Blood coagulation test cartridge, system, and method

• US 20050233466A1
• Filed: 07/15/2004
• Published: 10/20/2005
• Est. Priority Date: 04/19/2004
• Status: Active Grant

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Wright, David W., Cheek, Daniel S., Kriewall, Timothy J.
• Granted Patent: US 7,399,637 B2
• Time in Patent Office: Days
• US Class Current: 436/165
• CPC Class Codes: G01N 11/14 by using rotary bodies, e.g. vane G01N11/16 takes precedence
• CPC Class Codes: G01N 11/16 by measuring damping effect upon oscillatory body
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56
• CPC Class Codes: Y10T 436/111666 Utilizing a centrifuge or compartmented rotor

Abstract

A system and method for determining a coagulation time, e.g., TT, PT, aPTT, and ACT, of a blood test sample deposited in a test cartridge is disclosed. A cartridge housing having upper and lower major sides and a minor sidewall encloses a test chamber having a test chamber pivot element and is provided with a cartridge port for introducing a test sample into the test chamber,. Ferromagnetic agitator vane leaflets extend from an agitator pivot element supported by the test chamber pivot element intermediate the upper and lower major sides for rotational motion. The agitator vane leaflets can be swept, in response to an external magnetic field, through the test sample in the absence of coagulation. A timer is started when the agitator movement is commenced whereupon the agitator moves freely. Resistance to agitator movement due to coagulation is detected, and the coagulation time is measured.

Claims

1. A system that performs a test on a biologic test sample to determine a coagulation test time comprising:

a test cartridge formed of a cartridge housing having at least one test chamber therein into which a test sample is deposited to be tested and an agitator mounted at a pivot point in the test chamber having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber; and

a test instrument having an instrument housing including a cartridge receptacle for supporting the test cartridge, the test instrument further comprising

sweeping means for sweeping the agitator vane about the test chamber pivot point through the test sample;

detecting means for detecting a reduction of sweeping movement of the agitator vane; and

timing means for timing a coagulation test time elapsed from the commencement of sweeping of the agitator vane until the detection of reduction of the sweeping movement.

2. The system of claim 1, wherein:

the test cartridge is formed of a cartridge housing enclosing each test chamber into which a test sample is to be introduced and comprising a test chamber pivot element; and

the agitator vane comprises an agitator pivot element engaging the test chamber pivot element allowing rotational motion of the agitator vane about a pivot axis at the pivot point.

3. The system of claim 1, wherein the test cartridge is substantially transparent to enable visual verification of a test sample introduced into a test chamber.

4. The system of claim 1, wherein:

the agitator is formed of a ferromagnetic material whereby the agitator vane can be swept, in response to an external magnetic field, about the pivot point through the test sample unless impeded by coagulation.

the sweeping means comprises means for generating a magnetic field that varies spatially with time about each test chamber that sweeps the agitator vane through the test sample about the pivot point; and

the detecting means comprises;

an agitator sensor disposed in operative relation to the test cartridge receptacle that provides an agitator sensor output signal that varies in a signal parameter with each sweeping movement of an agitator vane, in a test chamber of a test cartridge housing received in the cartridge receptacle, with respect to the agitator sensor; and

means for detecting the reduction of sweeping movement of the agitator vane from a reduction in variation of the signal parameter of the agitator sensor output signal.

5. The system of claim 4, wherein:

the test chamber is substantially cylindrical having a test chamber diameter and a test chamber height;

the test chamber pivot element is disposed substantially in alignment with the axis of the cylindrical test chamber; and

the agitator vane comprises first and second agitator vane leaflets extending away from the agitator pivot element.

6. The system of claim 5, wherein each agitator vane leaflet has vane leaflet upper and lower major leaflet surfaces that are substantially parallel and joined at a vane leaflet sidewall or edge and that are supported at the pivot point substantially parallel with and between the upper and lower major sides.

7. The system of claim 5, wherein the agitator vane leaflets preferably extend from the agitator pivot element substantially across the test chamber radius.

8. The system of claim 5, wherein the agitator vane leaflets are surface treated to stimulate coagulation upon movement of the agitator vane through the test sample.

9. The system of claim 4, wherein the agitator vane sensor may comprise one of a proximity sensor, an inductive sensor, a magnetic sensor, a metal sensor, and an optical sensor disposed at an agitator sensor location of the test instrument with respect to the test chamber.

10. The system of claim 1, wherein:

the test sample is a blood test sample;

the cartridge housing comprises a filling channel into the test chamber that the blood test sample passes through; and

a reagent is located in the test chamber or the filling channel to react with the test sample to facilitate performance of the test on the blood test sample determining one of thrombin time (TT), prothrombin time (PT), partial thromboplastin time (aPTT), and activated clotting time (ACT).

11. The system of claim 10, wherein the sweeping means is selectively operable to sweep each agitator vane about the test chamber pivot point through the blood test sample to mix the blood test sample with the reagent in a mixing phase prior to conducting the coagulation test.

12. The system of claim 10, wherein the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

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

14. The system of claim 13, wherein the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

15. The system of claim 13, wherein the sweeping means is selectively operable to sweep each agitator vane about the test chamber pivot point through the blood test sample to mix the blood test sample with the reagent in a mixing phase prior to conducting the coagulation test.

16. The system of claim 1, wherein the agitator vane is surface treated to stimulate coagulation upon movement of the agitator vane through the test sample.

17. The system of claim 1, wherein the detecting means comprises:

an agitator sensor disposed in operative relation to the test cartridge receptacle that provides an agitator sensor output signal that varies in a signal parameter with each sweeping movement of an agitator vane, in a test chamber of a test cartridge housing received in the cartridge receptacle, with respect to the agitator sensor; and

means for detecting the reduction of sweeping movement of the agitator vane from a reduction in variation of the signal parameter of the agitator sensor output signal.

18. The system of claim 1, wherein:

each test chamber is substantially cylindrical having a test chamber diameter;

the test chamber pivot point is disposed substantially in alignment with the axis of the cylindrical test chamber; and

the agitator vane comprises first and second agitator vane leaflets extending away from the test chamber pivot point.

19. The system of claim 18, wherein the sweeping means is selectively operable continuously rotate the first and second agitator vane leaflets through 360°

revolutions around the pivot point or to selectively sweep the agitator vane back and forth about the pivot point through an arc of less than 360°

.

20. The system of claim 18, wherein the sweeping means is operable to continuously rotate the first and second agitator vane leaflets through 360°

revolutions around the pivot point during a mixing phase for mixing the test sample with a reagent and to sweep the agitator vane back and forth about the pivot point during the coagulation test through an arc of less than 360°

.

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

providing a test cartridge formed of a cartridge housing having at least one test chamber therein into which a test sample is deposited to be tested and an agitator mounted at a pivot point in the test chamber having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber;

filling the test chamber with a test sample;

inserting the test cartridge into a cartridge receptacle of a test instrument; and

operating the test instrument to;

sweep the agitator vane about the test chamber pivot point through the test sample;

detect a reduction of sweeping movement of the agitator vane; and

time a coagulation test time elapsed from the commencement of sweeping of the agitator vane until the detection of reduction of the sweeping movement.

22. The method of claim 21, wherein:

the test cartridge is formed of a cartridge housing enclosing each test chamber into which a test sample is to be introduced and comprising a test chamber pivot element; and

the agitator vane comprises an agitator pivot element engaging the test chamber pivot element allowing rotational motion of the agitator vane about a pivot axis at the pivot point.

23. The method of claim 21, wherein the test cartridge is substantially transparent to enable visual verification of blood introduced into a test chamber.

24. The method of claim 21, wherein the agitator is formed of a ferromagnetic material, whereby the agitator vane can be swept, in response to an external magnetic field, about the pivot point through the test sample unless deterred by coagulation.

25. The method of claim 24, wherein the step of operating the test instrument further comprises:

commencing a timer;

generating a magnetic field that varies spatially with time about each test chamber that sweeps the agitator vane through the test sample about the pivot point;

powering an agitator sensor disposed in operative relation to the test cartridge receptacle to provide an agitator sensor output signal that varies in a signal parameter with each sweeping movement of the agitator vane with respect to the agitator sensor;

detecting the reduction of sweeping movement of the agitator vane from a reduction in variation of the signal parameter of the agitator sensor output signal; and

determining the coagulation test time elapsed from the commencement of sweeping of the agitator vane until the detection of reduction of the sweeping movement.

26. The method of claim 25, wherein the agitator vane sensor may comprise one of a proximity sensor, an inductive sensor, a magnetic sensor, a metal sensor, and an optical sensor disposed at an agitator sensor location of the test instrument with respect to the test chamber.

27. The method of claim 21, further comprising locating a reagent in the test chamber to be mixed and react with the test sample.

28. The method of claim 27, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

29. The method of claim 27, wherein the step of operating the test instrument further comprises sweeping each agitator vane about the test chamber pivot point through the test sample to mix the blood test sample with the reagent in a mixing phase prior to conducting the coagulation test.

30. The method of claim 21, wherein:

the test chamber is substantially cylindrical having a test chamber diameter and a test chamber height between the upper and lower major sides;

the test chamber pivot element is disposed substantially in alignment with the axis of the cylindrical test chamber; and

the agitator vane comprises first and second agitator vane leaflets extending away from the agitator pivot element.

31. The method of claim 30, wherein each agitator vane leaflet has vane leaflet upper and lower major leaflet surfaces that are substantially parallel and joined at a vane leaflet edge.

32. The method of claim 30, wherein each agitator vane leaflet extends from the agitator pivot element substantially across the test chamber radius.

33. The method of claim 30, wherein the agitator vane leaflets are surface treated to stimulate coagulation upon movement of the agitator vane through the test sample.

34. The method of claim 21, wherein the agitator vane is surface treated to stimulate coagulation upon movement of the agitator vane through the test sample.

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

36. The method of claim 35, wherein the step of operating the test instrument further comprises sweeping each agitator vane about the test chamber pivot point through the blood test sample to mix the blood test sample with the reagent in a mixing phase prior to conducting the coagulation test.

37. The method of claim 35, wherein the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

38. The method of claim 21, wherein the detecting step comprises:

disposing an agitator sensor in operative relation to the test cartridge receptacle that provides an agitator sensor output signal that varies in a signal parameter with each sweeping movement of an agitator vane, in a test chamber of a test cartridge housing received in the cartridge receptacle, with respect to the agitator sensor; and

detecting the reduction of sweeping movement of the agitator vane from a reduction in variation of the signal parameter of the agitator sensor output signal.

39. The method of claim 21, wherein the step of operating the test instrument further comprises:

continuously rotating the agitator vane through 360°

revolutions around the pivot point during a mixing phase for mixing the test sample with a reagent; and

sweeping the agitator vane back and forth about the pivot point during the coagulation test through an arc of less than 360°

.

40. The method of claim 21, wherein the step of operating the test instrument further comprises continuously rotating the agitator vane through 360°

revolutions around the pivot point

41. The method of claim 21, wherein the step of operating the test instrument further comprises selectively sweeping the agitator vane back and forth about the pivot point through an arc of less than 360°

.

42. A test cartridge for use in a system and method that determines a coagulation test time of a biologic test sample, the test cartridge comprising:

a cartridge housing having at least one test chamber therein into which a test sample is deposited to be tested; and

an agitator mounted at a pivot point in the test chamber, the agitator having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber,

whereby a coagulation test time from the commencement of sweeping of the agitator vane until the detection of reduction of the sweeping movement is determinable.

43. The test cartridge of claim 42, wherein the test cartridge is substantially transparent to enable visual verification of blood introduced into a test chamber.

44. The test cartridge of claim 42, wherein:

the cartridge housing comprises a cartridge port for introducing a test sample into the test chamber and a test chamber pivot element; and

the agitator vane comprises an agitator pivot element engaging the test chamber pivot element allowing rotational motion of the agitator vane about a pivot axis at the pivot point.

45. The test cartridge of claim 44, wherein the agitator vane extends from an agitator pivot element supported by the test chamber pivot element intermediate the upper and lower major sides for rotational motion relative to the test chamber pivot element.

46. The test cartridge of claim 44, wherein:

the test chamber is substantially cylindrical having a test chamber diameter and a test chamber height between the upper and lower major sides and the test chamber pivot element is disposed substantially in alignment with the axis of the cylindrical test chamber; and

the agitator vane comprises first and second agitator vane leaflets extending away from the agitator pivot element.

47. The test cartridge of claim 46, wherein each agitator vane leaflet has vane leaflet upper and lower major leaflet surfaces that are substantially parallel and joined at a vane leaflet sidewall or edge and that are supported at the pivot point substantially parallel with and between the upper and lower major sides.

48. The test cartridge of claim 46, wherein the agitator vane leaflets preferably each extend from the agitator pivot element substantially across the test chamber radius.

49. The test cartridge of claim 48, wherein the agitator vane leaflets are surface treated to stimulate coagulation upon movement of the agitator vane through the blood test sample.

50. The test cartridge of claim 48, wherein the agitator vane leaflets are formed of a ferromagnetic material, whereby the agitator vane leaflets can be swept, in response to an external magnetic field, about the pivot point through the test sample in the absence of coagulation.

51. The test cartridge of claim 42, wherein a reagent is located in the test chamber to be mixed and react with the test sample.

52. The test cartridge of claim 51, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

53. The test cartridge of claim 42, wherein a reagent is deposited on the agitator vane to react with the test sample in the test chamber.

54. The test cartridge of claim 53, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

55. The test cartridge of claim 42, wherein the agitator vane is surface treated to stimulate coagulation upon movement of the agitator vane through the blood test sample.

56. The test cartridge of claim 42, wherein the cartridge housing comprises:

a cartridge port for receiving a test sample; and

a filling channel extending from the cartridge port to each the chamber through which the test sample flows.

57. The test cartridge of claim 56, wherein a reagent is disposed in the filling channel of one test chamber to react with the test sample deposited into one of the test chambers.

58. The test cartridge of claim 57, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

59. The test cartridge of claim 42, wherein the agitator vane is formed of a ferromagnetic material, whereby the agitator vane can be swept, in response to an external magnetic field, about the pivot point through the test sample in the absence of coagulation.

60. The test cartridge of claim 42, wherein the agitator vane can be continuously rotated through 360°

revolutions around the pivot point

61. The test cartridge of claim 42, wherein the agitator vane can be swept back and forth about the pivot point through an arc of less than 360°

.

62. The test cartridge of claim 42, wherein:

the cartridge housing having at least two test chambers therein to receive test samples to be tested, each test chamber having an agitator mounted at a pivot point in the test chamber having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber; and

the test sample in one of the test chambers is mixed with a reagent to react with the test sample and stimulate coagulation, whereby comparative coagulation test times of the test sample mixed with a reagent and a further test sample are facilitated.

63. The test cartridge of claim 62, wherein a reagent is located in one test chamber to be mixed and react with the test sample introduced into the test chamber.

64. The test cartridge of claim 63, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

65. The test cartridge of claim 62, wherein a reagent is deposited on one agitator vane to react with the test sample in one test chamber.

66. The test cartridge of claim 65, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

67. The test cartridge of claim 62, wherein the cartridge housing comprises:

a cartridge port for receiving a test sample; and

a filling channel extending from the cartridge port to each test chamber through which the test sample flows.

68. The test cartridge of claim 67, wherein a reagent is disposed in the filling channel of one test chamber to react with the test sample deposited into one of the test chambers.

69. The test cartridge of claim 68, wherein:

the test sample is a blood test sample; and

the reagent is selected from the group consisting of calcium, kaolin, celite, ellagic acid, glass particles, thrombin, thromboplastin, protamine, and heparinase.

70. The test cartridge of claim 62, wherein the agitator vane of one agitator is surface treated to stimulate coagulation upon movement of the agitator vane through the blood test sample.

71. A system that performs tests on biologic test samples to determine coagulation test times comprising:

a test cartridge formed of a cartridge housing having at least two test chambers therein to receive test samples to be tested, each test chamber having an agitator mounted at a pivot point in the test chamber having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber; and

a test instrument having an instrument housing including a cartridge receptacle for supporting the test cartridge, the test instrument further comprising

sweeping means for sweeping the agitator vanes about the test chamber pivot points through the test samples;

detecting means for detecting a reduction of sweeping movement of each agitator vane; and

timing means for timing coagulation test times elapsed from the commencement of sweeping of each agitator vane until the detection of reduction of the sweeping movement.

72. The system of claim 71, wherein the test instrument further comprises means for displaying the coagulation test times.

73. The system of claim 71, wherein the test sample in one of the test chambers is mixed with a reagent to react with the test sample, whereby comparative coagulation test times of the test sample mixed with a reagent and a further test sample are determined by the timing means.

74. The system of claim 73, wherein the test instrument further comprises:

means for calculating the average of the coagulation test times; and

means for displaying the average coagulation test time.

75. The system of claim 73, wherein the test instrument further comprises:

means for calculating the difference between the coagulation test times; and

means for displaying the difference between the coagulation test times.

76. The system of claim 71, wherein the test instrument further comprises:

means for calculating the average of the coagulation test times; and

means for displaying the average coagulation test time.

77. The system of claim 71, wherein the test instrument further comprises:

means for calculating the difference between the coagulation test times; and

means for displaying the difference between the coagulation test times.

78. A method of performing a test on a plurality of biologic test samples and determining coagulation test times comprising:

providing a test cartridge formed of a cartridge housing at least two test chambers therein to receive test samples to be tested, each test chamber having an agitator mounted at a pivot point in the test chamber having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber;

filling the test chambers with test samples;

inserting the test cartridge into a cartridge receptacle of a test instrument; and

operating the test instrument to;

sweep each agitator vane about the test chamber pivot point through the test sample;

detect a reduction of sweeping movement of each agitator vane; and

time a coagulation test time of the test sample in each test chamber elapsed from the commencement of sweeping of each agitator vane until the detection of reduction of the sweeping movement.

79. The method of claim 78, wherein the step of operating the test instrument further comprises displaying the coagulation test times.

80. The method of claim 78, further comprising mixing the test sample in one of the test chambers with a reagent to react with the test sample, whereby comparative coagulation test times of the test sample mixed with one of a reagent and a further test sample are determined in the timing step.

81. The method of claim 80, wherein the step of operating the test instrument further comprises:

calculating the average of the coagulation test times; and

displaying the average coagulation test time.

82. The system of claim 80, wherein the step of operating the test instrument further comprises:

calculating the difference between the coagulation test times; and

displaying the difference between the coagulation test times.

83. The method of claim 78, wherein the step of operating the test instrument further comprises:

calculating the average of the coagulation test times; and

means for displaying the average coagulation test time.

84. The method of claim 78, wherein the step of operating the test instrument further comprises:

calculating the difference between the coagulation test times; and

displaying the difference between the coagulation test times.

85. A method of performing a test on a biologic test sample and determining a coagulation test time comprising:

providing a test cartridge formed of a cartridge housing having at least one test chamber therein into which a test sample is deposited to be tested and an agitator mounted at a pivot point in the test chamber having an agitator vane adapted to be swept about the pivot point and through the test sample in the test chamber;

filling the test chamber with a test sample;

inserting the test cartridge into a cartridge receptacle of a test instrument; and

operating the test instrument to;

sweep the agitator vane about the test chamber pivot point through the test sample;

detect the sweeping movement of the agitator vane; and

display an image of the sweeping movement of the agitator vane, whereby changes in the sweeping movement due to coagulation and dissolution of coagulation are presented.

86. The method of claim 85, wherein the test sample is a blood test sample and the dissolution of coagulation is due to fibrinolysis of coagulation.