Implantable enzyme-based monitoring system having improved longevity due to improved exterior surfaces

• US 20030065254A1
• Filed: 10/31/2002
• Published: 04/03/2003
• Est. Priority Date: 10/20/1997
• Status: Active Grant

• Current Assignee: Alfred E. Mann Foundation For Scientific Research
• Original Assignee: Alfred E. Mann Foundation For Scientific Research
• Inventors: Schulman, Joseph H., Byers, Charles L., Adomian, Gerald E., Colvin, Michael S.
• Granted Patent: US 6,934,572 B2
• Time in Patent Office: Days
• US Class Current: 600/347
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors

Abstract

An implantable enzyme-based monitoring system suitable for long term in vivo use to measure the concentration of prescribed substances such as glucose is provided. In one embodiment, the implantable enzyme-based monitoring system includes at least one sensor assembly, an outer membrane surrounding the sensor assembly and having a window therein, and a polymeric window cover affixed to the outer membrane and covering the window. Preferably, the outer membrane of the monitoring system is silicone and the window cover is a polymer of 2-hydroxyethyl methacrylate (HEMA), N,N,-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA). Also provided herein is an implantable enzyme-based monitoring system having at least one sensor assembly, an outer membrane surrounding the sensor assembly and a coating affixed to the exterior surface of the outer membrane, wherein the coating resists blood coagulation and protein binding to the exterior surface of the outer membrane. Preferably, the coating is polyethylene glycol (PEG) and heparin in an 80:20 molar ratio. Finally, provided herein is a method of coating the exterior surface of the outer membrane of an implantable enzyme-based monitoring system comprising the steps of forming hydroxyl groups on the silicone surface by plasma etching; reacting the silicone surface with amino functionalized silane, thereby forming amino groups on the silicone surface; simultaneously, covalently binding polyethylene glycol (PEG) and heparin to the amino groups; and ionically binding heparin to the monitoring system surface.

Claims

1. An implantable monitoring system comprising:

at least one sensor assembly;

an outer membrane surrounding the sensor assembly, the outer membrane having at least one window therein; and

a window cover associated with the outer membrane such that the window is covered thereby.

2. An implantable monitoring system according to claim 1, further comprising an enzyme solution positioned between the sensor assembly and the window cover within the outer membrane.

3. An implantable monitoring system according to claim 2, wherein the enzyme solution comprises glucose oxidase and the window cover is glucose permeable.

4. An implantable monitoring system according to claim 1, wherein the window cover is glucose and oxygen permeable.

5. An implantable monitoring system according to claim 1 or claim 4, wherein the window cover comprises a polymeric system of 2-hydroxyethyl methacrylate (HEMA), N,N,-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA).

6. An implantable monitoring system according to claim 5, wherein the weight ratios of the components of the polymeric system are about 50:

25;

25, for the HEMA, DMAEMA and MA, respectively.

7. An implantable monitoring system according to claim 1, further comprising a coating on the exterior surface of the outer membrane and window cover, which coating resists blood coagulation and protein binding to the exterior surface of the outer membrane.

8. An implantable monitoring system according to claim 7, wherein the coating comprises polyethylene glycol (PEG) and heparin in an 80:

20 molar ratio.

9. An implantable monitoring system comprising:

at least one sensor assembly;

an outer membrane surrounding the sensor assembly; and

a coating on the exterior surface of the outer membrane, which coating resists blood coagulation and protein binding to the exterior surface of the outer membrane.

10. An implantable monitoring system according to claim 9, wherein the coating comprises polyethylene glycol (PEG) and heparin.

11. An implantable monitoring system according to claim 10, wherein the molar ratio of PEG to heparin in the coating is 80 to 20.

12. An implantable monitoring system according to claim 11, wherein the heparin is both covalently and ionically bound to the exterior surface of the outer membrane.

15. A method of coating the exterior surface of an implantable monitoring system according to claim 12 or claim 14, wherein the amino groups are bound to the hydroxyl groups by reacting with amino functionalized silane.

13. A method of coating the exterior surface of an implantable monitoring system comprising the steps of:

a) forming hydroxyl groups on the exterior surface of the monitoring system;

b) binding amino groups to the hydroxyl groups;

c) simultaneously covalently binding heparin and polyethylene glycol (PEG) to the amino groups; and

d) ionically binding heparin to the monitoring system surface.

14. A method of coating the exterior surface of an implantable monitoring system according to claim 13, wherein the hydroxyl groups are formed by plasma etching of the exterior surface of the monitoring system.

16. A method of coating the exterior surface of an implantable monitoring system, wherein the exterior surface is comprised of silicone, the method comprising the steps of:

a) forming hydroxyl groups on the silicone surface by plasma etching;

b) reacting the silicone surface with amino functionalized silane, thereby forming amino groups on the silicone surface;

c) simultaneously, covalently binding polyethylene glycol (PEG) and heparin to the amino groups; and

d) ionically binding heparin to the monitoring system surface.

17. An implantable monitoring system having a coating on its exterior surface, which coating resists blood coagulation and protein binding to the exterior surface of the outer membrane and is applied to the surface by the method of claim 16.

18. An implantable monitoring system comprising:

at least one sensor assembly;

an outer membrane surrounding the sensor assembly, the outer membrane having at least one window therein;

a window cover, comprised of 2-hydroxyethyl methacrylate (HEMA), N,N,-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA) in weight ratios of 50;

25;

25, respectively, which window cover is associated with the outer membrane such that the window is covered thereby; and

a coating on the exterior surface of the outer membrane and window cover, which coating comprises polyethylene glycol and heparin in about an 80;

20 molar ratio.

19. An implantable monitoring system according to claim 18, further comprising an enzyme solution between the sensor assembly and window cover and outer membrane.

20. An implantable monitoring system according to claim 19, wherein the enzyme solution comprises glucose oxidase.

21. An implantable glucose monitoring system comprising:

at least one sensor assembly;

an outer membrane surrounding the sensor assembly and having a window therein adjacent the sensor assembly, wherein the outer membrane is smooth and tapered to form the window edges;

a glucose permeable window cover comprising 2-hydroxyethyl methacrylate (HEMA), N,N,-dimethylaminoethyl methacrylate (DMAEMA) and methacrylic acid (MA) in weight ratios of about 50;

25;

25, respectively, which glucose permeable window cover is associated with the outer membrane such that the window is covered thereby;

a coating on the exterior surface of the outer membrane and glucose permeable window cover, which coating comprises covalently bound polyethylene glycol (PEG) and heparin and ionically bound heparin and wherein the molar ratio of PEG to heparin is about 80;

20.

22. An implantable monitoring system comprising;

a plurality of sensor assemblies housed within an outer membrane, wherein the configuration of the monitoring system is non-linear.

23. An implantable monitoring system according to claim 22, wherein the non-linear configuration is arcuate.

24. An implantable monitoring system according to claim 22, wherein the non-linear configuration is spiral.

25. An implantable monitoring system accoridng to claim 22 further comprising a plurality of windows within the outer membrane each of which windows is positioned in assoication with as single sensor assembly.

26. An implantable monitoring system according to claim 25 wherein the windows are positioned on the interior faces of the curves of the non-linearly shaped monitoring system.

27. An implantable monitring system comprising;

a A plurality of sensor assemblies, wherein the sensor assemblies are rotationally displaced with respect to one another.

28. An implantable monitoring system according to claim 27 further comprising;

an outer membrane within which the sensor assembles are housed, a plurality of windows within the outer memebrane each of which windows is associated with a single sensor assembly.