ANTIOXIDANT PROTECTION OF A CHEMICAL SENSOR

• US 20110236989A1
• Filed: 02/07/2011
• Published: 09/29/2011
• Est. Priority Date: 02/08/2010
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: GluMetrics, Inc.
• Inventors: PATTERSON, ERIC E., SURI, JEFF T., PEYSER, THOMAS A., GAMSEY, SOYA, WESSLING, RITCHIE A.
• Granted Patent: US 8,940,544 B2
• Time in Patent Office: Days
• US Class Current: 436/172
• CPC Class Codes: G01N 2021/6432 Quenching
• CPC Class Codes: G01N 2021/6484 Optical fibres
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/6408 with measurement of decay time, time resolved fluorescence
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/77 by observing the effect on a chemical indicator

Abstract

Analyte sensors having antioxidant protection are disclosed. By combining antioxidant and/or scavenger agents into polymer matrices that contain sensor moieties, the sensor moieties are protected from reactive oxygen species. Also disclosed are methods of making analyte sensors and methods of inhibiting oxidative degradation of sensing components in hydrated, polymerized analyte sensor systems.

Claims

1. An analyte sensor, comprising an equilibrium fluorescence indicator system and at least one antioxidant, wherein each of the equilibrium fluorescence indicator system and the at least one antioxidant is immobilized within a polymer matrix.

2. The analyte sensor of claim 1, wherein the equilibrium fluorescence indicator system and the at least one antioxidant is immobilized within a common polymer matrix.

3. The analyte sensor of claim 1, wherein the equilibrium fluorescence indicator system is immobilized within an first polymer matrix and the at least one antioxidant is immobilized within a second polymer matrix that forms an exterior coating around the first polymer matrix.

4. The analyte sensor of claim 2, further comprising a second polymer matrix that comprises at least one antioxidant, wherein said second polymer matrix forms an external coating around the common polymer matrix within which the equilibrium fluorescence indicator system and the at least one antioxidant are immobilized.

5. The analyte sensor of claim 1, wherein the at least one antioxidant is selected from the group consisting of a catalytic antioxidant, a scavenger and a synthetic antioxidant.

6. The analyte sensor of claim 5, wherein the catalytic antioxidant is selected from the group consisting of catalase (CAT), glutathione peroxidase (GSH-Px), selenium glutathione peroxidase and superoxide dismutase (SOD).

7. The analyte sensor of claim 5, wherein the catalytic antioxidant is selected from the group consisting of bioconjugates of catalase (CAT), glutathione peroxidase (GSH-Px), selenium glutathione peroxidase and superoxide dismutase (SOD).

8. The analyte sensor of claim 5, wherein the synthetic antioxidant is TEMPOL.

9. The analyte sensor of claim 5, wherein the scavenger antioxidant is selected from the group consisting of vitamin A, a retinol, a carotenoid, a limonoid, a phytosterol, a flavonoid, an anthocyanidin, a catechin, an isoflavone, an oligomeric proanthocyanidin, an isothiocyanate, a dithiolthione, a sulforaphane, an isoprenoid, a tocotrienol, a tocopherol, vitamin E, lipoic acid, ubiquinone, an ascorbate, vitamin C, 2,3-dihydro-1-benzofuran-5-ols, a chromanone, a water-soluble fullerene antioxidant, C60, C70, a phenolic antioxidant compound, butylated hydroxytoluene (BHT), Trolox™

, a polyphenolic antioxidant compound, caffeic acid, hydrocaffeic acid, vanillic acid, cinnamic acid, benzoic acid and pyruvate.

10. The analyte sensor of claim 5, wherein the synthetic antioxidant is a porphyrin-based synthetic antioxidant.

11. The analyte sensor of claim 5, wherein the synthetic antioxidant is a noble metal selected from the group consisting of platinum, palladium, silver, gold, and alloys thereof or a metal oxide or sulfide selected from the group consisting of manganese dioxide, ruthenium oxide, ruthenium sulfide, and silver oxide.

12. The analyte sensor of claim 11, wherein the synthetic antioxidant is in the form of a porous coating or in the form of colloidal particles or nanoparticles of silver oxide, or nanoparticles of platinum, silver, or gold.

13. The analyte sensor of claim 1, wherein the at least one antioxidant comprises a cocktail of two or more antioxidants.

14. The analyte sensor of claim 13, wherein said two or more antioxidants are a catalase and an antioxidant phenolic compound.

15. The anlalyte sensor of claim 14, wherein said antioxidant phenolic compound is Trolox™

or a Trolox™

derivative.

16. The analyte sensor of claim 13, wherein said two or more antioxidants are a catalase enzyme and vitamin E.

17. The analyte sensor of claim 3, wherein the first and second polymer matrices are physically separated by a semi-permeable membrane.

21. A method of making the analyte sensor of claim 2, comprising immobilizing an equilibrium fluorescence indicator system and at least one antioxidant within a common polymer matrix.

22. A method of making the analyte sensor of claim 3, comprising:

immobilizing an equilibrium fluorescence indicator system within an first polymer matrix; and

immobilizing at least one antioxidant within a second polymer matrix, wherein the second polymer matrix forms an exterior coating around the first polymer matrix.

23. A method of making the analyte sensor of claim 4, comprising:

immobilizing an equilibrium fluorescence indicator system and at least one antioxidant within a first polymer matrix; and

immobilizing at least one antioxidant in an second insoluble matrix, wherein the second polymer matrix forms an external coating around said first polymer matrix.

24. The analyte sensor of claim 1, wherein the equilibrium fluorescence indicator system comprises:

a fluorescent, organic dye;

a boronic acid functionalized viologen quencher; and

a hydrogel matrix.

25. The analyte sensor of claim 1, wherein the equilibrium fluorescence indicator system is protected against degradation caused by hydrogen peroxide.

18. An analyte sensor, comprising an equilibrium fluorescence indicator system immobilized within an insoluble polymer matrix and a porous metal coating surrounding said insoluble polymer matrix.

19. An analyte sensor, comprising:

an optical fiber with proximal and distal ends;

a chemical indicator system capable of generating an emission light signal in response to an excitation light signal, wherein the intensity of the emission light signal is related to the analyte concentration, and wherein the chemical indicator system is immobilized within a gap in the optical fiber by a polymer matrix;

a selectively permeable membrane disposed over the gap; and

a external coating that contains one or more antioxidant,

wherein the sensor is sized for deployment within a blood vessel.

20. The analyte sensor of claim 19, wherein said analyte is glucose and wherein said chemical indicator system comprises a fluorophore operably coupled to a glucose binding moiety, wherein glucose binding causes an apparent optical change in the fluorophore.

26. An analyte sensor comprising an equilibrium fluorescence indicator system and at least one antioxidant, wherein the equilibrium fluorescence indicator is immobilized within a polymer matrix and the at least one antioxidant is covalently bound to a semi-permeable membrane that surrounds the polymer matrix.

27. The analyte sensor of claim 26, wherein the semipermeable membrane is selected from the group consisting of polyethylene, polypropylene, polyurethane, polyethersulfone, polysulfone, polyacrylonitrile, and cellulose acetate.

28. The analyte sensor of claim 26, wherein the at least one antioxidant comprises catalase.