Combination reagent holding and test device

• US 5,888,826 A
• Filed: 11/25/1997
• Issued: 03/30/1999
• Est. Priority Date: 06/30/1994
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Dade Behring, Inc. (Siemens AG)
• Inventors: Ostgaard, Roy, Stone, Thomas R., Schoenberg, Stephen, Geiselman, Ted S., Kundu, Sourav K.
• Primary Examiner(s): Snay, Jeffrey
• Assistant Examiner(s): CARRILLO, BIBI SHARIDAN
• Application Number:
  US08/976,833
• Time in Patent Office: 490 Days
• Field of Search: 436/69, 436/70, 422/58, 422/61, 422/73, 422/82.05, 422/101, 422/102
• US Class Current: 436/69
• CPC Class Codes: B01L 3/502 with fluid transport, e.g. in multi-compartment structures centrifugal-type cuvettes G01N21/07; analysis by separation into components G01N30/00; automatic analysers G01N35/00
• CPC Class Codes: G01N 2035/00148 Test cards, e.g. Biomerieux or McDonnel multiwell test cards
• CPC Class Codes: G01N 35/1079 with means for piercing stoppers or septums

Abstract

The present invention provides novel test cartridges for use in the assay of liquid samples and methods of carrying out such assays. These test cartridges are particularly useful in assays which include at least one step during which the sample to be assayed and one or more components of the assay system are kept separated by a pierceable member. The test cartridges comprise a housing through which the sample flows during the assay. The housing includes a holding chamber for holding the sample and a test chamber separated by a pierceable member having a cut therein. The test chamber further includes a partition member which has an opening therethrough and includes at least one reagent for the assay. A transfer member movably mounted in the test chamber can move towards and pierce the pierceable member by moving through the cut and contact the liquid sample in the holding chamber. When the transfer member has been moved towards and pierces the pierceable member to contact the liquid sample and a negative pressure is created in the test chamber, liquid sample moves through the transfer member, into the test chamber and through the opening in the partition member.

Claims

1. A test cartridge for use in blood coagulation, enzyme immunoassays, cell ligand, cell-cell interactions, and platelet aggregation assays of a liquid sample, the test cartridge comprising a housing through which the liquid sample flows during the assay, the housing defining:

(a) a test chamber and a holding chamber for holding a liquid sample, wherein the holding chamber and test chamber are separated by a pierceable member having a cut therein;

(b) a partition member disposed in the test chamber, the member having an opening there through and comprising at least one reagent for the assay; and

(c) a transfer member movably mounted in the test chamber so that it can be moved towards and pierce the pierceable member by moving through the cut and contact the liquid sample in the holding chamber;

whereby when the transfer member has moved towards and pierces the pierceable member to contact the liquid sample and a negative pressure is created in the test chamber, liquid sample moves through the transfer member, into the test chamber and through the opening in the partition member.

2. A test cartridge in accordance with claim 1, further comprising a sample cup movably supported within the test chamber and a vacuum means sealably mating with said sample cup, whereby when said sample cup and said vacuum means exerts a downward pressure on the transfer member, said transfer member moves towards and pierces the pierceable member.

3. A test cartridge in accordance with claim 1, further comprising the partition member disposed in the sample cup.

4. A test cartridge in accordance with claim 1, wherein at least one reagent is collagen, an antigen, an antibody or a ligand for binding cells.

5. A test cartridge in accordance with claim 1, wherein the partition member comprises a porous material.

6. A test cartridge in accordance with claim 5, wherein the porous partition member comprises a porous material having an aperture and having incorporated therein at least one agent which initiates a blood coagulation process or platelet aggregation in blood.

7. A test cartridge according to claim 6, wherein the agent which initiates the blood coagulation process comprises at least one activator of the extrinsic or intrinsic pathways of prothrombin conversion.

8. A test cartridge according to claim 4, wherein the activator of the extrinsic or intrinsic pathways of prothrombin conversion comprises a thromboplastin reagent or an activated cephaloplastin reagent.

9. A porous partition member according to claim 8, wherein the thromboplastin reagent comprises THROMBOPLASTIN-C®

and the activated cephaloplastin reagent comprises ACTIN®

.

10. A test cartridge according to claim 6, wherein the agent which initiates platelet aggregation in blood comprises ADP, ristocetin, arachidonic acid, thrombin, epinephrine, platelet activator factor (PAF), or thrombin receptor agonist peptide (TRAP).

11. A test cartridge according to claim 10, further comprising collagen.

12. A test cartridge according to claim 6, wherein the porous partition member comprises a membrane, ceramic, nylon, polypropylene, polyvinylidene fluoride or fiberglass.

13. A test cartridge according to claim 6, wherein the membrane comprises a mixed cellulose ester membrane.

14. A test cartridge according to claim 1, wherein the holding chamber is L-shaped and a portion of the holding chamber is angled to form a bottom portion so that liquid sample placed in the holding chamber flows downwardly into the bottom portion of the holding chamber.

15. A test cartridge according to claim 14, wherein the bottom portion of the holding chamber comprises a material which is capable of enhancing heat transfer.

16. A test cartridge according to claim 1, wherein the housing further comprises a removable seal located on an upper surface of the housing which seals both holding and test chambers.

17. A test cartridge according to claim 16, wherein a portion of the removable seal disposed towards an interior portion of the housing is provided with a desiccant.

18. A test cartridge according to claim 1, wherein the housing further comprises a flange located on an upper surface of the housing, the flange having a type sense code thereon.

24. A test cartridge according to claim 13, wherein the mixed cellulose ester membrane comprises acetate and nitrate.

19. A test cartridge for use in an assay system for testing a coagulation function of blood, the test cartridge comprising a housing through which the blood flows, wherein the housing defines:

(a) a test chamber and a holding chamber for holding a sample of the blood to be tested, wherein the holding chamber and test chamber are separated by a pierceable member having a cut therein;

(b) a partition member disposed in the test chamber, the partition member having an opening there through and containing at least one reagent which activates at least one pathway of the coagulation of blood;

(c) a transfer member movably mounted in the test chamber so that it can be moved towards and pierce the pierceable member by moving through the cut; and

(d) a receiving chamber disposed in the test chamber between the partition member and the transfer member for receiving blood from the transfer member;

whereby when blood is disposed in the holding chamber and the transfer member has been moved towards and pierces the pierceable member to contact the blood and a negative pressure is created in the test chamber, blood moves through the transfer member into the receiving chamber and through the opening in the partition member.

20. A test cartridge according to claim 19, wherein the reagent comprises at least one activator of the extrinsic or intrinsic pathways of prothrombin conversion.

21. A test cartridge according to claim 20, wherein the activator of the extrinsic or intrinsic pathways of prothrombin conversion comprises a thromboplastin reagent or activated cephaloplastin reagent.

22. A test cartridge according to claim 21, wherein the thromboplastin reagent comprises THROMBOPLASTIN-C®

and the activated cephaloplastin reagent comprises ACTIN®

.

23. A method of testing platelet function which comprises passing blood through a test cartridge, the test cartridge comprising a housing through which the blood flows during the assay, wherein the housing defines:

(a) a test chamber and a holding chamber for holding a sample of the blood to be tested, wherein the holding chamber and test chamber are separated by a pierceable member having a cut therein;

(b) a partition member disposed in the test chamber, the partition member having an opening therethrough and containing at least one reagent which activates the aggregation of platelets;

(c) a transfer member movably mounted in the test chamber, wherein said transfer member can be moved towards and pierce the pierceable member by moving through the cut; and

(d) a receiving chamber disposed in the test chamber between the partition member and the transfer member for receiving blood from the transfer member;

wherein the method comprises the steps of;

(i) providing a sample of blood to the holding chamber;

(ii) preincubating the sample under predetermined conditions;

(iii) moving the transfer member towards and through the pierceable member by moving it through the cut and into contact with the blood in the holding chamber;

(iv) causing the pressure in the test chamber to become sufficiently negative to cause blood to flow through the transfer member into the receiving chamber and through the opening in the partition member;

(v) measuring the amount of time it takes for the formation of a platelet plug at the opening in the partition member thereby stopping the flow of blood; and

(vi) correlating the time determined in step (v) with a predetermined value.