Sheet-like diagnostic device

• US 4,861,711 A
• Filed: 12/13/1985
• Issued: 08/29/1989
• Est. Priority Date: 12/15/1984
• Status: Expired

• Current Assignee: DADE Behring Beteiligungs GmbH (Siemens AG)
• Original Assignee: Behringwerke Aktiengesellschaft (Sanofi )
• Inventors: Stark, Joseph, Pauly, Hans-Erwin, Grenner, Gerd, Habenstein, Klaus, Kohl, Helmut, Friesen, Heinz-Jurgen
• Primary Examiner(s): PRESTON, DAVID
• Application Number:
  US06/808,563
• Time in Patent Office: 1,355 Days
• Field of Search: 436/514, 436/810, 435/7, 435/805, 435/810, 422/56, 422/169, 422/61, 422/101
• US Class Current: 435/7.92
• CPC Class Codes: G01N 33/521 Single-layer analytical elements
• CPC Class Codes: G01N 33/525 Multi-layer analytical elements
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/558 using diffusion or migration of antigen or antibody immunochromatographic test strips G01N33/54387
• CPC Class Codes: Y10S 435/805 Test papers
• CPC Class Codes: Y10S 435/81 Packaged device or kit
• CPC Class Codes: Y10S 435/962 Prevention or removal of interfering materials or reactants or other treatment to enhance results, e.g. determining or preventing nonspecific binding
• CPC Class Codes: Y10S 435/97 Test strip or test slide
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

A solid diagnostic device for the quantitative determination of substances of biological affinity in biological fluids is described. A process is also described in which the biological fluid is brought into contact with a specific functional sector of the device, the fluid migrates through several functional sectors situated beside one another and containing suitable reagent components, and one or more substances of biological affinity are detected in such functional sectors which contain, for each substance to be detected, at least one combination partner of biological affinity, attached to a solid phase.

Claims

1. An analytical device for the detection or determination of a component in a fluid wherein said component is an analyte with bioaffinity binding properties, comprising a layer of a plurality of substantially planar zones adjacent one another and in absorbent contact with one another, said layer including:

a mobile phase application zone (MPAZ), an intermediate zone (IZ) and an adsorption zone (AZ), liquid being capable of moving by adsorption from said MPAZ through said IZ to said AZ, and wherein said IZ further comprises a solid phase zone (SPZ) having at least one unlabelled reactant, capable of interactions of biological affinity with at least one analyte;

at least one unattached, labelled reactant (conjugate), capable of interactions of biological affinity with said at least one analyte, disposed in an area between the MPAZ and the SPZ; and

an analyte application zone disposed at said MPAZ or in between said MPAZ and said AZ, wherein after application of said at least one analyte, said at least one analyte is reacted with said reactants in said layer and is detected in said layer.

2. A device as claimed in claim 1, wherein the MPAZ has the function of a volume metering element and releases to the subsequent zones at least sufficient liquid for the liquid, controlled by capillary forces, to reach the end of the AZ.

3. A device as claimed in claim 1, wherein the MPAZ is a plastic sponge or a particulate layer which is composed of hydrophilic polymers and which is capable of containing chemicals, buffer substances or other substances required for certain tests.

4. A device as claimed in claim 1, wherein the analyte application zone retains blood cells.

5. A device as claimed in claim 1, wherein all or some of the reagents required for the detection of the labelling are present in one or more of substantially planar zones of the device.

6. A device as claimed in claim 1, wherein said at least one unlabelled reactant is fixed to said SPZ by means of covalent bonds.

7. A device as claimed in claim 1, wherein said at least one unlabelled reactant is fixed to said SPZ by means of absorption.

8. A device as claimed in claim 1, wherein said at least one unlabelled reactant is fixed to said SPZ by means of an interaction of biological affinity.

9. A device as claimed in claim 1, further including a plurality of solid phase zones (SPZs) for the detection of a plurality of analytes, said analytes including at least one attachment point of biological affinity, each of said SPZs being adjacent one another in said layer and each of said SPZs including said unlabelled reactants fixed thereto, said unlabelled reactants of each SPZ being specific for a specific analyte to be detected in each of said SPZs.

10. A device as claimed in claim 1, wherein said layer includes a chromotographing section in at least a portion of said substantially planar zones, and further including a sample application zone laminated onto at least a portion of said chromatographing section and in adsorptive contact therewith.

11. A device as claimed in claim 1, wherein said layer includes a chromotographing section in at least a portion of said substantially planar zones, and further including a reagent zone laminated onto at least a portion of said chromotographing section and in adsorptive contact therewith, wherein at least some of the reagents required for the detection of the labelling are present in said reagent zone.

12. A process for the detection or determination of a component in a fluid wherein said component is an analyte with bioaffinity binding properties by rehydrating or solvating reactants and reagents by the fluid containing the analyte or by an additional fluid, said reactants and reagents being present in a dehydrated state in an analytical device for the detection or determination of a component in a fluid wherein said component is an analyte with bioaffinity binding properties, comprising a layer of a plurality of substantially planar zones adjacent one another and in absorbent contact with one another, aid layer including:

a mobile phase application zone (MPAZ), an intermediate zone (IZ) and an adsorption zone (AZ), liquid being capable of moving by adsorption from said MPAZ through said IZ to said AZ, and wherein said IZ further comprises a solid phase zone (SPZ) having at least one unlabelled reactant, capable of interactions of biological affinity with at least one analyte;

at least one unattached, labelled reactant (conjugate), capable of interactions of biological affinity with said at least one analyte, disposed in an area between the MPAZ and the SPZ; and

an analyte application zone disposed at said MPA or in between said MPAZ and said AZ,

said process comprising;

applying a sample to said analyte application zone, reacting the at least one analyte in the sample in said layer and detecting said at least one analyte in said layer.

13. The process as claimed in claim 12, wherein, after the liquid sample containing the analyte has been fed to the MPAZ or after the sample has been fed to a sample application zone and a mobile phase has been fed to the MPAZ, the liquid reaches the end of the AZ, under the control of capillary forces, and reactions between reactants contained in the device and the analyte are thereby set in operation, and, after the labelled reactants which are not attached to the solid phase have been removed chromatographically, the amount of the labelling in the solid phase zone, which is a measure of the analyte concentration in the sample, is determined.

14. The process as claimed in claim 12, wherein the reactions taking place in the device are based on the principals of at least one of immunological detection reactions, competitive immunometric or sandwich immunoassay, indirect antibody detection by means of a labelled antibody and antibody detection by means of a labelled antigen.

15. The process as claimed in claim 12, wherein said detecting includes using a fluorophor as a labelling agent which is detected or measured directly or is detected or measured after the addition of a reagent present in the device, or a fluorophor which is detected or measured directly or after the addition of a further reagent is formed from the labelling agent by the addition of a reagent present in the device.

16. The process as in claim 12, wherein said detecting includes using a compound which can be excited to give chemiluminescence as a labelling agent, the chemiluminescence being detectable or measurable after the addition of a reagent present in the device.

17. The process as claimed in claim 12, wherein said detecting includes using an enzyme as a labelling agent, the activity of which is determined with the aid of a reagent present in the device.

18. An analytical device for the detection or determination of a component in a fluid wherein said component is an analyte with bioaffinity binding properties, comprising a layer of a plurality of sheet-like zones adjacent one another and in absorbant contact with one another, said layer including:

a mobile phase application zone (MPAZ), an intermediate zone (IZ) and an adsorption zone (AZ), liquid being capable of moving by adsorption from said MPAZ through said IZ to said AZ, and wherein said IZ further comprises a solid phase zone (SPZ) capable of having at least one unlabelled reactant fixed thereto which is capable of interactions of bioaffinity with at least one analyte, during analysis said at least one unlabelled reactant being fixed to at least one second reactant which is fixed to said solid phase zone;

at least one unattached labelled reactant (conjugate), capable of interactions of biological affinity with said at least one analyte, disposed in an area between said MPAZ and said SPZ; and

an analyte application zone disposed at said MPAZ or in between said MPAZ and said AZ, wherein after application of said at least one analyte, said at least one analyte is reacted with said reactants in said layer and is detected in said layer.

19. A device as claimed in claim 18, wherein said at least one second reactant is fixed to said SPZ by means of covalent bonds.

20. A device as claimed in claim 18, wherein said at least one second reactant is fixed to said SPZ by means of adsorption.

21. A device as claimed in claim 18, wherein said at least one second reactant is fixed to said SPZ by means of an interaction of biological affinity.

22. A device as claimed in claim 18, further including a plurality of solid phase zones (SPZs) for the detection of a plurality of analytes, said analytes including at least one attachment point of biological affinity, each of said SPZs being adjacent one another in said layer and each of said SPZs including said unlabelled reactants fixed thereto, said unlabelled reactants of each SPZ being specific for a specific analyte to be detected in each of said SPZs.

23. A device as claimed in claim 18, wherein the MPAZ has the function of a volume metering element and releases to the subsequent zones at least sufficient liquid for the liquid, controlled by capillary forces, to reach the end of the AZ.

24. A device as claimed in claim 18, wherein the MPAZ is a plastic sponge or a particulate layer which is composed of hydrophilic polymers and which is capable of containing chemicals, buffer substances or other substances required for certain tests.

25. A device as claimed in claim 18, wherein the analyte application zone retains blood cells.

26. A device as claimed in claim 18, wherein said layer includes a chromotographing section in at least a portion of said substantially planar zones;

and further including a sample application zone laminated onto at least a portion of said chromatographing section and in adsorptive contact therewith.

27. A device as claimed in claim 18, wherein all or some of the reagents required for the detection of the labelling are present in one or more of the substantially planar zones of the device.

28. A device as claimed in claim 18, wherein said layer includes a chromotographing section in at least a portion of said substantially planar zones, and further including a reagent zone laminated onto at least a portion of said chromotographing section and in adsorptive contact therewith, wherein at least some of the reagents required for the detection of the labelling are present in said reagent zone.

29. A process for the detection or determination of a component in a fluid as an analyte with bioaffinity binding properties by rehydrating or solvating reactants and reagents by the fluid containing the analyte or by an additional fluid, said reactants and reagents being present in a dehydrated state in an analytical device for the detection or determination of the analyte, said device including a layer of a plurality of substantially planar zones adjacent one another and in absorbent contact with one another, said layer including:

a mobile phase application zone (MPAZ), an intermediate zone (IZ) and an adsorption zone (AZ), liquid being capable of moving by adsorption from said MPAZ through said IZ to said AZ;

a solid phase zone (SPZ) in said IZ capable of having at least one unlabelled reactant fixed thereto which is capable of interactions of bioaffinity with at least one analyte, during analysis said at least one unlabelled reactant being fixed to at least one second reactant which is fixed to said solid phase zone;

at least one unattached labelled reactant (conjugate), capable of interactions of biological affinity with said at least one analyte, disposed in a zone between the MPAZ and the SPZ; and

an analyte application zone disposed at said MPAZ or in between said MPAZ and said AZ;

said process comprising;

applying a sample to said analyte application zone, reacting the at least one analyte in the sample in said layer and detecting said at least one analyte in said layer.

30. The process as claimed in claim 29, wherein, after the liquid sample containing the analyte has been fed to the MPAZ or after the sample has been fed to a sample application zone and a mobile phase has been fed to the MPAZ, the liquid reaches the end of the AZ, under the control of capillary forces, and reactions between reactants contained in the device and the analyte are thereby set in operation, and, after the labelled reactants which are not attached to the solid phase have been removed chromatographically, the amount of the labelling in the solid phase zone, which is a measure of the analyte concentration in the sample, is determined.

31. The process as claimed in claim 29, wherein the reactions taking place in the device are based on the principals of at least one of immunological detection reactions, competitive immunometric or sandwich immunoassay, indirect antibody detection by means of a labelled antibody and antibody detection by means of a labelled antigen.

32. The process as claimed in claim 29, wherein said detecting includes using a fluorophor as a labelling agent which is detected or measured directly or is detected or measured after the addition of a reagent present in the device, or a fluorophor which is detected or measured directly or after the addition of a further reagent is formed from the labelling agent by the addition of a reagent present in the device.

33. The process as in claim 29, wherein said detecting includes using a compound which can be excited to give chemiluminescence as a labelling agent, the chemiluminescence being detectable or measurable after the addition of a reagent present in the device.

34. The process as claimed in claim 29, wherein said detecting includes using an enzyme as a labelling agent, the activity of which is determined with the aid of a reagent present in the device.