Multi-channel potentiostat for biosensor arrays

• US 8,604,810 B2
• Filed: 10/15/2010
• Issued: 12/10/2013
• Est. Priority Date: 10/16/2009
• Status: Expired due to Fees

• Current Assignee: DARE MB Incorporated
• Original Assignee: MicroCHIPS Inc.
• Inventors: Sheppard, Norman F. Jr.
• Primary Examiner(s): Hollington, Jermele M
• Application Number:
  US12/905,710
• Publication Number:
  US 20110089957A1
• Time in Patent Office: 1,152 Days
• Field of Search: None
• US Class Current: 324/692
• CPC Class Codes: G01N 27/3273 Devices therefor, e.g. test element readers, circuitry details not specific to biochemical electrodes G01N33/4875

Abstract

Arrays of biosensors are provided along with methods for operating the arrays of biosensors. The array of biosensors may include a first reference electrode that is connected to an input of a first control amplifier; a first working electrode and a second working electrode in proximity with the first reference electrode; and a counter electrode that is connected to at least an output of the first control amplifier, where the first control amplifier is operative with the counter electrode to maintain a first specified voltage between the first working electrode and the first reference electrode, and between the second working electrode and the first reference electrode. The array of biosensors optionally may further include a second reference electrode that is connected to an input of a second control amplifier, where the second control amplifier is operative with the counter electrode to maintain a second specified voltage between the first working electrode and the second reference electrode, and between the second working electrode and the second reference electrode.

Claims

1. A method for operating an array of biosensors, comprising:

operating a first control amplifier that receives a first input from a first reference electrode and provides a first output to a counter electrode;

enabling first current measurement circuitry for detecting at least one first current associated with a first working electrode while the first control amplifier is operative, wherein the counter electrode is operative with the first control amplifier to maintain a first specified voltage between the first reference electrode and the first working electrode;

enabling second current measurement circuitry for detecting at least one second current associated with a second working electrode while the first control amplifier is operative, wherein the counter electrode is operative with the first control amplifier to maintain the first specified voltage between the first reference electrode and the second working electrode;

disabling the first control amplifier subsequent to detecting the at least one second current associated with the second working electrode while the first control amplifier is operative;

operating, subsequent to disabling the first control amplifier, a second control amplifier that receives a second input from a second reference electrode and provides a second output to the counter electrode, wherein the first current measurement circuitry detects at least one third current associated with the first working electrode while the second control amplifier is operative, wherein the second current measurement circuitry detects at least one fourth current associated with the second working electrode while the second control amplifier is operative, wherein the counter electrode is operative with the second control amplifier to maintain a second specified voltage between the second reference electrode and the second working electrode.

2. The method of claim 1, wherein a first sensor is associated with the first working electrode, and wherein a second sensor is associated with the second working electrode, further comprising:

calibrating the second sensor by comparing the at least one third current to the at least one fourth current.

3. The method of claim 2, wherein the first sensor is associated with a first calibration function, wherein the first calibration function converts the at least one first current to a first value of interest, and wherein calibrating the second sensor comprising determining a second calibration function for the second sensor, wherein the calibration function converts the third working electrode current to a second value of interest, wherein the first value of interest and the second value of interest are substantially the same.

4. The method of claim 3, wherein a comparison of the at least one third current to the at least one fourth current is utilized to determine the second calibration function by scaling, offsetting, or time shifting the first calibration function for use as the second calibration function.

5. The method of claim 3, wherein the first calibration function is determined for the first sensor by correlating one or more values of the at least one first current to one or more corresponding analyte measurements obtained independently of the first sensor.

6. The method of claim 1, wherein the second current measurement circuitry is enabled when the first working electrode is near an end of its useful life.

7. The method of claim 1, wherein the first current measurement circuitry and the second measurement circuitry includes a respective transimpedance amplifier.

8. The method of claim 7, wherein the first current measurement circuitry and the second current measurement circuitry further includes a respective sensing resistor connected across an inverting input and an output of the respective transimpedance amplifier.

9. The method of claim 1, wherein at least one of the first working electrode and the second working electrode is coated with at least one layer of a biological recognition element.

10. The method of claim 9, wherein the biological recognition element, in the presence of an analyte, generates one or more electroactive active products or consumes one or more electroactive species, that induce current flow at the at least one of the first working electrode and the second working electrode.

11. The method of claim 10, wherein the biological recognition element is glucose oxidase, wherein the analyte is glucose, and wherein the generated electroactive product is hydrogen peroxide.

12. The method of claim 10, wherein the biological recognition element is glucose oxidase, wherein the analyte is glucose, and wherein the consumed electroactive species is oxygen.

13. The method of claim 1, wherein the first working electrode and the second working electrode are provided in respective reservoirs of a substrate.

14. The method of claim 13, wherein the respective reservoirs are sealed until the respective first and second working electrodes are to be utilized with the respective first current measurement circuitry or the second current measurement circuitry.

15. A method for operating an array of biosensors, comprising:

enabling a first sensor that comprises a first working electrode, wherein a first control amplifier receives an input from a first reference electrode and provides a first output to a counter electrode, wherein the first control amplifier maintains a first specified voltage between the first reference electrode and the first working electrode, wherein at least one first current is detected at the first sensor while the first control amplifier is operative;

prior to failure of the first sensor, enabling a second sensor that comprises a second working electrode, wherein the counter electrode is operative with the first control amplifier to maintain the first specified voltage between the first reference electrode and the second working electrode, wherein at least one second current is detected at the second sensor while the first control amplifier is operative;

disabling the first control amplifier subsequent to detecting the at least one second current at the second sensor; and

enabling, subsequent to disabling the first control amplifier, a second control amplifier that receives a second input from a second reference electrode and provides a second output to the counter electrode, wherein the counter electrode is operative with the second control amplifier to maintain a second specified voltage between the second reference electrode and the second working electrode, wherein at least one third current is detected at the first working electrode while the second control amplifier is operative, wherein at least one fourth current is detected at the second working electrode while the second control amplifier is operative.

16. The method of claim 15, wherein the first working electrode, the second working electrode, the first reference electrode, the second reference electrode, and the counter electrode are provided in a substrate, wherein the first control amplifier and the second control amplifier are provided in an integrated circuit, wherein the integrated circuit and the substrate is provided as part of an implantable device.

17. The method of claim 16, wherein the implantable device further includes a microcontroller for receiving the detected at least one first, second, third, and fourth current, wherein the microcontroller directs a wireless transmission of the detected at least one first, second, third, and fourth current to a receiving computer.

18. The method of claim 15, further comprising:

calibrating the second sensor by comparing (i) the at least one third current to the at least one fourth current, or (ii) the at least one first current to the at least one second current.

19. The method of claim 18, wherein a comparison of the at least one third current to the at least one fourth current, or the at least one first current to the at least one second current, is utilized to determine a second calibration function as a scaled version of a first calibration function, wherein the first calibration function is associated with the first sensor.

20. The method of claim 15, wherein at least one of the first working electrode and the second working electrode is coated with at least one layer of a biological recognition element.

21. The method of claim 15, wherein one or more sensing resistors are utilized in detecting one or more of the at least one first, second, third, and fourth current.

22. A device, comprising:

a plurality of control amplifiers, including at least a first control amplifier and a second control amplifier;

a plurality of current measurement circuitry, including at least first current measurement circuitry and second current measurement circuitry; and

a microcontroller in communication with the plurality of control amplifiers and the plurality of current measurement circuitry, wherein the microcontroller is configured to;

operate the first control amplifier that receives a first input from a first reference electrode and provides a first output to a counter electrode;

enable the first current measurement circuitry to detect at least one first current associated with a first working electrode while the first control amplifier is operative, wherein the counter electrode is operative with the first control amplifier to maintain a first specified voltage between the first reference electrode and the first working electrode;

enable the second current measurement circuitry to detect at least one second current associated with a second working electrode while the first control amplifier is operative, wherein the counter electrode is operative with the first control amplifier to maintain the first specified voltage between the first reference electrode and the second working electrode;

disable the first control amplifier subsequent to detecting the at least one second current associated with the second working electrode while the first control amplifier is operative;

operate, subsequent to disabling the first control amplifier, a second control amplifier that receives a second input from a second reference electrode and provides a second output to the counter electrode, wherein the first current measurement circuitry detects at least one third current associated with the first working electrode while the second control amplifier is operative, wherein the second current measurement circuitry detects at least one fourth current associated with the second working electrode while the second control amplifier is operative, wherein the counter electrode is operative with the second control amplifier to maintain a second specified voltage between the second reference electrode and the second working electrode.

23. The device of claim 22, wherein a first sensor is associated with the first working electrode, and wherein a second sensor is associated with the second working electrode, wherein the first sensor is associated with a first calibration function, wherein the first calibration function converts the at least one first current to a first value of interest, and the second sensor is calibrated to determine a second calibration function for the second sensor, wherein the calibration function converts the third working electrode current to a second value of interest, wherein the first value of interest and the second value of interest are substantially the same.

24. The device of claim 23, wherein the first calibration function is determined for the first sensor by correlating one or more values of the at least one first current to one or more corresponding analyte measurements obtained independently of the first sensor.

25. A sensor device, comprising:

a plurality of sensors, including at least a first sensor and a second sensor;

a plurality of control amplifiers, including at least a first control amplifier and a second control amplifier;

a microcontroller in communication with the plurality of sensors and the plurality of control amplifiers, wherein the microcontroller is configured to;

enable the first sensor that comprises a first working electrode, wherein the first control amplifier receives an input from a first reference electrode and provides a first output to a counter electrode, wherein the first control amplifier maintains a first specified voltage between the first reference electrode and the first working electrode, wherein at least one first current is detected at the first sensor while the first control amplifier is operative;

enable, prior to failure of the first sensor, a second sensor that comprises a second working electrode, wherein the counter electrode is operative with the first control amplifier to maintain the first specified voltage between the first reference electrode and the second working electrode, wherein at least one second current is detected at the second sensor while the first control amplifier is operative;

disable the first control amplifier subsequent to detecting the at least one second current associated with the second working electrode while the first control amplifier is operative; and

enable, subsequent to disabling the first control amplifier, the second control amplifier that receives a second input from a second reference electrode and provides a second output to the counter electrode, wherein the counter electrode is operative with the second control amplifier to maintain a second specified voltage between the second reference electrode and the second working electrode, wherein at least one third current is detected at the first working electrode while the second control amplifier is operative, wherein at least one fourth current is detected at the second working electrode while the second control amplifier is operative.

26. The sensor device of claim 25, wherein the second sensor is calibrated by comparing (i) the at least one third current to the at least one fourth current, or (ii) the at least one first current to the at least one second current.

27. The sensor device of claim 26, wherein a comparison of the at least one third current to the at least one fourth current, or the at least one first current to the at least one second current, is utilized to determine the second calibration function as a scaled version of a first calibration function, wherein the first calibration function is associated with the first sensor.