WO-2026095064-A1 - METHOD FOR CORRECTING ELECTROCHEMICAL SENSOR USING ELECTROCHEMICAL IMPEDANCE MEASUREMENT

Abstract

Provided is a method for managing the accuracy of an electrochemical sensor which includes a base material, an electrode pair that includes a counter electrode and a working electrode including an oxidoreductase electrode provided on the base material, and an outer layer film that covers the electrode pair and which quantitatively measures a target substance on the basis of an electrical signal generated by an oxidoreductase reaction, said method comprising periodically performing electrochemical impedance measurement between the working electrode and the counter electrode and monitoring a change in electrochemical impedance.

Inventors

• OKAWA, HIROYUKI

Assignees

• アークレイ株式会社

Dates

Publication Date

20260507

Application Date

20251031

Priority Date

20241031

Claims (8)

1. A method for quality control of an electrochemical sensor that quantitatively measures a target substance based on an electrical signal generated by an oxidoreductase reaction, comprising a substrate, an electrode pair including a working electrode and a counter electrode provided on the substrate, and an outer layer film covering the electrode pair, the method comprising periodically measuring the electrochemical impedance between the working electrode and the counter electrode to monitor changes in the electrochemical impedance.
2. A method for controlling the accuracy of an electrochemical sensor that quantitatively measures a target substance based on an electrical signal generated by an oxidoreductase reaction, comprising a substrate, an electrode pair including a working electrode and a counter electrode provided on the substrate, and an outer layer film covering the electrode pair, the method comprising: measuring the electrochemical impedance between the working electrode and the counter electrode; calculating the change in resistance from the measured electrochemical impedance; calculating the change in the electrical signal based on the change in resistance; and correcting the value of the electrical signal.
3. The method according to claim 1 or 2, wherein the electrochemical sensor is implantable in a biomedical environment.
4. The method according to claim 1 or 2, wherein the value of the electrical signal is a current value.
5. The method according to claim 1 or 2, wherein the oxidoreductase is a direct electron transfer type oxidoreductase.
6. The method according to claim 1 or 2, wherein the outer layer film comprises a hydrophilic polymer and a hydrophobic polymer.
7. The method according to claim 1 or 2, wherein the potential in the electrochemical impedance measurement is a potential at which the substance to be measured reacts sufficiently.
8. The method according to claim 1 or 2, wherein the measurement frequency band in the electrochemical impedance measurement is between 0.1 Hz and 100 kHz.

Description

Correction method for electrochemical sensors using electrochemical impedance measurement This invention relates to a technique for detecting changes in electrochemical properties that may occur due to external shocks, etc., in an electrochemical sensor used for implantation in the body, using electrochemical impedance measurement, and for correcting the measured values. In addition to the initial stabilization and wetting issues of electrochemical sensors, over their lifespan, electrochemical sensors may experience a reduction in electrode surface area or narrowing of diffusion channels for analytes and/or reaction by-products due to contaminants such as peptides and microprotein molecules, leading to decreased sensor accuracy. Determining when such contaminants begin to affect the sensor signal, and how to address this condition, remains unexplained. Therefore, as a real-time maintenance method and system, a technique has been proposed in which electrochemical impedance spectroscopy (EIS) is used to verify that the sensor is functioning correctly, and a voltage is applied to restore the sensor based on its impedance value (Patent Document 1). Figure 1 is a graph showing the chronoamperometry results (change in current value over time) evaluated in Comparative Example 1.Figure 2 is a graph showing the results of chronoamperometry (change in current value over time) evaluated in Example 1.Figure 3 is a graph showing the Nyquist plot measured in Comparative Example 1.Figure 4 is a graph showing the Nyquist plot measured in Example 1, illustrating the change in impedance value before and after external impact to the sensor.Figure 5 is a graph showing the results of electrochemical impedance measurements performed at varying glucose concentrations.Figure 6 is a graph plotting the change in resistance value, determined from the impedance value of the sensor before and after damage, against the change in glucose reaction current value. A method for controlling the accuracy of an electrochemical sensor according to one aspect of the present invention is characterized by monitoring changes in electrochemical impedance by periodically measuring the electrochemical impedance between the working electrode and the counter electrode in quantitative measurement using an electrochemical sensor that quantitatively measures a target substance based on an electrical signal generated by an oxidoreductase reaction, comprising a substrate, an electrode pair including a working electrode and a counter electrode provided on the substrate, and an outer layer film covering the electrode pair. Here, "periodically" includes measurements taken at intervals ranging from 10 minutes to 24 hours. Note that electrochemical impedance measurements may also be performed when the current changes abruptly or when abnormal values are observed. Furthermore, another aspect of the present invention relates to a method for controlling the accuracy of an electrochemical sensor, which comprises a substrate, an electrode pair including a working electrode and a counter electrode provided on the substrate and an oxidoreductase electrode, and an outer layer film covering the electrode pair, and in quantitative measurement using an electrochemical sensor that quantitatively measures a target substance based on an electrical signal generated by an oxidoreductase reaction, the method includes measuring the electrochemical impedance between the working electrode and the counter electrode, calculating the change in resistance from the measured value of the electrochemical impedance, calculating the change in the electrical signal based on the change in resistance, and correcting the value of the electrical signal. Here, the "change" in resistance or current can be a change from a predetermined reference point (for example, the initial measurement or the immediately preceding measurement) or a change relative to a predetermined reference value. (Electrochemical sensor) The electrochemical sensor used in the method of the present invention includes a substrate, an electrode pair including a working electrode and a counter electrode, which are provided on the substrate and contain an oxidoreductase electrode, and an outer layer film covering the electrode pair. The electrode pair is an electrode pair including an enzyme electrode (working electrode) containing an oxidoreductase and a counter electrode, but it may also be a three-electrode system comprising an enzyme electrode, a counter electrode, and a reference electrode. (Base material) The electrode, including the electrode pair, is provided on a substrate, and an insulating substrate is used as the substrate. The type of insulating substrate is not particularly limited, but for example, it can be made from various thermoplastic resins such as polyetherimide (PEI), polyethylene terephthalate (PET), and polyethylene (PE), various thermosetting resins such as polyimide resin and epoxy resin, or insulating mat