Application of electrochemical impedance spectroscopy in sensor systems, devices, and related methods

• US 9,989,491 B2
• Filed: 03/29/2017
• Issued: 06/05/2018
• Est. Priority Date: 06/08/2012
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Szyman, Catherine M., Miller, Michael E., Shah, Rajiv
• Primary Examiner(s): Weston, Tiffany
• Assistant Examiner(s): TRAN, THO Q
• Application Number:
  US15/472,575
• Publication Number:
  US 20170197030A1
• Time in Patent Office: 433 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 detecting m-cresol in close proximity to an electrode of a glucose sensor that is configured to be implanted or subcutaneously disposed in the body of a patient, said electrode being disposed inside an insulin-infusion catheter such that, when insulin is infused, said infused insulin is in close proximity to said electrode within the patient'"'"'s body, the method comprising:

periodically performing, by sensor electronics operably coupled to said glucose sensor, an electrochemical impedance spectroscopy (EIS) procedure to obtain values of impedance magnitude for said electrode;

obtaining values of measured current (Isig) for said electrode;

monitoring said Isig and said values of impedance magnitude for said electrode over time;

detecting a spike in the monitored Isig and determining whether, at about the time of said Isig spike, there is also an increase in the monitored value of the impedance magnitude;

determining that m-cresol exists in close proximity to the electrode if, at about the time of said spike in Isig, there is also an increase in the monitored values of the impedance magnitude; and

based on said determination that m-cresol exists in close proximity to the electrode, either changing the glucose sensor'"'"'s operating voltage to a point where m-cresol is not measured, or temporarily suspending reporting of glucose measurements to the patient until the monitored value of the impedance magnitude returns to a pre-defined level.

2. The method of claim 1, wherein consecutive applications of said EIS procedure are separated by a time interval therebetween, and wherein the time interval is determined based on the timing of insulin delivery through said insulin-infusion catheter.

3. The method of claim 1, wherein said values of impedance magnitude are obtained at a frequency of 1 kHz.

4. The method of claim 1, wherein, after said spike, the Isig is no longer responsive to glucose for a period of time thereafter.

5. The method of claim 4, wherein said period of time is less than one hour.

6. A method of detecting an interferent in close proximity to an electrode of a glucose sensor that is configured to be implanted or subcutaneously disposed in the body of a patient, said electrode being disposed inside an insulin-infusion catheter such that, when insulin is infused, said infused insulin is in close proximity to said electrode within the patient'"'"'s body, the method comprising:

periodically performing, by sensor electronics operably coupled to said glucose sensor, an electrochemical impedance spectroscopy (EIS) procedure to obtain values of impedance magnitude for said electrode;

obtaining values of measured current (Isig) for said electrode;

monitoring said Isig and said values of impedance magnitude for said electrode over time;

detecting a spike in the monitored Isig and determining whether, at about the time of said Isig spike, there is also an increase in the monitored value of the impedance magnitude;

determining that an interferent exists in close proximity to the electrode if, at about the time of said spike in Isig, there is also an increase in the monitored values of the impedance magnitude, wherein, after said spike, the Isig is no longer responsive to glucose for a period of time thereafter, and wherein the duration of said period of time is dependent upon the rate of diffusion of said interferent through the patient'"'"'s body, and wherein the interferent is m-cresol; and

based on said determination that said interferent exists in close proximity to the electrode, either changing the glucose sensor'"'"'s operating voltage to a point where the interferent is not measured, or temporarily suspending reporting of glucose measurements to the patient until the monitored value of the impedance magnitude returns to a pre-defined level.

7. The method of claim 6, wherein said period of time is less than one hour.

8. The method of claim 6, wherein the patient is notified that the sensor will not provide glucose measurements for the duration of said period of time.

9. The method of claim 6, wherein consecutive applications of said EIS procedure are separated by a time interval therebetween, and wherein the time interval is determined based on the timing of insulin delivery through said insulin-infusion catheter.

10. The method of claim 6, wherein said values of impedance magnitude are obtained at a frequency of 1 kHz.