Analyte sensors and methods for making and using them

• US 20080026473A1
• Filed: 07/25/2006
• Published: 01/31/2008
• Est. Priority Date: 10/18/2002
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Shah, Rajiv, Hoss, Udo, Wang, Yunbing, Van Antwerp, William P., Cochran, Brooks B., Wang, Jenn-Hann Larry
• Granted Patent: US 9,237,865 B2
• Time in Patent Office: Days
• US Class Current: 436/63
• 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: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: Y10T 29/49002 Electrical device making

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 a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety.

Claims

1. An analyte sensor apparatus for implantation within a mammal, the analyte sensor apparatus comprising:

a base layer;

a conductive layer disposed upon the base layer wherein the conductive layer includes a working electrode;

an analyte sensing layer disposed on the conductive layer, wherein the analyte sensing layer detectably alters the electrical current at the working electrode in the conductive layer in the presence of an analyte; and

an analyte modulating layer disposed on the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of the analyte therethrough;

the analyte modulating layer comprising a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety.

2. The analyte sensor apparatus of claim 1 further comprising a protein layer disposed between the analyte sensing layer and the analyte modulating layer.

3. The analyte sensor apparatus of claim 1, further comprising a cover layer disposed on at least a portion of the analyte modulating layer, wherein the cover layer further includes an aperture that exposes at least a portion of the analyte modulating layer to a solution comprising the analyte to be sensed.

4. The analyte sensor apparatus of claim 1, wherein the analyte sensing layer comprises an enzyme selected from the group consisting of glucose oxidase, glucose dehydrogenase, lactate oxidase, hexokinase and lactose dehydrogenase.

5. The analyte sensor apparatus of claim 1, wherein the at least one side chain moiety comprises a Silicon atom covalently bound to an Oxygen atom (—

Si—

O—

).

6. The analyte sensor apparatus of claim 1, wherein at least one side chain is hydrophilic.

7. The analyte sensor apparatus of claim 1, wherein at least one side chain is hydrophobic.

8. The analyte sensor apparatus of claim 1, wherein the central chain is hydrophilic.

9. The analyte sensor apparatus of claim 1, wherein the analyte modulating layer has a glucose diffusion coefficient (D_glucose) of from 1×

10<sup>−

9</sup> cm²/sec to 1×

10<sup>−

7</sup> cm²/sec

10. The analyte sensor apparatus of claim 1, wherein the analyte modulating layer has a oxygen diffusion coefficient (D_oxygen) to glucose diffusion coefficient (D_glucose) ratio (D_oxygen/D_glucose) of 5 to 2000.

11. A composition of matter comprising a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety.

12. The composition of claim 11, wherein the at least one side chain moiety comprising a silicone moiety comprises a Silicon atom covalently bound to an Oxygen atom (—

Si—

O—

).

13. The composition of claim 11, wherein at least one side chain is hydrophilic.

14. The composition of claim 11, wherein at least one side chain is hydrophobic.

15. The composition of claim 11, wherein the central chain is hydrophilic.

16. The composition of claim 11, wherein the central chain comprises a polyvinyl polymer.

17. The composition of claim 16, wherein the polyvinyl polymer comprises polyvinyl acetate, acrylate, acrylamide, acrylonitrile or pyrrolidone subunits.

18. The composition of claim 11, wherein the central chain comprises polyethylene or polypropylene subunits.

19. The composition of claim 11, wherein the composition is made by a process comprising free radical copolymerization.

20. A method of making a 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 a composition that can alter the electrical current at the working electrode in the conductive layer in the presence of an analyte;

optionally forming a protein layer on the analyte sensing layer;

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

forming an analyte modulating layer disposed on the adhesion promoting layer, wherein the analyte modulating layer includes a composition that modulates the diffusion of the analyte therethrough, the analyte modulating layer comprising a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety; and

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.

21. The method of claim 20, wherein the analyte modulating layer has a glucose diffusion coefficient (D_glucose) of from 1×

10<sup>−

9</sup> cm²/sec to 200×

10<sup>−

9</sup> cm²/sec

22. The method of claim 20, wherein the analyte modulating layer has a oxygen diffusion coefficient (D_oxygen) to glucose diffusion coefficient (D_glucose) ratio (D_oxygen/D_glucose) of from 5 to 2000.

23. The method of claim 20, wherein the backbone of at least one side chain comprises 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 atoms.

24. A method of sensing an analyte within the body of a mammal, the method comprising implanting an analyte sensor in to the mammal, the analyte sensor comprising:

a base layer;

a conductive layer disposed upon the base layer wherein the conductive layer includes a working electrode;

an analyte sensing layer disposed on the conductive layer, wherein the analyte sensing layer detectably alters the electrical current at the working electrode in the conductive layer in the presence of an analyte;

an analyte modulating layer disposed on the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of the analyte therethrough;

the analyte modulating layer comprising a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety; and

sensing an alteration in current at the working electrode and correlating the alteration in current with the presence of the analyte, so that the analyte is sensed.

25. A kit comprising a container and, within the container, an analyte sensor apparatus comprising:

a base layer;

a conductive layer disposed upon the base layer wherein the conductive layer includes a working electrode;

an analyte sensing layer disposed on the conductive layer, wherein the analyte sensing layer detectably alters the electrical current at the working electrode in the conductive layer in the presence of an analyte;

an analyte modulating layer disposed on the analyte sensing layer, wherein the analyte modulating layer modulates the diffusion of the analyte therethrough;

the analyte modulating layer comprising a hydrophilic comb-copolymer having a central chain and a plurality of side chains coupled to the central chain, wherein at least one side chain comprises a silicone moiety; and

instructions for using the analyte sensor apparatus.