ANALYTE SENSORS HAVING NANOSTRUCTURED ELECTRODES AND METHODS FOR MAKING AND USING THEM

• US 20090198117A1
• Filed: 01/28/2009
• Published: 08/06/2009
• Est. Priority Date: 01/29/2008
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Vejella, Ratnakar, Shah, Rajiv, Soundararajan, Gopikrishnan, Cooper, Kenneth W.
• Granted Patent: US 9,309,550 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• 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 5/6846 specially adapted to be brought in contact with an internal body part, i.e. invasive
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/001 Enzyme electrodes

Abstract

Embodiments of the invention provide analyte sensors having nanostructured electrodes as well as methods for making and using such sensors. In certain embodiments of the invention, the sensor includes a carbon nanotube electrode and a analyte limiting membrane that modulates the ability of a analyte to contact the carbon nanotube electrode.

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 comprising a plurality of conductive nanotubes;

an analyte sensing layer comprising an oxidoreductase disposed on the conductive nanotubes, wherein the oxidoreductase generates hydrogen peroxide in the presence of an analyte to be sensed; and

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

2. The analyte sensor apparatus of claim 1, wherein the conductive nanotube comprises a carbon nanotube material, a boron nanotube material, a doped nanotube material or an electrically modified nanotube material.

3. The analyte sensor apparatus of claim 1, wherein the conductive nanotube comprises a single-wall nanotube or a multiple-wall nanotube.

4. The analyte sensor apparatus of claim 1, wherein the conductive layer further or alternatively comprises a plurality of nanofibres, a plurality of nanowires, a plurality of nanococoons or a plurality of semiconducting nanoparticles.

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

6. The analyte sensor apparatus of claim 1, wherein the actual surface area of the plurality of conductive nanotubes is at least 100×

greater than the geometric surface area of the plurality of conductive nanotubes

7. The analyte sensor of claim 1, further comprising a reference electrode comprising a plurality of conductive nanotubes and a counter electrode comprising a plurality of conductive nanotubes.

8. The analyte sensor of claim 1, wherein the base layer comprises a surface formed from a gold composition.

9. The analyte sensor apparatus of claim 1, wherein the analyte modulating layer comprises 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, the central chain is hydrophilic, at least one side chain is hydrophilic and at least one side chain is hydrophobic.

10. A method of sensing an analyte within the body of a mammal, the method comprising implanting an analyte sensor of claim 1 into a mammal;

and

sensing an alteration in electrical potential at the working electrode that results from hydrogen peroxide produced by the oxidoreductase in the presence of an analyte to be sensed;

and correlating the alteration in electrical potential with the presence of the analyte, so that the analyte is sensed.

11. The method of claim 10, wherein the method comprises sensing an alteration in electrical potential at a plurality of operating potentials.

12. The method of claim 10, 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

13. The method of claim 10, 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.

14. The method of claim 10, wherein the oxidoreductase comprises an enzyme selected from the group consisting of glucose oxidase, glucose dehydrogenase, lactate oxidase, hexokinase and lactose dehydrogenase and further wherein the oxidoreductase is disposed on the conductive nanotubes by an electrodeposition process.

15. 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 comprising a plurality of conductive nanotubes;

forming an analyte sensing layer on the conductive layer, wherein the analyte sensing layer includes a composition that functions to alter electrical properties of the electrode in the presence of an analyte to be sensed;

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; 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.

16. The method of claim 15, wherein the conductive layer comprises a gold, silver or platinum composition.

17. The method of claim 15, wherein the conductive layer is formed using a plurality of conductive nanotubes uniformly dispersed within a dimethylformamide solution.

18. The method of claim 15, wherein the base layer comprises a ceramic composition.

19. The method of claim 15, wherein a plurality of working electrodes are formed on the base layer.

20. The method of claim 15, wherein the analyte sensing layer is made using a glucose oxidase polypeptide crosslinked with a dialdehyde.