APPLICATION OF ELECTROCHEMICAL IMPEDANCE SPECTROSCOPY IN SENSOR SYSTEMS, DEVICES, AND RELATED METHODS

• US 20170328861A1
• Filed: 08/02/2017
• Published: 11/16/2017
• Est. Priority Date: 06/08/2012
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: WANG, JENN-HANN LARRY, MILLER, MICHAEL E., GAUTHAM, RAGHAVENDHAR, LI, YIWEN, SHAH, RAJIV
• Granted Patent: US 9,863,911 B2
• Time in Patent Office: Days
• CPC Class Codes: A61B 2562/0214 Capacitive electrodes
• CPC Class Codes: A61B 2562/04 Arrangements of multiple sensors of the same type
• 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 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 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 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/6849 in combination with a needle set
• CPC Class Codes: A61B 5/6852 Catheters
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/7221 Determining signal validity, reliability or quality A61B5/7207 and A61B5/7217 take precedence
• CPC Class Codes: A61B 5/7225 Details of analog processing, e.g. isolation amplifier, gain or sensitivity adjustment, filtering, baseline or drift compensation A61B5/30, A61B5/316 take precedence; transformers for specific applications H01F38/00; amplifiers H03F
• CPC Class Codes: A61B 5/7242 using integration
• CPC Class Codes: A61B 5/746 Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms alarms per se G08B
• 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: A61M 5/1723 : using feedback of body parameters, e.g. blood-sugar, pressure measurement of body parameters A61B5/00
• CPC Class Codes: G01N 27/026 : Dielectric impedance spectroscopy electrochemical impedance spectroscopy for measuring corrosion G01N17/02
• CPC Class Codes: G01N 27/028 : Circuits therefor measuring impedance per se G01R27/02
• CPC Class Codes: G01N 27/416 : Systems G01N27/27 takes precedence
• CPC Class Codes: G01N 27/4163 : checking the operation of, or calibrating, the measuring apparatus G01N27/3274, G01N27/4175 and G01N33/0006 take precedence
• CPC Class Codes: G01N 33/49 : Blood chemical methods for determining blood cell populations G01N33/5094; chemical analysis of blood groups or blood types G01N33/80
• CPC Class Codes: G01N 33/66 : involving blood sugars, e.g. galactose
• CPC Class Codes: G01N 33/96 : involving blood or serum control standard
• CPC Class Codes: G01R 35/00 : Testing or calibrating of apparatus covered by the other groups of this subclass
• CPC Class Codes: G01R 35/005 : Calibrating; Standards or reference devices, e.g. voltage or resistance standards, "golden" references G01R33/0035, G01R35/002 take precedence

Abstract

A diagnostic Electrochemical Impedance Spectroscopy (EIS) procedure is applied to measure values of impedance-related parameters for one or more sensing electrodes. The parameters may include real impedance, imaginary impedance, impedance magnitude, and/or phase angle. The measured values of the impedance-related parameters are then used in performing sensor diagnostics, calculating a highly-reliable fused sensor glucose value based on signals from a plurality of redundant sensing electrodes, calibrating sensors, detecting interferents within close proximity of one or more sensing electrodes, and testing surface area characteristics of electroplated electrodes. Advantageously, impedance-related parameters can be defined that are substantially glucose-independent over specific ranges of frequencies. An Application Specific Integrated Circuit (ASIC) enables implementation of the EIS-based diagnostics, fusion algorithms, and other processes based on measurement of EIS-based parameters.

Claims

1. A method of performing real-time sensor diagnostics on a subcutaneous or implanted sensor of a sensor system, said sensor including at least one working electrode and said sensor system including a microprocessor that is operatively connected to said sensor, the method comprising:

(a) periodically performing an electrochemical impedance spectroscopy (EIS) procedure to generate multiple sets of impedance-related data for said at least one working electrode;

(b) calculating, by said microprocessor, respective values of a plurality of impedance-related parameters based on said multiple sets of impedance-related data, said plurality of parameters including impedance, phase angle, and Nyquist slope; and

(c) based on said respective values, determining, by said microprocessor, whether the sensor is functioning normally, wherein the microprocessor;

(i) performs a first test based on values of real impedance or phase angle;

(ii) performs a second test based on values of respective frequencies at which successive EIS procedures are performed;

(iii) performs a third test based on a comparison of current and post-sensor initialization impedance values at 1 kHz;

(iv) performs a fourth test based on the value of post-sensor initialization impedance at 0.1 Hz;

(v) performs a fifth test based on the global change in the value of Nyquist slope between 0.1 Hz and 1 Hz;

(vi) performs a sixth test based on the change, over time, in the magnitude of real impedance; and

(vii) determines that the sensor is functioning normally if at least 3 of said first through sixth tests are satisfied by generating results that fall within respective predetermined criteria.

2. The method of claim 1, wherein the microprocessor determines that the first test is satisfied if either |(Zn−

Z1)/Z1|>

30% at 1 kHz, wherein Z1 is the value of real impedance measured at a first EIS run and Zn is the value of real impedance measured at a subsequent EIS run, or the phase angle change is greater than 10°

at 0.1 Hz between said first and subsequent EIS runs.

3. The method of claim 1, wherein the microprocessor determines that the second test is satisfied if, at a phase angle of −

45°

, the difference in frequency between two consecutive EIS runs (f2−

f1) is greater than 10 Hz.

4. The method of claim 1, wherein the microprocessor determines that the third test is satisfied if the current value of impedance is less than the post-initialization value of impedance at 1 kHz.

5. The method of claim 1, wherein the microprocessor determines that the fourth test is satisfied if the value of impedance is less than 300 kOhms at 0.1 Hz during post-initialization sensor operation.

6. The method of claim 1, wherein the microprocessor determines that the fifth test is satisfied if the value of Nyquist slope is determined to be globally increasing from 0.1 Hz to 1 Hz.

7. The method of claim 1, wherein the microprocessor determines that the sixth test is satisfied if the value of real impedance is determined to be globally decreasing over successive EIS runs.

8. The method of claim 1, wherein, after step (b) but before step (c)(i), the microprocessor determines whether said sensor is properly inserted or implanted.

9. The method of claim 8, wherein the microprocessor determines that the sensor is not properly inserted or implanted if the slope of the absolute value of impedance is determined to be constant across a predetermined range of frequencies, or the phase angle is about −

90°

, or both.

10. The method of claim 1, wherein each of the first through sixth tests is weighted.

11. The method of claim 10, wherein the respective weight for at least one of the first through sixth tests is different than the weight for at least one other of the first through sixth tests.

12. A method of performing real-time sensor diagnostics on a subcutaneous or implanted sensor of a sensor system, said sensor including at least one working electrode and said sensor system including a microprocessor that is operatively connected to said sensor, the method comprising:

(a) periodically performing an electrochemical impedance spectroscopy (EIS) procedure to generate multiple sets of impedance-related data for said at least one working electrode;

(b) calculating, by said microprocessor, respective values of a plurality of impedance-related parameters based on said multiple sets of impedance-related data, said plurality of parameters including impedance, phase angle, and Nyquist slope; and

(c) based on said respective values, determining, by said microprocessor, whether the sensor is functioning normally, wherein the microprocessor;

(i) performs a first test based on values of real impedance or phase angle;

(ii) performs a second test based on values of sensor current (Isig) and impedance magnitude at 1 kHz;

(iii) performs a third test based on the global change in the value of Nyquist slope between 0.1 Hz and 1 Hz;

(iv) performs a fourth test based on the values of phase angle and impedance magnitude at 0.1 Hz;

(v) performs a fifth test based on values of impedance magnitude and Isig;

(vi) performs a sixth test based on values of Isig, phase angle, and imaginary impedance;

(vii) performs a seventh test based on values of Isig and imaginary impedance at 0.1 Hz; and

(viii) determines that the sensor is functioning normally if at least 4 of said first through seventh tests are satisfied by generating results that fall within respective predetermined criteria.

13. The method of claim 12, wherein the microprocessor determines that the first test is satisfied if either |(Zn−

Z1)/Z1|>

30% at 1 kHz, wherein Z1 is the value of real impedance measured at a first EIS run and Zn is the value of real impedance measured at a second EIS run that occurs 2 hours after the first EIS run, or the phase angle change is greater than 10°

at 0.1 Hz between said first and second EIS runs.

14. The method of claim 12, wherein the microprocessor determines that the second test is satisfied if the percentage change in the value of impedance magnitude at 1 kHz is less than or equal to 30%, or if the percentage change in the Isig is less than or equal to 30% between a first EIS run and a second EIS run performed 2 hours after said first EIS run.

15. The method of claim 12, wherein the microprocessor determines that the third test is satisfied if the value of Nyquist slope is determined to be globally increasing from 0.1 Hz to 1 Hz.

16. The method of claim 12, wherein the microprocessor determines that the fourth test is satisfied if the value of the phase angle at 0.1 Hz is determined not to be continuously increasing over time, and the value of impedance magnitude at 0.1 Hz is determined not to be continuously increasing over time.

17. The method of claim 12, wherein the microprocessor determines that the fifth test is satisfied if the percentage change in the value of impedance magnitude at 1 kHz is less than or equal to 30%, or if the percentage change in the Isig is less than or equal to 30% between a first EIS run and a second EIS run.

18. The method of claim 12, wherein the microprocessor determines that the sixth test is satisfied if at least two out of the following three criteria are met:

(a) Isig is greater than or equal to 10 nA;

(b) the value of imaginary impedance at 1 kHz is greater than or equal to −

1500 Ohm; and

(c) the phase angle at 1 kHz is greater than or equal to −

15°

.

19. The method of claim 12, wherein the microprocessor determines that the seventh test is satisfied if, at 0.1 Hz, the magnitude of the difference between the value of a first ratio of the imaginary impedance to the Isig from a first EIS run and the value of a second ratio of the imaginary impedance to the Isig from a second EIS run is less than or equal to 30% of the value of said ratio from the first EIS run.

20. The method of claim 12, wherein, after step (b) but before step (c)(i), the microprocessor determines whether said sensor is properly inserted or implanted.

21. The method of claim 20, wherein the microprocessor determines that the sensor is not properly inserted or implanted if the slope of the absolute value of impedance is determined to be constant across a predetermined range of frequencies, or the phase angle is about −

90°

, or both.

22. The method of claim 12, wherein each of the first through seventh tests is weighted.