Method of sampling substances using alternating polarity of iontophoretic current

• US 6,023,629 A
• Filed: 11/10/1997
• Issued: 02/08/2000
• 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:
  US08/968,700
• Time in Patent Office: 820 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 non-invasive method for sampling a substance from a subject comprising:

(a) placing a first sampling chamber and electrode in electrical communication with a first tissue surface of the subject;

(b) conducting electrical current through the first tissue surface in a first polarity;

(c) reversing the polarity and conducting electrical current through the tissue at a second polarity,

wherein at least one of the steps (b) and (c) extract a substance from the tissue of the subject into the first sampling chamber; and

(d) analyzing the first sampling chamber for the concentration of the substance or a substance metabolite after at least one of steps (b) and (c);

(e) repeating steps (b) through (d).

2. The method of claim 1, wherein step (d) is completed after steps (b) and (c).

3. The method of claim 1, wherein step (d) is completed after step (b) and prior to step (c).

4. The method of claim 1, wherein a second sampling chamber and electrode are placed in electrical communication with a second tissue surface and electrical current is conducted through the first and second tissue surfaces simultaneously and wherein the polarity of the current at the first and second tissue surfaces is opposite.

5. The method of claim 4, wherein at least one of the steps (b) and (c) extract a substance from the second tissue surface of the subject into the second sampling chamber;

and analyzing the second chamber for the concentration of the substance or a substance metabolite after at least one of steps (b) and (c).

6. The method of claim 5, wherein the step of analyzing the second chamber is completed after steps (b) and (c).

7. The method of claim 5, wherein the step of analyzing the second chamber is completed after step (b) and prior to step (c).

8. The method of claim 1, wherein the substance is glucose and the subject is human.

9. The method of claim 8, wherein glucose oxidase is present between the first tissue surface and electrode.

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

11. A method of determining the glucose concentration of a human subject, comprising:

placing an ionically conductive material on a surface of skin of the subject;

alternately applying positive and negative current to the ionically conductive material in an amount and for a time sufficient to draw glucose into the ionically conductive material;

reacting the glucose with oxygen in the presence of a glucose oxidase catalyst to form gluconic acid and hydrogen peroxide;

measuring current generated by the hydrogen peroxide reacting in the presence of a catalyst comprising platinum; and

relating the current measured to the subject'"'"'s glucose concentration.

12. The method of claim 11, wherein the current applied is in the range of about 0.01 to 2.0 mA/cm².

13. The method of claim 12, wherein the current is applied by an iontophoretic electrode comprising Ag/AgCl.

14. The method of claim 11, wherein the positive and negative currents are applied in a cycle frequency in a range of from about 1 cycle per 20 seconds to one cycle per 4 hours.

15. The method of claim 11, wherein the measuring is carried out using a sensing electrode comprised of platinum using pulsed amperometric detection.

16. An iontophoretic sampling device for sampling a substance from a subject, comprising

(a) an electrical power supply;

(b) a collection assembly comprising (i) a first sampling chamber for said substance comprising a first collection reservoir containing an electrically conductive medium in contact with a first electrode, and (ii) a second sampling chamber for said substance comprising a second collection reservoir containing an electrically conductive medium in contact with a second electrode, wherein said first and second electrodes are in contact with said power supply when the collection assembly is inserted into the sampling device;

(c) means for reversing polarity between said first and second electrodes during sampling, such that each electrode alternates between acting as a cathode and an anode during iontophoretic sampling; and

(d) means for analyzing the concentration of the substance in each sampling chamber.

17. The device of claim 16, wherein the means for reversing polarity reverses polarity of the first and second electrodes at a frequency of from about 1 cycle per 20 seconds to about 1 cycle per 4 hours.

18. The device of claim 17, wherein the means for reversing polarity reverses polarity of the first and second electrodes at a frequence of from about 1 cycle per 20 seconds to about 1 cycle per 2 hours.

19. The device of claim 18, wherein the means for reversing polarity reverses polarity of the first and second electrodes at a frequency of about 1 cycle per half hour.

20. The device of claim 17, wherein the collection reservoir in which the concentration of the substance is monitored alternates as the polarity of the electrodes alternates.

21. The device of claim 17, wherein each of said first and second electrodes comprises an Ag/AgCl electrode.

22. The device of claim 17, where said substance is glucose.