated by the methods discussed above with regard to other drive member and driver embodiments. FIG. 37 is an elevational view in longitudinal section of the penetrating member shaft 166 disposed within the penetrating member slot 378. The arrows 380 and 382 indicate in a general way, the path followed by the drive member 362 during a lancing cycle. During a lancing cycle, the drive member comes down into the penetrating member slot 378 as indicated by arrow 380 through an optional sterility barrier (not shown). The contoured jaws of the drive member then clamp about the penetrating member shaft 366 and move forward in a distal direction so as to drive the penetrating member into the skin of a patient as indicated by arrow 382.



FIGS. 38 and 39 show a portion of a lancing device 390 having a lid 392 that can be opened to expose a penetrating member cartridge cavity 394 for removal of a used penetrating member cartridge 396 and insertion of a new penetrating member cartridge 398. Depression of button 400 in the direction indicated by arrow 402 raises the drive member 404 from the surface of the penetrating member cartridge 396 by virtue of lever action about pivot point 406. Raising the lid 392 actuates the lever arm 408 in the direction indicated by arrow 410 which in turn applies a tensile force to cable 412 in the direction indicated by arrow 414. This action pulls the drive member back away from the penetrating member cartridge 396 so that the penetrating member cartridge 396 can be removed from the lancing device 390. A new penetrating member cartridge 398 can then be inserted into the lancing device 390 and the steps above reversed in order to position the drive member 404 above the penetrating member cartridge 398 in an operational position.



FIGS. 40 and 41 illustrate a penetrating member cartridge 420 that has penetrating member slots 422 on a top side 424 and a bottom side 426 of the penetrating member cartridge 420. This allows for a penetrating member cartridge 420 of a diameter D to store for use twice the number of penetrating members as a one sided penetrating member cartridge of the same diameter D.



FIGS. 42-44 illustrate end and perspective views of a penetrating member cartridge 430 having a plurality of penetrating member slots 432 formed from a corrugated surface 434 of the penetrating member cartridge 430. Penetrating members 436 are disposed on both sides of the penetrating member cartridge 430. A sterility barrier 438 is shown disposed over the penetrating member slots 432 in FIG. 44.



FIGS. 45-48 illustrate embodiments of a penetrating member 440 and drive member 442 wherein the penetrating member 440 has a transverse slot 444 in the penetrating member shaft 446 and the drive member 442 has a protuberance 448 configured to mate with the transverse slot 444 in the penetrating member shaft 446. FIG. 45 shows a protuberance 448 having a tapered configuration that matches a tapered configuration of the transverse slot 444 in the penetrating member shaft 446. FIG. 46 illustrates an optional alternative embodiment wherein the protuberance 448 has straight walled sides that are configured to match the straight walled sides of the transverse slot 444 shown in FIG. 46. FIG. 47 shows a tapered protuberance 448 that is configured to leave an end gap 450 between an end of the protuberance 448 and a bottom of the transverse slot in the penetrating member shaft 446.



FIG. 48 illustrates a mechanism 452 to lock the drive member 442 to the penetrating member shaft 446 that has a lever arm 454 with an optional bearing 456 on the first end 458 thereof disposed within a guide slot 459 of the drive member 442. The lever arm 454 has a pivot point 460 disposed between the first end 458 of the lever arm 454 and the second end 462 of the lever arm 454. A biasing force is disposed on the second end 462 of the lever arm 454 by a spring member 464 that is disposed between the second end 462 of the lever arm 454 and a base plate 466. The biasing force in the direction indicated by arrow 468 forces the penetrating member contact surface 470 of the drive member 442 against the outside surface of the penetrating member 446 and, in addition, forces the protuberance 448 of the drive member 442 into the transverse slot 444 of the penetrating member shaft 446.


Referring now to FIG. 49, another embodiment of a replaceable cartridge 500 suitable for housing a plurality of individually moveable penetrating members (not shown) will be described in further detail. Although cartridge 500 is shown with a chamfered outer periphery, it should also be understood that less chamfered and unchamfered embodiments of the cartridge 500 may also be adapted for use with any embodiment of the present invention disclosed herein. The penetrating members slidably coupled to the cartridge may be a bare lancet or bare elongate member without outer molded part or body pieces as seen in conventional lancet. The bare design reduces cost and simplifies manufacturing of penetrating members for use with the present invention. The penetrating members may be retractable and held within the cartridge so that they are not able to be used again. The cartridge is replaceable with a new cartridge once all the piercing members have been used. The lancets or penetrating members may be fully contained in the used cartridge so at to minimize the chance of patient contact with such waste.


As can be seen in FIG. 49, the cartridge 500 may include a plurality of cavities 501 for housing a penetrating member. In this embodiment, the cavity 501 may have a longitudinal opening 502 associated with the cavity. The cavity 501 may also have a lateral opening 503 allowing the penetrating member to exit radially outward from the cartridge. As seen in FIG. 49, the outer radial portion of the cavity may be narrowed. The upper portion of this narrowed area may also be sealed or swaged to close the top portion 505 and define an enclosed opening 506 as shown in FIG. 50. Optionally, the narrowed area 504 may retain an open top configuration, though in some embodiments, the foil over the gap is unbroken, preventing the penetrating member from lifting up or extending upward out of the cartridge. The narrowed portion 504 may act as a bearing and/or guide for the penetrating member. FIG. 51 shows that the opening 506 may have a variety of shapes such as but not limited to, circular, rectangular, triangular, hexagonal, square, or combinations of any or all of the previous shapes. Openings 507 (shown in phantom) for other microfluidics, capillary tubes, or the like may also be incorporated in the immediate vicinity of the opening 506. In some optional embodiments, such openings 507 may be configured to surround the opening 506 in a concentric or other manner.


Referring now to FIG. 52, the underside of a cartridge 500 will be described in further detail. This figures shows many features on one cartridge 500. It should be understood that a cartridge may include some, none, or all of these features, but they are shown in FIG. 52 for ease of illustration. The underside may include indentations or holes 510 close to the inner periphery for purpose of properly positioning the cartridge to engage a penetrating member gripper and/or to allow an advancing device (shown in FIGS. 56B and 56C) to rotate the cartridge 500. Indentations or holes 511 may be formed along various locations on the underside of cartridge 500 and may assume various shapes such as but not limited to, circular, rectangular, triangular, hexagonal, square, or combinations of any or all of the previous shapes. Notches 512 may also be formed along the inner surface of the cartridge 500 to assist in alignment and/or rotation of the cartridge. It should be understood of course that some of these features may also be placed on the topside of the cartridge in areas not occupied by cavities 501 that house the penetrating members. Notches 513 may also be incorporated along the outer periphery of the cartridge. These notches 513 may be used to gather excess material from the sterility barrier 28 (not shown) that may be used to cover the angled portion 514 of the cartridge. In the present embodiment, the cartridge has a flat top surface and an angled surface around the outside. Welding a foil type sterility barrier over that angled surface, the foil folds because of the change in the surfaces which is now at 45 degrees. This creates excess material. The grooves or notches 513 are there as a location for that excess material. Placing the foil down into those grooves 513 which may tightly stretch the material across the 45 degree angled surface. Although in this embodiment the surface is shown to be at 45 degrees, it should be understood that other angles may also be used. For example, the surface may be at any angle between about 3 degrees to 90 degrees, relative to horizontal. In some embodiments, the surface may be squared off. The surface may be unchamfered. The surface may also be a curved surface or it may be combinations of a variety of angled surfaces, curved and straights surfaces, or any combination of some or all of the above.


Referring now to FIGS. 53-54, the sequence in which the cartridge 500 is indexed and penetrating members are actuated will now be described. It should be understood that some steps described herein may be combined or taken out of order without departing from the spirit of the invention. These sequence of steps provides vertical and horizontal movement used with the present embodiment to load a penetrating member onto the driver.


As previously discussed, each cavity on the cartridge may be individually sealed with a foil cover or other sterile enclosure material to maintain sterility until or just before the time of use. In the present embodiment, penetrating members are released from their sterile environments just prior to actuation and are loaded onto a launcher mechanism for use. Releasing the penetrating member from the sterile environment prior to launch allows the penetrating member in the present embodiment to be actuated without having to pierce any sterile enclosure material which may dull the tip of the penetrating member or place contaminants on the member as it travels towards a target tissue. A variety of methods may be used accomplish this goal.



FIG. 53A shows one embodiment of penetrating member release device, which in this embodiment is a punch plate 520 that is shown in a see-through depiction for ease of illustration. The punch plate 520 may include a first portion 521 for piercing sterile material covering the longitudinal opening 502 and a second portion 522 for piercing material covering the lateral opening 503. A slot 523 allows the penetrating member gripper to pass through the punch plate 520 and engage a penetrating member housed in the cartridge 500. The second portion 522 of the punch plate down to engage sterility barrier angled at about a 45 degree slope. Of course, the slope of the barrier may be varied. The punch portion 522 first contacts the rear of the front pocket sterility barrier and as it goes down, the cracks runs down each side and the barrier is pressed down to the bottom of the front cavity. The rear edge of the barrier first contacted by the punch portion 522 is broken off and the barrier is pressed down, substantially cleared out of the way. These features may be more clearly seen in FIG. 53B. The punch portion 521 may include a blade portion down the centerline. As the punch comes down, that blade may be aligned with the center of the cavity, cutting the sterility barrier into two pieces. The wider part of the punch 521 then pushes down on the barrier so the they align parallel to the sides of the cavity. This creates a complete and clear path for the gripper throughout the longitudinal opening of the cavity. Additionally, as seen in FIGS. 53B and 54A, a plurality of protrusion 524 are positioned to engage a cam (FIG. 55A) which sequences the punching and other vertical movement of punch plate 520 and cartridge pusher 525. The drive shaft 526 from a force generator (not shown) which is used to actuate the penetrating member 527.


Referring now to FIGS. 54A-F, the release and loading of the penetrating members are achieved in the following sequence. FIG. 54A shows the release and loading mechanism in rest state with a dirty bare penetrating member 527 held in a penetrating member gripper 530. This is the condition of the device between lancing events. When the time comes for the patient to initiate another lancing event, the used penetrating member is cleared and a new penetrating member is loaded, just prior to the actual lancing event. The patient begins the loading of a new penetrating member by operating a setting lever or slider to initiate the process. The setting lever may operate mechanically to rotate a cam (see FIG. 55A) that moves the punch plate 520 and cartridge pusher 525. A variety of mechanisms can be used to link the slider to cause rotation of the cartridge. In other embodiments, a stepper motor or other mover such as but not limited to, a pneumatic actuator, hydraulic actuator, or the like are used to drive the loading sequence.



FIG. 54B shows one embodiment of penetrating member gripper 530 in more detail. The penetrating member gripper 530 may be in the form of a tuning fork with sharp edges along the inside of the legs contacting the penetrating member. In some embodiments, the penetrating member may be notched, recessed, or otherwise shaped to receive the penetrating member gripper. As the gripper 530 is pushed down on the penetrating member, the legs are spread open elastically to create a frictional grip with the penetrating member such as but not limited to bare elongate wires without attachments molded or otherwise attached thereon. In some embodiments, the penetrating member is made of a homogenous material without any additional attachments that are molded, adhered, glued or otherwise added onto the penetrating member.


In some embodiments, the gripper 530 may cut into the sides of the penetrating member. The penetrating member in one embodiment may be about 300 microns wide. The grooves that form in the side of the penetrating member by the knife edges are on the order of about 5-10 microns deep and are quite small. In this particular embodiment, the knife edges allow the apparatus to use a small insertion force to get the gripper onto the penetrating member, compared to the force to remove the penetrating member from the gripper the longitudinal axis of an elongate penetrating member. Thus, the risk of a penetrating member being detached during actuation are reduced. The gripper 530 may be made of a variety of materials such as, but not limited to high strength carbon steel that is heat treated to increased hardness, ceramic, substrates with diamond coating, composite reinforced plastic, elastomer, polymer, and sintered metals. Additionally, the steel may be surface treated. The gripper 130 may have high gripping force with low friction drag on solenoid or other driver.


As seen in FIG. 54C, the sequence begins with punch plate 520 being pushed down. This results in the opening of the next sterile cavity 532. In some embodiment, this movement of punch plate 520 may also result in the crimping of the dirty penetrating member to prevent it from being used again. This crimping may result from a protrusion on the punch plate bending the penetrating member or pushing the penetrating member into a groove in the cartridge that hold the penetrating member in place through an interference fit. As seen in FIGS. 53B and 54C, the punch plate 520 has a protrusion or punch shaped to penetrate a longitudinal opening 502 and a lateral opening 503 on the cartridge. The first portion 521 of the punch that opens cavity 532 is shaped to first pierce the sterility barrier and then push, compresses, or otherwise moves sterile enclosure material towards the sides of the longitudinal opening 502. The second portion 522 of the punch pushes down the sterility barrier at lateral opening or penetrating member exit 503 such that the penetrating member does not pierce any materials when it is actuated toward a tissue site.


Referring now to FIG. 54D, the cartridge pusher 525 is engaged by the cam 550 (not shown) and begins to push down on the cartridge 500. The punch plate 520 may also travel downward with the cartridge 500 until it is pushed down to it maximum downward position, while the penetrating member gripper 530 remains vertically stationary. This joint downward motion away from the penetrating member gripper 530 will remove the penetrating member from the gripper. The punch plate 520 essentially pushes against the penetrating member with protrusion 534 (FIG. 55A), holding the penetrating member with the cartridge, while the cartridge 500 and the punch plate 520 is lowered away from the penetrating member gripper 530 which in this embodiment remains vertically stationary. This causes the stripping of the used penetrating member from the gripper 530 (FIG. 45D) as the cartridge moves relative to the gripper.


At this point as seen in FIG. 54E, the punch plate 520 retracts upward and the cartridge 500 is pushed fully down, clear of the gripper 530. Now cleared of obstructions and in a rotatable position, the cartridge 500 increments one pocket or cavity in the direction that brings the newly released, sterile penetrating member in cavity 532 into alignment with the penetrating member gripper 530, as see in FIG. 54F. The rotation of the cartridge occurs due to fingers engaging the holes or indentations 533 on the cartridge, as seen in FIG. 54A. In some embodiments, these indentations 533 do not pass completely through cartridge 500. In other embodiments, these indentations are holes passing completely through. The cartridge has a plurality of little indentations 533 on the top surface near the center of the cartridge, along the inside diameter. In the one embodiment, the sterility barrier is cut short so as not to cover these plurality of indentations 533. It should be understood of course that these holes may be located on bottom, side or other accessible surface. These indentations 533 have two purposes. The apparatus may have one or a plurality of locator pins, static pins, or other keying feature that dos not move. In this embodiment, the cartridge will only set down into positions where the gripper 530 is gripping the penetrating member. To index the cassette, the cartridge is lifted off those pins or other keyed feature, rotated around, and dropped onto those pins for the next position. The rotating device is through the use of two fingers: one is a static pawl and the other one is a sliding finger. They engage with the holes 533. The fingers are driven by a slider that may be automatically actuated or actuated by the user. This maybe occur mechanically or through electric or other powered devices. Halfway through the stroke, a finger may engage and rotate around the cartridge. A more complete description can be found with text associated with FIGS. 56B-56C.


Referring now to FIG. 54G, with the sterile penetrating member in alignment, the cartridge 500 is released as indicated by arrows 540 and brought back into contact with the penetrating member gripper 530. The new penetrating member 541 is inserted into the gripper 530, and the apparatus is ready to fire once again. After launch and in between lancing events for the present embodiment, the bare lancet or penetrating member 541 is held in place by gripper 530, preventing the penetrating member from accidentally protruding or sliding out of the cartridge 500.


It should be understood of course, that variations can be added to the above embodiment without departing from the spirit of the invention. For example, the penetrating member 541 may be placed in a parked position in the cartridge 500 prior to launch. As seen in FIG. 55A, the penetrating member may be held by a narrowed portion 542 of the cartridge, creating an interference fit which pinches the proximal end of the penetrating member. Friction from the molding or cartridge holds the penetrating member during rest, preventing the penetrating member from sliding back and forth. Of course, other methods of holding the penetrating member may also be used. As seen in FIG. 55B prior to launch, the penetrating member gripper 530 may pull the penetrating member 541 out of the portion 542. The penetrating member 541 may remain in this portion until actuated by the solenoid or other force generator coupled to the penetrating member gripper. A cam surface 544 may be used to pull the penetrating member out of the portion 542. This mechanical cam surface may be coupled to the mechanical slider driven by the patient, which may be considered a separate force generator. Thus, energy from the patient extracts the penetrating member and this reduces the drain on the device's battery if the solenoid or electric driver were to pull out the penetrating member. The penetrating member may be moved forward a small distance (on the order of about 1 mm or less) from its parked position to pull the penetrating member from the rest position gripper. After penetrating tissue, the penetrating member may be returned to the cartridge and eventually placed into the parked position. This may also occur, though not necessarily, through force provided by the patient. In one embodiment, the placing of the lancet into the parked position does not occur until the process for loading a new penetrating member is initiated by the patient. In other embodiments, the pulling out of the parked position occurs in the same motion as the penetrating member actuation. The return into the parked position may also be considered a continuous motion.



FIG. 55A also shows one embodiment of the cam and other surfaces used to coordinate the motion of the punch plate 520. For example, cam 550 in this embodiment is circular and engages the protrusions 524 on the punch plate 520 and the cartridge pusher 525. FIG. 55A also more clearly shows protrusion 534 which helps to hold the penetrating member in the cartridge 500 while the penetrating member gripper 530 pulls away from the member, relatively speaking. A ratchet surface 552 that rotates with the cam 550 may be used to prevent the cam from rotating backwards. The raising and lower of cartridge 500 and punch plate 50 used to load/unload penetrating members may be mechanically actuated by a variety of cam surfaces, springs, or the like as may be determined by one skilled in the art. Some embodiments may also use electrical or magnetic device to perform the loading, unloading, and release of bare penetrating members. Although the punch plate 520 is shown to be punching downward to displace, remove, or move the foil or other sterile environment enclosure, it should be understood that other methods such as but not limited to stripping, pulling, tearing, or some combination of one or more of these methods may be used to remove the foil or sterile enclosure. For example, in other embodiments, the punch plate 520 may be located on an underside of the cartridge and punch upward. In other embodiments, the cartridge may remain vertically stationary while other parts such as but not limited to the penetrating member gripper and punch plate move to load a sterile penetrating member on to the penetrating member gripper.



FIG. 55B also shows other features that may be included in the present apparatus. A fire button 560 may be included for the user to actuate the penetrating member. A front end interface 561 may be included to allow a patient to seat their finger or other target tissue for lancing. The interface 561 may be removable to be cleaned or replaced. A visual display 562 may be included to show device status, lancing performance, error reports, or the like to the patient.


Referring now to FIG. 56A, a mechanical slider 564 used by the patient to load new penetrating member may also be incorporated on the housing. The slider 564 may also be coupled to activate an LCD or visual display on the lancing apparatus. In addition to providing a source of energy to index the cartridge, the slider 564 may also switch the electronics to start the display. The user may use the display to select the depth of lancing or other feature. The display may go back to sleep again until it is activated again by motion of the slider 564. The underside the housing 566 may also be hinged or otherwise removable to allow the insertion of cartridge 500 into the device. The cartridge 500 may be inserted using technology current used for insertion of a compact disc or other disc into a compact disc player. In one embodiment, there may be a tray which is deployed outward to receive or to remove a cartridge. The tray may be withdrawn into the apparatus where it may be elevated, lowered, or otherwise transported into position for use with the penetrating member driver. In other embodiments, the apparatus may have a slot into which the cartridge is partially inserted at which point a mechanical apparatus will assist in completing insertion of the cartridge and load the cartridge into proper position inside the apparatus. Such device is akin to the type of compact disc player found on automobiles. The insertions/ejection and loading apparatus of these compact disc players uses gears, pulleys, cables, trays, and/or other parts that may be adapted for use with the present invention.


Referring now to FIG. 56B, a more detailed view of one embodiment of the slider 564 is provided. In this embodiment, the slider 564 will move initially as indicated by arrow 567. To complete the cycle, the patient will return the slider to its home position or original starting position as indicated by arrow 568. The slider 564 has an arm 569 which moves with the slider to rotate the cam 550 and engage portions 522. The motion of the slider 564 is also mechanically coupled to a finger 570 which engage the indentations 571 on cartridge 500. The finger 570 is synchronized to rotate the cartridge 500 by pulling as indicated by arrow 572 in the same plane as the cartridge. It should be understood that in some embodiments, the finger 570 pushes instead of pulls to rotate the cartridge in the correct direction. The finger 570 may also be adapted to engage ratchet surfaces 706 as seen in FIG. 66 to rotate a cartridge. The finger 570 may also incorporate vertical motion to coordinate with the rising and lowering of the cartridge 500. The motion of finger 570 may also be powered by electric actuators such as but not limited to a stepper motor or other device useful for achieving motion. FIG. 56B also shows a portion of the encoder 573 used in position sensing.


Referring now to FIG. 56C, a still further view of the slider 564 and arm 569 is shown. The arm 569 moves to engage portion 522 as indicated by arrow 575 and this causes the cam 550 to rotate as indicated by arrow 577. In this particular embodiment, the cam 550 rotates about ⅛ of an rotation with each pull of the slider 564. When the slider 564 is return to its home or start position, the arm 569 rides over the portion 522. The movement of the slider also allows the cam surface 544 to rotate about pivot point 579. A resilient member 580 may be coupled to the cam surface 544 to cause it to rotate counterclockwise when the arm 569 moves in the direction of arrow 567. The pin 580 will remain in contact with the arm 569. As the cam surface 544 rotates a first surface 582 will contact the pin 583 on the gripper block 584 and pull the pin 583 back to park a penetrating member into a coupling or narrowed portion 542 of the cartridge 500 as seen in FIG. 55A. As the arm 569 is brought back to the home position, the cam surface 544 rotates back and a second surface 586 that rotates clockwise and pushes the penetrating member forward to be released from the narrowed portion 542 resulting in a position as seen in FIG. 55B. It should be understood that in some embodiments, the release and/or parking of lancet from portion 542 may be powered by the driver 588 without using the mechanical assistance from cam surface 544.


In another embodiment of the cartridge device, a mechanical feature may be included on the cartridge so that there is only one way to load it into the apparatus. As a nonlimiting example, in one embodiment holding 50 penetrating members, the cartridge may have 51 pockets or cavities. The 51.sup.st pocket will go into the firing position when the device is loaded, thus providing a location for the gripper to rest in the cartridge without releasing a penetrating member from a sterile environment. The gripper 530 in that zeroth position is inside the pocket or cavity and that is the reason why one of the pockets may be empty. Of course, some embodiments may have the gripper 530 positioned to grip a penetrating member as the cartridge 500 is loaded into the device, with the patient lancing themselves soon afterwards so that the penetrating member is not contaminated due to prolonged exposure outside the sterile enclosure. That zeroth position may be the start and finish position. The cartridge may also be notched to engaged a protrusion on the apparatus, thus also providing a method for allowing the penetrating member to loaded or unloaded only in one orientation. Essentially, the cartridge 500 may be keyed or slotted in association with the apparatus so that the cartridge 500 can only be inserted or removed at one orientation. For example as seen in FIG. 56D, the cartridge 592 may have a keyed slot 593 that matches the outline of a protrusion 594 such that the cartridge 592 may only be removed upon alignment of the slot 593 and protrusion 594 upon at the start or end positions. It should be understood that other keyed technology may be used and the slot or key may be located on an outer periphery or other location on the cartridge 592 in manner useful for allowing insertion or removal of the cartridge from only one or a select number of orientations.


Referring now to FIG. 57, a cross-section of another embodiment of a cavity 600 housing a penetrating member is shown. The cavity 600 may include a depression 602 for allowing the gripper 530 to penetrate sufficiently deeply into the cavity to frictionally engage the penetrating member 541. The penetrating member may also be housed in a groove 604 that holds the penetrating member in place prior to and after actuation. The penetrating member 541 is lifted upward to clear the groove 604 during actuation and exits through opening 506.


Referring now to FIG. 58, another variation on the system according to the present invention will now be described. FIG. 58 shows a lancing system 610 wherein the penetrating members have their sharpened tip pointed radially inward. The finger or other tissue of the patient is inserted through the center hole 611 to be pierced by the member 612. The penetrating member gripper 530 coupled to drive force generator 613 operate in substantially the same manner as described in FIGS. 54A-G. The punch portions 521 and 522 operate in substantially the same manner to release the penetrating members from the sterile enclosures. The punch portion 522 may be placed on the inner periphery of the device, where the penetrating member exit is now located, so that sterile enclosure material is cleared out of the path of the penetrating member exit.


Referring now to FIG. 59, a still further variation on the lancing system according to the present invention will now be described. In the embodiments shown in FIGS. 53-54, the penetrating member gripper 530 approaches the penetrating member from above and at least a portion of the drive system is located in a different plane from that of the cartridge 500. FIG. 59 shows an embodiment where the penetrating member driver 620 is in substantially the same plane as the penetrating member 622. The coupler 624 engages a bent or L shaped portion 626 of the member 622. The cartridge 628 can rotate to engage a new penetrating member with the coupler 624 without having to move the cartridge or coupler vertically. The next penetrating member rotates into position in the slot provided by the coupler 624. A narrowed portion of the cartridge acts as a penetrating member guide 630 near the distal end of the penetrating member to align the penetrating member as it exits the cartridge.


The coupler 624 may come in a variety of configurations. For example, FIG. 60A shows a coupler 632 which can engage a penetrating member 633 that does not have a bent or L-shaped portion. A radial cartridge carrying such a penetrating member 633 may rotate to slide penetrating member into the groove 634 of the coupler 632. FIG. 60B is a front view showing that the coupler 632 may include a tapered portion 636 to guide the penetrating member 633 into the slot 634. FIG. 60C shows an embodiment of the driver 620 using a coupler 637 having a slot 638 for receiving a T-shaped penetrating member. The coupler 637 may further include a protrusion 639 that may be guided in an overhead slot to maintain alignment of the drive shaft during actuation.


Referring now to FIG. 61, a cartridge 640 for use with an in-plane driver 620 is shown. The cartridge 640 includes an empty slot 642 that allows the cartridge to be placed in position with the driver 620. In this embodiment, the empty slot 642 allows the coupler 644 to be positioned to engage an unused penetrating member 645 that may be rotated into position as shown by arrow 646. As seen in FIG. 61, the cartridge 640 may also be designed so that only the portion of the penetrating member that needs to remain sterile (i.e. the portions that may actually be penetrating into tissue) are enclosed. As seen in FIG. 61, a proximal portion 647 of the penetrating member is exposed. This exposed proximal portion may be about 70% of the penetrating member. In other embodiments it may be between about 69% to about 5% of the penetrating member. The cartridge 640 may further include, but not necessarily, sealing protrusions 648. These protrusions 648 are releasably coupled to the cartridge 640 and are removed from the cartridge 640 by remover 649 as the cartridge rotates to place penetrating member 645 into the position of the active penetrating member. The sterile environment is broken prior to actuation of the member 645 and the member does not penetrate sterile enclosure material that may dull the tip of the penetrating member during actuation. A fracturable seal material 650 may be applied to the member to seal against an inner peripheral portion of the cartridge.


Referring now to FIG. 62, a still further embodiment of a cartridge for use with the present invention will be described. This cartridge 652 includes a tapered portion 654 for allowing the coupler 655 to enter the cavity 656. A narrowed portion 657 guides the penetrating member 658. The coupler 655 may have, but does not necessarily have, movable jaws 659 that engage to grip the penetrating member 658. Allowing the coupler to enter the cavity 656 allows the alignment of the penetrating member to be better maintained during actuation. This tapered portion 654 may be adapted for use with any embodiment of the cartridge disclosed herein.


Referring now to FIG. 63, a linear cartridge 660 for use with the present invention will be described. Although the present invention has been shown in use with radial cartridges, the lancing system may be adapted for use with cartridges of other shapes. FIGS. 79-83 show other cartridges of varying shapes adaptable for use with the present invention. FIG. 63 illustrates a cartridge 660 with only a portion 662 providing sterile protection for the penetrating members. The cartridge 660, however, provides a base 664 on which a penetrating member 665 can rest. This provides a level of protection of the penetrating member during handling. The base 664 may also be shaped to provide slots 666 in which a penetrating member 667 may be held. The slot 666 may also be adapted to have a tapered portion 668. These configurations may be adapted for use with any of the embodiments disclosed herein, such as the cartridge 652.


Referring now to FIGS. 64A-64C, a variety of different devices are shown for releasing the sterility seal covering a lateral opening 503 on the cartridge 500. FIG. 64A shows a rotating punch device 670 that has protrusions 672 that punch out the sterility barrier creating openings 674 from which a penetrating member can exit without touching the sterility barrier material. FIG. 64B shows a vertically rotating device 676 with shaped protrusions 678 that punch down the sterility barrier 679 as it is rotated to be in the active, firing position. FIG. 64C shows a punch 680 which is positioned to punch out barrier 682 when the cartridge is lowered onto the punch. The cartridge is rotated and the punch 680 rotates with the cartridge. After the cartridge is rotated to the proper position and lifted up, the punch 680 is spring loaded or otherwise configured to return to the position to engage the sterility barrier covering the next unused penetrating member.


Referring now to FIG. 65A-65B, another type of punch mechanism for use with a punch plate 520 will now be described. The device shown in FIGS. 53-54 shows a mechanism that first punches and then rotates or indexes the released penetrating member into position. In this present embodiment, the cartridge is rotated first and then the gripper and punch may move down simultaneously. FIG. 65A shows one embodiment of a punch 685 having a first portion 686 and a second portion 687. As seen in cross-sectional view of FIG. 65B, the penetrating member gripper 690 is located inside the punch 685. Thus the penetrating of the sterility barrier is integrated into the step of engaging the penetrating member with the gripper 690. The punch 685 may include a slot 692 allowing a portion 694 of the gripper 690 to extend upward. A lateral opening 695 is provided from which a penetrating member may exit. In some embodiments, the punch portion 687 is not included with punch 686, instead relying on some other mechanism such as those shown in FIGS. 64A-64C to press down on barrier material covering a lateral opening 503.


Referring now to FIG. 66, a still further embodiment of a cartridge according to the present invention will be described. FIG. 66 shows a cartridge 700 with a plurality of cavities 702 and individual deflectable portions or fingers 704. The ends of the protective cavities 702 may be divided into individual fingers (such as one for each cavity) on the outer periphery of the disc. Each finger 704 may be individually sealed with a foil cover (not shown for ease of illustration) to maintain sterility until the time of use. Along the inner periphery of the cartridge 700 are raised step portions 706 to create a ratchet type mechanism. As seen in FIG. 67, a penetrating member 708 may be housed in each cavity. The penetrating member may rest on a raised portion 710. A narrowed portion 712 pinches the proximal portions of the penetration member 708. Each cavity may include a wall portion 714 into which the penetrating member 708 may be driven after the penetrating member has been used. FIG. 68 shows the penetrating member gripper 716 lowered to engage a penetrating member 708. For ease of illustration, a sterility barrier covering each of the cavities is not shown.


Referring now to FIGS. 69A-69L, the sequence of steps for actuating a penetrating member in a cartridge 700 will be described. It should be understood that in other embodiments, steps may be combined or reduced without departing from the sprit of the present invention. The last penetrating member to be used may be left in a retracted position, captured by a gripper 716. The end of the protective cavity 704 may be deflected downward by the previous actuation. The user may operate a mechanism such as but not limited to a thumbwheel, lever, crank, slider, etc . . . that advances a new penetrating member 720 into launch position as seen in FIG. 69A. The mechanism lifts a bar that allows the protective cavity to return to its original position in the plane of the disc.


In this embodiment as shown in FIG. 69B, the penetrating member guide 722 presses through foil in rear of pocket to “home” penetrating member and control vertical clearance. For ease of illustration, actuation devices for moving the penetrating member guide 722 and other mechanisms are not shown. They may be springs, cams, or other devices that can lower and move the components shown in these figures. In some embodiments, the cartridge 700 may be raised or lowered to engage the penetrating member guide 722 and other devices.


As seen in FIG. 69C, the plough or sterile enclosure release device 724 is lowered to engage the cartridge 700. In some embodiments, the disc or cartridge 700 may raised part way upward until a plough or plow blade 724 pierces the sterility barrier 726 which may be a foil covering.


Referring now to FIG. 69D, the plough 724 clears foil from front of pocket and leaves it attached to cartridge 700. The plough 724 is driven radially inward, cutting open the sterility barrier and rolling the scrap into a coil ahead of the plough. Foil naturally curls over and forms tight coil when plough lead angle is around 55 degs to horizontal. If angle of the plough may be between about 60-40 degs, preferably closer to 55 degs. In some embodiments, the foil may be removed in such a manner that the penetrating member does not need to pierce any sterile enclosure materials during launch.


Referring now to FIG. 69E, the gripper 716 may be lowered to engage the bare penetrating member or piercing member 720. Optionally, the disc or cartridge 8000 may be raised until the penetrating member 720 is pressed firmly into the gripper 716. Although not shown in the present figure, the penetrating member driver or actuator of the present embodiment may remain in the same horizontal plane as the penetrating member.


As seen in FIG. 69F, a bar 730 may be pressed downward on the outer end 732 of the protective cavity to deflect it so it is clear of the path of the penetrating member. In the present embodiment, the bar 730 is shaped to allow the bare penetrating member 720 to pass through. It should be understood that other shapes and orientations of the bar (such as contacting only one side or part of end 732) may be used to engage the end 732.


Referring now to FIG. 69G, an electrical solenoid or other electronic or feed-back controllable drive may actuate the gripper 716 radially outward, carrying the bare penetrating member 720 with it. The bare penetrating member projects from the protective case and into the skin of a finger or other tissue site that has been placed over the aperture of the actuator assembly. Suitable penetrating member drivers are described in commonly assigned, copending U.S. patent application Ser. No. 10/127,395 filed Apr. 19, 2002.


Referring now to FIG. 69H, the solenoid or other suitable penetrating member driver retracts the bare penetrating member 720 into a retracted position where it parks until the beginning of the next lancing cycle.


Referring now to FIG. 69I, bar 730 may be released so that the end 150 returns to an in-plane configuration with the cartridge 800.


As seen in FIG. 69J, the gripper 716 may drive a used bare penetrating member radially outward until the sharpened tip is embedded into a plastic wall 714 at or near the outward end 732 of the cavity thus immobilizing the contaminated penetrating member.


As seen in FIGS. 69K and 69L, the plough 724, the gripper 716, and penetrating member guide 722 may all be disengaged from the bare penetrating member 720. Optionally, it should be understood that the advance mechanism may lower the cartridge 700 from the gripper 716. The used penetrating member, restrained by the tip embedded in plastic, and by the cover foil at the opposite end, is stripped from the gripper. The disc or cartridge 700 may be rotated until a new, sealed; sterile penetrating member is in position under the launch mechanism.


Referring now to FIGS. 70 and 71, one object for some embodiments of the invention is to include blood sampling and sensing on this penetrating member actuation device. In the present embodiment, the drive mechanism (gripper 738 and solenoid drive coil 739) may be used to drive a penetrating member into the skin and couple this lancing event to acquire the blood sample as it forms at the surface of the finger. In a first embodiment shown in FIG. 70, microfluidic module 740 bearing the analyte detecting member chemistry and detection device 742 (FIG. 71) is couple on to the shaft of the penetrating member 720. The drive cycle described above may also actuate the module 740 so that it rests at the surface of the finger to acquire blood once the penetrating member retracts from the wound. The module 740 is allowed to remain on the surface of the finger or other tissue site until the gripper 738 has reached the back end 744 of the microfluidics module 740, at which point the module is also retracted into the casing. The amount of time the module 740 remains on the finger, in this embodiment, may be varied based on the distance the end 744 is located and the amount of time it takes the gripper to engage it on the withdrawal stroke. The blood filled module 740, filled while the module remains on pierced tissue site, may then undergo analyte detection by means such as but not limited to optical or electrochemical sensing.


The blood may be filled in the lumen that the penetrating member was in or the module may have separately defined sample chambers to the side of the penetrating member lumen. The analyte detecting member may also be placed right at the immediate vicinity or slightly setback from the module opening receiving blood so that low blood volumes will still reach the analyte detecting member. In some embodiments, the analyte sensing device and a visual display or other interface may be on board the apparatus and thus provide a readout of analyte levels without need to plug apparatus or a test strip into a separate reader device. As seen in FIG. 71, the cover 746 may also be clear to allow for light to pass through for optical sensing. The analyte detecting member may be used with low volumes such as less than about 1 microliter of sample, preferably less than about 0.6 microliter, more preferably less than about 0.3 microliter, and most preferably less than about 0.1 microliter of sample.


In another embodiment as seen in FIG. 72, sensing elements 760 may be directly printed or formed on the top of bottom of the penetrating member cartridge 700, depending on orientation. The bare penetrating member 720 is then actuated through a hole 762 in the plastic facing, withdrawn into the radial cavity followed by the blood sample. Electrochemical or optical detection for analyte sensing may then be carried out (FIG. 72). Again the cavity 766 may have a clear portion to allow light to pass for optical sensing. In one embodiment, a multiplicity of miniaturized analyte detecting member fields may be placed on the floor of the radial cavity as shown in FIG. 72 or on the microfluidic module shown in FIG. 71 to allow many tests on a single analyte form a single drop of blood to improve accuracy and precision of measurement. Although not limited in this manner, additional analyte detecting member fields or regions may also be included for calibration or other purposes.


Referring now to FIG. 73, a still further embodiment of a cartridge according to the present invention will be described. FIG. 73 shows one embodiment of a cartridge 800 which may be removably inserted into an apparatus for driving penetrating members to pierce skin or tissue. The cartridge 800 has a plurality of penetrating members 802 that may be individually or otherwise selectively actuated so that the penetrating members 802 may extend outward from the cartridge, as indicated by arrow 804, to penetrate tissue. In the present embodiment, the cartridge 800 may be based on a flat disc with a number of penetrating members such as, but in no way limited to, (25, 50, 75, 100, . . . ) arranged radially on the disc or cartridge 800. It should be understood that although the cartridge 800 is shown as a disc or a disc-shaped housing, other shapes or configurations of the cartridge may also work without departing from the spirit of the present invention of placing a plurality of penetrating members to be engaged, singly or in some combination, by a penetrating member driver.


Each penetrating member 802 may be contained in a cavity 806 in the cartridge 800 with the penetrating member's sharpened end facing radially outward and may be in the same plane as that of the cartridge. The cavity 806 may be molded, pressed, forged, or otherwise formed in the cartridge. Although not limited in this manner, the ends of the cavities 806 may be divided into individual fingers (such as one for each cavity) on the outer periphery of the disc. The particular shape of each cavity 806 may be designed to suit the size or shape of the penetrating member therein or the amount of space desired for placement of the analyte detecting members 808. For example and not limitation, the cavity 806 may have a V-shaped cross-section, a U-shaped cross-section, C-shaped cross-section, a multi-level cross section or the other cross-sections. The opening 810 through which a penetrating member 802 may exit to penetrate tissue may also have a variety of shapes, such as but not limited to, a circular opening, a square or rectangular opening, a U-shaped opening, a narrow opening that only allows the penetrating member to pass, an opening with more clearance on the sides, a slit, a configuration as shown in FIG. 75, or the other shapes.


In this embodiment, after actuation, the penetrating member 802 is returned into the cartridge and may be held within the cartridge 800 in a manner so that it is not able to be used again. By way of example and not limitation, a used penetrating member may be returned into the cartridge and held by the launcher in position until the next lancing event. At the time of the next lancing, the launcher may disengage the used penetrating member with the cartridge 800 turned or indexed to the next clean penetrating member such that the cavity holding the used penetrating member is position so that it is not accessible to the user (i.e. turn away from a penetrating member exit opening). In some embodiments, the tip of a used penetrating member may be driven into a protective stop that hold the penetrating member in place after use. The cartridge 800 is replaceable with a new cartridge 800 once all the penetrating members have been used or at such other time or condition as deemed desirable by the user.


Referring still to the embodiment in FIG. 73, the cartridge 800 may provide sterile environments for penetrating members via seals, foils, covers, polymeric, or similar materials used to seal the cavities and provide enclosed areas for the penetrating members to rest in. In the present embodiment, a foil or seal layer 820 is applied to one surface of the cartridge 800. The seal layer 820 may be made of a variety of materials such as but not limited to a metallic foil or other seal materials and may be of a tensile strength and other quality that may provide a sealed, sterile environment until the seal layer 820 is penetrate by a suitable or penetrating device providing a preselected or selected amount of force to open the sealed, sterile environment. Each cavity 806 may be individually sealed with a layer 820 in a manner such that the opening of one cavity does not interfere with the sterility in an adjacent or other cavity in the cartridge 800. As seen in the embodiment of FIG. 73, the seal layer 820 may be a planar material that is adhered to a top surface of the cartridge 800.


Depending on the orientation of the cartridge 800 in the penetrating member driver apparatus, the seal layer 820 may be on the top surface, side surface, bottom surface, or other positioned surface. For ease of illustration and discussion of the embodiment of FIG. 73, the layer 820 is placed on a top surface of the cartridge 800. The cavities 806 holding the penetrating members 802 are sealed on by the foil layer 820 and thus create the sterile environments for the penetrating members. The foil layer 820 may seal a plurality of cavities 806 or only a select number of cavities as desired.


In a still further feature of FIG. 73, the cartridge 800 may optionally include a plurality of analyte detecting members 808 on a substrate 822 which may be attached to a bottom surface of the cartridge 800. The substrate may be made of a material such as, but not limited to, a polymer, a foil, or other material suitable for attaching to a cartridge and holding the analyte detecting members 808. As seen in FIG. 73, the substrate 822 may hold a plurality of analyte detecting members, such as but not limited to, about 10-50, 50-100, or other combinations of analyte detecting members. This facilitates the assembly and integration of analyte detecting members 808 with cartridge 800. These analyte detecting members 808 may enable an integrated body fluid sampling system where the penetrating members 802 create a wound tract in a target tissue, which expresses body fluid that flows into the cartridge for analyte detection by at least one of the analyte detecting members 808. The substrate 822 may contain any number of analyte detecting members 808 suitable for detecting analytes in cartridge having a plurality of cavities 806. In one embodiment, many analyte detecting members 808 may be printed onto a single substrate 822 which is then adhered to the cartridge to facilitate manufacturing and simplify assembly. The analyte detecting members 808 may be electrochemical in nature. The analyte detecting members 808 may further contain enzymes, dyes, or other detectors which react when exposed to the desired analyte. Additionally, the analyte detecting members 808 may comprise of clear optical windows that allow light to pass into the body fluid for analyte analysis. The number, location, and type of analyte detecting member 808 may be varied as desired, based in part on the design of the cartridge, number of analytes to be measured, the need for analyte detecting member calibration, and the sensitivity of the analyte detecting members. If the cartridge 800 uses an analyte detecting member arrangement where the analyte detecting members are on a substrate attached to the bottom of the cartridge, there may be through holes (as shown in FIG. 76), wicking elements, capillary tube or other devices on the cartridge 800 to allow body fluid to flow from the cartridge to the analyte detecting members 808 for analysis. In other configurations, the analyte detecting members 808 may be printed, formed, or otherwise located directly in the cavities housing the penetrating members 802 or areas on the cartridge surface that receive blood after lancing.


The use of the seal layer 820 and substrate or analyte detecting member layer 822 may facilitate the manufacture of these cartridges 10. For example, a single seal layer 820 may be adhered, attached, or otherwise coupled to the cartridge 800 as indicated by arrows 824 to seal many of the cavities 806 at one time. A sheet 822 of analyte detecting members may also be adhered, attached, or otherwise coupled to the cartridge 800 as indicated by arrows 825 to provide many analyte detecting members on the cartridge at one time. During manufacturing of one embodiment of the present invention, the cartridge 800 may be loaded with penetrating members 802, sealed with layer 820 and a temporary layer (not shown) on the bottom where substrate 822 would later go, to provide a sealed environment for the penetrating members. This assembly with the temporary bottom layer is then taken to be sterilized. After sterilization, the assembly is taken to a clean room (or it may already be in a clear room or equivalent environment) where the temporary bottom layer is removed and the substrate 822 with analyte detecting members is coupled to the cartridge as shown in FIG. 73. This process allows for the sterile assembly of the cartridge with the penetrating members 802 using processes and/or temperatures that may degrade the accuracy or functionality of the analyte detecting members on substrate 822. As a nonlimiting example, the entire cartridge 800 may then be placed in a further sealed container such as but not limited to a pouch, bag, plastic molded container, etc . . . to facilitate contact, improve ruggedness, and/or allow for easier handling.


In some embodiments, more than one seal layer 820 may be used to seal the cavities 806. As examples of some embodiments, multiple layers may be placed over each cavity 806, half or some selected portion of the cavities may be sealed with one layer with the other half or selected portion of the cavities sealed with another sheet or layer, different shaped cavities may use different seal layer, or the like. The seal layer 820 may have different physical properties, such as those covering the penetrating members 802 near the end of the cartridge may have a different color such as but not limited to red to indicate to the user (if visually inspectable) that the user is down to say 10, 5, or other number of penetrating members before the cartridge should be changed out.


Referring now to FIGS. 74 and 75, one embodiment of the microfluidics used with the analyte detecting members 808 in cartridge 800 will now be described. For ease of illustration, the shape of cavity 806 has been simplified into a simple wedge shape. It should be understood that more sophisticated configurations such as but not limited to that shown in FIG. 73 may be used. FIG. 74 shows a channel 826 that assists in drawing body fluid towards the analyte detecting members 808. In the present embodiment, two analyte detecting members 808 are shown in the cavity 806. This is purely for illustrative purposes as the cavity 806 may have one analyte detecting member or any other number of analyte detecting members as desired. Body fluid entering cavity 806, while filling part of the cavity, will also be drawn by capillary action through the groove 826 towards the analyte detecting members 808. The analyte detecting members 808 may all perform the same analysis, they may each perform different types of analysis, or there may be some combination of the two (some sensors perform same analysis while others perform other analysis).



FIG. 75 shows a perspective view of a cutout of the cavity 806. The penetrating member 802 (shown in phantom) is housed in the cavity 806 and may extend outward through a penetrating member exit opening 830 as indicated by arrow 832. The position of the tip of penetrating member 802 may vary, such as but not limited to being near the penetrating member exit port or spaced apart from the exit. The location of the tip relative to the analyte detecting member 808 may also be varied, such as but not limited to being spaced apart or away from the analyte detecting member or collocated or in the immediate vicinity of the analyte detecting member. Fluid may then enter the cavity 806 and directed by channel 826. The channel 826 as shown in FIG. 75 is a groove that is open on top. The channel 826 may be entirely a groove with an open top or it may have a portion that is has a sealed top forming a lumen, or still further, the groove may be closed except for an opening near the penetrating member exit opening 830. It should be understood that capillary action can be achieved using a groove having one surface uncovered. In some embodiments, the analyte detecting member 808 is positioned close to the penetrating member exit opening 830 so that the analyte detecting member 808 may not need a capillary groove or channel to draw body fluid, such as in FIG. 78.


As seen in FIGS. 75 and 76, the cavity 806 may include the substrate 822 coupled to its bottom surface containing the analyte detecting members 808. With the analyte detecting members 808 located on the underside of the cartridge 800 as seen in the embodiment of FIG. 76, the cartridge 800 may include at least one through hole 834 to provide a passage for body fluid to pass from the cavity 806 to the analyte detecting member 808. The size, location, shape, and other features of the through hole 834 may be varied based on the cavity 806 and number of analyte detecting members 808 to be provided. In other embodiments, wicking elements or the like may be used to draw body fluid from the groove 826 to down to the analyte detecting member 808 via the through hole or holes 834.


Referring now to FIG. 77, a variety of groove and analyte detecting member configurations are shown on a single cartridge. These configurations are shown only for illustrative purposes and a single cartridge may not incorporate each of these configurations. Some embodiments may use any of the detecting members, singly or in combination. It should be understood, however, that analyte detecting member configuration could be customized for each cavity, such as but not limited to, using a different number and location of analyte detecting members depending lancing variables associated with that cavity, such as but not limited to, the time of day of the lancing event, the type of analyte to be measured, the test site to be lanced, stratum corneum hydration, or other lancing parameter. As a nonlimiting example, the detecting members may be moved closer towards the outer edge of the disc, more on the side walls, any combination, or the like.



FIG. 77 shows a penetrating member 802 in a cavity 838 with three analyte detecting members 808 in the cavity. For ease of illustration, the penetrating member 802 is omitted from the remaining cavities so that the analyte detecting member configurations can be more easily seen. Cavity 840 has a channel 826 with two analyte detecting members 808. Cavity 842 has a channel 844 coupled to a single analyte detecting member 808. Cavities 846 and 848 have one and two analyte detecting members 808, respectively. The analyte detecting members 808 in those cavities may be located directly at the penetrating member exit from the cartridge or substantially at the penetrating member exit. Other analyte detecting member configurations are also possible, such as but not limited to, placing one or more analyte detecting members on a side wall of the cavity, placing the analyte detecting members in particular arrays (for example, a linear array, triangular array, square array, etc . . . ) on the side wall or bottom surface, using mixed types of analyte detecting members (for example, electrochemical and optical, or some other combination), or mixed positioning of analyte detecting members (for example, at least one analyte detecting member on the substrate below the cartridge and at least one analyte detecting member in the cavity).



FIG. 78 shows an embodiment of cartridge 800 where the analyte detecting member 850 is located near the distal end of cavity 806. The analyte detecting member 850 may be formed, deposited, or otherwise attached there to the cartridge 800. In another embodiment, the analyte detecting member 850 may be a well or indentation having a bottom with sufficient transparency to allow an optical analyte detecting member to detect analytes in fluid deposited in the well or indentation. The well or indentation may also include some analyte reagent that reacts (fluoresces, changes colors, or presents other detectable qualities) when body fluid is placed in the well. In a still further embodiment, analyte detecting member 850 may be replaced with a through hole that allow fluid to pass there through. An analyte detecting member 808 on a substrate 822 may be attached to the underside of the cartridge 800, accessing fluid passing from the cavity 806 down to the analyte detecting member 808.


As mentioned above, the analyte detecting members 808 may also be placed right at the immediate vicinity or slightly setback from the module opening receiving blood so that low blood volumes will still reach the analyte detecting member. The analyte detecting members 808 may be used with low volumes such as less than about 1 microliter of sample, preferably less than about 0.6 microliter, more preferably less than about 0.3 microliter, and most preferably less than about 0.1 microliter of sample. Analyte detecting members 808 may also be directly printed or formed on the bottom of the penetrating member cartridge 800. In one embodiment, a multiplicity of miniaturized analyte detecting member fields may be placed on the floor of the radial cavity or on the microfluidic module to allow many tests on a single analyte form a single drop of blood to improve accuracy and precision of measurement. Although not limited in this manner, additional analyte detecting member fields or regions may also be included for calibration or other purposes.


Referring now to FIGS. 79-84, further embodiments of the cartridge 800 will now be described. FIG. 79 shows a cartridge 860 having a half-circular shape. FIG. 80 shows a cartridge 862 in the shape of a partial curve. FIG. 80 also shows that the cartridges 862 may be stacked in various configurations such as but not limited to vertically, horizontally, or in other orientations. FIG. 81 shows a cartridge 864 having a substantially straight, linear configuration. FIG. 82 shows a plurality of cartridges 864 arranged to extend radially outward from a center 866. Each cartridge may be on a slide (not shown for simplicity) that allows the cartridge 864 to slide radially outward to be aligned with a penetrating member launcher. After use, the cartridge 864 is slide back towards the center 866 and the entire assembly is rotated as indicated by arrow 868 to bring a new cartridge 864 into position for use with a penetrating member driver. FIG. 83 shows a still further embodiment where a plurality of cartridges 800 may be stacked for use with a penetrating member driver (see FIG. 85). The driver may be moved to align itself with each cartridge 800 or the cartridges may be moved to alight themselves with the driver. FIG. 84 shows a still further embodiment where a plurality of cartridge 864 are coupled together with a flexible support to define an array. A roller 870 may be used to move the cartridges 864 into position to be actuated by the penetrating member driver 872.


Referring now to FIG. 85, one embodiment of an apparatus 880 using a radial cartridge 800 with a penetrating member driver 882 is shown. A contoured surface 884 is located near a penetrating member exit port 886, allowing for a patient to place their finger in position for lancing. Although not shown, the apparatus 880 may include a human readable or other type of visual display to relay status to the user. The display may also show measured analyte levels or other measurement or feedback to the user without the need to plug apparatus 880 or a separate test strip into a separate analyte reader device. The apparatus 880 may include a processor or other logic for actuating the penetrating member or for measuring the analyte levels. The cartridge 800 may be loaded into the apparatus 880 by opening a top housing of the apparatus which may be hinged or removably coupled to a bottom housing. The cartridge 800 may also drawn into the apparatus 880 using a loading mechanism similar in spirit to that found on a compact disc player or the like. In such an embodiment, the apparatus may have a slot (similar to a CD player in an automobile) that allows for the insertion of the cartridge 800 into the apparatus 880 which is then automatically loaded into position or otherwise seated in the apparatus for operation therein. The loading mechanism may be mechanically powered or electrically powered. In some embodiments, the loading mechanism may use a loading tray in addition to the slot. The slot may be placed higher on the housing so that the cartridge 800 will have enough clearance to be loaded into the device and then dropped down over the penetrating member-driver 882. The cartridge 800 may have an indicator mark or indexing device that allows the cartridge to be properly aligned by the loading mechanism or an aligning mechanism once the cartridge 800 is placed into the apparatus 880. The cartridge 800 may rest on a radial platform that rotates about the penetrating member driver 882, thus providing a method for advancing the cartridge to bring unused penetrating members to engagement with the penetrating member driver. The cartridge 800 on its underside or other surface, may shaped or contoured such as but not limited to with notches, grooves, tractor holes, optical markers, or the like to facilitate handling and/or indexing of the cartridge. These shapes or surfaces may also be varied so as to indicate that the cartridge is almost out of unused penetrating members, that there are only five penetrating members left, or some other cartridge status indicator as desired.


A suitable method and apparatus for loading penetrating members has been described previously in commonly assigned, copending U.S. patent applications 60/393,706, filed Jul. 12, 2002 and 60/393,707, filed Jul. 1, 2002 are included here by reference for all purposes. Suitable devices for engaging the penetrating members and for removing protective materials associated with the penetrating member cavity are described in commonly assigned, copending U.S. patent applications 60/422,988, filed Nov. 1, 2002 and 60/424,429filed Nov. 6, 2002 are included here by reference for all purposes. For example in the embodiment of FIG. 78, the foil or seal layer 820 may cover the cavity by extending across the cavity along a top surface 890 and down along the angled surface 892 to provide a sealed, sterile environment for the penetrating member and analyte detecting members therein. A piercing element described in U.S. patent application 60/434,429, filed Nov. 6, 2002, has a piercing element and then a shaped portion behind the element which pushes the foil to the sides of the cavity or other position so that the penetrating member 802 may be actuated and body fluid may flow into the cavity.


Referring now to FIG. 86, a still further embodiment of a lancing system according to the present invention will be described. A radial cartridge 500 may be incorporated for use with a penetrating member driver 882. A penetrating member may be driven outward as indicated by arrow 894. A plurality of analyte detecting members are presented on a roll 895 that is laid out near a penetrating member exit. The roll 895 may be advanced as indicated by arrow 896 so that used analyte detecting members are moved away from the active site. The roll 895 may also be replaced by a disc holding a plurality of analyte detecting members, wherein the analyte detecting member disc (not shown) is oriented in a plane substantially orthogonal to the plane of cartridge 500. The analyte detecting member disc may also be at other angles not parallel to the plane of cartridge 500 so as to be able to rotate and present new, unused analyte detecting member in sequence with new unused penetrating members of cartridge 500.


Referring now to FIG. 87A, the cartridge 500 provides a high density packaging system for a lancing system. This form factor allows a patient to load a large number penetrating members through a single cartridge while maintaining a substantially handheld device. Of course such a cartridge 500 may also be used in non-handheld devices. The present cartridge 500 provide a high test density per volume of the disposable. For embodiments of a cartridge that includes analyte detecting members in addition to penetrating members such as cartridge 800, the density may also be measured in terms of density of analyte detecting members and penetrating members in a disposable. In other embodiments, the density may also be expressed in terms of analyte detecting members per disposable. For example, by taking the physical volume of one embodiment or the total envelope, this number can be divided by the number of penetrating members or number of tests. This result is the volume per penetrating member or per test in a cassetted fashion. For example, in one embodiment of the present invention, the total volume of the cartridge 500 is determined to be 4.53 cubic centimeters. In this one embodiment, the cartridge 500 holds 50 penetrating members. Dividing the volume by 50, the volume per test is arrived at 0.090 cubic centimeters. Conventional test devices such as drum is in the range of 0.720 or 0.670 cubic centimeters and that is simply the volume to hold a plurality of test strips. This does not include penetrating members as does the present embodiment 800. Thus, the present embodiment is at a substantially higher density. Even a slightly lower density device having penetrating members and analyte detecting members in the 0.500 cubic centimeter range would be a vast improvement over known devices since the numbers listed above for known devices does not include penetrating members, only packaging per test strip. Cartridges having volumes less than 4.53 may also be used.


Each penetrating member (or penetrating member and analyte detecting member, as the case may be) may have a packing density, or occupied volume, in cartridge 500. In various embodiments, the packing density or occupied volume of each penetrating member in cartridge 500 may be no more than about 0.66 cm.sup.3, 0.05 cm.sup.3, 0.4 cm.sup.3, 0.3 cm.sup.3, 0.2 cm.sup.3, 0.1 cm.sup.3, 0.075 cm.sup.3, 0.05 cm.sup.3, 0.025 cm.sup.3, 0.01 cm.sup.3, 0.090 cm.sup.3, 0.080 cm.sup.3, and the like. These numbers applicable to volumes for penetrating members alone, for combined penetrating members and analyte detecting members, and/or just analyte detecting members. In other words, the volume required for each penetrating member does not exceed 0.66 cm.sup.3/penetrating member, 0.05 cm.sup.3/penetrating member, 0.4 cm3/penetrating member, 0.3 cm.sup.3/penetrating member, 0.2 cm.sup.3/penetrating member, 0.1 cm.sup.3/penetrating member, 0.075 cm.sup.3/penetrating member, 0.05 cm.sup.3/penetrating member, 0.025 cm.sup.3/penetrating member, 0.01 cm.sup.3/penetrating member, 0.090 cm.sup.3/penetrating member and the like. So, if the total package volume of the cartridge is defined as X and the cartridge includes Y number of penetrating members, penetrating members and test area, or other unit 395, the volume for each unit does not exceed 0.66 cm.sup.3, 0.05 cm.sup.3, 0.4 cm.sup.3, 0.3 cm.sup.3, 0.2 cm.sup.3, 0.1 cm.sup.3, 0.075 cm.sup.3, 0.05 cm.sup.3, 0.025 cm.sup.3, 0.01 cm.sup.3, 0.090 cm.sup.3, 0.080 cm.sup.3, and the like.


Referring now to FIG. 87B, a still further embodiment of a cartridge according to the present invention will now be described. FIG. 87B shows a cross-section of a conical shaped cartridge with the penetrating member being oriented in one embodiment to move radially outward as indicated by arrow 897. In another embodiment, the penetrating member may be oriented to move radially inward as indicated by arrow 895. The gripper may be positioned to engage the penetrating member from an inner surface or an outer surface of the cartridge.


Referring now to FIG. 88, nanowires may also be used to create low volume analyte detecting members used with the cartridge 800. Further details of a nanowire device is described in commonly assigned, copending U.S. Provisional Patent Application Ser. No. 60/433,286 filed Dec. 13, 2002, fully incorporated herein by reference for all purposes. These nanowire analyte detecting members 898 may be incorporated into the cavity 806 housing the penetrating member 802. They may be placed on the floor or bottom surface of the cavity 806, on the wall, on the top surface, or any combinations of some or all of these possibilities. The analyte detecting members 898 may be designed to have different sensitivity ranges so as to enhance the overall sensitivity of an array of such analyte detecting members. Methods to achieve this may include, but are not limited to, using nanowires of varying sizes, varying the number of nanowires, or varying the amount of glucose oxidase or other glucose detection material on the nanowires. These nanowire analyte detecting members may be designed to use low volumes of body fluid for each sample, due to their size. In some embodiments, each of the analyte detecting members are accurate using volumes of body fluid sample less than about 500 nanoliters. In some embodiments, each of the analyte detecting members are accurate using volumes of body fluid sample less than about 300 nanoliters. In still other embodiments, each analyte detecting member is accurate with less than about 50 nanoliters, less than about 30 nanoliters, less than about 10 nanoliters, less than about 5 nanoliters, and less than about 1 nanoliters of body fluid sample. In some embodiments, the combined array of analyte detecting members uses less than 300 nanoliters of body fluid to arrive at an analyte measurement.


Referring now to FIG. 89, a still further embodiment of the present invention will be described. FIG. 89 shows one embodiment of an optical illumination system 910 for use with optical analyte detecting members (FIG. 91) that may be in contact with a body fluid sample. The overall system may include a plurality of analyte detecting members which provide some optical indicator, a light source 912 for providing light to shine on the analyte detecting members, at least one light detector 914, and a processor (not shown). The analyte detecting member or analyte detecting members are exposed to a sample of the fluid of unknown composition. A plurality of analyte detecting members may be arranged into an array of analyte detecting members exposed to one fluid sample, each group targeting a specific analyte and may contain an analyte-specific chemical that interacts more specifically with one analyte than with some other analytes to be analyzed. Each analyte detecting member may also have different sensitivity ranges so as to maximize overall sensitivity of an array of such analyte detecting members. The light source 912 shines light on at least one analyte detecting member to cause light interaction. The differences in the analyte detecting members may lead to differences in the light interaction. The light detector detects the light interaction by the analyte detecting members. The processor analyzes the light interaction by the analyte detecting members to take into account interference in light interaction among the analytes, thereby determining the concentration of the desired analyte in the fluid.


Referring still to the embodiment of FIG. 89, the light source 912 may be but is not limited to an LED. An alternative LED 915 may also be used with the present invention. Light, illumination, or excitation energy from LED 912 travels along a path through a pinhole 916, a filter 917, and a lens 918. The light then comes into contact with a beamsplitter 919 such as but not limited to a dichroic mirror or other device useful for beamsplitting. The light is then directed towards lens 920 as indicated by arrow 921. The lens 920 focuses light onto the analyte detecting member (FIG. 91). This excitation energy may cause a detectable optical indicator from the analyte detecting member. By way of example and not limitation, fluorescence energy may be reflected bay up the lens 920. This energy passes through the beamsplitter 919 and to lens 922 which is then received by detector 914 as indicated by arrow 923. The detector 914 measures the energy and this information is passed on to the processor (not shown) to determine analyte levels. The illumination system 910 may also include cells 924 on the disc surface. In this specific embodiment, a penetrating member 925 drive by a force generator 926 such as but not limited to a solenoid may be used to obtain the fluid sample. A detent 927 may also be included with the device along with other bare lancets or penetrating members 928.


Referring now to FIG. 90, another embodiment of the illumination system 910 is shown for use with a cartridge 929. Cartridge 929 is similar to cartridge 800. Cartridge 929 is a single cartridge having a plurality of penetrating members and a plurality of optical analyte detecting members (not shown). The cartridge 929 further includes a plurality of optically transparent portions 930 which may be but is not limited to windows or the like for the light from LED 912 to shine into a cavity of the cartridge 929. In one embodiment, each cavity of the cartridge 929 may include at least one transparent portion 930. This allows the light to generate energy that may be read by analyte detecting member 914. The cartridge 929 may be used a driver 882 to actuate penetrating members and the cartridge 929 may rotate as indicated by arrow 931.


Referring now to FIG. 91, a cross-section of a similar embodiment of the illumination system is shown. This system 932 has source 912 with a lens 933 having an excitation filter 934. This excitation filter 934, in one embodiment, only allows excitation energy to pass. This filter 934 allows the excitation energy to pass to dichroic mirror 935, but does not let it return to source 912. Excitation energy is reflected down as indicated by arrow 936. Lens 937 focuses the energy to optical analyte detecting member 938. Fluorescence energy 939 passes through the dichroic mirror 935 and towards a fluorescent filter 940. In one embodiment, the fluorescent filter 940 only allows fluorescent energy to pass through to lens 941. Thus, the detector 914 only receives fluorescent energy from the analyte detecting member 938. It should be understood of course, that the filter may be changed to allow the type of energy being generated by analyte detecting member 938 to pass. In some embodiments, no filter may be used. The dichroic mirror 935 may be a Bk7 substrate, 63×40×8 mm. The filters may also be a Bk7 substrate about 40 mm in diameter and about 6 mm thick. The lens 933, 937, and 941 may be achormat: bfl=53.6, working aperture 38 mm.


Referring now to FIG. 92, a still further embodiment of an illumination system 942 will be described. This system does not use a beamsplitter or dichroic mirror. Instead, both the source or LED 912 and detector 914 have direct line of sight to the optical analyte detecting member 938. In this embodiment, multiple elements are combined into a single housing. For example, lens 943, lens 944, and filter 945 are combined while lens 946, lens 947, and filter 948 are also combined.


Referring now to FIG. 93, a cross-section of a system similar to that of FIG. 89 is shown in a housing 950. LED 912 sends light to mirror 919 to a light path 951 to cells 924 on a surface of the disc. A finger access 952 allows a sample to be obtained and flow along a fluid pathway 953 to be analyzed. A processor 954 may be coupled to detector 914 to analyze the results.


Referring now to FIG. 94, a cross-section of a system similar to that of FIG. 90 will be further described. This shows a cartridge 929 used with a driver 882. This allows for a radial design where the penetrating members extend radially outward as indicated by arrow 955. The driver 882 may have a coupler portion that reciprocates as indicated by arrow 956. FIGS. 95 and 96 provide further views of a system similar to that of FIG. 89. The embodiment of FIGS. 95 and 96 may include additional lenses or filters as may be useful to refine energy detection.


Referring now to FIG. 97, one embodiment of a tissue penetrating device 1000 for use with digitally encoded information will now be described. A user interface 1002, including but not limited to an optical read out, and one or more detectors 1004 may be provided on the device. As a nonlimiting example, the detector 1004 can be a CMOS. The detector 1004 may provide a mechanism for digitally reading encoded information associated with the cartridge 1006, or any other information or aspect of the operation, use, and the like of the tissue penetrating system.


The tissue penetrating device 1000 may also include memory 1008. The memory 1008 can also include digitally encoded information associated with the tissue penetrating systems and its use. Examples of the digitally encoded information include but are not limited to number of penetrating members used, number of target tissue penetrating events, time and date of the last selected number of target tissue penetrating events, time interval between alarm and target tissue penetrating event, stratum corneum thickness, time of day, energy consumed by a penetrating member driver to drive a penetrating member into the target tissue, depth of penetrating member penetration, velocity of the penetrating member, desired velocity profile, velocity of the penetrating member into the target tissue, velocity of the penetrating member out of the target tissue, dwell time of the penetrating member in the target tissue, a target tissue relaxation parameter, force delivered on the target tissue, dwell time of the penetrating member, battery status, system status, consumed energy, speed profile of the penetrating member as the penetrating penetrates and advances through the target tissue, a tissue target tissue relaxation parameter, information relative to contact of a penetrating member with target tissue before penetration by the penetrating member, information relative to a change of speed of a penetrating member as in travels in the target tissue, type of electrochemical analyte detecting member used, the kind of test the analyte detecting member will be measuring, information relative to consumed sensors and/or information relative to consumed penetrating members. These features may also be included on a device without a lancing capability. Such a device may function mainly as an analyte detecting meter and may be designed to hold a cartridge that can be used for multiple measurement events. The digitally encoded information may be read via the user interface. It should be understood that bar coding and other techniques for relating information may also be used with the present invention.


Referring now to FIG. 98, one embodiment of a tissue penetrating device 1000 with an optical detection system that separates excitation and fluorescence images will now be described. One or more optical detectors or imagers 1010 are provided. In one embodiment, a grating 1012 is positioned at an aperture plane of a lens L. Excitation radiation is directed at an object O. In this embodiment, the object O may be a well with emulsions or other chemical compounds to detect the presence of at least one analyte. In the plane of the detector 1010, the diffraction of the grating 1012 causes the fluorescence image λf and excitation image λe to be separated. As a nonlimiting example, the detector 1010 can be a CMOS or CMOS array. This permits the excitation and fluorescence images to be separately detected.


As seen in FIG. 98, the lens aperture plane grating 1012 uses diffraction to separate the excitation image and fluorescent image. The filter 1014 may be used to attenuate the excitation so that saturation of the detector 1010 (which in this embodiment may be a CMOS array) can be prevented. The aim is to provide maximum focal plane information and reduce the need for a dichroic beamsplitter (although such a beamsplitter may be used in alternative embodiments). It should be understood that in some embodiments, a GRIN lens array may be used in place of lens L. Splitting of the image may allow for more accurate detection of the fluorescence image. Splitting may reduce the amount of noise associated with the fluorescence image. Splitting may also allow for referencing of the displaced images. The optical train of FIG. 98 may be adapted for use with the embodiments described in FIGS. 89-96 and with any of the embodiments disclosed herein. Although not limited to the following, the displaced images may be directed at one CMOS, one CMOS array, separate CMOS's, or separate CMOS arrays.


As described above, the tissue penetrating device such as but not limited to device 1000 may use photodetector arrays for fluorescence lifetime imaging to determine analyte levels. In one embodiment of the present invention, CMOS detector arrays are utilized to measure fluorescence lifetimes of the analyte detecting members. In one embodiment, each pixel in the array has a plurality of charge/voltage storage locations. A sample of the correct pixel light level can be stored at one or more of these storage locations, as illustrated in FIG. 99.


Referring now to FIG. 100, a time dependent optical image can be sampled and averaged, or integrated, on the array. This integration, as a function of time, is illustrated in FIG. 100. In the figure, “A” represents the averaged/integrated time dependent optical image on one capacitor. “B” is the averaged/integrated time dependent optical image on a different capacitor. A processor (not shown) in the device 1000 may be used to determine analyte levels using this lifetime information. Although not limited to the following, the capacitor may be on the cartridge or on the device 1000.


Referring now to FIG. 101, one embodiment of a tissue penetrating device and/or an analyte detecting meter, such as but not limited to device 1000, with a diffuser for illuminating well regions with homogenized light will now be described. In an optical detection system, in one embodiment, a diffuser 1020 may be utilized to uniformly illuminate several discrete analyte regions of wells 1022 from an extended light source 1024, including but not limited to LED's and the like.


In one embodiment, custom diffractive optical elements, including but not limited to kinoforms, illustrated in FIG. 102, can modify the phase in front of a focal plane of a lends to produce a highly uniform set of spots in back of the focal plane. Diffraction is utilized to rearrange the light fields. Algorithms, including but not limited to Gerchberg-Saxton, can be used to calculate the phase of the appropriate diffractive element in order to create an arbitrary distribution at the wells. The result is computation of a phase distribution that converts a light field, such as but not limited to that of an LED, to a specific and custom light distribution by means of diffraction. It should be understood that controller or processor associated with the tissue penetrating device 1000 may include logic for performing the phase and other calculations described above.


Referring now to FIG. 103, one embodiment of a tissue penetrating device and/or an analyte detecting meter with a device that maintains image quality of the wells will now be described. In one embodiment, the wells 1030 are maintained in focus through a combination of a light source 1032, an object, viewing lens 1034 and a detector 1036. If a well is warped, or becomes warped, and out of plane, the focus of the wells is maintained irrespective of the warping by use of a specific geometry to maintain focus. This corrects for out of plane errors of the wells. The lens position may be adjustable as indicated by arrows 1038. They may be movable in vertical, horizontal, tilted or other orientation other than shown by arrows in the FIG. 103.


Referring now to FIG. 104, one embodiment of a tissue penetrating device and/or an analyte detecting meter with auto fluorescence to reduce noise will now be described. In one embodiment, the effects of light that can interfere with a reading from the wells are removed. Examples of interfering light include but are not limited to, back-scattered illumination, auto fluorescence from the sample chamber, and the like. In this embodiment, interfering light levels from representative areas of the substrate that do not contain measurement signal. This is then used to compute the corrections for reading the response from the analyte detecting members in the wells. In one embodiment, the measurement may be made by a separate detector CMOS 1040. In one embodiment, a separate source 1042 (shown in phantom) may be used and aimed at a non-well portion of the object.


Referring now to FIG. 105, one embodiment of a tissue penetrating device and/or an analyte detecting meter with a dual luminescent analyte detecting member will now be described. In one embodiment, the analyte sensing system is a dual luminescent analyte detecting system that utilizes luminescent beads 1050 of the same color with different non-overlapping lifetimes ranges for their particular analyte. A slurry is laid over a well. Different portions of the slurry can be selected to be an oxygen sensor, a glucose sensor, and the like. The slurry has all of the properties needed for one or more analytes to be detected and/or measured. In one embodiment, the sample is selectively dispersed to different parts of the slurry with separate areas as demarked by dotted line 1052. Activation is dependent on the slurry and/or what is deposited. It should be understood that triple and other luminescent detecting systems may also be used.


Referring now to FIG. 106, one embodiment of a tissue penetrating device and/or an analyte detecting meter with a star geometry of wells will now be described. In one embodiment, a plurality of wells such as but not limited to W1 to W4 are provided and are arranged with a central fluid input port 1060 for receiving a body fluid with one or more analytes. The plurality of wells W1-W4 are coupled to the common input port 1060. In one specific embodiment, the wells are arranged in a star configuration, as illustrated in FIG. 106. Use of the common input port, which can be centrally positioned relative to each well W, and/or positioned the same distance from each well, provides that fluid is evenly distributed to each well. It should be understood that other configurations such as but not limited Y, asterisk, and other as shown in FIG. 107A may also be used. These wells may be combined with any of the cartridges described herein, such as but not limited to cartridge 500. In some embodiments, more than one well is associated with each glucose test event as seen in FIG. 107B. The disc-shaped cartridge 500 may have some, none, all, or combinations of the star and other shaped wells. The embodiment of FIG. 107B is purely exemplary.


Referring now to FIG. 108, one embodiment of a tissue penetrating device and/or an analyte detecting meter with equilibrium based measurement system with multiple channels will now be described. In one embodiment, each penetrating member 1070 is housed in a channel, as illustrated in FIG. 108. A multi-arm structure as seen in FIG. 109 is positioned adjacent to the channel housing the penetrating member. An equilibrium based measurement is utilized for analyte determination. In one embodiment, the chemistries of analyte detecting members, are separated in a channel in order to ease manufacturing challenges.


By way of illustration, and without limitation, glucose oxidase can be in one channel and Ru in an adjacent one. Oxygen is depleted from the glucose oxidase and the Ru then senses the depletion of the oxygen in the body fluid. It will be appreciated that this equilibrium bases measurement method and system can be used for any number of different chemistries and analytes.


In a still further embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with spectral encoding of well positions will now be described. In this embodiment of the present invention, one or more detectors or imagers are provided. In one embodiment, the detector is a plurality of discrete detectors.


Spectral encoding may be used in one embodiment of the invention to spectrally slice the fluorescence spectrum of multiple wells. Imaging homogenization may be used, along with complementary spectral filtering in the filter plane, to separate out the light from the wells. This makes the image position insensitive to the well positions. A processor in the device 1000 may include logic for handling the spectral encoding. A spectrofluorometer may be used to detect the signal. In one embodiment, the well may contain a plurality of beads and it may be possible to spectrally encode the beads used in wells.


In a still further embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with cylindrical optics to reduce image position sensitivity will now be described.


In one embodiment of the present invention, cylindrical optics are included. The cylindrical optics provide an afocal imaging system such that a point image from a well associated with a sensor is transformed to a line image. The line image overfills a linear detector array in a direction that is perpendicular to a scan of the array. This desensitizes an image position relative to a radical position of the well. In some embodiments, the cylindrical optics have a longitudinal axis orthogonal to the direction of the light reflected from the object. In other embodiments, the cylindrical optics have their longitudinal axis substantially parallel to the light from the object.


In a still further embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with detent placements will now be described. Detents may be positioned close to the penetrating members and/or the wells. The detents, or other equivalent structures, are utilized to reduce effects of position tolerances that can occur during manufacturing and alignment. These effects can be the direct result of maintaining mechanical tolerances. The detents can be utilized to hold the penetrating members in a plane of various optical components of the system.


In a still further embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with CMOS imager for multiple well sensors will now be described.


In one embodiment, an image integrated circuit is utilized with a plurality of disconnected areas. One or more CMOS imagers are utilized. This enables circuitry to be positioned around each image patch of the sensor wells. Parallel read-outs are produced. This embodiment also provides more correction of imperfections in the wells, including but not limited to well off-set. Issues relating to use of a regular array of pixels can be resolved.


In a still further embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with corrected importations in imager arrays for fluorescence lifetime measurement will now be described.


In one embodiment of the present invention, the performance of imager arrays, is improved for fluorescence lifetime or other optical measurements Means are provided for correcting, or adjusting, gains of individual pixels, or groups of pixels, in am imager array. The offsets can be corrected by injecting correction signals, into suitable correction circuits, using DAC's. An importation process is utilized to compute digital conversion values that are input into the DAC's. Suitable importation processes include, but are not limited, measuring offsets with no incident light, measuring gains using a fixed incident light level, and the like.


Referring now to FIG. 110, one embodiment of a tissue penetrating device and/or an analyte detecting meter with an optical imager array will now be described.


In one embodiment, the performance and multi-functionality of an optical imager array associated with the wells is improved. In one embodiment, the optical imager array is a CMOS. The optical imager can include one or more groups of pixels. By way of illustration, and without limitation, a mixture of pixel sizes and geometries for a task group is utilized. This reduces, and can minimize, the number of pixels and associated circuitry, and/or optimize the signal-to-noise ratio (SNR) of different pixels for different optical measurement functions for analytes in response to the analyte detecting members.


It should be understood that a variety of fluorescence lifetime measurement modalities may be used (ie pulse, phase, square wave) with any of the embodiments of the present invention. A CMOS array may have the following advantages:


It can increase the mechanical tolerances in the metering device. One implementation would be that the CMOS chip takes a full frame picture of the illuminated chemical wells, determines which pixels are looking at which wells, then proceeds to readout only the illuminated pixels. Any mechanical movement is compensated for in software. Excitation light over-flooding may be compensated for as provided by various embodiments discussed herein.


In one embodiment, a CMOS array can provide focus compensation (at the expense of collection the same amount of light from more pixels and perhaps reducing the SNR). A CMOS detector, in this nonlimiting example, can decrease cost by using 1 detector instead of 6 (assuming 6 chemical well). A CMOS detector decreases cost by allowing integration of detectors, pre-amp, and adc on same chip. The CMOS detector can centralize dc offset and gain drift to a single point, allows for automatic adjustment of offset and gain, decreases the cost by allowing other signal processing functions on the same chip.


As a nonlimiting example, a CMOS detector may make it easy to change chemical well geometry, referencing, etc. without redesign of the optical system. This may turn out to be one of the more important advantages of using CMOS arrays. Any change in chemical well geometry with discrete detectors, will require substantial changes in the optics. With sufficient pixel density and count, the addition of more wells, changes in well geometry, or changes in well spacing could be easily handled via software changes to the processor in a device such as but not limited to that of device 1000.


A CMOS detector provides the ability to read encoded data on cartridges such as bar codes. A separate system for reading data encoded into cartridges would be needed if discrete detectors are used. The CMOS detector also has the ability to determine the start time for the measurement by looking at the fluid front.


The present invention also compensates for disadvantages of known CMOS detectors. In some CMOS detectors, frame rate may be low. Frame rate is the time it takes to sample one image, move the signal from the pixels to ADC, digitize, then process that signal if needed. Each time sample for lifetime imaging may take one frame. Generally, pixel data is read out serially and the frame rate is dominated by this serialization. In one embodiment, fluorescent lifetimes are estimated by taking many frames and averaging the signals. For a given measurement interval (say 1 second), the more frames measured, the better the SNR. In some embodiments, individual detectors may be used where the signals are read out in parallel and the effective frame rate is very fast (limited by the modulation rate of the fluorescence). Fill factor of 40% is typical with current active pixel sensors. In the present invention, 98% is attainable with specialized buried structures and 98% is attainable with linear arrays.


In one embodiment of the present invention, fixed pattern noise (FPN) in detectors may be compensated for in the processor. Individual pixels have different gain and dark currents. This creates a noise signal which appears as a fixed pattern in the image. It does not always average out. Some CMOS designs, such as active column sensing, significantly reduce FPN. Compensation for FPN may also be accomplished using processor cycles. This can reduce frame rates. In addition, if the array is used to compensate for mechanical misalignment, then for a given chemical well position, different sets of pixels, with different FPN's will be used to detect signal each time the cartridge is moved.


It should be understood that over-flooding LED illumination may decrease signal levels. Compensation for misalignment may have the imaged area at the chemical well plane larger than the wells or measurement area alone. In order to see all possible positions of those chemical wells within the imaged area, all of the imaged area may be illuminated. That is, the spot of light from the LED would overfill the measurement area. Only a fraction of the illuminating photons would then go towards generating fluorescence.


In some embodiments, the frame rate is one of the primary specifications used in determining a given imaging array's applicability to measuring lifetimes. This is because frame-rate times pixel-count determines the pixel readout rate. The pixel readout rate sets the sampling rate used to estimate the fluorescent lifetime. Since multiple frames may be averaged to estimate lifetimes, the SNR will increase with increasing frame rate. The maximum frame rate is limited not only by the chip bandwidth, but also the maximum rate one can modulate Ruthenium fluorescence.


In one embodiment, to estimate a fluorescence lifetime, several samples or frames of the fluorescent signal may be taken at differing times. This does not include averaging used to achieve a certain SNR. For example, the number of frames required for phase and square wave modes are:


(1) for phase, assuming quadrature sampling=4 frames per modulation period (2 minimum, 4 needed to remove dc term)


(2) for square wave modulation=2 to 4 frames per modulation period (2 minimum, more needed to remove dc term)


(3) Assuming one sample per frame, the Ruthenium lifetime provides a fundamental limit to the frame rate one needs. Minimum Ruthenium lifetimes are approximately t=2 usec, implying maximum modulation rates f of: f≅1/2πτ=80 khz

square wave f≅1/6τ=83 khz(assuming 3τ to decay)


In one embodiment of the present invention, 10 nanowatts of fluorescence emission power was seen at the detector plane from a single chemical well of 200×200 microns. This gives a fluorescence emission intensity: I=250 milliwatts/meter2 (at the detector plane). Optical magnification was equal to 1, actual chemical well dimension was about 100×100 micron. The emission wavelength for this embodiment was approximately 650 nm. Each frame comprises one component of a multi-component lifetime determination. For example for phase: one frame for I, then one frame for Q; or for pulse excitation: one frame for the integral of the first half of the fluorescence decay, and one frame for the second half. All SNR estimates are for the one of these components (e.g. I or Q, ect.). The SNR for the estimate of T will be different. See section B. Ruthenium lifetime=2 usec, sample integration time=2 usec, max excitation modulation rate=80 Khz (limited by Ru response time). Read noise scales as square root of pixel area (due to KTC noise):


1. Averaging multiple frames improves the SNR by {square root over (number of frames)}







2.





SNR


/


well

=


(

SNR


/


pixel

)




Awell
Apix








where


Awell=area of the image of the chemical well at the detector plane


Apix=area of a single pixel


It was determined that source leakage (that is light from the excitation signal directly reaching the detector) was not an issue for square wave or pulse method.


Software may allow the detector to be driven in three modes such as but not limited to: pulse, phase, or amplitude. The frame rate, pixel rate, number of pixels, integration time, and sampling parameters for each of the measurement modes is changeable by the user. Timing diagrams for the three modes of operation are shown in Appendix C.


In one embodiment of the present invention, a circuit was designed and built which simulates Ruthenium fluorescence. In one embodiment, it can generate fluorescence decay profiles similar to that seen by either pulsed or sinusoidal excitation. For pulse excitation, a TTL input pulse is put through a first order exponential filter which then drives an LED, giving a light output with a first order exponential decay. The lifetime is adjustable from 2 to 5 microseconds. A red 650 nm LED is used to simulated Ruthenium emission fluorescence. For sinusoidal excitation, a second input accepts continuous TTL pulse trains of frequency equivalent to a sinusoidal excitation one would use in a phase type system. The output is a sinusoidal emission which is phase shifted by a first order exponential function. The circuit is shown in Appendix D.


Referring now to FIG. 110, a block diagram of one embodiment of the optical system is shown. In this particular embodiment, it comprise a red LED (650 nm), whose light is passed through a 100 micron pinhole. Light emanating from the pinhole is imaged via an afocal lens arrangement using two achromatic doublets. The space between the lenses was used to temporarily steer the beam for power measurements. Power from the pinhole was adjusted so that its image at the detector plane was approximately 2 nanowatts (peak). The pinhole is imaged onto the linear array with a magnification of 1:1. The array is mounted to an xy stage for fine tuning its position relative to the pinhole image. All beampaths were kept in light tight black anodized 1″ diameter tubing (Thor Labs).


Processing may be done on or off chip. The time slices may be generated to select out the required time samples of the fluorescent signal. These time slices may be taken as fast as possible to maximize SNR. The resultant high bandwidths have two major implications: First, the electronics, both on chip and off chip will require an added level of care and simulation in order to function properly with minimal excess noise impact. Second, the power consumption of this device and its associated ADC and signal processing could be significant. This should be kept in mind when designing the battery operated handheld version.


In another embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with improved storage stability will now be described. In this embodiment, penetrating members and their associated sample chambers are in a controlled environment during storage. A resealable septum, or other suitable device, is provided for the penetrating members, penetrating members and their associated sample chambers with analyte detecting members. The resealable septum can be utilized with multiple tissue penetrating members, and their associated multiple sample chambers with analyte detecting members. This improves the pre-use shelf-life and post-use storage.


The chemistry of the materials used for fluorescence detection of analytes will now be described.


Referring now to FIG. 111, a tissue penetrating device and/or an analyte detecting meter with single step deposition analyte detecting members will now be described. In one embodiment, a single step process is utilized to place the analyte detecting members in each well 1100. This simplifies the manufacturing steps for deposition of the different chemistries that make up the analyte detecting member.


As a nonlimiting example, the analyte detecting member may be a sensor layer of a single material that is deposited in one step. The sensor layer is a combination of everything that is deposited in a well 1100. This is achieved by forming an emulsion of a Ru sensing phase within a group of oxidase sensing materials. This emulsion is then deposited as a single step on the surface of the structure that houses all of the wells. A plurality of separators 1104 may be attached to the substrate 1106 as indicated by arrows 1108 to keep fluid from one area from flowing to wells in another area. In one embodiment, the separators 1104 may connected to have a hub-and-spoke configuration.


In another embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with multi-analyte sensing will now be described. It should be understood that any of the compounds described herein may be adapted for use with a cartridge 500 or with the embodiments show in FIGS. 89-96. In this embodiment, the analyte detecting members in the wells detect and/or measure multiple analytes. An emulsion based analyte detecting member is provided. The inside of the analyte detecting member includes an oxygen sensor and is surrounded by an enzyme. In one embodiment, a glucose detecting member can be created with an emulsion of beads. For a multi-analyte sensor, the dispersed elements are segregated so that one bead has one enzyme, and another bead has a different enzyme. In place of the beads, multi-phase emulsions can be utilized.


For other embodiments, the possible embodiments of the emulsion include 1) Use of emulsifiers with liquid silicone/hydrogel system, 2) Use of emulsifiers with x-linked silicone/hydrogel system, 4) Siloxane sol-gel/hydrogel system, and 5) Solid-supported O2 sensor/hydrogel. Candidate supports include silicas and zeolites. In one embodiment, hydrophile-lipophile balance (HLB) considerations are used to select candidate emulsifiers. Using simple, lab-available mixer, series of emulsions and dispersions varying, relative ratios of silicone/hydrogel, amount of emulsifier or dispersant, technique of addition (e.g. silicone/water pre-emulsion or direct emulsification into hydrogel solution), extent and degree of mixing, etc. are prepared.


The advantages of an emulsion system are its one-step application of the polymer system and an expectation that the increased interfacial area it provides will be desirable to achieve adequate signal sensitivity as the size of the polymer sensor system is progressively reduced. Interestingly, there is a hint that this dispersed configuration might be better than a two-layer configuration. O, S. Wolfbeis, I. Oehme, N. Papkovskaya and I. Klimant, Biosensors and Bioelectronics, 15, 69 (2000), provide a little limited data suggesting the dispersed approach gives longer operational stability (longer lifetime of product) than a two-layer approach.


On aspect of the present invention comprises identifying emulsifier candidates. In one embodiment, the desired HLB for polydimethylsiloxane (PDMS) silicone oil is 9-11. Paraffinic mineral oil has a similar required HLB of 10, more polar fluids have higher required HLBs (e.g. toluene is 15). This similar desired HLB for PDMS and aliphatic hydrocarbons is the reason why conventional hydrocarbon emulsifiers developed for hydrocarbon-in-water emulsions work well for silicone-in-water emulsions. The principal intermolecular interactions between PDMS molecules are the London forces between the methyl groups. The more polar siloxane backbone is shielded by the pendent methyl groups and has minor impact, causing the silicone to behave much like an aliphatic hydrocarbon in this respect. Consequently, it is not necessary to use silicone-based emulsifiers. Although they are available they are more expensive and can be obtained only in a more restricted range of HLBs than organic emulsifiers. The starting point for obtaining good emulsions is to match the required HLB of the oil to the HLB number of the emulsifier. Often two or more emulsifiers with a net average HLB of the required value is better than a single emulsifier. The conventional explanation of this is that the lower HLB component will usually be of smaller size and is likely to depress the interfacial tension more rapidly thereby aiding in emulsion formation. The higher HLB component will be bulkier and can bring steric repulsion factors that contribute to emulsion stability. The likelihood that a variety of low HLB/high HLB combinations will be tried is a good reason to focus on organic emulsifiers first and move to silicone-based emulsifiers only if the research direction requires it.


In one embodiment, TERGITOL TMN series of emulsifiers produced by Union Carbide Corporation (now a part of Dow Chemical) are used. They are the only line of organic emulsifiers specifically marketed as silicone-in-water emulsifiers. They are based on the trimethylnonyl hydrophobe (hence the TMN designation) and the poly(ethylene oxide) (EO) hydrophile. Their structure is (CH3)3 C(CH2)8 (EO)n. TMN-6 (n=6) has HLB 11.7. TMN-3 (HLB 8.1) and TMN-10 (HLB 16.1) are also available. Various mixtures will be tried starting with 50/25/25 TMN-6/TMN-3/TMN-10.


The well-known SPANS (sorbitan fatty acid esters) and TWEENS (ethoxylated adducts) are widely used in the pharmaceutical industry and known to be useful in emulsifying silicones, see, for example, German patent DE 19844262, Mar. 30, 2000 assigned to Beirsdorf A G or D-Y. Lee, C-N. Jung, K-D. Su, H-K. Choi and Y-H. Park, Kongop. Hwahak. 6, 1124 (1995). Several companies, including ICI, produce these materials under the SPAN, TWEEN and other trade names (e.g. ICI's ARLACEL). For example, TWEEN 85 is an ethoxylate sorbitan trioleate with a total of 21 ethylene oxide units and an HLB of 11.0. Many combinations for achieving this value are also possible. A TWEEN 60/SPAN 60 mixture will be amongst those tried initially. TWEEN 60 is POE (20) sorbitan monostearate with HLB 14.9; SPAN 60 is unethoxylated sorbitan monostearate with HLB 4.7. One attraction of these sorbitan-based emulsifiers is their compatibility with proteins (hence their pharmaceutical use) however, compatibility with the glucose oxidase chemistry might be an issue.


Alkylphenyl ethoxylates, e.g. the NONOXYNOLS based on nonylphenoxy(EO).sub.n and OCTOXYNOLS based on octylphenoxy have also been used to stabilize silicone emulsions. For example, a mixture of OCTOXYNOL-3 (n=3), HLB 8, and OCTOXYNOL-13 (n=13) is used in a Dow Corning patent, JP 61230734, Oct. 15, 1986. See also B. A. Saadevandi and J. L. Zakin, Chem. Eng. Comm. 156, 227 (1997) where NONOXYNOL-6 of HLB 10.8 is used, supplied by Rhodia under the trade name IGEPAL CO-530.30.


Note also that there are a number of silicone-polyether surfactants with HLBs in the 9 to 11 range. These include materials from GE, Th. Goldschmidt A G, and Dow Corning. However, most silicone-based emulsifiers are of much lower HLB and formulated as water-in-oil (inverse) emulsifiers and specialty wetting agents.


Based on the above, HEMA partitioned into trimethylsilylmethylmethacrylate in all cases within the examined range of water content. HEMA also partitioned into water in all combinations with acryloxypropyltris-(trimethylsiloxy)silane within the examined range of water content. However, this silane does not dissolve the Ru-complex.


HEMA also partitioned into water in all combinations with methacryloxypropyl-pentamethyldisiloxane and within the examined range of water content. However, trace amount of HEMA were also found in the siloxane monomer phase, and this amount did not seem to be water/HEMA content dependent. Importantly, Ru-complex is soluble in this disiloxane and for this reason it is presently the monomer of choice for emulsification studies with HEMA and water.


Additionally, seven different silicon-containing hydrophobic monomers and some dual mixtures of these monomers were evaluated for Ru complex solubility, ability to form emulsions, emulsion stability, and sensor properties of the resulting emulsions. Several different preparative procedures were developed (FIG. 1) and evaluated and the preferred hydrophilic-lipophilic balance (HLB) for each monomer and/or monomer mixture was determined (see FIG. 2). Emulsions containing UV sensitive initiators, Ru complex sensor and glucose oxidase (GOX) were made with hydroxyethyl methacrylate (HEMA) and poly-(ethylene glycol)methacrylate/poly(ethylene glycol)dimethacrylate (PEGMA/PEGDA). Over a dozen of these emulsions had stabilities ranging from 24 hours to several days. An example of a typical stable emulsion is shown in FIG. 3.


Formulation: Hydrophobic phase:hydrophilic phase=1:2 (v/v); In hydrophobic phase; Monomer 5:Monomer 1=4:1 (w/w); Surfactant: 1 wt. % of total monomers, Tergitol 15-S series (as indicated in the insert) with various HLB values; Excluded: GOX, Ru complex, benzoin ethyl ether (BEE) initiator.


Orange samples: Examples of stable emulsions containing Monomer 5, BEE, Ru complex, PEGDA, PEGMA, water, GOX and emulsifier Tergitol-15-S-15. Milky white samples: examples of separated unstable emulsion (these samples did not contain Ru complex). It should be understood that emulsions based on mixtures of Monomers 5 and 1 have shown improved sensor properties over the layer coating approach


Of the stable emulsions prepared, some of the best combinations of desired properties were obtained from those containing 4:1 (w/w) mixtures of 1,3-bis(3-methacryloxypro-pyl)tetramethyldisiloxane (Monomer 5) and trimethylsilylmethylmethacrylate (Monomer 1) in the hydrophobioc phase. These emulsions were prepared with various GOX concentrations (ranging from 1 to 21 mg/mL) and phase ratios (ranging from 1:1.5 to 1:4 hydrophobic:hydrophilic phase). Test results indicated the following improvements over the layered coating approach, including but not limited to, better reproducibility from well to well, significantly higher fluorescence intensity that may enable size reduction of the 2nd generation sensors to only 1/20 of the size of the 1st generation, improved mechanical robustness of emulsion coatings compared to hydrogel layers which significantly reduces or completely avoids leakage of GOX; and high GOX formulations showed very fast responses (less than 10 seconds).


One favorable emulsion formulation is an emulsion containing 1:2 (v/v) hydrophobic/hydrophilic phases, 4:1 (w/w) Monomer 5:Monomer 1 mixture for the hydrophobic phase and 1 mg/mL GOX content in the hydrophilic phase.


The obtained results confirm that emulsion approach offers better reproducibility, faster responsiveness and a higher signal output than the layer approach, but the dynamic range of florescence-life-time (FLT) can be improved. It will be possible to overcome this deficiency, which is a property of the hydrophobic monomer(s) used, by utilizing new, tailor-made monomers.


Even emulsions from the most-difficult-to-emulsify Monomer 1 can now be made adequately stable with life-times between 22 and 24 hours. Monomer 1 represented a problem from the beginning of this work: while it has very desirable oxygen quench properties, it is also very difficult to emulsify. This monomer's emulsions, however, can remain stable for at least 22 hours by using the phase inversion emulsification technique. For this reason, the phase inversion approach can be combined with utilization of mixed surfactants with higher and lower HLB values. This will prolong the life-time of Monomer 1 emulsions to as much as 3 days.


It should be understood that in some embodiments, emulsion formulations may be crosslinked. An emulsion curing approach has been developed using benzoin ethyl ether (BEE) a UV sensitive free radical initiator in the hydrophobic phase, and water-soluble (2,2-dimethoxy-2-phenyl acetophenone (Irgacure 651) in the hydrophilic phase. Upon exposure to UV light, these initiators effectively crosslink (cure) emulsions in an adequately short time (minutes).


Some nonlimiting examples of monomers that show better combinations of Ru complex solubility, oxygen quenching, emulsion lifetime stability, and synthetic reproducibility include but are not limited to: 1) End-capping one methacrylate end of Monomer 5 with SiR3 groups in order to improve its FLT dynamic range (i.e. oxygen quench property) while retaining highly favorable emulsification ability:




embedded image



2) preparing an analog of Monomer 1, such as CH2=CMeCOOCH(SiMe3)2 to improve emulsification ability while retaining good oxygen quench properties of Monomer 1:




embedded image


While remaining within the realm of micro-emulsions, the hydrophilic to hydrophobic phase ratio can be increased while retaining very good film robustness even without chemical crosslinking of the phases. This can be achieved by utilizing hydrophilic-hydrophobic block copolymers where mechanical integrity is provided by physical crosslinks between the constitutive blocks resulting from their microphase separation. Appropriate selection of the respective blocks may provide systems that can successfully contain well above 80% (w) water.


In one embodiment of the present invention, a tissue penetrating device and/or an analyte detecting meter with high sensitivity optical biosensor will now be described.


In one embodiment of the present invention, the natural pyrolloquiniline quinone (PQQ) containing enzyme is isolated from, by way of example, Acinetobacter calcoaceticus or preferably the more stable form obtained by cloning into Esherichia coli, and is used in conjunction with an autooxidisable electron acceptor. Suitable autooxidisable electron acceptors include but are not limited to phenazine methosulphate (PMS) or phenazine ethosulphate (PES). The combination produces a biochemical system which consumes oxygen in the presence of glucose. This is converted into the analyte detecting member by combining the system with an optical oxygen sensor that is based on fluorescence. The advantage is much higher turnover than alternatives, including but not limited to glucose oxidase (approximately 100 fold), and lower molecular weight. This facilitates smaller sensing areas in a miniaturized array type of device with higher sensitivity at low concentrations of glucose. In another embodiment, sensitive is further enhanced by adding a second enzyme, such as glucose oxidase, to recycle the products of GDH.


The present invention provides an analyte detecting member, that includes PQQ GDF or other PQQ enzymes in combination with an electron acceptor, which readily reacts with oxygen, immobilized in the vicinity of an optical (fluorescence-based) oxygen sensing system to form an optical biosensor where the PQQ enzyme's substrate is the analyte.


In one embodiment of the present invention, a method of creating virtual multi-sensors for a tissue penetrating system will now be described.


In one embodiment of the present invention, a single analyte detecting member is utilized. The chemistry is varied within each analyte detecting member. In one embodiment, a gradient is utilized for each analyte detecting member in a well. A continual gradient is created across the analyte detecting member, which increases the dynamic range of the analyte detecting member. By way of illustration, and without limitation, two separate drops of different concentrations are deposited into a well. As they diffuse, a gradient is created. In another embodiment, a gel is deposited in a well. A solution is then deposited, with the gel creating the gradient.


In yet another embodiment of the present invention, a method of manufacturing analyte detecting members of a tissue penetrating system will now be described.


In one embodiment, a platform is provided with multiple micro-channels. The platform is positioned above and in contact with the structure that contains the wells which will house the analyte detecting member. A liquid form of chemistry, to be immobilized in the wells, is introduced from the micro-channels into the wells. The platform is then removed. The top of the wells is scraped away, in order to level the amount of analyte detecting member in each well.


In one embodiment of the present invention, a method of sterilizing penetrating members of a tissue penetrating system will now be described.


In one embodiment the penetrating members and the analyte detecting members in the wells are sterilized at the same time. Gamma is used in combination with chemical treatments. In another embodiment, chemical treatments are used with the gamma. Examples of chemical treatments include but are not limited to glutaraldehyde, alcohol, peroxide, and the like.


Referring now to FIG. 112, a tissue penetrating device and/or an analyte detecting meter with solid microbeads 1120 in analyte detecting members will now be described.


In one embodiment, analyte detecting member is in the form of a micro-bead. The use of micro-beads eases manufacturing challenges. By way of illustration, and without limitation, a Ru bead can be coated with glucose oxidase. The handling of the chemistries is simplified to minimize wetting issues that can occur with the wells 1122. Use of the micro-beads also removes the need for highly controlled volume deposition when the analyte detecting member is integrated with the wells.


Referring now to FIG. 113, one embodiment of a method for manufacturing micro-array analyte detecting members will now be described. In one embodiment of the present invention, a process is provided for manufacturing an analyte detecting member array with a plurality of analyte detecting members, analyte detecting members. Each analyte detecting member can assess different parameters of interest and can require a plurality of chemistry layers. It should be understood that these method steps may be adapted for use in manufacturing a disc-shaped cartridge 500 or any of the cartridges described herein.


As seen in FIG. 113, with one embodiment of the method of the present invention, precise deposition of chemistries onto a reaction platform is not required. With the present invention, the method entails three major steps: (1) the manufacturing of reaction platform components that include channels and wells; (2) the deposition of analyte detecting member chemistries in a liquid phase; and (3) the assembly of platform components. These steps are distinct to minimize manufacturing complexity; e.g., the platform components can be manufactured at one location and then brought to a different location for the chemistry deposition step, with minimal transit between locations.


The reaction platform components may be designed in a manner that allows the analyte detecting member chemistries to be deposited in excess onto certain platform components. Specifically at Step 1, certain platform components include wells 1130, as well as potentially “inverse wells” and holes that expose features of other platform components that are layered on top of these platform components. Other platform components include channels, as well as potentially holes that when aligned with the inverse wells of other platform components effectively become wells themselves. Emulsion or other material are deposited in Step 2. The wells and effective wells created from inverse wells are designed so that that platform material between the analyte detecting member and the detector may be of the same thickness. The method of the present invention desires that the detector have a depth of field that is adequate for the difference in distance between the wells and the effective wells created from the inverse wells. The analyte detecting member chemistry that does not rest in the wells is scraped away from the platform at Step 3. The analyte detecting member chemistry is then set at Step 4, resulting in a solid or semi-solid phase. Step 5 shows that a top layer may be added to provide microfluidics to guide fluid to the wells 1130.


Referring now to FIG. 114, if the analyte detecting member chemistry desires the deposition of multiple layers of chemistries, subsequent layers can be deposited on the same platform components using the same scraping method if the earlier analyte detecting member chemistries volume becomes adequately reduced during the setting process as seen in Steps 6 and 7. Analyte detecting members sometimes desires layers of chemistries to organize certain chemistries into appropriate environment, such as hydrophilic environment for missing a liquid sample with certain chemistries and a hydrophobic environment for separating molecules in a gas phase from a liquid sample. Alternatively, another platform component may be assembled on top of the platform component onto which the earlier analyte detecting member chemistry had been deposited. This new platform component will have holes positioned such that when it is assembled with the earlier platform it effectively extends the depth of the wells, and the next layer of chemistries may therefore be deposited into the newly extended wells using the scraping method.


Referring now to FIG. 115, if it is desired to have analyte detecting members in an array that differ in their chemistries, all the analyte detecting members of one kind can be deposited onto a single platform component using the scraping method, and all of the analyte detecting members of other kinds can be deposited onto other platform components also using the scraping methods. Analyte detecting members comprised of different chemistries may be useful to calibrate other analyte detecting members, to assess the presence of substances that are known to interfere with other chemistries, and/or to have analyte detecting members that are tuned to specific ranges of concentration of a particular analyte. These platform components may be assembled adjacent to one another or on top of one another by lining up the wells in the upper platform components with holes in the lower components. FIG. 115 show the steps of one method for manufacturing multiple wells 1150 and 1152 on multiple levels. Microfluidic channels 1154 and 1156 may be formed in the layers to guide fluid the associated wells 1150 and 1152.


In another embodiment of the present invention, improved emulsion systems are described. One problems imagined was a possible difficulty with water loss from the continuous hydrophilic phase. In one embodiment, a block copolymer of hydrophobic and hydrophilic polymers such as polydimethylsiloxane (PDMS) and poly(ethylene oxide) (PEO) may be used. The technical field relates to block copolymers. The idea is based on the common, mutual insolubility of different polymers. If covalently bonded together they phase separate into domains. If an ABA type polymer or (AB)n polymer is used where A is the hydrophobic PDMS chain and B is the hydrophilic PBO chain, one A segment might be in one separated hydrophobic domain and the other A segment might be in another hydrophobic domain or droplet. Thus the hydrophobic domains might be chained together (held at their ends by covalent bonds with the hydrophilic chains, yet separated and unable to coalesce because of the mutual insolubility of PEO and PDMS chains. In some embodiments, a cross-linking of the PEO chains with each other may be desirable.


The present embodiments of the invention envisions block copolymers of hydrophiobic, oxygen permeable, Ru complex soluble, polymers such as PDMS with hydrophilic, water-soluble, GOX compatible, polymers such as PEO or polyacrylamide. Additional cross-linking in the hydrophilic phase may be desirable in the presence of water or blood as well.


In yet another embodiment of the present invention, improved emulsion systems are provided that make an emulsion particle size sufficiently small that it is geometrically impossible for a GOX molecule to fit inside it. One embodiment of the invention comprises a microemulsion of our preferred hydrophobic and hydrophilic phases.


The technical field relates to the field of so-called microemulsions. Ordinary emulsions are, in fact, dispersions on the micro-scale. Microemulsions are dispersions on the nano-scale. Thus a particle size in the 10 to 50 nm range, which is possible for certain microemulsions, could ensure that GOX molecules are excluded (assuming GOX is a typical, large protein of at least 100 nm in size).


Microemulsions are thermodynamically stable isotropic solutions containing hydrophobic oils, water and emulsifiers. In one embodiment, our hydrophobic oil is a silicone acrylate and contains Ru complex. Our water contains GOX and hydrogel materials. Nothing is known about how these extra additives will affect micremulsifiability. Several structural types of microemulsion are possible: nanodroplets, cylindrical structure, and bicontinuous. I suspect the nanodroplet type would be best for us as it minimizes the interfacial area which will already be very large (minimum area means minimum possibility of Brownian motion fluctuations causing GOX/Ru complex collisions and interaction). Certainly the bicontinuous arrangement where the two phases form interpenetrating networks separated by a layer of emulsifier would be the least desirable as it seems more a recipe for keeping the phases adjacent to each other than keeping them apart).


Phase diagrams were constructed at various compositions of emulsifier surfactant, hydrophilic phase and hydrophobic phase. Since much smaller dispersion sizes require much greater amounts of emulsifyer, it is desirable to have an emulsifier concentration at least 10× higher than the 1-2% region currently utilized for our conventional, macroemulsions. Compositions in the 20 to 45% emulsifier region may be prepared. The one property of microemulsions that we can most easily exploit is their transparency which results from their particle size being significantly less than the wavelength of light. Thus it is possible to make a variety of compositions and map out the phase diagram area between transparency and opaqueness. Microemulsions are thermodynamically stable and should not separate into two phases at all. Monitoring of this type of stability as we already do for our conventional emulsions will also be a useful indicator.


Referring now to FIG. 117, a still further embodiment of the present invention shows a disc-shaped cartridge 1170 and an analyte detecting member cartridge 1172. The cartridge 1172 may have electrochemical detecting members or optical-based detecting members. The members may be on the top side or the bottom side of the cartridge 1172. In one embodiment, a user may lance themselves via a penetrating member from the cartridge 1170. A user may then place the blood onto the detecting member on cartridge 1172. Both cartridge may fit into a device substantially similar to that of device 1000.


With any of the embodiments herein, fluid channels leading to the analyte detecting members may be configured to hold at least about 1.5 μl, 1.4 μl, 1.3 μl, 1.2 μl, 1.1 μl, 1.0 μl, 0.9 μl, 0.8 μl, 0.7 μl, 0.6 μl, 0.5 μl, 0.4 μl, 0.3 μl, 0.2 μl, 0.1 μl, 0.05 μl, or 0.01 μl. As another nonlimiting example, the fluid channels may also be viewed as holding no more than about 1.5 μl, 1.4 μl, 1.3 μl, 1.2 μl, 1.1 μl, 1.0 μl, 0.9 μl, 0.8 μl, 0.7 μl, 0.6 μl, 0.5 μl, 0.4 μl, 0.3 μl, 0.2 μl, 0.1 μl, 0.05 μl, or 0.01 μl, prior to the fluid entering the area 1130. In a still further embodiment, the chamber with the analyte detecting member may hold about 1.5 μl, 1.4 μl, 1.3 μl, 1.2 μl, 1.1 μl, 1.0 μl, 0.9 μl, 0.8 μl, 0.7 μl, 0.6 μl, 0.5 μl, 0.4 μl, 0.3 μl, 0.2 μl, 0.1 μl, 0.05 μl, or 0.01 μl. In some embodiments, the area 1130 is designed to hold a volume slightly less than the amount of that can be held in the channel prior to the fluid reaching the chamber.


As a nonlimiting example, the analyte detecting member used in the present embodiment can provide its analysis using no more than about 1.0 .mu.l, 0.9 .mu.l, 0.8 .mu.l, 0.7 .mu.l, 0.6 .mu.l, 0.5 .mu.l, 0.4 .mu.l, 0.3 .mu.l, 0.2 .mu.l, 0.1 .mu.l, 0.05 .mu.l, or 0.01 .mu.l of fluid. In some embodiments, the amount of fluid used by all analyte members associated with each sample chamber 1150 can provide its analysis using no more than about 1.0 .mu.l, 0.9 .mu.l, 0.8 .mu.l, 0.7 .mu.l, 0.6 .mu.l, 0.5 .mu.l, 0.4 .mu.l. 0.3 .mu.l, 0.2 .mu.l, 0.1 .mu.l, 0.05 .mu.l, or 0.01 .mu.l of fluid.


While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various adaptations, changes, modifications, substitutions, deletions, or additions of procedures and protocols may be made without departing from the spirit and scope of the invention. For example, with any of the above embodiments, the location of the penetrating member drive device may be varied, relative to the penetrating members or the cartridge. With any of the above embodiments, the penetrating member tips may be uncovered during actuation (i.e. penetrating members do not pierce the penetrating member enclosure or protective foil during launch). With any of the above embodiments, the penetrating members may be a bare penetrating member during launch. With any of the above embodiments, the penetrating members may be bare penetrating members prior to launch as this may allow for significantly tighter densities of penetrating members. In some embodiments, the penetrating members may be bent, curved, textured, shaped, or otherwise treated at a proximal end or area to facilitate handling by an actuator. The penetrating member may be configured to have a notch or groove to facilitate coupling to a gripper. The notch or groove may be formed along an elongate portion of the penetrating member. With any of the above embodiments, the cavity may be on the bottom or the top of the cartridge, with the gripper on the other side. In some embodiments, analyte detecting members may be printed on the top, bottom, or side of the cavities. The front end of the cartridge may be in contact with a user during lancing. The same driver may be used for advancing and retraction of the penetrating member. The penetrating member may have a diameters and length suitable for obtaining the blood volumes described herein. The penetrating member driver may also be in substantially the same plane as the cartridge. The driver may use a through hole or other opening to engage a proximal end of a penetrating member to actuate the penetrating member along a path into and out of the tissue.


Any of the features described in this application or any reference disclosed herein may be adapted for use with any embodiment of the present invention. For example, the devices of the present invention may also be combined for use with injection penetrating members or needles as described in commonly assigned, copending U.S. patent application Ser. No. 10/127,395 filed Apr. 19, 2002. An analyte detecting member to detect the presence of foil may also be included in the lancing apparatus. For example, if a cavity has been used before, the foil or sterility barrier will be punched. The analyte detecting member can detect if the cavity is fresh or not based on the status of the barrier. It should be understood that in optional embodiments, the sterility barrier may be designed to pierce a sterility barrier of thickness that does not dull a tip of the penetrating member. The lancing apparatus may also use improved drive mechanisms. For example, a solenoid force generator may be improved to try to increase the amount of force the solenoid can generate for a given current. A solenoid for use with the present invention may have five coils and in the present embodiment the slug is roughly the size of two coils. One change is to increase the thickness of the outer metal shell or windings surround the coils. By increasing the thickness, the flux will also be increased. The slug may be split; two smaller slugs may also be used and offset by ½ of a coil pitch. This allows more slugs to be approaching a coil where it could be accelerated. This creates more events where a slug is approaching a coil, creating a more efficient system.


In another optional alternative embodiment, a gripper in the inner end of the protective cavity may hold the penetrating member during shipment and after use, eliminating the feature of using the foil, protective end, or other part to retain the used penetrating member. Some other advantages of the disclosed embodiments and features of additional embodiments include: same mechanism for transferring the used penetrating members to a storage area; a high number of penetrating members such as but not limited to 25, 50, 75, 100, 500, or more penetrating members may be put on a disk or cartridge; molded body about a lancet becomes unnecessary; manufacturing of multiple penetrating member devices is simplified through the use of cartridges; handling is possible of bare rods metal wires, without any additional structural features, to actuate them into tissue; maintaining extreme (better than 50 micron—lateral—and better than 20 micron vertical) precision in guiding; and storage system for new and used penetrating members, with individual cavities/slots is provided. The housing of the lancing device may also be sized to be ergonomically pleasing. In one embodiment, the device has a width of about 56 mm, a length of about 105 mm and a thickness of about 15 mm. Additionally, some embodiments of the present invention may be used with non-electrical force generators or drive mechanism. For example, the punch device and methods for releasing the penetrating members from sterile enclosures could be adapted for use with spring based launchers. The gripper using a frictional coupling may also be adapted for use with other drive technologies.


Still further optional features may be included with the present invention. For example, with any of the above embodiments, the location of the penetrating member drive device may be varied, relative to the penetrating members or the cartridge. With any of the above embodiments, the penetrating member tips may be uncovered during actuation (i.e. penetrating members do not pierce the penetrating member enclosure or protective foil during launch). The penetrating members may be a bare penetrating member during launch. The same driver may be used for advancing and retraction of the penetrating member. Different analyte detecting members detecting different ranges of glucose concentration, different analytes, or the like may be combined for use with each penetrating member. Non-potentiometric measurement techniques may also be used for analyte detection. For example, direct electron transfer of glucose oxidase molecules adsorbed onto carbon nanotube powder microelectrode may be used to measure glucose levels. In some embodiments, the analyte detecting members may formed to flush with the cartridge so that a “well” is not formed. In some other embodiments, the analyte detecting members may formed to be substantially flush (within 200 microns or 100 microns) with the cartridge surfaces. In all methods, nanoscopic wire growth can be carried out via chemical vapor deposition (CVD) or other vapor deposition. In all of the embodiments of the invention, nanoscopic wires may be nanotubes. Any method useful for depositing a glucose oxidase or other analyte detection material on a nanowire or nanotube may be used with the present invention. Additionally, for some embodiments, any of the cartridge shown above may be configured without any of the penetrating members, so that the cartridge is simply an analyte detecting device. Still further, the indexing of the cartridge may be such that adjacent cavities may not necessarily be used serially or sequentially. As a nonlimiting example, every second cavity may be used sequentially, which means that the cartridge will go through two rotations before every or substantially all of the cavities are used. As another nonlimiting example, a cavity that is 3 cavities away, 4 cavities away, or N cavities away may be the next one used. This may allow for greater separation between cavities containing penetrating members that were just used and a fresh penetrating member to be used next. It should be understood that nanowires may be used with any embodiment of the cartridges described herein. The size and diameters of the radial cartridges described herein may also vary and are not limited to the sizes shown herein.


In some embodiments, in analyzing fluorescence lift times, frame rates in detectors are slow because of the time it takes to serialize many pixels, thus it is desirable to minimize the number of pixels. It may be desirable to select sub-arrays within the chip which have areas of interest (such as a chemical well fluorescent image). Parallel binning may also be desirable as it involves combining the charge on pixels before reading. This lowers the effective number of pixels to be read. These improvements may be achieved through the use of improved processors in a device similar to that of device 1000.


This application cross-references commonly assigned copending U.S. patent application Ser. No. 10/323,622 filed Dec. 18, 2002; commonly assigned copending U.S. patent application Ser. No. 10/323/623 filed Dec. 18, 2002; and commonly assigned copending U.S. patent application Ser. No. 10/324,053 filed Dec. 18, 2002. The present application is related to commonly assigned, co-pending U.S. patent application Ser. Nos. 10/335,215; 10/335,258; 10/335,099; 10/335,219; 10/335,052; 10/335,073; 10/335,220; 10/335,252; 10/335,218; 10/335,211; 10/335,257; 10/335,217; 10/335,212; 10/335,241; 10/335,183; 10/335,082; 10/335,240; 10/335,259; 10/335,182; filed Dec. 31, 2002. This application is related to commonly assigned, copending U.S. patent application Ser. No. 10/127,395 filed Apr. 19, 2002 and commonly assigned, copending U.S. patent application Ser. No. 10/237,261 filed Sep. 5, 2002. All applications listed above are fully incorporated herein by reference for all purposes. The publications discussed or cited herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed. All publications mentioned herein are incorporated herein by reference to disclose and describe the structures and/or methods in connection with which the publications are cited.


Expected variations or differences in the results are contemplated in accordance with the objects and practices of the present invention. It is intended, therefore, that the invention be defined by the scope of the claims which follow and that such claims be interpreted as broadly as is reasonable.

Claims
  • 1. A device for use in a metering device for measuring analyte levels in a sample fluid, said device comprising: a housing;a controllable electronic driver;a memory coupled to the drive force generator, the memory including time and date of a last selected number of target tissue penetrating events, the memory including a time interval between alarm and target tissue penetrating event, and energy consumed by a penetrating member driver to drive a penetrating member into the target tissue;a plurality of penetrating members;a cartridge;a plurality of analyte detecting members positioned on an analyte detecting member support that is positionable in the cartridge and each of an analyte detecting member being associated with a penetrating member, each of an analyte detecting member providing an indicator of analyte levels in said sample fluid; andthe analyte detecting member support being moveable in the cartridge so as to be able to move and present new, unused analyte detecting members in sequence with new unused penetrating members of cartridge.
  • 2. The device of claim 1, further comprising: a penetrating member sensor.
  • 3. The device of claim 1, further comprising: a processor coupled to the controllable electronic driver.
  • 4. The device of claim 3, further comprising: a feedback loop coupled to the processor.
  • 5. The device of claim 3, wherein processor includes control instructions for the penetrating member driver.
  • 6. The device of claim 5, wherein the processor includes a memory for storage and retrieval of a set of penetrating member profiles.
  • 7. The device of claim 1, further comprising: a first seal formed between the plurality of penetrating members and the cartridge.
  • 8. The device of claim 7, further comprising: a second seal located at least one of the distal port or proximal port of cartridge.
  • 9. The device of claim 1, wherein each penetrating member is an elongated member without molded attachments.
  • 10. The device of claim 1, further comprising: a penetrating member transport device for moving each of a penetrating member into a position aligned with the penetrating member driver.
  • 11. The device of claim 1, further comprising: a belt for holding the penetrating members in an array configuration.
  • 12. The device of claim 1, further comprising: a tape device configured to hold the penetrating members in an array configuration.
  • 13. The device of claim 1, further comprising: a support channel configured to hold the penetrating members in an array configuration.
  • 14. The device of claim 1, further comprising: a cog configured to hold the penetrating members in an array configuration.
  • 15. The device of claim 1, further comprising: a plurality of connectors between penetrating members for holding the penetrating members in an array configuration.
  • 16. The device of claim 1, further comprising: a support structure for receiving the penetrating members.
  • 17. The device of claim 16, wherein the support structure is a bandolier.
  • 18. The device of claim 16, wherein the support structure is a drum.
  • 19. The device of claim 16, wherein the support structure is a disc.
CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No. 10/541,124 filed Mar. 31, 2006 now U.S. Pat. No. 8,574,895 which is a §3.71 filing of PCT/US2003/014702 filed Dec. 30, 2003, which application claims the benefit of priority to U.S. Provisional Application Ser. No. 60/437,184 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,185 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,186 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,191 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,192 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,312 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,323 filed Dec. 31, 2002, U.S. Provisional Application Ser. No. 60/437,333 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,334 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,335 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,336 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,337 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,340 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,341 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,342 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,343 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,345 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,346 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,347 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,386 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,454 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,455 filed Dec. 30, 2002, U.S. Provisional Application Ser. No. 60/437,510 filed Dec. 30, 2002, and U.S. Provisional Application Ser. No. 60/437,514 filed Dec. 30, 2002. The applications listed in this paragraph are fully incorporated herein by reference for all purposes.

US Referenced Citations (3004)
Number Name Date Kind
2061 Osdel Apr 1841 A
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 Alfred Aug 1955 A
2763935 Whaley Sep 1956 A
2801633 Ehrlich Aug 1957 A
2880876 Dujardin Apr 1959 A
3046987 Ehrlich Jul 1962 A
3030959 Grunert Sep 1962 A
3063451 Kowalk Nov 1962 A
3086288 Balamuth 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 Rudolph Jun 1969 A
3494358 Grossenbacher Feb 1970 A
3607097 Auphan et al. Sep 1971 A
3620209 Kravitz Nov 1971 A
3626929 Sanz Dec 1971 A
3628026 Cronin Dec 1971 A
3665672 Speelman May 1972 A
3673475 Britton Jun 1972 A
3712292 Mielke, Jr. Jan 1973 A
3712293 Mielke, Jr. Jan 1973 A
3734812 Yazawa May 1973 A
3742954 Strickland Jul 1973 A
3780960 Tokuno Dec 1973 A
3832776 Sawyer Sep 1974 A
3836148 Manning Sep 1974 A
3851543 Krom Dec 1974 A
3853010 Christen Dec 1974 A
3924818 Pfeifle Dec 1975 A
3938526 Anderson Feb 1976 A
3953172 Shapiro Apr 1976 A
3971365 Smith Jul 1976 A
4057394 Genshaw Nov 1977 A
4077406 Sandhage Mar 1978 A
4109655 Chacornac Aug 1978 A
4139011 Benoit Feb 1979 A
4154228 Feldstein May 1979 A
4168130 Barth Sep 1979 A
4184486 Papa Jan 1980 A
4190420 Covington Feb 1980 A
4191193 Seo Mar 1980 A
4193690 Levenson Mar 1980 A
4203446 Hofert May 1980 A
4207870 Eldridge Jun 1980 A
4223674 Fluent Sep 1980 A
4224125 Nakamura Sep 1980 A
4224949 Scott Sep 1980 A
4230118 Holman et al. Oct 1980 A
4240439 Abe Dec 1980 A
4254083 Columbus Mar 1981 A
4258001 Pierce Mar 1981 A
4259653 McGonigal Mar 1981 A
4299230 Kubota Nov 1981 A
4301412 Hill Nov 1981 A
4321397 Nix Mar 1982 A
4338174 Tamura Jul 1982 A
4340669 Bauer Jul 1982 A
4350762 De Luca Sep 1982 A
4353984 Yamada Oct 1982 A
4356826 Kubota Nov 1982 A
4360016 Sarrine Nov 1982 A
4388922 Telang Jun 1983 A
4391905 Bauer Jul 1983 A
4391906 Bauer Jul 1983 A
4392933 Nakamura Jul 1983 A
4394512 Batz Jul 1983 A
4397556 Muller Aug 1983 A
4407008 Schmidt Sep 1983 A
4411266 Cosman Oct 1983 A
4414975 Ryder Nov 1983 A
4418037 Katsuyama Nov 1983 A
4420564 Tsuji Dec 1983 A
4425039 Grant Jan 1984 A
4426451 Columbus Jan 1984 A
4426884 Polchaninoff Jan 1984 A
4440301 Intengan Apr 1984 A
4442836 Meinecke Apr 1984 A
4442972 Sahay Apr 1984 A
4449529 Burns May 1984 A
4462405 Ehrlich Jul 1984 A
4469110 Slama Sep 1984 A
4490139 Huizenga et al. Dec 1984 A
4517978 Levin May 1985 A
4518384 Tarello May 1985 A
4523994 Shono 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 Sep 1985 A
4545382 Higgins Oct 1985 A
4553541 Burns Nov 1985 A
4561445 Berke Dec 1985 A
4577630 Nitzsche Mar 1986 A
4580564 Andersen Apr 1986 A
4580565 Cornell Apr 1986 A
4586819 Tochigi May 1986 A
4586926 Osborne May 1986 A
4590411 Kelly May 1986 A
4595479 Kimura Jun 1986 A
4600014 Beraha Jul 1986 A
4603209 Tsien Jul 1986 A
4608997 Conway Sep 1986 A
4615340 Cronenberg Oct 1986 A
4616649 Burns Oct 1986 A
4619754 Niki Oct 1986 A
4622974 Coleman Nov 1986 A
4624253 Burns Nov 1986 A
4627445 Garcia Dec 1986 A
4637393 Ray Jan 1987 A
4637403 Garcia Jan 1987 A
4643189 Mintz Feb 1987 A
4648408 Hutcheson Mar 1987 A
4648714 Benner Mar 1987 A
4653511 Goch Mar 1987 A
4653513 Dombrowski Mar 1987 A
4655225 Dahne 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 Jul 1987 A
4682892 Chawla Jul 1987 A
4695273 Brown Sep 1987 A
4702594 Grant Oct 1987 A
4711245 Higgins Dec 1987 A
4712460 Allen Dec 1987 A
4712548 Enstrom Dec 1987 A
4714462 DiDomenico Dec 1987 A
4715374 Maggio Dec 1987 A
4731330 Hill Mar 1988 A
4731726 Allen, III Mar 1988 A
4734360 Phillips Mar 1988 A
4735203 Ryder Apr 1988 A
4737458 Batz Apr 1988 A
4750489 Berkman Jun 1988 A
4753776 Hillman Jun 1988 A
4756884 Hillman Jul 1988 A
4757022 Shults Jul 1988 A
4758323 Davis Jul 1988 A
4774192 Terminiello Sep 1988 A
4784486 Van Wagenen Nov 1988 A
4787398 Garcia Nov 1988 A
4790979 Terminiello Dec 1988 A
4794926 Munsch et al. Jan 1989 A
4797283 Allen Jan 1989 A
4814142 Gleisner Mar 1989 A
4814661 Ratzlaff Mar 1989 A
4817603 Turner Apr 1989 A
4818493 Coville Apr 1989 A
4820010 Scifres Apr 1989 A
4820399 Senda Apr 1989 A
4823806 Bajada Apr 1989 A
4824639 Hildenbrand Apr 1989 A
RE32922 Levin et al. May 1989 E
4825711 Jensen May 1989 A
4827763 Bourland May 1989 A
4829011 Gibbons May 1989 A
4830959 McNeil May 1989 A
4836904 Armstron Jun 1989 A
4840893 Hill Jun 1989 A
4844095 Chiodo Jul 1989 A
4845392 Mumbower Jul 1989 A
4850973 Jordan Jul 1989 A
4857274 Simon Aug 1989 A
4868129 Gibbons Sep 1989 A
4869249 Crossman Sep 1989 A
4869265 McEwen Sep 1989 A
4873993 Meserol Oct 1989 A
4877026 de Laforcade Oct 1989 A
4882013 Turner Nov 1989 A
4883055 Merrick Nov 1989 A
4883068 Dechow Nov 1989 A
4886499 Cirelli Dec 1989 A
4889529 Haindl Dec 1989 A
4892097 Ranalletta Jan 1990 A
4895147 Bodicky Jan 1990 A
4895156 Schulze Jan 1990 A
4897173 Nankai Jan 1990 A
4900424 Birch Feb 1990 A
4900666 Phillips Feb 1990 A
4911794 Parce Mar 1990 A
4920977 Haynes May 1990 A
4924879 O'brien May 1990 A
4935346 Phillips Jun 1990 A
4938218 Goodman Jul 1990 A
4940468 Petillo Jul 1990 A
4944304 Nishina Jul 1990 A
4945045 Forrest Jul 1990 A
4946795 Gibbons Aug 1990 A
4948727 Cass Aug 1990 A
4948961 Hillman Aug 1990 A
4952373 Sugarman Aug 1990 A
4952515 Gleisner Aug 1990 A
4953552 DeMarzo Sep 1990 A
4953976 Adler-Golden Sep 1990 A
4963498 Hillman Oct 1990 A
4966581 Landau Oct 1990 A
4966646 Zdeblick Oct 1990 A
4966671 Nylander Oct 1990 A
4975581 Robinson Dec 1990 A
4976724 Nieto Dec 1990 A
4977910 Miyahara Dec 1990 A
4983178 Schnell Jan 1991 A
4984085 Landowski Jan 1991 A
4990154 Brown Feb 1991 A
4995402 Smith Feb 1991 A
4999582 Parks Mar 1991 A
5001054 Wagner Mar 1991 A
5001873 Rufin Mar 1991 A
5004923 Hillman Apr 1991 A
5010772 Bourland Apr 1991 A
5010774 Kikuo Apr 1991 A
5014718 Mitchen May 1991 A
5019974 Beckers May 1991 A
5026388 Ingalz Jun 1991 A
D318331 Phillips Jul 1991 S
5028142 Ostoich et al. Jul 1991 A
5029583 Meserol Jul 1991 A
5035704 Lambert Jul 1991 A
5039617 McDonald Aug 1991 A
5043143 Shaw Aug 1991 A
5046496 Betts Sep 1991 A
5047044 Smith Sep 1991 A
5049487 Phillips Sep 1991 A
5049673 Tsien Sep 1991 A
5054487 Clarke Oct 1991 A
5054499 Swierczek Oct 1991 A
5057082 Burchette, Jr. Oct 1991 A
5057277 Mauze Oct 1991 A
5059394 Phillips Oct 1991 A
5059789 Salcudean Oct 1991 A
5060174 Gross Oct 1991 A
5062898 McDermott Nov 1991 A
5064411 Gordon, III Nov 1991 A
5070874 Barnes Dec 1991 A
5070886 Mitchen Dec 1991 A
5073500 Saito et al. Dec 1991 A
5074872 Brown Dec 1991 A
5077017 Gorin Dec 1991 A
5077199 Basagni Dec 1991 A
5080865 Leiner Jan 1992 A
5086229 Rosenthal Feb 1992 A
5089112 Skotheim Feb 1992 A
5092842 Bechtold Mar 1992 A
5094943 Siedel Mar 1992 A
5096669 Lauks Mar 1992 A
5097810 Fishman Mar 1992 A
5100427 Crossman Mar 1992 A
5100428 Mumford Mar 1992 A
5104380 Holman Apr 1992 A
5104382 Brinkerhoff et al. Apr 1992 A
5104619 Castro Apr 1992 A
5104813 Besemer Apr 1992 A
5107764 Gasparrini Apr 1992 A
5108564 Szuminsky Apr 1992 A
5108889 Smith Apr 1992 A
5116759 Klainer May 1992 A
5120420 Nankai Jun 1992 A
5122244 Hoenes Jun 1992 A
5126034 Carter Jun 1992 A
5128015 Szuminsky Jul 1992 A
5128171 Gleisner Jul 1992 A
5132801 Yamano Jul 1992 A
5133730 Biro Jul 1992 A
5135719 Hillman Aug 1992 A
5139685 Castro Aug 1992 A
5140161 Hillman Aug 1992 A
5141868 Shanks Aug 1992 A
5144139 Hillman Sep 1992 A
5145565 Kater 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 Oct 1992 A
5162525 Masilamani Nov 1992 A
5163442 Ono Nov 1992 A
5164598 Hillman Nov 1992 A
5167619 Wuchinich Dec 1992 A
5170364 Gross Dec 1992 A
5174726 Findlay Dec 1992 A
D332490 Brown Jan 1993 S
5178142 Harjunmaa Jan 1993 A
5179005 Phillips Jan 1993 A
5181910 Scanlon Jan 1993 A
5181914 Zook Jan 1993 A
5183042 Harjunmaa Feb 1993 A
5185256 Nankai Feb 1993 A
5187100 Matzinger Feb 1993 A
5188118 Terwilliger Feb 1993 A
5189751 Giuliani Mar 1993 A
5192415 Yoshioka Mar 1993 A
5194391 Nauze Mar 1993 A
5196025 Ranalletta Mar 1993 A
5201324 Swierczek Apr 1993 A
5205920 Oyama Apr 1993 A
5208163 Charlton et al. May 1993 A
5209028 McDermott May 1993 A
5211652 Derbyshire May 1993 A
5212879 Biro May 1993 A
5215587 McConnellogue Jun 1993 A
5216597 Beckers Jun 1993 A
5217476 Wishinsky Jun 1993 A
5217480 Haber Jun 1993 A
5218966 Yamasawa Jun 1993 A
5222504 Solomon Jun 1993 A
5228972 Osaka Jul 1993 A
5229282 Yoshioka Jul 1993 A
5230866 Shartle Jul 1993 A
5231993 Haber et al. Aug 1993 A
5241969 Carson Sep 1993 A
5247932 Chung Sep 1993 A
5249583 Mallaby Oct 1993 A
5250066 Lambert Oct 1993 A
5251126 Kahn Oct 1993 A
5253656 Rincoe Oct 1993 A
5256998 Becker Oct 1993 A
5264103 Yoshioka Nov 1993 A
5264105 Gregg Nov 1993 A
5264106 McAleer Nov 1993 A
5266179 Nankai Nov 1993 A
5266359 Spielvogel Nov 1993 A
D342573 Cerola Dec 1993 S
5267974 Lambert Dec 1993 A
5272087 El Murr Dec 1993 A
5277181 Mendelson Jan 1994 A
5279294 Anderson Jan 1994 A
5279791 Aldrich Jan 1994 A
5282822 Macors Feb 1994 A
5286362 Hoenes Feb 1994 A
5286364 Yacynych Feb 1994 A
5288636 Pollmann Feb 1994 A
5294261 McDermott Mar 1994 A
5296378 Sakata Mar 1994 A
5300779 Hillman Apr 1994 A
5304192 Crouse Apr 1994 A
5304193 Zhadanov Apr 1994 A
5304347 Mann Apr 1994 A
5304468 Phillips Apr 1994 A
5306623 Kiser Apr 1994 A
5307263 Brown Apr 1994 A
5312590 Gunasingham May 1994 A
5314441 Cusack May 1994 A
5314442 Morita May 1994 A
5315793 Peterson May 1994 A
5316012 Siegal May 1994 A
5318583 Rabenau Jun 1994 A
5318584 Lange Jun 1994 A
5320607 Ishibashi Jun 1994 A
5320808 Holen Jun 1994 A
5324302 Crouse Jun 1994 A
5324303 Strong Jun 1994 A
5330634 Wong Jul 1994 A
5332479 Uenoyama Jul 1994 A
5341206 Pittaro Aug 1994 A
5342382 Brinkerhoff Aug 1994 A
5344703 Kovar Sep 1994 A
5350392 Purcell Sep 1994 A
5352351 White Oct 1994 A
5354287 Wacks Oct 1994 A
5354447 Uenoyama Oct 1994 A
5356420 Czernecki Oct 1994 A
5360410 Wacks Nov 1994 A
5365699 Armstrong Nov 1994 A
5366469 Steg Nov 1994 A
5366470 Ramel Nov 1994 A
5366609 White Nov 1994 A
5368047 Suzuki Nov 1994 A
5370509 Golding Dec 1994 A
5371687 Holmes Dec 1994 A
5372135 Mendelson Dec 1994 A
5375397 Ferrand Dec 1994 A
5378628 Gratzel Jan 1995 A
5382346 Uenoyama Jan 1995 A
5383885 Bland Jan 1995 A
5389534 Gentzkow Feb 1995 A
5390450 Goenka Feb 1995 A
5393903 Gratzel Feb 1995 A
5395339 Talonn Mar 1995 A
5395387 Burns Mar 1995 A
5397334 Schenk Mar 1995 A
5401376 Foos Mar 1995 A
5402798 Swierczek Apr 1995 A
5405283 Goenka Apr 1995 A
5405510 Betts Apr 1995 A
5405511 White Apr 1995 A
5407545 Hirose Apr 1995 A
5407554 Saurer Apr 1995 A
5407818 Gentzkow Apr 1995 A
5409583 Yoshioka Apr 1995 A
5409664 Allen Apr 1995 A
5410059 Fraser Apr 1995 A
5410474 Fox Apr 1995 A
5415169 Siczek May 1995 A
5418142 Kiser May 1995 A
5423847 Strong et al. Jun 1995 A
5424545 Block Jun 1995 A
5426032 Phillips Jun 1995 A
5436161 Bergstrom Jul 1995 A
5437999 Diebold Aug 1995 A
5438271 White Aug 1995 A
5443701 Willner Aug 1995 A
5445920 Saito 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 Oct 1995 A
5460182 Goodman Oct 1995 A
5462533 Daugherty Oct 1995 A
5464418 Schraga Nov 1995 A
5465722 Fort Nov 1995 A
5471102 Becker Nov 1995 A
5472427 Rammler Dec 1995 A
5474084 Cunniff Dec 1995 A
5476474 Davis Dec 1995 A
5480387 Gabriel Jan 1996 A
5487748 Marshall Jan 1996 A
D367109 Ryner Feb 1996 S
5490505 Diab Feb 1996 A
5496274 Graves Mar 1996 A
5496453 Uenoyama Mar 1996 A
5498542 Corey Mar 1996 A
5501836 Myerson Mar 1996 A
5501893 Laermer Mar 1996 A
5507288 Bocker Apr 1996 A
5507629 Jarvik Apr 1996 A
5508171 Walling Apr 1996 A
5509410 Hill Apr 1996 A
5510266 Bonner et al. Apr 1996 A
5512159 Yoshioka Apr 1996 A
5514152 Smith May 1996 A
5515170 Matzinger May 1996 A
5518006 Mawhirt May 1996 A
D371198 Savage Jun 1996 S
5524636 Sarvazyan Jun 1996 A
5525511 D'Costa Jun 1996 A
5525518 Lundsgaard Jun 1996 A
5526120 Jina Jun 1996 A
5527333 Nikkels Jun 1996 A
5527334 Kanner Jun 1996 A
5529074 Greenfield Jun 1996 A
5540676 Freiberg Jul 1996 A
5540709 Ramel Jul 1996 A
5543326 Heller Aug 1996 A
5545174 Schenk Aug 1996 A
5545291 Smith Aug 1996 A
5547702 Gleisner Aug 1996 A
D373419 Muramatsu Sep 1996 S
5554153 Costello Sep 1996 A
5554166 Lange Sep 1996 A
5558834 Chu Sep 1996 A
5562384 Alvite Oct 1996 A
5562696 Nobles Oct 1996 A
5563031 Yu Oct 1996 A
5563042 Phillips Oct 1996 A
5569286 Peckham Oct 1996 A
5569287 Tezuka Oct 1996 A
5571132 Mawhirt Nov 1996 A
5575284 Athan Nov 1996 A
5575403 Charlton Nov 1996 A
5575895 Ikeda Nov 1996 A
5582697 Ikeda Dec 1996 A
5584846 Mawhirt Dec 1996 A
5591139 Lin Jan 1997 A
5593852 Heller Jan 1997 A
5599501 Carey Feb 1997 A
5605837 Karimi Feb 1997 A
D378612 Clark Mar 1997 S
5608006 Myerson Mar 1997 A
5609749 Yamauchi Mar 1997 A
5611809 Marshall Mar 1997 A
5611810 Arnold Mar 1997 A
5613978 Harding Mar 1997 A
5616135 Thorne Apr 1997 A
5617851 Lipkovker Apr 1997 A
5618297 Hart Apr 1997 A
5620579 Genshaw Apr 1997 A
5620863 Tomasco Apr 1997 A
5624458 Lipscher Apr 1997 A
5624459 Kortenbach Apr 1997 A
5624537 Turner Apr 1997 A
D379516 Rutter May 1997 S
5628764 Schraga May 1997 A
5628765 Morita May 1997 A
5628890 Carter May 1997 A
5628961 Davis May 1997 A
5630828 Mawhirt May 1997 A
5630986 Charlton May 1997 A
5632410 Moulton May 1997 A
5640954 Pfeiffer Jun 1997 A
D381591 Rice Jul 1997 S
5643306 Schraga Jul 1997 A
5643308 Markman Jul 1997 A
5645555 Davis Jul 1997 A
5647851 Pokras Jul 1997 A
5650062 Ikeda Jul 1997 A
5653863 Genshaw Aug 1997 A
5657760 Ying Aug 1997 A
5658444 Black Aug 1997 A
5660791 Brenneman Aug 1997 A
D383550 Larson Sep 1997 S
5662127 De Vaughn Sep 1997 A
5662672 Pambianchi Sep 1997 A
5666966 Horie Sep 1997 A
5676143 Simonsen Oct 1997 A
5678306 Bozeman Oct 1997 A
5680858 Hansen et al. Oct 1997 A
5680872 Sesekura Oct 1997 A
5682233 Brinda Oct 1997 A
5682884 Hill Nov 1997 A
5683562 Schaffar Nov 1997 A
5691898 Rosenberg Nov 1997 A
5692514 Bowman Dec 1997 A
5695947 Guo Dec 1997 A
5700695 Yassinzadeh Dec 1997 A
5705045 Park Jan 1998 A
5707384 Kim Jan 1998 A
5708247 McAleer Jan 1998 A
5709668 Wacks Jan 1998 A
5709699 Warner Jan 1998 A
5710011 Forrow Jan 1998 A
5714123 Sohrab Feb 1998 A
5714390 Hallowitz Feb 1998 A
5719034 Kiser Feb 1998 A
5720862 Hamamoto Feb 1998 A
5720924 Eikmeier Feb 1998 A
D392391 Douglas Mar 1998 S
D392740 Yung Mar 1998 S
5723284 Ye Mar 1998 A
5727548 Hill Mar 1998 A
5729905 Mathiasmeier Mar 1998 A
5730753 Morita Mar 1998 A
5733085 Shida Mar 1998 A
5733300 Pambianchi Mar 1998 A
D393716 Brenneman Apr 1998 S
D393717 Brenneman Apr 1998 S
5735868 Lee Apr 1998 A
5736103 Pugh Apr 1998 A
5738244 Charlton Apr 1998 A
5741228 Lambrecht Apr 1998 A
5741634 Nozoe Apr 1998 A
RE35803 Lange May 1998 E
5746217 Erickson 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 May 1998 A
5755733 Morita May 1998 A
5758643 Wong Jun 1998 A
5759364 Charlton Jun 1998 A
5762770 Pritchard Jun 1998 A
5770086 Indriksons Jun 1998 A
5770369 Meade Jun 1998 A
5772586 Heinonen Jun 1998 A
5772677 Mawhirt Jun 1998 A
5773270 D'Orazio Jun 1998 A
5776157 Thorne Jul 1998 A
5776719 Douglas Jul 1998 A
5779365 Takaki Jul 1998 A
5780304 Matzinger Jul 1998 A
5782770 Mooradian Jul 1998 A
5782852 Foggia 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 Aug 1998 A
5795774 Matsumoto Aug 1998 A
5797940 Mawhirt Aug 1998 A
5797942 Schraga Aug 1998 A
5798030 Raguse Aug 1998 A
5798031 Charlton Aug 1998 A
5800781 Gavin Sep 1998 A
5801057 Smart Sep 1998 A
5807375 Gross Sep 1998 A
5810199 Charlton Sep 1998 A
D399566 Sohrab Oct 1998 S
5820551 Hill Oct 1998 A
5822715 Worthington Oct 1998 A
5823973 Racchini Oct 1998 A
5824491 Priest Oct 1998 A
5827181 Dias Oct 1998 A
5828943 Brown Oct 1998 A
5829589 Nguyen Nov 1998 A
5830219 Bird Nov 1998 A
5832448 Brown Nov 1998 A
5840020 Heinonen Nov 1998 A
5840171 Birch Nov 1998 A
5843691 Douglas Dec 1998 A
5843692 Phillips Dec 1998 A
5846216 Gonzales Dec 1998 A
5846486 Pugh Dec 1998 A
5846490 Yokota Dec 1998 A
5849174 Sanghera Dec 1998 A
5853373 Griffith Dec 1998 A
5854074 Charlton Dec 1998 A
D403975 Douglas Jan 1999 S
5855377 Murphy Jan 1999 A
5855801 Lin Jan 1999 A
5856174 Lipshutz Jan 1999 A
5856195 Charlton Jan 1999 A
5857967 Frid Jan 1999 A
5857983 Douglas Jan 1999 A
5858804 Zanzucchi Jan 1999 A
5860922 Gordon et al. Jan 1999 A
5863800 Eikmeier Jan 1999 A
5866353 Berneth Feb 1999 A
5868135 Kaufman Feb 1999 A
5868772 LeVaughn Feb 1999 A
5869972 Birch Feb 1999 A
5871494 Simons Feb 1999 A
5872713 Douglas Feb 1999 A
5873856 Hjertman et al. Feb 1999 A
5873887 King Feb 1999 A
5876351 Rohde Mar 1999 A
5876957 Douglas Mar 1999 A
5879163 Brown Mar 1999 A
5879310 Sopp Mar 1999 A
5879311 Duchon Mar 1999 A
5879373 Roper Mar 1999 A
5880829 Kauhaniemi Mar 1999 A
5882494 van Antwerp Mar 1999 A
5885211 Eppstein Mar 1999 A
5886056 Hershkowitz Mar 1999 A
5887133 Brown Mar 1999 A
5890128 Diaz Mar 1999 A
RE36191 Solomon Apr 1999 E
5891053 Sesekura Apr 1999 A
5892569 Van de Velde Apr 1999 A
5893848 Negus Apr 1999 A
5893870 Talen Apr 1999 A
5897493 Brown Apr 1999 A
5897569 Kellogg Apr 1999 A
5899855 Brown May 1999 A
5899915 Saadat May 1999 A
5900130 Benvegnu May 1999 A
5902731 Ouyang May 1999 A
5906921 Ikeda May 1999 A
D411619 Duchon Jun 1999 S
5908416 Costello Jun 1999 A
5911937 Hekal Jun 1999 A
5912134 Shartle Jun 1999 A
5913310 Brown Jun 1999 A
5916156 Hildenbrand Jun 1999 A
5916229 Evans Jun 1999 A
5916230 Brenneman Jun 1999 A
5918603 Brown Jul 1999 A
5919711 Boyd Jul 1999 A
5921963 Erez Jul 1999 A
5922188 Ikeda Jul 1999 A
5922530 Yu Jul 1999 A
5922591 Anderson Jul 1999 A
RE36268 Szuminsky 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 Aug 1999 A
5940153 Castaneda Aug 1999 A
5942102 Hodges Aug 1999 A
5942189 Wolfbeis Aug 1999 A
5947957 Morris Sep 1999 A
5951300 Brown Sep 1999 A
5951492 Douglas Sep 1999 A
5951493 Douglas Sep 1999 A
5951582 Thorne Sep 1999 A
5951836 McAleer Sep 1999 A
5954738 LeVaughn Sep 1999 A
5956501 Brown Sep 1999 A
5957846 Chiang Sep 1999 A
5958199 Miyamoto Sep 1999 A
5959098 Goldberg Sep 1999 A
5960403 Brown Sep 1999 A
5961451 Reber Oct 1999 A
5964718 Duchon Oct 1999 A
5965380 Heller Oct 1999 A
5968063 Chu Oct 1999 A
5968760 Phillips Oct 1999 A
5968836 Matzinger Oct 1999 A
5971941 Simons et al. Oct 1999 A
5972199 Heller Oct 1999 A
5972294 Smith Oct 1999 A
5972715 Celentano Oct 1999 A
5974124 Schlueter Oct 1999 A
5976085 Kimball Nov 1999 A
5983193 Heinonen Nov 1999 A
5985116 Ikeda Nov 1999 A
5985559 Brown Nov 1999 A
5986754 Harding Nov 1999 A
5993400 Rincoe Nov 1999 A
5993434 Dev Nov 1999 A
D417504 Love Dec 1999 S
5997476 Brown Dec 1999 A
5997509 Rosengart et al. Dec 1999 A
5997561 Bocker Dec 1999 A
5997817 Crismore Dec 1999 A
5997818 Hacker Dec 1999 A
6001067 Shults Dec 1999 A
6007497 Huitema Dec 1999 A
D418602 Prokop Jan 2000 S
6014577 Henning Jan 2000 A
6015392 Douglas Jan 2000 A
6018289 Sekura Jan 2000 A
6020110 Williams Feb 2000 A
6022324 Skinner Feb 2000 A
6022366 Schraga Feb 2000 A
6022748 Charych Feb 2000 A
6023629 Tamada Feb 2000 A
6023686 Brown Feb 2000 A
6027459 Shain Feb 2000 A
6030399 Ignotz Feb 2000 A
6030827 Davis Feb 2000 A
6030967 Marui Feb 2000 A
6032059 Henning Feb 2000 A
6032119 Brown Feb 2000 A
6033421 Theiss Mar 2000 A
6033866 Guo Mar 2000 A
6036924 Simons et al. Mar 2000 A
6037178 Leiner Mar 2000 A
6041253 Kost Mar 2000 A
6045567 Taylor Apr 2000 A
6046055 Wolfbeis Apr 2000 A
6048352 Douglas Apr 2000 A
D424696 Ray May 2000 S
6056701 Duchon May 2000 A
6059815 Lee May 2000 A
6060327 Keen May 2000 A
6061128 Zweig May 2000 A
6063039 Cunningham May 2000 A
6066103 Duchon May 2000 A
6066243 Anderson May 2000 A
6066296 Brady May 2000 A
6067463 Jeng May 2000 A
6068615 Brown May 2000 A
D426638 Ray Jun 2000 S
6070761 Bloom Jun 2000 A
6071249 Cunningham Jun 2000 A
6071250 Douglas Jun 2000 A
6071251 Cunningham Jun 2000 A
6071294 Simons Jun 2000 A
6071391 Gotoh Jun 2000 A
6074360 Haar et al. Jun 2000 A
6077408 Miyamoto Jun 2000 A
6080106 Lloyd Jun 2000 A
6080172 Fujiwara Jun 2000 A
D428150 Ruf Jul 2000 S
6083196 Trautman Jul 2000 A
6083710 Heller Jul 2000 A
6084660 Shartle Jul 2000 A
6085576 Sunshine Jul 2000 A
6086544 Hibner Jul 2000 A
6086545 Roe Jul 2000 A
6086562 Jacobsen Jul 2000 A
6090078 Erskine Jul 2000 A
6091975 Daddona Jul 2000 A
6093146 Filangeri Jul 2000 A
6093156 Cunningham Jul 2000 A
D428993 Lubs Aug 2000 S
6099484 Douglas Aug 2000 A
6099802 Pugh Aug 2000 A
6100107 Lei Aug 2000 A
6101478 Brown Aug 2000 A
6102933 Lee Aug 2000 A
6103033 Say Aug 2000 A
6103509 Sode Aug 2000 A
6104940 Watanabe Aug 2000 A
6106751 Talbot Aug 2000 A
6107083 Collins Aug 2000 A
6113578 Brown Sep 2000 A
6117155 Lee Sep 2000 A
6117630 Reber Sep 2000 A
6118126 Zanzucchi Sep 2000 A
6119033 Spigelman Sep 2000 A
6120462 Hibner Sep 2000 A
6120676 Heller Sep 2000 A
6121009 Heller Sep 2000 A
6122536 Sun Sep 2000 A
6126804 Andresen Oct 2000 A
6126899 Woudenberg Oct 2000 A
6129823 Hughes Oct 2000 A
6132449 Lum Oct 2000 A
6133837 Riley Oct 2000 A
6134461 Say Oct 2000 A
6136013 Marshall Oct 2000 A
6139562 Mauze Oct 2000 A
6143164 Heller 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 Nov 2000 A
6153069 Pottgen Nov 2000 A
RE36991 Yamamoto 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 Dec 2000 A
6159424 Kauhaniemi Dec 2000 A
6161095 Brown Dec 2000 A
6162397 Jurik Dec 2000 A
6162611 Heller Dec 2000 A
6167362 Brown Dec 2000 A
6167386 Brown Dec 2000 A
6168563 Brown Jan 2001 B1
6168957 Matzinger Jan 2001 B1
6171325 Mauze Jan 2001 B1
6172743 Kley et al. Jan 2001 B1
6175752 Say Jan 2001 B1
6176847 Humphreys Jan 2001 B1
6176865 Mauze Jan 2001 B1
6177000 Peterson Jan 2001 B1
6177931 Alexander Jan 2001 B1
6183489 Douglas Feb 2001 B1
6186145 Brown Feb 2001 B1
6190612 Berger Feb 2001 B1
6191852 Paffhausen Feb 2001 B1
6192891 Gravel Feb 2001 B1
6193673 Viola Feb 2001 B1
6193873 Ohara Feb 2001 B1
6194900 Freeman Feb 2001 B1
6197040 LeVaughn Mar 2001 B1
6197257 Raskas Mar 2001 B1
6200289 Hochman et al. Mar 2001 B1
6200773 Ouyang Mar 2001 B1
6203504 Latterell Mar 2001 B1
6206841 Cunningham et al. Mar 2001 B1
6210133 Aboul-Hosn Apr 2001 B1
6210272 Brown Apr 2001 B1
6210369 Wilmot Apr 2001 B1
6210420 Mauze Apr 2001 B1
6210421 Bocker Apr 2001 B1
6212417 Ikeda Apr 2001 B1
6214626 Meller Apr 2001 B1
6214804 Felgner Apr 2001 B1
6218571 Zheng Apr 2001 B1
6219574 Cormier Apr 2001 B1
6221023 Matsuba Apr 2001 B1
6221238 Grundig Apr 2001 B1
6224617 Saadat et al. May 2001 B1
6225078 Ikeda May 2001 B1
6228100 Schraga May 2001 B1
6230051 Cormier May 2001 B1
6230501 Bailey May 2001 B1
6231531 Lum May 2001 B1
6233471 Berner May 2001 B1
6233539 Brown May 2001 B1
6234772 Wampler May 2001 B1
6240393 Brown May 2001 B1
D444235 Roberts Jun 2001 S
6241862 McAleer Jun 2001 B1
6242207 Douglas Jun 2001 B1
6245060 Loomis Jun 2001 B1
6245215 Douglas Jun 2001 B1
6246992 Brown Jun 2001 B1
6248065 Brown Jun 2001 B1
6251083 Yum Jun 2001 B1
6251121 Saadat Jun 2001 B1
6251260 Heller Jun 2001 B1
6251344 Goldstein Jun 2001 B1
D444557 Levaughn Jul 2001 S
6254831 Barnard Jul 2001 B1
6256533 Vuzhakov Jul 2001 B1
6258111 Ross Jul 2001 B1
6258229 Winarta Jul 2001 B1
6258254 Miyamoto Jul 2001 B1
6261241 Burbank Jul 2001 B1
6261245 Kawai Jul 2001 B1
6261519 Harding Jul 2001 B1
6264635 Wampler Jul 2001 B1
6268161 Han Jul 2001 B1
6268162 Phillips Jul 2001 B1
6269314 Iitawaki Jul 2001 B1
6270455 Brown Aug 2001 B1
6270637 Crismore Aug 2001 B1
6272359 Kivela Aug 2001 B1
6272364 Kurnik Aug 2001 B1
6275717 Gross Aug 2001 B1
6280254 Wu Aug 2001 B1
6281006 Heller Aug 2001 B1
6283926 Cunningham Sep 2001 B1
6283982 Levaughn Sep 2001 B1
6284478 Heller Sep 2001 B1
6285448 Kuenstner Sep 2001 B1
6285454 Douglas Sep 2001 B1
6289254 Shimizu Sep 2001 B1
6290683 Erez Sep 2001 B1
6294897 Champlin Sep 2001 B1
6295506 Heinonen Sep 2001 B1
6299578 Kurnik Oct 2001 B1
6299596 Ding Oct 2001 B1
6299757 Feldman Oct 2001 B1
6302844 Walker Oct 2001 B1
6302855 Lav Oct 2001 B1
6305804 Rice Oct 2001 B1
6306104 Cunningham Oct 2001 B1
6306152 Verdonk Oct 2001 B1
6306347 Mason Oct 2001 B1
6309351 Kurnik Oct 2001 B1
6309370 Haim et al. Oct 2001 B1
6309535 Williams Oct 2001 B1
6312612 Sherman Nov 2001 B1
6315738 Nishikawa Nov 2001 B1
6318970 Backhouse Nov 2001 B1
6319210 Douglas Nov 2001 B1
6322574 Lloyd Nov 2001 B1
6322808 Trautman Nov 2001 B1
6322963 Bauer Nov 2001 B1
6329161 Heller Dec 2001 B1
6330426 Brown Dec 2001 B2
6331163 Kaplan Dec 2001 B1
6332871 Douglas Dec 2001 B1
6334363 Testud Jan 2002 B1
6334778 Brown Jan 2002 B1
6334856 Allen Jan 2002 B1
6335203 Patel Jan 2002 B1
6336900 Alleckson Jan 2002 B1
6338790 Feldman Jan 2002 B1
6346120 Yamazaki Feb 2002 B1
6349229 Watanabe Feb 2002 B1
6350273 Minagawa Feb 2002 B1
6350451 Horn Feb 2002 B1
6352514 Douglas Mar 2002 B1
6352523 Brown Mar 2002 B1
6353753 Flock Mar 2002 B1
6358196 Rayman Mar 2002 B1
6364889 Kheiri Apr 2002 B1
6364890 Lum Apr 2002 B1
6368273 Brown Apr 2002 B1
6375469 Brown Apr 2002 B1
6375626 Allen et al. Apr 2002 B1
6375627 Mauze Apr 2002 B1
6379301 Worthington Apr 2002 B1
6379317 Kintzig Apr 2002 B1
6379324 Gartstein Apr 2002 B1
6379969 Mauze Apr 2002 B1
6381577 Brown Apr 2002 B1
D456910 Clark May 2002 S
6387709 Mason May 2002 B1
6391005 Lum May 2002 B1
6395227 Kiser May 2002 B1
6398522 Skill Jun 2002 B2
6398562 Butler Jun 2002 B1
6399394 Dahm Jun 2002 B1
6402701 Kaplan Jun 2002 B1
6402704 Mcmorrow Jun 2002 B1
6409740 Kuhr Jun 2002 B1
6413410 Hodges Jul 2002 B1
6413411 Pottgen Jul 2002 B1
6415821 Kamholz Jul 2002 B2
6419661 Kuhr et al. Jul 2002 B1
6420128 Ouyang Jul 2002 B1
6421633 Heinonen Jul 2002 B1
6423014 Churchill Jul 2002 B1
6428664 Bhullar Aug 2002 B1
6436055 Roe Aug 2002 B1
6436256 Williams Aug 2002 B1
6436721 Kuo Aug 2002 B1
6440645 Yon-Hin Aug 2002 B1
6444115 Hodges Sep 2002 B1
6447119 Stewart et al. Sep 2002 B1
6447265 Antaki Sep 2002 B1
6451040 Purcell Sep 2002 B1
6453810 Rossmeisl Sep 2002 B1
6458258 Taniike Oct 2002 B2
6461496 Feldman Oct 2002 B1
6462162 van Antwerp Oct 2002 B2
6464649 Duchon Oct 2002 B1
6471903 Sherman Oct 2002 B2
6472220 Simons Oct 2002 B1
6475360 Hodges Nov 2002 B1
6475372 Ohara Nov 2002 B1
6475436 Schabbach Nov 2002 B1
6475750 Han Nov 2002 B1
6477394 Rice Nov 2002 B2
6477424 Thompson Nov 2002 B1
6484046 Say Nov 2002 B1
6485439 Roe Nov 2002 B1
6485461 Mason Nov 2002 B1
6485923 Yani Nov 2002 B1
6488827 Shartle Dec 2002 B1
6488872 Beebe et al. Dec 2002 B1
6488891 Mason Dec 2002 B2
6489133 Phillips Dec 2002 B2
6491709 Sharma Dec 2002 B2
6491870 Patel Dec 2002 B2
6494830 Wessel Dec 2002 B1
6497845 Sacherer Dec 2002 B1
6501404 Walker Dec 2002 B2
6501976 Sohrab Dec 2002 B1
6503210 Hirao Jan 2003 B1
6503231 Prausnitz Jan 2003 B1
6503290 Jarosinski Jan 2003 B1
6503381 Gotoh Jan 2003 B1
6506165 Sweeney Jan 2003 B1
6506168 Fathallah Jan 2003 B1
6506575 Knappe 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 Feb 2003 B2
6521110 Hodges Feb 2003 B1
6521182 Shartle Feb 2003 B1
6527521 Noda Mar 2003 B2
6527716 Eppstein Mar 2003 B1
6527778 Athanasiou Mar 2003 B2
6529377 Nelson Mar 2003 B1
6530892 Kelly Mar 2003 B1
6530937 Schraga Mar 2003 B1
6531322 Jurik Mar 2003 B1
6533949 Yeshurun Mar 2003 B1
6537207 Rice Mar 2003 B1
6537242 Palmer Mar 2003 B1
6537264 Cormier et al. Mar 2003 B1
6537292 Lee Mar 2003 B1
6540672 Simonsen Apr 2003 B1
6540675 Aceti Apr 2003 B2
6540762 Bertling Apr 2003 B1
6540891 Stewart Apr 2003 B1
6541266 Modzelewski Apr 2003 B2
6547954 Ikeda Apr 2003 B2
6549796 Sohrab Apr 2003 B2
6551494 Heller Apr 2003 B1
6553244 Lesho Apr 2003 B2
6554381 Locher Apr 2003 B2
6555061 Leong Apr 2003 B1
D475136 Taniguchi May 2003 S
6558320 Causey May 2003 B1
6558361 Yeshurun May 2003 B1
6558402 Chelak May 2003 B1
6558528 Matzinger May 2003 B1
6560471 Heller May 2003 B1
6561978 Conn May 2003 B1
6561989 Whitson May 2003 B2
6562210 Bhullar May 2003 B1
6565509 Say May 2003 B1
6565808 Hudak May 2003 B2
6569157 Shain May 2003 B1
6571651 Hodges Jun 2003 B1
6572566 Effenhauser Jun 2003 B2
6572822 Jurik Jun 2003 B2
6574490 Abbink Jun 2003 B2
6575905 Knobbe Jun 2003 B2
6576101 Heller Jun 2003 B1
6576117 Iketaki et al. Jun 2003 B1
6576416 Haviland Jun 2003 B2
6579690 Bonnecaze Jun 2003 B1
6582573 Douglas Jun 2003 B2
6584338 Van Muiswinkel Jun 2003 B1
D477670 Jurik Jul 2003 S
6586199 Ouyang Jul 2003 B2
6587705 Kim Jul 2003 B1
6589260 Schmelzeisen-R Jul 2003 B1
6589261 Abulhaj Jul 2003 B1
6591124 Sherman Jul 2003 B2
6591125 Buse Jul 2003 B1
6592744 Hodges Jul 2003 B1
6592745 Feldman Jul 2003 B1
6595919 Berner Jul 2003 B2
6599281 Struys et al. Jul 2003 B1
6599407 Taniike Jul 2003 B2
6599693 Webb Jul 2003 B1
6599769 Kondo Jul 2003 B2
6601534 Hebrank Aug 2003 B2
6602205 Erickson Aug 2003 B1
6602268 Kuhr Aug 2003 B2
6602678 Kwon Aug 2003 B2
6604050 Trippel Aug 2003 B2
6607362 Lum Aug 2003 B2
6607494 Fowler Aug 2003 B1
6607658 Heller Aug 2003 B1
6612111 Hodges Sep 2003 B1
6616616 Fritz Sep 2003 B2
6616819 Liamos Sep 2003 B1
6618934 Feldman Sep 2003 B1
6620112 Klitmose Sep 2003 B2
6620310 Ohara Sep 2003 B1
6623501 Heller Sep 2003 B2
6626851 Hirao Sep 2003 B2
6632349 Hodges Oct 2003 B1
6635222 Kent Oct 2003 B2
6638415 Hodges Oct 2003 B1
6638772 Douglas Oct 2003 B1
6641533 Causey Nov 2003 B2
6645142 Braig Nov 2003 B2
6645219 Roe Nov 2003 B2
6645368 Beatty Nov 2003 B1
6649416 Kauer Nov 2003 B1
6650915 Routt Nov 2003 B2
6652720 Mansouri Nov 2003 B1
6652734 Hodges Nov 2003 B1
6652814 House Nov 2003 B1
D484600 Kaar Dec 2003 S
6656428 Clark et al. Dec 2003 B1
6656697 Ouyang Dec 2003 B1
6656702 Yugawa Dec 2003 B1
6659966 Essenpreis Dec 2003 B2
6660018 Lum Dec 2003 B2
6662439 Bhullar Dec 2003 B1
6669669 Flaherty Dec 2003 B2
6671527 Petersson Dec 2003 B2
D484980 Hartwein Jan 2004 S
6673617 Patel Jan 2004 B2
6676995 Dick Jan 2004 B2
6679841 Bojan Jan 2004 B2
6679852 Forster Jan 2004 B1
6682933 Patel Jan 2004 B2
6689411 Dick Feb 2004 B2
6706000 Perez Mar 2004 B2
6706049 Moerman Mar 2004 B2
6706159 Moerman Mar 2004 B2
6706232 Hasegawa Mar 2004 B2
6709692 Sudor Mar 2004 B2
6713660 Roe Mar 2004 B1
6716577 Yu Apr 2004 B1
6719887 Hasegawa Apr 2004 B2
6719923 Stiene Apr 2004 B2
6721586 Kiser Apr 2004 B2
6723046 Lichtenstein Apr 2004 B2
6723111 Abulhaj 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 May 2004 B1
6731966 Spigelman May 2004 B1
6733493 Gruzdev May 2004 B2
6736777 Kim May 2004 B2
6738654 Sohrab May 2004 B2
6740215 Nakaminami et al. May 2004 B1
6743211 PraUsnitz Jun 2004 B1
6743597 Guo Jun 2004 B1
6743635 Neel Jun 2004 B2
6746872 Zheng Jun 2004 B2
6749618 Levaughn Jun 2004 B2
6749740 Liamos Jun 2004 B2
6749792 Olson Jun 2004 B2
6749887 Dick Jun 2004 B1
6751491 Lew Jun 2004 B2
6752817 Flora Jun 2004 B2
6753187 Cizdziel Jun 2004 B2
6759190 Lin Jul 2004 B2
6764496 Schraga Jul 2004 B2
6764581 Forrow Jul 2004 B1
6767441 Cai Jul 2004 B1
6773671 Lewis Aug 2004 B1
6776888 Yamamoto Aug 2004 B2
6780645 Hayter Aug 2004 B2
6780647 Fujiwara Aug 2004 B2
6783502 Orloff Aug 2004 B2
6783537 Kuhr Aug 2004 B1
6784274 van Antwerp Aug 2004 B2
6786874 Grace Sep 2004 B2
6787013 Chang Sep 2004 B2
6787109 Haar Sep 2004 B2
6790327 Ikeda Sep 2004 B2
6790599 Madou Sep 2004 B1
6792791 Sato Sep 2004 B2
6793632 Sohrab Sep 2004 B2
6793633 Douglas Sep 2004 B2
6793802 Lee Sep 2004 B2
6797150 Kermani Sep 2004 B2
6800488 Khan Oct 2004 B2
6801041 Karinka Oct 2004 B2
6801804 Miller Oct 2004 B2
6802199 Hilgers Oct 2004 B2
6802811 Slepian Oct 2004 B1
6802957 Jung Oct 2004 B2
6805780 Ryu Oct 2004 B1
6808499 Churchill Oct 2004 B1
6808908 Yao Oct 2004 B2
6808937 Ligler Oct 2004 B2
6809807 Erickson Oct 2004 B1
6811406 Grube Nov 2004 B2
6811557 Schraga Nov 2004 B2
6811659 Vachon Nov 2004 B2
6811753 Hirao Nov 2004 B2
6811792 Roser Nov 2004 B2
6812031 Carlsson Nov 2004 B1
6814843 Bhullar Nov 2004 B1
6814844 Bhullar Nov 2004 B2
6814845 Wilson Nov 2004 B2
6815186 Clark Nov 2004 B2
6816742 Kim Nov 2004 B2
6818180 Douglas Nov 2004 B2
6821483 Phillips Nov 2004 B2
6823750 Hodges Nov 2004 B2
6825047 Woudenberg Nov 2004 B1
6827250 Uhland Dec 2004 B2
6827829 Kawanaka Dec 2004 B2
6829507 Lidman Dec 2004 B1
6830551 Uchigaki Dec 2004 B1
6830668 Musho Dec 2004 B2
6830669 Miyazaki Dec 2004 B2
6830934 Harding Dec 2004 B1
6833540 MacKenzie Dec 2004 B2
6835184 Sage Dec 2004 B1
6835553 Han Dec 2004 B2
6835570 Patel Dec 2004 B2
6837858 Cunningham Jan 2005 B2
6837976 Cai Jan 2005 B2
6837988 Leong Jan 2005 B2
6840912 Kloepfer Jan 2005 B2
6841052 Musho Jan 2005 B2
6843254 Tapper Jan 2005 B2
6843902 Penner Jan 2005 B1
6844149 Goldman Jan 2005 B2
6847451 Pugh Jan 2005 B2
6849052 Uchigaki Feb 2005 B2
6849168 Crumly Feb 2005 B2
6849216 Rappin Feb 2005 B2
6849456 Patel Feb 2005 B2
6850790 Berner Feb 2005 B2
6852119 Abulhaj Feb 2005 B1
6852212 Maxwell Feb 2005 B2
6852500 Hoss Feb 2005 B1
6853854 Proniewicz 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 Feb 2005 B2
6859738 Bush Feb 2005 B2
6862466 Ackerman Mar 2005 B2
6862534 Sterling Mar 2005 B2
6863800 Karinka Mar 2005 B2
6863801 Hodges Mar 2005 B2
6865408 Abbink Mar 2005 B1
6866641 Marshall Mar 2005 B2
6866675 Perez Mar 2005 B2
6866758 Bhullar Mar 2005 B2
6866822 House Mar 2005 B1
6869418 Marano-Ford Mar 2005 B2
6872200 Mann Mar 2005 B2
6872297 Mansouri Mar 2005 B2
6872298 Kermani Mar 2005 B2
6872299 Kermani Mar 2005 B2
6872358 Hagen Mar 2005 B2
6875208 Santini Apr 2005 B2
6875223 Argauer Apr 2005 B2
6875327 Miyazaki Apr 2005 B1
6875613 Shartle Apr 2005 B2
6878120 Roe Apr 2005 B2
6878251 Hodges Apr 2005 B2
6878255 Wang Apr 2005 B1
6878262 Taniike Apr 2005 B2
6880968 Haar Apr 2005 B1
6881203 Delmore Apr 2005 B2
6881322 Tokunaga Apr 2005 B2
6881378 Zimmer Apr 2005 B1
6881541 Petersen Apr 2005 B2
6881550 Phillips Apr 2005 B2
6881551 Heller Apr 2005 B2
6881578 Otake Apr 2005 B2
6882940 Potts Apr 2005 B2
6884592 Matzinger Apr 2005 B2
6885196 Taniike Apr 2005 B2
6885883 Parris Apr 2005 B2
6887202 Currie May 2005 B2
6887239 Elstrom May 2005 B2
6887253 Schraga May 2005 B2
6887254 Curie May 2005 B1
6887426 Phillips May 2005 B2
6887709 Leong May 2005 B2
6889069 Routt May 2005 B2
6890319 Crocker May 2005 B1
6890421 Ohara May 2005 B2
6890484 Bautista May 2005 B2
6891936 Kai May 2005 B2
6892085 McIvor May 2005 B2
6893396 Schulze May 2005 B2
6893545 Gotoh May 2005 B2
6893552 Wang May 2005 B1
6895263 Shin May 2005 B2
6895264 Rice May 2005 B2
6895265 Silver May 2005 B2
6896793 Erdosy May 2005 B2
6897788 Khair May 2005 B2
6902905 Burson Jun 2005 B2
6904301 Raskas Jun 2005 B2
6905733 Russel Jun 2005 B2
6908008 Pugh Jun 2005 B2
6908535 Rankin Jun 2005 B2
6908591 MacPhee Jun 2005 B2
6908593 Shartle Jun 2005 B1
6911130 Brenneman Jun 2005 B2
6911131 Miyazaki Jun 2005 B2
6911621 Bhullar Jun 2005 B2
6911937 Sparrow Jun 2005 B1
6913210 Baasch Jul 2005 B2
6913668 Matzinger Jul 2005 B2
6916410 Katsuki Jul 2005 B2
6918874 Hatch Jul 2005 B1
6918901 Theeuwes Jul 2005 B1
6918918 Schraga Jul 2005 B1
6922576 Raskas Jul 2005 B2
6922578 Eppstein Jul 2005 B2
6923764 Aceti Aug 2005 B2
6923894 Huang Aug 2005 B2
6923936 Swanson Aug 2005 B2
6924093 Haviland Aug 2005 B2
6925317 Samuels Aug 2005 B1
6925393 Kalatz Aug 2005 B1
6929631 Brugger Aug 2005 B1
6929649 Pugh Aug 2005 B2
6929650 Fukuzawa Aug 2005 B2
6931327 Goode Aug 2005 B2
6931328 Braig Aug 2005 B2
RE38803 Rodgers, Jr. Sep 2005 E
6939310 Matzinger Sep 2005 B2
6939312 Hodges Sep 2005 B2
6939450 Karinka Sep 2005 B2
6939685 Ouyang Sep 2005 B2
6940591 Sopp Sep 2005 B2
6942518 Liamos Sep 2005 B2
6942769 Cheng Sep 2005 B2
6942770 Cai Sep 2005 B2
6944486 Braig Sep 2005 B2
6945943 Pugh Sep 2005 B2
6946067 Hodges Sep 2005 B2
6946098 Miekka Sep 2005 B2
6946299 Neel Sep 2005 B2
6949111 Schraga Sep 2005 B2
6949221 Kiser Sep 2005 B2
6951631 Catt Oct 2005 B1
6951728 Qian Oct 2005 B2
6952603 Gerber Oct 2005 B2
6952604 DeNuzzio Oct 2005 B2
6953693 Neel Oct 2005 B2
6954662 Freger Oct 2005 B2
6958072 Schraga Oct 2005 B2
6958129 Galen Oct 2005 B2
6958809 Sterling Oct 2005 B2
6959211 Rule Oct 2005 B2
6959247 Neel Oct 2005 B2
6960287 Charlton Nov 2005 B2
6960289 Hodges Nov 2005 B2
6960323 Guo Nov 2005 B2
6964871 Bell Nov 2005 B2
6965791 Hitchcock Nov 2005 B1
6966880 Boecker Nov 2005 B2
6966977 Hasegawa Nov 2005 B2
6967105 Nomura Nov 2005 B2
6968375 Brown Nov 2005 B1
6969359 Duchon Nov 2005 B2
6969450 Taniike Nov 2005 B2
6969451 Shin Nov 2005 B2
6973706 Say Dec 2005 B2
6975893 Say Dec 2005 B2
6977032 Hasegawa Dec 2005 B2
6977722 Wohlstadter et al. Dec 2005 B2
6979544 Keen Dec 2005 B2
6979571 Modzelewski Dec 2005 B2
6982027 Yagi Jan 2006 B2
6982431 Modlin Jan 2006 B2
6983176 Gardner Jan 2006 B2
6983177 Rule Jan 2006 B2
6984307 Zweig Jan 2006 B2
6986777 Kim Jan 2006 B2
6986869 Tuohy Jan 2006 B2
6988996 Roe Jan 2006 B2
6989243 Yani Jan 2006 B2
6989891 Braig Jan 2006 B2
6990365 Parker Jan 2006 B1
6990366 Say Jan 2006 B2
6990367 Kiser Jan 2006 B2
6990849 Bohm Jan 2006 B2
6991918 Keith Jan 2006 B2
6991940 Carroll Jan 2006 B2
6994825 Haviland Feb 2006 B2
6997317 Catelli Feb 2006 B2
6997343 May Feb 2006 B2
6997344 Brown Feb 2006 B2
6997936 Marshall Feb 2006 B2
6998247 Monfre Feb 2006 B2
6998248 Yani Feb 2006 B2
6999810 Berner Feb 2006 B2
7001343 Erickson Feb 2006 B2
7001344 Freeman Feb 2006 B2
7003337 Harjunmaa Feb 2006 B2
7003340 Say Feb 2006 B2
7003341 Say Feb 2006 B2
7004928 Aceti Feb 2006 B2
7005048 Watanabe Feb 2006 B1
7005273 Heller Feb 2006 B2
7005459 Hekal Feb 2006 B2
7005857 Stiene Feb 2006 B2
7006857 Braig Feb 2006 B2
7006858 Silver Feb 2006 B2
7008384 Tapper Mar 2006 B2
7010432 Kermani Mar 2006 B2
7011630 Desai Mar 2006 B2
7011954 Ouyang Mar 2006 B2
7014615 Erickson Mar 2006 B2
7015262 Leong Mar 2006 B2
7016713 Gardner Mar 2006 B2
7018568 Tierney Mar 2006 B2
7018848 Douglas Mar 2006 B2
7022217 Hodges Apr 2006 B2
7022218 Taniike Apr 2006 B2
7022286 Lemke Apr 2006 B2
7024236 Ford Apr 2006 B2
7024248 Penner Apr 2006 B2
7024399 Sumner Apr 2006 B2
7025425 Kovatchev Apr 2006 B2
7025774 Freeman Apr 2006 B2
7027848 Robinson Apr 2006 B2
7029444 Shin Apr 2006 B2
7033322 Silver Apr 2006 B2
7033371 Alden Apr 2006 B2
7039560 Kawatahara May 2006 B2
7041057 Faupel May 2006 B1
7041063 Abreu May 2006 B2
7041068 Freeman May 2006 B2
7041210 Hodges May 2006 B2
7041254 Haviland May 2006 B2
7041468 Drucker May 2006 B2
7043287 Khalil May 2006 B1
7043821 Hodges May 2006 B2
7044911 Drinan May 2006 B2
7045046 Chambers May 2006 B2
7045054 Buck May 2006 B1
7045097 Kovacs May 2006 B2
7045310 Buck May 2006 B2
7045361 Heiss May 2006 B2
7047070 Wilkinson May 2006 B2
7047795 Sato May 2006 B2
7049087 Jenny May 2006 B2
7049130 Carroll May 2006 B2
7050843 Shartle May 2006 B2
7051495 Lang May 2006 B2
7052268 Powell May 2006 B2
7052591 Gao May 2006 B2
7052652 Zanzucchi May 2006 B2
7052864 Durkop May 2006 B2
7054682 Young May 2006 B2
7054759 Fukunaga May 2006 B2
D522656 Orr Jun 2006 S
D523555 Loerwald Jun 2006 S
7056425 Hasegawa Jun 2006 B2
7056495 Roser Jun 2006 B2
7058437 Buse Jun 2006 B2
7059352 Bohm Jun 2006 B2
7060059 Keith Jun 2006 B2
7060168 Taniike Jun 2006 B2
7060192 Yuzhakov Jun 2006 B2
7061593 Braig Jun 2006 B2
7063234 Giraud Jun 2006 B2
7063774 Bhullar Jun 2006 B2
7063775 Yamaoka Jun 2006 B2
7063776 Huang Jun 2006 B2
7066884 Custer Jun 2006 B2
7066885 Erickson Jun 2006 B2
7070564 Matzinger Jul 2006 B2
7070680 Bae Jul 2006 B2
7073246 Bhullar Jul 2006 B2
7074307 Simpson Jul 2006 B2
7074308 Mao Jul 2006 B2
7077328 Krishnaswamy Jul 2006 B2
7077828 Kuhr Jul 2006 B2
7078480 Nagel Jul 2006 B2
7079252 Debreczeny Jul 2006 B1
7081188 Cho Jul 2006 B1
7083712 Morita Aug 2006 B2
7086277 Tess Aug 2006 B2
7087149 Muguruma Aug 2006 B1
7090764 Iyengar Aug 2006 B2
7096053 Loeb Aug 2006 B2
7096124 Sterling Aug 2006 B2
7097631 Trautman Aug 2006 B2
7098038 Fukuoka Aug 2006 B2
7103578 Beck Sep 2006 B2
7105066 Schraga Sep 2006 B2
7107253 Sumner Sep 2006 B1
7108680 Rohr Sep 2006 B2
7108778 Simpson Sep 2006 B2
7109271 Liu Sep 2006 B2
7110112 Uchida Sep 2006 B2
7110803 Shults Sep 2006 B2
7112265 McAleer Sep 2006 B1
7112451 Takahashi Sep 2006 B2
7113172 Hohl Sep 2006 B2
7115362 Douglas Oct 2006 B2
7118351 Effenhauser Oct 2006 B2
7118667 Lee Oct 2006 B2
7118668 Edelbrock Oct 2006 B1
7118916 Matzinger Oct 2006 B2
7118919 Yatscoff Oct 2006 B2
7120483 Russell Oct 2006 B2
7122102 Wogoman Oct 2006 B2
7122110 Deng Oct 2006 B2
7122111 Tokunaga Oct 2006 B2
7125481 Musho Oct 2006 B2
7129038 Gopalan Oct 2006 B2
RE39390 Hasegawa Nov 2006 E
D531725 Loerwald Nov 2006 S
7131342 Hodges Nov 2006 B2
7131984 Sato Nov 2006 B2
7132041 Deng Nov 2006 B2
7133710 Acosta Nov 2006 B2
7134550 Groth Nov 2006 B2
7134999 Brauker Nov 2006 B2
7135100 Lau Nov 2006 B1
7137957 Erickson Nov 2006 B2
7138041 Su Nov 2006 B2
7138089 Aitken Nov 2006 B2
7141034 Eppstein Nov 2006 B2
7141058 Briggs Nov 2006 B2
7144404 Whitson Dec 2006 B2
7144485 Hsu Dec 2006 B2
7144495 Teodorczyk Dec 2006 B2
7144496 Meserol Dec 2006 B2
7144709 Ouyang Dec 2006 B2
7147825 Matsuda Dec 2006 B2
7150755 Levaughn Dec 2006 B2
7150975 Tamada Dec 2006 B2
7150995 Xie Dec 2006 B2
7153696 Fukuoka Dec 2006 B2
7155371 Kawatahara Dec 2006 B2
7156117 Bohm Jan 2007 B2
7156810 Cho Jan 2007 B2
7157723 Colvin Jan 2007 B2
7160251 Neel Jan 2007 B2
7160313 Galloway Jan 2007 B2
7160678 Kayyem Jan 2007 B1
7162289 Shah Jan 2007 B2
7163616 Vreeke Jan 2007 B2
7166074 Reghabi Jan 2007 B2
7166208 Zweig Jan 2007 B2
7167734 Khalil Jan 2007 B2
7167735 Uchida Jan 2007 B2
7167818 Brown Jan 2007 B2
7169116 Day Jan 2007 B2
7169117 Allen Jan 2007 B2
7169289 Schulein Jan 2007 B2
7169600 Hoss Jan 2007 B2
7172728 Otake Feb 2007 B2
7174199 Berner Feb 2007 B2
7175641 Schraga Feb 2007 B1
7175642 Briggs Feb 2007 B2
7179233 Chang Feb 2007 B2
7182910 Allen Feb 2007 B2
7183068 Burson Feb 2007 B2
7183102 Kasai Feb 2007 B2
7188034 Staib Mar 2007 B2
7189576 Fukuoka Mar 2007 B2
7190988 Say Mar 2007 B2
7192405 DeNuzzio Mar 2007 B2
7192450 Brauker Mar 2007 B2
7195704 Kermani Mar 2007 B2
7198606 Boecker Apr 2007 B2
7199594 Kermani Apr 2007 B2
7202854 Hohl Apr 2007 B2
7206620 Erickson Apr 2007 B2
7206623 Blank Apr 2007 B2
D542681 Young May 2007 S
7211052 Roe May 2007 B2
7211096 Kuhr May 2007 B2
7212925 Genshaw May 2007 B2
7213720 Giraud May 2007 B2
7215982 Oshima May 2007 B2
7215983 Cho May 2007 B2
7223248 Erickson May 2007 B2
7225008 Ward May 2007 B1
D543878 Castillo Jun 2007 S
D545438 Huang Jun 2007 S
7225535 Feldman Jun 2007 B2
7226414 Ballerstadt Jun 2007 B2
7226461 Boecker Jun 2007 B2
7226978 Tapsak Jun 2007 B2
7227156 Colvin Jun 2007 B2
7228159 Petersson Jun 2007 B2
7228162 Ward Jun 2007 B2
7228163 Ackerman Jun 2007 B2
7229458 Freeman Jun 2007 B2
7232451 Boecker Jun 2007 B2
7232510 Miyazaki Jun 2007 B2
7233816 Blank Jun 2007 B2
7235056 Duchon Jun 2007 B2
7235170 Watanabe Jun 2007 B2
7235378 Yonehara Jun 2007 B2
7236812 Ballerstadt Jun 2007 B1
7236814 Shioi Jun 2007 B2
D545705 Voege Jul 2007 S
D546216 Bolognesi Jul 2007 S
D546218 Grasso Jul 2007 S
7238192 List Jul 2007 B2
7238534 Zimmer Jul 2007 B1
7241265 Cummings Jul 2007 B2
7244264 Roe Jul 2007 B2
7244265 Freeman Jul 2007 B2
7244266 Garthe Jul 2007 B2
7247138 Reghabi Jul 2007 B2
7247144 Douglas Jul 2007 B2
7250037 Shermer Jul 2007 B2
7250056 Hamamoto Jul 2007 B2
7250095 Black Jul 2007 B2
7250105 Davies Jul 2007 B1
7251513 Kondoh Jul 2007 B2
7251514 Cho Jul 2007 B2
7251515 Cho Jul 2007 B2
7251516 Walker Jul 2007 B2
7251517 Cho Jul 2007 B2
7251518 Herrmann Jul 2007 B2
7252804 Miyashita Aug 2007 B2
7254426 Cho Aug 2007 B2
7254427 Cho Aug 2007 B2
7254428 Cho Aug 2007 B2
7254429 Schurman Aug 2007 B2
7254430 Cho Aug 2007 B2
7254432 Fine Aug 2007 B2
7258673 Racchini Aug 2007 B2
7258693 Freeman Aug 2007 B2
7262061 Petrich Aug 2007 B2
7264139 Brickwood Sep 2007 B2
7264627 Perez Sep 2007 B2
7266400 Fine Sep 2007 B2
7267665 Steil Sep 2007 B2
7267750 Watanabe Sep 2007 B2
7270247 Charlton Sep 2007 B2
7271912 Sterling Sep 2007 B2
7273484 Thoes Sep 2007 B2
7276027 Haar Oct 2007 B2
7276029 Goode Oct 2007 B2
7276146 Wilsey Oct 2007 B2
7276147 Wilsey Oct 2007 B2
7276380 Fukuyama Oct 2007 B2
7277740 Rohleder Oct 2007 B2
7278983 Ireland Oct 2007 B2
7279130 Brown Oct 2007 B2
7282058 Levin Oct 2007 B2
7287318 Bhullar Oct 2007 B2
7288073 Effenhauser Oct 2007 B2
7288102 Griffin Oct 2007 B2
7288174 Cui Oct 2007 B2
7289836 Colvin Oct 2007 B2
7291117 Boecker Nov 2007 B2
7291159 Schmelzeisen-R Nov 2007 B2
7291256 Teodorczyk Nov 2007 B2
7291497 Holmes Nov 2007 B2
7294246 Gundel Nov 2007 B2
7295867 Berner Nov 2007 B2
7297122 Boecker Nov 2007 B2
7297151 Boecker Nov 2007 B2
7297152 Fukuzawa Nov 2007 B2
7297241 Kontschieder Nov 2007 B2
7297248 Bae Nov 2007 B2
7297627 Shah Nov 2007 B2
7299079 Rebec Nov 2007 B2
7299080 Acosta Nov 2007 B2
7299081 Mace Nov 2007 B2
7299082 Feldman Nov 2007 B2
7300402 Iliff Nov 2007 B2
7301629 Bambot Nov 2007 B2
7303573 D'Agostino Dec 2007 B2
7303726 McAllister Dec 2007 B2
7303922 Jeng Dec 2007 B2
7305896 Howell Dec 2007 B2
7306560 Iliff Dec 2007 B2
7308164 Banks Dec 2007 B1
7308292 Colvin Dec 2007 B2
7310542 Jeon Dec 2007 B2
7310543 Smart Dec 2007 B2
7310544 Brister Dec 2007 B2
7311718 Schraga Dec 2007 B2
7311812 Forrow Dec 2007 B2
7312042 Petyt Dec 2007 B1
7313425 Finarov Dec 2007 B2
7314453 Kuo Jan 2008 B2
7315752 Kraemer Jan 2008 B2
7316700 Alden Jan 2008 B2
7316766 Chen Jan 2008 B2
7316929 Purcell Jan 2008 B2
7317938 Lorenz Jan 2008 B2
7317939 Fine Jan 2008 B2
7322942 Roe Jan 2008 B2
7322996 Taylor Jan 2008 B2
7322997 Shi Jan 2008 B2
7322998 Kuhr Jan 2008 B2
7323098 Miyashita Jan 2008 B2
7323141 Kirchhevel Jan 2008 B2
7323315 Marfurt Jan 2008 B2
7324012 Mann Jan 2008 B2
7328052 Samsoondar Feb 2008 B2
7331931 Freeman Feb 2008 B2
7335292 Hodges Feb 2008 B2
7335294 Heller Feb 2008 B2
7337918 Fowler Mar 2008 B2
7338639 Burke Mar 2008 B2
7343188 Sohrab Mar 2008 B2
7344499 Prausnitz Mar 2008 B1
7344500 Talbot Mar 2008 B2
7344507 Briggs Mar 2008 B2
7344626 Harding Mar 2008 B2
7347925 Hsieh Mar 2008 B2
7347926 Morita Mar 2008 B2
7347973 Douglas Mar 2008 B2
RE40198 Buck Apr 2008 E
7351213 Wong Apr 2008 B2
7351323 Iketaki Apr 2008 B2
7351375 Noda Apr 2008 B2
7351770 Liu Apr 2008 B2
7357808 Kennedy Apr 2008 B2
7357851 Reid Apr 2008 B2
7361182 Fukuda Apr 2008 B2
7361307 Shartle Apr 2008 B2
7371247 Boecker May 2008 B2
7372277 Diamond May 2008 B2
7374544 Freeman May 2008 B2
7374546 Roe May 2008 B2
7378007 Moerman May 2008 B2
7378720 Fu May 2008 B2
7402616 Rodgers Jul 2008 B2
7404815 Kollias Jul 2008 B2
7410468 Freeman Aug 2008 B2
7429630 Liu Sep 2008 B2
7431814 Hodges Oct 2008 B2
7431820 Hodges Oct 2008 B2
7438694 Boozer Oct 2008 B2
D579652 Lim Nov 2008 S
D579653 Lim Nov 2008 S
7458956 Adams Dec 2008 B1
7462265 Leach Dec 2008 B2
7465380 Rodgers Dec 2008 B2
7468125 Kraft Dec 2008 B2
D585314 Schvetz Jan 2009 S
7473264 Allen Jan 2009 B2
7474390 Robinson Jan 2009 B2
7474391 Baskeyfield Jan 2009 B2
7481776 Boecker Jan 2009 B2
7481818 Allen Jan 2009 B2
D586465 Faulkner Feb 2009 S
D586466 Smith Feb 2009 S
D586678 Schvetz Feb 2009 S
D586916 Faulkner Feb 2009 S
7485128 Boecker Feb 2009 B2
7491178 Boecker Feb 2009 B2
7498132 Yu Mar 2009 B2
7501052 Iyengar Mar 2009 B2
7501093 Demelo Mar 2009 B2
7521019 Polak Apr 2009 B2
7524293 Freeman Apr 2009 B2
7537571 Freeman May 2009 B2
7547287 Boecker Jun 2009 B2
7548772 Shartle Jun 2009 B2
7553511 Hleong Jun 2009 B2
7563232 Freeman Jul 2009 B2
D598126 Alvarez-Icaza Aug 2009 S
7572356 Rodgers Aug 2009 B2
7575558 Boecker Aug 2009 B2
D600349 Bell Sep 2009 S
D600812 Lei Sep 2009 S
D600813 Bell Sep 2009 S
D601255 Schvetz Sep 2009 S
D601258 Bell Sep 2009 S
7582063 Wurster Sep 2009 B2
7582099 Freeman Sep 2009 B2
7586590 Baskeyfield Sep 2009 B2
7588670 Rodgers Sep 2009 B2
7589828 Robinson Sep 2009 B2
7592151 Liu Sep 2009 B2
7593097 Robinson Sep 2009 B2
7604592 Freeman Oct 2009 B2
7604722 Hodges Oct 2009 B2
7608175 Hodges Oct 2009 B2
7618522 Davies Nov 2009 B2
7645263 Angel et al. Jan 2010 B2
7648468 Boecker Jan 2010 B2
7648469 Boecker Jan 2010 B2
7653492 Davies Jan 2010 B2
7654127 Krulevitch Feb 2010 B2
7655119 Davies Feb 2010 B2
7665303 Bohm Feb 2010 B2
7666287 Zhao Feb 2010 B2
D611151 Lei Mar 2010 S
D611372 Salter Mar 2010 S
D611489 Bell Mar 2010 S
D611853 Salter Mar 2010 S
D612274 Heidemann Mar 2010 S
D612275 Salter Mar 2010 S
D612279 Heidemann Mar 2010 S
7674232 Boecker Mar 2010 B2
7682318 Alden Mar 2010 B2
7713214 Freeman et al. May 2010 B2
7749174 Alden et al. Jul 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
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
8282576 Marsot et al. Oct 2012 B2
8388639 Nicholls et al. Mar 2013 B2
8491500 Briggs et al. Jul 2013 B2
20010011157 Latterell Aug 2001 A1
20010016682 Berner Aug 2001 A1
20010017269 Heller Aug 2001 A1
20010018353 Ishigaki Aug 2001 A1
20010023349 Van Tassel et al. Sep 2001 A1
20010027328 Lum Oct 2001 A1
20010031931 Cunningham Oct 2001 A1
20010037072 Virtanen Nov 2001 A1
20010037355 Britt Nov 2001 A1
20010042004 Taub Nov 2001 A1
20010045355 Gephart Nov 2001 A1
20010054319 Heller Dec 2001 A1
20020002326 Causey Jan 2002 A1
20020002344 Douglas Jan 2002 A1
20020004196 Whitson Jan 2002 A1
20020016568 Lebel Feb 2002 A1
20020016606 Moerman Feb 2002 A1
20020016923 Knaus Feb 2002 A1
20020019606 Lebel Feb 2002 A1
20020019747 Ware Feb 2002 A1
20020019748 Brown Feb 2002 A1
20020020646 Groth et al. Feb 2002 A1
20020025469 Heller Feb 2002 A1
20020029058 Levaughn Mar 2002 A1
20020040208 Flaherty Apr 2002 A1
20020040230 Kuhr Apr 2002 A1
20020042090 Heller Apr 2002 A1
20020042594 Lum Apr 2002 A1
20020044890 Black Apr 2002 A1
20020052618 Haar May 2002 A1
20020053523 Liamos May 2002 A1
20020057993 Maisey May 2002 A1
20020058902 Kollias et al. May 2002 A1
20020076349 Aitken Jun 2002 A1
20020078091 Vu Jun 2002 A1
20020081559 Brown Jun 2002 A1
20020081588 Lumley-Woodyear Jun 2002 A1
20020082543 Park Jun 2002 A1
20020084196 Liamos Jul 2002 A1
20020087056 Aceti Jul 2002 A1
20020092612 Davies Jul 2002 A1
20020099308 Bojan Jul 2002 A1
20020103499 Perez Aug 2002 A1
20020109600 Mault et al. Aug 2002 A1
20020111634 Stoianovici et al. Aug 2002 A1
20020120216 Fritz Aug 2002 A1
20020120261 Morris Aug 2002 A1
20020123335 Luna Sep 2002 A1
20020130042 Moerman Sep 2002 A1
20020133377 Brown Sep 2002 A1
20020136667 Subramanian Sep 2002 A1
20020136863 Subramanian Sep 2002 A1
20020137998 Smart Sep 2002 A1
20020138040 Flora Sep 2002 A1
20020141032 Guarr et al. Oct 2002 A1
20020148739 Liamos Oct 2002 A2
20020156355 Gough Oct 2002 A1
20020160520 Orloff Oct 2002 A1
20020161289 Hopkins Oct 2002 A1
20020168290 Yuzhakov Nov 2002 A1
20020169393 Cunningham Nov 2002 A1
20020169394 Eppstein Nov 2002 A1
20020176984 Smart Nov 2002 A1
20020177761 Orloff Nov 2002 A1
20020177763 Burns Nov 2002 A1
20020188224 Roe Dec 2002 A1
20030014010 Carpenter Jan 2003 A1
20030018282 Effenhauser Jan 2003 A1
20030018300 Duchon Jan 2003 A1
20030028125 Yuzhakov Feb 2003 A1
20030028126 List Feb 2003 A1
20030032077 Itoh Feb 2003 A1
20030038047 Sleva Feb 2003 A1
20030050537 Wessel Mar 2003 A1
20030050573 Kuhr Mar 2003 A1
20030050656 Schraga Mar 2003 A1
20030057391 Krulevitch 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 Apr 2003 A1
20030073229 Greenstein Apr 2003 A1
20030073931 Boecker Apr 2003 A1
20030083685 Freeman May 2003 A1
20030083686 Freeman May 2003 A1
20030088160 Halleck May 2003 A1
20030088191 Freeman et al. May 2003 A1
20030089730 May May 2003 A1
20030092982 Eppstein May 2003 A1
20030093010 Essenpreis May 2003 A1
20030100040 Bonnecaze May 2003 A1
20030106810 Douglas Jun 2003 A1
20030109777 Kloepfer Jun 2003 A1
20030109860 Black Jun 2003 A1
20030111357 Black Jun 2003 A1
20030113827 Burkoth Jun 2003 A1
20030116447 Surridge Jun 2003 A1
20030120297 Beyerlein Jun 2003 A1
20030135333 Aceti Jul 2003 A1
20030136189 Lauman Jul 2003 A1
20030139653 Manser Jul 2003 A1
20030143113 Yuzhakov Jul 2003 A2
20030144608 Kojima Jul 2003 A1
20030144609 Kennedy Jul 2003 A1
20030146110 Karinka Aug 2003 A1
20030149348 Raskas Aug 2003 A1
20030149377 Erickson Aug 2003 A1
20030150745 Teodorczyk et al. Aug 2003 A1
20030153900 Aceti Aug 2003 A1
20030159944 Pottgen Aug 2003 A1
20030163351 Brown Aug 2003 A1
20030178322 Iyengar Sep 2003 A1
20030191376 Samuels Oct 2003 A1
20030191415 Moerman Oct 2003 A1
20030195435 Williams Oct 2003 A1
20030195540 Moerman Oct 2003 A1
20030199744 Buse Oct 2003 A1
20030199789 Boecker Oct 2003 A1
20030199790 Boecker Oct 2003 A1
20030199791 Boecker Oct 2003 A1
20030199891 Argauer Oct 2003 A1
20030199893 Boecker Oct 2003 A1
20030199894 Boecker Oct 2003 A1
20030199895 Boecker Oct 2003 A1
20030199896 Boecker Oct 2003 A1
20030199897 Boecker Oct 2003 A1
20030199898 Boecker Oct 2003 A1
20030199899 Boecker Oct 2003 A1
20030199900 Boecker Oct 2003 A1
20030199901 Boecker Oct 2003 A1
20030199902 Boecker Oct 2003 A1
20030199903 Boecker Oct 2003 A1
20030199904 Boecker Oct 2003 A1
20030199905 Boecker Oct 2003 A1
20030199906 Boecker Oct 2003 A1
20030199907 Boecker Oct 2003 A1
20030199908 Boecker Oct 2003 A1
20030199909 Boecker Oct 2003 A1
20030199910 Boecker Oct 2003 A1
20030199911 Boecker Oct 2003 A1
20030199912 Pugh Oct 2003 A1
20030201194 Heller Oct 2003 A1
20030203352 Haviland Oct 2003 A1
20030206828 Bell Nov 2003 A1
20030208140 Pugh Nov 2003 A1
20030210811 Dubowsky Nov 2003 A1
20030211619 Olson et al. Nov 2003 A1
20030212344 Yuzhakov Nov 2003 A1
20030212345 McAllister Nov 2003 A1
20030212346 McAllister Nov 2003 A1
20030212347 Sohrab Nov 2003 A1
20030212379 Bylund Nov 2003 A1
20030212423 Pugh Nov 2003 A1
20030212424 Briggs Nov 2003 A1
20030212579 Brown Nov 2003 A1
20030216767 List Nov 2003 A1
20030217918 Davies Nov 2003 A1
20030220552 Reghabi Nov 2003 A1
20030220663 Fletcher Nov 2003 A1
20030223906 McAllister Dec 2003 A1
20030225317 Schell Dec 2003 A1
20030225429 Garthe 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 Dec 2003 A1
20030233112 Alden et al. Dec 2003 A1
20030233113 Alden et al. Dec 2003 A1
20040006285 Douglas Jan 2004 A1
20040007585 Griffith Jan 2004 A1
20040009100 Simons Jan 2004 A1
20040010279 Freeman Jan 2004 A1
20040015064 Parsons Jan 2004 A1
20040019250 Catelli Jan 2004 A1
20040019259 Brown Jan 2004 A1
20040026243 Davies Feb 2004 A1
20040026244 Hodges Feb 2004 A1
20040030353 Schmelzeisen-R Feb 2004 A1
20040031682 Wilsey Feb 2004 A1
20040034318 Fritz Feb 2004 A1
20040038045 Smart Feb 2004 A1
20040039303 Wurster Feb 2004 A1
20040039342 Eppstein Feb 2004 A1
20040039407 Schraga Feb 2004 A1
20040039408 Abulhaj Feb 2004 A1
20040049219 Briggs Mar 2004 A1
20040049220 Boecker et al. Mar 2004 A1
20040050694 Yang Mar 2004 A1
20040054267 Feldman Mar 2004 A1
20040055898 Heller Mar 2004 A1
20040059256 Perez Mar 2004 A1
20040060818 Feldman Apr 2004 A1
20040061841 Black Apr 2004 A1
20040064068 DeNuzzio 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 Apr 2004 A1
20040087990 Boecker May 2004 A1
20040092842 Boecker May 2004 A1
20040092994 Briggs May 2004 A1
20040092995 Boecker May 2004 A1
20040096991 Zhang May 2004 A1
20040098009 Boecker May 2004 A1
20040098010 Davison May 2004 A1
20040102803 Boecker May 2004 A1
20040106855 Brown Jun 2004 A1
20040106858 Say Jun 2004 A1
20040106859 Say Jun 2004 A1
20040106860 Say Jun 2004 A1
20040106904 Gonnelli Jun 2004 A1
20040106941 Roe Jun 2004 A1
20040107116 Brown Jun 2004 A1
20040115754 Chang Jun 2004 A1
20040115831 Meathrel Jun 2004 A1
20040116780 Brown Jun 2004 A1
20040116829 Raney 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 Jul 2004 A1
20040127819 Roe Jul 2004 A1
20040127928 Whitson Jul 2004 A1
20040127929 Roe Jul 2004 A1
20040132167 Rule Jul 2004 A1
20040133125 Miyashita Jul 2004 A1
20040133127 Roe Jul 2004 A1
20040137640 Hirao Jul 2004 A1
20040138541 Ward Jul 2004 A1
20040138588 Saikley Jul 2004 A1
20040138688 Giraud Jul 2004 A1
20040146958 Bae Jul 2004 A1
20040154932 Deng Aug 2004 A1
20040157017 Mauze Aug 2004 A1
20040157149 Hofmann Aug 2004 A1
20040157319 Keen Aug 2004 A1
20040157338 Burke Aug 2004 A1
20040157339 Burke Aug 2004 A1
20040158137 Eppstein Aug 2004 A1
20040158271 Hamamoto Aug 2004 A1
20040161737 Yang Aug 2004 A1
20040162473 Sohrab Aug 2004 A1
20040162474 Kiser Aug 2004 A1
20040162506 Duchon Aug 2004 A1
20040162573 Kheiri Aug 2004 A1
20040167383 Kim Aug 2004 A1
20040171057 Yang Sep 2004 A1
20040171968 Katsuki Sep 2004 A1
20040172000 Roe Sep 2004 A1
20040173472 Jung Sep 2004 A1
20040173488 Griffin Sep 2004 A1
20040176705 Stevens Sep 2004 A1
20040176732 Frazier Sep 2004 A1
20040178066 Miyazaki Sep 2004 A1
20040178067 Miyazaki Sep 2004 A1
20040178216 Brickwood Sep 2004 A1
20040180379 van Duyne Sep 2004 A1
20040182703 Bell Sep 2004 A1
20040185568 Matsumoto Sep 2004 A1
20040186359 Beaudoin Sep 2004 A1
20040186394 Roe Sep 2004 A1
20040186500 Koike Sep 2004 A1
20040193201 Kim Sep 2004 A1
20040193377 Brown Sep 2004 A1
20040194302 Bhullar Oct 2004 A1
20040197231 Katsuki Oct 2004 A1
20040197821 Bauer Oct 2004 A1
20040199062 Petersson Oct 2004 A1
20040199409 Brown Oct 2004 A1
20040200720 Musho Oct 2004 A1
20040200721 Bhullar Oct 2004 A1
20040202576 Aceti Oct 2004 A1
20040204662 Perez Oct 2004 A1
20040206625 Bhullar Oct 2004 A1
20040206636 Hodges Oct 2004 A1
20040206658 Hammerstedt Oct 2004 A1
20040209307 Valkirs Oct 2004 A1
20040209350 Sakata Oct 2004 A1
20040209354 Mathies Oct 2004 A1
20040210279 Gruzdev Oct 2004 A1
20040211666 Pamidi Oct 2004 A1
20040214253 Paek Oct 2004 A1
20040215224 Sakata Oct 2004 A1
20040215225 Nakayama Oct 2004 A1
20040216516 Sato Nov 2004 A1
20040217019 Cai Nov 2004 A1
20040219500 Brown Nov 2004 A1
20040219535 Bell Nov 2004 A1
20040220456 Eppstein Nov 2004 A1
20040220495 Cahir Nov 2004 A1
20040220564 Ho Nov 2004 A1
20040220603 Rutynowski Nov 2004 A1
20040222092 Musho Nov 2004 A1
20040224369 Cai Nov 2004 A1
20040225230 Liamos Nov 2004 A1
20040225311 Levaughn Nov 2004 A1
20040225312 Orloff Nov 2004 A1
20040230216 Levaughn Nov 2004 A1
20040231983 Shen Nov 2004 A1
20040231984 Lauks Nov 2004 A1
20040232009 Okuda Nov 2004 A1
20040236250 Hodges Nov 2004 A1
20040236251 Roe Nov 2004 A1
20040236268 Mitragotri Nov 2004 A1
20040236362 Schraga Nov 2004 A1
20040238357 Bhullar Dec 2004 A1
20040238358 Forrow Dec 2004 A1
20040238359 Ikeda Dec 2004 A1
20040241746 Adlassnig Dec 2004 A1
20040242977 Dosmann Dec 2004 A1
20040243164 D'Agostino Dec 2004 A1
20040243165 Koike Dec 2004 A1
20040245101 Willner Dec 2004 A1
20040248282 Sobha Dec 2004 A1
20040248312 Vreeke Dec 2004 A1
20040249254 Racchini Dec 2004 A1
20040249310 Shartle Dec 2004 A1
20040249311 Haar Dec 2004 A1
20040249405 Watanabe Dec 2004 A1
20040249406 Griffin Dec 2004 A1
20040251131 Ueno Dec 2004 A1
20040253634 Wang Dec 2004 A1
20040254434 Goodnow Dec 2004 A1
20040254599 Lipoma Dec 2004 A1
20040256228 Huang Dec 2004 A1
20040256248 Burke Dec 2004 A1
20040256685 Chou Dec 2004 A1
20040258564 Charlton Dec 2004 A1
20040260204 Boecker Dec 2004 A1
20040260324 Fukuzawa Dec 2004 A1
20040260325 Kuhr Dec 2004 A1
20040260326 Lipoma Dec 2004 A1
20040260511 Burke Dec 2004 A1
20040267105 Monfre Dec 2004 A1
20040267121 Sarvazyan et al. Dec 2004 A1
20040267160 Perez Dec 2004 A9
20040267229 Moerman Dec 2004 A1
20040267299 Kuriger Dec 2004 A1
20040267300 Mace Dec 2004 A1
20050000806 Hsieh Jan 2005 A1
20050000807 Wang Jan 2005 A1
20050000808 Cui Jan 2005 A1
20050003470 Nelson Jan 2005 A1
20050004437 Kaufmann Jan 2005 A1
20050004494 Perez Jan 2005 A1
20050008537 Mosoiu Jan 2005 A1
20050008851 Ezoe Jan 2005 A1
20050009191 Swenson Jan 2005 A1
20050010090 Acosta Jan 2005 A1
20050010093 Ford Jan 2005 A1
20050010134 Douglas Jan 2005 A1
20050010137 Hodges Jan 2005 A1
20050010198 Marchitto Jan 2005 A1
20050011759 Moerman Jan 2005 A1
20050013731 Burke Jan 2005 A1
20050014997 Ruchti Jan 2005 A1
20050015020 Levaughn Jan 2005 A1
20050016844 Burke Jan 2005 A1
20050019212 Bhullar Jan 2005 A1
20050019219 Oshiman Jan 2005 A1
20050019805 Groll Jan 2005 A1
20050019945 Groll Jan 2005 A1
20050019953 Groll Jan 2005 A1
20050021066 Kuhr Jan 2005 A1
20050027181 Goode, Jr. Feb 2005 A1
20050027211 Kuhr Feb 2005 A1
20050027562 Brown Feb 2005 A1
20050033340 Lipoma Feb 2005 A1
20050033341 Vreeke Feb 2005 A1
20050034983 Chambers Feb 2005 A1
20050036020 Li Feb 2005 A1
20050036146 Braig Feb 2005 A1
20050036906 Nakahara et al. Feb 2005 A1
20050036909 Erickson Feb 2005 A1
20050037482 Braig Feb 2005 A1
20050038329 Morris Feb 2005 A1
20050038330 Jansen Feb 2005 A1
20050038463 Davar Feb 2005 A1
20050038464 Shraga Feb 2005 A1
20050038465 Shraga Feb 2005 A1
20050038674 Braig Feb 2005 A1
20050042766 Ohman Feb 2005 A1
20050043894 Fernandez Feb 2005 A1
20050043965 Heller Feb 2005 A1
20050045476 Neel Mar 2005 A1
20050049472 Manda Mar 2005 A1
20050049473 Desai et al. Mar 2005 A1
20050050859 Coppeta Mar 2005 A1
20050054082 Pachl Mar 2005 A1
20050054908 Blank Mar 2005 A1
20050059872 Shartle Mar 2005 A1
20050059895 Brown Mar 2005 A1
20050060194 Brown Mar 2005 A1
20050061668 Brenneman Mar 2005 A1
20050064528 Kwon Mar 2005 A1
20050067280 Reid Mar 2005 A1
20050067737 Rappin Mar 2005 A1
20050070771 Rule Mar 2005 A1
20050070819 Poux Mar 2005 A1
20050070945 Schraga Mar 2005 A1
20050072670 Hasegawa Apr 2005 A1
20050077176 Hodges Apr 2005 A1
20050077584 Uhland Apr 2005 A1
20050079542 Cullen Apr 2005 A1
20050080652 Brown Apr 2005 A1
20050085839 Allen Apr 2005 A1
20050085840 Yi Apr 2005 A1
20050086083 Brown Apr 2005 A1
20050090754 Wolff Apr 2005 A1
20050090850 Thoes Apr 2005 A1
20050096520 Maekawa May 2005 A1
20050096565 Chang May 2005 A1
20050096586 Trautman May 2005 A1
20050096587 Santini May 2005 A1
20050096686 Allen May 2005 A1
20050098431 Hodges 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 May 2005 A9
20050101979 Alden May 2005 A1
20050101980 Alden May 2005 A1
20050101981 Alden May 2005 A1
20050103624 Bhullar May 2005 A1
20050106713 Phan May 2005 A1
20050109637 Iyengar May 2005 A1
20050112712 Ouyang May 2005 A1
20050112782 Buechler May 2005 A1
20050113658 Jacobson May 2005 A1
20050113717 Matzinger May 2005 A1
20050114062 Davies May 2005 A1
20050114154 Wolkowicz May 2005 A1
20050114444 Brown May 2005 A1
20050118056 Swanson Jun 2005 A1
20050118062 Otake Jun 2005 A1
20050119681 Marshall Jun 2005 A1
20050123443 Fujiwara Jun 2005 A1
20050123680 Kang Jun 2005 A1
20050124869 Hefti Jun 2005 A1
20050125017 Kudrna Jun 2005 A1
20050125018 Galloway Jun 2005 A1
20050125019 Kudrna Jun 2005 A1
20050126929 Mansouri Jun 2005 A1
20050130248 Willner Jun 2005 A1
20050130249 Parris Jun 2005 A1
20050130292 Ahn Jun 2005 A1
20050131286 Parker Jun 2005 A1
20050131440 Starnes Jun 2005 A1
20050131441 Iio Jun 2005 A1
20050133368 Davies Jun 2005 A1
20050136471 Bhullar Jun 2005 A1
20050136501 Kuriger Jun 2005 A1
20050136529 Yang Jun 2005 A1
20050136550 Yang Jun 2005 A1
20050137531 Prausnitz et al. Jun 2005 A1
20050137536 Gonnelli Jun 2005 A1
20050140659 Hohl Jun 2005 A1
20050143675 Neel Jun 2005 A1
20050143713 Delmore Jun 2005 A1
20050143771 Stout Jun 2005 A1
20050145490 Shinno Jul 2005 A1
20050145491 Amano Jul 2005 A1
20050145520 Ilo Jul 2005 A1
20050149088 Fukuda Jul 2005 A1
20050149089 Trissel Jul 2005 A1
20050149090 Morita et al. Jul 2005 A1
20050150762 Butters Jul 2005 A1
20050150763 Butters Jul 2005 A1
20050154277 Tang Jul 2005 A1
20050154374 Hunter Jul 2005 A1
20050154410 Conway Jul 2005 A1
20050154616 Iliff Jul 2005 A1
20050158850 Kubo Jul 2005 A1
20050159656 Hockersmith Jul 2005 A1
20050159768 Boehm Jul 2005 A1
20050163176 You et al. Jul 2005 A1
20050164299 Stewart Jul 2005 A1
20050164322 Heller Jul 2005 A1
20050164329 Wallace-Davis Jul 2005 A1
20050165285 Iliff Jul 2005 A1
20050165393 Eppstein Jul 2005 A1
20050165622 Neel Jul 2005 A1
20050169810 Hagen Aug 2005 A1
20050169961 Hunter Aug 2005 A1
20050170448 Burson Aug 2005 A1
20050171567 DeHart Aug 2005 A1
20050172021 Brown Aug 2005 A1
20050172022 Brown Aug 2005 A1
20050173245 Feldman Aug 2005 A1
20050173246 Hodges Aug 2005 A1
20050175509 Nakaminami Aug 2005 A1
20050176084 Burkoth Aug 2005 A1
20050176133 Miyashita Aug 2005 A1
20050176153 O'hara Aug 2005 A1
20050177071 Nakayama Aug 2005 A1
20050177201 Freeman Aug 2005 A1
20050177398 Watanabe Aug 2005 A1
20050178218 Montagu Aug 2005 A1
20050181010 Hunter Aug 2005 A1
20050181497 Salto Aug 2005 A1
20050182307 Currie Aug 2005 A1
20050187439 Blank Aug 2005 A1
20050187442 Cho et al. Aug 2005 A1
20050187444 Hubner Aug 2005 A1
20050192488 Bryenton Sep 2005 A1
20050196821 Monfre Sep 2005 A1
20050197666 Raney Sep 2005 A1
20050201897 Zimmer Sep 2005 A1
20050202567 Zanzucchi Sep 2005 A1
20050203358 Monfre Sep 2005 A1
20050203364 Monfre Sep 2005 A1
20050204939 Krejci Sep 2005 A1
20050205136 Freeman Sep 2005 A1
20050205422 Moser Sep 2005 A1
20050205816 Hayenga Sep 2005 A1
20050209515 Hockersmith Sep 2005 A1
20050209564 Bonner Sep 2005 A1
20050209625 Chan Sep 2005 A1
20050211571 Schulein Sep 2005 A1
20050211572 Buck Sep 2005 A1
20050214881 Azarnia Sep 2005 A1
20050214892 Kovatchev Sep 2005 A1
20050215871 Feldman Sep 2005 A1
20050215872 Berner Sep 2005 A1
20050215923 Wiegel Sep 2005 A1
20050215925 Chan Sep 2005 A1
20050216046 Yeoh Sep 2005 A1
20050218024 Lang Oct 2005 A1
20050221276 Rozakis Oct 2005 A1
20050221470 Matsumoto Oct 2005 A1
20050222599 Czernecki Oct 2005 A1
20050227372 Khan Oct 2005 A1
20050228242 Kawamura Oct 2005 A1
20050228883 Brown Oct 2005 A1
20050230252 Tsai Oct 2005 A1
20050230253 Marquant Oct 2005 A1
20050232813 Karmali Oct 2005 A1
20050232815 Ruhl Oct 2005 A1
20050234368 Wong Oct 2005 A1
20050234486 Allen Oct 2005 A1
20050234487 Shi Oct 2005 A1
20050234488 Allen Oct 2005 A1
20050234489 Allen Oct 2005 A1
20050234490 Allen Oct 2005 A1
20050234491 Allen Oct 2005 A1
20050234492 Tsai Oct 2005 A1
20050234494 Conway Oct 2005 A1
20050234495 Schraga Oct 2005 A1
20050235060 Brown Oct 2005 A1
20050239154 Feldman Oct 2005 A1
20050239156 Drucker Oct 2005 A1
20050239194 Takahashi Oct 2005 A1
20050240090 Ruchti Oct 2005 A1
20050240119 Draudt Oct 2005 A1
20050240207 Marshall Oct 2005 A1
20050240778 Saito Oct 2005 A1
20050245798 Yamaguchi Nov 2005 A1
20050245843 Day Nov 2005 A1
20050245844 Mace Nov 2005 A1
20050245845 Roe Nov 2005 A1
20050245846 Casey Nov 2005 A1
20050245954 Roe Nov 2005 A1
20050245955 Schraga Nov 2005 A1
20050256534 Alden Nov 2005 A1
20050258035 Harding Nov 2005 A1
20050258036 Harding Nov 2005 A1
20050258050 Harding Nov 2005 A1
20050265094 Harding Dec 2005 A1
20050276133 Harding Dec 2005 A1
20050278945 Feldman Dec 2005 A1
20050279631 Celentano Dec 2005 A1
20050279647 Beaty Dec 2005 A1
20050283094 Thym Dec 2005 A1
20050284110 Lang Dec 2005 A1
20050284757 Allen Dec 2005 A1
20050287620 Heller Dec 2005 A1
20050288637 Kuhr Dec 2005 A1
20050288698 Matsumoto Dec 2005 A1
20050288699 Schraga Dec 2005 A1
20060000549 Lang Jan 2006 A1
20060003398 Heller Jan 2006 A1
20060004270 Bedard Jan 2006 A1
20060004271 Peyser Jan 2006 A1
20060004272 Shah Jan 2006 A1
20060006574 Lang Jan 2006 A1
20060008389 Sacherer Jan 2006 A1
20060015129 Shahrokni Jan 2006 A1
20060016698 Lee Jan 2006 A1
20060020228 Fowler Jan 2006 A1
20060024774 Zocchi Feb 2006 A1
20060025662 Buse Feb 2006 A1
20060029979 Bai Feb 2006 A1
20060029991 Hagino Feb 2006 A1
20060030028 Nakaminami Feb 2006 A1
20060030050 Milne Feb 2006 A1
20060030761 Raskas Feb 2006 A1
20060030788 Wong Feb 2006 A1
20060034728 Kloepfer Feb 2006 A1
20060037859 Hodges Feb 2006 A1
20060040333 Zocchi Feb 2006 A1
20060047220 Sakata Mar 2006 A1
20060047294 Mori Mar 2006 A1
20060052723 Roe Mar 2006 A1
20060052724 Roe Mar 2006 A1
20060052809 Karbowniczek Mar 2006 A1
20060052810 Freeman Mar 2006 A1
20060058827 Sakata Mar 2006 A1
20060058828 Shi Mar 2006 A1
20060062852 Holmes Mar 2006 A1
20060063988 Schurman Mar 2006 A1
20060064035 Wang Mar 2006 A1
20060079739 Chen Wang Apr 2006 A1
20060079810 Patel Apr 2006 A1
20060079811 Roe Apr 2006 A1
20060079920 Schraga Apr 2006 A1
20060081469 Lee Apr 2006 A1
20060085020 Freeman Apr 2006 A1
20060085137 Bartkowiak Apr 2006 A1
20060086624 Tapsak Apr 2006 A1
20060088945 Douglas Apr 2006 A1
20060089566 DeHart Apr 2006 A1
20060091006 Wang May 2006 A1
20060094944 Chuang May 2006 A1
20060094947 Kovatchev May 2006 A1
20060094985 Aceti May 2006 A1
20060094986 Neel May 2006 A1
20060095061 Trautman May 2006 A1
20060096859 Lau May 2006 A1
20060099107 Yamamoto May 2006 A1
20060099703 Choi May 2006 A1
20060100542 Wong May 2006 A9
20060100543 Raney May 2006 A1
20060100654 Fukuda May 2006 A1
20060100655 Leong May 2006 A1
20060100656 Olson May 2006 A1
20060106373 Cahir May 2006 A1
20060108236 Kasielke May 2006 A1
20060113187 Deng Jun 2006 A1
20060115857 Keen Jun 2006 A1
20060116562 Acosta Jun 2006 A1
20060116704 Ashby Jun 2006 A1
20060116705 Schraga Jun 2006 A1
20060119362 Kermani Jun 2006 A1
20060121547 McIntire Jun 2006 A1
20060121625 Clemens Jun 2006 A1
20060121759 Kasai Jun 2006 A1
20060122099 Aoki Jun 2006 A1
20060122536 Haar Jun 2006 A1
20060129065 Matsumoto Jun 2006 A1
20060129172 Crossman Jun 2006 A1
20060129173 Wilkinson Jun 2006 A1
20060134713 Rylatt Jun 2006 A1
20060140457 Simshauser Jun 2006 A1
20060144704 Ghesquiere Jul 2006 A1
20060151323 Cho Jul 2006 A1
20060151342 Yaguchi Jul 2006 A1
20060155215 Cha Jul 2006 A1
20060155316 Perez Jul 2006 A1
20060155317 List Jul 2006 A1
20060156796 Burke Jul 2006 A1
20060157362 Schraga Jul 2006 A1
20060160100 Gao Jul 2006 A1
20060161078 Schraga Jul 2006 A1
20060161194 Freeman Jul 2006 A1
20060163061 Hodges Jul 2006 A1
20060166302 Clarke Jul 2006 A1
20060167382 Deshmukh Jul 2006 A1
20060169599 Feldman Aug 2006 A1
20060173254 Acosta Aug 2006 A1
20060173255 Acosta Aug 2006 A1
20060173379 Rasch-Menges Aug 2006 A1
20060173380 Hoenes Aug 2006 A1
20060173478 Schraga Aug 2006 A1
20060175216 Freeman Aug 2006 A1
20060178573 Kermani Aug 2006 A1
20060178599 Faupel Aug 2006 A1
20060178600 Kennedy Aug 2006 A1
20060178686 Schraga Aug 2006 A1
20060178687 Freeman Aug 2006 A1
20060178688 Freeman Aug 2006 A1
20060178689 Freeman Aug 2006 A1
20060178690 Freeman Aug 2006 A1
20060183871 Ward Aug 2006 A1
20060183983 Acosta Aug 2006 A1
20060184065 Deshmukh Aug 2006 A1
20060184101 Srinivasan Aug 2006 A1
20060188395 Taniike Aug 2006 A1
20060189895 Neel Aug 2006 A1
20060191787 Wang Aug 2006 A1
20060195023 Acosta Aug 2006 A1
20060195047 Freeman Aug 2006 A1
20060195128 Alden Aug 2006 A1
20060195129 Freeman Aug 2006 A1
20060195130 Freeman Aug 2006 A1
20060195131 Freeman Aug 2006 A1
20060195132 Freeman Aug 2006 A1
20060195133 Freeman Aug 2006 A1
20060196031 Hoenes Sep 2006 A1
20060196795 Windus-Smith Sep 2006 A1
20060200044 Freeman Sep 2006 A1
20060200045 Roe Sep 2006 A1
20060200046 Windus-Smith Sep 2006 A1
20060200181 Fukuzawa Sep 2006 A1
20060200981 Bhullar Sep 2006 A1
20060200982 Bhullar Sep 2006 A1
20060201804 Chambers Sep 2006 A1
20060204399 Freeman Sep 2006 A1
20060205029 Heller Sep 2006 A1
20060205060 Kim Sep 2006 A1
20060206135 Uehata Sep 2006 A1
20060211127 Iwaki Sep 2006 A1
20060211927 Acosta Sep 2006 A1
20060211931 Blank Sep 2006 A1
20060219551 Edelbrock Oct 2006 A1
20060222566 Brauker et al. Oct 2006 A1
20060222567 Kloepfer Oct 2006 A1
20060224171 Sakata Oct 2006 A1
20060224172 Levaughn Oct 2006 A1
20060229532 Wong Oct 2006 A1
20060229533 Hoenes Oct 2006 A1
20060229651 Marshall Oct 2006 A1
20060229652 Iio et al. Oct 2006 A1
20060231396 Yamaoka Oct 2006 A1
20060231418 Harding Oct 2006 A1
20060231421 Diamond Oct 2006 A1
20060231423 Harding Oct 2006 A1
20060231425 Harding Oct 2006 A1
20060231442 Windus-Smith Oct 2006 A1
20060232278 Diamond Oct 2006 A1
20060232528 Harding Oct 2006 A1
20060233666 Vu Oct 2006 A1
20060234263 Light, II Oct 2006 A1
20060234369 Sih Oct 2006 A1
20060235284 Lee Oct 2006 A1
20060235454 LeVaughn Oct 2006 A1
20060241517 Fowler Oct 2006 A1
20060241666 Briggs Oct 2006 A1
20060241667 Freeman Oct 2006 A1
20060241668 Schraga Oct 2006 A1
20060241669 Stout Oct 2006 A1
20060247154 Palmieri Nov 2006 A1
20060247554 Roe Nov 2006 A1
20060247555 Harttig Nov 2006 A1
20060247670 LeVaughn Nov 2006 A1
20060247671 Levaughn Nov 2006 A1
20060254932 Hodges Nov 2006 A1
20060259057 Kim Nov 2006 A1
20060259058 Schiff Nov 2006 A1
20060259060 Whitson Nov 2006 A1
20060264718 Ruchti Nov 2006 A1
20060264996 Levaughn Nov 2006 A1
20060264997 Colonna Nov 2006 A1
20060266644 Pugh Nov 2006 A1
20060266765 Pugh Nov 2006 A1
20060271083 Boecker Nov 2006 A1
20060271084 Schraga Nov 2006 A1
20060276724 Freeman Dec 2006 A1
20060277048 Kintzig Dec 2006 A1
20060278545 Henning Dec 2006 A1
20060279431 Bakarania Dec 2006 A1
20060281187 Emery Dec 2006 A1
20060282109 Jansen Dec 2006 A1
20060286620 Werner Dec 2006 A1
20060287664 Grage Dec 2006 A1
20060293577 Morrison Dec 2006 A1
20070004989 Dhillon Jan 2007 A1
20070004990 Kistner Jan 2007 A1
20070007183 Schulat Jan 2007 A1
20070009381 Schulat Jan 2007 A1
20070010839 Galloway Jan 2007 A1
20070010841 Teo Jan 2007 A1
20070015978 Kanayama Jan 2007 A1
20070016079 Freeman Jan 2007 A1
20070016103 Calasso Jan 2007 A1
20070016104 Jansen Jan 2007 A1
20070016239 Sato Jan 2007 A1
20070017805 Hodges Jan 2007 A1
20070027370 Brauker Feb 2007 A1
20070027427 Trautman Feb 2007 A1
20070032812 Loerwald Feb 2007 A1
20070032813 Flynn Feb 2007 A1
20070038149 Calasso Feb 2007 A1
20070038235 Freeman Feb 2007 A1
20070043305 Boecker Feb 2007 A1
20070043386 Freeman Feb 2007 A1
20070049901 Wu Mar 2007 A1
20070049959 Feaster Mar 2007 A1
20070055174 Freeman Mar 2007 A1
20070055297 Fukuzawa Mar 2007 A1
20070055298 Uehata et al. Mar 2007 A1
20070060842 Alvarez-Icaza Mar 2007 A1
20070060843 Alvarez-Icaza Mar 2007 A1
20070060844 Alvarez-Icaza Mar 2007 A1
20070060845 Perez Mar 2007 A1
20070061393 Chen Mar 2007 A1
20070062250 Krulevitch Mar 2007 A1
20070062251 Anex Mar 2007 A1
20070062315 Hodges Mar 2007 A1
20070064516 Briggs Mar 2007 A1
20070066939 Krulevitch Mar 2007 A1
20070066940 Karunaratne Mar 2007 A1
20070068807 Feldman Mar 2007 A1
20070073188 Freeman Mar 2007 A1
20070073189 Freeman Mar 2007 A1
20070074977 Guo Apr 2007 A1
20070078358 Escutia Apr 2007 A1
20070078360 Matsumoto Apr 2007 A1
20070078474 Kim Apr 2007 A1
20070080093 Boozer Apr 2007 A1
20070083130 Thomson Apr 2007 A1
20070083131 Escutia Apr 2007 A1
20070083222 Schraga Apr 2007 A1
20070083335 Moerman Apr 2007 A1
20070084749 Demelo Apr 2007 A1
20070088377 LeVaughn Apr 2007 A1
20070092923 Chang Apr 2007 A1
20070093728 Douglas Apr 2007 A1
20070093752 Zhao Apr 2007 A1
20070093753 Krulevitch Apr 2007 A1
20070093863 Pugh Apr 2007 A1
20070093864 Pugh Apr 2007 A1
20070095178 Schraga May 2007 A1
20070100255 Boecker May 2007 A1
20070100256 Sansom May 2007 A1
20070100364 Sansom May 2007 A1
20070102312 Cha May 2007 A1
20070106178 Roe May 2007 A1
20070108048 Wang May 2007 A1
20070112281 Olson May 2007 A1
20070112367 Olson May 2007 A1
20070118051 Korner et al. May 2007 A1
20070119710 Goldberger May 2007 A1
20070123801 Goldberger May 2007 A1
20070123802 Freeman May 2007 A1
20070123803 Fujiwara et al. May 2007 A1
20070129618 Goldberger Jun 2007 A1
20070129650 Freeman Jun 2007 A1
20070131565 Fujiwara Jun 2007 A1
20070135828 Rutynowski Jun 2007 A1
20070142747 Boecker Jun 2007 A1
20070142748 Freeman Jun 2007 A1
20070142776 Kovelman Jun 2007 A9
20070142854 Schraga Jun 2007 A1
20070144235 Werner Jun 2007 A1
20070149875 Ouyang Jun 2007 A1
20070149897 Ghesquiere Jun 2007 A1
20070161960 Chen Jul 2007 A1
20070162064 Starnes Jul 2007 A1
20070162065 Li Jul 2007 A1
20070167869 Roe Jul 2007 A1
20070167870 Freeman Jul 2007 A1
20070167871 Freeman Jul 2007 A1
20070167872 Freeman Jul 2007 A1
20070167873 Freeman Jul 2007 A1
20070167874 Freeman Jul 2007 A1
20070167875 Freeman Jul 2007 A1
20070173739 Chan Jul 2007 A1
20070173740 Chan Jul 2007 A1
20070173741 Boecker Jul 2007 A1
20070173742 Freeman et al. Jul 2007 A1
20070173743 Freeman Jul 2007 A1
20070173874 Uschold Jul 2007 A1
20070173875 Uschold Jul 2007 A1
20070173876 Aylett Jul 2007 A1
20070176120 Schwind Aug 2007 A1
20070179356 Wessel Aug 2007 A1
20070179404 Escutia Aug 2007 A1
20070179405 Emery Aug 2007 A1
20070179406 DeNuzzio Aug 2007 A1
20070182051 Harttig Aug 2007 A1
20070185412 Boecker Aug 2007 A1
20070185515 Stout Aug 2007 A1
20070185516 Schosnig Aug 2007 A1
20070191702 Yodfat Aug 2007 A1
20070191737 Freeman Aug 2007 A1
20070191738 Raney Aug 2007 A1
20070191739 Roe Aug 2007 A1
20070193019 Feldman Aug 2007 A1
20070193882 Dai Aug 2007 A1
20070196240 Boozer Aug 2007 A1
20070196242 Boozer Aug 2007 A1
20070203514 Flaherty Aug 2007 A1
20070203903 Attaran Rezaei Aug 2007 A1
20070205103 Hodges Sep 2007 A1
20070207498 Palmieri Sep 2007 A1
20070213601 Freeman Sep 2007 A1
20070213637 Boozer Sep 2007 A1
20070213682 Haar Sep 2007 A1
20070213756 Freeman Sep 2007 A1
20070218543 Flaherty Sep 2007 A1
20070219346 Trifiro Sep 2007 A1
20070219432 Thompson Sep 2007 A1
20070219436 Takase Sep 2007 A1
20070219462 Briggs Sep 2007 A1
20070219463 Briggs Sep 2007 A1
20070219572 Deck Sep 2007 A1
20070219573 Freeman Sep 2007 A1
20070219574 Freeman Sep 2007 A1
20070225741 Ikeda Sep 2007 A1
20070225742 Abe Sep 2007 A1
20070227907 Shah Oct 2007 A1
20070227911 Wang Oct 2007 A1
20070227912 Chatelier Oct 2007 A1
20070229085 Kawai Oct 2007 A1
20070232872 Prough Oct 2007 A1
20070232956 Harman Oct 2007 A1
20070233013 Schoenberg Oct 2007 A1
20070233166 Stout Oct 2007 A1
20070233167 Weiss Oct 2007 A1
20070233395 Neel Oct 2007 A1
20070235329 Harding Oct 2007 A1
20070235347 Chatelier Oct 2007 A1
20070239068 Rasch-Menges Oct 2007 A1
20070239188 Boozer Oct 2007 A1
20070239189 Freeman Oct 2007 A1
20070239190 Alden Oct 2007 A1
20070240984 Popovich Oct 2007 A1
20070240986 Reymond Oct 2007 A1
20070244380 Say Oct 2007 A1
20070244412 Lav Oct 2007 A1
20070244498 Steg Oct 2007 A1
20070244499 Briggs Oct 2007 A1
20070249921 Groll Oct 2007 A1
20070249962 Alden Oct 2007 A1
20070249963 Alden Oct 2007 A1
20070250099 Flora Oct 2007 A1
20070251836 Hsu Nov 2007 A1
20070254359 Rezania Nov 2007 A1
20070255141 Esenaliev Nov 2007 A1
20070255178 Alvarez-Icaza Nov 2007 A1
20070255179 Alvarez-Icaza Nov 2007 A1
20070255180 Alvarez-Icaza Nov 2007 A1
20070255181 Alvarez-Icaza Nov 2007 A1
20070255300 Vanhiel Nov 2007 A1
20070255301 Freeman Nov 2007 A1
20070255302 Koeppel Nov 2007 A1
20070260271 Freeman Nov 2007 A1
20070260272 Weiss Nov 2007 A1
20070264721 Buck Nov 2007 A1
20070265511 Renouf Nov 2007 A1
20070265532 Maynard Nov 2007 A1
20070265654 Iio Nov 2007 A1
20070273901 Baskeyfield Nov 2007 A1
20070273903 Baskeyfield Nov 2007 A1
20070273904 Robinson Nov 2007 A1
20070273928 Robinson Nov 2007 A1
20070276197 Harmon Nov 2007 A1
20070276211 Mir Nov 2007 A1
20070276290 Boecker Nov 2007 A1
20070276425 Kim Nov 2007 A1
20070276621 Davies Nov 2007 A1
20070278097 Bhullar Dec 2007 A1
20070282186 Gilmore Dec 2007 A1
20070282362 Berg Dec 2007 A1
20070288047 Thoes Dec 2007 A1
20070293743 Monfre Dec 2007 A1
20070293744 Monfre Dec 2007 A1
20070293790 Bainczyk Dec 2007 A1
20070293882 Harttig Dec 2007 A1
20070293883 Horie Dec 2007 A1
20070295616 Harding Dec 2007 A1
20080004651 Nicholls Jan 2008 A1
20080007141 Deck Jan 2008 A1
20080009767 Effenhauser Jan 2008 A1
20080009768 Sohrab Jan 2008 A1
20080009892 Freeman Jan 2008 A1
20080009893 LeVaughn Jan 2008 A1
20080015425 Douglas Jan 2008 A1
20080015623 Deck Jan 2008 A1
20080017522 Heller Jan 2008 A1
20080019870 Newman Jan 2008 A1
20080021291 Zocchi Jan 2008 A1
20080021293 Schurman Jan 2008 A1
20080021295 Wang Jan 2008 A1
20080021296 Creaven Jan 2008 A1
20080021346 Haar Jan 2008 A1
20080021490 Briggs Jan 2008 A1
20080021491 Freeman Jan 2008 A1
20080021492 Freeman Jan 2008 A1
20080021493 Levaughn Jan 2008 A1
20080021494 Schmelzeisen-R Jan 2008 A1
20080027385 Freeman Jan 2008 A1
20080031778 Kramer Feb 2008 A1
20080033268 Stafford Feb 2008 A1
20080033318 Mace Feb 2008 A1
20080033319 Kloepfer Feb 2008 A1
20080033468 Lathrop Feb 2008 A1
20080033469 Winheim 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 Feb 2008 A1
20080040919 Griss Feb 2008 A1
20080045825 Melker Feb 2008 A1
20080045992 Schraga Feb 2008 A1
20080047764 Lee Feb 2008 A1
20080053201 Roesicke Mar 2008 A1
20080057484 Miyata Mar 2008 A1
20080058624 Smart Mar 2008 A1
20080058626 Miyata Mar 2008 A1
20080058631 Draudt Mar 2008 A1
20080058847 Abe Mar 2008 A1
20080058848 Griffin Mar 2008 A1
20080058849 Conway Mar 2008 A1
20080060424 Babic Mar 2008 A1
20080064986 Kraemer Mar 2008 A1
20080064987 Escutia Mar 2008 A1
20080065130 Patel Mar 2008 A1
20080065131 List Mar 2008 A1
20080065132 Trissel Mar 2008 A1
20080065133 Kennedy Mar 2008 A1
20080065134 Conway Mar 2008 A1
20080073224 Diamond Mar 2008 A1
20080077048 Escutia Mar 2008 A1
20080077167 Flynn Mar 2008 A1
20080077168 Nicholls Mar 2008 A1
20080081969 Feldman Apr 2008 A1
20080081976 Hodges Apr 2008 A1
20080082023 Deck Apr 2008 A1
20080082116 Lathrop Apr 2008 A1
20080082117 Ruf Apr 2008 A1
20080086042 Brister Apr 2008 A1
20080086044 Brister Apr 2008 A1
20080086273 Shults Apr 2008 A1
20080093227 Diamond Apr 2008 A1
20080093228 Diamond Apr 2008 A1
20080093230 Diamond Apr 2008 A1
20080094804 Reynolds Apr 2008 A1
20080097171 Smart Apr 2008 A1
20080097241 Maltezos Apr 2008 A1
20080097503 Creaven Apr 2008 A1
20080098802 Burke May 2008 A1
20080103396 Johnson May 2008 A1
20080103415 Roe May 2008 A1
20080103517 Takemoto May 2008 A1
20080105024 Creaven May 2008 A1
20080105568 Wu May 2008 A1
20080108130 Nakaminami May 2008 A1
20080108942 Brister May 2008 A1
20080109024 Berkovitch May 2008 A1
20080109025 Yang May 2008 A1
20080109259 Thompson May 2008 A1
20080114227 Haar May 2008 A1
20080114228 McCluskey May 2008 A1
20080118400 Neel May 2008 A1
20080119703 Brister May 2008 A1
20080119704 Brister May 2008 A1
20080119706 Brister May 2008 A1
20080119761 Boecker May 2008 A1
20080119883 Conway May 2008 A1
20080119884 Flora May 2008 A1
20080121533 Hodges May 2008 A1
20080125800 List May 2008 A1
20080125801 List May 2008 A1
20080134806 Capriccio Jun 2008 A1
20080134810 Neel Jun 2008 A1
20080135559 Byrd Jun 2008 A1
20080140105 Zhong Jun 2008 A1
20080144022 Schulat Jun 2008 A1
20080146899 Ruchti Jun 2008 A1
20080146966 LeVaughn Jun 2008 A1
20080147108 Kennedy Jun 2008 A1
20080149268 Zhao Jun 2008 A1
20080149599 Bohm Jun 2008 A1
20080152507 Bohm Jun 2008 A1
20080154187 Krulevitch Jun 2008 A1
20080154513 Kovatchev Jun 2008 A1
20080159913 Jung Jul 2008 A1
20080161664 Mastrototaro Jul 2008 A1
20080161724 Roe Jul 2008 A1
20080161725 Wong Jul 2008 A1
20080166269 Jansen Jul 2008 A1
20080167578 Bryer Jul 2008 A1
20080167673 Zhong Jul 2008 A1
20080188771 Boecker Aug 2008 A1
20080194987 Boecker Aug 2008 A1
20080194989 Briggs Aug 2008 A1
20080208026 Noujaim Aug 2008 A1
20080208079 Hein Aug 2008 A1
20080210574 Boecker Sep 2008 A1
20080214909 Fuerst Sep 2008 A1
20080214917 Boecker Sep 2008 A1
20080214919 Harmon Sep 2008 A1
20080214956 Briggs Sep 2008 A1
20080228212 List Sep 2008 A1
20080249435 Haar Oct 2008 A1
20080249554 Freeman Oct 2008 A1
20080255598 LeVaughn et al. Oct 2008 A1
20080262387 List Oct 2008 A1
20080262388 List Oct 2008 A1
20080267822 List Oct 2008 A1
20080269723 Mastrototaro Oct 2008 A1
20080269791 Hoenes Oct 2008 A1
20080275365 Guthrie Nov 2008 A1
20080275384 Mastrototaro Nov 2008 A1
20080277291 Heller Nov 2008 A1
20080277292 Heller Nov 2008 A1
20080277293 Heller Nov 2008 A1
20080277294 Heller Nov 2008 A1
20080286149 Roe Nov 2008 A1
20080294068 Briggs Nov 2008 A1
20080300614 Freeman Dec 2008 A1
20080318193 Alvarez-Icaza Dec 2008 A1
20080319284 Alvarez-Icaza Dec 2008 A1
20080319291 Freeman Dec 2008 A1
20090005664 Freeman Jan 2009 A1
20090020438 Hodges Jan 2009 A1
20090024009 Freeman Jan 2009 A1
20090026075 Harding Jan 2009 A1
20090026091 Harding Jan 2009 A1
20090027040 Kermani Jan 2009 A1
20090029479 Docherty Jan 2009 A1
20090030441 Kudrna Jan 2009 A1
20090043177 Milledge Feb 2009 A1
20090043183 Kermani Feb 2009 A1
20090048536 Freeman Feb 2009 A1
20090054813 Freeman Feb 2009 A1
20090057146 Teodorczyk Mar 2009 A1
20090069716 Freeman Mar 2009 A1
20090076415 Moerman Mar 2009 A1
20090084687 Chatelier Apr 2009 A1
20090099477 Hoenes et al. Apr 2009 A1
20090105572 Malecha Apr 2009 A1
20090105573 Malecha Apr 2009 A1
20090112123 Freeman Apr 2009 A1
20090112155 Zhao Apr 2009 A1
20090112180 Krulevitch Apr 2009 A1
20090112185 Krulevitch 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 May 2009 A1
20090131829 Freeman May 2009 A1
20090131830 Freeman May 2009 A1
20090131964 Freeman May 2009 A1
20090131965 Freeman May 2009 A1
20090137930 Freeman May 2009 A1
20090138032 Freeman May 2009 A1
20090139300 Pugh Jun 2009 A1
20090177117 Amano et al. Jul 2009 A1
20090184004 Chatelier Jul 2009 A1
20090187351 Orr Jul 2009 A1
20090192410 Freeman Jul 2009 A1
20090192411 Freeman Jul 2009 A1
20090196580 Freeman Aug 2009 A1
20090204025 Marsot Aug 2009 A1
20090216100 Ebner Aug 2009 A1
20090237262 Smith Sep 2009 A1
20090240127 Ray Sep 2009 A1
20090247838 Cummings Oct 2009 A1
20090247982 Krulevitch Oct 2009 A1
20090259146 Freeman Oct 2009 A1
20090270765 Ghesquiere et al. Oct 2009 A1
20090280551 Cardosi Nov 2009 A1
20090281457 Faulkner Nov 2009 A1
20090281458 Faulkner Nov 2009 A1
20090281459 Faulkner Nov 2009 A1
20090301899 Hodges Dec 2009 A1
20090302872 Haggett Dec 2009 A1
20090302873 Haggett Dec 2009 A1
20090322630 Friman Dec 2009 A1
20090325307 Haggett Dec 2009 A1
20100016700 Sieh Jan 2010 A1
20100018878 Davies Jan 2010 A1
20100030110 Choi Feb 2010 A1
20100041084 Stephens Feb 2010 A1
20100094170 Wilson et al. Apr 2010 A1
20100094324 Huang et al. Apr 2010 A1
20100113981 Oki et al. May 2010 A1
20100198107 Groll 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
20100324582 Nicholls et al. Dec 2010 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 (394)
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
4420232 Dec 1995 DE
29800611 Jul 1998 DE
19819407 Nov 1999 DE
20009475 Oct 2000 DE
29824204 Oct 2000 DE
10053974 Dec 2000 DE
10032042 Jan 2002 DE
10057832 Feb 2002 DE
10057832 Feb 2002 DE
10142232 Mar 2003 DE
10208575 Aug 2003 DE
10208575 Aug 2003 DE
10245721 Dec 2003 DE
10245721 Dec 2003 DE
10361560 Jul 2005 DE
10361560 Jul 2005 DE
0112498 Jul 1984 EP
0160768 Nov 1985 EP
199484 Oct 1986 EP
0199484 Oct 1986 EP
0254246 Jan 1988 EP
0289 269 Nov 1988 EP
0317847 May 1989 EP
0320109 Jun 1989 EP
359831 Mar 1990 EP
364208 Apr 1990 EP
0364208 Apr 1990 EP
0170375 May 1990 EP
0136362 Dec 1990 EP
406304 Jan 1991 EP
0449525 Oct 1991 EP
0453283 Oct 1991 EP
0263948 Feb 1992 EP
0449147 Aug 1992 EP
505475 Sep 1992 EP
505494 Sep 1992 EP
505504 Sep 1992 EP
0530994 Mar 1993 EP
0374355 Jun 1993 EP
552223 Jul 1993 EP
0351891 Sep 1993 EP
0593096 Apr 1994 EP
0630609 Dec 1994 EP
0415388 May 1995 EP
0654659 May 1995 EP
0505494 Jul 1995 EP
0662367 Jul 1995 EP
0359831 Aug 1995 EP
0471986 Oct 1995 EP
0368474 Dec 1995 EP
0461601 Dec 1995 EP
0429076 Jan 1996 EP
0552223 Jul 1996 EP
0735363 Oct 1996 EP
759553 Feb 1997 EP
0505504 Mar 1997 EP
0777123 Jun 1997 EP
0406304 Aug 1997 EP
0537761 Aug 1997 EP
0795601 Sep 1997 EP
0562370 Nov 1997 EP
0415393 Dec 1997 EP
817809 Jan 1998 EP
0823239 Feb 1998 EP
0560336 May 1998 EP
847447 Jun 1998 EP
0878 708 Nov 1998 EP
874984 Nov 1998 EP
0505475 Mar 1999 EP
0898936 Mar 1999 EP
898936 Mar 1999 EP
0901018 Mar 1999 EP
0470649 Jun 1999 EP
937249 Aug 1999 EP
938493 Sep 1999 EP
0951939 Oct 1999 EP
951939 Oct 1999 EP
0847447 Nov 1999 EP
0964059 Dec 1999 EP
0964060 Dec 1999 EP
0969097 Jan 2000 EP
0985376 Mar 2000 EP
985376 Mar 2000 EP
1021950 Jul 2000 EP
0894869 Feb 2001 EP
1074832 Feb 2001 EP
1093854 Apr 2001 EP
1101443 May 2001 EP
1114995 Jul 2001 EP
0736607 Aug 2001 EP
0874984 Nov 2001 EP
1157660 Nov 2001 EP
0730037 Dec 2001 EP
0636879 Jan 2002 EP
01174083 Jan 2002 EP
1174083 Jan 2002 EP
0851224 Mar 2002 EP
0759553 May 2002 EP
0856586 May 2002 EP
0817809 Jul 2002 EP
0872728 Jul 2002 EP
0795748 Aug 2002 EP
0685737 Sep 2002 EP
0958495 Nov 2002 EP
0937249 Dec 2002 EP
1337182 Aug 2003 EP
1337182 Aug 2003 EP
0880692 Jan 2004 EP
01374770 Jan 2004 EP
1374770 Jan 2004 EP
1401233 Mar 2004 EP
1404232 Apr 2004 EP
1404232 Apr 2004 EP
1404233 Apr 2004 EP
1246688 May 2004 EP
1486766 Dec 2004 EP
1502614 Feb 2005 EP
1502614 Feb 2005 EP
1643908 Apr 2006 EP
1790288 May 2007 EP
1881322 Jan 2008 EP
1921992 May 2008 EP
1921992 May 2008 EP
2039294 Mar 2009 EP
2130493 Dec 2009 EP
WO 2007010087 Jan 2007 FI
2555432 May 1985 FR
2555432 May 1985 FR
2622457 Nov 1987 FR
1558111 Dec 1979 GB
2168815 Jun 1986 GB
2331936 Jun 1999 GB
2331936 Jun 1999 GB
2335860 Oct 1999 GB
2335860 Oct 1999 GB
2335990 Oct 1999 GB
2335990 Oct 1999 GB
2335990 Oct 1999 GB
WO 2005045414 May 2005 GB
WO 2010109461 Sep 2010 IL
HEI 4 194660 Jul 1992 JP
1996010208 Dec 1992 JP
9-276235 Oct 1997 JP
10-104906 Jan 1998 JP
1014906 Jan 1998 JP
2000-116768 Apr 2000 JP
WO 2007088905 Aug 2007 JP
04-194660 Dec 2008 JP
WO 2008085052 Jul 2008 NL
WO 8001389 Jul 1980 WO
137975 Apr 1985 WO
WO 8504089 Sep 1985 WO
WO8605966 Oct 1986 WO
WO 8607632 Dec 1986 WO
WO 9109139 Jun 1991 WO
WO9203099 Mar 1992 WO
WO9206971 Apr 1992 WO
WO9207263 Apr 1992 WO
WO9207468 May 1992 WO
WO9300044 Jan 1993 WO
WO 9302720 Feb 1993 WO
WO 9306979 Apr 1993 WO
WO9309723 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
WO9512583 May 1995 WO
WO 9522597 Aug 1995 WO
WO9614799 May 1996 WO
WO 9630431 Oct 1996 WO
WO9637148 Nov 1996 WO
WO 9702359 Jan 1997 WO
WO 9702487 Jan 1997 WO
WO 9711883 Apr 1997 WO
WO 9718464 May 1997 WO
WO9728741 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
WO9814436 Apr 1998 WO
WO 9819159 May 1998 WO
WO9819609 May 1998 WO
WO 9820332 May 1998 WO
WO 9820348 May 1998 WO
WO9820867 May 1998 WO
WO 9824366 Jun 1998 WO
WO 98 24373 Jun 1998 WO
WO 9835225 Aug 1998 WO
WO9845276 Oct 1998 WO
WO 9903584 Jan 1999 WO
WO 9905966 Feb 1999 WO
WO9907295 Feb 1999 WO
WO 9907431 Feb 1999 WO
WO 9962576 Mar 1999 WO
WO 9917854 Apr 1999 WO
WO 9918532 Apr 1999 WO
WO 9919507 Apr 1999 WO
WO 9919717 Apr 1999 WO
WO 9927483 Jun 1999 WO
WO 9927852 Jun 1999 WO
WO 9913100 Dec 1999 WO
WO 9964580 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
WO0029577 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
WO0046854 Aug 2000 WO
WO 0050771 Aug 2000 WO
WO0055915 Sep 2000 WO
WO 0060340 Oct 2000 WO
WO 0064022 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 0175433 Mar 2001 WO
WO 0123885 Apr 2001 WO
WO 0125775 Apr 2001 WO
WO 0126813 Apr 2001 WO
WO0129037 Apr 2001 WO
WO 0133216 May 2001 WO
WO 0134029 May 2001 WO
WO 0136955 May 2001 WO
WO 0137174 May 2001 WO
WO 0145014 Jun 2001 WO
WO 0140788 Jul 2001 WO
WO 0157510 Aug 2001 WO
WO 0163271 Aug 2001 WO
WO 0164105 Sep 2001 WO
WO 0166010 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 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
WO0249507 Jun 2002 WO
WO 02056769 Jul 2002 WO
WO 02059734 Aug 2002 WO
WO 02069791 Sep 2002 WO
WO 02077638 Oct 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 03042691 May 2003 WO
WO 03039369 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 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 2004091693 Oct 2004 WO
WO 2004098405 Nov 2004 WO
WO 2004003147 Dec 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 2005035018 Apr 2005 WO
WO 2005037095 Apr 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
WO2005084546 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 2005120365 Dec 2005 WO
WO 2005121759 Dec 2005 WO
WO 2006001797 Jan 2006 WO
WO 2006001973 Jan 2006 WO
WO 2006005545 Jan 2006 WO
WO-2006005545 Jan 2006 WO
WO 2006011062 Feb 2006 WO
WO 2006013045 Feb 2006 WO
WO 2006015615 Feb 2006 WO
WO 2006027702 Mar 2006 WO
WO 2006031920 Mar 2006 WO
WO 2006032391 Mar 2006 WO
1643908 Apr 2006 WO
WO 2006072004 Jul 2006 WO
WO 2006105146 Oct 2006 WO
WO 2006116441 Nov 2006 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 2007106470 Sep 2007 WO
WO 2007119900 Oct 2007 WO
WO 2008112268 Sep 2008 WO
WO 2008112279 Sep 2008 WO
WO-2008112268 Sep 2008 WO
WO-2008112279 Sep 2008 WO
Non-Patent Literature Citations (4)
Entry
G. Jarzabek, Z. Borkowska, On the Real Surface Area of Smooth Solid Electrodes, 1997, Electrochimica Acta, vol. 42, No. 19, pp. 2915-2918.
Wolfbeis et al. (Sol-gel based glucose biosensors employing optical oxygen transducers, and a method for compensating for variable oxygen background, Biosensors & Bioelectronics 15 (2000) pp. 69-76).
Machine translation of DE 10053974 pp. 1-4, provided by epo.org.
A. Bott, W. Heineman, Chronocoulometry, Current Separations, 2004, 20, pp. 121.
Related Publications (1)
Number Date Country
20120264204 A1 Oct 2012 US
Provisional Applications (24)
Number Date Country
60437184 Dec 2002 US
60437185 Dec 2002 US
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Continuations (1)
Number Date Country
Parent 10541124 US
Child 13532927 US