Analysis element and method for determination of an analyte in a liquid sample

• US 5,424,220 A
• Filed: 01/29/1993
• Issued: 06/13/1995
• Est. Priority Date: 01/31/1992
• Status: Expired due to Fees

• Current Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Original Assignee: Boehringer Mannheim GmbH (Roche Holding AG)
• Inventors: Naegele, Ulrich, Goerlach-Graw, Ada, Wilk, Hans-Erich, Graw, Reiner
• Primary Examiner(s): Scheiner, Toni R.
• Assistant Examiner(s): Chin, Christopher L.
• Application Number:
  US08/010,985
• Time in Patent Office: 865 Days
• Field of Search: 422/56-58, 435/7.92, 435/7.93, 435/7.94, 435/805, 435/810, 435/967, 435/970, 435/973, 436/514, 436/518, 436/530, 436/164, 436/169, 436/805, 436/807, 436/810
• US Class Current: 436/518
• 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 435/967 Standards, controls, materials, e.g. validation studies, buffer systems
• CPC Class Codes: Y10S 435/97 Test strip or test slide
• CPC Class Codes: Y10S 435/973 Simultaneous determination of more than one analyte
• CPC Class Codes: Y10S 436/805 Optical property
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/81 Tube, bottle, or dipstick

Abstract

The invention addresses an analysis element for the determination of an analyte according to the principle of a heterogeneous immunoassay. Said analysis element is made of a chromatographic porous carrier material and has a reaction zone, at least two detection zones and absorptive zones following said detection zones. The reaction zone contains analyte-specific and labelled binding partners which are present in a number of soluble compartments which are close together, but nevertheless spatially separated. The detection zones are adjacent to the reaction zones and contain an immobilized binding reagent for one of the binding partners present in the reaction zone. At least one detection zone contains a binding reagent for the analyte-specific unlabelled binding partner.

Claims

1. Analysis element for determination of an analyte in a sample liquid by a heterogeneous immunoassay, said element comprising:

a chromatographic porous carrier material having a reaction zone thereupon;

at least two spatially separated detection zones, wherein said detection zones are arranged around the reaction zone such that said detection zones are all adjacent to said reaction zone, and at least one absorptive zone provided adjacent the detection zones, facing away from the reaction zone, wherein said reaction zone comprises a plurality of soluble compartments which are close together and spatially separated, each of said compartments has one of an unlabelled analyte specific binding partner and a labelled binding partner which is a labelled analyte specific binding partner or a labelled analyte analogue therein, and wherein each detection zone comprises an immobilized specific binding reagent for one of said binding partners present on the reaction zone, and wherein at least one of said detection zones comprises a specific binding reagent for the unlabelled analyte specific binding partner.

2. Analysis element according to claim 1, wherein said at least two detection zones are provided at essentially the same distance from the reaction zone.

3. Analysis element according to claim 1, wherein the immobilized binding reagent for the analyte-specific binding partner is one of streptavidin and avidin.

4. Analysis element according to claim 1, wherein at least one of the detection zones contains a binding reagent for the labelled binding partner.

5. Analysis element according to claim 4, wherein the binding reagent for the labelled binding partner is an antibody.

6. Analysis element according to claim 1, wherein the compartments are spaced less than 1 mm apart from one another.

7. Analysis element according to claim 1, wherein the compartments of the reaction zone have a dimension of less than 2 mm in one surface direction.

8. Analysis element according to claim 7, wherein the dimension in one surface direction ranges from 15 μ

m to 1 mm.

9. Analysis element according to claim 1, wherein the compartments are configured to form lines.

10. Analysis element according to claim 1, wherein the compartments are configured to form dots.

11. Analysis element according to claim 1, wherein compartments containing identical reagents are separated from each other by compartments containing different reagents.

12. Analysis element according to claim 1, wherein the compartments of the reaction zone are applied with an ink-jet technique.

13. Analysis element according to claim 1, wherein the compartments of the reaction zone are applied with a bubble-jet technique.

14. Analysis element according to claim 1, wherein the compartments are applied with an air-brush technique.

15. A process for determination of an analyte in a sample liquid by a heterogeneous immunoassay, comprising the steps of:

providing an analysis element having a chromatographic porous carrier material having a reaction zone thereupon, with at least two spatially separated detection zones, wherein said detection zones are arranged around the reaction zone such that said detection zones are all adjacent to said reaction zone, and at least one absorptive zone provided adjacent the detection zones and facing away from the reaction zone, wherein said reaction zone comprises a plurality of soluble compartments which are close together and spatially separated, with each of the compartments having one of an unlabelled analyte specific binding partner and a labelled binding partner which is a labelled analyte specific binding partner or a labelled analyte analogue therein, and wherein each detection zone comprises an immobilized specific binding reagent for one of said binding partners present on the reaction zone, and wherein at least one of the detection zones comprises a binding reagent for the unlabelled analyte specific binding partner;

said method further comprising the steps of

applying a sample liquid onto said reaction zone;

applying a wash liquid onto the reaction zone such that dissolved reagents are, in a chromatographic process, transferred out of the reaction zone in a direction toward the detection zones;

measuring labelled reaction components bound in said detection zones, wherein measurement of one of said detection zones comprising a binding reagent for the unlabelled analyte specific binding partner is used for a first determination of the analyte in the sample, and measurement of one or more further detection zones is used for at least one of qualitative control and quantitative correction of the first determination.

16. Process according to claim 15, further comprising a step of determining a mean value from measurements obtained from at least two detection zones which contain a binding reagent for the unlabelled analyte-specific binding partner.

17. Process according to claim 16, wherein the measurements of at least two detection zones which contain a binding reagent for the unlabelled analyte-specific binding partner are carried out at different wavelengths.

18. Process according to claim 15, wherein measurements of at least one detection zone which contains a binding reagent for the labelled binding partner is used for positive reaction control.

19. Process according to claim 15, wherein measurements of at least one detection zone which contains a binding reagent for the labelled binding partner is used for quantitative correction of analyte determination.

20. Process according to claim 15, wherein the labelled binding partner is a labelled analyte or analyte analogue.