Apparatus for assaying viscosity changes in fluid samples and method of conducting same

• US 5,628,961 A
• Filed: 03/30/1995
• Issued: 05/13/1997
• Est. Priority Date: 10/28/1993
• Status: Expired due to Term

• Current Assignee: Abbott Point Of Care Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: i STAT Corporation (Abbott Laboratories Incorporated)
• Inventors: Davis, Graham, Zelin, Michael P., Lauks, Imants R.
• Primary Examiner(s): Redding, David A.
• Application Number:
  US08/413,836
• Time in Patent Office: 775 Days
• Field of Search: 422/73, 422/63, 422/81, 422/82.02, 422/82.05, 436/66, 436/69, 23/54.04, 23/54.07, 23/64.41, 23/64.43, 435/286.5, 435/287.3, 435/288.7
• US Class Current: 422/63
• CPC Class Codes: G01N 11/04 through a restricted passage, e.g. tube, aperture
• CPC Class Codes: G01N 2474/20 Immunohistochemistry assay
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• CPC Class Codes: Y10S 435/975 Kit
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property
• CPC Class Codes: Y10S 436/807 Apparatus included in process claim, e.g. physical support structures
• CPC Class Codes: Y10S 436/816 Alkaloids, amphetamines, and barbiturates
• CPC Class Codes: Y10S 436/901 Drugs of abuse, e.g. narcotics, amphetamine
• CPC Class Codes: Y10T 436/115831 Condition or time responsive
• CPC Class Codes: Y10T 436/12 Condition responsive control
• CPC Class Codes: Y10T 436/14 Heterocyclic carbon compound [i.e. , O, S, N, Se, Te, as only ring hetero atom]
• CPC Class Codes: Y10T 436/141111 Diverse hetero atoms in same or different rings [e.g., alkaloids, opiates, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

The present invention relates to an apparatus for conducting a variety of assays that are responsive to a change in the viscosity of a sample fluid and relates to methods of conducting such assays. In particular, the present invention is related to the use of a cartridge for conducting one or more coagulation assays or, conversely, fibrinolysis assays. The disclosed device enjoys simplicity and is adaptable to the point-of-care clinical diagnostic area, including use in accident sites, emergency rooms, surgery or intensive care units.

Claims

1. A cartridge for measuring a change in the viscosity of a fluid sample comprising:

(a) a housing capable of being charged with a fluid sample and equipped with a sample displacement means for applying a force against said fluid sample effective to displace at least a portion of said fluid sample within said housing;

(b) at least one reagent, contained within said housing, capable after contact with said fluid sample of promoting a change in the viscosity of said fluid sample;

(c) at least one sensing means, contained within said housing, capable of detecting the displacement of said fluid sample.

2. The cartridge of claim 1 in which said housing is equipped with one or more connecting means for engaging said housing with one or more mechanical, electronic or optical devices.

3. The cartridge of claim 2 in which one said device comprises an external reading device.

4. The cartridge of claim 2 in which one said device comprises a sample retaining means capable of charging said housing with said fluid sample.

5. The cartridge of claim 4 in which said sample retaining means includes a fluid sampling means.

6. The cartridge of claim 1 which further comprises a sample retaining means that forms an integral part of said housing.

7. The cartridge of claim 6 in which said sample retaining means retains said fluid sample out of contact with said sensing means and said reagent.

8. The cartridge of claim 1 in which said sample displacement means comprises a pump means that forms an integral part of said housing.

9. The cartridge of claim 1 or 8 in which said sample displacement means is capable of applying said force against said fluid sample such that at least a portion of said fluid sample is displaced across said sensing means.

10. The cartridge of claim 9 in which said force is reversible, such that at least a portion of said fluid sample is displaced back and forth across said sensing means in a substantially reciprocating manner.

11. The cartridge of claim 1 or 8 in which said displacement causes said fluid sample to come in contact with said reagent.

12. The cartridge of claim 1 in which said sensing means is capable of detecting electrical changes in a fluid.

13. The cartridge of claim 1 in which said sensing means is capable of detecting the position of the interface between a gas and a liquid.

14. The cartridge of claim 13 in which said liquid is said fluid sample or a calibrant.

15. The cartridge of claim 12 in which said sensing means comprises a conductivity sensor.

16. The cartridge of claim 12, 13 or 15 in which said sensing means is microfabricated.

17. The cartridge of claim 16 in which said sensing means comprises a conductivity sensor.

18. The cartridge of claim 17 in which said sensor comprises a pair of metal electrodes.

19. The cartridge of claim 18 in which said metal is a noble metal selected from the group consisting of gold, platinum, and iridium.

20. The cartridge of claim 18 in which said pair of electrodes is arranged in a configuration that is substantially parallel to the fluid sample flow.

21. The cartridge of claim 18 in which said pair of electrodes is arranged in a configuration that is substantially orthogonal to the fluid sample flow.

22. The cartridge of claim 18 having a variable distance between said electrodes of said pair.

23. The cartridge of claim 22 in which the distance between said pair of electrodes at the distal end of said sensor is substantially reduced relative to the distance at the proximal end of said sensor.

24. The cartridge of claim 1 in which said reagent is for an assay selected from the group consisting of prothrombin time (PT), partial thromboplastin time (PTT), activated partial thromboplastin time (APTT), thrombin clotting time (TCT), activated clotting time (ACT), and fibrinogen assay.

59. The cartridge of claim 1, 25, 26, or 54 which further comprises a calibrant fluid, contained in said housing, at least a portion of which may be displaced across said sensor to calibrate same.

60. The cartridge of claim 59 in which said calibrant fluid is in fluid communication with said fluid or blood sample, such that the displacement of said fluid or blood sample results in the displacement of at least a portion of said calibrant fluid across said sensor.

61. The cartridge of claim 60 in which at least a portion of said calibrant fluid is displaced back and forth across said sensor in a substantially reciprocating manner.

62. The cartridge of claim 1, 25, 26 or 54 in which at least one element of said cartridge may be attached or detached in modular form.

25. A cartridge for measuring a change in the viscosity of a fluid sample comprising:

(a) a housing capable of being charged with a fluid sample and equipped with a pump means capable of applying a force against said fluid sample effective to displace said fluid sample within said housing;

(b) at least one reagent, contained within said housing, capable after contact with said fluid sample of promoting a change in the viscosity of said fluid sample;

(c) at least one sensing means, contained within said housing, capable of detecting the displacement of said fluid sample.

27. The cartridge of claim 25 or 26 which further comprises at least one conduit connecting said fluid sample to said sensing means.

28. The cartridge of claim 27 in which said reagent is located in said conduit.

29. The cartridge of claim 27 in which at least two conduits are connected to said fluid sample, at least one of which conduits is connected to said sensing means.

30. The cartridge of claim 29 in which the same reagent is located in each conduit.

31. The cartridge of claim 29 in which a different reagent is located in each conduit.

32. The cartridge of claim 25 or 26 in which said sensing means comprises a conductivity sensor.

33. The cartridge of claim 25 or 26 in which said sensing means is capable of sensing the fluid sample oscillation frequency, amplitude or changes therein.

48. The cartridge of claim 25 or 26 in which said pump means comprises a resilient diaphragm in fluid communication with said sample retaining means.

49. The cartridge of claim 48 in which said diaphragm is equipped with an internal spring to promote the rapid, reproducible compression and decompression of said diaphragm.

50. The cartridge of claim 48 in which said diaphragm is equipped with an internal sponge to promote the rapid, reproducible compression and decompression of said diaphragm.

51. The cartridge of claim 25 or 26 in which said sensing means provides a signal to an external reading device that actuates a plunger for compressing and decompressing said diaphragm.

52. The cartridge of claim 51 in which said sensing means is a conductivity sensor and said signal relates to the conductivity output of said sensor whereby an output below a first preselected conductivity value causes said reading device to actuate said plunger to compress said diaphragm and an output above a second preselected conductivity value causes said reading device to actuate said plunger to decompress said diaphragm.

53. The cartridge of claim 52 in which said first and second preselected values are the same.

26. A cartridge for measuring a change in the viscosity of a fluid sample comprising:

(a) a housing equipped with (i) sample retaining means capable of being charged with a fluid sample, and (ii) pump means capable of applying a force against said fluid sample contained in said sample retaining means effective to displace at least a portion of said fluid sample within said housing;

(b) at least one reagent, contained within said housing, capable after contact with said fluid sample of promoting a change in the viscosity of said fluid sample;

(c) at least one sensing means, contained within said housing, capable of detecting the displacement of said fluid sample.

34. The cartridge of claim 26 in which said reagent includes a reagent for a fluid coagulation test.

35. The cartridge of claim 26 in which said reagent includes a reagent for a fluid agglutination assay.

36. The cartridge of claim 26 in which said reagent includes a reagent for an immunoassay.

37. The cartridge of claim 26 in which said reagent includes a reagent for an activated partial thromboplastin time (APTT).

38. The cartridge of claim 26 in said reagent includes a reagent for a prothrombin time (PT).

39. The cartridge of claim 26 in which said reagent includes a reagent for an activated clotting time (ACT).

40. The cartridge of claim 37 in which said reagent comprises calcium and a phospholipid.

41. The cartridge of claim 38 in which said reagent comprises calcium and tissue thromboplastin.

42. The cartridge of claim 39 in which said reagent comprises a particulate material selected from the group consisting of kaolin, diatomaceous earth, celite, finely divided glass or mixtures thereof.

43. The cartridge of claim 26 in which said reagent is formulated to promote its dissolution in said fluid sample.

44. The cartridge of claim 43 in which said formulation includes an additive that promotes the dissolution of said reagent in said fluid sample.

45. The cartridge of claim 44 in which said additive is selected from the group consisting of salts, gelatins, and saccharides.

46. The cartridge of claim 26 in which said reagent is established into said housing in a manner that promotes the dissolution of said reagent in said fluid sample.

47. The cartridge of claim 46 in which said reagent is established as microdroplets from a microsyringe.

63. The cartridge of claim 26 or 54 in which said sample retaining means may be attached or detached in modular form.

64. The cartridge of claim 63 in which said sample retaining means may be used, detached from said cartridge, to collect said fluid or blood sample.

54. A cartridge for conducting a blood test comprising:

(a) a housing equipped with (i) sample retaining means capable of being charged with a blood sample, and (ii) pump means capable of applying a force against said blood sample contained in said sample retaining means effective to displace at least a portion of said blood sample within said housing;

(b) at least one reagent, contained within said housing, capable after contact with said blood sample of promoting a change in the viscosity of said blood sample;

(c) at least one sensing means comprising a conductivity sensor, contained within said housing, capable of detecting the displacement of said blood sample, said pump means capable of reversibly applying said force such that at least a portion of said blood sample is displaced back and forth across said sensor in a substantially reciprocating manner.

55. The cartridge of claim 54 in which said test provides a prothrombin time and said reagent is a mixture comprising thromboplastin and calcium ions.

56. The cartridge of claim 54 in which said test provides an activated partial thromboplastin time and said reagent is a mixture comprising phospholipid and calcium ions.

57. The cartridge of claim 54 in which said test comprises a fibrinolysis test land said reagent is capable of promoting the coagulation or partial coagulation of said blood sample.

58. The cartridge of claim 57 in which said pump means is capable of maintaining said reversibly applied force against said coagulated or partially coagulated blood sample until fibrinolytic processes cause said coagulated or partially coagulated blood sample to become less viscous, allowing increased displacement of at least a portion of said lysed blood sample across said sensor.

65. A cartridge for facilitating the measurement of a change in the viscosity of a fluid sample comprising:

(a) a housing capable of being charged with a fluid sample and equipped with a sample displacement means for applying a force against said fluid sample effective to displace at least a portion of said fluid sample within said housing;

(b) at least one reagent, contained within said housing, capable after contact with said fluid sample of promoting a change in the viscosity of said fluid sample;

(c) at least one region, defined within said housing, in which the position of the interface of said fluid sample and air can be monitored as said interface moves with the displacement of said fluid sample.

66. The cartridge of claim 65 in which said region comprises a transparent window through which the position of said interface may be determined by optical detection means.

67. The cartridge of claim 66 in which said optical detection means comprises a light detector positioned on one face of said housing.

68. The cartridge of claim 67 in which said optical detection means further comprises a light source positioned on the face of said housing opposite said light detector.

69. The cartridge of claim 66 in which said transparent window is equipped with a reflective material that allows the position of said interface to be determined by an optical detection means comprising a light detector and a light source positioned on the same face of said housing.

70. The cartridge of claim 69 in which said reflective material comprises a mirror.