System and method for operating an electrochemical analyte sensor

• US 7,751,864 B2
• Filed: 03/01/2007
• Issued: 07/06/2010
• Est. Priority Date: 03/01/2007
• Status: Active Grant

• Current Assignee: Roche Diabetes Care Inc. (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Buck, Harvey B. Jr.
• Primary Examiner(s): Nasser; Robert L
• Assistant Examiner(s): D'Angelo; Michael
• Application Number:
  US11/680,963
• Publication Number:
  US 20080214910A1
• Time in Patent Office: 1,223 Days
• Field of Search: 600345-350, 600365-366, 205/775, 204193-194, 204/400, 204/401, 204/403.01
• US Class Current: 600/345
• 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 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: G01N 27/3274 Corrective measures, e.g. error detection, compensation for temperature or hematocrit, calibration coding of calibration information G01N33/48771

Abstract

A method of operating an electrochemical analyte sensor having one or more electrodes may comprise applying a time-varying input signal to at least one of the one or more electrodes, monitoring a time-varying output signal produced by the sensor in response to application of the time-varying input signal, determining a complex impedance of the sensor based on the time-varying input and output signals, and determining from the complex impedance information relating to operation of the sensor.

Claims

1. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying for a test period a time-varying input signal to at least one of the one or more electrodes,

monitoring a time-varying output signal produced by the sensor in response to application for the test period of the time-varying input signal,

determining a complex impedance of the sensor based on the time-varying input signal applied for the test period and on the time-varying output signal,

applying for an entirety of the test period a constant-valued DC input signal to the at least one of the one or more electrodes,

monitoring a DC output signal produced by the sensor in response to the application of the DC input signal, and

determining at least one measured value of the analyte based on the complex impedance of the sensor and on the DC output signal using a processor.

2. The method of claim 1 wherein determining at least one measured value of an analyte to which the sensor is exposed comprises:

selecting a mathematical model of the sensor having a number of model components,

fitting values of the complex impedance to the mathematical model of the sensor to determine values of the number of model components,

identifying one or a functional combination of the number of model components having a response over time that, when combined with the DC output signal, produces a sensor response that has minimal undesirable variations in magnitude over time, and

computing the at least one measured value of the analyte based on values of the identified one or functional combination of the number of model components and on the DC output signal.

3. The method of claim 2 wherein applying a time-varying input signal to at least one of the one or more electrodes comprises applying the time-varying input signal at a number of different frequencies.

4. The method of claim 2 further comprising:

identifying another one or a functional combination of the model components having a response over time that is substantially insensitive to variations in analyte concentration and sensor sensitivity,

identifying as stable only ones of the one or a functional combination of the number of model components for which the values of corresponding ones of the another one or a functional combination of the model components fall within a range of response values, and

using only the stable ones of the one or a functional combination of the number of model components to compute the at least one measured value of the analyte.

5. The method of claim 1 wherein applying for a test period a time-varying input signal to at least one of the one or more electrodes and applying for an entirety of the test period a constant-valued DC input signal to the at least one of the one or more electrodes together comprise applying a single input signal to the at least one of the one or more electrodes that has a time-varying component and a constant-valued DC component.

6. The method of claim 1 wherein the time-varying input signal and the constant-valued DC signal are separate signals each applied to the at least one of the one or more electrodes.

7. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying a time-varying input signal to at least one of the one or more electrodes,

monitoring a time-varying output signal produced by the sensor in response to application of the time-varying input signal,

determining a complex impedance of the sensor based on the time-varying input and output signals, and

determining at least one measured value of an analyte to which the sensor is exposed based, at least in part, on the complex impedance,

wherein determining at least one measured value of an analyte to which the sensor is exposed comprises;

selecting a mathematical model of the sensor having a number of model components,

fitting values of the complex impedance to the mathematical model of the sensor to determine values of the number of model components,

identifying one or a functional combination of the number of model components having a response over time that produces a sensor response that has minimal undesirable variations in magnitude over time, and

computing the at least one measured value of the analyte based on values of the identified one or functional combination of the number of model components using a processor.

8. The method of claim 7 wherein applying a time-varying input signal to at least one of the one or more electrodes comprises applying the time-varying input signal at a number of different frequencies.

9. The method of claim 7 further comprising:

identifying another one or a functional combination of the model components having a response over time that is substantially insensitive to variations in analyte concentration and sensor sensitivity,

identifying as stable only ones of the one or a functional combination of the number of model components for which the values of corresponding ones of the another one or a functional combination of the model components fall within a range of response values, and

using only the stable ones of the one or a functional combination of the number of model components to compute the at least one measured value of the analyte.

10. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying a time-varying input signal to at least one of the one or more electrodes,

monitoring a time-varying output signal produced by the sensor in response to application of the time-varying input signal,

determining a complex impedance of the sensor based on the time-varying input and output signals, and

determining from the complex impedance whether an output response of the sensor is stable by;

selecting a mathematical model of the sensor having a number of model components,

fitting values of the complex impedance to the mathematical model of the sensor to determine values of the number of model components,

identifying one or a functional combination of the model components having a response over time that is substantially insensitive to variations in analyte concentration and sensor sensitivity, and

identifying as stable only sensor output response samples for which the values of corresponding ones of the one or a functional combination of the model components fall within a range of response values using a processor.

11. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying a time-varying input signal to at least one of the one or more electrodes,

monitoring a time-varying output signal produced by the sensor in response to application of the time-varying input signal,

determining a complex impedance of the sensor based on the time-varying input and output signals,

determining from the complex impedance whether an output response of the sensor is stable, and

producing a signal when the output response of the sensor is not stable by;

selecting a mathematical model of the sensor having a number of model components,

fitting values of the complex impedance to the mathematical model of the sensor to determine values of the number of model components,

identifying one or a functional combination of the model components having a response over time that is substantially insensitive to variations in analyte concentration and sensor sensitivity, and

producing the signal if a number of values of the one or functional combination of the model components fall outside of a range of constant response values using a processor.

12. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying a time-varying input signal to at least one of the one or more electrodes,

monitoring a time-varying output signal produced by the sensor in response to application of the time-varying input signal,

determining a complex impedance of the sensor based on the time-varying input and output signals,

determining from the complex impedance whether an output response of the sensor is stable, and

executing a sensor calibration procedure if the output response of the sensor is not stable by;

selecting a mathematical model of the sensor having a number of model components,

fitting values of the complex impedance to the mathematical model of the sensor to determine values of the number of model components,

identifying one or a functional combination of the model components having a response over time that is substantially insensitive to variations in analyte concentration and sensor sensitivity, and

executing the sensor calibration procedure if a number of values of the one or functional combination of the model components fall outside of a range of constant response values using a processor.

13. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying a time-varying input signal to at least one of the one or more electrodes and applying at the same time a constant-value DC input signal to the at least one of the one or more electrodes,

monitoring a time-varying output signal produced by the sensor in response to application of the time-varying input signal,

monitoring a DC output signal produced by the sensor in response to application of the constant-valued DC input signal,

determining a complex impedance of the sensor based on the time-varying input and output signals, and

computing measured values of an analyte to which the sensor is exposed based, at least in part, on the complex impedance by

selecting a model of the sensor having model components,

fitting values of the complex impedance to the model of the sensor to determine complex values of the model components,

determining one or a functional combination of the model components that, when the complex values of the one or functional combination of the model components are mathematically combined with the DC output signal, compensates for an effect on the measured values of the analyte of at least one undesirable characteristic of the DC output signal of the sensor, and

computing the measured values of the analyte based the DC output of the sensor and the one or functional combination of the complex values of the model components using a processor.

14. The method of claim 13 wherein selecting a model of the sensor comprises selecting an equivalent mathematical circuit model of the sensor having model components in the form of mathematical electrical components that are interconnected to define the circuit model.

15. The method of claim 14 wherein fitting the values of the complex impedance to the model of the sensor comprises mathematically fitting the values of the complex impedance to a number of mathematical equations defining the equivalent mathematical circuit model to determine a corresponding set of values for each of the mathematical electrical components.

16. The method of claim 13 wherein determining one or a functional combination of the model components comprises determining one or a functional combination of the model components that, when the values of the one or functional combination of the model components are combined with the DC output signal of the sensor, compensates for an effect on the measured values of the analyte of a sensitivity drift of the DC output signal of the sensor over time.

17. The method of claim 13 wherein computing the measured values of the analyte comprises performing a statistical procedure on the DC output signal of the sensor and on the values of the one or functional combination of the model components.

18. The method of claim 17 wherein computing the measured values of the analyte comprises:

performing a principle component statistical procedure on the values of the one or functional combination of the model components to determine a number of principle components,

fitting at least some of the principle components to a set of principle component model equations that model the measured value of the analyte, and

applying the DC output signal of the sensor to the set of principle component model equations and solving for the measured values of the analyte.

19. The method of claim 17 wherein computing the measured values of the analyte comprises:

fitting at least some of the values of the one or functional combination of the model components to a set of empirical model equations that model the measured value of the analyte, and

applying the DC output signal of the sensor to the set of empirical model equations and solving for the measured values of the analyte.

20. A method of operating an electrochemical analyte sensor having one or more electrodes, comprising:

applying a time-varying input signal to at least one of the one or more electrodes,

varying a frequency of the time-varying input signal over a spectrum of frequencies,

monitoring a time and frequency varying output signal produced by the sensor in response to application of the time and frequency varying input signal, and

determining a corresponding spectrum of complex impedance values of the sensor based on the time and frequency varying input and output signals,

wherein varying a frequency of the time-varying input signal over a spectrum of frequencies comprises providing the time-varying input signal as a complex mixture of frequencies within the spectrum of frequencies in a manner that allows a magnitude of the time-varying input signal to remain small, and

determining at least one measured value of the analyte based on the spectrum of complex impedance values of the sensor by;

selecting a mathematical model of the sensor having a number of model components,

fitting values of the spectrum of complex impedance values to the mathematical model of the sensor to determine values of the number of model components,

identifying one or a functional combination of the number of model components having a response over time that produces a sensor response that has minimal undesirable variations in magnitude over time, and

computing the at least one measured value of the analyte based on values of the identified one or functional combination of the number of model components using a processor.