Device and method for sampling of substances using alternating polarity

• US 5,771,890 A
• Filed: 06/24/1994
• Issued: 06/30/1998
• 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): Sykes, Angela D.
• Assistant Examiner(s): WINAKUR, ERIC FRANK
• Application Number:
  US08/265,844
• Time in Patent Office: 1,467 Days
• Field of Search: 128/632, 128/635, 128/639, 128/640, 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 a substance from a subject which comprises:

(a) placing a device comprising a first and second sampling chamber each sampling chamber comprising an electrode in electrical communication with the tissue 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 the first sampling chamber;

(c) analyzing the first sampling chamber for the concentration of the substance or a substance metabolite;

(d) reversing the polarity of the electrodes in the first and second sampling chamber and conducting electrical current through the tissue in a second opposite polarity to the collection site to extract a substance from the subject into the second sampling chamber;

(e) analyzing the second sampling chamber for the concentration of the substance or a substance metabolite.

2. The method of claim 1 wherein the polarity reversing step comprises the step of using a switch to reverse polarity.

3. The method of claim 1 wherein the step of reversing polarity is performed at a frequency of from about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

4. The method of claim 3 wherein the frequency of polarity switching is from about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

5. The method of claim 4 wherein the frequency of polarity switching is from about 1 cycle per minute to about 1 cycle per 2 hours.

6. The method of claim 5 wherein the frequency of polarity switching is from about 1 cycle per 10 minutes to about 1 cycle per hour.

7. The method of claim 6 wherein the frequency of polarity switching is about 1 cycle per half hour.

8. The method of claim 1 wherein the sampling chamber comprises an Ag/AgCl electrode, the conducting step comprising conducting current through the electrode.

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 step of placing a sampling chamber on a collection site on a tissue surface comprises the step of placing a sampling chamber on a collection site on a stratum corneum surface.

12. The method of claim 1 wherein the step of placing a sampling chamber on a collection site comprises the step of placing a sampling chamber comprising an adhesive patch enclosing electrodes and open to the tissue surface.

13. The method of claim 1 further comprising the step of placing 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 to the collection site.

16. The method of claim 13 wherein the step of placing electrodes comprises the step of placing on the tissue surface electrodes which 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 collection medium.

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 the step of using pulsed amperometric detection.

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

23. 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.

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

25. The method of claim 24 further comprising the step of providing correlation data between a sampling chamber substance level and the blood substance levels.

26. The method of claim 25 wherein the correlating step comprises calculating substance flux from the collection site into the sampling chamber.

27. The method of claim 26 wherein the correlating step also comprises compensating for time lag between blood substance level values and substance flux.

28. The method of claim 27 wherein the correlating step also comprises compensating for substance flux value drift.

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

30. The method of claim 1 further comprising the step of treating the patient in response to the substance level determined. 10 minutes to about 1 cycle per hour.

31. An iontophoresis sampling device comprising

(a) an electrical power supply;

(b) a transdermal system that contains a sampling chamber for receiving a sample, wherein the sampling chamber is connected with said electrical power supply;

(c) means for reversing polarity of the sampling chamber, wherein the sampling chamber functions as both an anode and a cathode during iontophoretic sampling; and

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

32. The device of claim 31 wherein the means for reversing comprises means for reversing the polarity of the sampling chamber at a frequency of from about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

33. The device of claim 32 wherein the frequency of polarity switching is from about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

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

37. The device of claim 31 wherein the sampling chamber comprises an Ag/AgCl electrode.