Antioxidant protection of a chemical sensor

• US 8,940,544 B2
• Filed: 02/07/2011
• Issued: 01/27/2015
• Est. Priority Date: 02/08/2010
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Suri, Jeff T., Wessling, Ritchie A., Peyser, Thomas A., Gamsey, Soya, Patterson, Eric E.
• Primary Examiner(s): Xu, Robert
• Application Number:
  US13/022,494
• Publication Number:
  US 20110236989A1
• Time in Patent Office: 1,450 Days
• Field of Search: None
• 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 are immobilized within a polymer matrix, wherein said equilibrium fluorescence indicator system comprises a fluorophore operably coupled to a glucose binding moiety functionalized with boronic acid, wherein the equilibrium fluorescence indicator system provides a fluorescence signal intensity related to glucose concentration, and wherein the equilibrium fluorescence indicator system is protected by said at least one antioxidant against degradation caused by hydrogen peroxide such that a presence of the hydrogen peroxide provides no change in the fluorescence signal intensity related to glucose concentration.

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 a 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), and selenium glutathione peroxidase.

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) and selenium glutathione peroxidase.

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 analyte 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.

18. 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.