Method and apparatus for determination of chemical species in body fluid

• US 5,203,327 A
• Filed: 08/15/1990
• Issued: 04/20/1993
• Est. Priority Date: 09/08/1988
• Status: Expired due to Term

• Current Assignee: Sudormed Incorporated
• Original Assignee: Sudor Partners
• Inventors: Miller, William R., Schoendorfer, Donald W.
• Primary Examiner(s): Cohen, Lee S.
• Application Number:
  US07/569,007
• Time in Patent Office: 979 Days
• Field of Search: 128/632, 128/636, 128/637, 128/760, 128/771, 604/312
• US Class Current: 600/362
• 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 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 5/411 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 5/6833 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

Disclosed is a method and apparatus for the non-invasive determination of one or more preselected analytes in a body fluid expressed through the skin. The fluid is collected in a dermal concentration patch and concentrated by driving off a portion of the substantial water fraction under the influence of body heat. The analyte is optimally complexed with an immobilized specific binding partner and an indicium of the presence of the analyte is visually expressed. The patch may comprise a plurality of test zones for screening for a plurality of analytes. Additional positive and negative control zones are also disclosed. The patch may comprise a feature to detect tampering with the patch to produce false negative results, especially when used in screens for drugs of abuse. In addition to being useful as a drug of abuse screen, the patch is useful for diagnostic purposes.

Claims

1. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, comprising:

a water permeable support layer having a first and a second side;

at least one first and at least one second reagent immobilized in the support layer; and

means for removably securing the first side of the support layer in fluid communication with the subject'"'"'s skin, wherein said patch is water permeable so that water vapor is permitted to escape through the support layer and outside of the concentration patch, and wherein the first reagent comprises a specific binding partner for the analyte to be determined, and the second reagent comprises a specific binding partner for a reference substituent in the perspiration.

2. A dermal concentration patch as in claim 1, wherein the first and second reagents are contained in discrete regions on the patch.

3. A dermal concentration patch as in claim 1, wherein the means for securing comprises adhesive tape.

4. A method of detecting false negative results in an assay of a body fluid from a subject which are the result of noncompliance with the testing procedure by the subject, comprising the steps of:

securing a test patch to the subject in communication with a source of body fluid, the test patch comprising first detection chemistry for detecting the presence of an analyte in the body fluid and second detection chemistry for detecting the presence of a reference substituent in the body fluid;

removing the test patch from the subject after a sufficient test period of time to enable the first detection chemistry to detect the analyte, if present;

determining the amount of reference substituent detected by the second detection chemistry; and

comparing the amount of reference substituent detected to a predetermined value to determine whether the test patch remained secured to the subject for substantially all of the test period of time.

5. A method of detecting false negative results as in claim 4, further comprising the step of determining whether any analyte was detected by the first detection chemistry.

6. A method of detecting false negative results as in claim 4, wherein the analyte to be detected by the first detection chemistry comprises a drug of abuse or its metabolite.

7. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, in which false negative results produced through elution of the patch with a solvent can be detected, comprising:

a water permeable support layer having a first side and a second side, said first side being applicable to the subject'"'"'s skin;

means for removably securing the first side of the support layer in fluid communication with the subject'"'"'s skin; and

a soluble marker within the support layer, the presence of which can be detected after the patch is removed,

said patch having sufficient permeability to allow water to escape said patch in the vapor phase, wherein a substantial loss in the quantity of soluble marker present in the patch after the patch is removed is indicative of false negative results.

8. The dermal concentration patch of claim 7, wherein the marker is soluble in non-aqueous solvents.

9. The dermal concentration patch of claim 7, wherein the marker is a visible marker which will not cause significant trauma to the skin upon prolonged skin contact and is not readily absorbed by the skin.

10. A method of detecting false negative results in an assay for an analyte in a body fluid from a subject which are the result of elution of a test patch with a solvent, comprising the steps of:

securing the test patch to the subject in communication with a source of body fluid, the test patch containing a marker soluble in the solvent used for elution;

removing the test patch from the subject after a sufficient test period of time to enable the analyte to be detected by an assay for the analyte;

determining the amount of marker remaining in the test patch; and

comparing the amount of marker remaining in the test patch with a control, the control being the amount of marker empirically determined to be remaining in a test patch worn continuously by a subject for the same length of time,

wherein an amount of marker remaining in the test patch lower than the control is indicative of false results.

11. The method of claim 10, wherein the control is assumed to be substantially all the marker remaining in the patch.

12. The method of claim 11, wherein the marker comprises a visible dye and the comparing step comprises comparing the color of the test patch after removal of the patch to the color of a test patch before application.

13. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, in which false negative results produced through the addition of adulterants to the patch can be detected, comprising:

a water permeable support layer having a first side being applicable to the subject'"'"'s skin;

means for removably securing the first side of the support layer in fluid communication with the subject'"'"'s skin; and

a test region on said patch for detecting the presence of an adulterant capable of producing false negative results in an assay for the analyte, wherein the test region comprises color change chemistry responsive to the presence of an adulterant selected from the group consisting of;

aluminum, chromate, cobalt, copper, iron, nickel, nitrate, peroxide, sulphite, tin, calcium, high pH, low pH, glucose, protein, and ketones,

wherein water is permitted to escape through the support layer and outside of said concentration patch.

14. A method of detecting false negative results in an analyte binding assay of a body fluid from a subject which are the result of the addition of an adulterant to a test patch, comprising the steps of:

securing said test patch to the subject in communication with the source of said body fluid, said test patch comprising a test strip capable of detecting the adulterant by the development of a detectable change on the strip;

removing said test patch from the subject after a sufficient test period of time to enable an analyte to be detected by an assay for said analyte; and

determining the presence of adulterant from the presence of the detectable change on the test strip.

15. The method of claim 14, wherein the detectable change is a color change.

16. The method of claim 14, wherein the adulterant is selected from the group consisting of:

aluminum, ammonium, chromate, chlorine, cobalt, copper, ion, nickel, nitrate, peroxide, sulphite, tin, calcium, high pH, low pH, glucose, protein, and ketones.

17. A method of detecting false negative results in an assay for an analyte in perspiration from a subject having skin, said negative results being the result of noncompliance with a testing procedure for said assay, comprising the steps of:

securing a test patch to the subject in fluid communication with the skin of said subject, said test patch comprising detection chemistry for detecting a reference substituent from perspiration;

accumulating perspiration in said test patch;

removing the test patch from the skin of said subject after sufficient test period of time to allow a detectable amount of said analyte to accumulate in said test patch if the analyte is present in said perspiration;

determining the amount of reference substituent detected by said reference substituent; and

comparing the amount of reference substituent detected to a predetermined value to determine whether the test patch was removed at a time after the securing step and before the removing step.

18. The method of claim 17, further comprising the step of determining whether analyte is present in said test patch after the accumulating step.

19. The method of claim 17, wherein said analyte comprises a drug of abuse or its metabolite.

20. The method of claim 17, wherein water is permitted to escape the test patch.

21. The method of claim 20, wherein water is permitted to escape the test patch in the vapor phase, but not in the liquid phase.

22. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, comprising:

a water permeable support layer having a first and a second side;

a permeable outer protective layer disposed adjacent the second side of said support layer;

at least one first and at least one second reagent immobilized in the support layer; and

means for removably securing the first side of the support layer in fluid communication with the subject'"'"'s skin,

wherein water is permitted to escape through the support layer and outside of the concentration patch, and wherein the first reagent comprises a specific binding partner for the analyte to be determined, and the second reagent comprises a specific binding partner for a reference substituent in the perspiration.

23. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, comprising:

a water permeable support layer having a first and a second side;

at least one first and at least one second reagent immobilized in the support layer;

wherein the first reagent is a specific binding partner for a drug of abuse or its metabolite; and

means for removably securing the first side of the support layer in fluid communication with the subject'"'"'s skin,

wherein water is permitted to escape through the support layer and outside of the concentration patch the first reagent comprises binding partner for the analyte to be determined, and the second reagent comprises a specific binding partner for a reference substituent in the perspiration.

24. A dermal patch for the non-invasive determination of at least one preselected low-concentration analyte in a body fluid expressed through the skin as perspiration without the need for conventional instrumentation, comprising:

a water-permeable support layer for concentrating components of perspiration, said layer having a single reference zone and at least two analyte detection zones;

at least one analyte detection reagent immobilized to each of said analyte detection zones for detecting the presence of the at least one analyte;

at least one reference detection reagent immobilized to each of said reference zones for detecting the presence of a reference substituent known to be present in perspiration;

the analyte detection reagent in at least one of the analyte detection zones comprising an antibody having an affinity for a drug of abuse or a metabolite thereof cable of passing through the skin; and

means for removably securing the support layer in fluid communication with the subject'"'"'s skin,

wherein each analyte detection reagent contained on each analyte detection zone comprises a specific binding partner for an analyte to be determined, and each reference detection reagent contained on each reference zone comprises a specific binding partner for a reference substituent in the perspiration.

25. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, in which false negative results produced through the addition of adulterants to the patch can be detected, comprising:

a water permeable support layer having a first side and a second side, said first side being applicable to the subject'"'"'s skin;

means for removably securing the first side of the support layer in fluid communication with the subject'"'"'s skin; and

a test region on said patch for detecting the presence of an adulterant capable of producing false negative results in an assay for the analyte, said test region being on a strip disposed within a region of the patch hidden from the subject'"'"'s view while the patch is worn by the subject, thereby providing the subject with no visible indication of the test region,

wherein water is permitted to escape through the support layer and outside of said concentration patch.

26. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, comprising:

a water permeable support layer in which said analyte can be concentrated

means for removably securing the support layer in fluid communication with the subject'"'"'s skin; and

a reagent which is a specific binding partner for a reference substituent in perspiration immobilized in the support layer, said reference substituent being selected from the group consisting of albumin and IgG,

wherein water is permitted to escape through the support layer and outside of the concentration patch, thereby allowing said analyte to be concentrated in said support layer.

27. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, comprising:

a water permeable support layer in which said analyte can be concentrated

means for removably securing the support layer in fluid communication with the subject'"'"'s skin; and

a reagent which is a specific binding partner for a reference substituent in perspiration immobilized in the support layer, said reagent being selected from the group consisting of an antibody and an antigen,

wherein water is permitted to escape through the support layer and outside of the concentration patch, thereby allowing said analyte to be concentrated in said support layer.

28. A dermal concentration patch for determining the presence of an analyte in a subject mammal'"'"'s perspiration, comprising:

a water permeable support layer in which said analyte can be concentrated

means for removably securing the support layer in fluid communication with the subject'"'"'s skin; and

a reagent which is a specific binding partner for a reference substituent in perspiration immobilized in the support layer; and

indicator chemistry within the patch for providing an indication of the binding of said reference substituent to said reagent,

wherein water is permitted to escape through the support layer and outside of the concentration patch, thereby allowing said analyte to be concentrated in said support layer.

29. The patch of claim 28, wherein said indication is a color change.

30. A method of determining the presence of a drug of abuse or metabolite thereof in a subject mammal'"'"'s perspiration, comprising:

removably securing a water permeable support layer in fluid communication with the subject'"'"'s skin, said support layer being in combination with a concentration patch;

accumulating perspiration from said subject in said support layer for a test period of time;

permitting water to escape through the support layer, thereby concentrating the drug of abuse or metabolite thereof in the support layer; and

detecting false test results if present by including a soluble marker within said patch and detecting the presence of the quantity of said marker after completion of the test period,

wherein a substantial loss in the quantity of soluble marker present in the patch is indicative of a false negative result.