Device and method for detecting the coagulation functions of global, especially primary hemostasis

• US 20030130596A1
• Filed: 11/18/2002
• Published: 07/10/2003
• Est. Priority Date: 01/25/2000
• Status: Active Grant

• Current Assignee: Volker Freiherr Von Der Goltz
• Original Assignee: Volker Freiherr Von Der Goltz
• Inventors: Von Der Goltz, Volker Freiherr
• Granted Patent: US 7,223,365 B2
• Time in Patent Office: Days
• US Class Current: 600/573
• CPC Class Codes: G01N 11/08 by measuring pressure required to produce a known flow
• CPC Class Codes: G01N 33/4905 Determining clotting time of blood by chemical methods G01N33/86, C12Q1/56

Abstract

The invention relates to a method and to a device for examining the properties of the global, in particular the primary, hemostasis functions in whole blood or platelet-rich plasma, comprising

a storage chamber (15) for the blood to be examined,

a reaction device (39) having at least one flow path (5, 16) via which the blood to be examined is transported for carrying out certain reactions,

a conveyor device (1) which conveys a volumetric flow for the transport of the blood through the reaction device (39), thereby generating a conveyor pressure,

a pressure gauge (8, 9) which in a blood-free pressure gauge chamber (3) measures changes in the conveyor pressure which appear depending on the reactions of the blood to be examined which have taken place in the reaction device (39),

a blood collection chamber (10) for collecting the blood transported through the reaction device (39),

the conveyor pressure in a pressure-sealed working chamber (12) being generated by a piston-cylinder system (1),

a working surface (33) of the piston (4) forming a boundary of the working chamber (12), and

the working chamber (12) being formed by the blood collection chamber (10) and the blood-free pressure gauge chamber (3).

According to the method of the invention, the volumetric flow is preferably adjusted, depending on the measured pressure of the volumetric flow, in such a way that the shear rate or the shear force, whose action in the reaction opening causes blood components, in particular thrombocytes, to deposit, follows a predetermined characteristic curve and in particular is held constant.

Claims

1. Device for examining the properties of the global, in particular the primary, hemostasis functions in whole blood or platelet-rich plasma, comprising

a storage chamber (15) for the blood to be examined,

a reaction device (39) having at least one flow path (5, 7, 11, 16) via which blood to be examined is transported for carrying out certain reactions,

a conveyor device (1) which conveys a volumetric flow for the transport of the blood through the reaction device (39), thereby generating a conveyor pressure,

a pressure gauge (8, 9) which in a blood-free pressure gauge chamber (3) measures changes in the conveyor pressure which appear depending on the reactions of the blood to be examined which have taken place in the reaction device (39),

a blood collection chamber (10) for collecting the blood transported through the reaction device (39),

the pressure gauge chamber (3) being situated below the storage chamber (15) and above the surface of the blood which is led through the reaction device (39) into the blood collection chamber (10),

the conveyor pressure in a pressure-sealed working chamber (12) being generated by a piston-cylinder system (1),

a working surface (33) of the piston (4) forming a boundary of the working chamber (12), and

the working chamber (12) being formed by the blood collection chamber (10) and the blood-free pressure gauge chamber (3).

4. Device according to one of claims 1 or 2, characterized in that the pressure gauge chamber (3) is formed by a portion of the reaction device (39) and the cylinder (25) of the piston-cylinder system (1).

5. Device according to one of claims 1 through 4, characterized in that the piston-cylinder system (1) is formed by a syringe.

6. Device according to one of claims 1 through 5, characterized in that the pressure is detectable in the pressure gauge chamber (3) using a pressure line (8) introduced in a leak-tight manner into the pressure gauge chamber (3).

7. Device according to one of claims 1 through 5, characterized in that the pressure line (8) is designed as a hollow needle and is guided through a wall (37) or a sealing insert (26) in the pressure gauge chamber (8).

8. Device according to one of claims 1 through 7, characterized in that the piston-cylinder system (36) designed as a withdrawal syringe is connectable to the reaction device (39) via a hollow needle (43;

55).

9. Device according to claim 8, characterized in that the hollow needle (55) is provided on the reaction device.

10. Device according to one of claims 1 through 9, characterized in that the storage chamber (15) is formed in a withdrawal syringe.

11. Device according to claim 6 or 7, characterized in that the pressure line (8) is connected to a pressure gauge (9).

12. Device according to one of claims 1 through 11, characterized in that the piston-cylinder system (1) is integrated into a housing (38) which includes a blood collection chamber (10).

13. Device according to one of claims 1 through 12, characterized in that the conveyor device (36) is led into the collection chamber (10), which also includes the pressure gauge chamber (3), via the pressure-sealed pressure line (8) which is guided through the wall (37).

14. Device according to one of claims 1 through 13, characterized in that the pressure line (8) is designed with a tapering end (42) and projects into the pressure gauge chamber (3) through the container wall (37), or through the boundary wall of a withdrawal syringe (45), or through the wall of a syringe adapter (22), or through the sealing insert (26) of the withdrawal syringe (45).

15. Device according to one of claims 1 through 14, characterized in that the piston-cylinder system (1;

36) is driven by an electrically operated drive device (17).

16. Device according to one of claims 1 through 15, characterized in that the piston (4) may be moved back and forth under the measurement conditions, with the result that the blood to be measured is led through the reaction device from different directions.

17. Device according to one of claims 1 through 16, characterized in that the piston (4) is connectable to the drive device (17) via a detachable coupling (13).

18. Device according to one of claims 1 through 17, characterized in that a pressure gauge line (41) connected to the pressure sensor (9) is branched from the pressure line (8) between the piston-cylinder system (36) and the end of the pressure line (8) which is guided into the pressure gauge chamber (3).

19. Device according to one of claims 1 through 18, characterized in that the reaction device (39) is situated above the blood collection chamber (10) in a common housing (38) which includes the blood collection chamber (10).

20. Device according to one of claims 1 through 19, characterized in that the storage chamber (15) is situated above or below the reaction device (39).

21. Device according to one of claims 1 through 20, characterized in that the storage chamber (15) is situated in the common housing (38) or in a separate housing.

22. Device according to one of claims 1 through 21, characterized in that the reaction device (39) is insertable in a liquid-sealed manner into the common housing (38) or separate housing, or is situated in a liquid-sealed manner in the common housing (38).

23. Device according to one of claims 1 through 22, characterized in that a hollow needle (43;

55) or tube (16) is provided or can be provided between the storage chamber (15) and the reaction device (39) and/or between the reaction device (39) and the blood collection chamber (10).

24. Device according to claim 23, characterized in that the hollow needle and/or the tube act as a feed opening and/or a shear opening.

25. Device according to one of claims 1 through 24, characterized in that the storage chamber (15) is provided inside the cylinder of a withdrawal syringe (45) and is connectable to the reaction device (39) via the hollow needle (43;

55).

26. Device according to one of claims 23 through 25, characterized in that the hollow needle (43) is formed by the cannula of the withdrawal syringe (45).

27. Device according to one of claims 23 through 26, characterized in that the hollow needle (55) is attached in a pressure-sealed manner to the housing (64) which includes the reaction device (39), and with its free needle end (47) the hollow needle may be pushed in a pressure-sealed manner through a sealing wall (69) of the storage chamber (15).

28. Device according to claim 27, characterized in that the sealing wall (69) is made of plastic or another sealing material which makes pressure-sealed contact with the hollow needle (55;

43) when the free needle end (47) is pushed through.

29. Device according to one of claims 23 through 28, characterized in that the hollow needle (43;

55) may be pushed through the sealing insert (26) of the syringe adapter (22) or of the withdrawal syringe (45).

30. Device according to one of claims 1 through 29, characterized in that the reaction device (39) is formed in the base region of a storage vessel (2) which includes the storage chamber (15) or blood collection chamber.

31. Device according to one of claims 1 through 32, characterized in that the reaction device (39) has one or multiple flow openings which are designed as feed openings and/or as shear openings and/or as reaction openings.

32. Device according to claim 31, characterized in that boundary surfaces of the respective reaction opening have a total or partial bioactive design or bioactive coating, depending on the diagnosis.

33. Device according to one of claims 1 through 32, characterized in that the respective bioactively acting boundary surface-or, for platelets, the boundary surface capable of deposition-of a flow path or plurality of flow paths may be removed from the reaction device (39).

34. Device according to one of claims 1 through 27, characterized in that the respective flow path is led between an outer region and a central flow opening (11) which opens into the working chamber (12) or which is connected to the storage chamber, or is led in the opposite direction.

35. Device according to one of claims 31 or 32, characterized in that the respective flow path runs essentially horizontally.

36. Device according to one of claims 31 through 34, characterized in that the flow path(s) run at an angle with respect to the horizontal.

37. Device according to one of claims 1 through 36, characterized in that an insert (14) which may be removed from the storage vessel (2) is provided in order to form one or multiple boundary surfaces for the flow paths in the reaction device (39).

38. Device according to claim 37, characterized in that a bioactive coating or a surface capable of deposition is provided on the insert (14).

39. Device according to claim 37 or 38, characterized in that the insert (14) is made of plastic, in particular polystyrene, or glass.

40. Device according to one of claims 1 through 39, characterized in that the base of the storage vessel (2) forms a boundary surface (30;

54) for a respective flow path in the reaction device (39).

41. Device according to one of claims 31 through 40, characterized in that the flow paths (21) in the reaction device (39) are formed between boundary surfaces (29 and 30, 54) molded on the vessel base (31) or intermediate base (50) of the storage vessel (2) and on the insert (14).

42. Device according to one of claims 31 through 41, characterized in that the boundary surfaces (29, 30, 54) run approximately parallel to one another.

43. Device according to one of claims 31 through 42, characterized in that the distance between boundary surfaces (29, 30, 54) perpendicular to the direction of blood flow is significantly less than the length of the flow path.

44. Device according to one of claims 31 through 43, characterized in that indentations, particularly in the form of impressions, are provided on at least one of the boundary surfaces (29, 30, 54) in order to form the flow paths.

45. Device according to one of claims 31 through 43, characterized in that the reaction device (39) has one or multiple reaction openings (5, 7) whose boundary surfaces are coated with or made of a material that is bioactive or capable of deposition.

46. Device according to claim 45, characterized in that the reaction opening (7) is formed in a film or membrane made of a bioactive material.

47. Device according to claim 45 or 46, characterized in that the film or membrane is made of collagen or polystyrene.

48. Device according to claim 45, characterized in that the at least one reaction opening (7) is formed in a partition (34) made of a nonporous material which is provided with a bioactive coating (35) on at least one of its two partition surfaces and/or on the respective boundary surface (6) of the reaction opening (7).

49. Device according to one of claims 45 through 48, characterized in that the diameter of the reaction opening (7) is approximately 0.100 to 0.500 mm.

50. Device according to one of claims 45 through 49, characterized in that a tube (16) or hollow needle (55;

43) in the reaction device (39) which acts as a feed opening and/or a shear opening is provided upstream from the reaction opening (7).

51. Device according to one of claims 45 through 50, characterized in that a tube (16), which preferably is used as a feed tube for supplying blood to the blood collection chamber (10), is provided downstream from the reaction opening (7).

52. Device according to one of claims 1 through 50, characterized in that a coating comprising erythrocytes and/or leucocytes, in particular of blood type 0 and/or containing von Willebrand factor, is provided in the region of the reaction opening or reaction surface.

53. Device according to one of claims 45 through 52, characterized in that the partition (34) in which the at least one reaction opening (7) is formed has a sandwich construction.

54. Device according to claim 53, characterized in that the partition (34) is formed from a film which is provided with a porous layer (70) on one or both sides.

55. Device according to claim 54, characterized in that the respective porous layer (70) is coated or impregnated with a bioactive material.

63. Method for detecting the global hemostasis function, in particular the primary hemostasis, according to one of claims 56 through 62, characterized in that the reaction device is used as a disposable part according to one of claims 1 through 55.

2. Device for examining the properties of the global, in particular the primary, hemostasis functions in whole blood or platelet-rich plasma, comprising

a storage chamber (15) for the blood to be examined,

a reaction device (39) having at least one flow path (5, 7, 11, 16) via which blood to be examined is transported for carrying out certain reactions,

a conveyor device (1) which conveys a volumetric flow for the transport of the blood through the reaction device (39), thereby generating a conveyor pressure in a working chamber (12),

a pressure gauge (8, 9) which in a blood-free pressure gauge chamber (3) measures changes in the conveyor pressure which appear depending on the reactions of the blood to be examined which have taken place in the reaction device (39),

a blood collection chamber (10) for collecting the blood transported through the reaction device (39),

the pressure gauge chamber (3) being situated below the blood collection chamber (10) and above the surface of the blood to be transported through the reaction device (39),

the conveyor pressure in a pressure-sealed working chamber (12) being generated by a piston-cylinder system (1),

a working surface (33) of the piston (4) forming a boundary of the working chamber (12), and

the working chamber (12) being formed by the storage chamber (15) and the blood-free pressure gauge chamber (3).

3. Device for examining the properties of the global, in particular the primary, hemostasis functions in whole blood or platelet-rich plasma, comprising

a storage chamber (15) for the blood to be examined,

a reaction device (39) having at least one flow path (5, 7, 11, 16) via which blood to be examined is transported for carrying out certain reactions,

a conveyor device (36) which conveys a volumetric flow for the transport of the blood through the reaction device (39), thereby generating a conveyor pressure,

a pressure gauge (8, 9) which in a blood-free pressure gauge chamber (3) measures changes in the conveyor pressure which appear depending on the reactions of the blood to be examined which have taken place in the reaction device (39),

a pressure-sealed blood collection chamber (10) for collecting the blood transported through the reaction device (39),

the pressure gauge chamber (3) being situated below the storage chamber (15) and above the surface of the blood which is led through the reaction device (39) into the pressure-sealed blood collection chamber (10),

the conveyor pressure being generated by a piston-cylinder system (36),

a working surface (33) of the piston (4) forming a boundary of the working chamber (12), and

the working chamber (12) being connected to the blood-free pressure gauge chamber (3) via a pressure line (8).

56. Method for detecting the global hemostasis function, in particular the primary hemostasis, in which blood to be examined is conveyed from a storage chamber under predetermined flow conditions through at least one reaction opening of a reaction device, and when blood components are deposited on the reaction surfaces under the action of shear forces in the at least one reaction opening, a variable pressure is measured, characterized in that the volumetric flow of the blood conveyed through the reaction device is adjusted, depending on the respective measured pressure, in such a way that the shear rate or the shear force which acts in at least one reaction opening follows a predetermined characteristic curve for the shear rate or shear force.

57. Method according to claim 58, characterized in that the shear rate or shear force is held constant.

58. Method according to claim 56 or 57, characterized in that the time and/or the flow volume are evaluated until a predetermined volumetric flow is reached in the reaction opening.

59. Method according to one of claims 56 through 58, characterized in that the flow volume and/or the volumetric flow present at the time after a predetermined measurement time has elapsed, or the elapsed time for a predetermined volumetric flow and/or the volumetric flow present at the time, is/are used for the clinical evaluation.

60. Method according to one of claims 56 through 59, characterized in that the pressure rise at the end of a predetermined time, or the time until a specified pressure is reached, is used for the clinical evaluation.

61. Method for detecting the global hemostasis function, in particular the primary hemostasis, in which blood to be examined is conveyed from a storage chamber under predetermined flow conditions through at least one reaction opening of a reaction device, and when blood components are deposited on the reaction surfaces under the action of shear forces in the at least one reaction opening, a variable pressure is measured, in particular according to one of claims 56 through 60, characterized in that before the measurement is begun the viscosity of the blood is determined and the shear rate or shear force is adjusted, depending on said viscosity.

62. Method according to claim 61, characterized in that the viscosity measurement is carried out in the reaction device.