Blood coagulation test cartridge, system, and method

• US 20050255601A1
• Filed: 01/31/2005
• Published: 11/17/2005
• Est. Priority Date: 02/27/2004
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Ericson, Daniel G., Clague, Cynthia T., Nippoldt, Douglas D.
• Granted Patent: US 7,439,069 B2
• Time in Patent Office: Days
• US Class Current: 436/69
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/54
• CPC Class Codes: G01N 33/86 involving blood coagulating time or factors, or their receptors
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A system and method for determining a coagulation time, e.g., thrombin time, PT, aPTT, and ACT, of a blood sample deposited in a test cartridge is disclosed. The test cartridge comprises a blood receptacle that is open to the atmosphere into which a blood sample is to be deposited, a vacuum port that is open to atmosphere, and a spiral capillary within the test cartridge having a capillary length and cross-section area, a first capillary end of the spiral capillary open to the blood receptacle and a second capillary end of the spiral capillary open to the vacuum port, whereby the spiral capillary is closed to atmosphere. When a blood sample is deposited in the blood receptacle, a vacuum is drawn through the vacuum port and the blood is drawn through the spiral capillary until coagulation occurs. A pressure change is detected, and the coagulation time is measured.

Claims

1. A system for performing a test on a blood sample determining a coagulation time comprising:

a test cartridge comprising a blood receptacle that is open to the atmosphere into which a blood sample is to be deposited, a vacuum port that is open to atmosphere, and a spiral capillary within the test cartridge having a capillary length and cross-section area, a first capillary end of the spiral capillary open to the blood receptacle and a second capillary end of the spiral capillary open to the vacuum port, whereby the spiral capillary is closed to atmosphere; and

a vacuum applicator having a vacuum applicator port adapted to be fitted to the vacuum port to close the vacuum port from atmosphere and further comprising;

a vacuum applicator housing enclosing a vacuum chamber and extending between the vacuum applicator port and a vacuum cylinder;

a piston fitted within the vacuum cylinder;

a drive motor coupled to the piston adapted to be powered upon deposition of the blood sample in the blood receptacle to move the piston at a predetermined fixed rate within the vacuum cylinder that creates a vacuum in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that blocks further blood aspiration;

a pressure sensor coupled to the vacuum chamber that is operable to measure the vacuum within the vacuum chamber and develop an air pressure signal during movement of the piston;

a pressure change detection circuit for comparing successive pressure signals to detect a change in pressure occurring when a blood clot blocks aspiration of blood through the spiral capillary and generate a clot detection signal; and

a timer for timing the elapsed time from the commencement of the vacuum and generation of a clot detection signal, thereby determining a coagulation time.

2. The system of claim 1, wherein the test cartridge is substantially transparent to enable visual verification of aspiration of blood along the spiral capillary.

3. The system of claim 2, wherein the test cartridge is formed of a cartridge housing having a substantially prismatic shape with first and second major sides and a minor sidewall extending between the first and second major sides and maintaining the first and second major sides in substantially parallel relation.

4. The system of claim 3, wherein the blood receptacle is formed in a receptacle portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side.

5. The system of claim 4, wherein the vacuum port is formed in a port portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side.

6. The system of claim 5, wherein the spiral capillary is formed in a capillary portion of the cartridge housing between the first and second major sides surrounding the vacuum port.

7. The system of claim 3, wherein:

the blood receptacle is formed in a receptacle portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side, and a blood mixing impeller is supported in the blood receptacle; and

further comprising a mixing motor adapted to engage the impeller to mix the blood sample deposited in the blood receptacle.

8. The system of claim 7, wherein one of a reagent and a coagulent is deposited in the blood receptacle to be mixed and react with the blood sample to facilitate performance of the test.

9. The system of claim 1, wherein:

the test cartridge includes a blood mixing impeller supported in the blood receptacle; and

further comprising a mixing motor adapted to engage the impeller to mix and the blood sample deposited in the blood receptacle.

10. The system of claim 9, wherein one of a reagent and a coagulant is deposited in the blood receptacle to be mixed and react with the blood sample to facilitate performance of the test on a blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), and activated clotting time (ACT).

11. The system of claim 1, wherein one of a reagent and a coagulent is deposited in the blood receptacle to react with the blood sample to facilitate performance of a test on the blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), and activated clotting time (ACT).

12. The system of claim 11, wherein the reagent or coagulant is selected from the group consisting of kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin or other activating reagents or protamine or other deactivating reagents.

13. The system of claim 1, wherein one of a reagent and a coagulent is deposited along the spiral capillary to react with the blood sample to facilitate performance of a test on the blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), and activated clotting time (ACT).

14. The system of claim 13, wherein the reagent or coagulent is selected from the group consisting of kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin or other activating reagents or protamine or other deactivating reagents.

15. The system of claim 1, wherein the spiral capillary has a cross-section in the range of about 0.2 mm² to about 2.0 mm², and preferably about 1.0 mm.

16. The system of claim 1, wherein the spiral capillary has a length in the range of about 100 mm to about 1000 mm.

17. The system of claim 1, wherein the predetermined fixed rate of movement of the piston within the vacuum cylinder is in the range of about 0.01 ml/min to about 10 ml/min.

18. The system of claim 17, wherein the vacuum drawn in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that increases the pressure rate of change significantly.

19. The system of claim 1, wherein the vacuum drawn in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed increases the pressure rate of change significantly.

20. The system of claim 18, wherein the rate of change in vacuum occurring when a blood clot forms in the spiral capillary increases significantly.

21. A method of performing a test on a blood sample determining a coagulation time comprising:

providing a test cartridge comprising a blood receptacle that is open to the atmosphere into which a blood sample is to be deposited, a vacuum port that is open to atmosphere, and a spiral capillary within the test cartridge having a capillary length and cross-section area, a first capillary end of the spiral capillary open to the blood receptacle and a second capillary end of the spiral capillary open to the vacuum port, whereby the spiral capillary is closed to atmosphere;

depositing a blood sample in the blood receptacle;

drawing a vacuum through the vacuum port that creates a vacuum in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that blocks further blood aspiration;

measuring the vacuum drawn within the spiral capillary as blood is aspirated along the spiral capillary;

detecting a change in the measured vacuum upon formation of a blood clot that blocks further blood aspiration; and

timing the elapsed time between the commencement of the vacuum and detection of the change, thereby determining a coagulation time.

22. The method of claim 21, wherein the test cartridge is substantially transparent to enable visual verification of aspiration of blood along the spiral capillary.

23. The method of claim 22, wherein the test cartridge is formed of a cartridge housing having a substantially prismatic shape with first and second major sides and a minor sidewall extending between the first and second major sides and maintaining the first and second major sides in substantially parallel relation.

24. The method of claim 23, wherein the blood receptacle is formed in a receptacle portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side.

25. The method of claim 24, wherein the vacuum port is formed in a port portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side.

26. The method of claim 25, wherein the spiral capillary is formed in a capillary portion of the cartridge housing between the first and second major sides surrounding the vacuum port.

27. The method of claim 23, wherein the blood receptacle is formed in a receptacle portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side, and a blood mixing impeller is supported in the blood receptacle;

and further comprising;

operating a mixing motor to rotate the impeller to mix the blood sample deposited in the blood receptacle.

28. The method of claim 27, wherein one of a reagent and a coagulent is deposited in the blood receptacle to be mixed and react with the blood sample to facilitate performance of the test.

29. The method of claim 21, wherein the test cartridge includes a blood mixing impeller supported in the blood receptacle, and further comprising:

operating a mixing motor to rotate the impeller to mix and the blood sample deposited in the blood receptacle.

30. The method of claim 29, wherein one of a reagent and a coagulent is deposited in the blood receptacle to be mixed and react with the blood sample to facilitate performance of the test.

31. The method of claim 21, wherein one of a reagent and a coagulent is deposited in the blood receptacle to react with the blood sample to facilitate performance of a test on the blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), activated clotting time (ACT).

32. The method of claim 31, wherein the reagent or coagulent is selected from the group consisting of kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin or other activating reagents or protamine or other deactivating reagents.

33. The method of claim 21, wherein one of a reagent and a coagulent is deposited along the spiral capillary to react with the blood sample to facilitate performance of a test on the blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), activated clotting time (ACT).

34. The method of claim 33, wherein the reagent or coagulent is selected from the group consisting of kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin or other activating reagents or protamine or other deactivating reagents.

35. The method of claim 21, wherein the spiral capillary has a cross-section in the range of about 0.2 mm² to about 2.0 mm², and preferably about 1.0 mm.

36. The method of claim 21, wherein the spiral capillary has a length in the range of about 100 mm to about 1000 mm.

37. The method of claim 21, wherein the predetermined fixed rate of movement of the piston within the vacuum cylinder is in the range of about 0.01 ml/min to about 10 ml/min.

38. The method of claim 37, wherein the vacuum drawn in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that increases the pressure rate of change significantly.

39. The method of claim 21, wherein the vacuum drawn in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed increases the pressure rate of change significantly.

40. The method of claim 21, wherein the vacuum drawing step comprises:

applying a vacuum applicator port of a vacuum applicator to the vacuum port of the cartridge to close the vacuum port from atmosphere, the vacuum applicator further comprising a vacuum applicator housing enclosing a vacuum chamber and extending between the vacuum applicator port and a vacuum cylinder and a piston fitted within the vacuum cylinder adapted to be moved along the vacuum cylinder by a drive motor; and

operating the drive motor coupled to the piston upon deposition of the blood sample in the blood receptacle to move the piston at a predetermined fixed rate within the vacuum cylinder that creates a vacuum in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that blocks further blood aspiration.

41. The method of claim 40, wherein the measuring step comprises:

coupling a pressure sensor to the vacuum chamber; and

operating the pressure sensor to measure the vacuum within the vacuum chamber and develop an air pressure signal during movement of the piston.

42. The method of claim 41, wherein:

the detecting step comprises comparing successive pressure signals to detect a change in vacuum occurring when a blood clot blocks aspiration of blood through the spiral capillary and generate a clot detection signal; and

the timing step comprises timing the elapsed time between the deposition of the blood sample in the blood receptacle and generation of a clot detection signal, thereby determining one of thrombin time, PT, aPTT, and ACT.

43. The method of claim 42, wherein the vacuum drawn in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed increases the pressure rate of change significantly.

44. A system for of performing a test on a blood sample determining a coagulation time comprising:

a test cartridge comprising a blood receptacle that is open to the atmosphere into which a blood sample is to be deposited, a vacuum port that is open to atmosphere, and a spiral capillary within the test cartridge having a capillary length and cross-section area, a first capillary end of the spiral capillary open to the blood receptacle and a second capillary end of the spiral capillary open to the vacuum port, whereby the spiral capillary is closed to atmosphere;

means operable after deposition of a blood sample in the blood receptacle for drawing a vacuum through the vacuum port that creates a vacuum in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that blocks further blood aspiration;

means for measuring the vacuum drawn within the spiral capillary as blood is aspirated along the spiral capillary;

means for detecting a change in the measured vacuum upon formation of a blood clot that blocks further blood aspiration; and

means for timing the elapsed time between the commencement of the vacuum and detection of the change, thereby determining a coagulation time.

45. The system of claim 44, wherein the means for drawing a vacuum comprises:

a vacuum applicator comprising a vacuum applicator housing enclosing a vacuum chamber and extending between the vacuum applicator port adapted to be coupled to the vacuum port of the cartridge to close the vacuum port from atmosphere and a vacuum cylinder and a piston fitted within the vacuum cylinder adapted to be moved along the vacuum cylinder by a drive motor; and

means for operating the drive motor coupled to the piston upon deposition of the blood sample in the blood receptacle to move the piston at a predetermined fixed rate within the vacuum cylinder that creates a vacuum in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that blocks further blood aspiration.

46. The system of claim 45, wherein the measuring means comprises:

a pressure sensor coupled to the vacuum chamber; and

means for operating the pressure sensor to measure the vacuum within the vacuum chamber and develop an air pressure signal during movement of the piston.

47. The system of claim 46, wherein:

the detecting means compares successive pressure signals to detect a change in vacuum occurring when a blood clot blocks aspiration of blood through the spiral capillary and generate a clot detection signal; and

the timing means times the elapsed time between the deposition of the blood sample in the blood receptacle and generation of a clot detection signal, thereby determining one of thrombin time, PT, aPTT, and ACT.

48. The system of claim 44, wherein the test cartridge is substantially transparent to enable visual verification of aspiration of blood along the spiral capillary.

49. The system of claim 47, wherein the test cartridge is formed of a cartridge housing having a substantially prismatic shape with first and second major sides and a minor sidewall extending between the first and second major sides and maintaining the first and second major sides in substantially parallel relation.

50. The system of claim 49, wherein the blood receptacle is formed in a receptacle portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side.

51. The system of claim 50, wherein the vacuum port is formed in a port portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side.

52. The system of claim 51, wherein the spiral capillary is formed in a capillary portion of the cartridge housing between the first and second major sides surrounding the vacuum port.

53. The system of claim 44, wherein:

the blood receptacle is formed in a receptacle portion of the cartridge housing between the first and second major sides and is open to atmosphere through the first major side, and a blood mixing impeller is supported in the blood receptacle; and

further comprising a mixing motor adapted to engage the impeller to mix the blood sample deposited in the blood receptacle.

54. The system of claim 53, wherein one of a reagent and a coagulent is deposited in the blood receptacle to be mixed and react with the blood sample to facilitate performance of the test.

55. The system of claim 44, wherein one of a reagent and a coagulent is deposited in the blood receptacle to react with the blood sample to facilitate performance of a test on the blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), activated clotting time (ACT).

56. The system of claim 55, wherein the reagent or coagulent is selected from the group consisting of kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin or other activating reagents or protamine or other deactivating reagents.

57. The system of claim 44, wherein one of a reagent and a coagulant is deposited along the spiral capillary to react with the blood sample to facilitate performance of a test on the blood sample determining one of thrombin time, prothrombin time (PT), partial thromboplastin time (aPTT), activated clotting time (ACT).

58. The system of claim 57, wherein the reagent or coagulent is selected from the group consisting of kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin or other activating reagents or protamine or other deactivating reagents.

59. The system of claim 44, wherein the spiral capillary has a cross-section in the range of about 0.2 mm² to about 2.0 mm², and preferably about 1.0 mm².

60. The system of claim 44, wherein the spiral capillary has a length in the range of about 100 mm to about 1000 mm.

61. The system of claim 44, wherein the predetermined fixed rate of movement of the piston within the vacuum cylinder is in the range of about 0.01 ml/min to about 10 ml/min.

62. The system of claim 44, wherein the vacuum drawn in the spiral capillary sufficient to aspirate the blood in the receptacle along the spiral capillary toward the vacuum port until a blood clot is formed that increases the pressure rate of change significantly.