LAYERED ENZYME COMPOSITIONS FOR USE WITH ANALYTE SENSORS

• US 20120186997A1
• Filed: 01/20/2011
• Published: 07/26/2012
• Est. Priority Date: 01/20/2011
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Shah, Rajiv, Yang, Qingling, Li, Xiaolong, Li, Yiwen, Pham, Barry Phong
• Granted Patent: US 8,608,921 B2
• Time in Patent Office: Days
• US Class Current: 205/778
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: C12Q 1/00 Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• 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

Abstract

Embodiments of the invention provide amperometric analyte sensors having optimized elements such as electrodes formed from sputtered platinum compositions as well as layers of material selected to optimize the characteristics of a wide variety of sensor elements and sensors. While embodiments of the innovation can be used in a variety of contexts, typical embodiments of the invention include glucose sensors used in the management of diabetes.

Claims

1. An amperometric analyte sensor apparatus comprising:

a base layer;

a conductive layer disposed on the base layer and comprising a working electrode;

a first analyte sensing layer disposed over the conductive layer and comprising a first concentration of glucose oxidase;

a second analyte sensing layer disposed over the first analyte sensing layer and comprising a second concentration of glucose oxidase;

a third analyte sensing layer disposed over the second analyte sensing layer and comprising a third concentration of glucose oxidase; and

an analyte modulating layer disposed over the first, second and third analyte sensing layers.

2. The analyte sensor apparatus of claim 1, wherein the first concentration of glucose oxidase is greater than the second concentration of glucose oxidase and the third concentration of glucose oxidase.

3. The analyte sensor apparatus of claim 1, wherein:

the first concentration of glucose oxidase is between 35 KU/mL and 55 KU/mL;

the second concentration of glucose oxidase is between 30 KU/mL and 55 KU/mL;

or

the third concentration of glucose oxidase is between 5 KU/mL and 15 KU/mL.

4. The analyte sensor apparatus of claim 1, wherein the glucose oxidase is crosslinked to poly(vinyl alcohol)-styrylpyridinium (PVA-SbQ) polymers.

5. The analyte sensor apparatus of claim 4, wherein a surface of the analyte sensing layer comprises chemical moieties crosslinked by a plasma deposition process.

6. The analyte sensor apparatus of claim 1, wherein the working electrode comprises a sputtered platinum composition and the sensor apparatus further comprises an electrolyte retaining layer in operable contact with the conductive layer, wherein the electrolyte retaining layer is formed from a composition selected to absorb 10% to 50% water by weight.

7. The analyte sensor apparatus of claim 1, wherein the analyte modulating layer comprises a blended mixture of a linear polyurethane/polyurea polymer and a branched acrylate polymer blended together at a ratio of between 1:

1 and 1;

20 by weight %.

8. The analyte sensor apparatus of claim 7, wherein the analyte modulating layer comprises a blended mixture of:

(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

(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.

9. The analyte sensor apparatus of claim 1, wherein the analyte modulating layer exhibits a permeability to glucose that changes less than 2% per degree centigrade over a temperature range of 22 to 40 degrees centigrade.

10. The analyte sensor apparatus of claim 1, further comprising at least one of:

a protein layer;

an interference rejection membrane;

an adhesion promoting layer;

or

a cover layer disposed over the analyte sensor apparatus, wherein the cover layer comprises an aperture positioned on the cover layer so as to facilitate an analyte present in the mammal contacting and diffusing through an analyte modulating layer; and

contacting the analyte sensing layer.

11. A method of modulating a flux of hydrogen peroxide molecules within a layered glucose sensor apparatus, the method comprising organizing layers in the apparatus to comprise:

a base layer;

a conductive layer disposed on the base layer and comprising a working electrode;

a first analyte sensing layer disposed over the conductive layer and comprising a first concentration of glucose oxidase;

a second analyte sensing layer disposed over the first analyte sensing layer and comprising a second concentration of glucose oxidase;

a third analyte sensing layer disposed over the second analyte sensing layer and comprising a third concentration of glucose oxidase; and

an analyte modulating layer disposed over the first, second and third analyte sensing layers;

wherein the first, second and third concentrations of glucose oxidase within the first, second and third analyte sensing layers of the layered glucose sensor apparatus alters an angle of the flux of hydrogen peroxide molecules in the first second and third layers that is generated by glucose oxidase in the presence of glucose so that the flux of hydrogen peroxide molecules within the layered glucose sensor apparatus is modulated.

12. The method of claim 11, wherein the first concentration of glucose oxidase is greater than the second concentration of glucose oxidase and the third concentration of glucose oxidase.

13. The method of claim 11, wherein:

the first concentration of glucose oxidase is between 35 KU/mL and 55 KU/mL;

the second concentration of glucose oxidase is between 30 KU/mL and 55 KU/mL;

or

the third concentration of glucose oxidase is between 5 KU/mL and 15 KU/mL.

14. The method of claim 11, wherein:

the first concentration of glucose oxidase is 45 KU/mL;

the second concentration of glucose oxidase is 45 KU/mL;

or

the third concentration of glucose oxidase is 5 KU/mL.

15. The method of claim 11, wherein:

the thickness of the first analyte sensing layer is between 0.5 and 1.5 microns;

the thickness of the second analyte sensing layer is between 0.5 and 1.5 microns;

or

the thickness of the third analyte sensing layer is between 0.5 and 1.5 microns.

16. The method of claim 11, wherein the glucose oxidase in the first, second and third analyte sensing layers alters an angle of the flux of hydrogen peroxide molecules generated by glucose oxidase in the presence of glucose so that the flux of hydrogen peroxide molecules within the layered glucose sensor is directed to an electroactive surface on the working electrode.

17. The method of claim 11, wherein the glucose oxidase is crosslinked to poly(vinyl alcohol)-styrylpyridinium (PVA-SbQ) polymers.

18. The method of claim 11, wherein the analyte modulating layer is formed to comprise a blended mixture of:

(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

(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.

19. The method of claim 11, wherein the analyte modulating layer is formed to exhibit a permeability to glucose that changes less than 2% per degree centigrade over a temperature range of 22 to 40 degrees centigrade.

20. A composition of matter comprising:

a metallic electrode;

a first analyte sensing layer disposed over the metallic electrode and comprising a first concentration of glucose oxidase;

a second analyte sensing layer disposed over the first analyte sensing layer and comprising a second concentration of glucose oxidase;

a third analyte sensing layer disposed over the second analyte sensing layer and comprising a third concentration of glucose oxidase; and

an analyte modulating layer disposed over the first, second and third analyte sensing layers.