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