Particle filter method

• US 5,951,877 A
• Filed: 07/05/1996
• Issued: 09/14/1999
• Est. Priority Date: 04/18/1995
• Status: Expired due to Term

• Current Assignee: Terumo BCT, Inc. (Terumo Corporation)
• Original Assignee: Cobe Cardiovascular Incorporated (LivaNova Plc)
• Inventors: Taylor, Linda A., Langley, Robert, Hlavinka, Dennis, Walker, John C.
• Primary Examiner(s): Kim, John
• Application Number:
  US08/676,041
• Time in Patent Office: 1,166 Days
• Field of Search: 210/645, 210/767, 210/782, 210/787, 210/789, 210/806, 210/786, 604/4, 604/5, 604/6, 494/37, 422/139, 422/140, 422/145, 422/147, 435/2
• US Class Current: 210/782
• CPC Class Codes: A61M 1/0227 and means for securing the filter against damage, e.g. during centrifugation
• CPC Class Codes: A61M 1/0236 with sampling means, e.g. sample bag or sampling port
• CPC Class Codes: A61M 1/3618 Magnetic separation
• CPC Class Codes: A61M 1/362 changing physical properties of target cells by binding them to added particles to facilitate their subsequent separation from other cells, e.g. immunoaffinity
• CPC Class Codes: A61M 1/3633 Blood component filters, e.g. leukocyte filters
• CPC Class Codes: A61M 1/3693 using separation based on different densities of components, e.g. centrifuging
• CPC Class Codes: A61M 1/3696 with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation
• CPC Class Codes: B04B 2005/045 having annular separation channels
• CPC Class Codes: B04B 2005/0471 with additional elutriation separation of different particles
• CPC Class Codes: B04B 5/0442 with means for adding or withdrawing liquid substances during the centrifugation, e.g. continuous centrifugation

Abstract

An apparatus and method are disclosed for filtering or separating particles. The apparatus has a motor coupled to a centrifuge rotor rotatable about an axis of rotation. A fluid chamber rotates with the rotor. A substance is supplied to the inlet of the chamber. At least one of the motor and the substance supply are controlled to maintain a saturated fluidized bed of first particles within the fluid chamber while causing second particles to be retained in the chamber.

Claims

1. A method of separating first particles from second particles, the method comprising the steps of:

rotating a centrifuge rotor about an axis of rotation, the rotor having a fluid chamber;

passing second particles into an inlet of the fluid chamber;

forming, with the second particles, a saturated fluidized bed within the fluid chamber; and

flowing the liquid having at least first particles into the fluid chamber inlet while maintaining the bed within the fluid chamber, so that the bed substantially prevents flow of first particles from the fluid chamber inlet to a fluid chamber outlet while substantially permitting flow of the liquid to the outlet.

2. The method of claim 1 wherein the step of flowing includes flowing liquid and second particles.

3. The method of claim 1, wherein both the step of passing and the step of flowing includes conveying plasma into the fluid chamber.

4. The method of claim 1, wherein the first particles include white blood cells and the second particles include platelets.

5. The method of claim 1, wherein the first particles include white blood cells and the second particles include red blood cells.

6. The method of claim 1, wherein the first particles include stem cells and the second particles include tumor cells.

7. The method of claim 1, wherein the first particles include tumor cells and the second particles include stem cells.

8. The method of claim 1, wherein a fluid flow rate during the flowing step is within a range of 1 ml/min to 15 ml/min.

9. The method of claim 1, further comprising, after the step of flowing, the step of removing second particles retained in the fluid chamber.

10. The method of claim 9, further comprising the step of removing first particles from the fluid chamber after the step of removing second particles.

11. The method of claim 1, wherein the step of flowing includes the substeps of conveying blood components into a separation chamber, separating the blood components within the separation chamber, and directing at least a portion of the separated components into the fluid chamber inlet.

12. The method of claim 11, wherein the portion of separated components includes at least plasma, platelets, and white blood cells.

13. The method of claim 11, wherein the portion of separated components includes at least plasma, platelets, and red blood cells.

14. The method of claim 11, wherein the portion of separated components includes at least plasma, red blood cells, and white blood cells.

15. The method of claim 11, further comprising the step of directing platelets retained in the separation chamber into the fluid chamber inlet while maintaining the bed within the fluid chamber.

16. The method of claim 1, further comprising the step of flowing the liquid from the fluid chamber outlet into an inlet of an auxiliary fluid chamber.

17. The method of claim 1, wherein the method further comprises controlling rotation of the rotor.

18. The method of claim 17, wherein the step of controlling includes the substeps of sequentially lowering, and then increasing a rotational speed of the rotor, and the step of flowing includes the substep of increasing flow of liquid having first particles simultaneously with the substep of increasing rotational speed of the rotor.

19. The method of claim 17, wherein the step of controlling includes the substeps of sequentially lowering the speed of the rotor to a first speed N_i, and then increasing the rotor speed to a second speed, N, and wherein the step of flowing includes the substeps of sequentially maintaining flow of liquid having first particles at a first flow rate, Q_i, and then, simultaneously with the substep of increasing the rotor speed, increasing the flow rate to a second flow rate, Q, wherein Q/N² =Q_i /N_i².

20. The method of claim 17, wherein the step of controlling includes the substep of substantially maintaining rotational speed of the rotor, and the step of flowing includes the substep of rapidly increasing a flow rate of the liquid having first particles.

21. The method of claim 17, wherein the step of controlling includes the substep of substantially maintaining rotational speed of the rotor, and the step of flowing includes the substep of gradually increasing a flow rate of the liquid having first particles.

22. The method of claim 17, wherein the step of controlling includes the substep of substantially maintaining rotational speed of the rotor, and the substep of flowing includes the substeps of gradually increasing a flow rate of the liquid having first particles to a first flow rate, maintaining the first flow rate of the liquid, and gradually increasing the flow rate of the liquid.

23. The method of claim 17, wherein the step of controlling includes the substep of regulating rotation of the rotor in a speed range to maintain a gravitational field in the fluid chamber ranging from approximately 500 G to 800 G.

50. The method of claim 1, wherein the liquid having at least first particles includes components of blood removed from an umbilical cord.

51. The method of claim 50, wherein the components of blood include at least red blood cells and white blood cells, wherein the first particles include the white blood cells, and wherein the method further comprises reducing the number of red blood cells prior to the flowing of the liquid into the fluid chamber.

52. The method of claim 51, wherein the reducing of the number of red blood cells includes removing red blood cells from a separation channel on the centrifuge rotor.

24. A method of separating white blood cells from a liquid, the method comprising the steps of:

passing at least particles into an inlet of a fluid chamber;

forming within the fluid chamber a substantial barrier to white blood cell flow through the fluid chamber, the barrier including a saturated fluidized bed of the particles;

flowing into the fluid chamber a liquid having at least the particles and the white blood cells to be separated;

obstructing with the fluidized bed, while permitting the liquid to pass through the fluid chamber, white blood cell movement through the fluid chamber, at least a portion of the obstructing step occurring during at least a portion of the flowing step; and

releasing a portion of the particles from the fluidized bed while maintaining a saturated bed of the particles in the fluid chamber.

25. The method of claim 24, wherein the particles include platelets.

26. The method of claim 25, further comprising the step of separating particle constituents from the white blood cells before the flowing step.

27. The method of claim 24, wherein the particles include red blood cells.

28. The method of claim 24, wherein the liquid includes components of blood removed from an umbilical cord.

29. The method of claim 24, further including the step of priming the fluid chamber with a priming fluid having a density less than a density of the liquid.

30. The method of claim 29, wherein said priming fluid comprises one of saline solution and air.

31. The method of claim 24, further including the step of priming the fluid chamber with the liquid.

53. The method of claim 28, wherein the components of blood include red blood cells, and wherein the method further comprises reducing the number of red blood cells prior to the flowing of the liquid into the fluid chamber.

54. The method of claim 53, wherein the reducing of the number of red blood cells includes applying centrifugal force to separate the components of blood and removing red blood cells during the application of the centrifugal force.

32. A method of separating blood components, the method comprising the steps of:

applying a centrifugal force to blood to separate the blood into components including at least plasma, platelets, and white blood cells,

whereby at least a portion of the platelets become at least partially activated during the applying step;

flowing the separated blood components into a fluid chamber; and

rotating the fluid chamber about an axis of rotation; and

filtering the components in the rotating fluid chamber with a barrier for obstructing white blood cells, to remove white blood cells, while a substantial number of platelets remain activated,

wherein at least a portion of the filtering step occurs during at least a portion of the flowing step and during at least a portion of the applying step.

33. The method of claim 32, further comprising, after the step of filtering, the step of recovering at least 95% of the platelets separated in the applying step.

34. The method of claim 32, further comprising, after the step of filtering, the step of recovering at least 98% of the platelets separated in the applying step.

35. A method of separating blood components, the method comprising the steps of:

applying a centrifugal force to blood to separate the blood into components including at least plasma, platelets, and white blood cells.

whereby at least a portion of the platelets become at least partially activated during the applying step;

flowing the separated blood components into a fluid chamber; and

filtering the components in the fluid chamber to remove white blood cells, while a substantial number of platelets remain activated, the filtering including flowing the components into a saturated fluidized bed of platelets,

wherein at least a portion of the filtering step occurs during at least a portion of the flowing step and during at least a portion of the applying step.

36. A method of separating particles in a liquid, the method comprising the steps of:

initially separating particles in a liquid according to at least one of different densities and different sedimentation velocities;

flowing at least a portion of the particles separated in the initial separating step into a fluid chamber;

forming a saturated fluidized bed of particles in the fluid chamber, the particles forming the saturated fluidized bed including particles flowing in the fluid chamber during the flowing step; and

further separating the particles within the fluid chamber according to different sedimentation velocities, the further separating step including filtering particles with the saturated fluidized bed of particles.

37. The method of claim 36, wherein the particles comprise blood components.

42. The method of claim 36, wherein at least a portion of the further separating step occurs during at least a portion of the initially separating step.

38. A method of separating blood components, the method comprising the steps of:

rotating a centrifuge rotor about an axis of rotation, the rotor having a separation chamber and a fluid chamber;

conveying blood components into the separation chamber;

separating the blood components within the separation chamber into at least first blood components and second blood components;

directing second blood components and at least a portion of the first blood components from the separation chamber into the fluid chamber; and

filtering within the fluid chamber, while the fluid chamber is on the centrifuge rotor, the first blood components with a barrier for obstructing first particles, to remove at least a portion of first particles from the second blood components.

40. The method of claim 38, wherein the directing step includes the substep of flushing a substantial number of second components retained in the separation chamber into the fluid chamber.

43. The method of claim 38, wherein the method further comprises controlling rotation of the rotor.

44. The method of claim 38, wherein at least a portion of the filtering step occurs during at least a portion of the separating step.

45. The method of claim 38 wherein the filtering step occurs during at least a portion of the rotating step.

39. A method of separating blood components, the method comprising the steps of:

rotating a centrifuge rotor about an axis of rotation, the rotor having a separation chamber and a fluid chamber;

conveying blood components into the separation chamber;

separating the blood components within the separation chamber into at least first blood components and second blood components;

directing second blood components and at least a portion of the first blood components from the separation chamber into the fluid chamber; and

filtering within the fluid chamber, while the fluid chamber is on the centrifuge rotor, the first blood components to remove at least a portion of first particles from the second blood components, the filtering including obstructing passage of first particles using a saturated fluidized bed of second particles.

41. A method of separating first and second particles within a fluid chamber provided on a centrifuge rotor, the method comprising the steps of:

rotating the centrifuge rotor about an axis of rotation;

flowing liquid carrying at least first and second particles from a source into an inlet of the fluid chamber, the second particles entering the fluid chamber inlet at a first concentration; and

forming a saturated fluidized bed including the second particles, the saturated fluidized bed preventing a substantial number of first particles from flowing from the fluid chamber inlet to a fluid chamber outlet while permitting liquid and a second concentration of second particles to flow to the outlet, the second concentration of second particles being substantially equal to the first concentration, wherein at least a portion of the flowing step occurs during at least a portion of the forming step.

55. The method of claim 41, wherein the liquid having the first and second particles includes components of blood removed from an umbilical cord.

56. The method of claim 55, wherein the components of blood include at least red blood cells and white blood cells, wherein the first particles include the white blood cells, and wherein the method further comprises reducing the number of red blood cells prior to the flowing of the liquid into the fluid chamber.

57. The method of claim 56, wherein the reducing of the number of red blood cells includes removing red blood cells from a separation channel on the centrifuge rotor.

46. A method of separating first particles from liquid and second particles, the method comprising:

rotating a centrifuge rotor about an axis of rotation, the rotor having a separation chamber and a fluid chamber;

conveying at least liquid, first particles, and second particles into the separation chamber;

separating within the separation chamber a first portion of the first particles from the liquid, a second portion of the first particles, and the second particles;

directing at least some of the liquid, the second portion of the first particles, and the second particles from the separation chamber into the fluid chamber; and

filtering within the fluid chamber, while the fluid chamber is on the centrifuge rotor, the second portion of the first particles with a barrier for obstructing first particles, to remove at least some of the first particles from the liquid and from the second particles.

47. The method of claim 46, wherein the liquid includes plasma, the first particles include white blood cells, and the second particles include platelets.

48. The method of claim 46, wherein the liquid includes plasma and the second particles include red blood cells.

49. The method of claim 46, wherein the barrier for obstructing first particles is a saturated fluidized bed including second particles.

58. The method of claim 46, wherein the liquid, first particles, and second particles directed into the fluid chamber include components of blood removed from an umbilical cord.

59. The method of claim 58, wherein the components of blood include at least red blood cells and white blood cells, wherein the first particles include the white blood cells, and wherein the method further comprises reducing the number of red blood cells prior to the filtering.