Device for sampling substances using alternating polarity of iontophoretic current

• US 6,298,254 B2
• Filed: 11/01/1999
• Issued: 10/02/2001
• Est. Priority Date: 06/24/1994
• Status: Expired due to Term

• Current Assignee: Animas Technologies LLC (Johnson & Johnson)
• Original Assignee: Cygnus, Inc. (Johnson & Johnson)
• Inventors: Tamada, Janet
• Primary Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US09/430,914
• Publication Number:
  US 20010020124A1
• Time in Patent Office: 701 Days
• Field of Search: 600/309, 600/345, 600/347, 600/348, 600/354, 600/355, 600/357, 600/372, 600/382, 600/384, 600/396, 600/397, 604/20, 204/153.12
• 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 at least one substance from a subject which comprises:

(a) conducting electrical current in a first polarity through a tissue of the subject, said conducting in a first polarity from a first sampling chamber on a surface of the tissue to a second sampling chamber on the surface of the tissue to extract a substance from the subject into the first sampling chamber;

(b) conducting electrical current in a second polarity through a tissue of the subject, said conducting in a second polarity from the second sampling chamber to the first sampling chamber to extract the substance from the subject into the second sampling chamber; and

(c) analyzing each sampling chamber for a concentration or amount of the substance.

2. The method of claim 1, wherein said conducting in a first polarity and said second conducting in a second polarity comprises reversing polarity, said reversing polarity comprises using a switch.

3. The method of claim 1, wherein said conducting in a first polarity and said second conducting in a second polarity is performed at a frequency comprising about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

4. The method of claim 3, wherein said conducting in a first polarity and said second conducting in a second polarity is performed at a frequency comprising about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

5. The method of claim 4, wherein said conducting in a first polarity and said second conducting in a second polarity is performed at a frequency comprising about 1 cycle per minute to about 1 cycle per 2 hours.

6. The method of claim 5, wherein said conducting in a first polarity and said second conducting in a second polarity is performed at a frequency comprising about 1 cycle per 10 minutes to about 1 cycle per hour.

7. The method of claim 6, wherein said conducting in a first polarity and said second conducting in a second polarity is performed at a frequency comprising 1 cycle per half hour.

8. The method of claim 1, wherein (i) said first sampling chamber comprises a first Ag/AgCl electrode, (ii) said second sampling chamber comprises a second Ag/AgCl electrode, and (iii) said conducting comprises conducting current between said first and second electrodes.

9. The method of claim 1, wherein said conducting in a first polarity and said second conducting in a second polarity comprises an alternating polarity current.

10. The method of claim 9, wherein said alternating polarity current is applied continuously.

11. The method of claim 9, wherein the alternating polarity current is applied intermittently.

12. The method of claim 1, wherein said surface of the tissue is a stratum corneum surface.

13. The method of claim 1, wherein said first and second sampling chamber each comprise electrodes that are integral with the sampling chamber.

14. The method of claim 1, wherein each sampling chamber comprises a collection medium.

15. The method of claim 14, wherein said conducting comprises applying electrical energy to the collection medium.

16. The method of claim 1, wherein said conducting comprises iontophoresis.

17. 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.

18. The method of claim 1, wherein the step of conducting electrical current comprises the step of ceasing the conducting electrical current during the analyzing step.

19. The method of claim 1, wherein the analyzing step is performed periodically.

20. The method of claim 1, wherein the analyzing step comprises the step of using high performance liquid chromatography.

21. 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.

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

23. The method of claim 1, further comprising the step of (d) providing correlation data between a sampling chamber substance level and blood substance levels.

24. The method of claim 1, further comprising (d) a correlating step that comprises calculating substance flux from the collection site into the sampling chamber.

25. The method of claim 24, wherein the correlating step also comprises compensating for time lag between blood substance level values and substance flux.

26. The method of claim 24, wherein the correlating step also comprises compensating for substance flux value drift.

27. The method of claim 1, wherein the steps are performed repeatedly for about 2 hours to about 72 hours.

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

29. The method of claim 1, wherein said substance is glucose.

30. The method of claim 1, wherein more than one substance is being sampled.

31. The method of claim 1, wherein said analyzing further comprises analyzing each sampling chamber for a concentration or amount of the substance or a substance metabolite.

32. The method of claim 1, wherein said analyzing comprises pulsed amperometric detection.

33. A method for sampling of glucose from a subject, said method comprising

(a) conducting electrical current in a first polarity through a tissue of the subject, said conducting in a first polarity from a first sampling chamber on a surface of the tissue to a second sampling chamber on the surface of the tissue to extract the glucose from the subject into the first sampling chamber, wherein (i) each sampling chamber comprises a collection medium, (ii) said conducting comprises applying electrical energy to the collection medium;

and (iii) said conducting and extracting comprises iontophoresis;

(b) conducting electrical current in a second polarity through a tissue of the subject, said conducting in a second polarity from the second sampling chamber to the first sampling chamber, to extract the glucose from the subject into the second sampling chamber, wherein (i) said conducting comprises applying electrical energy to the collection medium; and

(ii) said conducting and extracting comprises iontophoresis; and

(c) analyzing each sampling chamber for a concentration or amount of the glucose.

34. The method of claim 33, further comprising (d) correlating the concentration determined in step (c) with a blood glucose level.

35. The method of claim 33, further comprising (d) providing correlation data between sampling chamber glucose levels and the subject'"'"'s glucose levels.

36. The method of claim 33, wherein said conducting in a first polarity and said second conducting in a second polarity comprises an alternating polarity current and said alternating polarity current is applied intermittently.

37. The method of claim 33, wherein said analyzing comprises pulsed amperometric detection.

38. An iontophoresis sampling device comprising

(a) a transdermal system that comprises (i) a first sampling chamber for receiving a sample, wherein the first sampling chamber comprises a first electrode that is connectable with an electrical power supply, and (ii) at least a second electrode that is connectable with said power supply;

and

(b) means for reversing polarity between the first electrode and the second electrode, wherein the first electrode functions as both an anode and a cathode during iontophoretic sampling.

39. The device of claim 38, wherein said second electrode comprises an indifferent counter electrode that also alternates polarity.

40. The device of claim 38, wherein said transdermal system further comprises a second sampling chamber, said second sampling chamber comprising said second electrode, wherein said second electrode alternates function as both an anode and a cathode during iontophoretic sampling.

41. The device of claim 40, further comprising

(c) means for analyzing a concentration or amount of a substance or a substance metabolite received in the first and second sampling chambers.

42. The device of claim 41, further comprising (d) a programmed processor for correlating the concentration or amount determined in step (c) with a blood substance level.

43. The device of claim 41, further comprising (d) a programmed processor for providing correlation data between a sampling chamber substance level and blood substance levels.

44. The device of claim 41, wherein said analyzing comprises pulsed amperometric detection.

45. The device of claim 40, wherein each sampling chamber comprises an Ag/AgCl electrode.

46. The device of claim 45, wherein each sampling chamber comprises a collection medium.

47. The device of claim 38, further comprising

(c) means for analyzing a concentration or amount of a substance or a substance metabolite received in the first sampling chamber.

48. The device of claim 47, wherein said analyzing comprises pulsed amperometric detection.

49. The device of claim 38, wherein said reversing of polarity is performed at a frequency comprising about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

50. The device of claim 49, wherein said reversing of polarity is performed at a frequency comprising about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

51. The device of claim 50, wherein said reversing of polarity is performed at a frequency comprising about 1 cycle per minute to about 1 cycle per 2 hours.

52. The device of claim 51, wherein said reversing of polarity is performed at a frequency comprising about 1 cycle per 10 minutes to about 1 cycle per hour.

53. The device of claim 52, wherein said reversing of polarity is performed at a frequency comprising about 1 cycle per half hour.

54. The device of claim 38, wherein the first sampling chamber comprises an Ag/AgCl electrode.

55. The device of claim 54, wherein the first sampling chamber comprises a collection medium.

56. The device of claim 38, wherein said means for reversing polarity comprises a switch.

57. The device of claim 38, further comprising an electrical power supply.

58. The device of claim 38, wherein said sample comprises glucose.

59. The device of claim 38, wherein said sample comprises more than one substance.

60. An iontophoresis device for sampling glucose, said device comprising

(a) a transdermal system that comprises (i) a first sampling chamber for receiving a sample, wherein the first sampling chamber comprises a first electrode that is connectable with an electrical power supply and a collection medium, and (ii) a second sampling chamber for receiving a sample, wherein the second sampling chamber comprises a second electrode that is connectable with an electrical power supply and a collection medium;

and

(b) means for reversing polarity between the first electrode and the second electrode, wherein the first and second electrodes each alternately function as both an anode and a cathode during iontophoretic sampling.

61. The device of claim 60, wherein said first and second electrodes comprise Ag/AgCl.

62. The device of claim 60, further comprising

(c) means for analyzing a concentration or amount of glucose received in the first and second sampling chambers.

63. The device of claim 62, further comprising (d) a programmed processor for correlating the concentration or amount determined in step (c) with a blood glucose level.

64. The device of claim 62, further comprising (d) a programmed processor for providing correlation data between a sampling chamber glucose level and blood glucose level.

65. The device of claim 62, wherein said analyzing comprises pulsed amperometric detection.

66. The device of claim 60, further comprising an electrical power supply.

67. The device of claim 60, wherein said reversing of polarity comprises an alternating polarity current and said alternating polarity current is applied intermittently.