ANALYTE SENSORS COMPRISING BLENDED MEMBRANE COMPOSITIONS AND METHODS FOR MAKING AND USING THEM

• US 20110152654A1
• Filed: 12/21/2009
• Published: 06/23/2011
• Est. Priority Date: 12/21/2009
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Cochran, Brooks B., Wang, Jenn-Hann Larry, Dang, Tri T., Shah, Rajiv, Mastrototaro, John J.
• Granted Patent: US 8,660,628 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: G01N 27/307 Disposable laminated or multilayered electrodes G01N27/3272 takes precedence
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding

Abstract

Embodiments of the invention provide analyte sensors having elements designed to modulate their chemical reactions as well as methods for making and using such sensors. In certain embodiments of the invention, the sensor includes an analyte modulating membrane that comprises a blended mixture of a linear polyurethane/polyurea polymer, and a branched acrylate polymer.

Claims

1. An amperometric analyte sensor apparatus comprising:

a base layer;

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

an analyte sensing layer disposed on the conductive layer; and

an analyte modulating layer disposed on the analyte sensing layer, wherein;

the analyte modulating layer comprises a blended mixture of;

a linear polyurethane/polyurea polymer, and

a branched acrylate polymer; and

the linear polyurethane/polyurea polymer and the branched acrylate polymer are blended at a ratio of between 1;

1 and 1;

20 by weight %.

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

the linear polyurethane/polyurea polymer exhibits a permeability to glucose that decreases by between 1% and 8% per degree centigrade as temperature is increased from 22 to 40 degrees centigrade; and

the branched acrylate polymer exhibits a permeability to glucose that increases by between 1% and 8% per degree centigrade as temperature is increased from 22 to 40 degrees centigrade.

3. The analyte sensor apparatus of claim 1, wherein the blended 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.

4. The analyte sensor apparatus of claim 1, wherein the analyte sensor apparatus comprises an architecture compatible with biological tissue and elements made from biocompatible materials so as to be implantable in vivo.

5. The analyte sensor apparatus of claim 4, wherein the analyte modulating layer facilitates in vivo hydration of the sensor so that levels of an in vivo analyte can be sensed less than 45 minutes after sensor implantation into an in vivo environment.

6. The analyte sensor apparatus of claim 1, wherein the sensor does not include a separate layer of an adhesion promoting material disposed between the analyte sensing layer and the analyte modulating layer.

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

a protein layer disposed on the analyte sensing layer;

or

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

contacting the analyte sensing layer.

8. The analyte sensor apparatus of claim 1, wherein the analyte sensing layer comprises glucose oxidase.

9. The analyte sensor apparatus of claim 1, wherein the conductive layer comprises a plurality of electrodes including the working electrode, a counter electrode and a reference electrode.

10. The analyte sensor of claim 9, wherein the conductive layer comprises a plurality of working electrodes, counter electrodes and reference electrodes;

and

the plurality of working, counter and reference electrodes are grouped together as a unit and positionally distributed on the conductive layer in a repeating pattern of units.

11. The analyte sensor of claim 1, wherein a pulsed voltage is used to obtain a signal from an electrode.

12. The analyte sensor apparatus of claim 1, wherein the analyte modulating layer comprises a blend 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.

13. The analyte sensor apparatus of claim 12, wherein the branched acrylate polymer is formed from a reaction mixture further comprising a hydroxyl-acrylate.

14. The analyte sensor of claim 12, wherein the analyte modulating layer comprises a blend 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 methyl methacrylate;

(b) a 2-(dimethylamino)ethyl methacrylate;

(c) a polydimethyl siloxane monomethacryloxypropyl;

(d) a poly(ethylene oxide)methyl ether methacrylate; and

(e) a 2-hydroxyethyl methacrylate.

15. A method of making an analyte sensor apparatus for implantation within a mammal comprising the steps of:

providing a base layer;

forming a conductive layer on the base layer, wherein the conductive layer includes a working electrode;

forming an analyte sensing layer on the conductive layer, wherein the analyte sensing layer includes an oxidoreductase;

forming an analyte modulating layer on the analyte sensing layer, wherein;

the analyte modulating layer comprises a blended mixture of;

a linear polyurethane/polyurea polymer, and

a branched acrylate polymer; and

the linear polyurethane/polyurea polymer and the branched acrylate polymer are blended at a ratio of between 1;

1 and 1;

20 by weight %; and

forming a cover layer on the analyte modulating layer.

16. The method of claim 15, wherein the analyte modulating layer composition exhibits a permeability to glucose that changes less than 2% per degree centigrade over a temperature range of 21 to 40 degrees centigrade.

17. The method of claim 15, wherein:

the analyte modulating layer composition comprises a blend of;

(1) a first polymer formed from a mixture comprising;

(a) a diisocyanate;

(b) at least one hydrophilic diol or hydrophilic diamine; and

(c) a siloxane; and

(2) a second polymer formed from a mixture comprising;

(a) a 2-(dimethylamino)ethyl methacrylate;

(b) a methyl methacrylate;

(c) a polydimethyl siloxane monomethacryloxypropyl; and

(d) a poly(ethylene oxide)methyl ether methacrylate.

18. The method of claim 17, wherein the second polymer is formed from a reaction mixture further comprising a 2-hydroxyethyl methacrylate.

19. The method of claim 17, wherein the analyte modulating layer composition is formed to exhibit adhesive properties that allow the analyte modulating layer composition to adhere to adjacent layers in the analyte sensing apparatus so that the analyte sensor apparatus does not include an adhesion promoting layer disposed between the analyte sensing layer and an adjacent layer.

20. A composition of matter comprising a blend of:

(1) a first polymer formed from a mixture comprising;

(a) a diisocyanate compound;

(b) at least one hydrophilic diol or hydrophilic diamine compound; and

(c) a siloxane compound; and

(2) a second polymer formed from a mixture comprising;

(a) 5-45 weight % of a 2-(dimethylamino)ethyl methacrylate compound;

(b) 15-55 weight % of a methyl methacrylate compound;

(c) 15-55 weight % of a polydimethyl siloxane monomethacryloxypropyl compound; and

(d) 5-35 weight % of a poly(ethylene oxide)methyl ether methacrylate compound;

wherein the first polymer and the second polymer are blended together at a ratio between 1;

1 and 1;

20 weight %.

22. The composition of claim 20, wherein the acrylate polymer is formed from a reaction mixture further comprising 1-20 weight % 2-hydroxyethyl methacrylate.

23. The composition of claim 20, wherein the diisocyanate compound comprises about 50 mol % of reactants in the first polymer mixture.

24. The composition of claim 20, wherein:

the linear polyurethane/polyurea polymer exhibits a permeability to glucose that decreases by between 1% and 8% per degree centigrade as temperature is increased from 22 to 40 degrees centigrade; and

the branched acrylate polymer exhibits a permeability to glucose that increases by between 1% and 8% per degree centigrade as temperature is increased from 22 to 40 degrees centigrade.

25. The composition of claim 20, wherein the polymer blend exhibits a permeability to glucose that changes less than 2% per degree centigrade over a temperature range of 22 to 40 degrees centigrade.

21. The composition of 20, wherein the first polymer further comprises a compound that functions as a chain extender.