Device and method for sampling of substances using alternating polarity

• US 20020002328A1
• Filed: 06/28/2001
• Published: 01/03/2002
• Est. Priority Date: 06/24/1994
• Status: Active Grant

• Current Assignee: Animas Technologies LLC (Johnson & Johnson)
• Original Assignee: Cygnus, Inc. (Johnson & Johnson)
• Inventors: Tamada, Janet
• Granted Patent: US 6,687,522 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 5/6833 Adhesive patches

Abstract

A method for sampling of a substance from a subject is provided, which comprises placing one or more sampling chambers on a collection site on a tissue surface on the subject; conducting electric current through the tissue to extract a substance from the subject in a first direction in one or more sampling chambers that functions alternatively as both an anode and cathode during the course of the method; reversing the polarity to cause direct current to flow in second direction opposite the first direction; and analyzing the sampling chamber or chambers for the concentration of a substance or a substance metabolite. There is also provided a device for sampling of a substance from an organism on continuously or intermittently using alternating polarity method based on the application of low intensity electric fields of alternating polarity across the skin (iontophoresis) to enhance the transport of a substance (such as glucose, lactic acid, pyruvic acid, and the like) from body tissues to a sampling chamber. The device comprises an electrical power supply; a transdermal system that contains one or more sampling chambers that function as both anode and cathode during the course of sampling; a means to alternates or reverses the polarity during the iontophoretic sampling; and means for analyzing for the concentration of a substance or a substance metabolite.

Claims

1. A method for sampling of a substance from a subject, which comprises

(a) placing one or more sampling chambers on a collection site on a tissue surface on the subject;

(b) conducting electrical current through the tissue in a first polarity to the collection site to extract a substance from the subject into one or more sampling chambers;

(c) reversing polarity to apply electrical energy in a second polarity during the course of the method; and

(d) analyzing the sampling chamber or chambers for the concentration of the substance or a substance metabolite.

2. The method of claim 1 wherein the one or more sampling chambers has electrode means selected from the group consisting of (1) a single electrode, which alternates polarity, with an indifferent counterelectrode which also alternates polarity, (2) two chambers in which the anode and cathode chambers are on alternate extraction sites as the polarity alternates, and (3) two or more electrodes in which the polarity alternates during the treatment, but the extraction sites remain fixed as the polarity alternates.

3. The method of claim 2 wherein the one or more sampling chambers comprises a single sampling chamber which comprises a single electrode, which alternates polarity, with an indifferent counterelectrode which also alternates polarity.

4. The method of claim 2 wherein the one or more sampling chambers comprises two chambers in which the anode and cathode chambers are on alternate sites as the polarity alternates.

5. The method of claim 2 wherein the one or more sampling chambers comprises two chambers comprising a total of two or more electrodes in which the polarity alternates during the treatment, but the extraction sites remain fixed as the polarity alternates.

6. The method of claim 1 wherein the polarity reversing is by means of a switch.

7. The method of claim 1 wherein the of the frequency of polarity switching is from about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

8. The method of claim 1 wherein the anode and the cathode comprise an Ag/AgCl.

9. The method of claim 1 wherein the alternating polarity current is applied continuously.

10. The method of claim 1 wherein the alternating polarity current is applied intermittently.

11. The method of claim 1 wherein the tissue surface is a stratum corneum surface of the patient'"'"'s skin.

12. The method of claim 2 wherein the sampling chamber comprises an adhesive patch enclosing electrodes and open to the patient'"'"'s skin.

13. The method of claim 1 further comprising the step of placing the electrodes on a tissue surface before the step of conducting electrical current.

14. The method of claim 13 wherein the electrodes are placed at the collection site.

15. The method of claim 13 wherein the electrodes are placed adjacent the collection site.

16. The method of claim 13 wherein the electrodes are integral with the sampling chamber.

17. The method of claim 1 wherein the sampling chamber contains a collection medium, the step of conducting electrical current to the collection site comprising the step of applying electrical energy to the sampling chamber.

18. The method of claim 1 wherein the step of conducting electrical current comprises iontophoresis.

19. The method of claim 1 wherein the step of conducting electrical current comprises applying a current density in the range of 0.01 to 2 mA/cm².

20. The method of claim 1 wherein the step of conducting electrical current comprises the step of ceasing the application of electrical energy during the analyzing step.

21. The method of claim 1 wherein the analyzing step comprises pulsed amperometric detection.

22. The method of claim 1 wherein the analyzing step comprises high performance liquid chromatography (HPLC).

23. The method of claim 1 wherein the tissue surface is a stratum corneum surface of the patient'"'"'s skin, the analyzing step comprising the step of delaying the time between the applying step and the analyzing step to allow for depletion of any non-systemic substance in the patient'"'"'s skin.

24. The method of claim 23 wherein the delaying step comprises delaying performance of the analyzing step for about one hour after commencing the applying step.

25. The method of claim 1 wherein the sampling chamber contains a collection medium, the analyzing step comprising the step of extracting at least a portion of the collection medium from the sampling chamber.

26. The method of claim 1 further comprising correlating the concentration determined in step (c) with blood substance level.

27. The method of claim 26 further comprising the step of providing correlation data between sampling chamber substance levels and patient blood substance levels.

28. The method of claim 27 wherein the correlating step comprises calculating substance flux from the collection site into the sampling chamber.

29. The method of claim 28 wherein the correlating step also comprises compensating for time lag between blood substance level values and substance flux.

30. The method of claim 29 wherein the correlating step also comprises compensating for substance flux value drift.

31. The method of claim 1 wherein the steps are performed substantially continuously for about 2 hours to about 72 hours.

32. The method of claim 1 further comprising the step of treating the patient in response to the substance level determined.

33. The method of claim 7 wherein the frequency of polarity switvhing is from about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

34. The method of claim 33 wherein the frequency of polarity switching is from about 1 cycle per minute to about 1 cycle per 2 hours.

35. The method of claim 34 wherein the frequency of polarity switching is from about 1 cycle per 10 minutes to about 1 cycle per hour.

36. The method of claim 35 wherein the frequency of polarity switching is about 1 cycle per half hour.

37. An iontophoresis sampling device comprising

(a) an electrical power supply means;

(b) a transdermal system that contains one or more sampling chambers for receiving a sample that function as both anode and cathode during the course of iontophoretic sampling;

(c) means for reversing the polarity of the power source during the iontophoretic sampling; and

(d) means for analyzing for the concentration of a substance or a substance metabolite.

38. The device of claim 37 wherein the sampling chamber comprises one selected from the group consisting of (1) a single electrode, which alternates polarity, with an indifferent counterelectrode which also alternates polarity, (2) two chambers in which the anode and cathode chambers are on alternate sites as the polarity alternates and (3) two or more electrodes in which the polarity alternates during the treatment.

39. The device of claim 38 wherein the sampling chamber comprises a single electrode, which alternates polarity, with an indifferent counterelectrode which also alternates polarity.

40. The device of claim 38 wherein the sampling chamber comprises two chambers in which the anode and cathode chambers are on alternate sites as the polarity alternates.

41. The device of claim 38 wherein the sampling chamber comprises two or more electrodes in which the polarity alternates during the treatment.

42. The device of claim 37 wherein the frequency of polarity switching is from about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

43. The device of claim 37 wherein the anode and the cathode comprise an Ag/AgCl.

44. The device of claim 37 wherein the current is applied continuously.

45. The device of claim 37 wherein the current is applied intermittently.

46. The method of claim 42 wherein the frequency of polarity switvhing is from about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

47. The method of claim 46 wherein the frequency of polarity switching is from about 1 cycle per minute to about 1 cycle per 2 hours.

48. The method of claim 47 wherein the frequency of polarity switching is from about 1 cycle per 10 minutes to about 1 cycle per hour.

49. The method of claim 48 wherein the frequency of polarity switching is about 1 cycle per half hour.

50. A substance monitor comprising:

first and second substance sampling chambers each containing substance collection medium selected from the group consisting of water, saline solutions, buffer solutions, and polyols;

a power supply means having a positive connector and a negative connector;

conductors and a switch electrically connecting the first and second sampling chambers to the power supply means positive connector and the power supply means negative connector, the switch having a first position in which the first sampling chamber is electrically connected to the positive connector and the second sampling chamber is electrically connected to the negative connector and a second position in which the second sampling chamber is electrically connected to the positive connector and the first sampling chamber is electrically connected to the negative connector.

51. The monitor of claim 50 wherein the first and second sampling chambers each further comprise an electrode in electrical communication with the collection medium and with the power supply through a conductor and the switch.

52. The monitor of claim 51 further comprising a collection medium substance concentration analyzer and calibration means for correlating collection medium substance concentration with blood substance concentration.

53. The monitor of claim 50 further comprising a collection medium substance concentration analyzer and calibration means for correlating collection medium substance concentration with blood substance concentration.