METHOD FOR FUNCTIONALIZING A POROUS MEMBRANE COVERING OF AN OPTICAL SENSOR TO FACILITATE COUPLING OF AN ANTITHROM-BOGENIC AGENT

• US 20140242710A1
• Filed: 09/25/2012
• Published: 08/28/2014
• 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
• Granted Patent: US 10,352,941 B2
• Time in Patent Office: Days
• US Class Current: 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 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.

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, wherein said spacer is polyethylene glycol.

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

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

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

8. The method of claim 1, 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.

9. The method of claim 1, wherein said membrane is PES membrane.

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

11. An analyte sensor comprising a membrane to which heparin is covalently attached by a method according to claim 1.

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 in a blood vessel;

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

a coating comprising heparin covalently bound to at least a portion of the semipermeable membrane,

wherein said heparin is indirectly attached via a spacer to an 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.

13. The sensor of claim 12, wherein said spacer is polyethylene glycol.

14. The sensor of claim 12, wherein said semipermeable membrane is a porous membrane.

15. The sensor of claim 12, wherein said semipermeable membrane is associated with a hollow fiber that encloses the analyte responsive indicator.

16. The sensor of claim 12, wherein a cross-sectional geometry of at least a portion of the sensor is tapered so as to produce generally desirable blood flow characteristics when the sensor is placed in a blood vessel lumen.