Device for monitoring changes in analyte concentration

• US 6,212,416 B1
• Filed: 05/22/1998
• Issued: 04/03/2001
• Est. Priority Date: 11/22/1995
• Status: Expired due to Term

• Current Assignee: Legacy Good Samaritan Hospital And Medical Center
• Original Assignee: Good Samaritan Hospital Medical Center (Catholic Health Services of Long Island)
• Inventors: Ward, W. Kenneth, Wilgus, Eric S.
• Primary Examiner(s): O'Connor, Cary
• Assistant Examiner(s): CARTER, RYAN CHRISTOPHER
• Application Number:
  US09/083,520
• Time in Patent Office: 1,047 Days
• Field of Search: 600/345, 600/347, 600/365, 600/373-381, 204/403, 204/415, 435/288, 435/291, 435/817, 422/68.1, 422/82.03, 422/82.01
• US Class Current: 600/345
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• 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: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: Y10S 435/817 Enzyme or microbe electrode

Abstract

The invention provides an electrochemical sensor system for measuring analyte concentrations in a fluid sample. The invention is particularly useful for measuring analytes such as glucose in a patient. An implantable glucose sensor includes a disc-shaped sensor body containing multiple anodes on opposing sides of the sensor body. Electrodes including an anode and a cathode are connected to a transmitter which transmits radio signals to an external receiver and computer where data is processed to yield glucose concentration figures. An enzyme layer coating the anodes specifically reacts with glucose to increase signals generated by the anodes in response to the presence of glucose. In an alternate embodiment, some of the anodes are coated with the enzyme to generate a first signal, and other anodes that are not coated generate a second signal for comparison with the first signal to eliminate effects of interfering substances on the accuracy of the glucose measurement.

Claims

1. A system for monitoring analyte concentrations in the blood of a mammal comprising

an organization of implantable sensors, each sensor including an anode and a cathode covered by a membrane which is semi-permeable to the analyte.

2. The system of claim 1 wherein the analyte is glucose, further comprising an enzyme layer between the anodes and the membrane.

3. The system of claim 1 further comprising a sensor body substantially containing all of the sensors.

4. The system of claim 3 wherein the sensor body is substantially disc-shaped and has two opposing sides, the sensors being disposed on both sides of the sensor body.

5. The system of claim 4 wherein each side of the sensor body has four sensors.

6. The system of claim 1 further comprising of plurality of sensor bodies, each sensor being provided in a separate sensor body.

7. The system of claim 1 wherein all anodes lead to a common anode conductor and all cathodes lead to a common cathode conductor.

8. A device for electrochemically sensing changes in the concentration of an analyte of interest comprising

a wholly subcutaneously implantable sensor body,

an analyte detection mechanism contained within the sensor body, and

a fibrotic coat interference inhibitor in close proximity to and exterior to the sensor body for decreasing interference with analyte detection due to formation of a fibrotic coat around the sensor body.

9. The device of claim 8 wherein the analyte is glucose.

10. The device of claim 8 wherein the inhibitor has the property of decreasing the rate of collagen deposition on the sensor body.

11. The device of claim 8 wherein the inhibitor has the property of increasing vascularity in a fibrotic coat.

12. The device of claim 8 wherein the inhibitor is a steroid.

13. The device of claim 8 wherein the inhibitor is a vascular growth factor.

14. The device of claim 12 wherein the inhibitor is selected from the group consisting of dexamethasone, relaxin, gamma interferon, and mixtures thereof.

15. The device of claim 13 wherein the inhibitor is selected from the group consisting of vascular endothelial growth factor, endothelial cell growth factor, and mixtures thereof.

16. The device of claim 8 wherein the inhibitor is incorporated in a polymer matrix which provides controlled and relatively constant release of the inhibitor over time into tissue surrounding the sensor body.

17. The device of claim 16 wherein the polymer matrix includes a material selected from the group consisting of polydimethylsiloxane, poly-1-lactic acid, polyglycolic lactic acid and mixtures thereof.

18. The device of claim 16 wherein the polymer matrix is in the form of a tape impregnated with the inhibitor.

19. The device of claim 8 wherein the sensor body is substantially disc-shaped.

20. The device of claim 19 wherein the sensor body has a peripheral edge, the inhibitor being impregnated in a time-release polymer matrix associated with the peripheral edge of the sensor body.

21. The device of claim 8 wherein the inhibitor is dexamethasone.

22. The device of claim 16 wherein the inhibitor comprises dexamethasone and the polymer matrix comprises polydimethylsiloxane.

23. The device of claim 8 wherein the sensor body has a pair of spaced facial expanses, each expanse of the sensor body including at least one anode and at least one cathode spaced apart from each other and covered by a membrane which is semipermeable to the analyte of interest.

24. The device of claim 23 wherein the analyte of interest is glucose.

25. The device of claim 8 wherein the effective dose of inhibitor is large enough to significantly decrease interference with analyte detection caused by fibrotic capsule formation, but small enough to avoid adverse systemic effects.

26. A device for electrochemically sensing changes in the concentration of an analyte of interest comprising

an implantable sensor body supporting and defining multiple analyte detection sites, each site having an analyte-sensing electrode pair, each electrode pair including an anode and a cathode, and

an enzyme composition covering at least one but not all of the electrode pairs, wherein the enzyme reacts with the analyte of interest.

27. The device of claim 26 wherein the analyte of interest is glucose and the enzyme composition includes glucose oxidase.

28. The device of claim 26 wherein

the electrode pairs covered by the enzyme composition generate a first signal, and

the electrode pairs that are not covered by the enzyme composition generate a second signal.

29. The device of claim 28 further comprising a subtraction device for comparing the first signal to the second signal to substantially eliminate the effect on the first and second signals of an interfering substance.

30. The device of claim 26 wherein each analyte-sensing electrode pair includes a plurality of anodes.

31. The device of claim 26 wherein

the sensor body has a pair of spaced facial expanses, and

the electrode pairs are distributed on both of the expanses.

32. The device of claim 26 wherein the sensor body is disc-shaped.

33. The device of claim 26 further comprising

a fibrotic coat interference inhibitor in close proximity to and exterior to the sensor body for decreasing interference with analyte detection due to formation of a fibrotic coat around the sensor body.

34. The device of claim 26 further comprising

a membrane covering at least one of the analyte detection sites, wherein the membrane is semi-permeable to the analyte of interest.

35. The device of claim 34 wherein the membrane comprises polyparaxylxylene or a carbonate-based polyurethane.

36. A device for electrochemically sensing changes in the concentration of an analyte of interest comprising

a first implantable sensor body generating a first signal,

a second implantable sensor body generating a second signal, each of the first and second sensor bodies supporting and defining at least one analyte detection site, each analyte detection site having an analyte-sensing electrode pair, each electrode pair including an anode and a cathode, and

an enzyme composition covering the anode of each electrode pair of the first sensor body, wherein the enzyme reacts specifically with the analyte of interest.

37. The device of claim 36, further comprising a subtraction device for comparing the first signal to the second signal to isolate the effect on the first and second signals of the analyte of interest apart from an interfering substance.

38. A device for electrochemically sensing changes in the concentration of an analyte of interest comprising

an implantable sensor body supporting and defining an organization of analyte-sensing electrodes including a cathode, a first anode generating a first signal, and a second anode generating a second signal, and

an enzyme composition covering the first anode, wherein the enzyme reacts specifically with the analyte of interest.

39. The device of claim 38, further comprising a subtraction device for comparing the first signal to the second signal to isolate the effect on the first and second signals of the analyte of interest apart from an interfering substance.

40. The device of claim 38 wherein the first anode includes a first electrically coupled plurality of electrodes, and the second anode includes a second electrically coupled plurality of electrodes electrically isolated from the first plurality of electrodes.

41. A method electrochemically sensing changes in the concentration in a fluid of an analyte of interest comprising

exposing a first sensor to the fluid, wherein the first sensor generates a first signal indicative of the concentration in the fluid of an interfering substance,

exposing a second sensor to the fluid, wherein the second sensor includes an enzyme that reacts specifically with the analyte of interest so that the second sensor generates a second signal indicative of the concentration in the fluid of the analyte of interest and the interfering substance, and

comparing the first signal to the second signal to determine the concentration in the fluid of the analyte of interest substantially isolated from the concentration in the fluid of the interfering substance.