Systems for Measuring Properties of a Physiological Fluid Suspension

• US 20090225316A1
• Filed: 03/05/2009
• Published: 09/10/2009
• Est. Priority Date: 03/05/2008
• Status: Active Grant

• Current Assignee: Aggredyne, Inc.
• Original Assignee: Aggredyne, Inc.
• Inventors: Sukavaneshvar, Sivaprasad, Teitel, Edward R., Mohammad, Syed F.
• Granted Patent: US 8,289,514 B2
• Time in Patent Office: Days
• US Class Current: 356/337
• CPC Class Codes: G01F 1/74 Devices for measuring flow of a fluid or flow of a fluent solid material in suspension in another fluid
• CPC Class Codes: G01N 21/49 within a body or fluid
• CPC Class Codes: G01N 21/53 within a flowing fluid, e.g. smoke
• 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

A method of evaluating a property of a physiological fluid suspension comprises measuring a value of the property of a liquid portion of the physiological fluid suspension via light scattering, and comparing the measured value with a reference value to evaluate the property of the liquid portion of the physiological fluid suspension.

Claims

1. A method of evaluating a property of a liquid portion of a physiological fluid suspension, comprising:

establishing a first value for the property of the liquid portion of the physiological fluid suspension;

inducing a change in the property;

measuring a second value for the property using light scattering after inducing the change; and

comparing the first value with the second value.

2. The method of claim 1, further comprising:

measuring via light scattering a baseline value of the property of the liquid portion of the suspension;

introducing a change in the suspension;

measuring via light scattering a changed value of the property of the liquid portion of the physiological fluid suspension; and

comparing the changed value of the property of the liquid portion to the baseline value of the property of the liquid portion to evaluate the property of the physiological fluid suspension.

3. The method of claim 2, further comprising calculating a rate of change of the property of the liquid portion of the physiological fluid suspension.

4. The method of claim 3, wherein calculating the rate of change of the property of the liquid portion is based upon a time elapsed in reaching the changed value of the property.

5. The method of claim 1, wherein the multi-component suspension is selected from the group consisting of whole blood, platelet suspensions, leukocyte suspensions, red blood cell suspensions, blood plasmas, blood plasma components, protein solution, protein suspensions, suspension of modified proteins, suspension of cells, suspension of modified cells, suspension of particulates and combinations thereof.

6. The method of claim 5, wherein measuring the baseline value of the liquid portion of the blood or plasma, and measuring the changed value of the liquid portion of the blood or plasma, includes utilizing platelet aggregates as optical markers.

7. The method of claim 4, wherein the physiological fluid suspension includes blood or plasma, and wherein measuring the baseline value of the liquid portion of the blood or plasma, and measuring the changed value of the liquid portion of the blood or plasma, includes utilizing blood cells as optical markers.

8. The method of claim 4, wherein the physiological fluid suspension includes blood or plasma, and wherein measuring the baseline value of the liquid portion of the blood or plasma, and measuring the changed value of the liquid portion of the blood or plasma, includes utilizing extraneous particulates as optical markers.

9. The method of claim 8, wherein the extraneous particulates include microspheres or nanoparticles.

10. The method of claim 4, wherein the physiological fluid suspension includes blood or plasma, and wherein measuring the baseline value of the liquid portion of the blood or plasma, and measuring the changed value of the liquid portion of the blood or plasma, includes utilizing features external to the blood or plasma as optical markers.

11. The method of claim 2, wherein the baseline value and the changed value are measured when the physiological fluid suspension is stationary.

12. The method of claim 2, wherein the baseline value and the changed value are measured when the physiological fluid suspension is in motion.

13. The method of claim 2, wherein at least one of the baseline value and the changed value is measured when the physiological fluid suspension is in motion.

14. The method of claim 13, wherein the baseline value is measured when the fluid is stationary and wherein the changed value is measured when the fluid is in motion.

15. The method of claim 13, wherein the baseline value is measured when the fluid is in motion and wherein the changed value is measured when the fluid is stationary.

16. The method of claim 1, wherein the property to be evaluated is the ability of the physiological fluid suspension to clot.

17. The method of claim 1, wherein the property to be evaluated is a viscosity of the liquid portion of the physiological fluid suspension.

18. The method of claim 1, wherein the property to be evaluated is a turbidity of the liquid portion of the physiological fluid suspension.

19. The method of claim 1, wherein the property to be evaluated is a distribution of constituents in the physiological fluid suspension.

20. The method of claim 1, wherein the property to be evaluated is a color of one or more constituents of the physiological fluid suspension.

21. The method of claim 1, wherein the property to be evaluated is an increase or a decrease in viscosity of the liquid portion of the physiological fluid suspension.

22. A method of evaluating the ability of a fluid to clot, comprising:

inducing flow of a fluid within a fluid container by exerting force on the fluid;

measuring a baseline flow rate of the fluid;

inducing clotting within the fluid;

measuring a secondary flow of the fluid during or after inducing clotting and while the fluid is acted upon by the force; and

determining a degree of clotting in the fluid based on a difference between the baseline flow rate and the secondary flow rate of the fluid.

23. The method of claim 22, wherein the fluid is selected from the group consisting of whole blood, platelet suspensions, leukocyte suspensions, red blood cell suspensions, plasmas, and combinations thereof.

24. The method of claim 23, wherein the fluid is blood or plasma, and the method further comprises inducing platelet aggregation in the blood or plasma prior to measuring the baseline flow rate of the blood or plasma.

25. The method of claim 24, wherein measuring the baseline flow rate of the blood or plasma, and measuring the secondary flow rate of the blood or plasma, includes utilizing platelet aggregates as optical markers.

26. The method of claim 22, further comprising mixing the fluid after inducing clotting in the fluid and prior to measuring the secondary flow rate of the fluid.

27. The method of claim 22, wherein measuring the baseline flow rate and measuring the secondary flow rate includes utilization of an optical fluid flow measurement system.

28. The method of claim 22, wherein measuring the baseline flow rate and measuring the secondary flow rate includes utilization of a light scattering measurement system.

29. The method of claim 22, wherein inducing clotting within the fluid comprises adding a clotting agent to the fluid.

30. The method of claim 29, wherein the clotting agent is introduced into the container prior to introducing the fluid into the container.

31. The method of claim 29, wherein the clotting agent is selected from the group consisting of calcium salts, thromboplastin, actin, thrombin, silica, diatomaceous earth, kaolin, russel viper venom, ristocetin, clotting factors, and mixtures or combinations thereof.

32. The method of claim 22, wherein inducing flow of the fluid, measuring the baseline flow rate and the secondary flow rate, and determining the degree of clotting in the fluid are automated processes performed by an integral testing system.

33. The method of claim 22, wherein the flow is induced by at least one of:

a rotor, stir bar, plunger, roller pump, vacuum, or pneumatic drive.

34. The method of claim 33, wherein the flow is induced by a rotor.

35. The method of claim 22, wherein inducing flow of the fluid does not detrimentally alter properties of the fluid.

36. The method of claim 22, wherein the flow of the fluid is recirculated flow.

37. A method for determining a degree of clotting in a fluid suspension, comprising:

inducing flow of the fluid suspension by exerting force on the fluid;

inducing platelet aggregation in the fluid suspension;

determining a baseline fluid flow rate of the fluid suspension after platelet aggregation using platelet aggregates as optical markers;

inducing clotting in the fluid suspension;

determining a secondary fluid flow rate of the fluid suspension after clotting and while the fluid is acted upon by the force using platelet aggregates as optical markers; and

determining an extent of clotting of the fluid suspension based on the difference between the secondary fluid flow rate and the baseline fluid flow rate.

38. The method of claim 37, wherein the fluid suspension is whole blood or a plasma suspension.

39. The method of claim 37, wherein measuring the baseline flow rate and measuring the secondary flow rate includes utilization of an optical fluid flow measurement system.

40. The method of claim 37, wherein measuring the baseline flow rate and measuring the secondary flow rate includes utilization of light scattering measurement system.

41. The method of claim 37, wherein inducing clotting within the fluid comprises adding a clotting agent to the fluid.

42. The method of claim 41, wherein the clotting agent is selected from the group consisting of calcium salts, thromboplastin, actin, thrombin, silica, diatomaceous earth, kaolin, russel viper venom, ristocetin, clotting factors, and mixtures thereof.

43. The method of claim 37, wherein inducing flow of the fluid, measuring the baseline flow rate and the secondary flow rate, and determining the degree of clotting in the fluid are automated processes performed by an integral testing system.

44. The method of claim 37, wherein the flow is induced by at least one of:

a rotor, stir bar, plunger, roller pump, vacuum or pneumatic drive.

45. The method of claim 44, wherein the flow is induced by a rotor.

46. A system for determining a degree of clotting within a fluid, comprising:

a container for retaining a fluid therein;

a flow inducing system operable to induce flow of the fluid retained within the container both before and after the fluid undergoes clotting;

a clot inducing system, operable to induce clotting in the fluid retained within the container; and

a fluid flow measurement system operable to measure at least a baseline fluid flow rate of the fluid retained in the container, and a secondary flow rate of the fluid retained in the container;

wherein a degree of clotting of the fluid is determined by comparing the baseline flow rate of the fluid and the secondary flow rate of the fluid.

47. The system of claim 46, wherein the fluid is present in the container and is selected from the group consisting of whole blood, platelet suspension, leukocyte suspension, red blood cell suspension, plasma, and mixtures thereof.

48. The system of claim 46, wherein the fluid flow measurement system is an optical fluid flow measurement system.

49. The system of claim 46, wherein the fluid flow measurement system is a light scattering measurement system.

50. The system of claim 46, wherein the clot inducing system includes an opening providing selective communication between an internal environment of the container and an environment external to the container, to allow an operator to selectively introduce a clotting agent into the container.

51. The system of claim 46, further comprising a comparator, operable to receive information from the fluid flow measurement system to determine the degree of clotting of the fluid, or a rate of change of clotting of the fluid.

52. The system of claim 46, wherein the flow inducing system includes at least one of:

a rotor, stir bar, plunger, roller pump, vacuum or pneumatic drive.

53. The system of claim 46, wherein the flow inducing system includes a rotor.

54. The system of claim 46, further comprising a disruption member operable to induce or enhance mixing of the fluid within the container.

55. A method of evaluating the ability of a fluid suspension to clot, comprising:

inducing flow of a fluid suspension within a fluid container by exerting force on the fluid;

measuring a baseline flow rate of the fluid suspension;

inducing clotting within the fluid suspension;

measuring a secondary flow of the fluid suspension during or after inducing clotting and while the fluid suspension is acted upon by the force;

determining a rate of change of flow rate of the fluid suspension; and

determining a degree of clotting in the fluid suspension based on the rate of change of flow rate of the fluid suspension.

56. The method of claim 55, wherein the fluid suspension includes an anticoagulant.

57. The method of claim 56, wherein the anticoagulant is introduced into the fluid suspension prior to, along with, or after the clotting agent.

58. The method of claim 56, wherein the anticoagulant is selected from the group consisting of unfractionated heparin, low molecular weight heparin, hirudin, direct thrombin inhibitors, Factor Xa inhibitors, sodium citrate, ethylene di-amine tetra acetic acid (EDTA), antithrombin III, and combinations thereof.

59. The method of claim 55, wherein the fluid includes a thrombolytic agent.

60. The method of claim 59, wherein the thrombolytic agent is introduced into the fluid suspension prior to, along with, or after the clotting agent.

61. The method of claim 59, wherein the thrombolytic agent is selected from the group consisting of tissue plasminogen activator (tPA), streptokinase, urokinase, plasmin, serine endopeptidases, and combinations thereof.

62. The method of claim 55, wherein the fluid suspension includes a platelet aggregating agent.

63. The method of claim 62, wherein the platelet aggregating agent is introduced into the fluid suspension prior to, along with, or after an antiplatelet agent.

64. The method of claim 62, wherein the platelet aggregating agent is selected from the group consisting of adenosine di-phosphate, thrombin receptor agonist peptide, arachidonic acid, epinephrine, collagen, ristocetin, calcium ionophone, platelet factor 4, thrombin, thromboxane, vasodilator-stimulated phosphoprotein.

65. The method of claim 63, wherein the antiplatelet agent is selected from the group consisting of aspirin, thienopyridines and its metabolites, glycoprotein inhibitors (abciximab, tirofiban, eptifibatide), dipyridamole.