Self-calibrating body analyte monitoring system

• US 20050209518A1
• Filed: 03/16/2005
• Published: 09/22/2005
• Est. Priority Date: 03/17/2004
• Status: Abandoned Application

• Current Assignee: TheraFuse, Inc.
• Original Assignee: TheraFuse, Inc.
• Inventors: Sage, Burton H. Jr., Gillett, David, Brandell, Brian
• Application Number:
  US11/083,362
• Publication Number:
  US 20050209518A1
• Time in Patent Office: Days
• US Class Current: 600/366
• CPC Class Codes: A61B 2560/0223 of calibration, e.g. protocols for calibrating sensors
• CPC Class Codes: A61B 5/14525 using microdialysis
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61M 2005/14506 mechanically driven, e.g. spring or clockwork
• CPC Class Codes: A61M 2202/0413 Blood
• CPC Class Codes: A61M 2205/0244 Micromachined materials, e.g. made from silicon wafers, microelectromechanical systems [MEMS] or comprising nanotechnology

Abstract

A self-calibrating monitoring system based on microdialysis for measurement of a body analyte is disclosed. In one embodiment, perfusate containing a known concentration of body analyte is mixed with an enzyme solution after passing through a microdialysis needle and instead of passing through the microdialysis needle to measure the body analyte and to calibrate the analysis chamber that measures the body analyte.

Claims

1. A device for measuring a concentration of a body analyte concentration comprising:

a) a reservoir containing a perfusate comprising a known concentration of the body analyte,

b) an interface including an inlet in liquid communication with the reservoir and an outlet, wherein the interface is adapted to allow exchange of the body analyte between the perfusate and the body fluid when there is perfusate in the interface and the interface is in contact with the body fluid,

c) a measurement path for measuring the body analyte concentration downstream from the outlet and the reservoir such that an entrance to the measurement path is in liquid communication with both the reservoir and the outlet of the interface, and

d) a valving system for controlling flow into the measurement path such that liquid flowing into the measurement path is either liquid from the reservoir or liquid from the outlet.

2. The device of claim 1 wherein the flow of the perfusate through the interface is such that the dwell time of the perfusate in the interface is greater than three times the characteristic diffusion time of the body analyte in the interface.

3. The device of claim 1 wherein the interface and the measurement path reside on a common support.

4. The device of claim 1 wherein the interface has a lumen along which the perfusate flows, the lumen being rectangular in section with a depth less than 100 microns.

5. The device of claim 1 wherein the measurement path comprises a first chamber and a second chamber downstream from the first chamber.

6. The device of claim 5 wherein the first chamber comprises an immobilized enzyme.

7. The device of claim 5 wherein the device is adapted so that a measurement related to the concentration of the body analyte is made at the second chamber.

8. The device of claim 1 wherein the measurement path comprises a first chamber, a second chamber downstream from the first chamber, and a third chamber downstream from the second chamber.

9. The device of claim 8 wherein the interface and the measurement path reside on a common support.

10. The device of claim 9 wherein the interface has a lumen along which the solution flows, the lumen being rectangular in section with a depth less than 100 microns.

11. The device of claim 8 wherein the first chamber comprises an oxidation chamber.

12. The device of claim 8 wherein the second chamber comprises an immobilized enzyme.

13. The device of claim 8 wherein the third chamber comprises a measurement chamber.

14. The device of claim 11 wherein the oxidation chamber both removes potential interferents and generates oxygen.

15. The device of claim 13 wherein the measurement chamber is a body analyte concentration measurement chamber

39. The device of claim 1 further comprising a drug delivery device such that the amount or rate of drug delivery by the drug delivery device is based on a measurement made by the device.

17. A device for measuring a concentration of a body analyte in a body fluid, comprising:

a) a first reservoir containing a perfusate comprising a known concentration of the body analyte,

b) a second reservoir containing an enzyme solution,

c) an interface including an inlet in liquid communication with the first reservoir and an outlet, wherein the interface is adapted to allow exchange of the body analyte between the perfusate and the body fluid when there is perfusate in the interface and the interface is in contact with the body fluid,

c) a measurement path for measuring the body analyte concentration downstream from the outlet and the reservoir such that an entrance of the measurement path is in liquid communication with the first reservoir, the second reservoir, and the outlet of the interface, and

d) a valving system for controlling flow into the measurement path such that the liquid flowing into the measurement path is either perfusate from the reservoir mixed with the enzyme solution or dialysate from the outlet mixed with the enzyme solution.

18. The device of claim 17 wherein the flow of the perfusate through the interface is such that the dwell time of the perfusate in the interface is greater than three times the characteristic diffusion time of the body analyte.

19. The device of claim 17 wherein the interface and the measurement path reside on a common support.

20. The device of claim 17 wherein the interface has a lumen along which the perfusate flows, the lumen being rectangular in section with a depth less than 100 microns.

21. The device of claim 17 wherein the measurement path comprises a first chamber and a second chamber downstream from the first chamber.

22. The device of claim 21 wherein the first chamber is adapted to mix the dialysate from the outlet and the solution from the second reservoir.

23. The device of claim 21 wherein the second chamber is a body analyte concentration measurement chamber.

40. The device of claim 17 further comprising a drug delivery device such that the amount or rate of drug delivery by the drug delivery device is based on a measurement made by the device.

24. A device for measuring a concentration of a body analyte in a body fluid, comprising:

a) a first reservoir for containing a perfusate comprising a known concentration of the body analyte,

b) a second reservoir for containing an enzyme solution,

c) an interface including an inlet in liquid communication with the first reservoir and an outlet, wherein the interface is adapted to allow exchange of the body analyte between the perfusate and the body fluid when there is perfusate in the interface and the interface is in contact with the body fluid,

c) a measurement path comprising a first chamber, a second chamber downstream from the first chamber, and a third chamber downstream from the second chamber such that the first chamber may receive perfusate from the first reservoir and the dialysate from the outlet and the second chamber may receive either perfusate or dialysate from the first chamber and enzyme solution from the second reservoir, and

d) a valving system for controlling liquid flow along the measurement path such that the liquid flowing into the second chamber is either (i) dialysate from the outlet that has passed through the first chamber and enzyme solution from the second reservoir, or (ii) perfusate from the first reservoir that has passed through the first chamber and enzyme solution from the second reservoir.

25. The device of claim 24 wherein the interface and the measurement path reside on a common support.

26. The device of claim 24 wherein the interface has a lumen along which the perfusate flows, the lumen being rectangular in section with a depth less than 100 microns.

27. The device of claim 24 wherein the first chamber is an oxidation chamber.

28. The device of claim 27 wherein the oxidation chamber both removes potential interferents and generates oxygen.

29. The device of claim 24 wherein mixing of perfusate or dialysate from the first chamber with enzyme solution from the second reservoir occurs in the second chamber.

30. The device of claim 24 wherein the device is adapted so that a measurement relating to the concentration of the body analyte is made at the third chamber.

41. The device of claim 24 further comprising a drug delivery device such that the amount or rate of drug delivery by the drug delivery device is based on a measurement made by the device.

31. A microdialysis based body analyte monitoring system comprising:

an electrochemical chamber to process dialysate operating at a potential to oxidize potential body analyte interferents and oxidize water to oxygen.

32. A method of calibrating a microdialysis based body analyte monitoring system comprising:

providing a perfusate solution with a known concentration of the body analyte and alternating an analysis of a concentration of the body analyte of (a) dialysate that has passed through an interface in contact with a body fluid such that diffusion of the body analyte into or out of the interface has reached essential equilibrium before exiting the interface, and (b) perfusate that has bypassed the interface such that it retains its original body analyte concentration.

33. The method of claim 32, further comprising:

modifying the results of the analysis of the body analyte of the dialysate that has passed through the interface in contact with the body fluid such that diffusion of the body analyte into or out of the interface has reached essential equilibrium before exiting the interface, wherein modification of the results includes scaling the results according to a comparison of (i) the results of the analysis of the perfusate that has bypassed the interface such that it retains its original body analyte concentration and (ii) the known concentration of the body analyte.

34. A method of providing oxygen to the measurement path of the microdialysis based body analyte monitoring system comprising the steps of a) providing an oxidation chamber in the measurement path, and b) operating the oxidation chamber at a potential sufficient to electrolyze water.

35. A method of operating a microdialysis based body analyte monitoring system including the step of electrochemically processing dialysate at a potential sufficiently high to oxidize potential body analyte interferents in the dialysate and to oxidize water to oxygen.

36. A device for measuring a concentration of a body analyte in a body fluid, comprising:

a) a reservoir containing a perfusate comprising a known concentration of the body analyte;

b) a lumen adapted to be inserted into human skin, the lumen including a liquid flow path, wherein the lumen is further adapted to permit the diffusion of the body analyte into the liquid flow path and out of the liquid flow path when the lumen lies inserted into human skin and in contact with body fluid;

c) a valving system, wherein the valving system is adapted to alternately direct perfusate from the reservoir (i) through the liquid flow path in the lumen and then through a measurement path and (ii) to bypass the lumen and flow through the measurement path; and

d) a microcontroller/microprocessor assembly adapted to control the valving system to alternately direct perfusate from the reservoir (i) through the liquid flow path in the lumen and then through the measurement path and (ii) to bypass the lumen and flow through the measurement path;

wherein the device is adapted to measure the body analyte concentration of the perfusate passing through the measurement path,

wherein the microcontroller/microprocessor assembly is further adapted to compare (1) a first value of a measurement of the body analyte concentration of perfusate in the measurement path that has been directed to bypass the lumen and flow through the measurement path to (2) the known concentration of the body analyte in the perfusate of the reservoir;

wherein the microcontroller/microprocessor assembly is further adapted to identify a conversion factor based on the comparison of (1) and (2); and

wherein the microcontroller/microprocessor assembly is further adapted to obtain a second value of a measurement of the body analyte concentration of perfusate in the measurement path that has been directed through the lumen and then into the measurement path and output a modified body analyte concentration value, the modified body analyte concentration value being the second value as modified by the conversion factor.

37. The device of claim 36, wherein the device is adapted to be worn on a human body part.

38. A device for measuring a concentration of a body analyte in a body fluid, comprising:

a lumen adapted to be inserted into human skin, the lumen including a liquid flow path, wherein the lumen is further adapted to permit the diffusion of the body analyte into the liquid flow path and out of the liquid flow path when the lumen lies inserted into human skin and is in contact with body fluid; and

a measurement assembly adapted to measure the concentration of body analyte in a fluid passing through a measurement path;

wherein the device is adapted to alternately (i) pass perfusate containing a known concentration of the body analyte through the lumen and through the measurement path and (ii) to bypass the lumen and direct the perfusate to through the measurement path;

wherein the device is further adapted to calibrate itself by comparing the measured concentration of the body analyte in the fluid passing through the measurement path to the known concentration of the body analyte and modify the measured value of the concentration of body analyte in the perfusate that has passed through the lumen and through the measurement path based on this comparison.