Method for functionalizing a porous membrane covering of an optical sensor to facilitate coupling of an antithrom-bogenic agent

• US 10,352,941 B2
• Filed: 09/25/2012
• Issued: 07/16/2019
• Est. Priority Date: 09/27/2011
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Suri, Jeff T., Patterson, Eric
• Primary Examiner(s): Fritchman, Rebecca M
• Application Number:
  US14/347,567
• Publication Number:
  US 20140242710A1
• Time in Patent Office: 2,485 Days
• Field of Search: 436 95
• CPC Class Codes: A61L 33/0023 using a quaternized group or a protonated amine group of the substrate
• CPC Class Codes: B05D 3/142 Pretreatment
• CPC Class Codes: G01N 2400/40 Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides
• CPC Class Codes: G01N 2650/00 Assays involving polymers whose constituent monomers bore biological functional groups before polymerization, i.e. vinyl, acryl derivatives of amino acids, sugars
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

Methods of covalently attaching heparin to a membrane comprising plasma treating the membrane to produce an amino-functionalized membrane; and reacting the amino-functionalized membrane with heparin under conditions in which heparin becomes covalently attached to the amino-functionalized membrane, wherein said heparin is indirectly attached via a spacer to said amino-functionalized membrane and/or said heparin is attached from a single site in said heparin to a single site on said amino-functionalized membrane or to said spacer. Also disclosed are analyte sensors.

Claims

1. A method of covalently attaching heparin to an analyte-permeable membrane on an analyte sensor comprising:

providing an analyte sensor, the analyte sensor including

an optical fiber defining a light path;

an analyte-responsive chemical indicator system comprising a fluorophore operably coupled to an analyte binding moiety, wherein the chemical indicator system is disposed within the light path along a distal portion of the optical fiber and wherein said indicator system is capable of generating a signal related to a concentration of analyte, and wherein the fluorophore generates a fluorescence emission signal when excited by light and a glucose binding moiety to modulate the florescence emission signal; and

an analyte-permeable membrane covering the indicator system at least along the distal portion of the optical fiber;

plasma treating the analyte-permeable membrane to produce an amino-functionalized membrane; and

reacting the amino-functionalized membrane with heparin under conditions in which heparin becomes covalently attached to the amino-functionalized membrane, wherein said heparin is indirectly attached via a spacer to said amino-functionalized membrane and/or said heparin is attached from a single site in said heparin to a single site on said amino-functionalized membrane or to said spacer.

2. The method of claim 1, wherein said plasma treatment is conducted with radio frequency glow discharge plasma.

3. The method of claim 1, wherein said plasma is selected from the group consisting of, allylamine and NH₃.

4. The method of claim 1, comprising the following step:

5. The method of claim 1 comprising the following steps:

6. The method of claim 4 or 5, wherein said EDC/NHS concentration is 10 mM.

7. The method of claim 1, wherein said analyte-permeable membrane is PES membrane.

8. The method of claim 1, wherein said analyte-permeable membrane is associated with a hollow fiber that encloses an analyte-responsive indicator.

13. The method of claim 1, wherein said spacer is polyethylene glycol and wherein said membrane is selected from the group consisting of polyethersulfone (PES) membrane, polyethersulfone/polyvinylpyrrolidone (PES/PVP) blend membrane and High Density Polyethylene (HDPE) membrane.

14. The method of claim 1, wherein the fluorophore is HPTS-triCysMA.

15. The method of claim 1, further including contacting the analyte-permeablfe membrane with a solution of benzalkonium and heparin.

16. The method of claim 1, wherein the reacting the amino-functionalized membrane with heparin includes soaking the amino-functionalized membrane in an aqueous heparin solution for at least one hour.

9. An analyte sensor comprising:

an optical fiber defining a light path;

an analyte-responsive chemical indicator system comprising a fluorophore operably coupled to an analyte binding moiety, wherein the chemical indicator system is disposed within the light path along a distal portion of the optical fiber, and wherein said indicator system is capable of generating a signal related to a concentration of analyte, and wherein the fluorophore generates a fluorescence emission signal when excited by light and a glucose binding moiety to modulate the florescence emission signal; and

an analyte-permeable membrane covering the indicator system at least along the distal portion of the optical fiber;

a coating comprising heparin covalently bound to at least a portion of the analyte-permeable membrane,

wherein said heparin is indirectly attached via a spacer to said analyte-permeable membrane and/or said heparin is attached from a single site in said heparin to a single site on said analyte-permeable membrane or to said spacer.

10. The sensor of claim 9, wherein said analyte-permeable membrane is a porous membrane.

11. The sensor of claim 9, wherein said analyte-permeable membrane is associated with a hollow fiber that encloses the analyte responsive indicator.

12. The sensor of claim 9, wherein a cross-sectional geometry of at least a portion of the sensor is placed in a blood vessel lumen.

17. The sensor of claim 9, wherein the fluorophore is HPTS-triCysMA.

18. The sensor of claim 9, wherein the fluorophore and the analyte binding moiety are immobilized within a water-insoluble organic polymer.

19. The sensor of claim 18, wherein the analyte binding moiety is 3,3′

-oBBV and the water-insoluble organic polymer is a DMAA (N,N-dimethylacrylamide) hydrogel matrix.