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

Patent metadata

Field	Value
Publication number	US-11844598-B2
Application number	US-201916391666-A
Country	US
Kind code	B2
Filing date	Apr 23, 2019
Priority date	Dec 16, 2013
Publication date	Dec 19, 2023
Grant date	Dec 19, 2023

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.

First claim

What is claimed is:

1. A method for real-time self-calibration of a glucose sensor, the glucose sensor including sensor electronics, a microcontroller, and at least one working electrode and one counter electrode, the method comprising:
applying a plurality of AC potential signals to the glucose sensor over time;
measuring a plurality of AC current signals at the at least one working electrode over time;
calibrating the glucose sensor in real-time without finger-stick or meter data by:
performing, by the microcontroller, a plurality of electrochemical impedance spectroscopy (EIS) procedures over time for the at least one working electrode based on the AC potential signals and the AC current signals;
generating, by the microcontroller, a plurality of Nyquist plots over time based on respective outputs of the plurality of EIS procedures;
setting a baseline Nyquist plot length;
setting a baseline higher-frequency Nyquist slope;
monitoring, by the microcontroller, Nyquist plot length and higher-frequency Nyquist slope across the plurality of Nyquist plots over time to detect changes in the Nyquist plot length and the higher-frequency Nyquist slope over time; and
calibrating the glucose sensor based on the detected changes in the Nyquist plot length and in the higher-frequency Nyquist slope over time; and

providing a level of glucose in the user's body using the calibrated glucose sensor.

2. The method of claim 1 , further comprising monitoring a value of the voltage at the counter electrode (Vcntr).

3. The method of claim 2 , further comprising adjusting or resetting the baseline Nyquist plot length when Vcntr rails.

4. The method of claim 1 , wherein the glucose sensor measures a plurality of glucose values over time, and
the method further comprising discarding one or more of the plurality of measured glucose values when the monitored slope becomes negative.

5. The method of claim 1 , wherein the glucose sensor measures a plurality of glucose values over time,
the method further comprising discarding one or more of the plurality of measured glucose values when the monitored Nyquist plot length increases above a calculated threshold.

6. The method of claim 1 , wherein the baseline Nyquist plot length and baseline higher-frequency Nyquist slope are set at respective values that are reflective of an EIS state at the beginning of the glucose sensor's life.

7. The method of claim 1 , further comprising calculating, by the microcontroller, an amount of insulin to be delivered to the user based on the calculated level of glucose in the user's body.

8. The method of claim 1 , further comprising transmitting the calculated level of glucose to an insulin delivery device.

9. The method of claim 8 , wherein the insulin delivery device is an insulin pump.

10. The method of claim 9 , wherein the glucose sensor and the insulin pump cooperate in a closed-loop system.

11. A glucose sensor configured to measure a level of glucose in a body of a user, the glucose sensor comprising:
at least one working electrode;
at least one counter electrode;
sensor electronics configured to measure a plurality of AC current signals for the at least one working electrode over time and for the at least one counter electrode based on a plurality of AC potential signals applied to the glucose sensor over time; and
a microcontroller configured to:
calibrate the glucose sensor in real-time without finger-stick or meter data by:
performing a plurality of electrochemical impedance spectroscopy (EIS) procedures over time for the at least one working electrode based on the AC potential signals and the AC current signals;
generating a plurality of Nyquist plots over time based on respective outputs of the plurality of EIS procedures;
setting a baseline Nyquist plot length;
setting a baseline higher-frequency Nyquist slope;
monitoring Nyquist plot length and higher-frequency Nyquist slope across the plurality of Nyquist plots over time to detect changes in the Nyquist plot length and the higher-frequency Nyquist slope over time; and
calibrating the glucose sensor based on the detected changes in the Nyquist plot length and in the higher-frequency Nyquist slope over time; and

provide a level of glucose in the user's body using the calibrated glucose sensor.

12. The glucose sensor of claim 11 , wherein the microcontroller is further configured to monitor a value of the voltage at the counter electrode (Vcntr).

13. The glucose sensor of claim 12 , wherein the microcontroller is further configured to adjust or reset the baseline Nyquist plot length when Vcntr rails.

14. The glucose sensor of claim 11 , wherein the glucose sensor measures a plurality of glucose values over time, and
wherein the microcontroller is further configured to discard one or more of the plurality of measured glucose values when the monitored slope becomes negative.

15. The glucose sensor of claim 11 , wherein the glucose sensor measures a plurality of glucose values over time, and
wherein the microcontroller is further configured to discard one or more of the plurality of measured glucose values when the monitored Nyquist plot length increases above a calculated threshold.

16. The glucose sensor of claim 11 , wherein the baseline Nyquist plot length and baseline higher-frequency Nyquist slope are set at respective values that are reflective of an EIS state at the beginning of the glucose sensor's life.

17. The glucose sensor of claim 11 , wherein the microcontroller is further configured to calculate an amount of insulin to be delivered to the user based on the calculated level of glucose in the user's body.

18. The glucose sensor of claim 11 , wherein the microcontroller is further configured to transmitting the calculated level of glucose to an insulin delivery device.

19. The glucose sensor of claim 18 , wherein the insulin delivery device is an insulin pump.

20. The glucose sensor of claim 19 , wherein the glucose sensor and the insulin pump cooperate in a closed-loop system.

Assignees

• Medtronic Minimed Inc

Inventors

• Varsavsky Andrea
• Yu Fei
• Miller Michael E
• Yang Ning

Classifications

• A61B5/0537 Primary

  Measuring body composition by impedance, e.g. tissue hydration or fat content · CPC title

• A61B5/0538

  invasively, e.g. using a catheter · CPC title

• A61B5/1468

  using chemical or electrochemical methods, e.g. by polarographic means · CPC title

• A61B5/1473

  invasive, e.g. introduced into the body by a catheter · CPC title

• A61B5/1495

  Calibrating or testing of in-vivo probes · CPC title