PORTABLE COAGULATION MONITORING DEVICES, SYSTEMS, AND METHODS

• US 20150253343A1
• Filed: 05/20/2015
• Published: 09/10/2015
• Est. Priority Date: 12/18/2009
• Status: Active Grant

• Current Assignee: Entegrion, Inc.
• Original Assignee: Entegrion, Inc.
• Inventors: PEARCE, MATTHEW, HALL, RICHARD, DACORTA, JOSEPH Anthony
• Granted Patent: US 10,739,358 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: G01N 2011/008 optical properties
• 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

Abstract

Portable coagulation monitoring devices, systems, and methods are disclosed. Namely, a test cartridge is provided for use in a portable coagulation monitor (PCM) device. Further, the test cartridge comprises two glass-filled thermoplastic polymer plates and a disposable blood introduction device. The two glass-filled thermoplastic polymer plates are arranged substantially in parallel with a small gap therebetween for receiving a sample of blood to be tested. Using the PCM device, the two glass-filled thermoplastic polymer plates can be moved linearly relative to each other. Methods of measuring coagulation response in a blood sample using the test cartridge and the PCM device are provided. A method of introducing blood into the test cartridge using the disposable blood introduction device is provided.

Claims

1. A device for measuring coagulation response in a blood sample, comprising:

a. a set of test components comprising a first member having a first surface, and a second member having a second surface, the first member positioned for having the first surface facing the second surface of the second member, and spaced an amount sufficient to allow a sample droplet of blood to contact the first surface and the second surface and initiate coagulation, and the first member and second member being linearly movable relative to each other, wherein the first and second members comprise a glass-filled thermoplastic polymer;

b. a drive mechanism connected to at least one of the first member and the second member for linearly moving the first member and the second member relative to each other in parallel when a blood sample is in contact with the first surface and the second surface; and

c. an optical detection sensor system for detecting interaction of light with a blood sample located between the first member and second member, as an indication of coagulation response of the blood sample.

2. The device of claim 1, wherein the first surface and the second surface are spaced apart from about 50 μ

m to about 250 μ

m.

3. The device of claim 1, wherein the glass-filled thermoplastic polymer is selected from the group consisting of nylon (polyamide), polycarbonate, polypropylene, polyethylene and polyester.

4. The device of claim 1, wherein the glass-filled thermoplastic polymer comprises one or more of glass beads and glass fibers, and the amount of the one or more of glass beads and glass fibers within the glass-filled thermoplastic polymer is between about 5% to about 60%.

5. The device of claim 4, wherein the amount of the one or more of glass beads and glass fibers within the glass-filled thermoplastic polymer is about 30%.

6. The device of claim 1, wherein at least one member is a plate.

7. The device of claim 1, wherein at least one member is a rod that can rotate to initiate coagulation.

8. The device of claim 7, further comprising a third member having a third surface spaced an amount sufficient to allow a sample droplet of blood to contact the surface of the rod and initiate coagulation.

9. The device of claim 1, wherein the first set of test components are housed in a blood sample collection cartridge which is removable from the device.

10. The device of claim 9, wherein the blood sample collection cartridge is disposable after use.

11. The device of claim 9, wherein the blood sample collection cartridge further comprises a memory device on the cartridge for storing data relating to a blood sample tested.

12. The device of claim 9, wherein the blood sample collection cartridge further comprises pinch contact ribs, wherein the pinch contact ribs securely couple engagement features of the set of test components in the cartridge with the drive mechanism of the device.

13. The device of claim 1 further comprising a memory device for storing data relating to a blood sample tested.

14. The device of claim 1, wherein the drive mechanism is programmed for moving the first member and second member at different speeds relative to each other for detecting different mechanisms involved in a coagulation response of a blood sample.

15. The device of claim 1 wherein the drive mechanism comprises piezo motors.

16. The device of claim 1, wherein the optical detector sensor system is adapted for detecting binding of the blood sample to the first surface and the second surface as an indication of platelet response during coagulation.

17. The device of claim 1, wherein one or both of the first and second surface has been treated to induce, slow, or modify the coagulation process for selecting in favor of or against specific aspects of coagulation of the sample.

18. The device of claim 17, wherein the treatment of the surfaces enhances at least one characteristic selected from the group consisting of platelet or blood protein binding, reactivity, and activation.

19. The device of claim 17, wherein the treatment of the surfaces reduces at least one characteristic selected from the group consisting of platelet or blood protein binding, reactivity, and activation.

20. The device of claim 1, configured for analyzing blood rheology and coagulation of fresh whole blood or some fraction thereof without adding external reagents.

21. The device of claim 1, configured for measuring, with no functional delay, the dynamic balance between pro- and anti-thrombotic hemostatic status by sequential samples from the same person or animal.

22. The device of claim 1, further comprising at least one microcontroller for controlling operation of the drive mechanism and optical detection sensor system.

23. The device of claim 1, further comprising at least one displacement sensor for detecting and controlling the amount of relative movement between the first member and the second member.

24. The device of claim 1, further comprising a connection interface module for connecting and communicating between the device and an external system.

25. The device of claim 1, wherein the drive mechanism comprises a device capable of driving linear motion.

26. The device of claim 1, further comprising an analog to digital converter coupled to the optical detection sensor system for converting analog signals indicative of coagulation response of a blood sample into digital signals for storage thereof.

27. The device of claim 1 comprising a first channel and a second channel, wherein the first channel comprises the set of test components, the drive mechanism, and the optical detection sensor system, and the second channel comprises a second set of test components, a second drive mechanism, and a second optical detection sensor system, and further wherein the first and second channels operate independently of one another and enable the device to perform measurements of two blood samples at the same time.

28. The device of claim 27 wherein the first channel and second channel perform distinct measurements.

29. The device of claim 28 wherein the distinct measurements include any one of a thrombelastogram test, a fibrinogen test, a heparin test, and other platelet function test.

30. The device of claim 27 wherein the set of test components of the first channel make up a first blood sample collection cartridge and the second set of test components of the second channel make up a second blood sample collection cartridge, and further wherein the first and second blood sample collection cartridges are independently removable from the device.

31. The device of claim 30 wherein the first and second blood sample collection cartridges further comprise pinch contact ribs, wherein the pinch contact ribs securely couple engagement features of the respective sets of test components in the cartridges with the respective drive mechanisms of the device.

32. The device of claim 1 further comprising a temperature control mechanism for maintaining a desired temperature within the device.

33. The device of claim 32 wherein the temperature control mechanism comprises a heater.

34. The device of claim 32 wherein the temperature control mechanism comprises a cooling device.

35. The device of claim 1 further comprising a humidity control mechanism.

36. The device of claim 35 wherein the humidity control mechanism comprises a sponge-like pad inside a humidity pouch, and further wherein the humidity pouch comprises a removable cover.

37. The device of claim 36 wherein the removable cover may be optionally removed to expose the sponge-like pad to an interior environment of the device.

38. A method of measuring coagulation response in a blood sample, comprising the steps of:

a. placing a sample droplet of blood between and in contact with a first surface and a second surface of oppositely disposed glass-filled thermoplastic polymer members;

b. moving at least one member linearly with respect to the other member at a predetermined speed sufficient to activate platelets through exposure to shear forces; and

c. optically detecting, via measurement of mechanical displacement, the interaction between the first and second surfaces resulting from changes in the viscosity of the sample fluid and binding to the member surfaces in order to measure coagulation response of the droplet of blood.

39. The method of claim 38, further comprising obtaining the sample droplet of blood directly from the body of a subject.

40. The method of claim 38, further comprising moving at least one member at a first speed and optically detecting adherence of the sample droplet of blood to the surface of the members to determine platelet response during coagulation.

41. The method of claim 40, further comprising subsequently moving at least one member at a second speed slower than the first speed, and optically detecting the level of coagulation of the blood sample as indicative of fibrin polymerization response.

42. The method of claim 41, wherein the relative motion between the two members is controlled to generate arbitrarily selected waveforms to induce desired fluid shear rates at selected amplitudes, frequency, duration, and sequence such that the device is enabled to emulate fluid shear as desired over a broad range including from about DC (zero shear) to shear rates that would cause fluid cavitation and subsequent destruction of the cellular components of the sample, and continuously including all points in the shear rate spectrum between these two points.

43. The method of claim 42, wherein the shear rate is controlled in a sequence of values to generate specific protocols or plate motion paradigms for targeted diagnostic or analytic objectives, wherein such targeted diagnostic or analytic objectives include rapid initiation of primary coagulation, destructive or non-destructive viscoelastic evaluation of early, mid-phase, or late-phase clotting, emulation of clinically-accepted or otherwise recognized shear rate protocols for comparison with other commercial or experimental devices, or validation testing against known standards.

44. The method of claim 38, wherein the members are part of a blood sample collection cartridge which is removable from a device for measuring coagulation.

45. The method of claim 44, wherein the blood sample collection cartridge further comprises memory and further comprising storing information about coagulation response resulting from the optical detection.

46. The method of claim 38, wherein the optical detection is conducted by transmitting electromagnetic waves into the sample droplet, and detecting at least one of transmission, absorption, reflection and refraction of the electromagnetic waves through the sample droplet at respective light detectors, to generate analog signals representative of coagulation properties of the blood in the sample droplet for primary and secondary coagulation mechanisms.

47. The method of claim 46, further comprising converting the signals to digital signals, storing the digital signals and analyzing the stored digital signals in a predetermined manner to obtain selected information about the coagulation response of the blood in the sample droplet.

48. The method of claim 38, further comprising at least one drive mechanism connectable to at least one member for moving the at least one member, and moving the at least one member with the at least one motor.

49. The method of claim 48 wherein the at least one drive mechanism comprises a piezo motor.

50. The method of claim 48, further comprising a processor connected to the motor and controlling the operation thereof with the processor in a predetermined manner.

51. The method of claim 38, further comprising moving one member relative to the other member in a manner causing the other member to move due to visco elastic coupling between the blood and the other member;

and determining the visco elastic properties of the blood from the movement of the other member.

52. The method of claim 38, further comprising detecting strain rates caused by movement of the one member and the other member caused by visco elastic coupling between the one member and the other member caused by the blood sample;

and determining the coagulation state of the blood by inference analysis based on visco elasticity of the blood sample determined from mechanical coupling between the two members and the resulting strain rates.

53. The method of claim 38, further comprising continually measuring the visco elasticity of the blood over time to monitor changes over time of the coagulation response of the blood.

54. A method of measuring coagulation response in a blood sample comprising:

a. placing a sample droplet of blood between and in contact with facing surfaces of oppositely disposed glass-filled thermoplastic polymer members;

b. moving at least one member linearly with respect to the other member at a first speed;

c. optically detecting a first coagulation response of the blood indicative of platelet response in the blood;

d. moving at least one member linearly with respect to the other member at a second speed; and

e. optically detecting a second coagulation response of the blood indicative of fibrin polymerization.

55. The method of claim 54, further comprising continually measuring the visco elasticity of the blood over time to monitor changes over time of the coagulation response of the blood.

56. A test cartridge for use with a device for measuring coagulation response in a blood sample, comprising a first member having a first surface, and a second member having a second surface, the first member positioned for having the first surface facing the second surface of the second member, and spaced an amount sufficient to allow a sample droplet of blood to contact the first surface and the second surface and initiate coagulation, and the first member and second member being linearly movable relative to each other, wherein the first and second members comprise a glass-filled thermoplastic polymer.

57. The test cartridge of claim 56 wherein the test cartridge is disposable after use.

58. The test cartridge of claim 56 further comprising a humidity control mechanism.

59. The test cartridge of claim 58 wherein the humidity control mechanism comprises a sponge-like pad inside a humidity pouch, and further wherein the humidity pouch comprises a removable cover.

60. The test cartridge of claim 59 wherein the removable cover may be optionally removed to expose the sponge-like pad to an interior environment of the device.

61. The test cartridge of claim 56 further comprising a temperature control mechanism for maintaining a desired temperature within the device.

62. The device of claim 61 wherein the temperature control mechanism comprises a heater.

63. The device of claim 61 wherein the temperature control mechanism comprises a cooling device.

64. The test cartridge of claim 56 wherein the first member and second member further comprise engagement features for engaging with a drive mechanism in the measuring device.

65. The test cartridge of claim 64 wherein the engagement features comprise one or more of pinch contract ribs and ridges.

66. The test cartridge of claim 56 further comprising a receptacle for a blood introduction mechanism, wherein the receptacle provides a path for the sample droplet of blood to pass form the blood introduction mechanism to a point between the first surface and the second surface.

67. The test cartridge of claim 66 further comprising the blood introduction mechanism, wherein the blood introduction mechanism comprises an open top;

a funnel portion;

a flat bottom; and

a lip attached to the funnel portion;

wherein the open top comprises an opening larger than an opening at the flat bottom, and further wherein a desired amount of blood introduced to the open top may pass through the blood introduction mechanism and into the receptacle of the test cartridge, thereby providing the sample droplet of blood into the device.

68. A disposable blood introduction apparatus for the introduction of blood to a test cartridge, the apparatus comprising an open top;

a substantially funnel shaped portion;

a lower cylindrical portion with a flat bottom; and

a lip attached to an upper portion of the funnel shaped portion;

wherein the open top comprises an opening larger than an opening at the flat bottom.

69. The disposable blood introduction apparatus of claim 68 further comprising a solid plug cap attached to the apparatus, wherein the solid plug cap sealingly nests within the opening of the open top.

70. The disposable blood introduction apparatus of claim 68 wherein the disposable material is selected from the group consisting of a polymer and glass.

71. The disposable blood introduction apparatus of claim 70 wherein the disposable material is selected from the group consisting of nylon (polyamide), polycarbonate, polypropylene, and polyester.

72. The disposable blood introduction apparatus of claim 68 further comprising a pair of alignment features disposed on the funnel portion.