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

• US 20130331674A1
• Filed: 02/27/2013
• Published: 12/12/2013
• Est. Priority Date: 06/08/2012
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Yang, Ning, Gautham, Raghavendhar, Liang, Bradley C., Shah, Rajiv, Szyman, Catherine M., Miller, Michael E., Wang, Jenn-Hann Larry, Li, Yiwen, Morgan, Wayne A., Chen, Paris, Mucic, Robert C., de Barros, Genival D., Callirgos, Carlos A., Sirigiri, Manjunath, Brinson, Joseph Paul
• Granted Patent: US 10,156,543 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• 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 having at least one working electrode, comprising:

(a) performing a first electrochemical impedance spectroscopy (EIS) procedure to generate a first set of impedance-related data for the at least one working electrode;

(b) after a predetermined time interval, performing a second EIS procedure to generate a second set of impedance-related data for the at least one electrode; and

(c) based on the first and second sets of impedance-related data, determining whether the sensor is functioning normally.

2. A method of calculating a single, fused sensor glucose value based on respective glucose measurement signals of a plurality of redundant sensing electrodes, comprising:

performing respective electrochemical impedance spectroscopy (EIS) procedures for each of the plurality of redundant sensing electrodes to obtain values of at least one impedance-based parameter for each said sensing electrode;

measuring the electrode current (Isig) for each of the plurality of redundant sensing electrodes;

independently calibrating each of the measured Isigs to obtain respective calibrated sensor glucose values;

performing a bound check and a noise check on said measured Isig and said values of the at least one impedance-based parameter and assigning a bound-check reliability index and a noise-check reliability index to each said sensing electrode;

performing signal-dip analysis based on one or more of said at least one impedance-based parameter and assigning a dip reliability index to each said sensing electrode;

performing sensitivity-loss analysis based on one or more of said at least one impedance-based parameter and assigning a sensitivity-loss index to each said sensing electrode;

for each of the plurality of electrodes, calculating a total reliability index based on said electrode'"'"'s bound-check reliability index, noise-check reliability index, dip reliability index, and sensitivity-loss reliability index;

for each of the plurality of electrodes, calculating a weight based on said electrode'"'"'s total reliability index; and

calculating said single, fused sensor glucose value based on the respective weights and calibrated sensor glucose values of each of the plurality of redundant sensing electrodes.

3. A method of detecting an interferent in close proximity to an electrode of a glucose sensor that is implanted or subcutaneously disposed in the body of a patient, comprising:

periodically performing 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 a large increase in the monitored value of the impedance magnitude; and

determining that an interferent exists in close proximity to the electrode if, at about the time of said spike in Isig, there is also a large increase in the monitored values of the impedance magnitude.

4. A method of testing the surface area characteristics of an electroplated electrode, comprising:

performing an electrochemical impedance spectroscopy (EIS) procedure to obtain a value of an impedance-related parameter for said electrode;

correlating said obtained value to said electrode'"'"'s electrochemical surface area;

based on said correlation, determining lower and upper threshold values for said value of the impedance-related parameter;

and determining whether the electrode is acceptable based on whether said value of the impedance-related parameter falls within said lower and upper threshold values.

5. A method of calibrating a sensor during a period of sensor transition, the method comprising:

defining an electrochemical impedance spectroscopy (EIS)-based sensor status vector (V) for each one of a plurality of sensor current (Isig)-blood glucose (BG) pairs;

monitoring the status vectors for the plurality of Isig-BG pairs over time;

detecting when there is a difference between a first status vector for a first Isig-BG pair and a subsequent status vector for a subsequent Isig-BG pair, said first Isig-BG pair having assigned thereto a first offset value; and

if a magnitude of said difference is larger than a predetermined threshold, assigning a dynamic offset value for said subsequent Isig-BG pair that is different from said first offset value so as to maintain a substantially linear relationship between said subsequent Isig and said subsequent BG.

6. A method of calibrating a sensor, comprising:

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

performing a bound check on said values of the at least one impedance-based parameter to determine whether said at least one impedance-based parameter is in-bounds and, based on said bound check, calculating a reliability-index value for said working electrode; and

determining, based on the value of said reliability index, whether calibration should be performed, or whether calibration should be delayed until a later time.

7. A method for real-time detection of low start-up for a working electrode of a sensor, the method comprising:

inserting the sensor into subcutaneous tissue;

performing a first electrochemical impedance spectroscopy (EIS) procedure to generate a first set of impedance-related data for said working electrode; and

based on the first set of impedance-related data, determining whether said working electrode is experiencing low start-up.

8. A method for real-time detection of a signal dip for a working electrode of a sensor, the method comprising:

periodically performing an electrochemical impedance spectroscopy (EIS) procedure to obtain values of real impedance for said electrode;

monitoring said values of real impedance over time; and

based on said values of real impedance, determining whether a dip exists in the signal generated by said working electrode.

9. A method for real-time detection of sensitivity loss for a working electrode of a sensor, the method comprising:

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

calculating values of one or more impedance-related parameters based on said multiple sets of impedance-related data;

monitoring said values over time; and

based on said values, determining whether said working electrode is experiencing sensitivity loss.

10. A sensor system, comprising:

a subcutaneous or implanted sensor, said sensor having a plurality of independent working electrodes, a counter electrode, and a reference electrode; and

sensor electronics operably coupled to said sensor and including;

electronic circuitry configured to selectively perform an electrochemical impedance spectroscopy (EIS) procedure for one or more of said plurality of independent working electrodes to generate impedance-related data for said one or more working electrodes;

a programmable sequencer configured to provide a start stimulus and a stop stimulus for performing said EIS procedure; and

a microcontroller interface configured to operably couple the sensor electronics to a microcontroller.