Automated diagnostic analyzers having vertically arranged carousels and related methods

Information

  • Patent Grant
  • 10775398
  • Patent Number
    10,775,398
  • Date Filed
    Friday, January 4, 2019
    5 years ago
  • Date Issued
    Tuesday, September 15, 2020
    4 years ago
Abstract
Example automated diagnostic analyzers and methods for using the same are disclosed herein. An example apparatus described herein includes a first carousel rotatably coupled to a base and having a first axis of rotation. The example apparatus includes a second carousel rotatably coupled to the base and vertically spaced over the first carousel such that at least a portion of the second carousel is disposed over the first carousel. In the example apparatus, the second carousel has a second axis of rotation and a plurality of vessels. The example apparatus also includes a pipetting mechanism offset from the second axis of rotation. The example pipetting mechanism is to access the first carousel and the second carousel.
Description
FIELD OF THE DISCLOSURE

The present disclosure relates generally to automated diagnostic analyzers and, more particularly, to automated diagnostic analyzers having vertically arranged carousels and related methods.


BACKGROUND

Automated diagnostic analyzers employ multiple carousels and multiple pipetting mechanisms to automatically aspirate fluid from and dispense fluid to different areas in the analyzer to perform diagnostic analysis procedures. The carousels may include a carousel for reaction vessels, a carousel for samples and/or a carousel for reagents. By arranging multiple containers on the respective carousels, these known analyzers are capable of conducting multiple tests on multiple test samples as the carousels rotate. Some known carousels are arranged in a coplanar orientation, and a number of different modules or stations are disposed around the carousels to perform specific functions such as, for example, mixing the contents of a reaction vessel, washing a reaction vessel and/or a pipette, incubating a test sample, and analyzing the contents of a reaction vessel. Due to the multiple coplanar carousels and the number of modules and stations, these known automated clinical analyzers typically require a relatively large space.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 is a partial exploded perspective view of example components of an example diagnostic analyzer having stacked carousels in accordance with the teachings of this disclosure.



FIG. 2 shows a top view of an example diagnostic analyzer incorporating the example components of FIG. 1.



FIG. 3 is a partial exploded front side view of the example components of FIG. 1.



FIG. 4 shows a rear view of the example diagnostic analyzer of FIG. 2.



FIG. 5 is a schematic a plan view of an example diagnostic analyzer with an alternative carousel configuration.



FIG. 6 is a block diagram of an example processing system for the example analyzers shown in FIGS. 1-5.



FIG. 7 is a flowchart illustrating an example diagnostic testing process.



FIG. 8 is a timeline illustrating timing sequences of various components in the example analyzer shown in FIGS. 1-4.



FIG. 9 is a diagram of a processor platform that may be used with the examples disclosed herein.





DETAILED DESCRIPTION

Certain examples are shown in the above-identified figures and disclosed in detail below. In describing these examples, like or identical reference numbers are used to identify the same or similar elements. The figures are not necessarily to scale and certain features and certain views of the figures may be shown exaggerated in scale or in schematic for clarity and/or conciseness. Additionally, several examples have been described throughout this specification. Any features from any example may be included with, a replacement for, or otherwise combined with other features from other examples.


Diagnostics laboratories employ diagnostic instruments such as those for testing and analyzing specimens or samples including, for example, clinical chemistry analyzers, immunoassay analyzers and hematology analyzers. Specimens and biological samples are analyzed to, for example, check for the presence or absence of an item of interest including, for example, a specific region of DNA, mitochondrial DNA, a specific region of RNA, messenger RNA, transfer RNA, mitochondrial RNA, a fragment, a complement, a peptide, a polypeptide, an enzyme, a prion, a protein, an antibody, an antigen, an allergen, a part of a biological entity such as a cell or a viron, a surface protein, and/or functional equivalent(s) of the above. Specimens such as a patient's body fluids (e.g., serum, whole blood, urine, swabs, plasma, cerebra-spinal fluid, lymph fluids, tissue solids) can be analyzed using a number of different tests to provide information about the patient's health.


Generally, analysis of a test sample involves the reaction of test samples with one or more reagents with respect to one or more analytes. The reaction mixtures are analyzed by an apparatus for one or more characteristics such as, for example, the presence and/or concentration of a certain analyte in the test sample. Use of automated diagnostic analyzers improves the efficiency of the laboratory procedures because the technician (e.g., an operator) has fewer tasks to perform and, thus, the potential for operator or technician error is reduced. In addition, automated diagnostic analyzers also provide results much more rapidly and with increased accuracy and repeatability.


Automated diagnostic analyzers use multiple pipettes to move liquids between storage containers (e.g., receptacles such as open topped tubes) and containers in which the specimens are to be processed (e.g., reaction vessels). For example, a specimen may be contained in a tube loaded in a rack on an analyzer, and a head carrying a pipette moves the pipette into the tube where a vacuum is applied to extract a selected amount of the specimen from the tube into the pipette. The head retracts the pipette from the tube and moves to another tube or reaction vessel located at a processing station and deposits the extracted specimen from the pipette into the reaction vessel. A reagent is similarly acquired from a reagent supply.


The example automated diagnostic analyzers disclosed herein position a first carousel (e.g., a reaction carousel, a reagent carousel, a sample carousel) above at least a portion of a second carousel (e.g., a reaction carousel, a reagent carousel, a sample carousel) to reduce lab space, increase throughput and decrease sample testing time (e.g., turnaround time). The example automated diagnostic analyzers also locate one or more pipetting mechanism(s) within the outer diameters of one of more of the carousels to further reduce the dimensions (e.g., the footprint) of the analyzer and decrease the distanced traveled by the respective pipetting mechanisms. The example automated diagnostic analyzers can simultaneously perform two or more tests on a plurality of test samples in a continuous and random access fashion. Test steps such as aspirating/dispensing, incubations, washes and specimen dilution are performed automatically by the instrument as scheduled. By utilizing vertically arranged or stacked carousels, the foot print or floor space required for the overall system is reduced. Additionally, the distanced traveled by the pipetting mechanism is also reduced, which decreases turnaround time and, thus, increases the throughput of the example analyzer. For example, in some examples, the example analyzers disclosed herein perform up to about 956 tests per hour. Further, because the carousels are stacked vertically, carousels with larger diameters and, thus, higher capacity than known analyzers may be incorporated into the example analyzers. The higher capacity analyzers occupy less space than lower capacity analyzers that have a coplanar carousel configuration. The example analyzers with smaller footprints, higher throughputs and shorter turnaround times are advantageous to the operations of hospitals, laboratories, and other research facilities that utilize diagnostic analyzers.


An example apparatus disclosed herein includes a first carousel rotatably coupled to a base and having a first diameter and a first axis of rotation. The example apparatus includes a second carousel rotatably coupled to the base and vertically spaced over the first carousel such that at least a portion of the second carousel is disposed over the first carousel. In the example apparatus, the second carousel has a second diameter, a second axis of rotation and a plurality of vessels. The example apparatus also includes a first pipetting mechanism offset from the second axis of rotation. The example first pipetting mechanism is to access the first carousel and the second carousel. In some examples, the example first pipetting mechanism is disposed within the first diameter and the second diameter and offset from the second axis of rotation.


In some examples, the first axis of rotation and the second axis are parallel to and offset from each other. In some examples, the second diameter is less than the first diameter.


In some examples, the apparatus includes a second pipetting mechanism to access the first carousel and the second carousel. In some examples, the second pipetting mechanism is disposed within the first diameter and outside of the second diameter. In some examples, the first carousel comprises an outer annular array of containers and an inner annular array of containers concentric with the outer annular array and the first pipetting mechanism is to access at least one of the inner annular array of containers or the vessels, and the second pipetting mechanism to access at least one of the outer annular array of containers or the vessels. In some examples, the first pipetting mechanism comprises a first pipette arm movable (e.g., rotatable) along a first path of travel over a first inner container of the inner annular array of containers and a first vessel of the plurality of vessels. In some such examples, the second pipette mechanism comprises a second pipette arm movable (e.g., rotatable) along a second path of travel over a second outer container of the outer annular array of containers and a second vessel of the plurality of vessels. In some examples, the second pipetting mechanism is offset from the first axis of rotation.


In some examples, the apparatus comprises a third pipetting mechanism. In some examples, the third pipetting mechanism is to access only the first carousel. In some examples, the third pipetting mechanism is disposed outside of the first diameter and outside of the second diameter. In some such examples, the third pipetting mechanism comprises a third pipette arm movable (e.g., rotatable) along a third path of travel over a container outside of the first diameter and the second diameter and over a third vessel of the plurality of vessels.


In some examples, the apparatus includes a plate coupled to the base disposed between the first carousel and the second carousel, the second carousel being rotatably coupled to the plate. In some such examples, the second pipetting mechanism is coupled to the plate.


In some examples, first carousel further comprises a middle annular array of containers spaced radially between the outer annular array of containers and the inner annular array of containers.


In some examples, the second carousel is to rotate in a plurality of intervals, each interval comprising an advancement and a stop. In some such examples, the second carousel is operable to rotate approximately 90° during the advancement of one of the intervals. In some examples, the second carousel is stationary during the stop of one of the intervals, a duration of the stop being greater than a duration of the advancement of the interval.


In some examples, the first carousel is to rotate in a plurality of intervals, each interval comprising an advancement and a stop. In some such examples, the first carousel is operable to rotate approximately 180° during the advancement of one of the intervals, a duration of the advancement being about one second of the interval.


In some examples, the apparatus includes a servo motor to rotate one or more of the first carousel or the second carousel.


In some examples, the outer annular array of containers on the first carousel contain a first type of reagent and the inner annular array of containers on the first carousel contain a second type of reagent different than the first type of reagent.


In some examples, the containers of the first carousel are reagent containers, and the vessels of the second carousel are reaction vessels. In some examples, the first pipetting mechanism comprises a probe arm having a vertically descending portion


In another example disclosed herein, an apparatus includes a reagent carousel rotatably coupled to a base about a first axis of rotation. The example apparatus also includes a reaction carousel rotatably coupled to the base about a second axis of rotation, the reaction carousel disposed above the reagent carousel. In addition, the example apparatus includes a first pipette in fluid communication with the reagent carousel and the reaction carousel.


Also, in some examples disclosed herein the example apparatus includes a reagent container disposed on the reagent carousel and a reagent in the reagent container. In addition, the example apparatus includes a reaction vessel disposed on the reaction carousel. In such examples, the first pipette is to aspirate a portion of the reagent from the reagent container, move upward vertically, then dispense the portion of the reagent into the reaction vessel.


In some examples, the example apparatus also includes a second pipette to aspirate a sample from a sample container apart from the reagent carousel and the reaction carousel and dispense the sample into the reaction vessel.


An example method disclosed herein includes rotating a first carousel relative to a base, the first carousel having a first diameter, a first axis of rotation, an outer annular array of containers and an inner annular array of containers concentric with the outer annular array. The example method includes rotating a second carousel relative to the base, the second carousel having a second diameter, a second axis of rotation and a plurality of vessels and being vertically spaced over the first carousel such that at least a portion of the second carousel is disposed over the first carousel. The example method also includes aspirating a first fluid from a first carousel via a first pipetting mechanism offset from the second axis of rotation. In some examples, the first pipetting mechanism is disposed within the first diameter and within the second diameter.


In some examples, the method includes aspirating a second fluid from the first carousel via a second pipetting mechanism. In some examples, the second pipetting mechanism is disposed within the first diameter an outside of the second diameter. In some examples, the method also includes accessing at least one of the inner annular array of containers or the vessels with the first pipetting mechanism and accessing at least one of the outer annular array of containers or the vessels with the second pipetting mechanism. In some examples, the method includes rotating a first pipette arm of the first pipetting mechanism along a first path of travel over a first inner container of the inner annular array of containers and a first vessel. In some such examples, the method also includes rotating a second pipette arm of the second pipetting mechanism along a second path of travel over a first outer container of the outer annular array of containers and a second vessel. In some examples, the second pipetting mechanism is offset from the first axis of rotation.


In some examples, the method includes aspirating a third fluid via a third pipetting mechanism. In some examples, the third pipetting mechanism is disposed outside of the first diameter and outside of the second diameter. In some such examples, the method includes rotating a third pipette arm of the third pipetting mechanism along a third path of travel over a container outside of the first diameter and the second diameter and over a third vessel of the plurality of vessels.


In some examples, the method includes rotating the second carousel in a plurality of intervals, each interval comprising an advancement and a stop. In some such examples, the method includes rotating the second carousel approximately 90° during the advancement of one of the intervals. In some examples, the method includes idling the second carousel during the stop of one of the intervals, a duration of the stop being greater than a duration of an advancement of the interval.


In some examples, the method includes accessing a first vessel on the second carousel with the first pipetting mechanism, rotating the second carousel in a plurality of intervals, and rotating the second carousel for two or more intervals for the first pipetting mechanism to access a second vessel, the second vessel being physically adjacent to the first vessel.


In some examples, the method includes rotating the first carousel in a plurality of intervals, each interval comprising an advancement and a stop. In some such examples, the method includes rotating the first carousel approximately 180° during the advancement of one of the intervals, a duration of the advancement being about one second of the interval.


In some examples, the method includes activating a servo motor to rotate one or more of the first carousel or the second carousel.


Turning now to the figures, a portion of an example automated diagnostic analyzer 100 is shown in partially exploded views FIGS. 1 and 3, and an assembled example analyzer 100 is shown in FIGS. 2 and 4. The example analyzer 100 includes a first carousel 102 and a second carousel 104. As shown in FIGS. 2 and 4, the first carousel 102 and the second carousel 104 are rotatably coupled to a base station 106 independent of each other. The base station 106 houses different subassemblies and other components used for testing (e.g., performing diagnostic analyses) such as, for example, wash fluid, bulk reagents, a vacuum source, a pressure source, a refrigeration system, temperature sensors, a processor, motors, etc.


In the example shown in FIGS. 1-4, the second carousel 104 is vertically spaced above the first carousel 102, and at least a portion of the second carousel 104 is disposed over (e.g., above, on top of) the first carousel 102. In the illustrated examples, the first carousel 102 is a reagent carousel and the second carousel 104 is a reaction vessel carousel. The first carousel 102 is to support multiple reagent containers that may store one or more type(s) of reagent(s). The second carousel 104 is used for conducting tests on samples. However, in other examples, either of the first and/or second carousels 102, 104 may hold reagents, samples, reaction vessels or any combination thereof.


In view of the example analyzer 100 shown in FIG. 1, the base station 106 and other components have been removed for a clear view of the first carousel 102 and the second carousel 104. In the example shown, the first carousel 102 includes a plate having a plurality of slots 103a-n. In the example shown, the first carousel 102 has a bore 105 (e.g., an opening, an aperture, a hole, etc.). In other examples the first carousel 102 may be continuous such that the first carousel 102 does not have a bore. In the example, shown, each of the slots 103a-n is to hold one or more containers or a container carrier having one or more containers. In the example shown, the second carousel 104 is housed within a casing 107. In some examples, the second carousel 104 is a reaction carousel, and some diagnostic testing utilize light signals (e.g., during chemiluminescence analysis), and readings during such testing are conducted in a dark environment to effectively read light from a reaction. Thus, in some examples, the second carousel 104 is disposed within the casing 107 to prevent light from interfering with the readings.



FIG. 2 shows a plan view of the example analyzer 100. In the example, the first carousel 102 has an outer annular array of containers 108a-n that travel along a first annular path 109 and an inner annular array of containers 110a-n that travel a second annular path 111. The outer annular array of containers 108a-n and the inner annular array of containers 110a-n are concentric. Some diagnostic tests involve one reagent and other tests utilize another, different reagent and/or two or more reagents to react with a given sample/specimen. Therefore, in some examples, the outer annular array of containers 108a-n may contain, for example, a first type of a reagent and the inner annular array of containers 110a-n may contain, for example, a second type of reagent different than the first type of reagent. Also, in some examples, the type(s) of reagent(s) within one of the annular arrays 108a-n, 110a-n may be different among the different cartridges within that array.


In some examples, the first carousel 102 has more than two annular arrays of containers (e.g., three, four or more) spaced radially apart from one another on the first carousel 102. In some examples, the containers are disposed in carriers that are loaded into the slots 103a-n of the first carousel 102. In some examples, each of the carriers may container one, two, three, four or more containers and, when disposed on the first carousel 102, define the annular arrays of containers. In some examples, the first carousel 102 includes 72 slots 103a-n to receive up to 72 carriers. In other examples, the first carousel 102 may include 45 slots 103a-n to receive up to 45 carriers. In some examples, each carrier (e.g., a kit) includes a volume of testing liquid (e.g., reagent) to supply or support about 50 to about 1700 tests. Other examples include different numbers of slots, different numbers of carriers and different volumes of testing liquids.


In the example shown, the second carousel 104 has a plurality of reaction vessels 112a-n disposed around an outer circumference of the second carousel 104. In the example shown, the reaction vessels 112a-n are reusable cuvettes (e.g., washable glass cuvettes). After a test has been completed in one of the reaction vessels 112a-n, the vessel 112a-n is cleaned (e.g., sterilized), and the vessel 112a-n may be used for another test. However, in other examples, the reaction vessels 112a-n are disposable cuvettes (e.g., plastic cuvettes) that are discarded after one or more tests. In some examples, the second carousel 104 includes an unloading mechanism 113 (e.g., a passive unloader or an active unloader) for removing the reaction vessels 112a-n (e.g., disposable cuvettes) from the second carousel 104. In some examples, the unloading mechanism 113 is positioned such that when one of the reaction vessels 112a-n is unloaded from the second carousel 104, the unloaded reaction vessel 112a-n falls through the bore 105 of the first carousel 102 and into a waste container or other receptacle disposed within the base station 106. In some examples, the second carousel 104 includes more than one unloading mechanism, and the unloading mechanisms may be disposed in other locations around the second carousel 104.



FIG. 3 illustrates a front side view of the first carousel 102 and the second carousel 104 without the base station and other components. As shown, the first carousel 102 rotates about a first axis 114 and the second carousel 104 rotates about a second axis 116. In the illustrated example, the first axis 114 and the second axis 116 are substantially parallel and offset from each other. However, in other examples, the second carousel 104 is disposed over the center of the first carousel 102 such that the first axis 114 and the second axis 116 are substantially coaxially aligned (e.g., the first carousel 102 and the second carousel 104 are concentric).


As illustrated more clearly in FIG. 2, the first carousel 102 has a first diameter 118 and the second carousel 104 has a second diameter 120. In the example shown, the second diameter 120 is less than the first diameter 118. However, in other examples, the second diameter 120 is the same as or larger than the first diameter 118. The second carousel 104 includes a bore 122 such that the second carousel forms a ring-like (e.g., annular) rack for the vessels 112a-n. As shown in this example, the second carousel 104 (e.g., the top carousel) is completely disposed above and over the first diameter 118 of the first carousel 102. In other examples, only a portion of the second diameter 120 is positioned above the first diameter 118.


In the example shown in FIG. 4, the first carousel 102 is rotatably coupled to a top 124 of the base station 106. The analyzer 100 includes a first motor 125 (e.g., a stepper motor or a servo motor) to rotate the first carousel 102 on the top 124 of base station 106. In the example shown, the analyzer 100 also includes a platform 126 (e.g., a plate, a mounting surface, a shield) mounted to the base station 106 via a plurality of legs 128a, 128b and disposed between the first carousel 102 and the second carousel 104. In other examples, the platform 126 may be mounted to the base station 106 with other fasteners. The platform 126 defines a partition or barrier between the first carousel 102 and the second carousel 104. In the example shown, the second carousel 104 is rotatably mounted to the platform 126. However, in other examples, the second carousel 104 may be rotatably supported on the base station 106 without the mounting platform 126. The second carousel 104 is rotated via a second motor 127 (e.g., a stepper motor or a servo motor). In the example shown, the first and second carousels 102, 104 may be rotated clockwise and/or counter-clockwise, depending on the scheduling protocols for the particular testing.


The example automated diagnostic analyzers disclosed herein also include one or more pipetting mechanisms (e.g., probe arms, automated pipettes, etc.). In the illustrated examples shown in FIGS. 1-4, the analyzer 100 includes a first pipetting mechanism 130 that is coupled (e.g., mounted) to the platform 126. The first pipetting mechanism 130 is coupled to the platform 126 above the first carousel 102 and within the bore 122 of the second carousel 104 (i.e., within the first diameter 118 of the first carousel 102 and within the second diameter 120 of the second carousel 104). In the example shown, the first pipetting mechanism 130 is offset from the second axis 116 (e.g., the center of the second carousel 104). However, in other examples the first pipetting mechanism 130 is aligned with the second axis 116. The first pipetting mechanism 130 has multiple degrees of freedom. In the example shown, the first pipetting mechanism 130 has a first probe arm 132 that moves in a first path of travel (e.g., along a horizontal arc) 134 and aspirates/dispenses fluid through a first pipette 136 located at a distal end of the first probe arm 132. The first pipetting mechanism 130 is also movable in the Z direction (e.g., the vertical direction).


As illustrated in FIG. 2, the first pipetting mechanism 130 accesses containers on the first carousel 102 through a first access port 138, which may be for example, an opening, an aperture, a hole, a gap, etc. formed in the platform 126. In operation, the first pipetting mechanism 130 moves the first probe arm 132 along the first path of travel 134 (e.g., rotates or pivots clockwise) until the first pipette 136 is aligned above the first access port 138. The first path of travel 134 may be circular, semicircular, linear or a combination thereof. The first pipetting mechanism 130 then moves vertically downward until the first pipette 136 accesses a container on the first carousel 102 to aspirate/dispense liquid (including, for example, microparticles contained in the liquid) from the container. In the example shown, the first pipetting mechanism 130 and the first access port 138 are positioned to allow the first pipetting mechanism 130 to aspirate from a container disposed on the first carousel 102 below the first access port 138. The first carousel 102 holds the outer annular array of containers 108a-n and the inner annular array of containers 110a-n, which may be, for example, first reagents used in a diagnostic test and second reagents used in the diagnostic test, respectively. In the illustrated example, the first pipetting mechanism 130 is positioned (e.g., aligned) to aspirate fluid from a container of the inner annular array of containers 110a-n on the first carousel 102. As shown, the inner annular array of containers 110a-n rotate along the second annular path 111, which intersects with the first access port 138 and, thus, the second path of travel 134. In the example shown, a silhouette of a carrier, having two containers (e.g., an outer annular container and an inner annular container), is depicted near the first access port 138 to illustrate the interaction of the containers, the first access port 138 and/or the first path of travel 134.


After aspirating fluid from the appropriate container on the first carousel 102, the first pipetting mechanism 130 moves vertically upward and moves the first probe arm 132 along the first path of travel 134 (e.g., rotates or pivots clockwise) until the first pipette 136 is at point A, at which point the first pipette 136 is aligned vertically over one of the plurality of vessels 112a-n on the second carousel 104. In some examples, the first pipetting mechanism 130 dispenses the liquid (e.g., the liquid including any microparticles aspirated from a container on the first carousel 102) into the vessel 112a-n on the second carousel 104 at this position (e.g., the height at which the first pipette 136 travels along the first path of travel 134). In other examples, the first pipetting mechanism 130 moves vertically downward toward the second carousel 104 and dispenses the liquid into the vessel 112a-n on the second carousel 104. In the illustrated example, the first pipetting mechanism 130 has only one access point, the first access port 138, for accessing containers on the first carousel 102 disposed below. However, in other examples, the platform 126 includes multiple access ports along the first path of travel 134 such that the first pipette 136 can access additional areas on the first carousel 102. In some examples, multiple annular arrays of containers (e.g., an inner array and an outer array or an inner array, a middle array and an outer array) are disposed on the first carousel 102 at different radial distances (e.g., along the slots 103 shown in FIG. 1) and, thus, multiple access points along the first path of travel 134 allow the first pipetting mechanism 130 to access these containers as needed and/or desired.


In the example shown, the analyzer 100 includes a second pipetting mechanism 140 that is coupled (e.g., mounted) to the platform 126. The second pipetting mechanism 140 is coupled to the platform 126 above the first carousel 102 and next to (e.g., adjacent) the second carousel 104 (i.e., within the first diameter 118 of the first carousel 102 and outside of the second diameter 120 of the second carousel 104). In the example shown, the second pipetting mechanism 140 is offset from the first axis 114 of the first carousel 102. However, in other examples, the second pipetting mechanism 140 is aligned with the first axis 114 of rotation. The second pipetting mechanism 140 has multiple degrees of freedom. In the example shown, the second pipetting mechanism 140 has a second probe arm 142 that moves along a second path of travel 144 (e.g., rotates or pivots along a horizontal arc) to aspirate/dispense fluid through a second pipette 146 disposed at a distal end of the second probe arm 142. The second path of travel 144 may be circular, semicircular, linear or a combination thereof. The second pipetting mechanism 140 is also movable in the Z direction (e.g., the vertical direction).


In the example shown, the second pipetting mechanism 140 accesses containers on the first carousel 102 through a second access port 148 formed in the platform 126. In operation, the second pipetting mechanism 140 moves (e.g., rotates or pivots) the second probe arm 142 along the second path of travel 144 until the second pipette 146 is aligned above the second access port 148. The second pipetting mechanism 140 then moves vertically downward for the second pipette 146 to access a container on the first carousel 102. In the example shown, the second pipetting mechanism 140 and the second access port 148 are positioned to allow the second pipetting mechanism to aspirate from a container disposed on the first carousel 102 below the second access port 148. As mentioned above, the first carousel 102 includes the outer annular array of containers 108a-n and the inner annular array of containers 110a-n, which may be, for example, reagents used first in a diagnostic test and reagents used second in the diagnostic test. In the illustrated example, the second pipetting mechanism 140 is positioned (e.g., aligned) to aspirate liquid including any microparticles from the outer annular array of containers 108a-n on the first carousel 102. As shown, the outer annular array of containers 108a-n rotate along the first annular path 109, which intersects with the second access port 148 and, thus, the second path of travel 144. In the example shown, a silhouette of a carrier, having two containers (e.g., an outer annular container and an inner annular container), is depicted near the second access port 148 to illustrate the interaction of the containers, the second access port 148 and/or the second path of travel 144.


After aspirating liquid and any associated microparticles from the appropriate container on the first carousel 102, the second pipetting mechanism 140 moves vertically upward and moves (e.g., rotates or pivots) the second probe arm 142 counter-clockwise along the second path of travel 144 until the second pipette 146 is at point B, at which point the second pipette 146 is aligned vertically over one of the plurality of vessels 112a-n on the second carousel 104. In some examples, the second pipetting mechanism 140 dispenses the liquid (e.g., the liquid including any microparticles aspirated from a container on the first carousel 102) into the vessel 112a-n on the second carousel 104 at this position (e.g., the height at which the second pipette 146 travels along the second path of travel 144). In other examples, the second pipetting mechanism 140 moves vertically downward toward the second carousel 104 and dispenses the liquid into the vessel 112a-n on the second carousel 104. In the illustrated example, the second pipetting mechanism 140 has one access point, the second access port 148, for accessing containers on the second carousel 104 disposed below. However, in other examples, the platform 126 includes multiple access ports along the second path of travel 144 such that the second pipette 146 can access additional areas on the first carousel 102. In some examples, multiple annular arrays of containers (e.g., an inner array and an outer array or an inner array, a middle array and an outer array) are disposed on the first carousel 102 at different radial distances and, thus, multiple access points along the second path of travel 144 will allow the second pipetting mechanism 140 to access the containers as needed.


In the illustrated examples, the analyzer 100 includes a third pipetting mechanism 150. In the example shown, the third pipetting mechanism 150 is coupled to the platform 126. In other examples, the third pipetting mechanism 150 may be coupled to the top 124 of the base station 106. In the example shown, the third pipetting mechanism 150 is disposed outside of the first diameter 118 of the first carousel 102 and outside of the second diameter 120 of the second carousel 104. However, in other examples, the third pipetting mechanism 150 is disposed within the first diameter 118 of the first carousel 102. In the example shown, the third pipetting mechanism 150 is mounted at a level above the first carousel 102. Specifically, the third pipetting mechanism 150 is mounted to the platform 126 above the first carousel 102.


The third pipetting mechanism 150 has multiple degrees of freedom. In the example shown, the third pipetting mechanism 150 has a third probe arm 152 that rotates along a third path of travel 154 (e.g., a horizontal arc) to aspirate/dispense liquid (e.g., a sample) through a third pipette 156 at a distal end of the third probe arm 152. The third path of travel 154 may be circular, semicircular, linear or a combination thereof. The third pipetting mechanism 150 is also movable in the Z direction (e.g., the vertical direction).


In the example shown, the third pipetting mechanism 150 may be used, for example, to dispense a sample (e.g., a test sample or a specimen) into one or more of the vessels 112a-n on the second carousel 104. In some examples, test samples are aspirated from sample containers (which may be in carriers) along the third path of travel 154 of the third pipetting mechanism 150. In some examples, test samples are transported to the rear of the analyzer 100 via a transporter or a positioner, and the third probe arm 152 moves (e.g., rotates or pivots) along the third path of travel 154 to align the third pipetting mechanism 150 above the sample tubes. After aspirating a sample from a sample tube, the third pipetting mechanism 150 moves (e.g., rotates or pivots) the third probe arm 152 along the third path of travel 154 until the third pipette 156 is at point C, where the third pipette 156 is vertically aligned above one of the reaction vessels 112a-n on the second carousel 104. The third pipetting mechanism 150 moves vertically downward toward the second carousel 104 and dispenses the sample into one of the vessels 112a-n on the second carousel 104.


In the example shown, three pipetting mechanisms 130, 140, 150 are employed to perform automated testing. However, in other example analyzers, more or fewer automated pipetting mechanisms may be utilized (such as, for example, one, two, four, five, etc.). For example, there may be a fourth pipetting mechanism, which also may be used to dispense samples into one of the vessels 112a-n on the second carousel 104. Also, in some examples, one or more of the pipetting mechanisms may include a double probe to enable the pipetting mechanism to aspirate from and/or dispense to two containers and/or vessels simultaneously. For example, with two probes on the third pipetting mechanism 150, the third pipetting mechanism 150 can dispense a first sample in a first vessel and a second sample in a second vessel. In addition, in some examples, the pipetting mechanisms may be located in different locations, to perform the steps for analysis. Further, in some example analyzers, the pipetting mechanisms 130, 140, 150 may aspirate from multiple sources and dispense into multiple locations (e.g., containers and vessels) along their respective paths of travel.


In the example analyzer 100 shown in FIGS. 1-4, the first and second pipetting mechanisms 130, 140 have a larger Z direction range (e.g., a vertical range or stroke) than pipetting mechanisms in known analyzers, because the first and second pipetting mechanisms 130, 140 is to access the containers 108a-n, 110a-n on the first carousel 102 at a lower level and the vessels 112a-n on the second carousel 104 at a higher level. Thus, in some examples, the height (e.g., the vertical position of the tip of the pipette 136, 146) at which the pipettes 136, 146 aspirate liquid from the containers 108a-n, 110a-n on the first carousel 102 is different than the height at which the pipettes 136, 146 dispense liquid into the vessels 112a-n. The example pipette 136, 146 tips are positioned at a first height to access the containers 108a-n, 110a-n on the first carousel 102 and a second height to access the vessels 112a-n on the first carousel 102, the first height being lower (e.g., closer to the base 106) than the second height. In some examples, each of the probe arms 132, 142 includes a downward or vertically descending portion 133, 143 to allow the pipetting mechanisms 130, 140 to incorporate a standard sized pipette or probe. In such examples, the downward portion 133, 143 of the probe arms 132, 142 displaces the pipettes or probes further from the probe arms 132, 142 to ensure the pipettes have access into the containers 108a-n, 110a-n on the first carousel 102. With the downward portions 133, 143, the pipettes are able to access the bottom of the containers 108a-n, 110a-n on the first carousel 102 without, for example, the platform 126 blocking a downward or vertical descent of the probe arms 132, 142. Use of a standard size pipette or probe, as compared to a longer pipette or probe, reduces the effects of vibrations (e.g., from the motors, mixers, etc.) on the pipette or probe, resulting in greater operation accuracy.


In some examples, the length of the probe arms 132, 142, 152 and/or the length of the paths of travel 134, 144, 154 are shorter than the probe arms of some known analyzers. The decreased probe arm length of the illustrated examples reduces the effects of vibrations (e.g., from the motors, mixers, etc.) on the pipetting mechanisms 130, 140, 150 because the respective pipettes 136, 146, 156 are closer to the base of the respective pipetting mechanisms 130, 140, 150 and, thus, are closer to the center of mass and are sturdier. The sturdier probes arms 132, 142, 152 enable the example pipetting mechanisms 130, 140, 150 to operate with greater accuracy. The example pipetting mechanisms 130, 140, 150 may also operate with greater speed because there is no need to wait for vibrations to dampen or otherwise subside before operation of the pipetting mechanisms 130, 140, 150. In the example shown, the first, second and third pipetting mechanisms 130, 140, 150 include respective base assemblies 135, 145, 155. In some examples, the base assemblies 135, 145, 155 include drive components and other actuating components to move the first, second and third probe arms 132, 142, 152 in the Z direction.


Although the first and second carousels 102, 104 are disclosed herein as being a reagent carousel and a reaction carousel, respectively, the teachings of this disclosure may be applied to examples in which either the first carousel 102 and/or the second carousel 104 includes reagents, reaction vessels and/or samples. Thus, the first carousel 102 may be a reaction carousel including a plurality of reaction vessels, and the second carousel 104 may be a reagent carousel including a plurality of reagent containers having reagent(s) for reacting with the samples in the reaction vessels.


In the example shown, the analyzer 100 also includes additional modules or components for performing different steps in the test process such as, for example, a mixer for mixing, a light source for lighting the reaction vessels, a reader for analyzing the test samples, a wash zone for cleaning the vessels, etc. As shown in FIG. 2, the example analyzer 100 includes a reader 158, a plurality of mixers 160a-d, and a wash station 162 for cleaning the reaction vessels. In some examples, the reaction vessels 112a-n are cleaned at the wash station 162 at point D. In some examples, the mixers 160a-d (e.g., in-track vortexers (ITV)) are coupled to the platform 126 disposed between the first carousel 102 and the second carousel 104, which may, for example, dampen the vibrating effects of the mixers 160a-d and reduce the influence they have on the pipetting mechanisms 130, 140, 150 and other components of the analyzer 100. In some examples, the mixers 160a-d are disposed beneath the vessels 112a-n on the second carousel 104. In some examples, the analyzer 100 includes one or more wash zones coupled to the platform 126 and disposed along the first, second and/or third paths of travel 134, 144, 154. In some examples, the pipettes 136, 146, 156 are cleaned between aspirating/dispensing functions in the wash zones.


In the example shown, the first and second carousels 102, 104 rotate in intervals or locksteps during a diagnostic test. Each interval has an advancement step wherein the carousel moves and stop step where the carousel is idle. Depending on the type of diagnostic test performed, the carousels 102, 104 may have different lockstep times and rotational degrees that are traversed during the advancement step. In the example shown, the second carousel 104 has total a lockstep time (the combination of an advancement step and a stop step) of about four seconds (i.e., the second carousel 104 rotates incrementally to a different position about every four seconds). During the advancement step of the lockstep, the second carousel 104 rotates about 90° (e.g., about a quarter turn). In other examples, the second carousel 104 may rotate more or less depending on the scheduling protocols designed for the specific analyzer and/or for a particular diagnostic testing protocol. In some examples, the second carousel 104 rotates about 1° to about 15° during the advancement step of the lockstep. In other examples, the second carousel rotates about 15° to about 90° during the advancement step of the lockstep.


In the example shown, the advancement step may take place during about one second of the four second lockstep, and the second carousel 104 may remain idle (e.g., stationary) for about three second during the stop step of the lockstep. During these three seconds, the first, second and third pipetting mechanisms 130, 140, 150 are aspirating and/or dispensing liquids (e.g., simultaneously or in sequence), including any microparticles contained therein, and other functional modules are operating around the carousels 102, 104. Some of the functional modules such as, for example, the reader 158, also operate during the advancement step of a lockstep. Additionally or alternatively, the reader 158 operates during the stop step of a lockstep.


In some examples, the first carousel 102 has a lockstep time of about two seconds. For each lockstep, the first carousel 102 rotates during one second (e.g., an advancement step) and is idle (e.g., stationary) for one second (e.g., a stop step). The lockstep time for the first carousel 102 is half of the lockstep time for the second carousel 104 so that the first carousel 102 may be repositioned during one lockstep of the second carousel 104, and a second reagent can be aspirated from the first carousel 102 and dispensed into the second carousel 104 during one lockstep of second carousel 104. For example, a first reagent container on the outer annular array of containers 108a-n and a second reagent container on the inner annular array of container 110a-n may be on the same radial slot 103a-n on the first carousel 102. In this example, if both reagents are to be used during a single lockstep of the second carousel 104, during the first lockstep for the first carousel 102, the second pipetting mechanism 140 may aspirate a reagent from the outer annular array of containers 108a-n. After the second pipette 146 has left the container, the first carousel 102 rotates to its second lockstep position so that the first pipetting mechanism 130 can aspirate its desired reagent from the inner annular array of container 110a-n during the same lockstep of the second carousel 104. In some examples, depending on the location of the pipetting mechanisms, the first carousel 102 is rotated approximately 180° to the next position so the next pipetting mechanism can aspirate and dispense in accordance with the testing protocol. Thus, both the first and second pipetting mechanisms 130, 140 can aspirate from containers in any of the slots 103a-n of the first carousel 102 in one lockstep of the second carousel 104. In addition, in some examples, the first and second pipetting mechanisms 130, 140 may interact with the first carousel 102 during the stop step portion of the lockstep of the first carousel 102 while the second carousel 104 rotates in the advancement step of the lockstep of the second carousel 104.



FIG. 5 illustrates an example analyzer 500 with an alternative configuration of carousels and pipetting mechanisms. In this example, the analyzer 500 includes a first carousel 502 and a second carousel 504 that are each rotatably coupled to a base 506. The second carousel 504 is disposed above and over the first carousel 502. The first carousel 502 may be, for example, a reagent carousel having a plurality of reagent containers and the second carousel 504 may be, for example, a reaction carousel having a plurality of reaction vessels.


In the example shown, the first carousel 502 has an outer annular section 508 for containers and an inner annular section 510 for containers. In some examples, containers on the outer annular section 508 may be, for example, reagent containers that hold a first reagent to be used in a first step in a test process, and containers on the inner annular section 510 may be, for example, reagent containers that hold a second reagent to be used either in a second step in the test process and/or in a second test process different than the first.


As shown, the first carousel 502 has a first bore 512 and a first diameter 514, and the second carousel 504 has a second bore 516 and a second diameter 518. In this example, a center of the second carousel 504 is offset from a center of the first carousel 502 and within the first diameter 516 (i.e., the second carousel 504 is disposed vertically above the first carousel 502 and positioned within the outer bounds of the first carousel 502).


The analyzer 500 includes a first pipetting mechanism 520 disposed within the first diameter 514 of the first carousel 502 and within the second diameter 518 of the second carousel 504. In the example shown, the first pipetting mechanism 520 is also disposed within the first bore 512 of the first carousel 502 and the second bore 516 of the second carousel 504. In some examples, the first pipetting mechanism 520 is mounted to the base 506. In other examples, the first pipetting mechanism 520 is mounted to a platform disposed between the first carousel 502 and the second carousel 504. In the example shown, the first pipetting mechanism 520 moves in the Z direction (e.g., vertically) and rotates or otherwise moves to aspirate/dispense liquid including liquids that have microparticles within a first probe arm radius or range of motion 522. The first probe arm radius 522 is capable of extending over a portion of the inner annular section 510 of the first carousel 502 and over a portion of the second carousel 504 such that the first pipetting mechanism 520 is able to aspirate/dispense from/to containers or vessels disposed on the inner annular section 510 of the first carousel 502 and/or containers or vessels on disposed on the second carousel 504. Thus, the first pipetting mechanism 520 may be used, for example, to aspirate a reagent from a container on the first carousel 502 and dispense the reagent into a reaction vessel on the second carousel 504.


The analyzer 500 includes a second pipetting mechanism 524 disposed outside the first diameter 514 of the first carousel 502 and outside of the second diameter 518 of the second carousel 504. In some examples, the second pipetting mechanism 524 is mounted to the base 506. In other examples, the second pipetting mechanism is mounted to a platform disposed between the first carousel 502 and the second carousel 504. The second pipetting mechanism 524 moves in the Z direction (e.g., vertically) and rotates or otherwise moves to aspirate/dispense fluid within a second probe arm radius or range of motion 526. As shown, the second probe arm radius 526 extends over a portion of the outer annular section 508 of the first carousel 502 and a portion of the second carousel 504 such that the second pipetting mechanism 524 is able to aspirate/dispense from/to containers or vessels disposed on the outer annular section 508 of the first carousel 502 and/or containers or vessels on disposed on the second carousel 504. Thus, the second pipetting mechanism 524 may be used, for example, to aspirate a reagent from a container on the first carousel 502 and dispense the reagent into a reaction vessel on the second carousel 504.


The example analyzer 500 includes a third pipetting mechanism 528 disposed outside the first diameter 514 of the first carousel 502 and outside of the second diameter 518 of the second carousel 504. In some examples, the third pipetting mechanism 528 is mounted to the base 506. In other examples, the third pipetting mechanism 528 is mounted to a platform disposed between the first carousel 502 and the second carousel 504. The third pipetting mechanism 528 moves in the Z direction (e.g., vertically) and rotates or otherwise moved to aspirate/dispense fluid within a third probe arm radius 530. As shown, the third probe arm radius or range of motion 530 extends over a portion of the outer annular section 508 of the first carousel 502, a portion of the second carousel 504, and a region outside of the base 506 of the analyzer 500. The third pipetting mechanism 528 may be used, for example, to aspirate sample from a test sample tube disposed outside of the base 506 (e.g., from another portion of the analyzer 500) and to dispense the sample into a container or vessel on the second carousel 504.


In the example shown, the inner annular section 510 and the outer annular section 508 are formed in the same carousel 502 and, thus, rotate together. However, in other examples, the inner annular section 510 and the outer annular section 508 may be separate carousels that are independently rotatable in either direction.


As shown, the first, second and third pipetting mechanisms 520, 524, 528 are disposed within the first and second diameters 514, 518 and/or in the corners of the base 506. In addition, the first carousel 502 and second carousel 504 are stacked. Thus, the footprint of the example analyzer 500 is less than an analyzer with coplanar carousels.



FIG. 6 is a block diagram of an example processing system 600 for use with an automated diagnostic analyzer such as, for example, the analyzers 100, 500 disclosed above. The example processing system 600 includes a station/instrument controller 602, which controls the instruments and mechanisms used during a diagnostic test. In the example shown, the station/instrument controller 602 is communicatively coupled to instruments 604a-n. The instruments 604a-n may include, for example, components of the example analyzer 100 disclosed above including the first pipetting mechanism 130, the second pipetting mechanism 140, the third pipetting mechanism 150, the ITVs 160a-d, the wash zone 162 and/or the reader 158. The example processing system 600 includes an example processor 606 that operates the station/instrument controller 602 and, thus, the instruments 604a-n in accordance with a schedule or testing protocol as disclosed herein.


The example processing system 600 also includes a carousel controller 608, which controls one or more carousels of the analyzer. In the example shown, the carousel controller 608 is communicatively coupled to a first carousel 610 and a second carousel 612. The first carousel 610 and the second carousel 612 may correspond, for example, to the first and second carousels 102, 104 disclosed above in connection with the example analyzer 100. The carousel controller 608 controls the rotation of the first and second carousels 610, 612, such as, for example, using a motor (e.g., the motors 125, 127 disclosed in connection with the analyzer 100). Also, the example processor 606 operates the carousel controller 608 and, thus, the carousels 610, 612 in accordance with a schedule or testing protocol.


The example processing system 600 also includes a database 614 that may store information related to the operation of the example system 600. The information may include, for example, the testing protocol, reagent identification information, reagent volume information, sample identification information, position information related to a position (e.g., reaction vessel, lockstep and/or rotation) of a sample, status information related to the contents and/or position of a reaction vessel, pipette position information, carousel position information, lockstep duration information, etc.


The example processing system 600 also includes a user interface such as, for example, a graphical user interface (GUI) 616. An operator or technician interacts with the processing system 600 and, thus, the analyzer 100, 500 via the interface 616 to provide, for example, commands related to the testing protocols, information related to the samples to be tested, information related to the reagents or other fluids to be used in the testing, etc. The interface 616 may also be used by the operator to obtain information related to the status and/or results of any testing completed and/or in progress.


In the example shown, the processing system components 602, 606, 608, 614 are communicatively coupled to other components of the example system 600 via communication links 618. The communication links 618 may be any type of wired connection (e.g., a databus, a USB connection, etc.) and/or any type of wireless communication (e.g., radio frequency, infrared, etc.) using any past, present or future communication protocol (e.g., BLUETOOTH®, USB 2.0, USB 3.0, etc.). Also, the components of the example system 600 may be integrated in one device or distributed over two or more devices.


While an example manner of implementing the analyzers 100, 500 of FIGS. 1-5 is illustrated in FIG. 6, one or more of the elements, processes and/or devices illustrated in FIG. 6 may be combined, divided, re-arranged, omitted, eliminated and/or implemented in any other way. Further, the example station/instrument controller 602, the example instruments 604a-n, the example processor 606, the example carousel controller 608, the example first carousel 610, the example second carousel 612, the example database 614, the example graphical user interface 616 and/or, more generally, the example processing system 600 of FIG. 6 may be implemented by hardware, software, firmware and/or any combination of hardware, software and/or firmware. Thus, for example, any of the example station/instrument controller 602, the example instruments 604a-n, the example processor 606, the example carousel controller 608, the example first carousel 610, the example second carousel 612, the example database 614, the example graphical user interface 616 and/or, more generally, the example processing system 600 could be implemented by one or more analog or digital circuit(s), logic circuits, programmable processor(s), application specific integrated circuit(s) (ASIC(s)), programmable logic device(s) (PLD(s)) and/or field programmable logic device(s) (FPLD(s)). When reading any of the apparatus or system claims of this patent to cover a purely software and/or firmware implementation, at least one of the example station/instrument controller 602, the example instruments 604a-n, the example processor 606, the example carousel controller 608, the example first carousel 610, the example second carousel 612, the example database 614 and/or the example graphical user interface 616 is/are hereby expressly defined to include a tangible computer readable storage device or storage disk such as a memory, a digital versatile disk (DVD), a compact disk (CD), a BLU-RAY-DISC™, etc. storing the software and/or firmware. Further still, the example processing system 600 of FIG. 6 may include one or more elements, processes and/or devices in addition to, or instead of, those illustrated in FIG. 6, and/or may include more than one of any or all of the illustrated elements, processes and devices.


A flowchart representative of an example method 700 for implementing the analyzers 100, 500 and/or the processing system 600 of FIGS. 1-6 is shown in FIG. 7. In this example, the method may be implemented as machine readable instructions comprising a program for execution by a processor such as the processor 912 shown in the example processor platform 900 discussed below in connection with FIG. 9. The program may be embodied in software stored on a tangible computer readable storage medium such as a CD-ROM, a floppy disk, a hard drive, a digital versatile disk (DVD), a BLU-RAY-DISC™, or a memory associated with the processor 912, but the entire program and/or parts thereof could alternatively be executed by a device other than the processor 912 and/or embodied in firmware or dedicated hardware. Further, although the example program is described with reference to the flowchart illustrated in FIG. 7, many other methods of implementing the example analyzers 100, 500 and/or processing system 600 may alternatively be used. For example, the order of execution of the blocks may be changed, and/or some of the blocks described may be changed, eliminated, or combined.


As mentioned above, the example process 700 of FIG. 7 may be implemented using coded instructions (e.g., computer and/or machine readable instructions) stored on a tangible computer readable storage medium such as a hard disk drive, a flash memory, a read-only memory (ROM), a compact disk (CD), a digital versatile disk (DVD), a cache, a random-access memory (RAM) and/or any other storage device or storage disk in which information is stored for any duration (e.g., for extended time periods, permanently, for brief instances, for temporarily buffering, and/or for caching of the information). As used herein, the term tangible computer readable storage medium is expressly defined to include any type of computer readable storage device and/or storage disk and to exclude propagating signals. As used herein, “tangible computer readable storage medium” and “tangible machine readable storage medium” are used interchangeably. Additionally or alternatively, the example process 700 of FIG. 7 may be implemented using coded instructions (e.g., computer and/or machine readable instructions) stored on a non-transitory computer and/or machine readable medium such as a hard disk drive, a flash memory, a read-only memory, a compact disk, a digital versatile disk, a cache, a random-access memory and/or any other storage device or storage disk in which information is stored for any duration (e.g., for extended time periods, permanently, for brief instances, for temporarily buffering, and/or for caching of the information). As used herein, the term non-transitory computer readable medium is expressly defined to include any type of computer readable device or disk and to exclude propagating signals. As used herein, when the phrase “at least” is used as the transition term in a preamble of a claim, it is open-ended in the same manner as the term “comprising” is open ended.



FIG. 7 illustrates the example process 700 for diagnostic testing, which may be implemented, for example, by the example analyzers 100, 500 and/or the processing system 600 disclosed herein. The example process 700 of FIG. 7 is described from the perspective of the operations for a single reaction vessel as the reaction vessel rotates on a carousel of an analyzer throughout multiple locksteps. However, the example process 700 is repeatedly implemented simultaneously and/or in sequence for multiple reaction vessels. The example diagnostic testing may be, for example, a clinical chemistry test. The example analyzer 100 disclosed above includes a reaction carousel (e.g., the second carousel 104) having a plurality of reaction vessels. In some examples, the reaction carousel has 187 reaction vessels (e.g., glass cuvettes) spaced around the outer circumference of the second carousel. The reaction carousel rotates in locksteps (e.g., discrete intervals). Each lockstep, the reaction carousel is rotated about a quarter (e.g., 90°) rotation in the counterclockwise direction. In this example, in each lockstep, the reaction carousel rotates (e.g., via a motor) for one second and remains idle (e.g., stationary) for three seconds.


In the example process 700, the number of complete rotations of the reaction carousel is represented by the variable X, which is set to 0 at the beginning of the example process 700, and a predetermined timing of a function or test operation to be performed is represented by N1, N2, N3 and N4. In particular, in this example, N1, N2, N3 and N4 are integers that represent numbers of elapsed locksteps to be used to trigger the performance of a respective function or test operation. In other words, when N1 locksteps have elapsed or completed, a first function or test operation may be performed, when N2 lockstep have elapsed or completed, a second function or test operation may be performed and so on. As mentioned above, the reaction carousel has a lockstep rotation that is slightly more than a quarter turn. In some examples, the rotation is such that after four locksteps, or one full rotation, a given reaction vessel will be indexed one position past where the reaction vessel was in the previous rotation.


The example process includes lockstep4X+1 (block 702). At the beginning, when a full rotation has not yet occurred, X is zero, and this is the first lockstep (i.e., lockstep(4*0)+1). In this first lockstep, a function is performed on the reaction vessel if 4X+1=N1 (block 704). As noted above, N1 represents the timing or lockstep at which a specific function or test operation is performed in connection with the reaction vessel. For example, in the example analyzer 100 disclosed above, the third pipetting mechanism 150 is disposed near the reaction carousel 104 and is to dispense a sample into a reaction vessel at point C. In some examples, the first lockstep of a given test in a given reaction vessel occurs when the reaction vessel is at point C. Therefore, the function of dispensing sample, N1, may be set to 1, such that if this is the first lockstep (block 704) for the reaction vessel, the function is performed (block 706) (i.e., sample is dispensed into the reaction vessel) because 4X+1=N1 (e.g., (4*0)+1=1). In subsequent rotations, wherein N1 continues to be set to 1, and X is not zero, the reaction vessel is idle (block 708) and, for example, no functions are performed on the reaction vessel by the operator or robotic mechanisms of the example analyzer 100, 500 at this lockstep because 4X+1≠N1 (e.g., (4*1)+1≠1). Thus, in this example, if the function is to occur only at the first lockstep (e.g., dispensing a sample), then the example system will sit idle during each subsequent occurrence of a first lockstep during subsequent rotations (e.g., when X>1) until, for example, the reaction vessel is washed and ready for a subsequent test and X is reset to zero for the subsequent implementation of the example process 700.


The example process 700 includes advancing to the next lockstep (block 710) and reading (e.g., analyzing) the contents of any reaction vessel passing the reader. As mentioned above, the reaction carousel rotates about a quarter rotation every lockstep. In some examples, the reaction carousel is rotated for about one second of the four second lockstep time. During the advancement in this lockstep, about a quarter of the reaction vessels on the reaction carousel are passed in front of an analyzer (e.g., the analyzer 158) where the contents of the reaction vessels are analyzed. During the first few locksteps, all or most of the reaction vessels may be empty. However, in some examples, the reader continues to read, even if the data acquired is not used. By reading during every lockstep, the reader acquires a full range of readings during each reaction as the reactions are taking place. In other examples, the reader may delay reading for a predetermined amount of time and/or after a predetermined number reaction vessels are filled with sample and/or reagent.


The example process includes lockstep4X+2 (block 712). Assuming one full rotation has not yet occurred, X is zero and this is the second lockstep (i.e., lockstep(4*0)+2). During this second lockstep, a second function or test operation may be performed in connection with the reaction vessel if 4X+2=N2 (block 714). Similar to N1, N2 represents the specific timing of a specific function or test operation to be performed in connection with the reaction vessel. For example, in the example analyzer 100 disclosed above, the second pipetting mechanism 140 is disposed near the second carousel 104 and dispenses a first reagent into reaction vessels at point B. In some examples, the first carousel 102 includes an outer annular array of containers such as, for example, reagents used for first reagent. The second pipetting mechanism 140 aspirates from one of the containers on the outer annular array of containers and dispenses the liquid into a reaction vessel on the second carousel 104 at point B. In some examples, a reagent is to be dispensed into a reaction vessel during the second lockstep, wherein the first lockstep included adding sample to that reaction vessel. Therefore, for the function of dispensing a first reagent, N2 may be set to 2, such that if this is the second lockstep (block 714) for the reaction vessel, the function is performed (block 716), and a first reagent is dispensed into the reaction vessel (block 716) because 4X+2=N2 (e.g., (4*0)+2=2). If X is not zero such as, for example, during subsequent rotations, then the reaction vessel is idle (block 718) and, for example, no functions are performed on the reaction vessel by the operator or robotic mechanisms of the example analyzer 100, 500 at this lockstep because 4X+2≠N2 (e.g., (4*1)+2≠2). Thus, in this example, if the function is to occur only at the second lockstep (e.g., dispensing a first reagent), then the example system will sit idle during each subsequent occurrence of a second lockstep during subsequent rotations until, for example, the reaction vessel is washed and ready for a subsequent test and X is reset to zero for the subsequent implementation of the example process 700.


The example process 700 includes advancing to the next lockstep (block 720) and reading (e.g., analyzing) the contents the reaction vessel. During the advancement in this lockstep, about a quarter of the reaction vessels are passed in front of an analyzer (e.g., the analyzer 158) where the contents of the reaction vessels are analyzed.


The example process includes lockstep4X+3 (block 722). Assuming one full rotation has not yet occurred, X is zero and this is the third lockstep (i.e., lockstep(4*0)+3). During this third lockstep, a third function or test operation may be performed in connection with the reaction vessel if 4X+3=N3 (block 724). Similar to N1 and N2, N3 represents the specific timing or lockstep of a specific function or test operation to be performed in connection with the reaction vessel. For example, in the example analyzer 100 disclosed above, a first pipetting mechanism 130 is disposed within the second diameter 120 of the second carousel 104 and is to dispense a second reagent into reaction vessels on the second carousel 104 point A. In some examples, the first carousel 102 includes an inner annular array of containers 110a-n such as, for example, reagents used for a second reagent. The first pipetting mechanism 130 aspirates from one of the containers on the inner annular array of containers 110a-n and dispenses the liquid into a reaction vessel at point A. Therefore, the function of dispensing a second reagent may be activated for a particular vessel by setting N3 to any number of locksteps. In some examples, a diagnostic test includes adding a sample to a reaction vessel, adding a first reagent to the reaction vessel, and then incubating for a certain amount of time before dispensing the second reagent. In some examples, N3 can be set to 79, such that the reaction vessel will be at the 79th lockstep, or third lockstep of the 19th rotation of a testing (i.e., X=19) when the second reagent is added. Assuming each lockstep is about four seconds, the contents of the reaction vessel incubate for about five minutes before a second reagent is dispensed into the reaction vessel. Therefore, the function of dispensing a second reagent may be triggered by setting N3 to 79 so that at the 79th lockstep (block 724), the function is performed (block 728) and a second reagent is dispensed into the reaction vessel because 4X+3=N3 (e.g., (4*19)+3=79). If X is not 19 such as, for example, during previous rotations or subsequent rotations, then the reaction vessel is idle (block 726) and, for example, no functions are performed on the reaction vessel by the operator or robotic mechanism of the example analyzer 100, 500 at this lockstep because 4X+3≠N3 (e.g., (4*0)+3≠79). Thus, in this example, if the function is to occur only at the 79th lockstep, i.e., the third lockstep of the 19th rotation (e.g., dispensing a second reagent), then the example system will sit idle during each previous and subsequent occurrence of the third lockstep during previous and subsequent rotations until, for example, the reaction vessel is washed and ready for a subsequent test and X is reset to zero for the subsequent implementation of the example process 700.


The example process 700 includes advancing to the next lockstep (block 730) and reading (e.g., analyzing) the contents the reaction vessels that pass the reader.


The example process includes lockstep4X+4 (block 732). At the beginning, when a full rotation has not occurred yet, X is zero and this is the fourth lockstep (i.e., lockstep(4*0)+4). (block 732). During this fourth lockstep, another function or test operation may be performed in connection with the reaction vessel if 4X+4=N4 (block 734). Similar to N1, N2 and N3, N4 represents the specific timing of a specific function or test operation to be performed on the reaction vessel. For example, in the example analyzer 100 disclosed above, the wash zone 162 is disposed to wash reaction vessels at point D. In some examples, a reaction vessel is washed after a test has finished in the reaction vessel. Therefore, N4 can be set at any number to trigger the washing of a vessel. In some examples, a full test of a given sample occurs over about 37 full rotations of the carousel. Therefore, N4 may be set to 152, such that when X=37, the reaction vessel is washed (block 738) because 4X+4=N3 (e.g., (4*38)+4=156). If X is not 37 such as, for example, during the previous 36 rotations, then the reaction vessel is idle (block 736) and, for example, no functions are performed on the reaction vessel by the operator or any robotic mechanism of the example analyzer 100, 500 at this lockstep because 4X+4≠N4 (e.g., (4*0)+4≠156). Thus, in this example, if the function is to occur only at the 156th lockstep, i.e., the fourth lockstep of the 37th rotation (e.g., washing a reaction vessel), then the example system will sit idle during each previous occurrence of the fourth lockstep during previous rotations. Once the reaction vessel is washed and ready for a subsequent test and X is reset to zero for the subsequent implementation of the example process 700.


As noted above, in some examples, if the reaction vessel is washed (block 740), the process 700 ends (block 742) and may start over with a clean reaction vessel for a subsequent test. If the diagnostic testing is not complete, the reaction vessel is idle (block 740), and the reaction carousel advances to the next lockstep (block 744). The example process includes continuing with lockstep4X+1 (block 702), where “1” has been added to X because one full rotation has occurred. Therefore, the start of the second rotation, i.e., the first lockstep of the second rotation will be the fifth lockstep (i.e., lockstep(4*1)+1) (block 702). This process 700 may continue as many times as determined by the testing protocols and scheduling sequences.


Additionally, this example is viewed from the perspective of one reaction vessel progressing through a diagnostic test. However, multiple other reactions may be occurring during the same locksteps and may be performed using this process as well. Although the lockstep triggers N1, N2, N3 and N4 are described above as being associated with adding a sample, a first reagent, a second reagent, and a wash zone, respectively, N1-N4 may be associated with any function, test operation or instrument used in diagnostic testing such as, for example, an in track vortexer (e.g., a mixer), an incubator (e.g., a heat source), etc. Therefore, the process 700 allows a diagnostic test to be customized in regards to the timing and sequencing of the various functions to be performed in connection with one or more vessels and samples disposed therein.


Additionally, this example includes functions N1, N2, N3, and N4, for the respective locksteps during each rotation. However, in other examples, more than one function can be arranged at the each lockstep and distinguished by the number of rotations completed. For example, a first function may be performed during the first lockstep of the first rotation and a second function may be performed during the fifth lockstep (i.e., the first lockstep of the second rotation).



FIG. 8 illustrates an example timeline 800 that represents the timing of use for a number of specific functions performed during a diagnostic test such as, for example, those performed in the example analyzers 100, 500 disclosed above. The example analyzer 100 disclosed above includes the third pipetting mechanism 150 for dispensing sample at point C, the second pipetting mechanism 140 for dispensing a first reagent at point B, the first pipetting mechanism 130 to dispense a second reagent at point B, and the wash zone 162 to wash a reaction vessel at point D. For illustrative purposes, it is assumed that a number of tests are to be performed sequentially and/or concurrently starting with the first sample being dispensed into a first reaction vessel at T1. In some examples, the reaction carousel rotates in discrete locksteps. Every lockstep, the third pipetting mechanism dispenses a sample into a reaction vessel at point C 802. As shown, this function continues from T1 to T7. For example, if 187 tests are to be performed in 187 reaction vessels on the reaction carousel, then the third pipetting mechanism dispenses one sample into each reaction vessel at every lockstep until all the samples have been dispensed. Therefore, in some examples, T7 may represent the timing of when or the lockstep at which the last sample is dispensed into a reaction vessel.


The example timeline 800 also includes dispensing a first reagent using the second pipetting mechanism at point B 804. As mentioned above, in some examples, a first reagent is to be dispensed into a reaction vessel that was previously at point C (i.e., a reaction vessel including a sample). In this example, the second pipetting mechanism begins dispensing a first reagent to a reaction vessel at point B at time or lockstep T2. In this example, T2 may be one lockstep after the lockstep during which sample is added to the first reaction vessel. The second pipetting mechanism continues to dispense the first reagent until T8, which may be, for example, one lockstep after the last sample is dispensed into the last reaction vessel (i.e., once a first reagent has been added to every sample).


The example timeline 800 includes reading 806 the reaction vessels. In some examples, the reader analyzes the reaction vessels as the reaction vessels pass in front of the reader during the advancement portion of the lockstep. Therefore, assuming that each lockstep rotation is a about quarter rotation, and the reaction carousel has 187 reaction vessels, about 47 reaction vessels pass in front of the reader during each lockstep. During the first few locksteps of a diagnostic test, all or a majority of the reaction vessels passing in front of the reader are empty. Therefore, as shown in this example, the reader begins reading at time or lockstep T4, which may be, for example, when the first reaction vessel having a sample and a reagent passes in front of the reader. During every rotation, each reaction vessel is analyzed. In some examples, a full diagnostic test requires 38 reads and, thus, 38 full rotations. Therefore, the reader continues to read until T10, which may be, for example, when the last reaction vessel that was dispensed to has been read 38 times.


The example timeline 800 includes dispensing a second reagent 808, via the first pipetting mechanism, beginning at time or lockstep T5. In some examples, a test sample and a first reagent react for a period of time and then a second reagent is added. To ensure adequate incubation time, the second reagent may be dispensed after a set period of time or number of locksteps, T5. Starting at T5, the first pipetting mechanism dispenses a second reagent into the reaction vessels at point A. This continues until T9, which may be, for example, when the last reaction vessel reaches point A and, thus, all the reaction vessels have had a second reagent dispensed therein.


The example timeline 800 also includes a wash at point D 810. In the example analyzer 100, the wash zone 162 washes reaction vessels at point D. As mentioned above, some reactions may occur over 38 full rotations. After the 38th rotation, the reaction is to be washed out of the reaction vessel. Therefore, the wash begins at T6, which may be, for example, the time or lockstep at which the first reaction vessel has completed its full 38 rotation testing. The wash 810 continues to wash each vessel until T11, which may be, for example, when the last reaction completes its 38 rotation test.


The functions illustrated in FIG. 8 may operate simultaneously as the reaction carousel rotates, and different timing sequencing may be determined based on the types of tests to be conducted and the types of procedures to be performed. In addition, the functions may operate continually. For example, if a first reaction vessel is washed at T7, sample may be dispensed into that first reaction vessel at T8 for a subsequent test, and the remaining functions also may continue.



FIG. 9 is a block diagram of an example processor platform 900 capable of executing the one or more instructions of FIG. 7 to implement one or more portions of the apparatus and/or systems of FIGS. 1-6. The processor platform 900 can be, for example, a server, a personal computer, a mobile device (e.g., a cell phone, a smart phone, a tablet such as an iPad™), a personal digital assistant (PDA), an Internet appliance, and/or or any other type of computing device.


The processor platform 900 of the illustrated example includes a processor 912. The processor 912 of the illustrated example is hardware. For example, the processor 912 can be implemented by one or more integrated circuits, logic circuits, microprocessors or controllers from any desired family or manufacturer.


The processor 912 of the illustrated example includes a local memory 913 (e.g., a cache). The processor 912 of the illustrated example is in communication with a main memory including a volatile memory 814 and a non-volatile memory 916 via a bus 918. The volatile memory 914 may be implemented by Synchronous Dynamic Random Access Memory (SDRAM), Dynamic Random Access Memory (DRAM), RAMBUS Dynamic Random Access Memory (RDRAM) and/or any other type of random access memory device. The non-volatile memory 916 may be implemented by flash memory and/or any other desired type of memory device. Access to the main memory 914, 916 is controlled by a memory controller.


The processor platform 900 of the illustrated example also includes an interface circuit 920. The interface circuit 920 may be implemented by any type of interface standard, such as an Ethernet interface, a universal serial bus (USB), and/or a PCI EXPRESS® interface.


In the illustrated example, one or more input devices 922 are connected to the interface circuit 920. The input device(s) 922 permit(s) a user to enter data and commands into the processor 912. The input device(s) can be implemented by, for example, an audio sensor, a microphone, a camera (still or video), a keyboard, a button, a mouse, a touchscreen, a track-pad, a trackball, isopoint and/or a voice recognition system.


One or more output devices 924 are also connected to the interface circuit 920 of the illustrated example. The output devices 924 can be implemented, for example, by display devices (e.g., a light emitting diode (LED), an organic light emitting diode (OLED), a liquid crystal display, a cathode ray tube display (CRT), a touchscreen, a tactile output device and/or a light emitting diode (LED). The interface circuit 920 of the illustrated example, thus, typically includes a graphics driver card, a graphics driver chip or a graphics driver processor.


The interface circuit 920 of the illustrated example also includes a communication device such as a transmitter, a receiver, a transceiver, a modem and/or network interface card to facilitate exchange of data with external machines (e.g., computing devices of any kind) via a network 926 (e.g., an Ethernet connection, a digital subscriber line (DSL), a telephone line, coaxial cable, a cellular telephone system, etc.).


The processor platform 900 of the illustrated example also includes one or more mass storage devices 928 for storing software and/or data. Examples of such mass storage devices 928 include floppy disk drives, hard drive disks, compact disk drives, BLU-RAY-DISC™ drives, RAID systems, and digital versatile disk (DVD) drives.


Coded instructions 932 to implement the method of FIG. 7 may be stored in the mass storage device 928, in the volatile memory 914, in the non-volatile memory 916, and/or on a removable tangible computer readable storage medium such as a CD or DVD.


The example analyzers 100 and 500 described herein locate a first carousel beneath a second carousel, thereby reducing the footprint (e.g., width and length dimensions) of the analyzer. The example analyzers 100 and 500 also locate pipetting mechanisms within the dimensions of the first and/or second carousel to reduce the footprint and distance traveled by the pipetting mechanisms. Additionally, by reducing the footprint of the analyzer, the carousels may be relatively wider (e.g., having a greater diameter) and/or high and, thus, include more containers (e.g., reagents) to perform more tests.


Although certain example methods, apparatus and articles of manufacture have been described herein, the scope of coverage of this patent is not limited thereto. On the contrary, this patent covers all methods, apparatus and articles of manufacture fairly falling within the scope of the claims of this patent.

Claims
  • 1. An apparatus comprising: a first carousel rotatably coupled to a base, the first carousel rotatable about a first axis of rotation;a second carousel rotatably coupled to the base, the second carousel rotatable about a second axis of rotation, the second carousel disposed above the first carousel and, from a top plan view, within a circumference of the first carousel, the second carousel having a smaller diameter than the first carousel; anda pipetting mechanism rotatable about a third axis of rotation, the third axis of rotation offset from the second axis of rotation, the pipetting mechanism to access at least one of the first carousel or the second carousel.
  • 2. The apparatus of claim 1, wherein the third axis of rotation is disposed within the circumference of the first carousel.
  • 3. The apparatus of claim 2, wherein the circumference is a first circumference, the third axis of rotation disposed within a second circumference of the second carousel.
  • 4. The apparatus of claim 3, wherein the pipetting mechanism is a first pipetting mechanism, further including a second pipetting mechanism rotatable about a fourth axis of rotation, the second pipetting mechanism to access at least one of the first carousel or the second carousel.
  • 5. The apparatus of claim 4, wherein the fourth axis of rotation is disposed within the first circumference of the first carousel and outside of the second circumference of the second carousel.
  • 6. The apparatus of claim 5, further including a computer processor to execute instructions to: control the first pipetting mechanism to aspirate a first liquid from a first container on the first carousel and dispense the first liquid into a second container on the second carousel; andcontrol the second pipetting mechanism to aspirate a second liquid from a third container on the second carousel and dispense the second liquid into the second container or a fourth container on the second carousel.
  • 7. The apparatus of claim 5, further including a third pipetting mechanism rotatable about a fifth axis of rotation disposed outside of the first circumference and outside of the second circumference, the third pipetting mechanism to access the second carousel.
  • 8. The apparatus of claim 1, wherein the second carousel includes an annular rack having a bore, the third axis of rotation defined by a base assembly extending through the bore.
  • 9. The apparatus of claim 8, wherein the pipetting mechanism includes a pipette that is moveable through the bore to access a container on the first carousel.
  • 10. The apparatus of claim 8, further including a platform disposed between the first carousel and the second carousel, the base coupled to the platform.
  • 11. An apparatus comprising: a first carousel rotatably coupled to a base, the first carousel rotatable about a first axis of rotation;a second carousel rotatably coupled to the base and vertically spaced over the first carousel such that at least a portion of the second carousel is disposed over the first carousel, the second carousel rotatable about a second axis of rotation, the second carousel defining an annular rack having a bore; anda first pipette to access the first carousel and the second carousel, the first pipette movable through the bore of the second carousel to access the first carousel.
  • 12. The apparatus of claim 11, wherein the first pipette is rotatable about a third axis of rotation, the third axis of rotation disposed within a first circumference of the first carousel and a second circumference of the second carousel.
  • 13. The apparatus of claim 12, wherein the third axis of rotation is offset from the second axis of rotation.
  • 14. The apparatus of claim 12, further including a second pipette rotatable about a fourth axis of rotation, the fourth axis of rotation disposed within the first circumference and outside of the second circumference.
  • 15. The apparatus of claim 14, further including a third pipette rotatable about a fifth axis of rotation, the fifth axis of rotation disposed outside of the first circumference and outside of the second circumference.
  • 16. The apparatus of claim 15, wherein the second pipette and the third pipette are to access the second carousel.
  • 17. The apparatus of claim 11, wherein the second carousel has a smaller diameter than the first carousel.
RELATED APPLICATION

This patent arises from a continuation of U.S. application Ser. No. 15/218,833 know U.S. Pat. No. 10,197,585), titled “AUTOMATED DIAGNOSTIC ANALYZERS HAVING VERTICALLY ARRANGED CAROUSELS AND RELATED METHODS,” filed Jul. 25, 2016, which is a continuation of U.S. application Ser. No. 14/213,018 (now U.S. Pat. No. 9,400,285), titled “AUTOMATED DIAGNOSTIC ANALYZERS HAVING VERTICALLY ARRANGED CAROUSELS AND RELATED METHODS,” filed Mar. 14, 2014, which claims priority to and the benefit of U.S. Provisional Application No. 61/794,060, titled “AUTOMATED DIAGNOSTIC ANALYZERS HAVING VERTICALLY ARRANGED CAROUSELS AND RELATED METHODS,” filed Mar. 15, 2013. U.S. application Ser. No. 15/218,833; U.S. application Ser. No. 14/213,018; and U.S. Provisional Application No. 61/794,060 are incorporated herein by this reference in their entireties.

US Referenced Citations (439)
Number Name Date Kind
3449959 Grimshaw Jun 1969 A
3451433 Cunningham et al. Jun 1969 A
3484206 Loebl Dec 1969 A
4738825 Kelln et al. Apr 1988 A
4774055 Wakatake et al. Sep 1988 A
4808380 Minekane Feb 1989 A
4848917 Benin et al. Jul 1989 A
4849177 Jordan Jul 1989 A
4906433 Minekane Mar 1990 A
5037612 Takahashi et al. Aug 1991 A
5051238 Umetsu et al. Sep 1991 A
5071625 Kelln et al. Dec 1991 A
5077013 Guigan Dec 1991 A
5154896 Mochida et al. Oct 1992 A
5244633 Jakubowicz et al. Sep 1993 A
5250440 Kelln et al. Oct 1993 A
5266268 Antocci et al. Nov 1993 A
5270212 Horiuchi et al. Dec 1993 A
5311426 Donohue et al. May 1994 A
5314825 Weyrauch et al. May 1994 A
5316726 Babson et al. May 1994 A
5352612 Huber et al. Oct 1994 A
5358691 Clark et al. Oct 1994 A
5360597 Jakubowicz et al. Nov 1994 A
5419871 Muszak et al. May 1995 A
5422271 Chen et al. Jun 1995 A
5424036 Ushikubo Jun 1995 A
5424212 Pinsl-Ober et al. Jun 1995 A
5434083 Mitsumaki et al. Jul 1995 A
5439645 Saralegui Aug 1995 A
5439646 Tanimizu et al. Aug 1995 A
5443791 Cathcart et al. Aug 1995 A
5445794 Wihlborg Aug 1995 A
5447687 Lewis et al. Sep 1995 A
5455175 Wittwer et al. Oct 1995 A
5460780 Devaney, Jr. et al. Oct 1995 A
5460968 Yoshida et al. Oct 1995 A
5462715 Koch et al. Oct 1995 A
5466574 Liberti et al. Nov 1995 A
5470744 Astle Nov 1995 A
5482834 Gillespie Jan 1996 A
5482839 Ashihara et al. Jan 1996 A
5482861 Clark et al. Jan 1996 A
5518693 Tomasso et al. May 1996 A
5525300 Danssaert et al. Jun 1996 A
5527673 Reinhartz et al. Jun 1996 A
5536475 Moubayed et al. Jul 1996 A
5536481 Mabire et al. Jul 1996 A
5538849 Uematsu et al. Jul 1996 A
5538976 Okada et al. Jul 1996 A
5548826 Sayers Aug 1996 A
5558839 Matte et al. Sep 1996 A
5559002 Uzan et al. Sep 1996 A
5567595 Kok Oct 1996 A
5571325 Ueyama et al. Nov 1996 A
5571481 Powell et al. Nov 1996 A
5575976 Choperena et al. Nov 1996 A
5576215 Burns et al. Nov 1996 A
5578269 Yaremko et al. Nov 1996 A
5578270 Reichler et al. Nov 1996 A
5580524 Forrest et al. Dec 1996 A
5582796 Carey et al. Dec 1996 A
5585068 Panetz et al. Dec 1996 A
5587129 Kurosaki et al. Dec 1996 A
5589137 Markin et al. Dec 1996 A
5595707 Copeland et al. Jan 1997 A
5599501 Carey et al. Feb 1997 A
5611994 Bailey et al. Mar 1997 A
5620898 Yaremko et al. Apr 1997 A
5632399 Palmieri et al. May 1997 A
5637275 Carey et al. Jun 1997 A
5639425 Komiyama et al. Jun 1997 A
5650327 Copeland et al. Jul 1997 A
5653940 Carey et al. Aug 1997 A
5654199 Copeland et al. Aug 1997 A
5654200 Copeland et al. Aug 1997 A
5656493 Mullis et al. Aug 1997 A
5658532 Kurosaki et al. Aug 1997 A
5658799 Choperena et al. Aug 1997 A
5670114 Sakazume et al. Sep 1997 A
5670120 Degenhardt et al. Sep 1997 A
5670375 Seaton et al. Sep 1997 A
5677188 Mitsumaki et al. Oct 1997 A
5679309 Bell Oct 1997 A
5681530 Kuster et al. Oct 1997 A
5682026 Auclair et al. Oct 1997 A
5686046 Malek et al. Nov 1997 A
5693292 Choperena et al. Dec 1997 A
5698450 Ringrose et al. Dec 1997 A
5702950 Tajima Dec 1997 A
5705062 Knobel Jan 1998 A
5714380 Neri et al. Feb 1998 A
5716583 Smethers et al. Feb 1998 A
5717148 Ely et al. Feb 1998 A
5720377 Lapeus et al. Feb 1998 A
5720923 Haff et al. Feb 1998 A
5721141 Babson et al. Feb 1998 A
5723092 Babson Mar 1998 A
5730938 Carbonari et al. Mar 1998 A
5730939 Kurumada et al. Mar 1998 A
5736101 Gianino Apr 1998 A
5736105 Astle Apr 1998 A
5736413 Uzan et al. Apr 1998 A
5738827 Marquiss Apr 1998 A
5741461 Takahashi et al. Apr 1998 A
5741708 Carey et al. Apr 1998 A
5746977 Imai et al. May 1998 A
5746978 Bienhaus et al. May 1998 A
5748978 Narayan et al. May 1998 A
5750338 Collins et al. May 1998 A
5762872 Bühler et al. Jun 1998 A
5762873 Fanning et al. Jun 1998 A
5773268 Korenberg et al. Jun 1998 A
5773296 Montalbano et al. Jun 1998 A
5773662 Imai et al. Jun 1998 A
5779981 Danssaert et al. Jul 1998 A
5786182 Catanzariti et al. Jul 1998 A
5789252 Fujita et al. Aug 1998 A
5795547 Moser et al. Aug 1998 A
5795784 Arnquist et al. Aug 1998 A
5807523 Watts et al. Sep 1998 A
5814277 Bell et al. Sep 1998 A
5816998 Silverstolpe et al. Oct 1998 A
5826129 Hasebe et al. Oct 1998 A
5827478 Carey et al. Oct 1998 A
5827479 Yamazaki et al. Oct 1998 A
5827653 Sammes et al. Oct 1998 A
5837195 Malek et al. Nov 1998 A
5843376 Ishihara et al. Dec 1998 A
5846491 Choperena et al. Dec 1998 A
5849247 Uzan et al. Dec 1998 A
5855847 Oonuma et al. Jan 1999 A
5856194 Arnquist et al. Jan 1999 A
5863506 Farren Jan 1999 A
5876668 Kawashima et al. Mar 1999 A
5876670 Mitsumaki et al. Mar 1999 A
5882594 Kawaguchi et al. Mar 1999 A
5882596 Breeser et al. Mar 1999 A
5882918 Goffe Mar 1999 A
5885353 Strodtbeck et al. Mar 1999 A
5885529 Babson et al. Mar 1999 A
5885530 Babson et al. Mar 1999 A
5888454 Leistner et al. Mar 1999 A
5897783 Howe et al. Apr 1999 A
5902549 Mimura et al. May 1999 A
5919622 Macho et al. Jul 1999 A
5928952 Hutchins et al. Jul 1999 A
5935522 Swerdlow et al. Aug 1999 A
5948691 Ekiriwang et al. Sep 1999 A
5955373 Hutchins et al. Sep 1999 A
5958763 Goffe Sep 1999 A
5972295 Hanawa et al. Oct 1999 A
5985215 Sakazume et al. Nov 1999 A
5985670 Markin Nov 1999 A
5985671 Leistner et al. Nov 1999 A
5985672 Kegelman et al. Nov 1999 A
5988869 Davidson et al. Nov 1999 A
6019945 Ohishi et al. Feb 2000 A
6027691 Watts et al. Feb 2000 A
6033574 Siddiqi Mar 2000 A
6033880 Haff et al. Mar 2000 A
6042786 Oonuma et al. Mar 2000 A
6043880 Andrews et al. Mar 2000 A
6051101 Ohtani et al. Apr 2000 A
6056923 Diamond et al. May 2000 A
6060022 Pang et al. May 2000 A
6063340 Lewis et al. May 2000 A
6068393 Hutchins et al. May 2000 A
6068978 Zaun et al. May 2000 A
6071395 Lange Jun 2000 A
6071477 Auclair et al. Jun 2000 A
6074615 Lewis et al. Jun 2000 A
6080364 Mimura et al. Jun 2000 A
6086827 Horner et al. Jul 2000 A
6096272 Clark et al. Aug 2000 A
6103193 Iwahashi et al. Aug 2000 A
6106781 Rosenberg Aug 2000 A
6110676 Coull et al. Aug 2000 A
6110678 Weisburg et al. Aug 2000 A
6117392 Hanawa et al. Sep 2000 A
6117398 Bienhaus et al. Sep 2000 A
6117683 Kodama et al. Sep 2000 A
6143578 Bendele et al. Nov 2000 A
6146592 Kawashima et al. Nov 2000 A
6156565 Maes et al. Dec 2000 A
6165778 Kedar Dec 2000 A
6174670 Wittwer et al. Jan 2001 B1
6232079 Wittwer et al. May 2001 B1
6245514 Wittwer Jun 2001 B1
6261521 Mimura et al. Jul 2001 B1
6267927 Pomar Longedo et al. Jul 2001 B1
6270726 Tyberg et al. Aug 2001 B1
6277332 Sucholeiki Aug 2001 B1
6293750 Cohen et al. Sep 2001 B1
6299567 Forrest et al. Oct 2001 B1
6300068 Burg et al. Oct 2001 B1
6300138 Gleason et al. Oct 2001 B1
6319718 Matsubara et al. Nov 2001 B1
6332636 Cohen et al. Dec 2001 B1
6335166 Ammann et al. Jan 2002 B1
6337050 Takahashi et al. Jan 2002 B1
6352861 Copeland et al. Mar 2002 B1
6374982 Cohen et al. Apr 2002 B1
6375898 Ulrich Apr 2002 B1
6377342 Coeurveille Apr 2002 B1
6386749 Watts et al. May 2002 B1
6399952 Maher et al. Jun 2002 B1
6436349 Carey et al. Aug 2002 B1
6444171 Sakazume et al. Sep 2002 B1
6455325 Tajima Sep 2002 B1
6461570 Ishihara Oct 2002 B2
6472217 Richards et al. Oct 2002 B1
6498037 Carey et al. Dec 2002 B1
6503751 Hugh Jan 2003 B2
6509193 Tajima Jan 2003 B1
6517782 Horner et al. Feb 2003 B1
6517783 Horner et al. Feb 2003 B2
6521183 Burri et al. Feb 2003 B1
6522976 Shiba et al. Feb 2003 B2
6551833 Lehtinen et al. Apr 2003 B1
6562298 Arnquist et al. May 2003 B1
6569627 Wittwer et al. May 2003 B2
6579717 Matsubara et al. Jun 2003 B1
6586234 Burg et al. Jul 2003 B1
6592818 Ishihara et al. Jul 2003 B2
6597450 Andrews et al. Jul 2003 B1
6599749 Kodama et al. Jul 2003 B1
6605213 Ammann et al. Aug 2003 B1
6632654 Gebrian et al. Oct 2003 B1
6709634 Okada et al. Mar 2004 B1
6723288 Devlin, Sr. et al. Apr 2004 B2
6733728 Mimura et al. May 2004 B1
6752967 Farina et al. Jun 2004 B2
6764649 Ammann Jul 2004 B2
6764650 Takahashi et al. Jul 2004 B2
6776961 Lindsey et al. Aug 2004 B2
6780617 Chen Aug 2004 B2
6787338 Wittwer et al. Sep 2004 B2
6825921 Modlin et al. Nov 2004 B1
6827901 Copeland et al. Dec 2004 B2
6866821 Friedlander et al. Mar 2005 B2
6878343 Sklar et al. Apr 2005 B2
6890742 Ammann et al. May 2005 B2
6911327 McMillan et al. Jun 2005 B2
6919058 Andersson et al. Jul 2005 B2
6919175 Bienhaus et al. Jul 2005 B1
6924152 Matsubara et al. Aug 2005 B2
6943029 Coepland et al. Sep 2005 B2
6958130 Gicquel et al. Oct 2005 B1
7011792 Mimura et al. Mar 2006 B2
7028831 Veiner Apr 2006 B2
7029922 Miller Apr 2006 B2
7033820 Ammann Apr 2006 B2
7081226 Wittwer et al. Jul 2006 B1
7105351 Matsubara et al. Sep 2006 B2
7115090 Lagarde Oct 2006 B2
7115384 Clark et al. Oct 2006 B2
7118892 Ammann et al. Oct 2006 B2
7118918 Copeland et al. Oct 2006 B2
7118982 Govyadinov et al. Oct 2006 B2
7132082 Aviles et al. Nov 2006 B2
7135145 Ammann et al. Nov 2006 B2
7138091 Lee et al. Nov 2006 B2
7141213 Pang et al. Nov 2006 B1
7160998 Wittwer et al. Jan 2007 B2
7169356 Gebrian et al. Jan 2007 B2
7171863 Tamura et al. Feb 2007 B2
7182912 Carey et al. Feb 2007 B2
7217391 Gjerdingen May 2007 B2
7217513 Parameswaran et al. May 2007 B2
7220589 Richards et al. May 2007 B2
7250303 Jakubowicz et al. Jul 2007 B2
7264111 Veiner Sep 2007 B2
7267795 Ammann et al. Sep 2007 B2
7270783 Takase et al. Sep 2007 B2
7273749 Wittwer et al. Sep 2007 B1
7276208 Sevigny et al. Oct 2007 B2
7303139 Rudloff Dec 2007 B1
7331474 Veiner et al. Feb 2008 B2
7341691 Tamura et al. Mar 2008 B2
7360984 Sugiyama et al. Apr 2008 B1
7361305 Mimura et al. Apr 2008 B2
7381370 Chow et al. Jun 2008 B2
7384600 Burns et al. Jun 2008 B2
7390458 Burow et al. Jun 2008 B2
7396509 Burns Jul 2008 B2
7402281 Huynh-Ba et al. Jul 2008 B2
7407627 Rosenberg et al. Aug 2008 B1
7482143 Ammann et al. Jan 2009 B2
7524652 Ammann et al. Apr 2009 B2
7560255 Ammann et al. Jul 2009 B2
7560256 Ammann et al. Jul 2009 B2
7575937 Wiggli et al. Aug 2009 B2
7611675 Sevigny et al. Nov 2009 B2
7622078 Pagés Pinyol Nov 2009 B2
7638337 Ammann et al. Dec 2009 B2
7641855 Farina et al. Jan 2010 B2
7666602 Ammann et al. Feb 2010 B2
7666681 Ammann et al. Feb 2010 B2
7670553 Babson Mar 2010 B2
7670554 Chow et al. Mar 2010 B2
7670832 Wittwer et al. Mar 2010 B2
7700042 Matsumoto et al. Apr 2010 B2
7700043 Mimura et al. Apr 2010 B2
7731414 Vincent et al. Jun 2010 B2
7731898 Burkhardt et al. Jun 2010 B2
7745205 Wittwer et al. Jun 2010 B2
7749441 Hanawa et al. Jul 2010 B2
7785534 Watari Aug 2010 B2
7815858 Sevigny et al. Oct 2010 B2
7827874 Tsujimura et al. Nov 2010 B2
7837452 Ignatiev et al. Nov 2010 B2
7842237 Shibuya et al. Nov 2010 B1
7842504 Devlin, Sr. Nov 2010 B2
7850914 Veiner et al. Dec 2010 B2
7854892 Veiner et al. Dec 2010 B2
7855084 Jakubowicz et al. Dec 2010 B2
7858032 Le Comte et al. Dec 2010 B2
7867777 Aviles et al. Jan 2011 B2
7910294 Karlsen Mar 2011 B2
7939036 Burkhardt et al. May 2011 B2
7941904 Smith May 2011 B2
7943100 Rousseau May 2011 B2
7947225 Itoh May 2011 B2
7951329 Malyarov et al. May 2011 B2
7964140 Watari Jun 2011 B2
7985375 Edens et al. Jul 2011 B2
7998409 Veiner et al. Aug 2011 B2
7998432 Rousseau Aug 2011 B2
7998751 Evers et al. Aug 2011 B2
8003050 Burkhardt et al. Aug 2011 B2
8012419 Ammann et al. Sep 2011 B2
8038941 Devlin, Sr. Oct 2011 B2
8038942 Pang et al. Oct 2011 B2
8047086 Smith Nov 2011 B2
8066943 Kegelman et al. Nov 2011 B2
8071053 Matsuzaki et al. Dec 2011 B2
8097211 Hamada et al. Jan 2012 B2
8114351 Degenhardt et al. Feb 2012 B2
8119080 Wiggli et al. Feb 2012 B2
8137620 Ammann et al. Mar 2012 B2
8142740 Self et al. Mar 2012 B2
8147777 Schacher et al. Apr 2012 B2
8153061 Walters et al. Apr 2012 B2
8154899 Degroot Apr 2012 B2
8158058 Shiba et al. Apr 2012 B2
8161831 Fukuma Apr 2012 B2
8163239 Fujita Apr 2012 B2
8178043 Burkhardt et al. May 2012 B2
8187558 Jacobs et al. May 2012 B2
8192992 Ammann et al. Jun 2012 B2
8221682 Ammann et al. Jul 2012 B2
8226387 Ignatiev Jul 2012 B2
8234941 Fukuda et al. Aug 2012 B2
8257650 Chow et al. Sep 2012 B2
8257664 Ogusu Sep 2012 B2
8262994 Hamada et al. Sep 2012 B2
8262999 Kaneblei et al. Sep 2012 B2
8266973 Maeda et al. Sep 2012 B2
8293191 Kohara et al. Oct 2012 B2
8309358 Ammann et al. Nov 2012 B2
8318500 Ammann et al. Nov 2012 B2
8329101 Fujita Dec 2012 B2
8333936 Miyashita et al. Dec 2012 B2
8337753 Ammann et al. Dec 2012 B2
8343423 Mori et al. Jan 2013 B2
8343754 Wittwer et al. Jan 2013 B2
8343770 Hamada et al. Jan 2013 B2
8354078 Shohmi et al. Jan 2013 B2
8355132 Xia et al. Jan 2013 B2
8356525 Hamada et al. Jan 2013 B2
8357538 Self et al. Jan 2013 B2
8366997 Degroot Feb 2013 B2
8383039 Zhou et al. Feb 2013 B2
8431079 Rosenberg et al. Apr 2013 B2
8501496 Zuk et al. Aug 2013 B2
8545757 Utsugi et al. Oct 2013 B2
8556564 Miller Oct 2013 B2
9274133 Kraemer et al. Mar 2016 B2
10197585 Ochranek et al. Feb 2019 B2
20020155590 Gerbian et al. Oct 2002 A1
20020164807 Itaya et al. Nov 2002 A1
20040134750 Luoma, II Jul 2004 A1
20050014285 Miller Jan 2005 A1
20050220670 Palmieri et al. Oct 2005 A1
20050249634 Devlin, Sr. Nov 2005 A1
20060159587 Fechtner et al. Jul 2006 A1
20060263248 Gomm et al. Nov 2006 A1
20060286004 Jacobs et al. Dec 2006 A1
20070010019 Luoma, II Jan 2007 A1
20070059209 Pang et al. Mar 2007 A1
20070092390 Ignatiev et al. Apr 2007 A1
20070172902 Zhang et al. Jul 2007 A1
20080145939 Jakubowicz et al. Jun 2008 A1
20080193332 Talmer et al. Aug 2008 A1
20090017491 Lemme et al. Jan 2009 A1
20090129979 Kegelman et al. May 2009 A1
20090148345 Hamazumi et al. Jun 2009 A1
20090227033 Hamada et al. Sep 2009 A1
20090258414 Wittwer et al. Oct 2009 A1
20100111765 Gomm et al. May 2010 A1
20100126286 Self et al. May 2010 A1
20100187253 Vincent et al. Jul 2010 A1
20100205139 Xia et al. Aug 2010 A1
20100276445 Jacobs et al. Nov 2010 A1
20100330609 Nagai et al. Dec 2010 A1
20100332144 Nagai et al. Dec 2010 A1
20110044834 Ignatiev Feb 2011 A1
20110097240 Yamashita et al. Apr 2011 A1
20110157580 Nogami et al. Jun 2011 A1
20110293475 Rosenberg et al. Dec 2011 A1
20110312082 Silverbrook et al. Dec 2011 A1
20120039748 Mimura et al. Feb 2012 A1
20120039771 Utsugi et al. Feb 2012 A1
20120114526 Watanabe et al. May 2012 A1
20120156764 Kondo Jun 2012 A1
20120183438 Shiba et al. Jul 2012 A1
20120218854 Behringer et al. Aug 2012 A1
20120258004 Ignatiev et al. Oct 2012 A1
20120294763 Fukuda et al. Nov 2012 A1
20120301359 Kraemer et al. Nov 2012 A1
20130017535 Frey et al. Jan 2013 A1
20130064737 Mori et al. Mar 2013 A1
20130065797 Silbert et al. Mar 2013 A1
20130078617 Ueda et al. Mar 2013 A1
20130089464 Sakashita et al. Apr 2013 A1
20130112014 Hamada et al. May 2013 A1
20130125675 Muller et al. May 2013 A1
20130280129 Watanabe et al. Oct 2013 A1
20130280130 Sarwar et al. Oct 2013 A1
20130323758 Oguri et al. Dec 2013 A1
20140011295 Ammann et al. Jan 2014 A1
20140093975 Wang et al. Apr 2014 A1
20140147922 Knofe et al. May 2014 A1
20140248619 Ammann et al. Sep 2014 A1
20140322080 Sarwar et al. Oct 2014 A1
20150037211 Wang et al. Feb 2015 A1
20150079695 Pollack et al. Mar 2015 A1
20160334430 Ochranek et al. Nov 2016 A1
Foreign Referenced Citations (66)
Number Date Country
100448969 Jan 2009 CN
102221625 Oct 2011 CN
102520200 Jun 2012 CN
112010001896 Jun 2012 DE
0576291 Dec 1993 EP
0779514 Jun 1997 EP
0871892 Jun 1997 EP
0831330 Mar 1998 EP
1414573 Mar 2003 EP
2068154 Jun 2009 EP
2362228 Aug 2011 EP
2808683 Dec 2014 EP
357019667 Feb 1982 JP
359116047 Jul 1984 JP
61095248 May 1986 JP
63-150375 Oct 1988 JP
S63150375 Oct 1988 JP
H01277761 Nov 1989 JP
H0526883 Feb 1993 JP
406027004 Feb 1994 JP
H0634641 Feb 1994 JP
H0666812 Mar 1994 JP
407181129 Jul 1995 JP
H1062432 Mar 1998 JP
2001165937 Jun 2001 JP
2001305145 Oct 2001 JP
2002503346 Jan 2002 JP
3582240 Oct 2004 JP
2005128037 May 2005 JP
2005533641 Nov 2005 JP
2006034639 Feb 2006 JP
2006506541 Feb 2006 JP
2008224439 Sep 2008 JP
2008309661 Dec 2008 JP
2009031204 Feb 2009 JP
2009053027 Mar 2009 JP
2009145202 Jul 2009 JP
2009288094 Dec 2009 JP
2010101726 May 2010 JP
2010217047 Sep 2010 JP
2010533299 Oct 2010 JP
2010267936 Nov 2010 JP
2011149832 Aug 2011 JP
2012021926 Feb 2012 JP
2012132721 Jul 2012 JP
2012173180 Sep 2012 JP
2012189611 Oct 2012 JP
2012233923 Nov 2012 JP
2012251804 Dec 2012 JP
2012251909 Dec 2012 JP
2012255664 Dec 2012 JP
5178891 Apr 2013 JP
227044 Jul 1994 TW
9315408 Aug 1993 WO
9722006 Jun 1997 WO
03018195 Mar 2003 WO
2009009419 Jan 2009 WO
2010026837 Mar 2010 WO
2010095375 Aug 2010 WO
2010106885 Sep 2010 WO
2012114675 Aug 2012 WO
2012137019 Oct 2012 WO
2013053023 Apr 2013 WO
2013064561 May 2013 WO
2013064562 May 2013 WO
2013111484 Aug 2013 WO
Non-Patent Literature Citations (24)
Entry
The International Searching Authority, “International Preliminary Report on Patentability and Written Opinion”, issued in connection with International patent Application No. PCT/US2014/029118, dated Sep. 24, 2015, 6 pages.
The European Patent Office, “Communication Pursuant to Rules 161 and 162 EPC”, issued in connection with European Patent Application 14717953.5, dated Oct. 23, 2015, 2 pages.
The International Searching Authority, “International Search Report and Written Opinion” issued in connection with International Patent Application No. PCT/US2013/07804, dated Sep. 19, 2014, 16 pages.
The International Searching Authority “International Search Report and Written Opinion”, issued in connection with corresponding International Patent Application No. PCT/US2014/029138, dated Jun. 23, 2014, 8 pages.
The International Searching Authority, “International Search Report and Written Opinion”, issued in connection with corresponding International Patent Application No. PCT/US2014/029118, dated Jun. 27, 2014, 9 pages.
The International Searching Authority, “Invitation to Pay Additional Fees and, Where Applicable, Protest Fee and Communication Relating to the Results of the Partial International Search”, issued in connection with corresponding International Patent Application No. PCT/US2013/078041, dated Apr. 9, 2014, 6 pages.
The Untied States Patent and Trademark Office “Office Action”, issued in connection with U.S. Appl. No. 14/213,048, dated Apr. 23, 2015, 12 pages.
The Untied States Patent and Trademark Office, “Notice of Allowance and Fee(s) Due”, issued by the in connection with U.S. Appl. No. 14/213,048, dated Jan. 12, 2016, 10 pages.
The Untied States Patent and Trademark Office, “Notice of Allowance and Fee(s) Due”, issued in connection with U.S. Appl. No. 14/213,048, dated Apr. 11, 2016, 4 pages.
The Untied States Patent and Trademark Office “Office Action”, issued in connection with U.S. Appl. No. 14/213,018, dated Apr. 29, 2015, 13 pages.
The Untied States Patent and Trademark Office, “Final Rejection”, issued in connection with U.S. Appl. No. 14/213,018, dated Jan. 7, 2016, 15 pages.
The Untied States Patent and Trademark Office, “Notice of Allowance and Fee(s) Due”, issued in connection with U.S. Appl. No. 14/213,018, dated Mar. 16, 2016, 2016, 10 pages.
The Untied States Patent and Trademark Office, “Notice of Allowance and Fee(s) Due”, issued in connection with U.S. Appl. No. 14/213,018, dated Jun. 15, 2016, 4 pages.
The Untied States Patent and Trademark Office, “Notice of Allowance and Fee(s) Due”, issued in connection with U.S. Appl. No. 14/213,018, dated Jun. 23, 2016, 4 pages.
The State Intellectual Property Office of the P.R. China, “Notification of the First Office Action and Search Report”, issued in connection with Chinese Patent Application No. 201480027844.3, dated Jul. 5 2016, 22 pages.
Japanese Patent Office, “Office Action,” issued in connection with Japanese Patent Application No. 2016-502992, dated Jan. 16, 2018, 8 pages.
Japanese Patent Office, “First Office Action,” issued in connection with Japanese Patent Application No. 2016-502992, dated May 30, 2017, 15 pages.
State Intellectual Property Office of China, “Second Office Action,” issued in connection with Chinese Patent Application No. 201480027844.3, dated Apr. 7, 2017, 19 pages.
State Intellectual Property Office of China, “Third Office Action,” issued in connection with Chinese Patent Application No. 201480027844.3, dated Oct. 26, 2017, 3 pages.
Untied States Patent & Trademark Office, “Restriction Requirement”, issued in connection with U.S. Appl. No. 15/218,833, dated Feb. 23, 2018, 7 pages.
Untied States Patent & Trademark Office, “Non-Final Office Action”, issued in connection with U.S. Appl. No. 15/218,833, dated May 8, 2018, 74 pages.
United States Patent & Trademark Office, “Non-Final Office Action”, issued in connection with U.S. Appl. No. 15/218,833, dated May 8, 2018, 74 pages.
Japanese Patent Office, “Decision of Patent”, issued in connection with Japanese Application No. 2018-107930, dated Jan. 28, 2020, 3 pages.
Japanese Paptent Office, “First Office Action”, issued in connection with Japanese Application No. 2018-107930, dated Jun. 25, 2019, 7 pages.
Related Publications (1)
Number Date Country
20190137530 A1 May 2019 US
Provisional Applications (1)
Number Date Country
61794060 Mar 2013 US
Continuations (2)
Number Date Country
Parent 15218833 Jul 2016 US
Child 16240105 US
Parent 14213018 Mar 2014 US
Child 15218833 US