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

Patent metadata

Field	Value
Publication number	US-10352941-B2
Application number	US-201214347567-A
Country	US
Kind code	B2
Filing date	Sep 25, 2012
Priority date	Sep 27, 2011
Publication date	Jul 16, 2019
Grant date	Jul 16, 2019

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.

First claim

What is claimed is:

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 NH 3 .

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.

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.

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.

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.

Assignees

• Medtronic Minimed Inc

Inventors

• Suri Jeff T
• Patterson Eric

Classifications

• Y10T436/144444

  Glucose · CPC title

• G01N2650/00

  Assays involving polymers whose constituent monomers bore biological functional groups before polymerization, i.e. vinyl, acryl derivatives of amino acids, sugars · CPC title

• B05D3/142

  Pretreatment · CPC title

• A61L33/0023 Primary

  using a quaternized group or a protonated amine group of the substrate · CPC title

• G01N2400/40

  Glycosaminoglycans, i.e. GAG or mucopolysaccharides, e.g. chondroitin sulfate, dermatan sulfate, hyaluronic acid, heparin, heparan sulfate, and related sulfated polysaccharides · CPC title