In-vivo electrochemical impedance spectroscopy (EIS)-based calibration

• US 10,321,844 B2
• Filed: 08/22/2014
• Issued: 06/18/2019
• Est. Priority Date: 12/16/2013
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Varsavsky, Andrea, Yu, Fei, Miller, Michael E., Yang, Ning
• Primary Examiner(s): Agahi, Puya
• Application Number:
  US14/466,138
• Publication Number:
  US 20150164386A1
• Time in Patent Office: 1,761 Days
• CPC Class Codes: A61B 5/0537 Measuring body composition by impedance, e.g. tissue hydration or fat content
• CPC Class Codes: A61B 5/0538 invasively, e.g. using a catheter
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1468 using chemical or electrochemical methods, e.g. by polarographic means A61B5/1486 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/6849 in combination with a needle set
• CPC Class Codes: A61B 5/7221 Determining signal validity, reliability or quality A61B5/7207 and A61B5/7217 take precedence
• CPC Class Codes: A61B 5/7246 using correlation, e.g. template matching or determination of similarity
• CPC Class Codes: A61M 2005/1726 the body parameters being measured at, or proximate to, the infusion site
• CPC Class Codes: A61M 5/14244 adapted to be carried by the patient, e.g. portable on the body
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/1582 Double lumen needles
• CPC Class Codes: G01N 27/026 Dielectric impedance spectroscopy electrochemical impedance spectroscopy for measuring corrosion G01N17/02

Abstract

Electrochemical Impedance Spectroscopy (EIS) is used in conjunction with continuous glucose monitors and continuous glucose monitoring (CGM) to enable in-vivo sensor calibration, gross (sensor) failure analysis, and intelligent sensor diagnostics and fault detection. An equivalent circuit model is defined, and circuit elements are used to characterize sensor behavior.

Claims

1. A method for real-time self-calibration of a glucose sensor, said glucose sensor including sensor electronics, a microcontroller, and at least one working electrode, the method comprising:

inserting said glucose sensor into subcutaneous tissue of a user;

periodically measuring, by said sensor electronics, a value of the electrode current (Isig) for the working electrode, wherein said Isig is the sum of a Faradaic current component and a non-Faradaic current component;

performing, by said microcontroller, an electrochemical impedance spectroscopy (EIS) procedure for said at least one working electrode to obtain values of at least one impedance-based parameter for the at least one working electrode;

periodically repeating, by said microcontroller, said EIS procedure for said working electrode to obtain additional values of said at least one impedance-based parameter;

calculating, by said microcontroller, values of at least one EIS-based parameter based on said obtained values and additional values of the at least one impedance-based parameter;

monitoring the calculated values of said at least one EIS-based parameter for variations in said calculated values;

adjusting, by said microcontroller, a calibration factor for said glucose sensor, based on said variations in the calculated values and on only the Faradaic current component of the Isig, to obtain an adjusted calibration factor; and

using, by said microcontroller, said adjusted calibration factor to calculate a level of glucose in said user'"'"'s body,

wherein the calibration factor is adjusted in accordance with the relation CF(t)=CF_reference−

m(R_reference−

R(t)), wherein CF(t) is the calibration factor at time t, CF_reference is a reference value for the calibration factor, R_reference is the value of membrane resistance when CF=CF_reference, R(t) is membrane resistance at time t, and m is the gradient of a correlation between CF and R.

2. The method of claim 1, wherein said at least one impedance-based parameter is real impedance.

3. The method of claim 1, wherein said at least one EIS-based parameter is membrane resistance.

4. The method of claim 1, wherein said at least one EIS-based parameter is membrane capacitance.

5. The method of claim 1, wherein the sensor electronics include a memory, and the method further includes storing said obtained values, said obtained additional values, and said calculated values in said memory.

6. The method of claim 1, wherein said calibration factor is defined as the BG/Isig, wherein BG is blood glucose and Isig is current measured through said working electrode.

7. The method of claim 1, further comprising detecting said variations in the calculated values based on a Nyquist plot of real impedance vs. imaginary impedance for said working electrode.

8. The method of claim 7, wherein said Nyquist plot has an inflection point, wherein said at least one EIS-based parameter includes membrane resistance, and wherein the calculated value of membrane resistance for each said EIS procedure is estimated by the magnitude of real impedance at said inflection point.

9. The method of claim 8, wherein each said EIS procedure is performed over a range of frequencies.

10. The method of claim 9, wherein a shift from left to right in the Nyquist plot over time is indicative of an increase in the calculated values of membrane resistance.

11. The method of claim 7, wherein the EIS-based parameter is membrane resistance, and wherein said variations are estimated by measuring a shift in the Nyquist slope.

12. The method of claim 7, wherein said at least one EIS-based parameter includes membrane capacitance, and wherein the appearance of a semicircle in the higher-frequency region of said Nyquist plot is indicative of an increase in the calculated value of membrane capacitance.

13. The method of claim 12, wherein the values of membrane capacitance are estimated by tracking a peak of said semicircle within a frequency range.

14. The method of claim 13, wherein said frequency range is between 1 kHz and 8 kHz.

15. A method for real-time self-calibration of a glucose sensor, said glucose sensor including sensor electronics, a microcontroller, and at least one working electrode, the method comprising:

inserting said glucose sensor into subcutaneous tissue of a user;

periodically measuring, by said sensor electronics, a value of the electrode current (Isig) for the working electrode, wherein said Isig is the sum of a Faradaic current component and a non-Faradaic current component;

performing, by said microcontroller, an electrochemical impedance spectroscopy (EIS) procedure for said at least one working electrode to obtain values of at least one impedance-based parameter for the at least one working electrode;

periodically repeating, by said microcontroller, said EIS procedure for said working electrode to obtain additional values of said at least one impedance-based parameter;

calculating, by said microcontroller, values of at least one EIS-based parameter based on said obtained values and additional values of the at least one impedance-based parameter;

monitoring the calculated values of said at least one EIS-based parameter for variations in said calculated values;

adjusting, by said microcontroller, a calibration factor for said glucose sensor, based on said variations in the calculated values and on only the Faradaic current component of the Isig, to obtain an adjusted calibration factor; and

using, by said microcontroller, said adjusted calibration factor to calculate a level of glucose in said user'"'"'s body,

wherein the calibration factor is adjusted in accordance with the relation CF(t)/CF_reference=−

m(R(t)/R_reference), wherein CF(t) is the calibration factor at time t, CF_reference is a reference value for the calibration factor, R_reference is the value of membrane resistance when CF=CF_reference, R(t) is membrane resistance at time t, and m is the gradient of a correlation between CF and R.