Multi-zoned reaction vessel having pressure-actuatable control means between zones

• US 4,426,451 A
• Filed: 01/28/1981
• Issued: 01/17/1984
• Est. Priority Date: 01/28/1981
• Status: Expired due to Term

• Current Assignee: Clinical Diagnostic Systems Inc.
• Original Assignee: Eastman Kodak Company
• Inventors: Columbus, Richard L.
• Primary Examiner(s): Turk, Arnold
• Application Number:
  US06/229,038
• Time in Patent Office: 1,084 Days
• Field of Search: 23/230 R, 23/230 B, 422/50, 422/55, 422/56, 422/57, 422/58, 422/100, 422/102, 422/138, 138/44, 356/246, 436/98, 436/113, 436/177, 436/165, 436/518, 436/531, 436/807, 435/7, 435/4, 435/287
• US Class Current: 436/518
• CPC Class Codes: B01L 2300/0825 Test strips
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: G01N 33/5304 Reaction vessels, e.g. agglutination plates for solid-phase systems G01N33/543
• CPC Class Codes: G01N 33/70 involving creatine or creatinine
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10T 436/147777 Plural nitrogen in the same ring [e.g., barbituates, creatinine, etc.]
• CPC Class Codes: Y10T 436/175383 Ammonia
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A reaction vessel, test device, and method of detection or measurement are disclosed, featuring the use of at least two operatively connected zones formed by transport surfaces spaced apart throughout most of the zones a capillary distance. The zones are fluidly connected by meniscus control means effective to stop capillary flow of the liquid from one zone to the other, until an externally generated actuation pressure is applied.

Claims

1. In a reaction vessel comprising

a first zone,

a second zone adapted to receive liquid flow from the first zone, at least one of said zones containing a reagent capable of interacting with a material of a liquid introduced into said one zone,

said zones comprising a first member, a cover member, and means for disposing said first member and said cover member in superposed relationship,

inlet means permitting the introduction of the liquid into said first zone,

and means providing a passageway fluidly connecting said zones;

the improvement wherein said first and said cover members provide opposed surfaces spaced apart a distance that is effective to induce capillary flow of said introduced liquid at least in the portion of said first zone contiguous to said passageway means, and in said second zone,

and wherein said passageway means includes meniscus control means for stopping the liquid meniscus from proceeding by capillary attraction into said second zone from said first zone, said control means being configured to permit the liquid to flow into said second zone only when an externally generated pressure is applied to the liquid in an amount sufficient to push the liquid meniscus into said second zone.

4. A vessel as defined in claim 1, 2 or 3, and further including sidewall surfaces cooperating with said two surfaces to define said zones, said sidewall surfaces forming in said passageway means an energy barrier to meniscus flow such that the liquid meniscus stops at said barrier.

5. A vessel as defined in claim 4, wherein said sidewall surfaces in said second zone adjacent to said passageway means diverge from said meniscus control means into said second zone at a constant or at an increasing rate.

6. A vessel as defined in claim 5, wherein the rate of divergence between said sidewall surfaces of said second zone increases with distance from said meniscus control means.

7. A vessel as defined in claim 1, 2, or 3, wherein said meniscus control means comprises a pair of opposed ridges in said two opposed surfaces that provide a reduction in said spaced-apart distance.

8. A vessel as defined in claim 7, wherein said distance reduction between said two opposed surfaces increases in rate as said meniscus control means is approached from said inlet means.

9. A vessel as defined in claim 1, 2, or 3, wherein said meniscus control means comprises a channel in at least one of said two opposed surfaces having a depth and width sufficient to stop the meniscus from flowing into said second zone.

10. A vessel as defined in claim 9, wherein said channel depth is at least about 0.02 mm greater than said spaced-apart distance between said two opposed surfaces.

11. A vessel as defined in claim 9, wherein said meniscus control means comprises two opposed channels, one in each of said opposed surfaces, having a combined depth that is at least 0.015 mm greater than said spaced-apart distance between said two opposed surfaces.

12. A vessel as defined in claim 1, 2 or 3, wherein at least said cover member is substantially rigid.

13. A vessel as defined in claim 1, 2, or 3, wherein said distance is effective to induce capillary flow of said introduced liquid from said inlet means to said passageway means.

14. A vessel as defined in claim 1, 2, or 3, and further including sidewall surfaces cooperating with said two surfaces to define said transport zones, said sidewall surfaces and said two surfaces forming said passageway means with a length in the direction of liquid flow therethrough that is no greater than about 0.03 cm.

15. A vessel as defined in claim 4, wherein said energy barrier comprises opposed edges in said sidewall surfaces.

2. In a reaction vessel comprising

a first zone,

a second zone adapted to receive the liquid from the first zone, at least one of said zones containing a reagent capable of interacting with a material of a liquid introduced into said one zone,

said zones comprising a first member, a cover member, and means for disposing said first member and said cover member in superposed relationship,

inlet means permitting the introduction of the liquid into said first zone,

and means providing a passageway fluidly connecting said zones;

the improvement wherein said first and said cover members provide opposed surfaces spaced apart a distance effective to induce capillary flow of said introduced liquid at least in the portion of said first zone contiguous to said passageway means, and in said second zone,

and wherein said passageway means includes meniscus control means for stopping the liquid meniscus from proceeding by capillary attraction into said second zone from said first zone, said control means being configured to permit the liquid to pass into said second zone only when an externally generated pressure is applied to the liquid in an amount sufficient to push the liquid meniscus into said second zone,

said distance of said second zone being less than said distance of said first zone by an amount effective to preferentially attract said liquid, in response to said push of the liquid by the pressure, into said second zone from said first zone and to confine the attracted liquid within the second zone.

3. In a reaction vessel comprising

a first zone,

a second zone adapted to receive the liquid from the first zone, at least one of said zones containing a reagent capable of interacting with a material of a liquid introduced into said one zone,

said zones comprising a first member, a cover member, and means for disposing said first member and said cover member in superposed relationship,

inlet means permitting the introduction of the liquid into said first zone,

and means providing a passageway fluidly connecting said zones;

the improvement wherein said first and said cover members provide opposed surfaces spaced apart a distance effective to induce capillary flow of said introduced liquid at least in the portion of said first zone contiguous to said passageway means, and in said second zone,

at least one of said two surfaces comprising, in both of said zones, a relatively non-wettable material coated with a surfactant soluble in the liquid and capable of making said surfaces wettable by the liquid,

and wherein said passageway means includes meniscus control means for stopping the liquid meniscus from proceeding by capillary attraction into said second zone from said first zone, said control means being configured to permit the liquid to pass into said second zone only when an externally generated pressure is applied to the liquid in an amount sufficient to push the liquid meniscus into said second zone.

16. A test device comprising two opposed transport surfaces and means for spacing them apart a distance to define at least two fluidly connected zones connected by a passageway, said distance being effective to induce capillary flow of introduced liquid in said zones, one of said zones containing inlet means permitting the introduction of a liquid into said one zone, and a reagent immobilized in said one zone, said reagent being capable of binding with a material of the liquid and with a known, labeled amount of said material;

the other of said zones being adapted to receive by said passageway liquid from said one zone and material contained in the liquid that is not bound to said reagent;

and meniscus control means associated with said passageway for stopping a liquid meniscus from proceeding into said other zone from said one zone, said control means being configured to permit the liquid and unbound material to pass into said other zone only when an externally generated pressure is applied to the liquid in an amount sufficient to push said meniscus into said other zone.

17. A device as defined in claim 16, wherein said meniscus control means comprises a pair of opposed ridges in said two surfaces that provide a reduction in said spaced-apart distance.

18. A device as defined in claim 16, wherein said meniscus control means comprises a channel in at least one of said two surfaces having a depth and width sufficient to stop the meniscus from flowing into said other zone.

19. A device as defined in claim 16, wherein at least one of said two surfaces comprises, in both of said zones, a relatively non-wettable material coated with a surfactant soluble in the liquid and capable of making said surfaces wettable by the liquid.

20. A device as defined in claim 16, wherein said means for spacing includes sidewall surfaces cooperating with said two surfaces to define said transport zones connected by said passageway, said sidewall surfaces and said two surfaces forming said passageway with a length in the direction of liquid flow therethrough no greater than about 0.03 cm.

21. A device as defined in claim 16, wherein said material is an immunogen present in a biological liquid, said reagent is the immunogen complement, and said other of said zones is adapted for detection of labeled material.

22. A device as defined in claim 21, wherein both of said zones are adapted for detection of said labeled material.

23. A device as defined in claim 16, wherein said means for spacing includes sidewall surfaces cooperating with said two surfaces to define said zones connected by said passageway, said sidewall surfaces forming in said passageway an energy barrier to meniscus flow such that the meniscus of the liquid stops at said meniscus control means.

24. A device as defined in claim 23, wherein said meniscus control means comprises opposed edges in said sidewall surfaces.

25. A device as defined in claim 16, wherein said spaced-apart distance is effective to induce capillary flow of said introduced liquid at least in the portion of said one zone contiguous to said passageway, and in said other zone.

26. A device as defined in claim 25, wherein said spaced-apart distance of said other zone is less than said spaced-apart distance of said one zone by an amount effective to preferentially attract said liquid in response to said push of the liquid by the pressure into said other zone from said one zone, and to confine the attracted liquid within said other zone.

27. A test device for the measurement of an analyte of whole blood, comprising

two opposed transport surfaces and means for spacing them apart a distance to define at least two fluidly connected zones and a passageway connecting them, said distance being effective to induce capillary flow of introduced liquid in said downstream zone and at least in the portion of the other zone contiguous to said passageway,

one of said zones containing a cell-agglutinating reagent immovably adhered to at least one of (i) said surfaces and (ii) said spacing means, and inlet means permitting the introduction of whole blood into said one zone;

the other of said zones being adapted to receive plasma from said one zone and containing a detection element including at least one detection reagent specific to the analysis of an analyte of the plasma;

and meniscus control means associated with said passageway for stopping the liquid meniscus from proceeding into said other zone from said one zone, said control means being configured to permit the plasma to pass into said other zone only when an externally generated pressure is applied to the liquid in an amount sufficient to push the liquid meniscus into said other zone.

28. A device as defined in claim 27, wherein said means for spacing includes sidewall surfaces cooperating with said two surfaces to define said connected zones connected by said passageway, said sidewall surfaces forming in said passageway an energy barrier to meniscus flow such that the meniscus of the liquid stops at said meniscus control means.

29. A device as defined in claim 27, wherein at least one of said two surfaces comprises, in both of said zones, a relatively non-wettable material coated with a surfactant soluble in the liquid and capable of making said surfaces wettable by the liquid.

30. A device as defined in claim 27, wherein said means for spacing includes sidewall surfaces cooperating with said two surfaces to define said transport zones connected by said passageway, said sidewall surfaces and said two surfaces forming said passageway with a length in the direction of liquid flow therethrough no greater than about 0.03 cm.

31. A device as defined in claim 27, and further including a third zone disposed between said two zones and fluidly connected thereto by two of said meniscus control means.

32. A device as defined in claim 31, wherein said detection element comprises detection reagents sufficient to generate a color change proportional to the amount of plasma ammonia as well as the amount of plasma creatinine that are present in the whole blood.

33. A device as defined in claim 27, wherein said spaced-apart distance is effective to induce capillary flow of said introduced liquid at least in the portion of said one zone contiguous to said passageway, and in said other zone.

34. A device as defined in claim 33, wherein said spaced-apart distance of said other zone is less than said spaced-apart distance of said one zone by an amount effective to preferentially attract said liquid in response to said push of the liquid by the pressure, into said other zone from said one zone and to confine the attracted liquid within said other zone.

35. A method for interacting with a reagent a material contained in a liquid, comprising the steps of

(a) filling with liquid a first zone of a device comprising two adjacent zones fluidly connected by a passageway, both of said zones comprising opposed liquid transport surfaces, two of said surfaces being spaced apart a distance that is effective to induce capillary flow of said introduced liquid at least in the portion of said first zone contiguous to said passageway, and in said second zone, at least one of said zones further including said reagent;

(b) retaining the liquid within said first zone while the reagent interacts with said material; and

thereafter,

(c) applying to the liquid in said first zone an externally generated pressure in an amount sufficient to force the liquid to start flowing under capillary attraction into said second zone, whereby the liquid flows into the second zone.

36. A method of combining together liquid containing a material a portion of which is labeled for detection, and a reagent capable of bonding with said material, and thereafter detecting the amount of labeled material free of said reagent, the method comprising the steps of

(a) flowing under capillary attraction (i) a liquid containing an unknown amount of unlabeled material, and (ii) a liquid containing a known amount of said labeled material, into a first zone of a device comprising two adjacent zones fluidly connected by a passageway, said first zone further including said reagent immobilized therein,

(b) retaining the liquid within said first zone while the reagent binds with and immobilizes some of said labeled material and said unlabeled material;

(c) applying to the liquid in said first zone an externally generated pressure in an amount sufficient to force the material that is free of said reagent to start flowing under capillary attraction into said second zone, and

(d) after the liquid has transferred into said said second zone, detecting the free labeled material in said second zone.

38. A method as defined in claim 36 or 37, wherein said material is an immunogen found in a biological liquid, and said reagent is the complement of said immunogen.

39. A method for determining the amount of unlabeled material in a liquid, comprising the steps (a), (b) and (c) of claim 36 or 37, followed by the steps of

(d) comparing the amount of labeled material detected in said zone against said known amount, and

(e) calculating the amount of unknown, unlabeled material that competed with the labeled material for said reagent.

37. A method of combining together for detection liquid containing a material a portion of which is labeled for detection, and a reagent capable of binding said material, the method comprising the steps of

(a) flowing under capillary attraction an amount of liquid containing (i) an unknown amount of unlabeled material, and (ii) a known amount of said labeled material into a first zone of a device comprising two adjacent zones fluidly connected by a passageway, said first zone further including said reagent immobilized therein,

(b) retaining the liquid within said first zone while the reagent binds with said labeled material and said unlabeled material;

(c) applying to the liquid in said first zone an externally generated pressure in an amount sufficient to force the liquid and material free of said reagent to start flowing under capillary attraction into said second zone, and

(d) after the liquid has transferred into said second zone, detecting the bound, immobilized labeled material in said first zone.

40. A method for determining the amount of an analyte of whole blood in a test device comprising two opposed transport surfaces providing at least two transport zones fluidly connected by a passageway, the first of said zones containing a cell-agglutinating reagent that is incapable of moving out of said first zone, and the second of said zones containing at least one detection reagent specific to said analyte;

the method comprising the steps of

(a) flowing under capillary attraction a quantity of whole blood into the first of said zones;

(b) retaining said quantity of whole blood in said first zone a length of time sufficient to cause blood cells to bind to said cell-agglutinating reagent and thus to separate from the blood plasma;

(c) applying to the zone containing the plasma an externally generated pressure in an amount sufficient to force the plasma, but not the cells, to flow under capillary attraction into the second of said zones, and

(d) detecting within said second zone a radiometric change resulting from the interaction between said at least one detection reagent and said analyte.

41. A method as defined in claim 40, and further including a third zone disposed between and fluidly connected to said two zones, said third zone containing a gas-releasing reagent, and

wherein prior to step (c), the method comprises the additional step of

(b'"'"') applying to the zone containing the liquid an externally generated pressure in an amount sufficient to force the plasma to flow into said third zone, so that gas is released from the plasma before said step (c).

42. In a reaction vessel comprising wall means forming first and second liquid receiving zones, means permitting the introduction of liquid into the first zone, and connecting passageway means for the passage of liquid from the first zone to the second, the improvement wherein

said wall means forming said zones are spaced apart a distance that induces capillary flow of liquid at least in the portion of the first zone contiguous to said passageway means, and in said second zone, and

said passageway means includes means for controlling the meniscus forming the leading edge of the capillary flow so as, first, to halt the passage of liquid into said second zone and, second, to permit flow of liquid into said second zone only when sufficient pressure other than that caused by the hydrostatic head of the liquid is subsequently applied to the liquid that has filled said first zone.