Multiple component chromatographic assay device

• US 6,168,956 B1
• Filed: 05/29/1991
• Issued: 01/02/2001
• Est. Priority Date: 05/29/1991
• Status: Expired due to Term

• Current Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Original Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Inventors: Chandler, Howard M.
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US07/706,639
• Time in Patent Office: 3,506 Days
• Field of Search: 436/514, 436/501, 436/517, 436/518, 436/807, 436/808, 436/809, 436/810, 435/6, 435/7.1, 435/7.92, 435/7.93, 435/7.94, 435/7.95, 435/970, 435/287.1, 435/287.2, 435/805, 435/810, 422/58, 422/56, 422/57
• US Class Current: 436/514
• CPC Class Codes: B01D 15/3804 Affinity chromatography
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/5023 with a sample being transported to, and subsequently stored in an absorbent for analysis
• CPC Class Codes: B01L 3/5055 Hinged, e.g. opposable surfaces
• CPC Class Codes: G01N 30/02 Column chromatography
• CPC Class Codes: G01N 30/30 of temperature
• CPC Class Codes: G01N 30/463 for multidimensional chromatography
• CPC Class Codes: G01N 30/90 Plate chromatography, e.g. thin layer or paper chromatography
• CPC Class Codes: G01N 30/91 Application of the sample
• CPC Class Codes: G01N 33/5302 Apparatus specially adapted for immunological test procedures
• CPC Class Codes: G01N 33/54388 based on lateral flow
• 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 435/97 Test strip or test slide
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

An assay device for the performance of immunochromatographic assays and other assays has two principal parts, a first opposable component and a second opposable component. The first opposable component can contain a sample preparation means and a second opposable component can contain a suitable chromatographic medium for detection of an analyte. Alternative embodiments of the invention can also exist. For example, the first opposable component can have a sample preparation means and a chromatographic medium that is not in communication with the sample preparation means and the second opposable component can contain a communicating means that, when the two components are brought into opposition, establishes a communication between the sample preparation means and the chromatographic medium. Assay devices according to the present invention can be used for both unidirectional and bidirectional assays.

Claims

1. A chromatographic assay device comprising:

a first opposable component including a sample preparation means for receiving a liquid sample to be assayed and containing a labeled mobile reagent to bind specifically to an analyte to be detected; and

a second opposable component including a chromatographic medium having at least one reagent binding specifically to an analyte to be detected, the reagent being bound at a detection zone on the chromatographic medium, the second opposable component being connected to the first opposable component;

wherein the first and second opposable components can be brought into opposition by direct manual closure from a position in which they are not in opposition so as to cause the sample preparation means to apply the liquid sample to be tested to the chromatographic medium and to cause the liquid sample to flow through the chromatographic medium, the chromatographic assay being performed as a result of migration of the sample within the chromatographic medium so that the analyte is detected within the chromatographic medium as a result of the migration by binding of the labeled mobile reagent, the analyte being detected at a position different than the position at which the sample is applied to the chromatographic medium, the analyte being detected on the chromatographic medium after migration by binding of the labeled mobile reagent to the analyte bound to the detection zone.

2. The device of claim 1 wherein the sample preparation means includes at least one reagent for the treatment of the sample before the sample is applied to the chromatographic medium.

3. The device of claim 2 wherein the first and second opposable components each further comprise engaging means which secure the first and second opposable components in opposition.

4. The device of claim 3 wherein the first and second opposable components are joined by a hinge.

5. The device of claim 1 wherein the first and second opposable components are each substantially planar.

6. A chromatographic assay device comprising:

a first opposable component, including (1) a sample preparation means for receiving a liquid sample to be assayed and (2) a chromatographic medium which is not in communication with the sample preparation means and having at least one reagent binding specifically to an analyte to be detected, the reagent being bound at a detection zone on the chromatographic medium; and

a second opposable component including a connecting member for transferring fluid from the sample preparation means to the chromatographic medium;

wherein the first and second opposable components can be brought into opposition by direct manual closure from a position in which they are not into opposition so as to cause the connecting member to establish a communication between the sample preparation means and the chromatographic medium so as to result in the application of the liquid sample to the chromatographic medium through the connecting member and in flow of the sample through the chromatographic medium, the chromatographic assay being performed in the detection zone as a result of migration of the sample within the chromatographic medium so that the analyte is detected within the chromatographic medium as the result of migration, the analyte being detected at a position different than the position at which the sample is applied to the chromatographic medium, the analyte being detected on the chromatographic medium at the detection zone by binding of a labeled mobile reagent that binds specifically to the analyte to be detected.

7. The device of claim 6 wherein the sample preparation means includes at least one reagent for the treatment of the sample before the sample is applied to the chromatographic medium.

8. The device of claim 7 wherein the first and second opposable components each further comprise engaging means which secure the first and second opposable components in opposition.

9. The device of claim 8 wherein the first and second opposable components are joined by a hinge.

10. The device of claim 6 wherein the first and second opposable components are hingedly connected.

11. The device of claim 6 wherein the first and second opposable components are each substantially planar.

12. A chromatographic assay device for detecting the presence of H. pylori antibodies in a sample comprising:

a first opposable component including;

(i) a chromatographic medium having first and second ends and a reagent that specifically binds H. pylori antibodies, the reagent being bound at a detection zone on the chromatographic medium and (ii) a first application means at the first end of the chromatographic medium, the detection zone being located between the first application means and the second end of the chromatographic medium; and

a second opposable component including a second application means and an absorbing means;

wherein addition of a first liquid sample to the first application means causes a first liquid sample to flow from the first end of the chromatographic medium toward the second end of the chromatographic medium; and

wherein bringing the first and second opposable components into opposition;

(1) causes the second application means to come into contact with the second end of the chromatographic medium so as to apply a second liquid to the second end of the chromatographic medium, said second liquid containing a labeled mobile reagent that specifically binds H. Pylori antibodies, and (2) causes the absorbing means to come into contact with the first application means so as to withdraw fluid from the chromatographic medium via the first application means, thus reversing the flow in the chromatographic medium, the chromatographic assay being performed as a result of migration of the sample within the chromatographic medium so that H. pylori antibodies are detected as the result of the migration of the sample in a first direction within the chromatographic medium and of the second liquid applied to the chromatographic medium in a second direction opposite to the first direction, the H. pylori antibodies being detected at a position different than the position at which the sample is applied to the chromatographic medium by binding of the labeled mobile reagent to the H. pylori antibodies bound to the detection zone.

13. The chromatographic assay device of claim 12 wherein said labeled mobile reagent that binds H. pylori antibodies comprises anti-human IgG antibodies labeled with pink colloidal gold.

14. The device of claim 12 wherein the first and second opposable components are joined by a hinge.

15. The device of claim 12 wherein the first and second opposable components are each substantially planar.

16. The device of claim 12 wherein said first and second opposable components are each substantially of paper board construction.

17. A method for detecting an analyte in a liquid sample using a chromatographic medium having a first end and second end with a detection zone located between said first end and said second end, said detection zone comprising an immobilized antigen for said analyte, said method comprising:

applying said sample to said first end of said chromatographic medium whereby said sample migrates toward said second end of said chromatographic medium into said detection zone and said analyte binds to said immobilized antigen to form an immobilized analyte,

applying to said second end of said chromatographic medium a solution containing labeled antibody reagent that binds to said analyte, whereby said solution migrates toward said first end of said chromatographic medium into said detection zone and said labeled antibody reagent binds to said immobilized analyte, permitting detection of said analyte.

18. The method of claim 17 wherein said chromatographic medium is substantially planar.

19. The method of claim 17 wherein said analyte is H. pylori antibodies.

20. The method of claim 17 wherein said labeled antibody reagent comprises anti-human IgG antibodies labeled with pink colloidal gold.

21. A method for detecting an analyte in a liquid sample using a chromatographic medium having

(a) a first end and second end with a detection zone located between said first end and said second end, said detection zone comprising an immobilized antigen for said analyte, and

(b) a labeled antibody reagent that binds to said analyte impregnated on said second end of said chromatographic medium, said method comprising:

applying said sample to said first end of said chromatographic medium whereby said sample migrates toward said second end of said chromatographic medium into said detection zone and said analyte binds to said immobilized antigen to form an immobilized analyte,

applying a liquid migrating agent to said second end of said chromatographic medium whereby said liquid migrates, along with said labeled antibody reagent, toward said first end of said chromatographic medium into said detection zone and said labeled antibody reagent binds to said immobilized analyte, permitting detection of said analyte.

22. The method of claim 21 wherein said chromatographic medium is substantially planar.

23. The method of claim 21 wherein said analyte is H. pylori antibodies.

24. The method of claim 21 wherein said labeled antibody reagent comprises anti-human IgG antibodies labeled with pink colloidal gold.

25. The method of claim 21 wherein said first end of said chromatographic medium is impregnated with an inert dye.

26. A chromatographic assay device comprising:

a first opposable component including;

(i) a chromatographic medium having first and second ends and a reagent that specifically binds an analyte to be detected, the reagent being bound at a detection zone on the chromatographic medium, (ii) a first application means impregnated with an inert dye adjacent to and in communication with the first end of the chromatographic medium, and (iii) a reagent pad impregnated with a labeled antibody reagent adjacent to and in communication with the second end of the chromatographic medium, the detection zone being located between the first application means and the reagent pad; and

a second opposable component including a second application means containing a buffer solution and an absorbing means;

wherein addition of a first liquid sample to the first application means causes the first liquid sample and the inert dye to flow from the first end of the chromatographic medium toward the second end of the chromatographic medium; and

wherein bringing the first and second opposable components into opposition;

(1) causes the second application means containing the buffer solution to come into contact with the reagent pad so as to apply the buffer solution and labeled antibody reagent to the second end of the chromatographic medium and

(2) causes the absorbing means to come into contact with the first application means so as to withdraw fluid from the chromatographic medium via the first application means, thus reversing the flow in the chromatographic medium, the chromatographic assay being performed as a result of migration of the sample and inert dye within the chromatographic medium so that an analyte is detected as the result of the migration of the sample and inert dye in a first direction within the chromatographic medium and of the buffer solution and labeled antibody reagent applied to the chromatographic medium in a second direction opposite to the first direction, the analyte being detected at a position different than the position at which the sample and inert dye are applied to the chromatographic medium by binding of the labeled reagent to the analyte bound to the detection zone.

27. The device of claim 26 wherein the first and second opposable components each further comprise engaging means which secure the first and secondopposable components in opposition.

28. The device of claim 27 wherein the first and second opposable components are joined by a hinge.

29. The device of claim 26 wherein the first and second opposable components are joined by a hinge.

30. The device of claim 26 wherein the first and second opposable components are each substantially planar.

31. The device of claim 26 wherein the second opposable component further includes a window for viewing the detection zone when the first and second opposable components are in opposition.

32. The device of claim 26 wherein said reagent analyte bound at a detection zone comprises H. pylori antigen.

33. The device of claim 26 wherein said labeled antibody reagent comprises anti-human IgG labeled with pink colloidal gold.