Device and method for detecting analytes by visualization and separation of agglutination

• US 7,754,472 B2
• Filed: 02/02/2005
• Issued: 07/13/2010
• Est. Priority Date: 02/02/2004
• Status: Active Grant

• Current Assignee: Medion Grifols Diagnostics AG (Grifols SA)
• Original Assignee: Medion Diagnostics AG (Grifols SA)
• Inventors: Monod, Philippe, Schwind, Peter
• Primary Examiner(s): NGUYEN, BAO THUY L
• Application Number:
  US10/587,964
• Publication Number:
  US 20090170062A1
• Time in Patent Office: 1,987 Days
• Field of Search: 435/7.1, 435/7.94, 435/283.1, 435/287.1, 435/288.2, 435/288.4, 435/297.4, 435/960, 436/514, 436/518, 436/523, 436/526, 436/535, 436/805, 422/58
• US Class Current: 435/283.1
• CPC Class Codes: B01L 2200/0684 Venting, avoiding backpressure, avoid gas bubbles
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: G01N 15/0255 with mechanical, e.g. inertial, classification, and investigation of sorted collections with centrifuges G01N15/042
• CPC Class Codes: G01N 2474/20 Immunohistochemistry assay
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

The invention relates to a device for detecting one or several analytes in a sample, characterized in that it comprises one or more reaction chambers and/or one or more reagent application channels, and one or more capillary systems and one or more negative vessels. The invention also relates to a method for detecting one or more analytes in a sample fluid by visualization of agglutination, characterized in that a) the sample fluid is brought into contact with a reagent, b) the reaction mixture is exposed to the effects of gravitation or magnetism, wherein the reaction mixture is strained through the capillary system of the inventive device with a negative vessel connected to the inventive device, and c) the reaction between the analyte and the reagent is determined. The invention also relates to one such method wherein the reaction mixture is brought into contact with another reagent during step b). The invention further relates to a method wherein the order of the individual steps consisting of a) and b) are reversed, particularly when the sample fluid is brought into contact with a reagent only during the effects of gravitation or magnetism.

Claims

1. A device for detecting one or more analytes in a sample, the device comprising:

one or more reaction chambers adapted to receive the sample,

optionally, one or more reagent application channels,

one or more capillary systems connected to the reaction chambers or the reagent application channels, and

one or more negative vessels connected to the capillary system or the capillary systems,

wherein each of the capillary systems comprises capillary planes of diminishing cross-section which are disposed one below the other and, each capillary system comprises at least one capillary.

2. The device according to claim 1, wherein in each capillary plane a plurality of capillaries are arranged in an adjoining or bundled fashion.

3. The device according to claim 2, wherein adjoining or bundled capillaries of a capillary plane additionally comprise connecting webs.

4. The device according to claim 2, wherein adjoining or bundled capillaries of a capillary plane have the same inner cross-sectional area.

5. The device according to claim 1, wherein, the more distant the inner cross-sectional area of the capillary planes is disposed from the reaction chamber, the smaller it becomes.

6. The device according to claim 1, wherein the capillary planes of the capillary system are connected by chambers, whose inner cross-sectional area is preferably the same as that of the largest capillary.

7. The device according to claim 1, wherein the reagent application channel has 1.2 times the volume compared with the capillary or the capillary system plus the negative vessel.

8. The device according to claim 1, wherein the negative vessel has a larger volume than a volume of compacted sediment of the cells or particles used.

9. The device according to claim 1, wherein the negative vessel has a shape, which tapers towards the bottom.

10. The device according to claim 1, further comprising one or more ventilation channels.

11. The device according to claim 1, wherein the capillary system forms an integral component of the carrier element.

12. A method for detecting one or more analytes in a sample fluid by the visualization of agglutination, the method comprising the steps of:

a) contacting the sample with a reagent to form a reaction mixture,

b) exposing the reaction mixture to the effects of gravitation or magnetism, and passing the reaction mixture through the capillary system of the device according to claim 1, followed by a negative vessel of the device according to claim 1,

and

c) determining the reaction between the analyte and the reagent.

13. The method according to claim 12, wherein the reaction mixture is brought into contact with a further reagent during process step b).

14. The method according to claim 12, wherein the order of the individual process steps consisting of a) and b) are reversed, in particular when the sample fluid is brought into contact with a reagent only during the action of gravitation or magnetism.

15. The method according to any one of claims 12 to 14, wherein the sample fluid and/or the reagent include one or more particles.

16. The method according to any one of claims 12 to 14, wherein the reaction is determined optically.

17. The method according to claim 15, wherein the particles have a natural color or are colored.

18. The method according to claim 15, wherein the particles are color-, radio-, fluorescent- or enzyme-coded.

19. The method according to claim 15, wherein the particles include erythrocytes and/or thrombocytes and/or leucocytes or parts thereof.

20. The method according to claim 15, wherein the particles are pre-treated with proteolytic enzymes in order to enhance the reaction.

21. The method according to claim 15, wherein the reagent comprises antibodies selected from the group consisting of peptides, proteins, carbohydrates, lipids, nucleic acids, viruses, bacteria, parasites, human cells, animal cells plant cells, and parts thereof bound to the particles.

22. The method according to claim 15, wherein antigens or other ligands are bound to the particles.

23. The method according to claim 15, wherein the particles comprise polystyrene, polybromostyrene, gelatine, melamine, polymerised agarose or polymethyl methacrylate.

24. The method according to claim 15, wherein the particles are magnetic or paramagnetic.

25. The method according to any one of claims 12 to 14, wherein the sample mixture is exposed to gravitation by being subjected to centrifuging.

26. The method according to any one of claims 12 to 14, wherein the sample mixture is exposed to magnetism.

27. The method according to any one of claims 12 to 14, wherein the sample fluid comprises human, animal or plant material.

28. The method according to any one of claims 12 to 14, wherein the reagent comprises antibodies, test cells, synthetic particles, buffers or booster solutions.

29. The method according to any one of claims 12 to 14, wherein glycerin or other molecules are added to the reagent in order to increase the specific density of the solution.

30. The method according to any one of claim 12 to 14 wherein the analyte is at least one of:

blood groups, antibodies against blood group characteristics, compatibilities between stored blood and recipients, thrombocyte characteristics and antibodies directed against thrombocytes, leucocyte characteristics and antibodies directed against leucocytes, haemagglutinating viruses, antibodies against proteins, viruses, bacteria, parasites, viral or bacterial or parasitic or other antigens, auto-antibodies, and antibodies directed against allergens.

31. The method according to claim 22 in which the other ligands are selected from the group consisting of peptides, proteins, carbohydrates, lipids, nucleic acids, viruses, bacteria, parasites, human cells, animal cells, plant cells, allergens, and parts thereof.