Sensors with thromboresistant coating

• US 8,715,589 B2
• Filed: 05/14/2013
• Issued: 05/06/2014
• Est. Priority Date: 09/30/2009
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Romey, Matthew A., Gamsey, Soya, Markle, David R.
• Primary Examiner(s): COLE, MONIQUE T
• Application Number:
  US13/894,228
• Publication Number:
  US 20130267801A1
• Time in Patent Office: 357 Days
• Field of Search: 422/403, 600/316
• US Class Current: 422/403
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14542 for measuring blood gases A61B5/14551 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 2021/773 Porous polymer jacket; Polymer matrix with indicator
• CPC Class Codes: G01N 2021/7786 Fluorescence
• CPC Class Codes: G01N 21/7703 using reagent-clad optical fibres or optical waveguides using measurement of total internal reflection or attenuated total reflection G01N21/552; optical fibres or waveguides per se G02B
• CPC Class Codes: G01N 21/80 Indicating pH value

Abstract

Embodiments of the present invention relate to analyte sensors comprising a heparin coating, and methods of coating analyte sensors. The heparin can be stably associated with at least a portion of a porous membrane that covers a portion of the analyte sensors. The heparin can be photochemically linked to the coating through the formation of covalent bonds.

Claims

1. An analyte sensor, comprising:

an elongate member;

an analyte-responsive indicator disposed along a distal portion of the elongate member, wherein said indicator is capable of generating a signal related to a concentration of analyte;

a porous membrane covering at least the indicator along the distal portion of the elongate member; and

a coating comprising heparin stably associated with at least a portion of the porous membrane, wherein the heparin is covalently bound to a chemical linking moiety comprising skeletal moiety selected from the group consisting of a C₁-C₁₀ alkyl group, a carbohydrate, a polyoxyethylene and a polypeptide, wherein the chemical linking moiety is covalently bound to the porous membrane.

2. The analyte sensor of claim 1, wherein the elongate member comprises an optical fiber comprising a light path.

3. The analyte sensor of claim 2, wherein the analyte-responsive indicator comprises a fluorophore operably coupled to an analyte binding moiety, wherein analyte binding causes a change in the emission intensity of the fluorophore, and wherein the analyte responsive indictor is disposed within the light path of the optical fiber.

4. The analyte sensor of claim 3, wherein the fluorophore is HPTS-triCysMA and the binding moiety is 3,3′

-oBBV.

5. The analyte sensor of claim 1, wherein the analyte-responsive indicator is immobilized within a hydrogel that comprises heparin.

6. The analyte sensor of claim 1, wherein the porous membrane is a microporous membrane.

7. The analyte sensor of claim 6, wherein the microporous membrane comprises one or more polymers selected from a group consisting of the polyolefins, the fluoropolymers, the polycarbonates, and the polysulfones.

8. The analyte sensor of claim 6, wherein the microporous membrane comprises at least one fluoropolymer.

9. The analyte sensor of claim 8, wherein the at least one fluoropolymer is selected from the group consisting of polytetrafluoroethylene, perfluoroalkoxy polymer, fluorinated ethylene-propylene, polyethylenetetrafluoroethylene, polyvinylfluoride, polyethylenechlorotrifluoroethylene, polyvinylidene fluoride, polychlorotrifluoroethylene, perfluoropolyether, perfluoroelastomer, and fluoroelastomer.

10. The analyte sensor of claim 6, wherein the microporous membrane comprises at least one polyolefin.

11. The analyte sensor of claim 10, wherein the at least one polyolefin is polyethylene.

12. An analyte sensor, comprising:

an elongate member;

an analyte-responsive indicator disposed along a distal portion of the elongate member, wherein said indicator is capable of generating a signal related to a concentration of analyte;

a porous membrane covering at least the indicator along the distal portion of the elongate member; and

a coating comprising heparin stably associated with at least a portion of the porous membrane, wherein the heparin is covalently bound to a chemical linking moiety that is covalently bound to the porous membrane;

wherein a least the portion of the elongate member coated by the coating comprises high molecular weight polyamine.

13. The analyte sensor of claim 12, wherein the elongate member comprises an optical fiber comprising a light path.

14. The analyte sensor of claim 13, wherein the analyte-responsive indicator comprises a fluorophore operably coupled to an analyte binding moiety, wherein analyte binding causes a change in the emission intensity of the fluorophore, and wherein the analyte responsive indictor is disposed within the light path of the optical fiber.

15. The analyte sensor of claim 14, wherein the fluorophore is HPTS-triCysMA and the binding moiety is 3,3′

-oBBV.

16. An analyte sensor, comprising:

an elongate member;

an analyte-responsive indicator disposed along a distal portion of the elongate member, wherein said indicator is capable of generating a signal related to a concentration of analyte;

a porous membrane covering at least the indicator along the distal portion of the elongate member; and

a coating comprising heparin stably associated with at least a portion of the porous membrane, wherein the heparin is covalently bound to a chemical linking moiety that is covalently bound to the porous membrane;

wherein the chemical linking moiety has the formula;

A-X—

B;

wherein A is a photochemically reactive group capable of covalently bonding to the porous membrane after activation by actinic radiation;

B is a different reactive group from A and capable of covalently bonding to heparin; and

X is a skeletal moiety that is resistant to cleavage in an aqueous physiological fluid and joins the A and B reactive groups.

17. The analyte sensor of claim 16, wherein the elongate member comprises an optical fiber comprising a light path.

18. The analyte sensor of claim 17, wherein the analyte-responsive indicator comprises a fluorophore operably coupled to an analyte binding moiety, wherein analyte binding causes a change in the emission intensity of the fluorophore, and wherein the analyte responsive indictor is disposed within the light path of the optical fiber.

19. The analyte sensor of claim 18, wherein the fluorophore is HPTS-triCysMA and the binding moiety is 3,3′

-oBBV.

20. An analyte sensor, comprising:

an elongate member;

an analyte-responsive indicator disposed along a distal portion of the elongate member, wherein said indicator is capable of generating a signal related to a concentration of analyte;

a porous membrane covering at least the indicator along the distal portion of the elongate member; and

a coating comprising heparin stably associated with at least a portion of the porous membrane, wherein the heparin is covalently bound to a chemical linking moiety that is covalently bound to the porous membrane;

wherein the chemical linking moiety has the formula;

21. The analyte sensor of claim 20, wherein the elongate member comprises an optical fiber comprising a light path.

22. The analyte sensor of claim 21, wherein the analyte-responsive indicator comprises a fluorophore operably coupled to an analyte binding moiety, wherein analyte binding causes a change in the emission intensity of the fluorophore, and wherein the analyte responsive indictor is disposed within the light path of the optical fiber.

23. The analyte sensor of claim 22, wherein the fluorophore is HPTS-triCysMA and the binding moiety is 3,3′

-oBBV.