Methods, computer program products, and devices for calibrating chronically tissue implanted sensors using chronically tissue

• US 7,171,252 B1
• Filed: 03/29/2000
• Issued: 01/30/2007
• Est. Priority Date: 09/30/1998
• Status: Expired due to Fees

• Current Assignee: North Carolina State University (University of North Carolina System), VTQ IP Holding Corporation
• Original Assignee: Sicel Technologies, Inc., North Carolina State University (University of North Carolina System)
• Inventors: Ufer, Stefan, Fiering, Jason, Nagle, H. Troy, Scarantino, Charles W., Kermani, Bahram Ghaffarzadeh, Kim, Chang-Soo
• Primary Examiner(s): Nasser; Robert L.
• Application Number:
  US10/089,483
• Time in Patent Office: 2,498 Days
• Field of Search: None
• US Class Current: 600/345
• CPC Class Codes: A61B 2562/028 Microscale sensors, e.g. electromechanical sensors [MEMS]
• CPC Class Codes: A61B 2562/085 combined with means for recording calibration data
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14539 for measuring pH
• 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: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/417 the bone marrow
• CPC Class Codes: A61B 6/507 for determination of haemodynamic parameters, e.g. perfusion CT
• CPC Class Codes: A61N 5/1048 Monitoring, verifying, controlling systems and methods
• CPC Class Codes: A61N 5/1071 for verifying the dose delivered by the treatment plan
• CPC Class Codes: G16H 20/40 relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
• CPC Class Codes: G16H 40/67 for remote operation
• CPC Class Codes: Y10S 128/903 Radio telemetry
• CPC Class Codes: Y10S 128/904 Telephone telemetry
• CPC Class Codes: Y10S 128/92 Computer assisted medical diagnostics

Abstract

Calibration of in vivo oxygen and pH sensor systems can be performed by generating a constituent element of an environment proximate to an in vivo sensor electrode via an in vivo generating electrode and determining a level of the constituent element in the tissue via the in vivo sensor electrode. Accordingly, accurate monitoring of tissue can be achieved while reducing the need to calibrate the in vivo sensor systems using invasive procedures. Related electrode assemblies are also discussed.

Claims

1. A method for calibrating an in vivo sensor system, the method comprising the steps of:

generating a constituent element of an environment proximate to an in vivo sensor electrode via an in vivo generating electrode; and

determining a level of the constituent element in the tissue via the in vivo sensor electrode, wherein the step of generating comprises the steps of;

generating a first constituent element at a first time at the in vivo generating electrode; and

generating a second constituent element at a second time at the in vivo generating electrode.

2. A method according to claim 1 further comprising the step of:

calibrating the in vivo sensor circuit based on the level of the constituent element using a chronically tissue-implanted device.

3. A method according to claim 1, wherein the step of determining comprises the steps of:

determining a first level of the constituent element between the first time and the second time; and

determining a second level of the constituent element after the second time.

4. A method according to claim 1, wherein the step of generating the first constituent element comprises the step of generating oxygen, and wherein the step of generating the second constituent element comprises the step of generating hydrogen.

5. A method according to claim 1, wherein the step of generating the first constituent element comprises the step of generating an oxygen saturated environment proximate to the in vivo sensor electrode, and wherein the step of generating the second constituent element comprises the step of generating a hydrogen saturated environment proximate to the in vivo sensor electrode.

6. A method according to claim 1, wherein the step of generating comprises the step of generating the constituent element using electrolysis.

7. A method according to claim 1, wherein the step of generating the second constituent element is preceded by the step of waiting a time interval to allow the generated first constituent element to dissipate.

8. A method according to claim 7, wherein the time interval comprises about 1 minute.

9. A method according to claim 1, wherein the step of generating the first constituent element comprises the step of conducting a current from a first in vivo generating electrode to a second in vivo generating electrode through the tissue.

10. A method according to claim 1, wherein the step of calibrating comprises the step of determining a relationship between a current conducted by the in vivo sensor electrode and a third level of the constituent element using the first and second levels of the constituent element.

11. A method according to claim 10, wherein the step of calibrating comprises the steps of:

determining a maximum rate of change of the voltage; and

associating the maximum rate of change of the voltage with a voltage level that is associated with a neutral pH level.

12. A method according to claim 1, wherein the step of generating a constituent element of an environment proximate to an in vivo sensor electrode via an in vivo generating electrode comprises the step of generating a changing H⁺/OH⁻

ion level proximate to the in vivo sensor electrode.

13. A method according to claim 12, wherein the step of determining comprises the step of determining a rate of change of a voltage generated at the in vivo sensor electrode in response to the changing H⁺/OH⁻

ion level.

14. A method for calibrating an in vivo sensor system, the method comprising the steps of:

generating a constituent element of an environment proximate to an in vivo sensor electrode via an in vivo generating electrode;

determining a level of the constituent element in the tissue via the in vivo sensor electrode, wherein the step of generating comprises the steps of;

generating a first constituent element at a first time at the in vivo generating electrode, wherein the step of generating the first constituent element comprises the step of conducting a current from a first in vivo generating electrode to a second in vivo generating electrode through the tissue;

generating a second constituent element at a second time at the in vivo generating electrode; and

wherein the step of generating the second constituent element comprises the step of conducting the current from the second in vivo generating electrode to the first in vivo generating electrode through the tissue.

15. A method for calibrating an in vivo sensor system, the method comprising the steps of:

generating a first constituent element of an environment proximate to an in vivo sensor electrode at an in vivo generating electrode;

determining a first level of the first constituent element via the in vivo sensor electrode;

generating a second constituent element of the environment proximate to the in vivo sensor electrode at the in vivo generating electrode; and

determining a second level of the second constituent element using an in vivo sensor electrode.

16. A method according to claim 15 further comprising the step of:

calibrating the in vivo sensor using an in vivo device.

17. A method according to claim 16, wherein the step of calibrating comprises the step of determining a relationship between a current in the environment and a third level of the first constituent element using the first and second levels of the constituent elements.

18. A method according to claim 15, wherein the step of generating the first constituent element comprises the step of generating oxygen, and wherein the step of generating the second constituent element comprises the step of generating hydrogen.

19. A method according to claim 15, wherein the step of generating the first constituent element comprises the step of generating an oxygen saturated environment, and wherein the step of generating the second constituent element comprises the step of generating an oxygen depleted environment.

20. A method according to claim 15, wherein the step of generating the first constituent element comprises the step of generating the first constituent element using electrolysis.

21. A method according to claim 15, wherein the step of generating the second constituent element is preceded by the step of waiting a time interval to allow the generated first level of the first constituent element to dissipate.

22. A method according to claim 21, wherein the time interval comprises about 1 minute.

23. A method according to claim 15, wherein the in vivo generating electrode comprises a first in vivo generating electrode wherein the step of generating the first constituent element comprises the step of conducting a current from the first in vivo generating electrode to a second in vivo generating electrode.

24. A method for calibrating an in vivo sensor system the method comprising the steps of:

generating a first constituent element of an environment proximate to an in vivo sensor electrode at a first in vivo generating electrode, wherein the step of generating the first constituent element comprises the step of conducting a current from the first in vivo generating electrode to a second in vivo generating electrode;

determining a first level of the first constituent element via the in vivo sensor electrode;

generating a second constituent element of the environment proximate to the in vivo sensor electrode at the in vivo generating electrode; and

determining a second level of the second constituent element using an in vivo sensor electrode, wherein the step of generating the second constituent element comprises the step of conducting a current from the second in vivo generating electrode to the first in vivo generating electrode.

25. A method for calibrating an in vivo sensor system, the method comprising the steps of:

generating a changing H⁺/OH⁻

ion level proximate to an in vivo sensor electrode;

determining a rate of change of a voltage at the in vivo sensor electrode generated in response to the changing H⁺/OH⁻

ion level; and

determining a rate of change of the voltage associated with the changing H⁺/OH⁻

ion level.

26. A method according to claim 25 further comprising the step of:

calibrating the in vivo sensor based on the determined rate of change of the voltage using an in vivo device.

27. A method according to claim 26, wherein the step of calibrating comprises the step of associating the rate of change of the voltage with a voltage level that is associated with a pH level.

28. A method according to claim 26, wherein the step of calibrating comprises the step of associating a maximum rate of change of the voltage with a voltage level that is associated with a neutral pH level.

29. A method according to claim 25, wherein the step of generating comprises the steps of:

generating an increase in OH⁻

ions and a decrease in H⁺ ions proximate to the in vivo sensor electrode; and

generating a decrease in OH⁻

ions and an increase in H⁺ ions proximate to the in vivo sensor electrode.

30. A method according to claim 29, wherein the generating steps are performed more than once.

31. A computer program product for calibrating a sensor system adapted for in vivo use, the computer program product comprising:

a computer readable storage medium having computer-readable program code embodied in said medium, said computer-readable program code comprising;

computer-readable program code for generating a constituent element of an environment proximate to a sensor electrode adapted for in vivo use via a generating electrode adapted for in vivo use; and

computer-readable program code for determining a level of the constituent element in the tissue using the sensor electrode, wherein the computer-readable program code for generating comprises;

computer-readable program code for generating a first constituent element at a first time at the generating electrode; and

computer-readable program code for generating a second constituent element at a second time at the generating electrode.

32. A computer program product according to claim 31 wherein the sensor electrode and the generating electrode are adapted for chronically tissue-implanted use.

33. A computer program product according to claim 31, wherein the computer-readable program code for determining comprises:

computer-readable program code for determining a first level of the constituent element between the first time and the second time; and

computer-readable program code for determining a second level of the constituent element after the second time.

34. A computer program product according to claim 31, wherein the computer-readable program code for generating the first constituent element comprises computer-readable program code for generating oxygen, and wherein the computer-readable program code for generating the second constituent element comprises computer-readable program code for generating hydrogen.

35. A computer program product according to claim 31, wherein the computer-readable program code for generating the first constituent element comprises computer-readable program code for generating an oxygen saturated environment proximate to the sensor electrode, and wherein the computer-readable program code for generating the second constituent element comprises computer-readable program code for generating a hydrogen saturated environment proximate to the sensor electrode.

36. A computer program product according to claim 31, wherein the computer-readable program code for generating comprises computer-readable program code for generating the constituent element using electrolysis.

37. A computer program product according to claim 31, wherein the computer-readable program code for generating the second constituent element waits a time interval to allow the generated first constituent element to dissipate.

38. A computer program product according to claim 37, wherein the time interval comprises about 1 minute.

39. A computer program product according to claim 31, wherein the computer-readable program code for generating the first constituent element comprises computer-readable program code for conducting a current from a first generating electrode adapted for in vivo use to a second generating electrode adapted for in vivo use through the tissue.

40. A computer program product according to claim 39, wherein the computer-readable program code for generating the second constituent element comprises computer-readable program code for conducting the current from the second generating electrode to the first generating electrode through the tissue.

41. A computer program product according to claim 31, wherein the computer-readable program code for calibrating comprises computer-readable program code for determining a relationship between a current conducted by the sensor electrode and a third level of the constituent element using the first and second levels of the constituent element.

42. A computer program product according to claim 41, wherein the computer-readable program code for calibrating comprises:

computer-readable program code for determining a maximum rate of change of the voltage; and

computer-readable program code for associating the maximum rate of change of the voltage with a voltage level that is associated with a neutral pH level.

43. A computer program product according to claim 31, wherein the computer-readable program code for generating comprises computer-readable program code for generating a changing H⁺/OH⁻

ion level proximate to the sensor electrode.

44. A computer program product according to claim 43, wherein the computer-readable program code for determining comprises computer-readable program code for determining a rate of change of a voltage generated at the sensor electrode in response to the changing H⁺/OH⁻

ion level.