Ph microsensor for glucose and other analyte sensor fault detection

Patent metadata

Field	Value
Publication number	US-2016249840-A1
Application number	US-201514632731-A
Country	US
Kind code	A1
Filing date	Feb 26, 2015
Priority date	Feb 26, 2015
Publication date	Sep 1, 2016
Grant date	—

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.

First claim

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 pr

Assignees

• Medtronic Minimed Inc

Inventors

• Pesantez Daniel E
• Yao Jia
• Liang Bradley C
• Shah Rajiv

Classifications

• G01N27/3272

  Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels (optical biosensors G01N33/52) · CPC title

• A61B5/14865 Primary

  invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors · CPC title

• A61B5/14539

  for measuring pH · CPC title

• A61B5/14532

  for measuring glucose, e.g. by tissue impedance measurement · CPC title

• C12Q1/005

  involving specific analytes or enzymes (including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence) · CPC title