Devices, systems, and methods for measuring analytes in interstitial fluid

Abstract

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

Description

[0001] Cross-reference to related applications

[0002] This invention claims the benefit of U.S. Provisional Patent Application No. 62 / 933,308, filed November 8, 2019, entitled “DEVICES, SYSTEMS, AND METHODS FORMEASURING ANALYTES IN INTERSTITIAL FLUID”, the disclosure of which is incorporated herein by reference in its entirety for all purposes. Technical Field

[0003] This disclosure relates to apparatus, systems, and methods suitable for measuring analytes in interstitial fluid. Background Technology

[0004] Continuous analyte sensing in in vivo and / or in vitro samples, such as continuous glucose monitoring (CGM), has become a routine sensing operation, especially in diabetes care. By providing real-time blood glucose concentrations, treatment / clinical interventions can be applied more promptly, and glycemic status can be better controlled.

[0005] During a CGM procedure, the biosensor is typically inserted subcutaneously and operates continuously in an environment surrounded by tissue and tissue fluid. The biosensor, inserted under the skin, signals the wireless CGM transmitter of the CGM sensor device, and this signal indicates the user's blood glucose level. These measurements can be taken automatically multiple times throughout the day (e.g., every few minutes or at some other interval).

[0006] The wireless CGM transmitter can adhere to the outer surface of the user's skin, such as on the abdomen or the back of the upper arm, while the biosensor is inserted through the skin to contact tissue fluid.

[0007] To ensure accurate blood glucose readings, CGM devices can periodically run self-tests to verify the correct operation of the biosensor and CGM transmitter. Self-test systems can increase the complexity and cost of the CGM transmitter by requiring additional switches and other hardware. Therefore, there is a need for improved systems, methods, and devices for verifying the correct operation of the CGM transmitter and biosensor. Summary of the Invention

[0008] According to a first aspect, an analyte monitor is disclosed. The analyte monitor includes a controller comprising a processor coupled to a memory having instructions stored therein, the instructions, when executed by the processor, causing the controller to: provide a working electrode voltage 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 provide a guard ring voltage to a guard ring at least partially surrounding a contact area of ​​the working electrode. The analyte monitor further includes a current measurement circuit coupled to the controller and configured to measure current flowing to the working electrode. The analyte monitor also includes a reference resistor electrically connected between the working electrode and the guard ring. The memory further includes instructions, when executed by the processor, causing 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 flowing to the working electrode using the current measurement circuit.

[0009] 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 reverse electrode; a guard ring surrounding at least a portion of a contact area of ​​the working electrode; a reference resistor electrically connected between the working electrode and the guard ring; and an analyte emitter coupled to the analyte sensor. The analyte monitor includes a controller including a processor coupled to a memory having instructions stored therein, the instructions, when executed by the processor, causing the controller to: provide a working electrode voltage to the working electrode of the analyte sensor; selectively provide a first reverse electrode voltage and a second reverse electrode voltage to the reverse electrode of the analyte sensor; and provide a guard ring voltage to the guard ring. The analyte emitter further includes a current measurement circuit coupled to the controller and configured to measure the current flowing to the working electrode. The memory also includes instructions that, when executed by the processor, cause the controller to perform at least one integrity check by: applying the working electrode voltage to the working electrode, applying a first reverse electrode voltage or a second reverse electrode voltage to the reverse electrode, applying the guard ring voltage to the guard ring, and measuring the current flowing to the working electrode using the current measurement circuit.

[0010] In a third aspect, a method for 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 a 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 the current flowing to the working electrode.

[0011] In another aspect, an analyte sensor configured to attach to the skin is disclosed. The analyte sensor includes: a working electrode; a guard ring surrounding at least a portion of a contact area of ​​the working electrode; and a reference resistor connected between the working electrode and the guard ring.

[0012] Other aspects, features, and advantages of this disclosure will readily become apparent from the following description of the numerous exemplary embodiments and implementations illustrated. This disclosure is also capable of other and different embodiments, and several details thereof may be modified in various aspects, all without departing from its scope. Therefore, the drawings and description are to be regarded as illustrative in nature and not restrictive. This disclosure covers all modifications, equivalents, and alternatives that fall within the scope of the claims. Attached Figure Description

[0013] The accompanying drawings described below are for illustrative purposes only and are not necessarily drawn to scale. The drawings are not intended to limit the scope of this disclosure in any way. The same numerals are used throughout to denote the same or similar elements.

[0014] Figure 1A A partial cross-sectional side view of a blood glucose monitoring system according to one or more embodiments is shown, the blood glucose monitoring system including a blood glucose sensor attached to the skin and a blood glucose transmitter detached from the blood glucose sensor.

[0015] Figure 1B A bottom view of a blood glucose transmitter according to one or more embodiments is shown.

[0016] Figure 1C A partial cross-sectional side view of a blood glucose monitoring system according to one or more embodiments is shown, wherein a blood glucose sensor is attached to a blood glucose transmitter.

[0017] Figure 2 A portion of a blood glucose monitoring system including a blood glucose sensor is illustrated schematically according to one or more embodiments disclosed herein.

[0018] Figure 3A portion of a blood glucose monitoring system including a blood glucose sensor, in operation according to one or more embodiments disclosed herein, is illustrated schematically.

[0019] Figure 4 A portion of a blood glucose monitoring system including a blood glucose sensor, in a first analysis state, is schematically shown according to one or more embodiments disclosed herein.

[0020] Figure 5 A portion of a blood glucose monitoring system including a blood glucose sensor in a second analysis state is schematically shown according to one or more embodiments disclosed herein.

[0021] Figure 6 A portion of a blood glucose monitoring system including a blood glucose sensor is illustrated schematically according to one or more embodiments disclosed herein.

[0022] Figure 7 A plan view of a blood glucose sensor having a resistor connected between a working electrode and a guard ring, according to one or more embodiments disclosed herein, is shown.

[0023] Figure 8 A flowchart illustrating a method of operating a blood glucose monitoring system according to one or more embodiments disclosed herein is shown. Detailed Implementation

[0024] Continuous Analyte Monitoring (CAM) systems can monitor current flow between two or more points in a tissue fluid to determine the concentration of an analyte (e.g., blood glucose concentration) in the tissue fluid. A CAM system may include an analyte emitter electrically connected to an analyte sensor (e.g., a blood glucose sensor). The analyte emitter may include an analog front end having a contact area electrically connected to a contact area of ​​an electrode of the analyte sensor, such as a working electrode, a reverse electrode, a reference electrode, etc., the analog front end creating an electrical connection between the CAM emitter and the electrodes of the analyte sensor.

[0025] An analyte sensor may be coupled to a substrate at a contact area. The substrate may be attached to a user's skin, and an analyte emitter may be coupled to the substrate. A needle of the analyte sensor is configured to extend from the substrate through the user's skin for subcutaneous placement to contact the user's tissue fluid. The needle includes electrodes of the analyte sensor, such as a working electrode, a counter electrode, and a reference electrode, and is positioned in contact with the tissue fluid beneath the user's skin. The analyte emitter and / or the substrate may include one or more protective 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 protective ring may surround more than 50% and / or substantially surround the contact area of ​​the electrode.

[0026] During CAM, a voltage is applied between the working electrode and the reverse electrode, and the current between the electrodes is measured. The current between the electrodes is proportional to the concentration of the analyte (e.g., blood glucose) in the tissue fluid. The same voltage applied to the working electrode can be applied to a guard ring associated with the working electrode to prevent current from flowing through contaminants on the substrate and / or to prevent the analyte emitter from interfering with the current measurement through the tissue fluid. The current through the tissue fluid can be very small, for example in the nanoamplitude range, making the analyte monitoring system highly sensitive. Integrity checks (e.g., self-test routines) can be performed by the CAM system to ensure proper system operation.

[0027] 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, guard ring, and reverse electrode are set to be equal. If the analyte emitter and / or analyte sensor is operating normally, there should be little or no current between the guard ring and the electrode, as they are all at the same voltage. Any current or a current exceeding a predetermined (e.g., threshold) ampere value may indicate a fault in the analyte monitoring system (e.g., due to incorrect electrical connections or contamination of the analyte emitter, substrate, or sensor).

[0028] During the second integrity check, the voltages applied to the working electrode and the reverse electrode can be equal, while the voltage applied to the guard ring can differ from the voltage applied to the working electrode. If the analyte emitter and / or analyte sensor are operating normally, there should be little or no current between the working electrode and the reverse electrode. However, current should only flow through the reference resistor between the guard ring and the working electrode. The magnitude of the current should be equal to the quotient of the voltage difference between the working electrode and the guard ring and the resistance of the reference resistor. If other currents are measured, a fault may exist in the analyte monitoring system (e.g., due to incorrect electrical connections or contamination of the analyte emitter, substrate, or sensor).

[0029] Refer to the text in this article Figure 1A-8 These and other embodiments are described in detail. Although the description is primarily concerned with the determination of blood glucose concentration using a blood glucose monitoring system, the embodiments described herein can also be used with other analyte monitoring systems (e.g., cholesterol, lactate, uric acid, alcohol, or other analyte monitoring systems).

[0030] Now for reference Figure 1A The image shows a partial cross-sectional side view of a blood glucose monitoring system 100, including a blood glucose transmitter 102 and a blood glucose sensor assembly 104. The blood glucose transmitter 102 is shown separated from the blood glucose sensor assembly 104 to illustrate the various features described below, and the blood glucose sensor assembly 104 is shown attached to the skin 106. Also referenced... Figure 1BThe diagram shows a bottom plan view of an embodiment of the blood glucose transmitter 102. Tissue fluid 108 is located beneath skin 106. Components of the blood glucose monitoring system 100 and skin 106 may be drawn out of scale. The blood glucose sensor assembly 104 may include a substrate 110 (e.g., a base plate) on which components of the blood glucose sensor assembly 104 are located. Portions 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 electrical traces (not shown) that conduct current to components within the substrate 110 or attach to the substrate. An adhesive 112, such as acrylic, silicone, etc., may attach the substrate 110 to the outer surface of skin 106.

[0031] exist Figure 1A-1B In some embodiments, the blood glucose sensor assembly 104 may include a sensor electrode contact area 114A, which includes a working electrode contact area 116A, a reference electrode contact area 118A, and a reverse electrode contact area 120A for contacting the working electrode 117, the reference electrode 119, and the reverse electrode 121, respectively, as further described below. Fewer or more electrode contact areas 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 employed. Electrodes 117, 119, and 121 may be formed and / or encapsulated within a needle 122 configured to be at least partially located in tissue fluid 108 beneath the skin 106, such that electrodes 117, 119, and 121 can contact the tissue fluid and conduct current to the sensor electrode contact areas 116A, 118A, and 120A.

[0032] The blood glucose transmitter 102 may include a surface 124 on which the transmitter contact area 114B is located. The transmitter contact area 114B may include individual contact areas corresponding to the sensor electrode contact area 114A. For example, the transmitter contact area 114B may include a working electrode contact area 116B, a reference electrode contact area 118B, and a reverse electrode contact area 120B. The individual contact areas of the sensor electrode contact area 114A and the transmitter contact area 114B may have any shape, such as circular, elliptical, square, and rectangular.

[0033] In addition to the contact areas described above, the blood glucose transmitter 102 and / or the blood glucose sensor assembly 104 may have a protective ring that at least partially surrounds at least one of the contact areas. Figure 1A and 1BIn the depicted embodiment, the blood glucose sensor assembly 104 includes a working electrode protection ring 128A surrounding at least a portion of the working electrode contact area 116A. The blood glucose sensor assembly 104 may also include a reference electrode protection ring 130A surrounding at least a portion of a reference electrode contact area 118A. The blood glucose transmitter 102 may include a working electrode protection ring 128B and a reference electrode protection ring 130B, the working electrode protection ring surrounding at least a portion of the working electrode contact area 116B and the reference electrode protection ring surrounding at least a portion of the reference electrode contact area 118B.

[0034] During the operation of the blood glucose monitoring system 100, the blood glucose transmitter 102 and the blood glucose sensor assembly 104 can, as Figure 1C As shown, they are attached together such that transmitter contact area 114B electrically contacts sensor electrode contact area 114A. The guard ring in blood glucose transmitter 102 can also electrically contact a corresponding guard ring in blood glucose sensor assembly 104. When blood glucose sensor assembly 104 is attached to blood glucose transmitter 102, working electrode contact areas 116A and 116B can electrically contact working electrode 117, reference electrode contact areas 118A and 118B can electrically contact reference electrode 119, and reverse electrode contact areas 120A and 120B can electrically contact reverse electrode 121. Additionally, working electrode guard rings 128A and 128B can form guard ring 128, and reference electrode guard rings 130A and 130B can form guard ring 130. Sensor electrode contact areas 114A and transmitter contact areas 114B can be collectively referred to as electrode contact areas 114. In some embodiments, the protective ring 128 and / or the protective ring 130 may have an annular shape. In some embodiments, at least one of the protective rings 128 and / or the protective ring 130 may have a circular, elliptical, rectangular or any other suitable shape.

[0035] Electrodes 117, 119, and 121 can apply voltage and / or conduct current through tissue fluid 108 via needle 122. For example, during operation of the blood glucose monitoring system 100, current can flow between the working electrode 117 and the reverse electrode 121. The reference electrode 119 may have no current or very little current and can be used to set the voltage of the reverse electrode 121. As described herein, the current between the working electrode 117 and the reverse electrode 121 is proportional to the blood glucose concentration in the tissue fluid 108. Therefore, the blood glucose monitoring system 100 can measure the current between the working electrode 117 and the reverse electrode 121 to determine the blood glucose concentration in the tissue fluid 108.

[0036] The guard ring 128 prevents stray currents from flowing on the surface 124 of the glucose transmitter 102 and / or the surface of the substrate 110, and prevents stray currents from being interpreted as currents flowing through the tissue fluid 108. The guard ring 128 may include a conductive ring surrounding at least a portion of the working electrode contact area 116 and contacting the surface 124. During operation of the glucose sensor assembly 104, the guard ring 128 can operate at the same voltage as the working electrode 117. Because the guard ring 128 and the working electrode 117 operate at the same voltage, no current should flow between the working electrode 117 and the guard ring 128. Therefore, only the current flowing through the tissue fluid 108 flows through the working electrode 117.

[0037] For further reference Figure 2 The illustration schematically shows an embodiment of a portion of the blood glucose monitoring system 100 provided herein. Figure 2 The blood glucose monitoring system 100 depicted may include a blood glucose transmitter 102 electrically connected to a blood glucose sensor assembly 104. The blood glucose transmitter 102 may include an analog front end 220, which may be configured to be electrically connected to a component of the blood glucose sensor assembly 104.

[0038] The blood glucose transmitter 102 may include a controller 222 configured to control and monitor components within the blood 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 blood glucose monitoring system 100 as described herein.

[0039] The processor 222P can be, for example, a computing resource, such as, but not limited to, a microprocessor, a microcontroller, an embedded microcontroller, a digital signal processor (DSP), a field-programmable gate array (FPGA) configured to operate as a microcontroller, and so on. The 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.

[0040] The analog front-end 220 may also include components configured to be electrically connected to the glucose sensor assembly 104 and multiple power supplies that can be controlled by the controller 222. For example, the power supplies may bias components such as electrodes 117, 119, and 121 with different predetermined voltages. Figure 2 In the depicted embodiment, analog front-end 220 may include three power sources, individually referred to as working electrode (WE) source 224, protection source 226, and counter electrode (CE) source 228. Analog front-end 220 may include other components not shown. For example, analog front-end 220 may include components for monitoring the voltage of reference electrode 119.

[0041] WE source 224 can be configured to output the working electrode voltage V WE The working electrode contact area 116A of the blood glucose sensor assembly 104 is applied. The WE source 224 may include a control input 224A coupled to the controller 222 and an input voltage V applied to the working electrode. WE And supply current I21 to the output 224B. For example, the controller 222 can transmit a command to the WE source 224 via the control input 224A, which causes the WE source 224 to output the working electrode voltage V via the output 224B. WE .

[0042] The analog front-end 220 may also include a current measurement circuit (e.g., an ammeter) 230 configured to measure the output current I21 of the WE source 224, which may be a current flowing to the working electrode 117. The ammeter 230 may generate a signal indicating the ampere number of the current I21 and may transmit these signals to the controller 222. In some embodiments, the memory 222M may include instructions that, when executed by the processor 222P, cause the controller 222 to generate a signal in response to the measured current of the ammeter 230 exceeding a predetermined (e.g., a threshold) ampere number or falling outside a predetermined (e.g., a threshold) ampere number range. 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 ampere number or less than a second predetermined ampere number. The signal generated by the controller 222 may indicate the presence of an error condition in the blood glucose monitoring system 100.

[0043] CE source 228 can be configured to provide two or more counter electrode voltages to counter electrode contact region 120. CE source 228 may include a control input 228A and an output 228B that outputs two or more counter electrode voltages. Control input 228A can be coupled to controller 222 and can receive commands regarding the voltage output at output 228B. CE source 228 can be configured to supply at least a first counter electrode (CE) voltage V. CE1 Second CE voltage V CE2 The output is sent to the reverse electrode 121. For example, the controller 222 can transmit a command to the CE source 228 via control input 228A, which causes the CE source 228 to output a first CE voltage V. CE1 Or the second CE voltage V CE2 At least one of them.

[0044] In some embodiments, the CE source 228 may output a first CE voltage V during normal operation of the blood glucose monitoring system 100. CE1 When the blood glucose monitoring system 100 is in the analysis (e.g., self-test) state as described herein, the CE source 228 can output a second CE voltage V.CE2 In some embodiments, the first CE voltage V CE1 Not equal to the working electrode voltage V WE The second CE voltage V CE2 Equal to working electrode voltage V WE Other suitable voltages can be used.

[0045] Protection source 226 can be configured to apply one or more protection ring voltages to protection ring 128. Figure 2 In the depicted embodiment, the protection source 226 can be configured to apply at least the first protection ring voltage V G1 Second protection ring voltage V G2 The output is sent to protection ring 128. Protection source 226 may include a control input 226A connected to controller 222 and an output 226B configured to be electrically connected to protection ring 128. Output 226B can deliver at least the first protection ring voltage V. G1 Or the voltage of the second protection ring V G2 The voltage is applied to the protection ring 128. For example, the controller 222 can transmit a command to the protection source 226 via control input 226A, which causes the protection source 226 to apply the first protection ring voltage V. G1 Or the voltage of the second protection ring V G2 At least one of the outputs is connected to the guard ring 128.

[0046] In some embodiments, the first guard ring voltage V G1 It can be equal to the working electrode voltage V WE And the second protection ring voltage V G2 It may not be equal to the working electrode voltage V WE Other suitable voltages can be used. In some embodiments, when the blood glucose monitoring system 100 is in operation, the protection source 226 can output a first protection loop voltage V. G1 When the blood glucose monitoring system 100 is in analysis mode, the protection source 226 can output the second protection loop voltage V. G2 In some embodiments, when the blood glucose monitoring system 100 is in the analysis state as described herein, the output 226B of the protection source 226 may have low impedance to the source current or sink current (e.g., current I21).

[0047] Reference resistor R21 can be configured to be electrically connected, for example, between working electrode 117 (e.g., at working electrode contact areas 116A and / or 116B) and guard ring 128. In some embodiments, reference resistor R21 can be electrically connected between the output of ammeter 230 and the output 226B of guard source 226. In some embodiments, reference resistor R21 may have a high resistance value, for example, about 5 MΩ, with an accuracy of 0.5% to 1%. Reference resistor R21 may have other suitable resistance and accuracy values. In some embodiments, reference resistor R21 may be located in blood glucose transmitter 102; in other embodiments, reference resistor R21 may be located in blood glucose sensor assembly 104 (e.g., as shown in the image). Figure 7 (As shown in the blood glucose sensor assembly 704).

[0048] In some embodiments, the blood glucose monitoring system 100 can operate in at least an operational state, a first analytical state, and a second analytical state. When the blood glucose monitoring system 100 is in the operational state, the blood glucose monitoring system 100 measures the blood glucose concentration in the tissue fluid 108 as described herein. Figure 1A The blood glucose concentration in tissue fluid 108 is proportional to the conductivity of tissue fluid 108. Therefore, the blood glucose concentration in tissue fluid 108 can be continuously measured by continuously measuring the current I21 flowing to the working electrode contact area 116A (e.g., under constant bias). For example, ammeter 230 can continuously measure current I21. Current I21 can be equal to the current flowing between working electrode 117 and counter electrode 121 plus the current flowing through reference resistor R21. During normal operation of the blood glucose monitoring system 100, which is monitoring blood glucose concentration, the working electrode voltage V... WE and the voltage V of the first protection ring G1 They can be equal, therefore no current flows through the reference resistor R21.

[0049] In all states of the blood glucose monitoring system 100 and blood glucose transmitter 102 described herein, the WE source 224 can transmit the working electrode voltage V WE The voltage is applied to the working electrode 117. For example, the controller 222 can send a command to the WE source 224, which causes the WE source 224 to output the working electrode voltage V at the output 224B. WE In some embodiments, the working electrode voltage V WE It can be approximately 1.5V, but other suitable values ​​can be used (e.g., greater than 1.5V, less than 1.5V, 1.0V, 0.5V, 0.1V, etc.). The output 224B of the WE source 224 can have low impedance so that the WE source 224 can source and / or sink current I21.

[0050] The blood glucose transmitter 102 can be in one or more analysis states to perform one or more self-tests or integrity checks. The blood glucose transmitter 102 can also be in an operational or normal state when processing signals from the blood glucose sensor assembly 104 to measure blood glucose concentration. Example states of the outputs of WE source 224, protection source 226, and CE source 228 are summarized by the relative values ​​shown in Table 1. V under different states WE V CE1 V CE2 V G1 and V G2 Example values ​​are shown in Table 2. Other suitable voltages can be used.

[0051] Table 1. Analysis status of blood glucose transmitter 102.

[0052]

[0053] Table 2.V WE V CE1 V CE2 , V G1 and V G2 Example values.

[0054]

[0055] Now for reference Figure 3 This schematically illustrates an embodiment of a blood glucose monitoring system 100 configured in an operational state. When the blood glucose monitoring system 100 is in an operational state, the CE source 228 can deliver a first CE voltage V. CE1 An application is made to the reverse electrode contact region 120A. For example, the controller 222 can transmit a command to the CE source 228 via control input 228A, which causes the CE source 228 to output a first CE voltage V at output 228B. CE1 When the blood glucose monitoring system 100 is in operation, the first CE voltage V output by the CE source 228... CE1 Not equal to the working electrode voltage V WE For example, the first reverse voltage V CE1 It can be less than the working electrode voltage V WE Or the first reverse voltage V CE1 It can be greater than the working electrode voltage V. WE Therefore, current can flow between the working electrode 117 and the counter electrode 121. In some embodiments, the working electrode voltage V WE With the first reverse voltage V CE1 The difference is approximately 0.5V. In some embodiments, the working electrode voltage V WE It is approximately 1.5V, and the first reverse voltage V CE1It is approximately 1.0V. Other suitable voltages can be used.

[0056] When the blood glucose monitoring system 100 is in operation, the protection source 226 can apply a first protection ring voltage V to the protection ring 128. G1 As described above, the first protection ring voltage V G1 It can be equal to the working electrode voltage V WE For example, controller 222 can transmit a command to protection source 226 via control input 226A, which causes protection source 226 to output a first protection loop voltage V at output 226B. G1 By setting it to be equal to the working electrode voltage V WE First guard ring voltage V G1 No current flows between the protective ring 128 and the working electrode contact area 116A. Therefore, the current flowing through the working electrode contact area 116A is the same as the current flowing through the tissue fluid 108. Figure 1A The current flowing through the working electrode 117 is proportional to the blood glucose concentration in the tissue fluid 108. In this embodiment, the current flowing through the working electrode 117 is not affected by contaminants on the surface 124 of the blood glucose transmitter 102 or the surface of the substrate 110. Figure 1A ).

[0057] To ensure accuracy, the blood glucose monitoring system 100 can perform periodic self-tests (e.g., integrity checks). Conventional blood glucose monitoring devices may include switches, etc., for use during self-tests. The blood glucose monitoring system 100 described herein includes a reference resistor R21, which can be continuously electrically connected between the working electrode contact area 116A and the guard ring 128. Therefore, the blood glucose monitoring system 100 described herein does not require additional switching circuitry.

[0058] Now for reference Figure 4 This schematically illustrates an embodiment of an analog front-end 220 configured to perform a first integrity check in a first analysis state. When the analog front-end 220 is in the first analysis state, the controller 222 sets the voltages of the electrodes to be the same. Therefore, the WE source 224, protection source 226, and CE source 228 are instructed to output the same voltage, such that V WE =V G1 =V CE2In some embodiments, all voltages may be set to 1.5V. Since the voltages at the working electrode 117, guard ring 128, and reverse electrode 121 are the same, no current is expected to flow between the electrodes. Therefore, the ammeter 230 should not measure any current. The controller 222 may generate a signal indicating a fault in the blood glucose monitoring system 100 in response to the current measured by the ammeter 230. 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) ampere. In some embodiments, the predetermined ampere for the controller 222 to generate a signal (e.g., an error message, fault signal, and / or alarm) may be about 10-20 nanoamps or greater, but other suitable values ​​may be used. For example, some stray currents associated with components may flow, where stray currents do not adversely affect the blood glucose monitoring system 100. In some embodiments, the predetermined ampere for the controller 222 to generate a signal may be set based on the permissible error and / or tolerance in the blood glucose monitoring system 100. Figure 1A ).

[0059] Now for reference Figure 5 This schematically illustrates an embodiment of an analog front-end 220 configured to perform a second integrity check in a second analysis state. When the analog front-end 220 is in the second analysis state, the voltages of all 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 It can be equal to the working electrode voltage V WE It can indicate that the output of protection source 226 is not equal to the working electrode voltage V. WE The second protection ring voltage V G2 In some embodiments, the second guard ring voltage V G2 Less than the working electrode voltage V WE For example, the working electrode voltage V WE It can be 1.5V, and the second guard ring voltage V G2 It can be 1.0v.

[0060] 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. Figure 5 As shown, this voltage difference exists across the reference resistor R21. The second CE voltage V output from CE source 228... CE2 Equal to the working electrode voltage V at working electrode 117 WE Therefore, no current flows between the working electrode 117 and the reverse electrode 121. If the blood glucose monitoring system 100 is operating correctly, the only current measured by the ammeter 230 is the current I21 flowing through the reference resistor R21. The reference resistor R21 can be a precision resistor, and the working electrode voltage VWE Second protection ring voltage V G2 It can be a precise voltage, such that the accuracy of the resistance and the voltage are proportional to the accuracy of the second self-test performed by the blood glucose monitoring system 100. Under ideal conditions, the current measured by the ammeter 230 is equal to the voltage difference (V). WE -V G2 The ratio of the resistance of the reference resistor R21 to the resistance of the reference resistor R21.

[0061] The controller 222 may generate a signal (e.g., an error message, a fault signal, and / or an alarm) in response to a current measured by the ammeter 230 during a second integrity test that is greater than a first predetermined (e.g., a threshold) ampere and / or less than a second predetermined (e.g., a threshold) ampere. For example, in some embodiments, the first predetermined ampere may be slightly larger than the current measured under ideal conditions (e.g., 2% larger, 5% larger, etc.), and the second predetermined ampere may be slightly smaller than the current measured under ideal conditions (e.g., 2% smaller, 5% smaller, etc.). Other suitable predetermined ampere values ​​may be used. The signal generated by the controller 222 may indicate a malfunction of the blood glucose monitoring system 100, such as contamination.

[0062] Now for reference Figure 6 The diagram schematically illustrates another embodiment of the analog front-end 620 of the blood glucose monitoring system 100. The analog front-end 620 may include a digital-to-analog converter (DAC) coupled to a controller 222, wherein the DAC outputs the aforementioned voltage to the blood glucose sensor assembly 104. For example, the controller 222 may output a digital (e.g., binary) value representing the voltage that each DAC will output.

[0063] Figure 6 The analog front-end 620 depicted may include a first DAC 640A having a digital input coupled to controller 222. The analog output of the first DAC 640A may be coupled to a non-inverting input of a first operational amplifier 642A, which may be configured as a buffer. The output of the first operational amplifier 642A may be configured to be coupled to working electrode contact 116. The analog front-end 620 may also include a second DAC 640B having a digital input coupled to controller 222. The analog output of the second DAC 640B may be coupled to a non-inverting input of the second operational amplifier 642B. The output of the second operational amplifier 642B may be configured to be coupled to 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 ammeter 230 and the output of the second operational amplifier 642B. In some embodiments, the reference resistor R21 may be located as follows: Figure 7 The blood glucose sensor assembly 104 shown is included.

[0064] The analog front-end 620 may also 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 a non-inverting input of a third operational amplifier 642C, which may be configured as a buffer. In some embodiments, the reverse electrode contact area 120 and the reference electrode contact area 118 may be coupled together by a switch SW61, which may be controlled by the controller 222. When the analog front-end 620 is in analysis mode, the controller 222 may close the switch SW61, and when the analog front-end 620 is in normal operation mode, the controller 222 may open the switch SW61. When the blood glucose transmitter 602 is in analysis mode, the switch SW61 may be closed, which applies the reverse electrode voltage as the reference electrode voltage. When the blood glucose transmitter 602 is in normal operation for measuring blood glucose concentration, the switch SW61 may be open. In some embodiments, a similar switching mechanism (not shown) may be included. Figure 2-5 In the blood glucose transmitter 102.

[0065] Analog front-end 620 can be compared with analog front-end 220 ( Figure 2-5 It operates in the same manner. For example, depending on the state of analog front-end 620 and / or glucose transmitter 602, analog front-end 620 can output voltage V. WE V CE1 V CE2 V G1 and V G2 .

[0066] In some embodiments, the reference resistor R21 may be located on or within the blood glucose sensor assembly 104. Figure 7 The diagram shows a plan view of a blood glucose sensor assembly 704, with a reference resistor R21 located thereon. For example, the reference resistor R21 may be electrically connected between the working electrode contact area 116 and the guard ring 128. In other embodiments, the reference resistor R21 may alternatively be directly connected between the working electrode 117 and the guard ring 128. Blood glucose transmitter 102 ( Figure 1A It can be electrically connected to the blood glucose sensor assembly 704 and function as described herein.

[0067] For reference Figure 8The document illustrates a flowchart 800 depicting a method of operating an analyte monitoring system (e.g., a blood glucose monitoring system 100) according to embodiments provided herein. The method includes providing an analyte sensor (e.g., a blood glucose sensor assembly 104 or 704) at 802, the analyte sensor having a working electrode (e.g., working electrode 117), a reverse electrode (e.g., reverse electrode 121), and a guard ring (e.g., guard ring 128) surrounding at least a portion of a contact area of ​​the working electrode. The method includes providing a reference resistor (e.g., a reference resistor R21) electrically connected between the working electrode of the analyte sensor and the guard ring at 804. The method includes applying a working electrode voltage (e.g., a working electrode voltage V) to the working electrode of the analyte sensor at 806. WE The method includes selectively applying a first counter-electrode voltage (e.g., a first CE voltage V) to the counter-electrode of the analyte sensor in 808. CE1 ) and the second counter electrode voltage (e.g., the second CE voltage V) CE2 One of the methods involves applying at least a first guard ring voltage (e.g., a first guard ring voltage V) to the guard ring of the analyte sensor at 810. G1 The method includes measuring the current flowing to the working electrode at 812.

[0068] In some embodiments, the first reverse electrode voltage V CE1 and the voltage V of the first protection ring G1 It can be related to the working electrode voltage V WE The same. In other embodiments, the first guard ring voltage V G1 It can be different from the working electrode voltage V WE The current flowing to the working electrode 117 can be measured to determine whether the blood glucose monitoring system 100 is functioning properly (e.g., whether the current is as expected based on the voltage applied to the working electrode 117, the reverse electrode 121, the guard ring 128, and / or the reference electrode 119).

[0069] In some embodiments, the reference electrode contact area 118A / 118B may include a protective ring 130 that at least partially surrounds the reference electrode contact area 118A / 118B.

[0070] While this disclosure is susceptible to various modifications and alternatives, specific components and device embodiments and methods thereof have been illustrated by way of example in the accompanying drawings and described in detail herein. However, it should be understood that the invention is not limited to the specific components, devices, or methods disclosed herein, but rather covers all modifications, equivalents, and alternatives that fall within the scope of the claims.

Claims

1. An analyte monitor, comprising: A working electrode source is configured to provide a working electrode voltage to the working electrode of the analyte sensor. A counter electrode source is configured to selectively provide a first counter electrode voltage and a second counter electrode voltage to the counter electrode of the analyte sensor, wherein the first counter electrode voltage is not equal to the working electrode voltage, and the second counter electrode voltage is equal to the working electrode voltage; A protection source is configured to provide a protection ring voltage to a protection ring that at least partially surrounds a contact area of ​​the working electrode, wherein the protection ring voltage is equal to or not equal to the working electrode voltage; The working electrode source, the reverse electrode source, and the protection source are separate sources, and each includes an output and a control input connected to the controller. The controller includes a processor coupled to a memory having instructions stored therein: A current measurement circuit, which is connected to the controller and configured to measure the current flowing to the working electrode; as well as A reference resistor is electrically connected between the working electrode and the guard ring; The instructions stored in the memory, when executed by the processor, cause the controller to perform at least one integrity check in the following manner: The control input to the working electrode source is provided with instructions to apply the working electrode voltage to the working electrode. Provide another instruction to the control input of the counter electrode source to apply the first counter electrode voltage or the second counter electrode voltage to the counter electrode. Provide another instruction to the control input of the protection source to apply the protection ring voltage to the protection ring, and The current measurement circuit is used to measure the current flowing to the working electrode to determine whether the analyte monitor is faulty based on the measured current.

2. The analyte monitor of claim 1, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to measure the analyte concentration in such a manner as follows: Apply the working electrode voltage to the working electrode. Applying a first counter-electrode voltage to the counter-electrode, wherein the first counter-electrode voltage is not equal to the working electrode voltage, and The guard ring voltage is applied to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage.

3. The analyte monitor of claim 2, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to generate a signal in response to a measured current flowing to the working electrode exceeding a predetermined number of amperes during analyte concentration measurement.

4. The analyte monitor of claim 1, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to perform a first integrity check in such a way as: Apply the working electrode voltage to the working electrode. A second counter-electrode voltage is applied to the counter-electrode, wherein the second counter-electrode voltage is equal to the working electrode voltage, and The guard ring voltage is applied to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage.

5. The analyte monitor of claim 4, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to generate a signal in response to a measured current flowing to the working electrode exceeding a predetermined number of amperes during the first integrity check.

6. The analyte monitor of claim 5, wherein the predetermined ampere is greater than 20 nanoamps during the first integrity check.

7. The analyte monitor of claim 4, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to apply a reference electrode voltage equal to the second reverse electrode voltage to the reference electrode of the analyte sensor during the first integrity check.

8. The analyte monitor according to claim 1, wherein: The memory also includes instructions that, when executed by the processor, cause the controller to selectively provide a first protection ring voltage and a second protection ring voltage to the protection ring; and The memory also includes instructions that, when executed by the processor, cause the controller to perform at least one integrity check in the following manner: Apply the working electrode voltage to the working electrode. A second counter-electrode voltage is applied to the counter-electrode, wherein the second counter-electrode voltage is equal to the working electrode voltage, and A second protection ring voltage is applied to the protection ring, wherein the second protection ring voltage is not equal to the working electrode voltage.

9. The analyte monitor of claim 8, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to generate a signal in response to a measured current flowing to the working electrode during the at least one integrity check exceeding a first predetermined ampere or being less than a second predetermined ampere.

10. The analyte monitor of claim 9, wherein during the at least one integrity check, the first predetermined ampere is at least 2% greater than the quotient of the difference between the working electrode voltage and the second guard ring voltage and the resistance of the reference resistor, and the second predetermined ampere is at least 2% less than the quotient of the difference between the working electrode voltage and the second guard ring voltage and the resistance of the reference resistor.

11. The analyte monitor of claim 8, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to apply a reference electrode voltage equal to the second reverse electrode voltage to the reference electrode of the analyte sensor during the at least one integrity check.

12. An analyte monitoring system, comprising: An analyte sensor having a working electrode and a counter electrode; A protective ring, the protective ring surrounding at least a portion of the contact area of ​​the working electrode; A reference resistor is electrically connected between the working electrode and the guard ring; as well as An analyte emitter connected to the analyte sensor, the analyte emitter comprising: A working electrode source is configured to provide a working electrode voltage to the working electrode; A counter electrode source is configured to selectively provide a first counter electrode voltage and a second counter electrode voltage to the counter electrode, wherein the first counter electrode voltage is not equal to the working electrode voltage, and the second counter electrode voltage is equal to the working electrode voltage; A protection source is configured to provide a protection ring voltage to the protection ring, wherein the protection ring voltage is equal to or not equal to the working electrode voltage; The working electrode source, the reverse electrode source, and the protection source are separate sources, and each includes an output and a control input connected to the controller. The controller includes a processor coupled to a memory having instructions stored therein; A current measurement circuit, which is connected to the controller and configured to measure the current flowing to the working electrode; The instructions stored in the memory, when executed by the processor, cause the controller to perform at least one integrity check in the following manner: The control input of the working electrode source is provided with an instruction to apply the working electrode voltage to the working electrode; another instruction is provided to the control input of the reverse electrode source to apply the first reverse electrode voltage or the second reverse electrode voltage to the reverse electrode; and another instruction is provided to the control input of the protection source to apply the protection ring voltage to the protection ring; and The current flowing to the working electrode is measured using the current measurement circuit to determine whether the analyte monitoring system is malfunctioning based on the measured current.

13. The analyte monitoring system of claim 12, wherein the memory further comprises instructions, which, when executed by the processor, cause the controller to measure the analyte concentration in such a manner as follows: Apply the working electrode voltage to the working electrode. Applying a first counter-electrode voltage to the counter-electrode, wherein the first counter-electrode voltage is not equal to the working electrode voltage, and The guard ring voltage is applied to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage.

14. The analyte monitoring system of claim 13, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to generate a signal in response to a measured current flowing to the working electrode exceeding a predetermined number of amperes during analyte concentration measurement.

15. The analyte monitoring system of claim 13, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to perform a first integrity check in such a way as: Apply the working electrode voltage to the working electrode. A second counter-electrode voltage is applied to the counter-electrode, wherein the second counter-electrode voltage is equal to the working electrode voltage, and The guard ring voltage is applied to the guard ring, wherein the guard ring voltage is equal to the working electrode voltage.

16. The analyte monitoring system of claim 15, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to generate a signal in response to a measured current flowing to the working electrode exceeding a predetermined number of amperes during the first integrity check.

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

18. The analyte monitoring system of claim 15, wherein the analyte sensor has a reference electrode, and wherein the memory further includes instructions that, when executed by the processor, cause the controller to apply a reference electrode voltage equal to the second reverse electrode voltage to the reference electrode during the first integrity check.

19. The analyte monitoring system according to claim 13, wherein: The memory has instructions stored therein, which, when executed by the processor, cause the controller to: Selectively provide a first guard ring voltage and a second guard ring voltage to the guard ring; and Perform at least one integrity check in the following ways: Apply the working electrode voltage to the working electrode. A second counter-electrode voltage is applied to the counter-electrode, wherein the second counter-electrode voltage is equal to the working electrode voltage, and A second protection ring voltage is applied to the protection ring, wherein the second protection ring voltage is not equal to the working electrode voltage.

20. The analyte monitoring system of claim 19, wherein the memory further comprises instructions that, when executed by the processor, cause the controller to generate a signal in response to a measured current flowing to the working electrode during the at least one integrity check exceeding a first predetermined ampere or being less than a second predetermined ampere.

21. The analyte monitoring system of claim 20, wherein during the at least one integrity check, the first predetermined ampere is at least 2% greater than the quotient of the difference between the working electrode voltage and the second guard ring voltage and the resistance of the reference resistor, and the second predetermined ampere is at least 2% less than the quotient of the difference between the working electrode voltage and the second guard ring voltage and the resistance of the reference resistor.

22. The analyte monitoring system of claim 19, wherein the analyte sensor has a reference electrode, and wherein the memory further includes instructions that, when executed by the processor, cause the controller to apply a reference electrode voltage equal to the first reverse electrode voltage to the reference electrode during the at least one integrity check.

23. A method for operating an analyte monitoring system, comprising: Provides analyte sensors with working and counter electrodes; Provide a protective ring around at least a portion of the contact area of ​​the working electrode; A reference resistor is provided between the working electrode and the guard ring; Provide instructions to the control input of the working electrode source to apply a working electrode voltage to the working electrode; Provide another instruction to the control input of the reverse electrode source to selectively apply one of a first reverse electrode voltage and a second reverse electrode voltage to the reverse electrode, wherein the first reverse electrode voltage is not equal to the working electrode voltage and the second reverse electrode voltage is equal to the working electrode voltage; Provide another instruction to the control input of the protection source to apply a protection ring voltage to the protection ring, wherein the protection ring voltage is equal to or not equal to the working electrode voltage; as well as An integrity check is performed by measuring the current flowing to the working electrode to determine whether the analyte monitoring system is faulty based on the measured current. The working electrode source, the reverse electrode source, and the protection source are separate sources, and each includes an output and a control input connected to the controller.

24. The method of claim 23, further comprising measuring the analyte concentration by: Applying a first counter-electrode voltage to the counter-electrode, wherein the first counter-electrode voltage is not equal to the working electrode voltage, and A first protection ring voltage is applied to the protection ring, wherein the first protection ring voltage is equal to the working electrode voltage.

25. The method of claim 23, further comprising performing the first integrity check by: Apply the second counter electrode voltage to the counter electrode, and A first guard ring voltage is applied to the guard ring. The voltage of the second reverse electrode and the voltage of the first guard ring are equal to the voltage of the working electrode.

26. The method of claim 23, further comprising performing a second integrity check by: A second counter-electrode voltage is applied to the counter-electrode, wherein the second counter-electrode voltage is equal to the working electrode voltage, and A second protection ring voltage is applied to the protection ring, wherein the second protection ring voltage is not equal to the working electrode voltage.

Images