CN117890449A - System and method for detecting the presence of insulin adjunct - Google Patents

System and method for detecting the presence of insulin adjunct Download PDF

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Publication number
CN117890449A
CN117890449A CN202311329138.1A CN202311329138A CN117890449A CN 117890449 A CN117890449 A CN 117890449A CN 202311329138 A CN202311329138 A CN 202311329138A CN 117890449 A CN117890449 A CN 117890449A
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China
Prior art keywords
isig
insulin
glucose sensor
eis
adjunct
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M·R·米勒
E·加莱
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Medtronic Minimed Inc
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Medtronic Minimed Inc
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Abstract

The present disclosure provides a glucose sensor comprising: a working electrode configured to provide a current signal (Isig WE1) based on a glucose level; a background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjuvant; and a controller. The controller is configured to monitor the Isig WE1 at the working electrode, monitor the Isig WE2 at the background electrode, monitor at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, and calculate a change in the at least one EIS parameter, detect the presence of the insulin adjunct based on the change. In the event that the presence of the insulin adjunct is detected, the controller is further configured to compensate the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2, and output the compensated Isig WE1(IsigCOMP.

Description

System and method for detecting the presence of insulin adjunct
Cross Reference to Related Applications
The present application claims the benefit and priority of U.S. patent application Ser. No. 63/416,005 filed on 10/14 of 2022, the entire contents of which are hereby incorporated by reference.
Technical Field
The present disclosure relates generally to glucose sensor technology for sensing a variety of physiological parameters (e.g., glucose concentration), and more particularly to glucose sensor systems and methods for detecting the presence of insulin adjunct.
Background
Continuous Glucose Monitoring (CGM) has been used to continuously monitor a user's glucose level and alert the user when the glucose level is outside of a normal range. Glucose levels may be measured based on raw glucose sensor values (e.g., sensor current) and counter voltages. Insulin is injected into the user when the glucose level is greater than the safe range. Typically, one or more excipients in insulin are also injected to provide stability and antimicrobial properties. However, the adjuvant may affect the sensor signal and thus the glucose level.
Disclosure of Invention
The present disclosure relates to systems and methods for detecting the presence of an adjunct in insulin so that proper glucose levels can be provided. When insulin is injected, the insulin adjunct is also injected and causes a change in the signal measured by the glucose sensor. Thus, by monitoring the change in these signals, the presence of auxiliary material can be detected. According to aspects of the present disclosure, a glucose sensor includes: a working electrode configured to provide a current signal (Isig WE1) based on a glucose level; a background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjuvant; and a controller. The controller is configured to monitor Isig WE1 at the working electrode, monitor Isig WE2 at the background electrode, monitor at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, calculate a change in the at least one EIS parameter after insulin injection, and detect the presence of insulin adjunct based on the change. In the event that the presence of the insulin bolus is detected, the controller is further configured to compensate Isig WE1 based on a predetermined relationship between Isig WE1 and Isig WE2, and output compensated IsigWE (Isig COMP).
In various aspects, the at least one EIS parameter is the real impedance at 0.1 Hz.
In various aspects, the at least one EIS parameter is a virtual impedance at 0.1 Hz.
In various aspects, the predetermined relationship between Isig WE1 and Isig WE2 is a linear relationship. This Isig COMP is equal to: isig WE1-α*IsigWE2, where α is the slope of the linear relationship.
In various aspects, the slope has a profile based on the number of insulin injections. The glucose sensor also includes a memory that stores the number of insulin injections and the profile.
In various aspects, the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
According to aspects of the present disclosure, a glucose sensor includes: a cannula connected to the insulin pump and configured to inject insulin therethrough; a working electrode configured to provide a current signal (Isig WE1) based on a glucose level; a background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjuvant; and a controller. The controller is configured to monitor IsigWE a at the working electrode, monitor Isig WE2 at the background electrode, monitor at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, calculate a change in the at least one EIS parameter after insulin injection, and detect the presence of insulin adjunct based on the change. In the event that the presence of the insulin adjunct is detected, the controller is further configured to compensate the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2 and output the compensated Isig WE1(IsigCOMP.
In various aspects, the at least one EIS parameter is the real impedance at 0.1 Hz.
In various aspects, the at least one EIS parameter is a virtual impedance at 0.1 Hz.
In various aspects, the predetermined relationship between Isig WE1 and Isig WE2 is a linear relationship. This Isig COMP is equal to: isig WE1-α*IsigWE2, where α is the slope of the linear relationship.
In various aspects, the slope has a profile based on the number of insulin injections. The glucose sensor also includes a memory that stores the number of insulin injections and the profile.
In various aspects, the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
According to aspects of the present disclosure, a method for compensating for glucose levels from a glucose sensor based on the presence of an insulin bolus includes monitoring a current signal at a working electrode of the glucose sensor (Isig WE1), monitoring a current signal at a background electrode of the glucose sensor (Isig WE2), monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, calculating a change in the at least one EIS parameter after insulin injection; and detecting the presence of insulin adjunct based on the change. In the event that the presence of insulin adjunct is detected, the method further includes compensating Isig WE1 based on a predetermined relationship between Isig WE1 and Isig WE2, and outputting the compensated Isig WE1(IsigCOMP.
In various aspects, the at least one EIS parameter is the real impedance at 0.1 Hz.
In various aspects, the at least one EIS parameter is a virtual impedance at 0.1 Hz.
In various aspects, the predetermined relationship between Isig WE1 and Isig WE2 is a linear relationship. This Isig COMP is equal to: isig WE1-α*IsigWE2, where α is the slope of the linear relationship.
In various aspects, the slope has a profile based on the number of insulin injections.
In various aspects, the method further comprises storing the number of insulin injections and the profile in a memory of the glucose sensor.
In various aspects, the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
According to aspects of the disclosure, a non-transitory computer-readable medium stores instructions that, when executed by a computing device, cause the computing device to perform a method for compensating for a glucose level from a glucose sensor based on the presence of an insulin bolus. The method comprises monitoring a current signal (Isig WE1) at a working electrode of the glucose sensor, monitoring a current signal (Isig WE2) at a background electrode of the glucose sensor, monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, calculating a change in the at least one EIS parameter after insulin injection; and detecting the presence of insulin adjunct based on the change. In the event that the presence of insulin adjunct is detected, the method further includes compensating Isig WE1 based on a predetermined relationship between Isig WE1 and Isig WE2, and outputting the compensated Isig WE1(IsigCOMP.
According to aspects of the present disclosure, a glucose sensor includes: a working electrode configured to provide a current signal (Isig WE1) based on a glucose level; a background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjuvant; and a controller. The controller is configured to monitor a current signal (IsigWE 1) at the working electrode, monitor a current signal (IsigWE) at the background electrode, calculate a change in IsigWE2 after injection of insulin, and detect the presence of insulin auxiliary material based on the change. In the event that the presence of the insulin adjunct is detected, the controller is further configured to compensate the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2 and output the compensated Isig WE1(IsigCOMP.
In various aspects, the predetermined relationship between Isig WE1 and Isig WE2 is a linear relationship. This Isig COMP is equal to: isig WE1-α*IsigWE2, where α is the slope of the linear relationship.
In various aspects, the slope has a profile based on the number of insulin injections.
In various aspects, the glucose sensor further comprises a memory that stores the number of insulin injections and the profile.
In various aspects, the voltage applied to the background electrode ranges from 500mV to 600mV.
In various aspects, the controller is further configured to monitor an Electrochemical Impedance Spectroscopy (EIS) signal at the working electrode and confirm the presence of insulin adjunct based on the EIS signal of the at least one parameter.
In various aspects, the at least one parameter is the real impedance of the EIS signal at 0.1 Hz.
In various aspects, the at least one parameter is a virtual impedance of the EIS signal at 0.1 Hz.
In various aspects, the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
According to aspects of the present disclosure, a glucose sensor system includes: a cannula connected to the insulin pump and configured to inject insulin therethrough; a working electrode configured to provide a current signal (Isig WE1) based on a glucose level; a background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjuvant; and a controller. The controller is configured to monitor Isig WE1 at the working electrode, monitor Isig WE2 at the background electrode, calculate a change in Isig WE2 after insulin injection, and detect the presence of insulin adjunct based on the change. In the event that the presence of the insulin adjunct is detected, the controller is further configured to compensate the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2 and output the compensated Isig WE1(IsigCOMP.
In various aspects, the predetermined relationship between Isig WE1 and Isig WE2 is a linear relationship. This Isig COMP is equal to: isig WE1-α*IsigWE2, where α is the slope of the linear relationship.
In various aspects, the slope depends on the distance between the cannula and the working electrode.
In various aspects, the slope has a profile based on the number of insulin injections. The profile is based on the distance between the sleeve and the background electrode. The glucose sensor system also includes a memory that stores the number of insulin injections and a profile.
In various aspects, the voltage applied to the background electrode ranges from 500mV to 600mV.
In various aspects, the controller is further configured to monitor at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, and confirm the presence of the insulin adjunct based on the at least one EIS parameter. The at least one EIS parameter is the real impedance of the EIS signal at 0.1 Hz. The at least one EIS parameter is a virtual impedance of the EIS signal at 0.1 Hz.
In various aspects, the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
According to aspects of the present disclosure, a method for compensating for glucose concentration from a glucose sensor based on the presence of insulin auxiliary material includes monitoring a current signal (IsigWE a) at a working electrode of the glucose sensor, monitoring a current signal (IsigWE 2) at a background electrode of the glucose sensor, calculating a change in IsigWE2 after insulin injection, and detecting the presence of insulin auxiliary material based on the change. In the event that the presence of insulin adjunct is detected, the method further includes compensating Isig WE1 based on a predetermined relationship between Isig WE1 and Isig WE2, and outputting the compensated Isig WE1(IsigCOMP.
In various aspects, the predetermined relationship between Isig WE1 and Isig WE2 is a linear relationship. This Isig COMP is equal to: isig WE1-α*IsigWE2, where α is the slope of the linear relationship.
In various aspects, the slope depends on the distance between the cannula through which insulin is injected and the working electrode.
In various aspects, the slope has a profile based on the number of insulin injections. The longer the insulin is injected, the lower the slope.
In various aspects, the voltage applied to the background electrode ranges from 500mV to 600mV.
In various aspects, the method further comprises monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode, and confirming the presence of insulin adjunct based on the at least one EIS parameter. The at least one EIS parameter is a real impedance at 0.1Hz, or the at least one EIS parameter is a imaginary impedance at 0.1 Hz.
In various aspects, the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
According to aspects of the disclosure, a non-transitory computer-readable medium stores instructions that, when executed by a computing device, cause the computing device to perform a method for compensating for a glucose level from a glucose sensor based on the presence of an insulin bolus. The method comprises monitoring a current signal (IsigWE) at a working electrode of the glucose sensor, monitoring a current signal (IsigWE) at a background electrode of the glucose sensor, calculating a change in IsigWE2 after insulin injection, and detecting the presence of insulin auxiliary material based on the change. In the event that the presence of insulin adjunct is detected, the method further includes compensating Isig WE1 based on a predetermined relationship between Isig WE1 and Isig WE2, and outputting the compensated Isig WE1(IsigCOMP.
The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the technology described in this disclosure will be apparent from the description and drawings, and from the claims.
Drawings
Aspects of the disclosure will be described in detail with reference to the drawings, wherein like numerals represent corresponding parts throughout the several views.
FIG. 1 illustrates a perspective view of a subcutaneous sensor insertion set and a block diagram of sensor electronics in accordance with one or more aspects.
Fig. 2 illustrates a substrate having two sides, a first side containing an electrode configuration and a second side containing electronic circuitry, in accordance with one or more aspects.
FIG. 3 illustrates a block diagram of an electronic circuit for sensing an output of a sensor, in accordance with one or more aspects.
FIG. 4 illustrates a block diagram of sensor electronics and a sensor including a plurality of electrodes, in accordance with one or more aspects.
Fig. 5 illustrates alternative aspects including a sensor and sensor electronics in accordance with one or more aspects.
FIG. 6 illustrates an electronic block diagram of a sensor electrode and a voltage applied to the sensor electrode, in accordance with one or more aspects.
FIG. 7 illustrates a block diagram of a glucose sensor system, in accordance with one or more aspects.
Fig. 8 shows a graphical representation of a false increase of the current signal (Isig) at the working electrode of the glucose sensor due to the presence of an auxiliary material in the insulin.
Fig. 9 illustrates a graphical representation of Isig and changes in voltage signal due to the presence of an excipient in insulin in accordance with one or more aspects.
FIG. 10 illustrates a graphical representation of the variation of real and imaginary impedance of an EIS signal at a working electrode, in accordance with one or more aspects.
FIG. 11 illustrates a graphical representation of the variation of real and imaginary impedance of an EIS signal at a background electrode in accordance with one or more aspects.
Fig. 12 illustrates a graphical representation of Isig and changes in voltage signal due to the presence of an excipient in insulin in accordance with one or more aspects.
FIG. 13 illustrates a graphical representation of the variation of real and imaginary impedance of an EIS signal at a working electrode, in accordance with one or more aspects.
FIG. 14 illustrates a graphical representation of the variation of real and imaginary impedance of an EIS signal at a background electrode in accordance with one or more aspects.
FIG. 15 illustrates a graphical representation of changes in Isig at a working electrode and EIS signals at a background electrode due to the presence of an excipient in insulin and a voltage applied to the working electrode, in accordance with one or more aspects.
FIG. 16 illustrates a graphical representation of a linear relationship between the magnitude of Isig at a working electrode and insulin concentration at the beginning of a first insulin injection in accordance with one or more aspects.
FIG. 17 illustrates a graphical representation of a linear relationship between the magnitude of Isig at a working electrode and insulin concentration at the end of a first insulin injection in accordance with one or more aspects.
FIG. 18 illustrates a graphical representation of a linear relationship between the magnitude of Isig at a working electrode and insulin concentration at the beginning of a second insulin injection in accordance with one or more aspects.
Fig. 19 illustrates a flow diagram of a method for detecting the presence of an adjunct in insulin, according to one or more aspects.
Fig. 20 illustrates a flow diagram of a method for detecting the presence of an adjunct in insulin, according to one or more aspects.
Detailed Description
In the following description, reference is made to the accompanying drawings which form a part hereof and which illustrate several aspects of the disclosure. It is to be understood that other aspects may be utilized and structural and operational changes may be made without departing from the scope of the present disclosure.
Aspects are described below with reference to flowchart illustrations of methods, systems, apparatus, devices, program products and computer program products. It will be understood that each block of the flowchart illustrations, and combinations of blocks in the flowchart illustrations, can be implemented by program instructions, including computer program instructions (such as any menu screen described in the figures). These computer program instructions may be loaded onto a computer or other programmable data processing apparatus, such as a controller, microcontroller, or processor in a sensor electronics, to produce a machine, such that the instructions which execute on the computer or other programmable data processing apparatus create instructions for implementing the functions specified in the flowchart block or blocks. These computer program instructions may also be stored in a computer-readable memory that can direct a computer or other programmable data processing apparatus to function in a particular manner, such that the instructions stored in the computer-readable memory produce an article of manufacture including instructions which implement the function specified in the flowchart block or blocks. The computer program instructions may also be loaded onto a computer or other programmable data processing apparatus to cause a series of operational steps to be performed on the computer or other programmable apparatus to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide steps for implementing the functions specified in the flowchart block or blocks and/or the menus presented herein. The programming instructions may also be stored in and/or implemented with electronic circuitry, including Integrated Circuits (ICs) and Application Specific Integrated Circuits (ASICs), for use with the sensor devices, apparatus, and systems.
Fig. 1 is a perspective view of a subcutaneous sensor insertion set and a block diagram of sensor electronics according to various aspects of the present disclosure. As shown in fig. 1, a subcutaneous sensor set 10 is provided for subcutaneous placement of a movable portion (see, e.g., fig. 2) or the like of a flexible sensor 12 at a selected location within a user's body. The subcutaneous or transcutaneous portion of sensor set 10 includes a hollow slotted insertion needle 14 and cannula 16. The needle 14 is used to facilitate quick and easy placement of the cannula 16 subcutaneously at the subcutaneous insertion site. Inside the cannula 16 is a sensing portion 18 of the sensor 12 for exposing one or more sensor electrodes 20 to a body fluid of a user through a window 22 formed in the cannula 16. In an aspect of the disclosure, the one or more sensor electrodes 20 can include a counter electrode, a reference electrode, and one or more working electrodes. After insertion, the insertion needle 14 is withdrawn, leaving the cannula 16 and sensing portion 18 and sensor electrode 20 in place at the selected insertion site.
In a particular aspect, the subcutaneous sensor set 10 facilitates accurate placement of a flexible thin film electrochemical sensor 12 of the type used to monitor a particular blood parameter indicative of a user's condition. The sensor 12 monitors glucose levels within the body and may be used in conjunction with an automatic or semi-automatic drug infusion pump of the external or implantable type described below to control insulin delivery to a diabetic patient: for example, U.S. patent No. 4,562,751; 4,678,408 th sheet; 4,685,903 or 4,573,994, the entire contents of which are incorporated herein by reference.
Particular aspects of the flexible electrochemical sensor 12 are constructed in accordance with thin film shielding techniques to include an elongated thin film conductor embedded or encased between a selected insulating material (such as a polyimide film or polyimide sheet) and a membrane. When the sensing portion 18 (or active portion) of the sensor 12 is placed subcutaneously at the insertion site, the sensor electrode 20 at the tip of the sensing portion 18 is exposed through one of the insulating layers to be in direct contact with the patient's blood or other body fluid. The sensing portion 18 is joined to a connection portion 24 that terminates in a conductive contact pad or the like that is also exposed through one of the insulating layers. In alternative aspects, other types of implantable sensors may be used, such as chemical-based sensors, optical-based sensors, and the like.
The connection portion 24 and contact pads are generally adapted for direct wired electrical connection to a suitable monitor or sensor electronics 100 for monitoring a user's condition in response to signals derived from the sensor electrodes 20, as is known in the art. Further description of this general type of flexible thin film sensor can be found, for example, in U.S. patent No. 5,391,250, which is incorporated herein by reference. The connection portion 24 may be conveniently electrically connected to the monitor or sensor electronics 100, or by a connector block 28 (or the like) as shown and described, for example, in U.S. patent No. 5,482,473, which is also incorporated herein by reference. Thus, in accordance with aspects of the present disclosure, the subcutaneous sensor set 10 may be configured or formed to work with a wired or wireless characteristic monitoring system.
The sensor electrode 20 may be used in a variety of sensing applications and may be configured in a variety of ways. For example, the sensor electrode 20 may be used in physiological parameter sensing applications where a certain type of biological molecule is used as a catalyst. For example, sensor electrode 20 may be used in a glucose and oxygen sensor having glucose oxidase (GOx) that catalyzes a reaction with sensor electrode 20. The reaction produces gluconic acid (C6H 12O 7) and hydrogen peroxide (H2O 2) in proportion to the amount of glucose present.
The sensor electrode 20 along with biomolecules or some other catalyst may be placed in a vascular or non-vascular environment within a human body. For example, the sensor electrode 20 and biomolecules may be placed in a vein and subjected to blood flow, or may be placed in a subcutaneous or peritoneal region of the human body.
The monitor 100 may also be referred to as a sensor electronics 100. Monitor 100 may include a power supply 110, a sensor interface 122, processing electronics 124, and data formatting electronics 128. Monitor 100 may be coupled to sensor set 10 by a cable 102 via a connector that is electrically coupled to connector block 28 of connection portion 24. In alternative aspects, the cable 102 may be omitted. In this aspect of the disclosure, the monitor 100 may include a suitable connector for directly connecting to the connecting portion 104 of the sensor set 10. The sensor set 10 may be modified such that the connector portion 104 is positioned at a different location, such as on top of the sensor set 10, to facilitate placement of the monitor 100 over the sensor set 10.
In aspects of the present disclosure, the sensor interface 122, the processing electronics 124, and the data formatting electronics 128 are formed as separate semiconductor chips, however, alternative aspects may combine the various semiconductor chips into a single or multiple custom semiconductor chips. The sensor interface 122 is connected to a cable 102 that is connected to the sensor set 10.
The power source 110 may be a battery. The battery may include three silver oxide cells connected in series. In alternative aspects, different battery chemistries, such as lithium-based chemistries, alkaline batteries, nickel metal hydrides, etc., may be utilized and different numbers of batteries may be used. Monitor 100 provides power to the sensor group via power source 110 through cable 102 and cable connector 104. In one aspect of the present disclosure, power is the voltage provided to the sensor group 10. In one aspect of the present disclosure, power is the current provided to the sensor group 10. In one aspect of the present disclosure, power is the voltage provided to the sensor group 10 at a particular voltage.
Fig. 2 illustrates an implantable sensor and electronics for driving the implantable sensor according to an aspect of the present disclosure. FIG. 2 shows a substrate or flexure 220 having two sides; the first side 222 contains an electrode configuration and the second side 224 contains electronic circuitry. As shown in fig. 2, the first side 222 of the substrate includes two counter electrode-working electrode pairs 240, 242, 244, 246 on opposite sides of a reference electrode 248. The second side 224 of the substrate includes electronic circuitry. As shown, the electronic circuitry may be enclosed in a hermetically sealed enclosure 226, providing a protective enclosure for the electronic circuitry. This allows the sensor substrate 220 to be inserted into a vascular environment or other environment that may subject the electronic circuitry to fluids. By sealing the electronic circuitry in the hermetically sealed enclosure 226, the electronic circuitry can operate without risk of being shorted by surrounding fluid. Also shown in fig. 2, pad 228 is connected to input and output lines of the electronic circuitry. The electronic circuitry itself may be manufactured in a variety of ways. In accordance with an aspect of the present disclosure, electronic circuitry may be fabricated as integrated circuits using techniques commonly used in the industry.
Fig. 3 illustrates a general block diagram of an electronic circuit for sensing an output of a sensor in accordance with aspects of the present disclosure. At least one pair of sensor electrodes 310 may interface to a data converter 312, the output of which may interface to a counter electrode 314. The counter electrode 314 may be controlled by control logic 316. The output of the counter electrode 314 may be connected to a line interface 318. Line interface 318 may be connected to input and output lines 320 and may also be connected to control logic 316. The input and output lines 320 may also be connected to a power rectifier 322.
The sensor electrode 310 may be used in a variety of sensing applications and may be configured in a variety of ways. For example, the sensor electrode 310 may be used in physiological parameter sensing applications where a certain type of biological molecule is used as a catalyst. For example, sensor electrode 310 may be used in a glucose and oxygen sensor having glucose oxidase (GOx) that catalyzes a reaction with sensor electrode 310. The sensor electrode 310 along with biomolecules or some other catalyst may be placed in a vascular or non-vascular environment within a human body. For example, the sensor electrode 310 and biomolecules may be placed in a vein and subjected to blood flow.
Fig. 4 illustrates a block diagram of sensor electronics and a sensor including multiple electrodes in accordance with an aspect of the disclosure. The sensor set or system 350 includes a sensor 355 and sensor electronics 360. Sensor 355 includes counter electrode 365, reference electrode 370, and working electrode 375. The sensor electronics 360 includes a power supply 380, a regulator 385, a signal processor 390, a measurement processor 395, and a display/transmission module 397. The power supply 380 provides power (in the form of voltage, current, or voltage including current) to a regulator 385. The regulator 385 transmits the regulated voltage to the sensor 355. In one aspect of the present disclosure, the regulator 385 transmits a voltage to the counter electrode 365 of the sensor 355.
The sensor 355 generates a sensor signal indicative of the concentration of the measured physiological characteristic. For example, the sensor signal may be indicative of a blood glucose reading. In aspects of the disclosure that utilize subcutaneous sensors, the sensor signal may be representative of hydrogen peroxide levels in the subject. In aspects of the present disclosure that utilize a blood or skull sensor, the oxygen level is measured by the sensor and represented by the sensor signal. In aspects of the disclosure that utilize an implantable or long-term sensor, the sensor signal may be representative of oxygen levels in the subject. The sensor signal may be measured at the working electrode 375. In an aspect of the disclosure, the sensor signal may be a current measured at the working electrode. In an aspect of the disclosure, the sensor signal may be a voltage measured at the working electrode.
After measuring the sensor signal at sensor 355 (e.g., the working electrode), signal processor 390 receives the sensor signal (e.g., the measured current or voltage). The signal processor 390 processes the sensor signals and generates processed sensor signals. The measurement processor 395 receives the processed sensor signals and calibrates the processed sensor signals with the reference values. In an aspect of the disclosure, the reference value is stored in a reference memory and provided to the measurement processor 395. The measurement processor 395 generates sensor measurements. The sensor measurements may be stored in a measurement memory (not shown). The sensor measurements may be sent to a display/transmission device for display with the sensor electronics on a display in the housing or transmitted to an external device.
The sensor electronics 360 may be a monitor that includes a display to display the physiological characteristic readings. The sensor electronics 360 may also be mounted on a desktop computer, pager, television including communication capabilities, notebook computer, server, network computer, personal Digital Assistant (PDA), portable telephone including computer functions, infusion pump including a display, glucose sensor including a display, and/or a combination infusion pump/glucose sensor. The sensor electronics 360 may be housed in a cellular telephone, a smart phone, a network device, a home network device, and/or other appliance connected to a home network.
Fig. 5 illustrates an alternative aspect including a sensor and sensor electronics in accordance with an aspect of the disclosure. Sensor set or sensor system 400 includes sensor electronics 360 and sensor 355. Sensor 355 includes counter electrode 365, reference electrode 370, and working electrode 375. The sensor electronics 360 includes a microcontroller 410 and a digital-to-analog converter (DAC) 420. The sensor electronics 360 may also include a current-to-frequency converter (I/F converter) 430.
The microcontroller 410 includes software program code or programmable logic that, when executed, causes the microcontroller 410 to transmit a signal to the DAC 420, wherein the signal is representative of a voltage level or value to be applied to the sensor 355. DAC 420 receives the signal and generates a voltage value at a level indicated by microcontroller 410. In aspects of the present disclosure, the microcontroller 410 may change the representation of the voltage level in the signal frequently or infrequently. Illustratively, the signal from the microcontroller 410 may instruct the DAC 420 to apply the first voltage value for one second and apply the second voltage value for two seconds.
The sensor 355 may receive a voltage level or value. In an aspect of the disclosure, counter electrode 365 may receive an output of an operational amplifier having as inputs a reference voltage and a voltage value from DAC 420. Application of the voltage level causes sensor 355 to generate a sensor signal indicative of the concentration of the measured physiological characteristic. In an aspect of the present disclosure, the microcontroller 410 may measure a sensor signal (e.g., a current value) from the working electrode. Illustratively, the sensor signal measurement circuit 431 may measure the sensor signal. In an aspect of the present disclosure, the sensor signal measurement circuit 431 may include a resistor, and a current may flow through the resistor to measure a value of the sensor signal. In an aspect of the disclosure, the sensor signal may be a current level signal and the sensor signal measurement circuit 431 may be a current-to-frequency (I/F) converter 430. The I/F converter 430 can measure the sensor signal represented by the current reading, convert the sensor signal to a frequency-based sensor signal or EIS signal, and transmit the frequency-based sensor signal or EIS signal to the microcontroller 410. In aspects of the present disclosure, the microcontroller 410 may be able to more easily receive a frequency-based sensor signal than a non-frequency-based sensor signal. The microcontroller 410 receives the sensor signal (whether frequency-based or non-frequency-based) and determines a value of a physiological characteristic of the subject, such as blood glucose level. The microcontroller 410 may include program code that, when executed or run, is capable of receiving the sensor signal and converting the sensor signal into a physiological characteristic value.
In one aspect of the present disclosure, the microcontroller 410 may convert the sensor signal to a blood glucose level. When converting the sensor signal to a blood glucose value, the microcontroller 410 may use one or more models that are specific ways to calculate the blood glucose value using the sensor signal. In some aspects, the microcontroller 410 may utilize measurements stored within the internal memory (e.g., sensor signals from the sensor 355 and Electrochemical Impedance Spectroscopy (EIS) signals) in order to determine the blood glucose level of the subject. In some aspects, the microcontroller 410 may utilize measurements stored in a memory external to the microcontroller 410 to assist in determining the blood glucose level of the subject.
After the microcontroller 410 determines the physiological characteristic value, the microcontroller 410 may store the measured value of the physiological characteristic value for several periods of time. For example, a blood glucose value (BG) may be sent from the sensor to the microcontroller 410 every second or every five seconds, and the microcontroller may save the sensor measurements within five or ten minutes of BG reading. The microcontroller 410 may transmit the measured value of the physiological characteristic value to a display on the sensor electronics 360. For example, the sensor electronics 360 may be a monitor that includes a display that provides a blood glucose reading of the subject. In one aspect of the present disclosure, the microcontroller 410 may communicate the measured value of the physiological characteristic value to an output interface of the microcontroller 410. The output interface of the microcontroller 410 may communicate the measured value of the physiological characteristic value, such as a blood glucose value, to an external device, such as an infusion pump, a combination infusion pump/blood glucose meter, a computer, a personal digital assistant, a pager, a network appliance, a server, a cellular telephone, or any computing device.
Fig. 6 illustrates an electronic block diagram of a sensor electrode and a voltage applied to the sensor electrode according to one aspect of the present disclosure. In the aspect shown in FIG. 6, an operational amplifier 530 or other servo control device may be connected to the sensor electrode 510 through a circuit/electrode interface 538. Operational amplifier 530 uses feedback through the sensor electrode to attempt to maintain a specified voltage between reference electrode 532 and working electrode 534 by adjusting the voltage at counter electrode 536 (the DAC may wish the applied voltage to be the specified voltage). Current may then flow from counter electrode 536 to working electrode 534. Such a current may be measured to determine the electrochemical reaction between the sensor electrode 510 and the biomolecules of the sensor that have been placed in the vicinity of the sensor electrode 510 and used as a catalyst. The circuitry disclosed in fig. 6 may be used in a long term or implantable sensor, or may be used in a short term or subcutaneous sensor.
In the long-term sensor aspect, where glucose oxidase (GOx) enzyme is used as a catalyst in the sensor, current can flow from counter electrode 536 to working electrode 534 only when oxygen is present in the vicinity of the enzyme and sensor electrode 510. Illustratively, if the voltage provided at the reference electrode 532 is maintained at about 0.5 volts, the amount of current flowing from the counter electrode 536 to the working electrode 534 has a fairly linear relationship with the unit slope of the amount of oxygen present in the region surrounding the enzyme and electrode. Thus, by maintaining the reference electrode 532 at about 0.5 volts and utilizing this region of the current-voltage curve to vary the blood oxygen level, improved accuracy in determining the amount of oxygen in the blood can be achieved. Different aspects of the present disclosure may utilize different sensors with biomolecules other than glucose oxidase, and thus may have voltages other than 0.5 volts set at the reference electrode. Many sensors require a stabilization period in order for the sensor 510 to provide an accurate reading of the physiological parameter of the subject. During the stabilization period, the sensor 510 does not provide an accurate blood glucose measurement. Users and manufacturers of sensors may wish to improve the stability timeframe of the sensor so that the sensor may be quickly utilized after insertion into a subject or into the subcutaneous layer of the subject.
Even after a stabilization time frame or during initial implantation or insertion of the sensor 510, the sensor 510 may provide inaccurate sensor signals due to signal noise in the sensor, electrochemical byproducts caused by oxidation and reduction, or foreign body responses that prevent oxygen from the interstitial tissue from reaching the chemical layer (particularly the glucose oxidase layer) on top of the working electrode. When the inaccuracy of the sensor signal becomes higher than the threshold, the working electrode 534 should be replaced and the user of the sensor needs to be notified. To extend the life of the working electrode 534, a medicament is coated on the working electrode 534. In one aspect, the agent is coated on a secondary polyimide flex disposed adjacent to a primary flex having a working electrode. The purpose of the agent is to suppress the foreign body response so that sufficient oxygen from the interstitial tissue reaches the chemical layer deposited on the working electrode. Such agents may be dexamethasone, dexamethasone phosphate, dexamethasone acetate, corticosteroids, NSAIDs, anti-fibrotic agents and/or siRNA. In the presence of the medicament coating, the lifetime of the working electrode 534 may be extended from about one week to about 16 days or more.
In an alternative aspect, the medicament may be coated on a primary flex having a working electrode. The medicament may be coated in a top portion of the primary flex and the working electrode may be located on a bottom portion of the primary flex. In one aspect, the medicament may be coated in a bottom portion of the primary flex and the working electrode may be located on a top portion. On the other hand, the medicament and the working electrode may be positioned at different positions from each other on the main flexible member. Regardless of the location of the medicament and working electrode, when the glucose sensor is mounted on the user, the primary flexible member enters the body of the user such that the medicament and working electrode also enter the body.
FIG. 7 illustrates a block diagram of an integrated glucose sensor system 700 in accordance with aspects of the present disclosure. Glucose sensor system 700 may include a housing 710, a glucose sensor 720 secured to a substrate, and an optional insulin delivery cannula 730. Electronic circuitry for the glucose sensor may be fabricated within the housing 710 and one or more electrodes that are subcutaneously accessed into the user's body may be placed over the glucose sensor 720. An optional insulin delivery cannula 730 of the glucose sensor system 700 is also inserted subcutaneously into the user and insulin may be injected through the insulin delivery cannula. In this regard, insulin pump 740 may optionally be incorporated into glucose sensor system 700. Insulin pump 740 may be connected to an insulin reservoir that stores insulin and may pump insulin to a user via optional insulin cannula 730.
The distance "d" between the glucose sensor 720 and the optional insulin delivery cannula 730 can affect how the excipients that are part of the injected insulin to enhance the stability of the insulin affect the glucose sensor's reading. The closer the distance "d", the faster and greater the effect of the adjuvant on the glucose sensor reading. In the case where the optional insulin delivery cannula 730 is integrated within the glucose sensor system 700, the distance "d" may be short so that the glucose sensor system 700 may be made small enough to be portable. In one aspect, the distance "d" may be less than or equal to 25mm.
The auxiliary materials can be the combination of the following substances: peroxide (H 2O2), phenol (C 6H6 O), m-cresol (CH 3C6H4 (OH)), glycerol (C 3H8O3), zinc (Zn), zinc oxide (ZnO), disodium phosphate (Na 2HPO4), sodium chloride (NaCl), sodium hydroxide (NaOH), hydrogen chloride (HCl), nicotinamide (C 6H6N2 O), and/or arginine hydrochloride (C 6H15ClN4O2), and the like.
The effect of insulin bolus on the current at the working electrode of the glucose sensor (Isig), which indicates the glucose concentration, is in each case shown in the curves 810 to 840 of fig. 8. The vertical axis represents the magnitude of Isig in nanoamperes (nA) and the horizontal axis represents time in minutes. During an exemplary scenario, insulin placebo containing no insulin but insulin excipients is injected at t 1 in the presence of glucose at a concentration of 100mg/dL, and 3ppm peroxide is introduced at t 2. At t 3, a new solution was prepared in the presence of glucose at a concentration of 100mg/dL, and another insulin placebo was introduced during these scenarios.
Curves 810 to 840 were obtained at insulin concentrations of 2.5%, 2.0%, 1.0% and 0.5%, respectively. When the first placebo is introduced at t 1, all curves 810 to 840 show a sudden increase at t 1. This increase is a false increase in glucose readings because there is no change in glucose levels. The abrupt increase may be detected by comparing the amount of increase during the predetermined period. For example, when the increase in Isig is greater than or equal to a predetermined threshold (e.g., 10 nA) during a predetermined period (e.g., 5 minutes), it is determined that there is a sudden increase or change.
The vertices of curves 810 through 840 are for u 1nA、u2nA、u3 nA and u 4 nA, respectively, where u 1>＝u2>u3>u4. Thus, the apex of Isig may depend on the insulin concentration, or in other words, the concentration of insulin adjuncts.
During the period from t 1 to t 2, the effect of the adjuvant inhibited Isig when 3ppm peroxide was introduced. However, after the introduction of 3ppm peroxide (which is one of the insulin excipients and one of the main excipients that causes a false increase in Isig value), curves 810 to 840 also show another abrupt increase during the predetermined period of time, even though the increase at this time is less than the increase when the first placebo is injected. As shown in these exemplary scenarios, the impact of insulin injection on Isig may decrease with continued introduction of insulin adjuncts.
The vertices of curves 810 through 840 are different from each other. In addition, the peak of curve 810 is highest because the insulin concentration of curve 810 is highest, and the peak of curve 840 is lowest because the insulin concentration of curve 840 is lowest. Thus, the apex of Isig may depend on insulin concentration.
Starting again at t 2 in the presence of glucose at a concentration of 100mg/dL, curves 810 to 840 show a substantially flat line indicating glucose at a concentration of 100 mg/dL. At about t 3, another placebo, different from the first placebo, was introduced, resulting in another pseudo-increase in Isig.
According to aspects of the present disclosure, to compensate for a false increase in Isig at the working electrode based on the introduction or injection of insulin, the presence of an adjunct as a preservative for insulin is detected. Fig. 9-18 illustrate various relationships between signals of a glucose sensor (e.g., isig at the working electrode and Isig at the background electrode). As used herein, the term "background electrode" refers to an electrode of a glucose sensor that can be used to detect the presence of an adjunct. Referring again to fig. 7, both the working electrode and the background electrode (not shown) may be located in the glucose sensor 720.
Fig. 9 provides a graphical representation of a scenario of insulin injections at t 1 and at t 2 starting from the scenario, according to aspects of the present disclosure. The top graph shows Isig curve 910 measured at the working electrode of the glucose sensor and Isig curve 920 measured at the background working electrode of the glucose sensor. The vertical axis represents the magnitude of Isig in nA and the horizontal axis represents the time of day.
Throughout the day, glucose was present at a concentration of 40mg/dL in this scenario. Prior to the first injection of insulin at t 1, isig at the working electrode stayed at u 1 nA, which indicates a glucose concentration of 40mg/dL, while Isig at the background electrode stayed at zero, which means that no insulin adjuvant was detected. At t 1, 2.5mL of insulin at a concentration of 0.5% is introduced or injected for a first injection period (e.g., 30 minutes). As a result of the addition of excipients to insulin, isig at the working electrode increased to u 2 nA and Isig at the background electrode also increased to u 3 nA. This increase is considered to be a sudden increase because it is greater than a predetermined threshold during a predetermined period of time, and is false because the glucose level remains the same. From t 1 to t 2, both isigs stabilize to u 1 because the adjuvant is dispersed and its effect becomes correspondingly reduced.
Now at t 2, another injection of 2.5mL of insulin at a concentration of 0.5% is made for a second injection period longer than the first injection period. Due to the slower injection of insulin of the same concentration, the vertex of Isig at the working electrode hits u 4 nA, which is lower than the vertex u 2 during the first injection, and the vertex of Isig at the background electrode is u 5 nA, which is lower than the vertex u 3 during the first injection. Further, due to the slower injection during the second injection period, the Isig at the working electrode and the Isig at the background electrode take a longer period to stabilize than during the first injection. In one aspect, the relationship between Isig at the working electrode and Isig at the background electrode may be linear during the first and second injections of insulin. The linear relationship may be represented by a ratio. In another aspect, the linear ratio between the Isig at the working electrode and the Isig at the background electrode during the first injection may be substantially the same during the first injection, and as such, the linear ratio between the Isig at the working electrode and the Isig at the background electrode during the second injection may be substantially the same during the second injection. However, the ratio during the first injection may be higher than the ratio during the second injection.
In various aspects, the linear ratio may depend on the number of injections. In other words, the linear ratio may decrease linearly or exponentially with the number of insulin injections. Thus, the ratio profile may be stored in the glucose sensor and provide a linear ratio variation with the number of insulin injections in order to properly compensate for spurious increases in Isig at the working electrode during insulin injections.
For example, the compensation may be achieved by the following equation (1):
IsigCOMP＝IsigWE1-α*IsigWE2(1)，
Where Isig COMP is compensated Isig WE1,IsigWE1 is Isig at the working electrode, isig WE2 is Isig at the background electrode, and α is the linear ratio between Isig WE1 and Isig WE2.
In the case of including a cannula (via which insulin is injected) in the glucose sensor, this linear ratio may also depend on the distance between the background electrode and the cannula (e.g., "d" in fig. 7).
The bottom graph of fig. 9 shows a voltage curve 930 across the background electrode with the vertical axis being the voltage in millivolts (mV). As shown in voltage curve 930, the voltage does not increase or decrease at or during the beginning of the first and second insulin injections and, therefore, may not be used as an indicator of detecting insulin injections.
Fig. 10 and 11 illustrate real and imaginary impedances at the working and background electrodes during the scenario of fig. 9, according to aspects of the present disclosure. The top graph of fig. 10 shows two curves 1040a and 1040b of an Electrochemical Impedance Spectroscopy (EIS) signal, measured at the working electrode during both scenarios. In particular, curves 1040a and 1040b are real impedances in units of 10 5 Ω at 0.1 Hz. Curve 1040a shows the increase in real impedance of the EIS signal during the first insulin injection and curve 1040b shows the increase in real impedance of the EIS signal during the second insulin injection. However, curve 1040a does not show a significant increase in real impedance during the second insulin injection, and curve 1040b does not show a significant increase in real impedance during the first insulin injection. Thus, the real impedance at 0.1Hz at the working electrode may not be used primarily or solely to detect the presence of insulin auxiliary material, but may be used to confirm the detection of the presence of auxiliary material.
The bottom graph of fig. 10 shows two curves 1050a and 1050b of EIS signal, measured at the working electrode during both scenarios. In particular, curves 1050a and 1050b are imaginary impedances in units of 10 5 Ω at 0.1 Hz. Curves 1050a and 1050b show the increase in imaginary impedance of the EIS signal during the first insulin injection and the second insulin injection during the predetermined period. The imaginary impedance of the EIS signal at 0.1Hz from the working electrode can be used to detect the presence of insulin injections or insulin excipients. The presence of insulin adjunct can be determined when the increase in virtual impedance at 0.1Hz during a predetermined period of time (e.g., 5 minutes) is greater than a threshold impedance (e.g., 5 x 10 6 Ω). In this way, the imaginary impedance of the EIS signal at 0.1Hz from the working electrode can be used to confirm the presence of insulin injections or insulin adjuncts.
The top graph of fig. 11 shows two curves 1140a and 1140b of EIS signals measured at the background electrode during both of these scenarios. In particular, curves 1140a and 1140b are real impedances in units of 10 5 Ω at 0.1 Hz. Curve 1140a shows the increase in real impedance of the EIS signal during the first insulin injection. Even though curve 1140b does not show a significant increase in the real impedance of the EIS signal during the first insulin injection, the increase in impedance may be greater than the threshold impedance because the unit is 10 5 Ω. The threshold impedance may be between 0.5 x 10 6 Ω and 5 x 10 6 Ω. Curve 1140a also shows the increase in real impedance during the second insulin injection, and curve 1140b also shows the increase in real impedance during the second insulin injection. Thus, the real impedance at 0.1Hz at the background electrode can be used to detect the presence of insulin adjuvant and confirm the detection of the presence of adjuvant.
The bottom graph of fig. 11 shows two curves 1150a and 1150b of EIS signal, measured at the background electrode during these two scenarios. In particular, curves 1150a and 1150b are imaginary impedances in units of 10 5 Ω at 0.1 Hz. Curves 1150a and 1150b show a small increase in the imaginary impedance of the EIS signal during the first and second insulin injections (which may be greater than the threshold impedance), while curves 1150a and 1150b show a general decrease in the imaginary impedance. Even though the increase appears to be small, the increase may be significant since the unit of magnitude is 10 5 Ω. Thus, the imaginary impedance of the EIS signal at 0.1Hz from the background electrode can be used to detect the presence of insulin injections or insulin supplements. In addition, the imaginary impedance of the EIS signal at 0.1Hz from the background electrode can be used to confirm the presence of insulin injections or insulin adjuncts.
Summarizing with respect to fig. 9-11, the presence of insulin adjunct can be detected by Isig from the background electrode and can be confirmed by a change in real or imaginary impedance at 0.1Hz of the EIS signal from one of the working electrode and the background electrode during a predetermined period of time.
Fig. 12 provides a graphical representation of a scene showing insulin injections at t 1 and at t 2 from the scene, according to aspects of the present disclosure. The top graph shows Isig curve 1210 measured at the working electrode of the glucose sensor and Isig curve 1220 measured at the background working electrode of the glucose sensor. The vertical axis represents the magnitude of Isig in nA and the horizontal axis represents time.
During this scenario, glucose was present at a concentration of 40 mg/dL. Thus, isig at the working electrode stays at a constant level u 1, which indicates a glucose concentration of 40mg/dL, while Isig at the background electrode stays at zero, which means that no insulin adjuvant is detected. At t 1, 2.5mL of insulin at a concentration of 2.5% is introduced or injected for a first injection period (e.g., 30 minutes). Due to the presence of excipients in the insulin, isig at the working electrode increases to u 2 nA and Isig at the background electrode also increases to u 3 nA during the predetermined period. This increase is false because the glucose level remains the same. For the next 1 hour or until t 2, both isigs become stabilized to the original value u 1, because the auxiliary material is dispersed and the effect of the auxiliary material becomes diminished. The vertex u 2 of Isig curve 1210 is about 2 or 3 times the vertex u 2 of Isig curve 910 of fig. 9, and the vertex u 3 of Isig curve 1220 is about 2 or 3 times the vertex u 3 of Isig curve 920 of fig. 9. Even though the insulin concentration increases 5 times from the scene of fig. 9 to the scene of fig. 12, the vertex ratio between the scene of fig. 9 and the scene of fig. 12 does not increase linearly. The relationship between insulin concentration and the apex of Isig during the first injection may be stored as a ratio profile in the memory of the glucose sensor and based on this relationship the apex of Isig at the background electrode may be used as an indication of insulin concentration. Further, at different concentrations of insulin, the relationship between the apex of Isig at the working electrode and the apex of Isig at the background electrode may be incorporated into the ratio profile.
Now at t 2, another injection of 2.5mL of insulin at a concentration of 2.5% is made for a second injection period longer than the first injection period. The apex of Isig at the working electrode is u 4 nA and the apex of Isig at the background electrode is u 5 nA due to the injection of insulin of the same concentration, which is slower than the first injection. Further, due to the slower injection during the second injection, the Isig at the working electrode and the Isig at the background electrode take longer to stabilize than the first injection. In one aspect, the relationship between Isig at the working electrode and Isig at the background electrode may be linear during the first and second injections of insulin. The linear relationship may be represented by a ratio. In another aspect, the linear ratio between the Isig at the working electrode and the Isig at the background electrode during the first injection may be substantially the same during the first injection, and as such, the linear ratio between the Isig at the working electrode and the Isig at the background electrode during the second injection may be substantially the same during the second injection. However, the ratio during the first injection may be higher than the ratio during the second injection.
In various aspects, the linear ratio may depend on the number of injections. In other words, the linear ratio may decrease linearly or exponentially with the number of insulin injections.
In the case of integrating the cannula (via which insulin is injected) in the glucose sensor, the linear ratio may also depend on the distance between the flexible circuit with the background electrode fixed or printed and the cannula (e.g., "d" in fig. 7).
The bottom plot shows the voltage curve 1230 for the voltage across the background electrode, and the vertical axis is the voltage in millivolts (mV). As shown in voltage curve 1230, the voltage does not increase or decrease at or during the beginning of the first and second insulin injections and, therefore, may not be used as an indicator to detect insulin injections.
The top graph of fig. 13 shows two curves 1340a and 1340b of EIS signals, measured at the working electrode during two scenarios. In particular, curves 1340a and 1340b are real impedances in 10 5 Ω at 0.1 Hz. Curves 1340a and 1340b show the increase in real impedance of the EIS signal during the first insulin injection. Curve 1340b shows the increase in real impedance during the second injection, while curve 1340a shows the small increase in real impedance during the second insulin injection, which is greater than the threshold impedance during the predetermined period. Thus, the real impedance at 0.1Hz at the working electrode can be used to detect the presence of insulin adjunct. Further, based on both scenarios, the real impedance of the EIS signal at 0.1Hz from the working electrode can be used to confirm the presence of insulin injections or insulin adjuncts after the presence of insulin injections or insulin adjuncts is detected.
The bottom graph of fig. 13 shows two curves 1350a and 1350b of EIS signal measured at the working electrode during these two scenarios. In particular, curves 1350a and 1350b are imaginary impedances in 10 5 Ω at 0.1 Hz. Curve 1350a shows the increase in imaginary impedance of the EIS signal during the first and second insulin injections, while curve 1350b shows the decrease during the first and second insulin injections. Thus, the imaginary impedance of the EIS signal at 0.1Hz from the working electrode may not be used primarily or solely to detect the presence of insulin auxiliary material, but may be used to confirm the presence of insulin injection or insulin auxiliary material.
The top graph of fig. 14 shows two curves 1440a and 1440b of EIS signal, measured at the background electrode during both scenes. In particular, curves 1440a and 1440b are real impedances in 10 5 Ω at 0.1 Hz. Curves 1440a and 1440b both show an increase in the real impedance of the EIS signal during the first insulin injection and the second insulin injection, which increase is greater than the threshold impedance during the predetermined period. Thus, the real impedance at 0.1Hz at the background electrode can be used to detect the presence of insulin adjunct.
The bottom graph of fig. 14 shows two curves 1450a and 1450b of EIS signals, measured at the background electrode during both scenarios. In particular, curves 1450a and 1450b are imaginary impedances in units of 10 5 Ω at 0.1 Hz. Curves 1450a and 1450b show tiny bumps of imaginary impedance of the EIS signal during the first and second insulin injections, while curves 1450a and 1450b show general decrease of imaginary impedance. Even though the increase appears to be small, the increase may be significant since the unit of magnitude is 10 5. Thus, an increase in the imaginary impedance of the EIS signal at 0.1Hz from the background electrode during a predetermined period of time can be used to detect the presence of an insulin injection or insulin supplement. Further, an increase in the imaginary impedance of the EIS signal at 0.1Hz from the background electrode during the predetermined period can be used to confirm the presence of insulin injections or insulin adjuncts.
Summarizing for fig. 12-14, the presence of insulin adjunct can be detected by Isig at the background electrode and can be confirmed by real or imaginary impedance at 0.1Hz of EIS signals from the working and background electrodes.
Fig. 15 provides a graphical representation of a scenario illustrating a change in voltage across a background electrode according to aspects of the present disclosure. Curves 1510a and 1510b are Isig curves measured at the working electrode, and curves 1520a and 1520b are Isig curves measured at the background electrode. During this scenario, glucose is not present, whereas 0.5% insulin is introduced or injected at t 1. Thus, until t 1, all of the curves 1510a, 1510b, 1520a and 1520b are substantially zero. Injection is performed starting at t 1.
After insulin is introduced at t 1, isig curves 1510a and 1510b suddenly increase, and the increase is false because glucose is not present. Similarly, isig curves 1520a and 1520b suddenly increase at the background electrode. Immediately after insulin injection, 535mV of voltage was applied to the background electrode per unit period (e.g., 5 minutes or 10 minutes). The Isig curves 1520a and 1520b show a similar proportional increase in Isig curves 1510a and 1510b during 535mV application, which means that there is a linear relationship between Isig at the working electrode and Isig at the background electrode in the presence of insulin auxiliary material.
Then, 200mV, 300mV, 400mV, 500mV, 600mV, 700mV, and 800mV were sequentially applied to the background electrode every unit period. Isig curves 1520a and 1520b are substantially zero during the application of 200mV, 300mV, and 400mV to the background electrode. However, during 500mV application, isig curves 1520a and 1520b show an increase and subsequent decrease that appears to be proportionally similar to the decrease shown in Isig curves 1510a and 1510b for the working electrode. On the other hand, during 600mV-800mV application, both increases and decreases in Isig curves 1520a and 1520b are abrupt. Thus, a voltage range from 500mV to 600mV to the background electrode can be used to detect the presence of insulin adjunct. In one aspect, 535mV may be applied to the background electrode to detect the presence of insulin adjunct.
Fig. 16 provides an example of a linear relationship 1610 between Isig signal and insulin concentration at the background electrode at the beginning of a first insulin injection in accordance with aspects of the present disclosure. The vertical axis represents peak amplitude of Isig in nA and the horizontal axis represents insulin concentration in percent. The linear relationship may be expressed as a linear function (1), for example:
Peak=α 1+s1 ×concentration (1) of Isig.
For example, when insulin is injected first at a concentration of 0.05%, the peak value of Isig at the background electrode can be calculated as 6.8nA based on the linear relationship (1) using α 1 and s 1, and when insulin is injected at a concentration of 0.2%, the peak value of Isig at the background electrode can be calculated as 18.14nA. The values of a 1 and s 1 at the beginning of the first injection may be predetermined depending on the characteristics of the glucose sensor.
In aspects, when insulin of unknown concentration is injected first, the insulin concentration may be calculated based on a linear relationship between the peak or peak of the Isig signal at the background electrode and the insulin concentration at the beginning of insulin injection. The linear relationship may be a function of the number of injections.
For example, in the case of measuring Isig at the background electrode at the beginning of the first injection, the insulin concentration can be calculated by the following equation (2):
Fig. 17 provides a linear relationship 1710 between Isig signal and insulin concentration at the background electrode at the end of the first insulin injection according to aspects of the present disclosure. The vertical axis represents the magnitude of Isig in nA and the horizontal axis represents the insulin concentration in percent. The linear relationship may be expressed as a linear function (3), for example:
isig=α 2+s2 x concentration (3).
For example, after the complete injection of 0.05% concentration of insulin, the value of Isig at the background electrode may be calculated to be about 2.49nA based on the relation (2), and when the complete injection of 0.2% concentration of insulin, the value of Isig at the background electrode may be calculated to be about 2.66nA based on the relation (2). The values of α 2 and s 2 may be predetermined depending on the characteristics of the glucose sensor.
In aspects, when insulin of unknown concentration is injected first, the insulin concentration may be calculated based on a linear relationship (3) between the Isig signal at the background electrode and the insulin concentration at the end of insulin injection. The linear relationship may be a function of the number of injections.
Fig. 18 provides a linear relationship 1810 between Isig signal and insulin concentration at the background electrode at the beginning of a second insulin injection in accordance with aspects of the present disclosure. The vertical axis represents peak amplitude of Isig in nA and the horizontal axis represents insulin concentration in percent. The linear relationship may be expressed as a linear function (4), for example:
Peak=α 3+s3 ×concentration of Isig (4).
Specifically, when insulin of 0.05% concentration is injected for the second time, the peak value of Isig at the background electrode may be calculated to be about 3.26nA based on the linear relationship (4), and when insulin of 0.2% concentration is injected for the second time, the peak value of Isig at the background electrode may be calculated to be about 4.20nA based on the linear relationship (4). The values of α 3 and s 3 may be predetermined depending on the characteristics of the glucose sensor.
Based on these linear relationships, when insulin of unknown concentration is injected a first, second, third, or any number of times, the insulin concentration can be calculated based on the peak value of Isig from the background electrode. In aspects, the glucose sensor may include a storage device that stores these relationships between peak values and insulin injection times, and may be capable of estimating insulin concentration. For example, when the peak value of Isig at the background electrode is measured to be 4.20nA after the start of the second insulin injection, the insulin concentration may be estimated to be 0.2% based on the following equation (5):
As shown in fig. 16 and 18, the peak value of Isig at the background electrode at the start of the second injection is smaller than the peak value at the start of the first injection. Thus, the peak value of Isig decreases with the number of insulin injections. The reduced pattern of peaks of Isig at the beginning of each injection may be stored in the ratio profile. Likewise, the pattern of reduction of the peak of Isig at the end of each injection may be stored in the ratio profile.
Fig. 19 illustrates a flow chart of a method 1900 for detecting the presence of an adjunct in insulin by a glucose sensor, according to aspects of the present disclosure. The glucose sensor may include a working electrode, a background electrode, and a processor. Method 1900 begins by monitoring a current signal (Isig WE1) at a working electrode with a controller of a glucose sensor in step 1910 and monitoring a current signal (Isig WE2) at a background electrode with the controller in step 1920.
In step 1930, the processor further monitors an Electrochemical Impedance Spectroscopy (EIS) signal at the working electrode. The variation of the EIS signal has at least one parameter that is the real or imaginary impedance at 0.1 Hz. The change in EIS signal is calculated by the controller in step 1940. In an aspect, the EIS signal may be measured at the background electrode in step 1930.
In step 1950, it is determined that no insulin bolus is present if the EIS signal does not change during the predetermined period of time, and that insulin bolus is present if there is a change in the EIS signal greater than a predetermined threshold.
In the event that it is determined that no insulin adjunct is present, isig WE1 indicative of insulin levels is output in step 1980.
In the event that the presence of insulin adjuncts is determined, isig WE1 is compensated in step 1980 based on the linear relationship between Isig WE1 and Isig WE2. As described above with respect to fig. 9, compensated Isig WE1(IsigCOMP) equals:
IsigCOMP＝IsigWE1-α*IsigWE2
isig COMP is then output in step 1970.
Fig. 20 illustrates a flow chart of a method 2000 for detecting the presence of an adjunct in insulin by a glucose sensor, according to aspects of the present disclosure. The glucose sensor may include a working electrode, a background electrode, and a controller. The method 2000 begins by monitoring the current signal at the working electrode (Isig WE1) by a controller of the glucose sensor in step 2010 and the current signal at the background electrode (Isig WE2) by the controller in step 2020. In step 2030, a change in Isig WE2 during a predetermined period of time is calculated by the controller.
In step 2040, a determination is made as to whether the change (e.g., increase or decrease) during the predetermined period is greater than a predetermined threshold. In case the change is determined to be greater than a predetermined threshold, insulin adjunct is present. In case the change in Isig WE2 is not greater than a predetermined threshold, it is determined that no insulin adjunct is present.
In the event that it is determined that no insulin adjunct is present, isig WE1 indicative of insulin levels is output in step 2090.
In the event that it is determined that insulin bolus is present, the controller further monitors the EIS signal at the working electrode in step 2050. It is further determined in step 2060 whether the presence of insulin adjunct is confirmed based on the EIS signal. Confirmation of the presence of insulin adjuvants may be optional. In an aspect, the acknowledgement may also be determined based on the EIS signal at the background electrode in step 2050. In another aspect, the EIS signal can have at least one parameter that is a real or imaginary impedance at 0.1 Hz.
In the case where the presence of insulin auxiliary is not confirmed in step 2060, isig WE1 is output in step 2090.
In case the presence of insulin auxiliary material is confirmed in step 2060, isig WE1 is compensated in step 2070 based on the linear relationship between Isig WE1 and Isig WE2. As described above with respect to fig. 9, compensated Isig WE1(IsigCOMP) equals:
IsigWE1-α*IsigWE2。
isig COMP is then output in step 2080.
It should be understood that the various aspects disclosed herein may be combined in different combinations than specifically presented in the specification and drawings. It should also be appreciated that, depending on the example, certain acts or events of any of the processes or methods described herein can be performed in a different order, may be added, combined, or omitted entirely (e.g., not all of the described acts or events may be required to perform the techniques). Additionally, although certain aspects of the present disclosure are described as being performed by a single module or unit for clarity, it should be understood that the techniques of the present disclosure may be performed by a combination of units or modules associated with, for example, the servers and computing devices described above.
While the foregoing description relates to specific aspects of the present disclosure, it will be appreciated that numerous modifications may be made without departing from the spirit of the disclosure. Additional steps and changes to the algorithm sequence may be made while still performing the key teachings of the present disclosure. It is therefore intended that the appended claims cover such modifications as fall within the true scope and spirit of the disclosure. The presently disclosed aspects are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the disclosure being indicated by the appended claims rather than the foregoing description. Any aspect disclosed herein may be combined with any other aspect disclosed herein unless the context indicates otherwise. All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.

Claims (60)

1. A glucose sensor, comprising:
A working electrode configured to provide a current signal (Isig WE1) based on a glucose level;
A background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjunct; and
A controller configured to:
monitoring the Isig WE1 at the working electrode;
monitoring the Isig WE2 at the background electrode;
Monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode;
calculating a change in the at least one EIS parameter after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
2. The glucose sensor of claim 1, wherein the at least one EIS parameter is real impedance at 0.1 Hz.
3. The glucose sensor of claim 1, wherein the at least one EIS parameter is a virtual impedance at 0.1 Hz.
4. The glucose sensor of claim 1, wherein the predetermined relationship between the Isig WE1 and the Isig WE2 is a linear relationship.
5. The glucose sensor of claim 4, wherein the Isig COMP is equal to:
IsigWE1-α*IsigWE2，
where α is the slope of the linear relationship.
6. The glucose sensor of claim 5, wherein the slope has a profile based on a number of insulin injections.
7. The glucose sensor of claim 6, further comprising:
a memory storing the number of insulin injections and the profile.
8. The glucose sensor of claim 1, wherein the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
9. A glucose sensor system, comprising:
An insulin cannula connected to an insulin pump and configured to inject insulin therethrough;
A working electrode configured to provide a current signal (Isig WE1) based on a glucose level;
A background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjunct; and
A controller configured to:
monitoring the Isig WE1 at the working electrode;
monitoring the Isig WE2 at the background electrode;
Monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode;
calculating a change in the at least one EIS parameter after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
10. The glucose sensor system of claim 9, wherein the at least one EIS parameter is a real impedance at 0.1 Hz.
11. The glucose sensor system of claim 9, wherein the at least one EIS parameter is a virtual impedance at 0.1 Hz.
12. The glucose sensor system of claim 9, wherein the predetermined relationship between the Isig WE1 and the Isig WE2 is a linear relationship.
13. The glucose sensor system of claim 12, wherein the Isig COMP is equal to:
IsigWE1-α*IsigWE2，
where α is the slope of the linear relationship.
14. The glucose sensor system of claim 13, wherein the slope has a profile based on a number of insulin injections.
15. The glucose sensor system of claim 14, wherein the profile is based on a distance between the sleeve and the background electrode.
16. The glucose sensor system of claim 15, further comprising:
a memory storing the number of insulin injections and the profile.
17. The glucose sensor system of claim 9, wherein the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
18. A method for compensating for glucose levels from a glucose sensor based on the presence of insulin adjuvant, the method comprising:
Monitoring a current signal (Isig WE1) at a working electrode of the glucose sensor;
Monitoring a current signal (Isig WE2) at a background electrode of the glucose sensor;
Monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode;
calculating a change in the at least one EIS parameter after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
19. The method of claim 18, wherein the at least one EIS parameter is real impedance at 0.1 Hz.
20. The method of claim 18, wherein the at least one EIS parameter is a virtual impedance at 0.1 Hz.
21. The method of claim 18, wherein the predetermined relationship between the Isig WE1 and the Isig WE2 is a linear relationship.
22. The method of claim 21, wherein the Isig COMP is equal to:
IsigWE1-α*IsigWE2，
where α is the slope of the linear relationship.
23. The method of claim 22, wherein the slope has a profile based on a number of insulin injections.
24. The method of claim 23, further comprising:
The number of insulin injections and the profile are stored in a memory of the glucose sensor.
25. The method of claim 18, wherein the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
26. A non-transitory computer-readable medium storing instructions that, when executed by a computing device, cause the computing device to perform a method for compensating for a glucose level from a glucose sensor based on a presence of an insulin bolus, the method comprising:
Monitoring a current signal (Isig WE1) at a working electrode of the glucose sensor;
Monitoring a current signal (Isig WE2) at a background electrode of the glucose sensor;
Monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode;
calculating a change in the at least one EIS parameter after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
27. A glucose sensor, comprising:
A working electrode configured to provide a current signal (Isig WE1) based on a glucose level;
A background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjunct;
A controller configured to:
monitoring the Isig WE1 at the working electrode;
monitoring the Isig WE2 at the background electrode;
Calculating the change in said Isig WE2 after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
28. The glucose sensor of claim 27, wherein the predetermined relationship between the Isig WE1 and the Isig WE2 is a linear relationship.
29. The glucose sensor of claim 28, wherein the Isig COMP is equal to:
IsigWE1-α*IsigWE2，
where α is the slope of the linear relationship.
30. The glucose sensor of claim 29, wherein the slope has a profile based on a number of insulin injections.
31. The glucose sensor of claim 30, further comprising:
a memory storing the number of insulin injections and the profile.
32. The glucose sensor of claim 27, wherein the voltage applied to the background electrode ranges from 500mV to 600mV.
33. The glucose sensor of claim 27, wherein the controller is further configured to:
monitoring an Electrochemical Impedance Spectroscopy (EIS) signal at the working electrode; and
Confirming the presence of the insulin adjunct based on the EIS signal of at least one parameter.
34. The glucose sensor of claim 33, wherein the at least one parameter is a real impedance of the EIS signal at 0.1 Hz.
35. The glucose sensor of claim 33, wherein the at least one parameter is a virtual impedance of the EIS signal at 0.1 Hz.
36. The glucose sensor of claim 27, wherein the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
37. A glucose sensor system, comprising:
An insulin cannula connected to an insulin pump and configured to inject insulin therethrough;
A working electrode configured to provide a current signal (Isig WE1) based on a glucose level;
A background electrode configured to provide a current signal (Isig WE2) based on the presence of insulin adjunct;
A controller configured to:
monitoring the Isig WE1 at the working electrode;
monitoring the Isig WE2 at the background electrode;
Calculating the change in said Isig WE2 after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
38. The glucose sensor system of claim 37, wherein the predetermined relationship between the Isig WE1 and the Isig WE2 is a linear relationship.
39. The glucose sensor system of claim 38, wherein the Isig COMP is equal to:
IsigWE1-α*IsigWE2，
where α is the slope of the linear relationship.
40. The glucose sensor system of claim 39, wherein the slope is dependent on a distance between the sleeve and the working electrode.
41. The glucose sensor system of claim 39, wherein the slope has a profile based on a number of insulin injections.
42. The glucose sensor system of claim 41, wherein the profile is based on a distance between the sleeve and the background electrode.
43. The glucose sensor system of claim 41, further comprising:
a memory storing the number of insulin injections and the profile.
44. The glucose sensor system of claim 37, wherein the voltage applied to the background electrode ranges from 500mV to 600mV.
45. The glucose sensor system of claim 37, wherein the controller is further configured to:
Monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode; and
Confirming the presence of the insulin adjunct based on the at least one EIS parameter.
46. The glucose sensor system of claim 45, wherein the at least one EIS parameter is a real impedance of the EIS signal at 0.1 Hz.
47. The glucose sensor system of claim 45, wherein the at least one EIS parameter is a virtual impedance of the EIS signal at 0.1 Hz.
48. The glucose sensor system of claim 37, wherein the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
49. A method for compensating for glucose levels from a glucose sensor based on the presence of insulin adjuvant, the method comprising:
Monitoring a current signal (Isig WE1) at a working electrode of the glucose sensor;
Monitoring a current signal (Isig WE2) at a background electrode of the glucose sensor;
Calculating the change in said Isig WE2 after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
50. The method of claim 49, wherein the predetermined relationship between the Isig WE1 and the Isig WE2 is a linear relationship.
51. The method of claim 50, wherein said Isig COMP is equal to:
IsigWE1-α*IsigWE2，
where α is the slope of the linear relationship.
52. The method of claim 51, wherein the slope is dependent on a distance between a cannula through which insulin is injected and the working electrode.
53. The method of claim 51, wherein the slope has a profile based on a number of insulin injections.
54. The method of claim 53, wherein the slope is lower the longer the insulin is injected.
55. The method of claim 49, wherein the voltage applied to the background electrode ranges from 500mV to 600mV.
56. The method of claim 49, further comprising:
Monitoring at least one Electrochemical Impedance Spectroscopy (EIS) parameter at the working electrode; and
Confirming the presence of the insulin adjunct based on the at least one EIS parameter.
57. The method of claim 56, wherein said at least one EIS parameter is real impedance at 0.1 Hz.
58. The method of claim 56, wherein said at least one EIS parameter is a virtual impedance at 0.1 Hz.
59. The method of claim 49, wherein the insulin adjuvant comprises one or more of peroxide, phenol, m-cresol, glycerol, zinc oxide, disodium phosphate, sodium chloride, sodium hydroxide, hydrogen chloride, nicotinamide, and arginine hydrochloride.
60. A non-transitory computer-readable medium storing instructions that, when executed by a computing device, cause the computing device to perform a method for compensating for a glucose level from a glucose sensor based on a presence of an insulin bolus, the method comprising:
Monitoring a current signal (Isig WE1) at a working electrode of the glucose sensor;
Monitoring a current signal (Isig WE2) at a background electrode of the glucose sensor;
Calculating the change in said Isig WE2 after insulin injection;
Detecting the presence of the insulin adjunct based on the change; and
In case said presence of said insulin adjunct is detected,
Compensating the Isig WE1 based on a predetermined relationship between the Isig WE1 and the Isig WE2; and
Outputting the compensated Isig WE1(IsigCOMP).
CN202311329138.1A 2022-10-14 2023-10-13 System and method for detecting the presence of insulin adjunct Pending CN117890449A (en)

Applications Claiming Priority (3)

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US63/416,005 2022-10-14
US202318470633A 2023-09-20 2023-09-20
US18/470,633 2023-09-20

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