Apparatus and method for the collection of analytes on a dermal patch

• US 5,438,984 A
• Filed: 03/30/1993
• Issued: 08/08/1995
• Est. Priority Date: 09/08/1988
• Status: Expired due to Fees

• Current Assignee: Sudormed Incorporated
• Original Assignee: Sudor Partners
• Inventors: Schoendorfer, Donald W.
• Primary Examiner(s): Cohen, Lee S.
• Application Number:
  US08/039,631
• Time in Patent Office: 861 Days
• Field of Search: 128/632, 128/636, 128/637, 128/760, 128/771, 604/312
• US Class Current: 600/573
• CPC Class Codes: A61B 10/0035 Vaccination diagnosis other than by injuring the skin, e.g. allergy test patches
• CPC Class Codes: A61B 10/0051 for taking saliva or sputum samples devices for receiving spittle A61J9/00
• CPC Class Codes: A61B 10/0064 for taking sweat or sebum samples measuring sweat production A61B5/4266
• CPC Class Codes: A61B 2010/0009 Testing for drug or alcohol abuse
• CPC Class Codes: A61B 2505/01 Emergency care
• CPC Class Codes: A61B 2505/09 Rehabilitation or training
• CPC Class Codes: A61B 2562/164 the sensor is mounted in or on a conformable substrate or carrier
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14521 using means for promoting sweat production, e.g. heating the skin measuring sweat secretion A61B5/4266
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1477 non-invasive
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 5/415 the glands, e.g. tonsils, adenoids or thymus
• CPC Class Codes: A61B 5/418 lymph vessels, ducts or nodes
• CPC Class Codes: A61B 5/4266 sweat secretion
• CPC Class Codes: A61B 5/4845 Toxicology, e.g. by detection of alcohol, drug or toxic products A61B5/4848 takes precedence
• CPC Class Codes: A61B 5/6833 Adhesive patches
• CPC Class Codes: A61F 2013/00195 electric warmer
• CPC Class Codes: A61F 2013/00434 : Epicutaneous test
• CPC Class Codes: A61F 2013/00608 : with reinforcing layers
• CPC Class Codes: A61F 2013/00642 : soluble, e.g. in water
• CPC Class Codes: A61F 2013/00646 : Medication patches, e.g. transcutaneous
• CPC Class Codes: A61F 2013/00655 : adhesive wound bandages with alginate A61F2013/00229; plasters with a double adhesive layer A61F2013/00421; with cyano-acrylic adhesive A61F2013/00459; plasters for treating burn with hydrogel A61F2013/00523; with adhesive connecting means A61F2013/00561; adhesive for plasters, with hydrogel A61F2013/00676; for use on mucosae A61F2013/00714; for use on wounds A61F2013/00719; wound humidity control with hydrocolloids or superabsorbers A61F2013/00748; with absorbent adhesives A61F2013/00757; with fumed silica A61F2013/00787; with viscoelastic oil-elastomer gel A61F2013/00893; with permeable adhesive layers A61F2013/00761; different adhesion of different adhesive layers A61F2013/00804; changing the adhesion force with strain value A61F2013/00838
• CPC Class Codes: A61F 2013/00731 : with absorbing pads
• CPC Class Codes: A61F 2013/00863 : with pores
• CPC Class Codes: A61F 2013/00902 : containing means
• CPC Class Codes: A61F 2013/8411 : in controlling solution Ph
• CPC Class Codes: A61F 2013/842 : with active charcoal
• CPC Class Codes: A61F 2013/8473 : for diagnostic purposes
• CPC Class Codes: A61F 2013/8491 : including test methods
• CPC Class Codes: A61M 35/006 : using sponges, foams, absorbent pads or swabs as spreading means
• CPC Class Codes: B01L 3/505 : flexible containers not provided for above
• CPC Class Codes: G01N 33/54386 : Analytical elements

Abstract

The invention is an improved method and apparatus for collecting analytes on a dermal patch, where the patch controls the ionization state of the analyte. This can be accomplished by delivering electricity to the patch or by a buffer or other means for controlling the pH of fluids entering the patch. Analytes in perspiration can be concentrated on the patch without the occurrence of significant back-diffusion of the analytes.

Claims

1. A method of collecting and detecting an analyte contained in the perspiration of a subject mammal while minimizing back-diffusion of the analyte into the subject mammal, said analyte having a plurality of ionization states, wherein said analyte exists in an ionized form thereof in at least one such ionization state and in a nonionized form in another such ionization state, said method comprising the steps of:

a. placing a dermal patch on the outer surface of the skin of said mammal, said patch comprising an absorbent material capable of containing perspiration of said mammal;

b. passing perspiration through the skin of said mammal into said absorbent material, thereby passing said analyte into the patch, if said analyte is present in said perspiration;

c. controlling the ionization state of said analyte in said patch so that the ratio of the amount of said analyte in said patch in the ionized form to the amount of said analyte in the nonionized form is greater than 1000; and

thereafter

d. detecting said analyte in said patch.

2. The method of claim 1, wherein the controlling step comprises controlling the pH of the outer surface of the skin of said subject underneath said patch so that the pH of said outer surface is maintained within a selected range, said range being calculated to at least substantially prevent the back-diffusion of said analyte from said patch.

3. The method of claim 2, wherein the controlling step comprises maintaining the pH of the outer surface of the skin of said subject below about 7.0.

4. The method of claim 3, wherein the controlling step comprises maintaining the pH of the outer surface of the skin of said subject below about 5.0.

5. The method of claim 2, wherein the controlling step comprises providing a buffer in fluid contact with the outer surface of the skin of said subject, said buffer being designed to maintain the pH of the surface of the skin of said mammal within said selected range.

6. The method of claim 1, additionally comprising the step of determining the amount of said analyte present in said patch.

7. The method of claim 1, additionally comprising the step of permitting water to escape from said patch, thereby concentrating said analyte in said patch.

8. The method of claim 1, wherein the controlling step comprises producing a ratio of the amount of the ionized form of said analyte to the amount of the nonionized form of said analyte in said patch that is greater than 5000.

9. The method of claim 1, additionally comprising the step of preventing water from escaping from said patch during the passing step.

10. The method of claim 1, wherein said analyte has a pK_a within the range of about 7.2 to 10.0.

11. A dermal patch to be worn on the skin of a subject mammal for detecting an analyte in said subject'"'"'s perspiration, said analyte having a plurality of ionization states, including at least one ionization state wherein said analyte is in an ionized form and at least one ionization state wherein said analyte is in a nonionized form, said patch comprising:

an absorbent material, said absorbent material having a first and second side, said first side of said absorbent material being adapted to be in fluid communication with the outer surface of the skin of said subject for collecting perspiration which passes through said skin and into said patch; and

means for controlling the ionization state of said analyte such that the ratio of said analyte in the ionized form to the nonionized form thereof within said patch is greater than 1000.

12. The patch of claim 11 wherein said means for controlling the ionization state comprises means for controlling the pH of the outer surface of the skin of said subject beneath said absorbent material of said patch so that said pH is maintained within a selected range, said range being calculated to cause said analyte to concentrate on said patch and not back-diffuse.

13. The patch of claim 12, wherein said means for controlling the pH of the outer surface of the skin of said subject comprises a buffer in said absorbent material which is adapted to be in fluid contact with the surface of the skin of said subject.

14. The patch of claim 11, wherein said patch additionally comprises a water permeable outer membrane to permit water to escape from the patch, so as to concentrate said analyte in said patch, said water permeable outer membrane having a first and second side, wherein said first side of said water permeable outer membrane is adjacent said second side of said absorbent material.

15. The patch of claim 11, wherein said patch additionally comprises a water impermeable outer membrane to prevent water from escaping from said patch, said water impermeable outer membrane having a first and second side, wherein said first side of said water impermeable outer membrane is adjacent said second side of said absorbent material.

16. The patch claim 11, wherein said analyte has a pK_a within the range of about 7.2 to 10.0.

17. A dermal patch to be worn on the skin of a subject mammal for detecting an analyte in said subject'"'"'s perspiration, said patch comprising:

an absorbent material adapted to be in fluid communication with the outer surface of the skin of said subject for collecting perspiration which passes through said skin and into said patch; and

a buffer in said absorbent material, wherein said buffer is capable of maintaining a pH within a selected range, said range being calculated to cause said analyte to ionize and thereby concentrate in said patch.

18. The method of claim 17, wherein said analyte has a pK_a within the range of about 7.2 to 10.0.

19. A method of collecting and detecting an analyte contained in the interstitial fluid of a subject mammal while minimizing the back-diffusion of said analyte into said subject mammal, said method comprising the steps of:

a. placing a dermal patch on the outer surface of the skin of said mammal, said patch comprising an absorbent material capable of containing perspiration of said mammal;

b. passing perspiration through the skin of said subject mammal into said absorbent material, thereby passing said analyte into the patch, if said analyte is present in said perspiration of said subject mammal;

c. controlling the ratio of the amount of said analyte obtained in said patch to the amount of said analyte in the interstitial fluid of said subject mammal so that said ratio is greater than 10; and

thereafter

d. detecting said analyte in said patch.

20. The method of claim 19, wherein said ratio of the amount of said analyte obtained in said patch to the amount of said analyte in the interstitial fluid of said subject mammal is greater than 100.

21. The method of claim 19, additionally comprising the step of preventing water from escaping from said patch during the passing step.

22. A dermal patch to be worn on the skin of a subject mammal for detecting an analyte in said subject'"'"'s interstitial fluid, said patch comprising:

an absorbent material, said absorbent material having a first and second side, said first side of said absorbent material being adapted to be in fluid communication with the outer surface of the skin of said subject for collecting perspiration which passes through said skin and into said patch; and

means for obtaining a ratio of the amount of said analyte in said patch to the amount of said analyte in said interstitial fluid of said subject of greater than 10.

23. The patch of claim 22, wherein said means for obtaining comprises means for obtaining a ratio of the amount of said analyte in said patch to the amount of said analyte in said interstitial fluid of greater than 100.

24. The patch of claim 22, wherein said means for obtaining comprises means for controlling the pH of the outer surface of the skin of said subject beneath said absorbent material of said patch so that said pH is maintained within a selected range, said range being calculated to cause said analyte to concentrate on said patch and not back-diffuse.

25. The patch of claim 24, wherein said means for obtaining comprises a buffer in said absorbent material adapted to be in fluid contact with the surface of the skin of said subject.

26. The patch of claim 22, wherein said patch additionally comprises a water permeable outer membrane to permit water to escape from said patch, so as to concentrate said analyte in said patch, said water permeable outer membrane having a first and second side, wherein said first side of said water permeable outer membrane is adjacent said second side of said absorbent material.

27. The patch of claim 22, wherein said patch additionally comprises a water impermeable outer membrane to prevent water from escaping from said patch, said water impermeable outer membrane having a first and second side, wherein said first side of said water impermeable outer membrane is adjacent said second side of said absorbent material.

28. The patch of claim 22, wherein said analyte has a pK_a within the range of about 7.2 to 10.0.