PH MICROSENSOR FOR GLUCOSE AND OTHER ANALYTE SENSOR FAULT DETECTION

• US 20160249840A1
• Filed: 02/26/2015
• Published: 09/01/2016
• Est. Priority Date: 02/26/2015
• Status: Abandoned Application

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Yao, Jia, Pesantez, Daniel E., Liang, Bradley C., Shah, Rajiv
• Application Number:
  US14/632,731
• Publication Number:
  US 20160249840A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• 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: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52

Abstract

Embodiments of the invention provide amperometric analyte sensor systems comprising a plurality of electrodes including one or more electrodes designed to monitor pH in order to facilitate the sensing of analytes at different pH levels within a sensor environment. Typical embodiments of the invention include glucose oxidase based amperometric sensors used in the management of diabetes.

Claims

1. An amperometric analyte sensor system comprising:

a base;

a plurality of electrodes disposed on the base including;

a working electrode;

a counter electrode;

a reference electrode;

a pH electrode responsive to changes in pH within the sensor system;

a processor; and

a computer-readable program having instructions which cause the processor to assess signal data obtained from the working electrode and the pH electrode;

wherein;

the working electrode and the processor are coupled so that the working electrode monitors analyte within the sensor system;

the pH electrode and the processor are coupled so that the pH electrode monitors pH within the sensor system; and

the processor uses a first algorithm to calculate a concentration of analyte when the pH of the sensor system is at or above pH 7.1; and

the processor uses a second algorithm to calculate a concentration of analyte when the pH of the sensor system is below pH 6.9.

2. The amperometric analyte sensor system of claim 1, wherein the second algorithm calculates the concentration of analyte considering an at least 10% drop in analyte signal that results from the pH of the sensor system changing from at or above pH 7.1 to below pH 6.9.

3. The amperometric analyte sensor system of claim 1, wherein the working electrode is coated with a plurality of layered materials comprising:

an analyte sensing layer comprising an oxidoreductase that produces an acidic compound in the presence of analyte;

an interference rejection layer;

a protein layer;

an adhesion promoting layer; and

/or

an analyte modulating layer, wherein the analyte modulating layer comprises a composition that modulates the diffusion of an analyte diffusing through the analyte modulating layer.

4. The amperometric analyte sensor system of claim 1, wherein the working electrode comprises platinum black coated with a glucose oxidase composition that forms gluconic acid and hydrogen peroxide in the presence of glucose.

5. The amperometric analyte sensor system of claim 1, wherein the pH electrode comprises a metal, a metal oxide, a polymer and/or a hydrogel.

6. The amperometric analyte sensor system of claim 1, wherein the pH electrode and the working electrode are both in operable contact with the reference electrode and the counter electrode.

7. The amperometric analyte sensor system of claim 1, wherein the pH electrode continuously monitors the open circuit potential between the pH electrode and the reference electrode.

8. The amperometric analyte sensor system of claim 7, wherein the first and second algorithms include a determination of how pH modulates amperometric current observed at the working electrode in the presence of analyte.

9. The amperometric analyte sensor system of claim 1, wherein the pH electrode functions as the working electrode.

10. A method of calculating the concentration of glucose at a plurality of different pH values within an amperometric glucose sensor, the method comprising:

(a) placing an amperometric glucose sensor into an environment comprising glucose, where the amperometric analyte sensor is disposed within a system comprising;

a base;

a plurality of electrodes disposed on the base including;

a working electrode, wherein the working electrode is coated with;

an analyte sensing layer comprising glucose oxidase that produces gluconic acid and hydrogen peroxide in the presence of glucose; and

an analyte modulating layer, wherein the analyte modulating layer comprises a composition that modulates the diffusion of an analyte diffusing through the analyte modulating layer;

a counter electrode;

a reference electrode;

a pH electrode responsive to changes in pH within the local sensor system environment;

a processor; and

a computer-readable program having instructions which cause the processor to;

assess signal data obtained from the working electrode and the pH electrode;

wherein;

the working electrode and the processor are coupled so that the working electrode monitors glucose within the sensor system;

the pH electrode and the processor are coupled so that the pH electrode monitors the pH of the sensor within the sensor system;

(b) monitoring the pH of the sensor within the sensor system;

(c) monitoring glucose within the sensor system; and

(d) calculating the concentration of glucose, wherein;

the processor uses a first set of parameters to calculate a concentration of glucose when the pH of the analyte sensing layer is at or above pH 7.1; and

the processor uses a second set of parameters to calculate a concentration of glucose when the pH of the analyte sensing layer is below pH 6.9.

11. The method of claim 10, wherein the second set of parameters calculates the concentration of analyte using an at least 10% drop in analyte signal that results from the pH of the sensor system changing from at or above pH 7.1 to below pH 6.9.

12. The method of claim 10, wherein the pH electrode continuously monitors the open circuit potential between the pH electrode and the reference electrode.

13. The method of claim 12, wherein the system switches from using the first set of parameters to using the second set of parameters when the open circuit potential is above or below a predefined value that is between 20 millivolts and 180 millivolts.

14. The method of claim 10, wherein the method includes using a calibration curve of the relationship between current and pH at the working electrode within the sensor.

15. A method of making an analyte sensor comprising the steps of:

providing a base layer;

forming a conductive layer on the base layer, wherein the conductive layer includes a plurality of electrodes including a pH electrode, a working electrode, a reference electrode and a counter electrode;

forming an analyte sensing layer over the working electrode, wherein the analyte sensing layer comprises a polypeptide that forms an acidic compound in the presence of the analyte; and

forming an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer includes a composition that modulates the diffusion of the analyte therethrough.

forming an adhesion promoting layer on the analyte sensing layer or the protein layer;

or

forming a cover layer disposed on at least a portion of the analyte modulating layer, wherein the cover layer further includes an aperture over at least a portion of the analyte modulating layer.

16. The method of claim 15, wherein the analyte modulating layer comprises:

(1) a polyurethane/polyurea polymer formed from a mixture comprising;

(a) a diisocyanate;

(b) a hydrophilic polymer comprising a hydrophilic diol or hydrophilic diamine; and

(c) a siloxane having an amino, hydroxyl or carboxylic acid functional group at a terminus; and

/or

(2) a branched acrylate polymer formed from a mixture comprising;

(a) a butyl, propyl, ethyl or methyl-acrylate;

(b) an amino-acrylate;

(c) a siloxane-acrylate; and

(d) a poly(ethylene oxide)-acrylate.

17. The method of claim 15, wherein the analyte sensor apparatus operably coupled to a process comprising a computer-readable program having instructions which cause the processor to assess signal data obtained from the working electrode and the pH electrode;

wherein;

the pH electrode and the processor are coupled so that the pH electrode monitors pH of the sensor within the sensor system; and

the processor uses a first algorithm to calculate a concentration of analyte when the pH of the sensor system is at or above pH 7.1; and

the processor uses a second algorithm to calculate a concentration of analyte when the pH of the sensor system is below pH 6.9.

18. The method of claim 15, wherein the pH electrode is adapted to continuously monitor open circuit potential between the pH electrode and the reference electrode.

19. The method of claim 18, wherein the system switches from using the first algorithm to using the algorithm when the open circuit potential is above or below a predefined value that is between 20 millivolts and 180 millivolts.

20. The method of claim 15, wherein a single electrode functions the pH electrode and the working electrode.