Apparatus, system, and method for analyte measurement in interstitial fluid

Abstract

The analyte monitor includes a controller including a processor coupled to a memory. The memory has stored therein instructions that, when executed by the processor, cause the controller to provide a working electrode voltage to a working electrode of the analyte sensor; selectively provide a first counter electrode voltage and a second counter electrode voltage to a counter electrode of the analyte sensor; and provide a guard ring voltage to a guard ring associated with the working electrode. The analyte monitor further includes a current measurement circuit coupled to the controller and configured to measure a current to the working electrode, and a reference resistor electrically coupled between the working electrode and the guard ring associated with the working electrode. Other monitors, systems, sensors, and methods are disclosed.

Description

Technical Field

[0001] Cross - Reference to Related Applications This application claims the benefit of U.S. Provisional Patent Application No. 62 / 933,308, filed on November 8, 2019, entitled "DEVICES, SYSTEMS, AND METHODS FOR MEASURING ANALYTES IN INTERSTITIAL FLUID", the disclosure of which is hereby incorporated by reference in its entirety for all purposes.

[0002] This disclosure relates to devices, systems, and methods adapted to measure analytes in interstitial fluid.

Background Art

[0003] Sustained analyte detection in in - vivo and / or in - vitro samples, such as continuous glucose monitoring (CGM), has become routine, especially in diabetes care. By providing real - time glucose concentrations, treatment / clinical actions can be applied more timely, and glycemic status can be better controlled.

[0004] During CGM operation, a biosensor is typically inserted subcutaneously and operates continuously in an environment surrounded by tissue and interstitial fluid. The subcutaneously inserted biosensor provides a signal to a wireless CGM transmitter of a CGM sensor device, and that signal indicates the user's blood glucose value. These measurements can be automatically performed many times throughout the day (e.g., every few minutes or at other intervals).

[0005] The wireless CGM transmitter can be attached to the outer surface of the user's skin, such as the abdomen or the posterior upper arm, while the biosensor is inserted through the skin to contact the interstitial fluid.

[0006] To ensure accurate glucose measurements, a CGM device may perform self-diagnostics periodically to confirm proper operation of the biosensor and the CGM transmitter. Since a self-test system requires additional switches and other hardware, it may increase the complexity and cost of the CGM transmitter. Therefore, an improved system, method, and apparatus for confirming proper operation of a CGM transmitter and a biosensor are desired.

SUMMARY OF THE INVENTION

[0007] According to a first aspect, an analyte monitor is disclosed. The analyte monitor includes a controller that includes a processor coupled to a memory, the memory having instructions stored therein that, when executed by the processor, cause the controller to: cause an operating electrode voltage to be provided to the working electrode of an analyte sensor; selectively cause a first counter electrode voltage and a second counter electrode voltage to be provided to the counter electrode of the analyte sensor; cause a guard ring voltage to be provided to a guard ring that at least partially surrounds a contact area of the working electrode. The analyte monitor also includes a current measurement circuit coupled to the controller and configured to measure a current to the working electrode. The analyte monitor further includes a reference resistor electrically coupled between the working electrode and the guard ring. The memory further includes instructions that, when executed by the processor, cause the controller to perform at least one integrity check by applying the operating electrode voltage to the working electrode, applying the first counter electrode voltage or the second counter electrode voltage to the counter electrode, applying the guard ring voltage to the guard ring, and measuring the current to the working electrode using the current measurement circuit.

[0008] According to a second aspect, an analyte monitoring system is disclosed. The analyte monitoring system includes: an analyte sensor having a working electrode and a counter electrode; a guard ring surrounding at least a portion of the contact area of the working electrode; a reference resistor electrically connected between the working electrode and the guard ring; and an analyte transmitter coupled to the analyte sensor. The analyte transmitter includes a controller that includes a processor coupled to a memory, the memory having instructions stored therein that, when executed by the processor, cause the controller to: provide a working electrode voltage to the working electrode of the analyte sensor, selectively provide a first counter electrode voltage and a second counter electrode voltage to the counter electrode of the analyte sensor, and provide a guard ring voltage to the guard ring. The analyte transmitter also includes a current measurement circuit coupled to the controller and configured to measure a current to the working electrode. The memory, when executed by the processor, further causes the controller to perform at least one integrity check by: applying the working electrode voltage to the working electrode, applying the first counter electrode voltage or the second counter electrode voltage to the counter electrode, applying the guard ring voltage to the guard ring, and measuring the current to the working electrode using the current measurement circuit.

[0009] In a third aspect, a method of operating an analyte monitoring system is disclosed. The method includes: providing an analyte sensor having a working electrode and a counter electrode; providing a guard ring surrounding at least a portion of the contact area of the working electrode; providing a reference resistor connected between the working electrode and the guard ring; applying a working electrode voltage to the working electrode; selectively applying one of a first counter electrode voltage and a second counter electrode voltage to the counter electrode; applying at least a first guard ring voltage to the guard ring; and measuring a current to the working electrode.

[0010] In another aspect, an analyte sensor configured to be attached to the skin is disclosed. The analyte sensor includes: a working electrode; a guard ring surrounding at least a portion of the contact area of the working electrode; and a reference resistor connected between the working electrode and the guard ring.

[0011] Further other aspects, features, and advantages of the present disclosure may be readily apparent from the following description that explains some exemplary embodiments and examples. The present disclosure can also take other different embodiments, and some of its details can be modified in various respects without departing from its scope. Accordingly, the drawings and description are to be regarded essentially as illustrative and not as restrictive. The present disclosure encompasses all modifications, equivalents, and alternatives included in the claims.

Brief Description of the Drawings

[0012] The drawings described below are for illustrative purposes only and are not necessarily drawn to an exact scale. The drawings are not intended to limit the scope of the present disclosure in any way. The same numerals are used throughout to indicate the same or similar elements.

[0013]

Fig. 1A

[0014]

Fig. 1B

[0015]

Fig. 1C

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Fig. 2

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Fig. 3

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Fig. 4

[0019]

Fig. 5

[0020]

Fig. 6

[0021]

Fig. 7

[0022]

Fig. 8

[0023] A Continuous Analyte Monitoring (CAM) system can monitor the current between two or more points in interstitial fluid and determine the analyte concentration (e.g., glucose concentration) in the interstitial fluid. The CAM system can include an analyte transmitter electrically coupled to an analyte sensor (e.g., a glucose sensor). The analyte transmitter can include an analog front end having a contact area that electrically couples to the contact area of the electrodes of the analyte sensor, such as a working electrode, a counter electrode, a reference electrode, and / or the like, which creates an electrical connection between the CAM transmitter and the electrodes of the analyte sensor.

[0024] The analyte sensor can be coupled to a base plate at a contact area of the base plate. The base plate can be attached to the user's skin, and the analyte transmitter can be coupled to the base plate. The needle of the analyte sensor extends from the base plate through the user's skin and is configured to be disposed subcutaneously to contact the user's interstitial fluid. The needle includes electrodes of the analyte sensor, such as a working electrode, a counter electrode, and a reference electrode, which contact the interstitial fluid under the user's skin. The analyte transmitter and / or the base plate can include one or more guard rings that at least partially surround the contact area of the working electrode and / or the reference electrode of the analyte sensor. For example, in some embodiments, the guard ring can surround 50% or more of, and / or substantially surround, the contact area of the electrode.

[0025] During CAM, a voltage is applied between the working electrode and the counter electrode, and the current between the electrodes is measured. The current between the electrodes is proportional to the concentration of the analyte (e.g., glucose) in the interstitial fluid. The same voltage applied to the working electrode is applied to the guard ring associated with the working electrode to prevent current from passing through contaminants on the base plate and / or to prevent the analyte transmitter from interfering with the current measurement through the interstitial fluid. The current through the interstitial fluid can be very small, such as in the nanoampere range, thereby making the sensitivity of the analyte monitoring system very high. Integrity checks (e.g., self-diagnostic routines) can be performed by the CAM system to ensure that the system is operating accurately.

[0026] Embodiments of the analyte monitoring system disclosed herein may include a reference resistor electrically connected between a guard ring (associated with the working electrode) and the working electrode. During a first integrity check, the voltages applied to the working electrode, the guard ring, and the counter electrode are set equal. If the analyte transmitter and / or the analyte sensor are operating properly, since all are set to the same voltage, there will be little or no current between the guard ring and the electrode. Any current or current exceeding a predetermined (e.g., threshold) number of amperes may indicate a malfunction in the analyte monitoring system (e.g., due to an electrical connection error or contamination of the analyte transmitter, baseplate or sensor).

[0027] During a second integrity check, the voltages applied to the working electrode and the counter electrode may be equal, while the voltage applied to the guard ring may be different from the voltage applied to the working electrode. If the analyte transmitter and / or the analyte sensor are operating properly, little or no current will flow between the working electrode and the counter electrode. However, between the guard ring and the working electrode, current must flow only through the reference resistor. The magnitude of the current must be equal to the voltage difference between the working electrode and the guard ring divided by the resistance of the reference resistor. If other current is measured, there may be a malfunction in the analyte monitoring system (e.g., due to an electrical connection error or contamination of the analyte transmitter, baseplate or sensor).

[0028] These and other embodiments are described in detail with reference to FIGS. 1A-8 of this specification. Although mainly described with respect to glucose concentration determination using a glucose monitoring system, the embodiments described herein can be used with other analyte monitoring systems (e.g., cholesterol, lactate, uric acid, alcohol, or other analyte monitoring systems).

[0029] Refer to FIG. 1A, which shows a partial cross-sectional side view of a glucose monitoring system 100 including a glucose transmitter 102 and a glucose sensor assembly 104. The glucose transmitter 102 is shown separated from the glucose sensor assembly 104 and shows various features described below, and the glucose sensor assembly 104 is shown attached to the skin 106. Also refer to FIG. 1B, which shows a bottom view of one embodiment of the glucose transmitter 102. The interstitial fluid 108 is located below the skin 106. The components of the glucose monitoring system 100 and the skin 106 may not be drawn to scale. The glucose sensor assembly 104 may include a substrate 110 (e.g., a base plate) on which the components of the glucose sensor assembly 104 are located. The portion of the substrate 110 may be made of a non-conductive material such as plastic, ceramic, or another suitable material. In some embodiments, the substrate 110 may include a laminated material. The substrate 110 may include an electrical trace (not shown) that conducts current to or through components located in or attached to the substrate 110. An adhesive 112 such as acrylic or silicone may attach the substrate 110 to the outer surface of the skin 106.

[0030] In the embodiments of FIGS. 1A-1B, the glucose sensor assembly 104 may include a sensor electrode contact region 114A including a working electrode contact region 116A, a reference electrode contact region 118A, and a counter electrode contact region 120A for contacting a working electrode 117, a reference electrode 119, and a counter electrode 121, respectively, as further described below. Fewer or more electrode contact regions and / or electrodes, and / or other suitable electrode configurations may be used. For example, in some embodiments, a second working electrode (e.g., a background electrode) may be used. The electrodes 117, 119, and 121 may be formed by and / or encapsulated in a needle 122 configured to be positioned at least partially below the skin 106 of the interstitial fluid 108 such that the electrodes 117, 119, and 121 contact the interstitial fluid and can conduct current through the sensor electrode contact regions 116A, 118A, and 120A.

[0031] The glucose transmitter 102 may include a surface 124 where the transmitter contact region 114B is located. The transmitter contact region 114B may include corresponding individual contact regions as the sensor electrode contact region 114A. For example, the transmitter contact region 114B may include a working electrode contact region 116B, a reference electrode contact region 118B, and a counter electrode contact region 120B. The individual contact regions of the sensor electrode contact region 114A and the transmitter contact region 114B may have any shape such as circular, elliptical, square, and rectangular.

[0032] In addition to the contact regions described above, the glucose transmitter 102 and / or the glucose sensor assembly 104 may have a guard ring that at least partially surrounds at least one of the contact regions. In the embodiments illustrated in FIGS. 1A and 1B, the glucose sensor assembly 104 includes a working electrode guard ring 128A that surrounds at least a portion of the working electrode contact region 116A. The glucose sensor assembly 104 may also include a reference electrode guard ring 130A that surrounds at least a portion of the reference electrode contact region 118A. The glucose transmitter 102 may include a working electrode guard ring 128B that surrounds at least a portion of the working electrode contact region 116B, and a reference electrode guard ring 130B that surrounds at least a portion of the reference electrode contact region 118B.

[0033] During operation of the glucose monitoring system 100, the glucose transmitter 102 and the glucose sensor assembly 104 can be attached together as shown in FIG. 1C such that the transmitter contact region 114B is in electrical contact with the sensor electrode contact region 114A. The guard ring of the glucose transmitter 102 can also be in electrical contact with each guard ring of the glucose sensor assembly 104. When the glucose sensor assembly 104 is attached to the glucose transmitter 102, the working electrode contact region 116A and the working electrode contact region 116B can be in electrical contact with the working electrode 117, the reference electrode contact region 118A and the reference electrode contact region 118B can be in electrical contact with the reference electrode 119, and the counter electrode contact regions 120A and 120B can be in electrical contact with the counter electrode 121. Additionally, the working electrode guard rings 128A and 128B can form the guard ring 128, and the reference electrode guard rings 130A and 130B can form the guard ring 130. The sensor electrode contact region 114A and the transmitter contact region 114B can be collectively referred to as the electrode contact region 114. In some embodiments, the guard ring 128 and / or the guard ring 130 can have an annular shape. In some embodiments, at least one of the guard ring 128 and / or the guard ring 130 can have a circular, elliptical, rectangular, or any other suitable shape.

[0034] The electrodes 117, 119, and 121 can apply a voltage and / or pass a current through the interstitial fluid 108 via the needle 122. For example, during operation of the glucose monitoring system 100, a current can flow between the working electrode 117 and the counter electrode 121. The reference electrode 119 can function to set the voltage of the counter electrode 121 with little or no current flowing. As described herein, the current between the working electrode 117 and the counter electrode 121 is proportional to the glucose concentration of the interstitial fluid 108. Accordingly, the glucose monitoring system 100 can measure the current between the working electrode 117 and the counter electrode 121 and determine the glucose concentration of the interstitial fluid 108.

[0035] The guard ring 128 prevents stray current from flowing on the surface 124 of the glucose transmitter 102 and / or on the surface of the substrate 110, and prevents it from being interpreted as current flowing through the interstitial fluid 108. The guard ring 128 may include a conductive ring that surrounds at least a portion of the working electrode contact region 116 and may contact the surface 124. During operation of the glucose sensor assembly 104, the guard ring 128 may operate at the same voltage as the working electrode 117. Since the guard ring 128 and the working electrode 117 operate at the same voltage, no current will flow between the working electrode 117 and the guard ring 128. Thus, only the current flowing through the interstitial fluid 108 flows through the working electrode 117.

[0036] Further reference is made to FIG. 2, which schematically illustrates an embodiment of a portion of the glucose monitoring system 100 provided herein. The glucose monitoring system 100 illustrated in FIG. 2 may include a glucose transmitter 102 electrically coupled to a glucose sensor assembly 104. The glucose transmitter 102 may include an analog front end 220 configured to be electrically coupled to components of the glucose sensor assembly 104.

[0037] The glucose transmitter 102 may include a controller 222 configured to control and monitor components within the glucose monitoring system 100 and / or the analog front end 220. The controller 222 may include a processor 222P coupled to a memory 222M. The memory 222M may have instructions stored therein that, when executed by the processor 222P, cause the controller 222 to control and / or monitor various components of the glucose monitoring system 100 described herein.

[0038] Processor 222P can be a computing resource such as, but not limited to, for example, a microprocessor, a microcontroller, an embedded microcontroller, a digital signal processor (DSP), a field programmable gate array (FPGA) configured to operate as a microcontroller, etc. Memory 222M can be any suitable type of memory such as, but not limited to, one or more of volatile memory and / or non-volatile memory.

[0039] Analog front end 220 can also include a plurality of power supplies configured to be electrically coupled to components of glucose sensor assembly 104 and controllable by controller 222. For example, the power supplies can bias components such as electrodes 117, 119, and 121 at different predetermined voltages. In the embodiment shown in FIG. 2, analog front end 220 can include three power supplies individually referred to as working electrode (WE) source 224, guard source 226, and counter electrode (CE) source 228. Analog front end 220 can include other components not shown. For example, analog front end 220 can include components that monitor the voltage of reference electrode 119.

[0040] WE source 224 can be configured to apply working electrode voltage V WE to working electrode contact region 116A of glucose sensor assembly 104. WE source 224 can include a control input 224A coupled to controller 222 and an output 224B that applies working electrode voltage V WE and supplies current I21. For example, controller 222 can send a command to WE source 224 via control input 224A, thereby causing WE source 224 to output working electrode voltage V WE via output 224B.

[0041] The analog front end 220 may also include a current measurement circuit (e.g., ammeter) 230 configured to measure the output current I21 of the WE source 224, which can be the current flowing through the working electrode 117. The ammeter 230 may generate signals indicating the number of amperes of the current I21 and transmit these signals to the controller 222. In some embodiments, the memory 222M, when executed by the processor 222P, may include instructions for causing the controller 222 to generate a signal in response to the measured current of the ammeter 230 exceeding a predetermined (e.g., threshold) number of amperes or being outside a predetermined (e.g., threshold) range of amperes. For example, in some embodiments, the controller 222 may be configured to generate a signal in response to the current I21 measured by the ammeter 230 being greater than a first predetermined number of amperes or less than a second predetermined number of amperes. The signal generated by the controller 222 may indicate that an error condition exists in the glucose monitoring system 100.

[0042] The CE source 228 may be configured to provide two or more counter electrode voltages to the counter electrode contact region 120. The CE source 228 may include a control input 228A and an output 228B that output two or more counter electrode voltages. The control input 228A may be coupled to the controller 222 and may receive instructions regarding the voltage to be output at the output 228B. The CE source 228 may be configured to output at least a first counter electrode (CE) voltage V CE1 and a second CE voltage V CE2 to the counter electrode 121. For example, the controller 222 may transmit instructions to the CE source 228 via the control input 228A to cause the CE source 228 to output at least one of the first CE voltage V CE1 or the second CE voltage V CE2 .

[0043] In some embodiments, the CE source 228 outputs the first CE voltage V CE1can output. The CE source 228 outputs a second CE voltage V when the glucose monitoring system 100 is in an analysis (e.g., self-diagnosis) state as described herein. CE2 can output. In some embodiments, the first CE voltage V CE1 is not equal to the working electrode voltage V WE , and the second CE voltage V CE2 is equal to the working electrode voltage V WE . Other suitable voltages may be used.

[0044] The guard source 226 can be configured to apply one or more guard ring voltages to the guard ring 128. In the embodiment illustrated in FIG. 2, the guard source 226 can be configured to output at least a first guard ring voltage V G1 and a second guard ring voltage V G2 to the guard ring 128. The guard source 226 can include a control input 226A coupled to the controller 222 and an output 226B configured to be electrically coupled to the guard ring 128. The output 226B can apply at least the first guard ring voltage V G1 or the second guard ring voltage V G2 to the guard ring 128. For example, the controller 222 can send a command to the guard source 226 via the control input 226A to cause the guard source 226 to output at least one of the first guard ring voltage V G1 or the second guard ring voltage V G2 to the guard ring 128.

[0045] In some embodiments, the first guard ring voltage V G1 may be equal to the working electrode voltage V WE , and the second guard ring voltage V G2 may not be equal to the working electrode voltage V WE . Other suitable voltages may be used. In some embodiments, the guard source 226 outputs the first guard ring voltage V G1can output. The guard source 226 outputs a second guard ring voltage V G2 when the glucose monitoring system 100 is in the analysis state. In some embodiments, the output 226B of the guard source 226 may have a low impedance to the source or sink current (e.g., current I21) when the glucose monitoring system 100 is in the analysis state as described herein.

[0046] The reference resistor R21 may be configured to be electrically connected between the working electrode 117 (e.g., the working electrode contact regions 116A and / or 116B) and, for example, the guard ring 128. In some embodiments, the reference resistor R21 may be electrically connected between the output of the ammeter 230 and the output 226B of the guard source 226. In some embodiments, the reference resistor R21 may have a high resistance value, such as about 5 MΩ with an accuracy of, for example, 0.5 to 1%. The reference resistor R21 may have other suitable resistance and accuracy values. In some embodiments, the reference resistor R21 may be located within the glucose transmitter 102, and in other embodiments, the reference resistor R21 may be located within the glucose sensor assembly 104 (e.g., as shown in the glucose sensor assembly 704 of FIG. 7).

[0047] In some embodiments, the glucose monitoring system 100 can operate in at least an operating state, a first analysis state, and a second analysis state. When the glucose monitoring system 100 is in the operating state, as described herein, the glucose monitoring system 100 measures the glucose concentration of the interstitial fluid 108 (FIG. 1A). The glucose concentration in the interstitial fluid 108 is proportional to the conductivity of the interstitial fluid 108. Thus, the glucose concentration in the interstitial fluid 108 can be continuously measured by continuously measuring the current I21 flowing through the working electrode contact region 116A (e.g., under a constant bias). For example, the ammeter 230 can continuously measure the current I21. The current I21 may be equal to the current flowing between the working electrode 117 and the counter electrode 121 plus the current flowing through the reference resistor R21. In the normal operation of the glucose monitoring system 100 for monitoring the glucose concentration, the working electrode voltage V WE and the first guard ring voltage V G1 may be equal, and thus no current flows through the reference resistor R21.

[0048] In all states of the glucose monitoring system 100 and the glucose transmitter 102 described herein, the WE source 224 can apply the working electrode voltage V WE to the working electrode 117. For example, the controller 222 can send a command to the WE source 224, thereby causing the WE source 224 to output the working electrode voltage V WE on the output 224B. In some embodiments, the working electrode voltage V WE can be about 1.5V, but other suitable values (e.g., greater than 1.5 volts, 1.5 volts, 1.0 volts, 0.5 volts, less than 0.1 volts, etc.) can be used. The output 224B of the WE source 224 can have a low impedance so that the WE source 224 can source and / or sink the current I21.

[0049] The glucose transmitter 102 is in one or more analysis states and can perform one or more self - diagnostics or integrity checks. The glucose transmitter 102 can also be in an operating state or a normal state when it processes signals from the glucose sensor assembly 104 to measure glucose concentration. Examples of the output states of the WE source 224, the guard source 226, and the CE source 228 are summarized by the relative values shown in Table 1. The V of different states WE , V CE1 , V CE2 , V G1 , and V G2 Exemplary values are shown in Table 2. Other suitable voltages may be used.

[0050]

Table 1

[0051]

Table 2

[0052] Referring now to FIG. 3, an embodiment of the glucose monitoring system 100 configured in an operating state is schematically shown. When the glucose monitoring system 100 is in the operating state, the CE source 228 can apply a first CE voltage V CE1 to the counter - electrode contact region 120A. For example, the controller 222 can send a command to the CE source 228 via the control input 228A to cause the CE source 228 to output a first CE voltage V CE1 at the output 228B. The first CE voltage V CE1 output by the CE source 228 when the glucose monitoring system 100 is in the operating state is not equal to the working - electrode voltage V WE . For example, the first counter - electrode voltage V CE1 may be less than the working - electrode voltage V WE , or the first counter - electrode voltage V CE1 may be greater than the working - electrode voltage V WEIt may also be larger. Therefore, current can flow between the working electrode 117 and the counter electrode 121. In some embodiments, the working electrode voltage V WE and the first counter electrode voltage V CE1 The difference between them is about 0.5V. In some embodiments, the working electrode voltage V WE is about 1.5V, and the first counter electrode voltage V CE1 is about 1.0V. Other suitable voltages can be used.

[0053] When the glucose monitoring system 100 is in an operating state, the guard source 226 may apply the first guard ring voltage V G1 to the guard ring 128. As described above, the first guard ring voltage V G1 may be equal to the working electrode voltage V WE . For example, the controller 222 may send a command to the guard source 226 via the control input 226A, and cause the guard source 226 to output the first guard ring voltage V G1 at the output 226B. By setting the first guard ring voltage V G1 equal to the working electrode voltage V WE , no current flows between the guard ring 128 and the working electrode contact region 116A. Therefore, the current flowing through the working electrode contact region 116A is the current flowing through the interstitial fluid 108 (FIG. 1A), and is proportional to the glucose concentration of the interstitial fluid 108. In such embodiments, the current flowing through the working electrode 117 is not affected by contaminants on the surface 124 of the glucose transmitter 102 or on the surface of the substrate 110 (FIG. 1A).

[0054] To ensure accuracy, the glucose monitoring system 100 may perform periodic self-diagnostics (e.g., integrity checks). Conventional glucose monitoring devices may include switches and the like for use during self-diagnostics. The glucose monitoring system 100 described herein includes a reference resistor R21 that can be continuously electrically connected between the working electrode contact region 116A and the guard ring 128. Therefore, the glucose monitoring system 100 described herein does not require an additional switching circuit.

[0055] Referring now to FIG. 4, an embodiment of the analog front end 220 in a first analysis state is schematically shown for performing a first consistency check. When the analog front end 220 is in the first analysis state, the voltages of the electrodes are set by the controller 222 to be equal. Thus, the WE source 224, the guard source 226, and the CE source 228 are commanded to output the same voltage as follows: V WE =V G1 =V CE2 . In some embodiments, all voltages may be set to 1.5 v. Since the voltages of the working electrode 117, the guard ring 128, and the counter electrode 121 are the same, no current should flow between the electrodes. Thus, the ammeter 230 cannot measure any current. The controller 222 may generate a signal indicating a malfunction within the glucose monitoring system 100 in response to the ammeter 230 measuring a current. In some embodiments, the controller 222 may generate a signal in response to the ammeter 230 measuring a current greater than a predetermined (e.g., threshold) number of amperes. In some embodiments, the predetermined number of amperes that causes the controller 222 to generate a signal (e.g., an error message, a malfunction signal, and / or an alarm) may be about 10 to 20 nanoamperes or more, although other suitable values may be used. For example, some stray current associated with the components may flow such that the stray current does not adversely affect the glucose monitoring system 100. In some embodiments, the predetermined number of amperes that causes the controller 222 to generate a signal may be set based on the allowable error in the glucose monitoring system 100 (FIG. 1A).

[0056] Referring now to FIG. 5, an embodiment of the analog front end 220 in a second analysis state is schematically shown for performing a second consistency check. When the analog front end 220 is in the second analysis state, the voltages of all the electrodes are set by the controller 222 such that a current I21 is drawn through the reference resistor R21. For example, the second CE voltage V CE2 is the working electrode voltage VWE may be equal to. The guard source 226 is the working electrode voltage V WE and a second guard ring voltage V that is not equal to G2 may be commanded to output. In some embodiments, the second guard ring voltage V G2 is the working electrode voltage V WE is smaller. For example, the working electrode voltage V WE can be 1.5 v, and the second guard ring voltage V G2 can be 1.0 v.

[0057] As described above, when the analog front end 220 is in the second analysis state, there is a voltage difference between the working electrode 117 and the guard ring 128. As shown in FIG. 5, this voltage difference exists across the reference resistor R21. The second CE voltage V CE2 output by the CE source 228 is the working electrode voltage V at the working electrode 117 WE Since they are equal, no current flows between the working electrode 117 and the counter electrode 121. When the glucose monitoring system 100 is operating correctly, the current measured by the ammeter 230 is only the current I21 flowing through the reference resistor R21. The reference resistor R21 can be a precision resistor, and the working electrode voltage V WE and the second guard ring voltage V G2 can be precision voltages. As a result, the accuracy of the resistance and voltage is proportional to the accuracy of the second self-diagnosis performed by the glucose monitoring system 100. Under ideal conditions, the current measured by the ammeter 230 is the voltage difference (V WE ~V G2 ) divided by the resistance of the reference resistor R21.

[0058] During the second consistency check, the controller 222 may generate a signal (e.g., an error message, a fault signal, and / or an alarm) in response to the current measured by the ammeter 230 being greater than a first predetermined (e.g., threshold) number of amperes and / or less than a second predetermined (e.g., threshold) number of amperes. For example, in some embodiments, the first predetermined number of amperes may be slightly greater (e.g., 2% greater, 5% greater, etc.) than the current measured under ideal conditions, and the second predetermined number of amperes may be slightly less (e.g., 2% less, 5% less, etc.) than the current measured under ideal conditions. Other suitable predetermined numbers of amperes may be used. The signal generated by the controller 222 may indicate to the glucose monitoring system 100 that there is a fault such as contamination.

[0059] Referring now to FIG. 6, which schematically illustrates another embodiment of the analog front end 620 of the glucose monitoring system 100. The analog front end 620 may include a digital-to-analog converter (DAC) coupled to the controller 222, and the DAC outputs the voltage described above to the glucose sensor assembly 104. For example, the controller 222 may output a digital (e.g., binary) value representing the voltage output by the individual DACs.

[0060] The analog front end 620 shown in FIG. 6 may include a first DAC 640A having a digital input coupled to the controller 222. The analog output of the first DAC 640A may be coupled to the non-inverting input of a first operational amplifier 642A configured as a buffer. The output of the first operational amplifier 642A may be configured to be coupled to the working electrode contact region 116. The analog front end 620 may also include a second DAC 640B having a digital input coupled to the controller 222. The analog output of the second DAC 640B may be coupled to the non-inverting input of a second operational amplifier 642B. The output of the second operational amplifier 642B may be configured to be coupled to the guard ring 128. The second operational amplifier 642B may be configured as a buffer. The analog front end 620 may also include a reference resistor R21 coupled between the output of the current meter 230 and the output of the second operational amplifier 642B. In some embodiments, the reference resistor R21 may be located in the glucose sensor assembly 104 shown in FIG. 7.

[0061] The analog front end 620 may further include a third DAC 640C having a digital input coupled to the controller 222. The analog output of the third DAC 640C may be coupled to the non-inverting input of a third operational amplifier 642C configured as a buffer. In some embodiments, the counter electrode contact region 120 and the reference electrode contact region 118 may be coupled together by a switch SW61 controlled by the controller 222. The controller 222 may close the switch SW61 when the analog front end 620 is in an analysis state, and the controller 222 may open the switch SW61 when the analog front end 620 is in a normal operating state. The switch SW61 may be closed when the glucose transmitter 602 is in an analysis state, which applies the counter electrode voltage as the reference electrode voltage. The switch SW61 may open when the glucose transmitter 602 is in normal operation for measuring glucose concentration. In some embodiments, a similar switching mechanism (not shown) may be included in the glucose transmitter 102 of FIGS. 2-5.

[0062] The analog front end 620 can operate in the same manner as the analog front end 220 (Figs. 2-5). For example, the analog front end 620 can output voltages V WE , V CE1 , V CE2 , V G1 , and V G2 depending on the state of the analog front end 620 and / or the glucose transmitter 602.

[0063] In some embodiments, the reference resistor R21 can be located on or within the glucose sensor assembly 104. Referring to FIG. 7, a plan view of the glucose sensor assembly 704 on which the reference resistor R21 is located is shown. The reference resistor R21 can be electrically connected, for example, between the working electrode contact region 116 and the guard ring 128. Alternatively, in other embodiments, the reference resistor R21 can be directly connected between the working electrode 117 and the guard ring 128. The glucose transmitter 102 (FIG. 1A) can be electrically connected to the glucose sensor assembly 704 and can function as described herein.

[0064] Referring now to FIG. 8, a flowchart 800 illustrating a method of operating an analyte monitoring system (e.g., the glucose monitoring system 100) according to an embodiment provided herein is shown. The method includes, at 802, providing an analyte sensor (e.g., the glucose sensor assembly 104 or 704) having a working electrode (e.g., the working electrode 117), a counter electrode (e.g., the counter electrode 121), and a guard ring (e.g., the guard ring 128) surrounding at least a portion of the working electrode contact region. The method includes, at 804, providing a reference resistor (e.g., the reference resistor R21) electrically connected between the working electrode and the guard ring of the analyte sensor. The method includes, at 806, applying a working electrode voltage (e.g., the working electrode voltage V WE ) to the working electrode of the analyte sensor. The method includes, at 808, applying a first counter electrode voltage (e.g., the first CE voltage V CE1 ) and a second counter electrode voltage (e.g., the second CE voltage V CE2including selectively applying one of them to the counter electrode of the analyte sensor. The method includes, at 810, applying at least a first guard ring voltage (e.g., the first guard ring voltage V G1 ) to the guard ring of the analyte sensor. The method includes, at 812, measuring the current to the working electrode.

[0065] In some embodiments, the first counter electrode voltage V CE1 and the first guard ring voltage V G1 can be the same as the working electrode voltage V WE . In other embodiments, the first guard ring voltage V G1 can be different from the working electrode voltage V WE . The current to the working electrode 117 can be measured to determine whether the glucose monitoring system 100 is functioning properly (e.g., whether the current based on the voltages applied to the working electrode 117, counter electrode 121, guard ring 128, and / or reference electrode 119 is as expected).

[0066] In some embodiments, the reference electrode contact regions 118A / 118B can include a guard ring 130 that at least partially surrounds the reference electrode contact regions 118A / 118B.

[0067] Although the present disclosure can take various modifications and alternative forms, specific embodiments of assemblies and devices and their methods are shown by way of example in the drawings and are described in detail herein. However, the invention is not limited to the specific assemblies, devices, or methods disclosed herein. On the contrary, the invention encompasses all modifications, equivalents, and alternatives included within the scope of the claims.

Claims

**Claim 1** An analyte monitor, comprising a controller including a processor coupled to a memory, wherein the memory stores instructions that, when executed by the processor, cause the controller to: cause an operating voltage to be provided to a working electrode of an analyte sensor; selectively provide a first counter electrode voltage and a second counter electrode voltage to a counter electrode of the analyte sensor; and cause a guard ring voltage to be provided to a guard ring at least partially surrounding a contact area of the working electrode; a current measurement circuit coupled to the controller and configured to measure a current to the working electrode; and a reference resistor electrically coupled between the working electrode and the guard ring; wherein the memory stores instructions that, when executed by the processor, cause the controller to include an integrity check comprising: applying the operating voltage to the working electrode, applying the first counter electrode voltage or the second counter electrode voltage to the counter electrode, and applying the guard ring voltage to the guard ring, wherein the integrity check is performed based on measuring, using the current measurement circuit, a current to the working electrode. An analyte monitor. **Claim 2** The analyte monitor of claim 1, wherein the memory of the controller of the analyte monitor stores instructions that, when executed by the processor, cause the controller to further include instructions to cause the controller to measure an analyte concentration by: applying the operating voltage to the working electrode, applying the first counter electrode voltage to the counter electrode, wherein the first counter electrode voltage is not equal to the operating voltage, and applying the guard ring voltage to the guard ring, wherein the guard ring voltage is equal to the operating voltage. **Claim 3** The analyte monitor of claim 2, wherein the memory stores instructions that, when executed by the processor, cause the controller to further include instructions to generate a signal in response to a measured current to the working electrode exceeding a predetermined number of amperes during measurement of the analyte concentration. **Claim 4** The memory stores instructions that, when executed by the processor, cause the controller to: apply the operating voltage to the working electrode, ​ Applying the second counter electrode voltage to the counter electrode, wherein the second counter electrode voltage is equal to the working electrode voltage, and Applying the guard ring voltage to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage, further including an instruction to perform a first consistency check, the analyte monitor according to claim 1.

5. When the memory is executed by the processor, the controller is further included an instruction to generate a signal in response to the measured current to the working electrode exceeding a predetermined number of amperes during the first consistency check, the analyte monitor according to claim 4.

6. The analyte monitor according to claim 5, wherein the predetermined number of amperes is greater than 20 nanoamperes during the first consistency check.

7. When the memory is executed by the processor, the controller is further included an instruction to apply a reference electrode voltage equal to the second counter electrode voltage to the reference electrode of the analyte sensor during the first consistency check, the analyte monitor according to claim 4.

8. When the memory is executed by the processor, the controller is further included an instruction to selectively provide a first guard ring voltage and a second guard ring voltage to the guard ring, and When the memory is executed by the processor, the controller: Applying the working electrode voltage to the working electrode, Applying the second counter electrode voltage to the counter electrode, wherein the second counter electrode voltage is equal to the working electrode voltage, and Applying the second guard ring voltage to the guard ring, wherein the second guard ring voltage is not equal to the working electrode voltage, further including an instruction to perform a consistency check, the analyte monitor according to claim 1.

9. When the memory is executed by the processor, the controller is further included an instruction to generate a signal in response to the measured current to the working electrode exceeding a first predetermined number of amperes or being less than a second predetermined number of amperes during the consistency check, the analyte monitor according to claim 8.

10. During the integrity check, the first predetermined number of amperes is at least 2% greater than the value obtained by dividing the difference between the working electrode voltage and the second guard ring voltage by the resistance value of the reference resistor, and the second predetermined number of amperes is at least 2% less than the value obtained by dividing the difference between the working electrode voltage and the second guard ring voltage by the resistance value of the reference resistor. The analyte monitor according to claim 9.

11. When executed by the processor, the memory further includes instructions for causing the controller to apply a reference electrode voltage equal to the second counter electrode voltage to the reference electrode of the analyte sensor during the integrity check. The analyte monitor according to claim 8.

12. An analyte monitoring system, An analyte sensor having a working electrode and a counter electrode; A guard ring surrounding at least a portion of the contact area of the working electrode; A reference resistor electrically connected between the working electrode and the guard ring; and, An analyte transmitter connected to the analyte sensor, comprising: A controller including a processor connected to a memory, wherein when the memory is executed by the processor, the controller: Cause a working electrode voltage to be provided to the working electrode; Selectively provide a first counter electrode voltage and a second counter electrode voltage to the counter electrode; and, Provide a guard ring voltage to the guard ring, A controller having stored instructions; and, An analyte transmitter including a current measurement circuit connected to the controller and configured to measure the current to the working electrode. When executed by the processor, the memory includes an integrity check for the controller that: Applying the working electrode voltage to the working electrode, applying the first counter electrode voltage or the second counter electrode voltage to the counter electrode, and applying the guard ring voltage to the guard ring; To be implemented, The integrity check is performed based on measuring the current to the working electrode using the current measurement circuit. An analyte monitoring system.

13. When executed by the processor, the memory causes the controller to: Apply the working electrode voltage to the working electrode, Applying the first counter electrode voltage to the counter electrode, wherein the first counter electrode voltage is not equal to the working electrode voltage. Applying the guard ring voltage to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage, and further including an instruction to measure the analyte concentration thereby, the analyte monitoring system according to claim 12.

14. When the memory is executed by the processor, the controller is further included with an instruction to generate a signal in response to the measured current on the working electrode exceeding a predetermined number of amperes during the measurement of the analyte concentration, the analyte monitoring system according to claim 13.

15. When the memory is executed by the processor, the controller: Applying the working electrode voltage to the working electrode, Applying the second counter electrode voltage to the counter electrode, wherein the second counter electrode voltage is equal to the working electrode voltage, and applying, and, Applying the guard ring voltage to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage, and further including an instruction to perform a first consistency check thereby, the analyte monitoring system according to claim 13.

16. When the memory is executed by the processor, the controller is further included with an instruction to generate a signal in response to the measured current on the working electrode exceeding a predetermined number of amperes during the first consistency check, the analyte monitoring system according to claim 15.

17. The analyte monitoring system according to claim 16, wherein the predetermined number of amperes is greater than 20.0 nanoamperes.

18. The analyte sensor has a reference electrode, and when the memory is executed by the processor, the controller is further included with an instruction to apply a reference electrode voltage equal to the second counter electrode voltage to the reference electrode during the first consistency check, the analyte monitoring system according to claim 15.

19. When the memory is executed by the processor, the controller: Selectively provide a first guard ring voltage and a second guard ring voltage to the guard ring; and, The following: Applying the working electrode voltage to the working electrode, Applying the second counter electrode voltage to the counter electrode, wherein the second counter electrode voltage is equal to the working electrode voltage, and applying, and, Applying the second guard ring voltage to the guard ring, wherein the second guard ring voltage is not equal to the working electrode voltage, and further including an instruction to perform a consistency check by this application, the analyte monitoring system according to claim 13.

20. When the memory is executed by the processor, the memory further includes an instruction to cause the controller to generate a signal in response to the measured current to the working electrode exceeding a first predetermined number of amperes or being less than a second predetermined number of amperes during the consistency check, the analyte monitoring system according to claim 19.

21. During the consistency check, the first predetermined number of amperes is at least 2% greater than the value obtained by dividing the difference between the working electrode voltage and the second guard ring voltage by the resistance value of the reference resistor, and the second predetermined number of amperes is at least 2% less than the value obtained by dividing the difference between the working electrode voltage and the second guard ring voltage by the resistance value of the reference resistor, the analyte monitoring system according to claim 20.

22. The analyte sensor has a reference electrode, and when the memory is executed by the processor, the memory further includes an instruction to cause the controller to apply a reference electrode voltage equal to the first counter electrode voltage to the reference electrode during the consistency check, the analyte monitoring system according to claim 19.

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