Techniques to improve polyurethane membranes for implantable glucose sensors

• US 20060086624A1
• Filed: 11/16/2005
• Published: 04/27/2006
• Est. Priority Date: 05/22/2002
• Status: Active Grant

• Current Assignee: DexCom Incorporated
• Original Assignee: DexCom Incorporated
• Inventors: Shults, Mark C., Tapsak, Mark A., Rhodes, Rathbun K., McClure, Jason D.
• Granted Patent: US 8,050,731 B2
• Time in Patent Office: Days
• US Class Current: 205/775
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61L 31/12 Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
• CPC Class Codes: B01D 69/141 Heterogeneous membranes, e.g. containing dispersed material; Mixed matrix membranes
• CPC Class Codes: B01D 69/1411 containing dispersed material in a continuous matrix
• CPC Class Codes: B01D 71/54 Polyureas; Polyurethanes
• CPC Class Codes: B01D 71/80 Block polymers
• CPC Class Codes: B05D 3/007 After-treatment
• CPC Class Codes: B05D 5/00 Processes for applying liquids or other fluent materials to surfaces to obtain special surface effects, finishes or structures
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: Y10T 428/31551 Of polyamidoester [polyurethane, polyisocyanate, polycarbamate, etc.]

Abstract

The invention provides an implantable membrane for regulating the transport of analytes therethrough that includes a matrix including a first polymer; and a second polymer dispersed throughout the matrix, wherein the second polymer forms a network of microdomains which when hydrated are not observable using photomicroscopy at 400× magnification or less. In one aspect, the homogeneous membrane of the present invention has hydrophilic domains dispersed substantially throughout a hydrophobic matrix to provide an optimum balance between oxygen and glucose transport to an electrochemical glucose sensor.

Claims

1. An electrochemical sensor for measuring an analyte in a bodily fluid, the sensor comprising:

at least one electrode; and

a membrane disposed on the electrode and configured to control transport of an analyte to the electrode, the membrane comprising;

a matrix comprising a substantially hydrophobic polymer; and

a hydrophobic-hydrophilic polymer dispersed throughout the matrix, wherein a hydrophobic component of the hydrophobic-hydrophilic polymer and a hydrophobic component of the substantially hydrophobic polymer have similar backbone structures.

2. The electrochemical sensor of claim 1, wherein a backbone of the hydrophobic-hydrophilic polymer and a backbone of the substantially hydrophobic polymer are substantially miscible.

3. The electrochemical sensor of claim 1, wherein the substantially hydrophobic polymer is a homopolymer.

4. The electrochemical sensor of claim 1, wherein the hydrophobic-hydrophilic polymer is a copolymer.

5. The electrochemical sensor of claim 1, wherein the hydrophobic-hydrophilic polymer is a random copolymer or an ordered block copolymer.

6. The electrochemical sensor of claim 1, wherein at least one of the random copolymer and the ordered block copolymer are selected from the group consisting of hydrophobic-hydrophilic-hydrophobic block copolymers, hydrophilic-hydrophobic-hydrophilic block copolymers, hydrophobic-hydrophilic random alternating block copolymers, hydrophobic-hydrophilic regularly alternating block copolymers, and combinations thereof.

7. The electrochemical sensor of claim 1, wherein the analyte is glucose.

8. The electrochemical sensor of claim 1, further comprising a proximal layer comprising an enzyme capable of reacting with the analyte.

9. The electrochemical sensor of claim 1, wherein the enzyme is glucose oxidase.

10. An electrochemical sensor for measuring an analyte in a bodily fluid, the sensor comprising:

at least one electrode; and

a membrane disposed over the electrode, the membrane comprising;

a first layer comprising a blend of a substantially hydrophobic polymer and a substantially hydrophobic-hydrophilic polymer, and

a second layer comprising an enzyme capable of reacting with the analyte, wherein the second layer is more proximal to the electrode than the first layer.

11. The electrochemical sensor of claim 10, wherein the membrane is configured to produce a substantially uniform flux of the analyte through the membrane when the membrane is placed in an aqueous environment, wherein the membrane is formed by blending the hydrophobic-hydrophilic polymer and the substantially hydrophobic polymer to yield a mixture while maintaining the mixture at a temperature sufficient to maintain solubility of the polymers.

12. The electrochemical sensor of claim 10, wherein the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer have a similar backbone structure.

13. The electrochemical sensor of claim 10, wherein the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer are substantially miscible.

14. The electrochemical sensor of claim 10, wherein the hydrophobic component of the substantially hydrophobic polymer and the hydrophobic component of the hydrophobic-hydrophilic polymer each comprise polyurethane.

15. The electrochemical sensor of claim 10, wherein the polyurethane comprises polyetherurethaneurea.

16. The electrochemical sensor of claim 10, wherein a hydrophilic component of the hydrophobic-hydrophilic polymer comprises polyethylene oxide.

17. The electrochemical sensor of claim 10, wherein the membrane is formed substantially without chemical reaction between the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer.

18. The electrochemical sensor of claim 10, wherein the membrane is formed substantially without a solvent.

19. The electrochemical sensor of claim 10, wherein the electrode comprises an electrochemically reactive surface area, and wherein the blend of the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer form microdomains in the first layer that are substantially smaller than the electrochemically reactive surface area.

20. A device for measuring an analyte in a bodily fluid, the device comprising:

a sensor configured to measure the analyte or a product of a reaction representative of the analyte; and

a membrane disposed over the sensor, the membrane comprising;

a first layer formed from a physical blend of a substantially hydrophobic polymer and a substantially hydrophobic-hydrophilic polymer, and a second layer comprising an enzyme reactive with the analyte, wherein the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer are blended so as to maintain substantial solubility between the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer while forming the membrane.

21. The device of claim 20, wherein the substantially hydrophobic polymer and the substantially hydrophobic-hydrophilic polymer are not substantially chemically reacted.