ANALYTE SENSOR

• US 20110186429A1
• Filed: 08/25/2009
• Published: 08/04/2011
• Est. Priority Date: 08/27/2008
• Status: Active Grant

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Edwards Lifesciences Corporation
• Inventors: Curry, Kenneth, Oviatt, Henry, Valiket, Mena, Petisce, James R.
• Granted Patent: US 8,900,431 B2
• Time in Patent Office: Days
• US Class Current: 204/403.12
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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 5/6853 with a balloon
• CPC Class Codes: C12Q 1/26 involving oxidoreductase
• CPC Class Codes: C12Q 1/54 involving glucose or galactose

Abstract

Electrochemical sensors for measuring an analyte in a subject are described. More particularly, devices for measurement of an analyte incorporating a sensor comprising a hydrophilic polymer-enzyme composition covering an electroactive surface providing rapid and accurate analyte levels upon deployment are disclosed.

Claims

1. An electrochemical analyte sensor comprising:

at least one electrode having an electroactive surface;

optionally an interference layer in contact with at least a portion of the electroactive surface; and

an enzyme layer comprising a hydrophilic polymer-enzyme composition, at least a portion of the enzyme layer covering the electroactive surface, the enzyme layer providing an electrochemically detectable species capable of providing a detectable output;

wherein sensor break-in is about 30 minutes or less immediately following deployment.

2. The electrochemical analyte sensor of claim 1, wherein the hydrophilic polymer-enzyme composition includes reaction products of a cross-linking agent with the hydrophilic polymer-enzyme composition in an amount sufficient to immobilize the enzyme.

3. The electrochemical analyte sensor of claim 1, wherein said enzyme layer is substantially free of a cross-linking agent or reaction products of a crosslinking agent with the hydrophilic polymer-enzyme composition.

4. The electrochemical analyte sensor of claim 1, wherein the electrochemically detectable species is glucose and sensor break-in is defined as a detectable output corresponding to within about +/−

5 mg/dL of the glucose present at deployment.

5. The electrochemical analyte sensor as in any one of the preceding claims, characterized by wherein the sensor is

substantially absent a separate intervening hydrophilic layer between the electroactive surface and the interference layer;

substantially absent a separate intervening electrolyte layer between the electroactive surface and the interference layer;

substantially absent a separate intervening hydrophilic layer between the interference layer and the enzyme layer;

or

substantially absent a separate intervening electrolyte layer between the interference layer and the enzyme layer.

6. The electrochemical analyte sensor of claim 1, wherein the interference layer is cellulose acetate butyrate.

7. The electrochemical analyte sensor of claim 6, characterized by wherein the cellulose acetate butyrate comprises

(i) less than about 35% acetyl groups and less than about 25% butyryl groups;

(ii) from about 25% to about 34% acetyl groups and from about 15% to about 20% butyryl groups;

(iii) about 29.5% acetyl groups and about 17% butyryl groups;

(iv) a number average molecular weight of about 65,000 Daltons;

or

(v) a combination of (iii) and (iv).

8. The electrochemical analyte sensor of claim 1, wherein the hydrophilic polymer of the hydrophilic polymer-enzyme composition comprises a material selected from the group consisting of poly-N-vinylpyrrolidone, poly-N-vinyl-3-ethyl-2-pyrrolidone, poly-N-vinyl-4,5-dimethyl-2-pyrrolidone, polyvinylimidazole, poly-N—

N-dimethylacrylamide, polyurethane, polyacrylamide, and copolymers thereof.

9. The electrochemical analyte sensor of any one of claim 1 or 8, wherein the hydrophilic polymer of the hydrophilic-enzyme composition is poly-N-vinylpyrrolidone.

10. The electrochemical analyte sensor as in any one of claim 1 or 8, wherein the hydrophilic polymer-enzyme composition comprises poly-N-vinylpyrrolidone, glucose oxidase and at least one protein, or natural or synthetic material, such as a serum albumin.

11. The electrochemical analyte sensor of claim 1, wherein the sensor is constructed on a flex circuit supporting and electrically coupling to at least one electrode, preferably wherein the flex circuit comprises at least one reference electrode, at least one working electrode, and at least one counter electrode.

12. The electrochemical analyte sensor of claim 11, wherein the flex circuit is configurable to a catheter for intravenously measuring an analyte concentration in a subject or a continuous blood glucose monitor for continuously measuring the glucose concentration in a subject.

13. The electrochemical analyte sensor of claim 11, further characterized by:

a flex circuit comprising at least one reference electrode and at least one conductive ink working electrode, the at least one conductive ink working electrode having the electroactive surface capable of providing a detectable electrical output upon interaction with an electrochemically detectable species;

an optional cellulosic derivative layer; and

the enzyme layer covering at least a portion of the electroactive surface of the working electrode;

wherein the flex circuit is electrically configurable to a control unit capable of at least receiving the detectable electrical output;

wherein sensor break-in is about 30 minutes or less immediately following deployment;

optionally wherein the enzyme layer is substantially free of a cross-linking agent or the reaction products of a cross-linking agent and the glucose oxidase.

14. The electrochemical analyte sensor of claim 11, further characterized by

a flex circuit comprising at least one reference electrode and at least one working electrode, the at least one working electrode having an electroactive surface capable of providing a detectable electrical output upon interaction with an electrochemically detectable species;

a cellulose acetate butyrate layer;

an enzyme layer comprising poly-N-vinylpyrrolidone and glucose oxidase, the enzyme layer in contact with at least a portion of the interference layer, and

a membrane comprising vinyl ester monomeric units, the membrane covering the enzyme layer, the interference layer and at least a portion of the electroactive surface of the working electrode;

wherein the flex circuit is electrically configurable to a control unit capable of at least receiving the detectable electrical output.

15. The electrochemical analyte sensor of any one of the claim 1, 6, 8, 11, 13 or 14, further comprising a flux-limiting membrane comprising vinyl acetate monomeric units.

16. The electrochemical analyte sensor of any one of the claim 1, 6, 8, 11, 13 or 14, further comprising a flux-limiting membrane comprising an ethylene vinyl acetate polymer.

17. The electrochemical analyte sensor of any one of the claim 1, 6, 8, 11, 13 or 14, further comprising a flux-limiting membrane comprising an ethylene vinyl acetate polymer comprising about 5-40 wt % vinyl acetate.

18. The electrochemical analyte sensor of any one of the claim 1, 6, 8, 11, 13 or 14, characterized in that the sensor is substantially absent silicone polymers, polyurethane polymers, and their copolymers.