Particle separation method and apparatus

• US 6,071,422 A
• Filed: 05/26/1998
• Issued: 06/06/2000
• Est. Priority Date: 04/18/1995
• Status: Expired due to Term

• Current Assignee: Terumo BCT, Inc. (Terumo Corporation)
• Original Assignee: COBE Laboratories Incorporated (Terumo Corporation)
• Inventors: Corbin, Frank, Hlavinka, Dennis
• Primary Examiner(s): Kim, John
• Application Number:
  US09/084,132
• Time in Patent Office: 742 Days
• Field of Search: 210/782, 210/786, 210/787, 210/789, 210/806, 435/2, 435/372, 435/372.3, 494/7, 494/36, 494/5, 494/37, 494/45
• 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 1/3693 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 2005/0471 with additional elutriation separation of different particles
• CPC Class Codes: B04B 5/0428 with flexible receptacles
• 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 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. A saturated fluidized bed of first particles forms within the fluid chamber and obstructs flow of second particles through the chamber. Additive substances alter sedimentation velocity of the first particles to modify the filtration characteristics of the saturated fluidized bed.

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 an associated fluid chamber rotatable therewith, the fluid chamber having an inlet and an outlet;

controlling rotation of the rotor;

altering sedimentation velocity of the first particles;

passing a quantity of the first particles into the inlet of the rotating fluid chamber;

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

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

2. The method of claim 1, wherein the liquid in the step of flowing additionally includes first particles disbursed therein.

3. The method of claim 1, wherein the first particles include red blood cells, and the second particles include cells chosen from a group consisting of stem cells and tumor cells.

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

5. The method of claim 1 wherein the altering step includes the substep of changing size of the first particles.

6. The method of claim 1, wherein the altering step includes the substep of contacting the first particles with a solution that is hypertonic as compared to the first particles so that osmosis decreases size of the first particles.

7. The method of claim 1, wherein the altering step includes the substep of contacting the first particles with a solution that is hypotonic as compared to the first particles so that osmosis increases size of the first particles.

8. The method of claim 1, wherein the altering step includes the substep of changing tonicity of the liquid so that osmosis decreases size of the first particles.

9. The method of claim 1, wherein the altering step includes the substep of changing tonicity of the liquid so that osmosis increases size of the first particles.

10. The method of claim 1, wherein the altering step includes the substep of changing at least one of density and viscosity of the liquid.

11. The method of claim 1, wherein the altering step includes the substep of linking a number of the first particles to form a series of first particle groups.

12. The method of claim 1, wherein the first particles are red blood cells, and wherein the altering step includes the substep of contacting the red blood cells with a substance for causing the red blood cells to rouleau.

13. The method of claim 1, wherein the altering step precedes the flowing step.

14. The method of claim 1, wherein at least a portion of the altering step is simultaneously conducted with the flowing step.

15. The method of claim 1, further comprising the step of separating the portion of the first particles flowing to the outlet of the fluid chamber from the liquid flowing to the outlet of the fluid chamber.

16. 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 an associated fluid chamber rotatable therewith, the fluid chamber having an inlet and an outlet;

controlling rotation of the rotor;

altering sedimentation velocity of the first particles;

passing a quantity of the first particles into the inlet of the rotating fluid chamber;

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

flowing into the fluid chamber inlet liquid having at least a quantity of the second particles dispersed therein while simultaneously maintaining the bed within the fluid chamber, so that the bed substantially prevents flow of the second particles from the fluid chamber inlet to the fluid chamber outlet while substantially permitting flow of the liquid and a portion of the first particles from the outlet; and

separating the portion of the first particles flowing from the outlet of the fluid chamber from the liquid flowing from the outlet of the fluid chamber.

17. An apparatus for separating first particles from second particles, the apparatus comprising:

a motor;

a centrifuge rotor coupled to the motor for rotation about an axis of rotation;

a holder for holding a fluid chamber on the rotor with an outlet of the fluid chamber positioned closer to the axis of rotation than an inlet of the fluid chamber;

means for supplying liquid and first and second particles to the inlet of the fluid chamber;

means for altering sedimentation velocity of the first particles; and

means for controlling at least one of the motor and the supplying means to maintain a saturated fluidized bed of first particles within the fluid chamber and to cause second particles to be retained in the fluid chamber.

18. The apparatus of claim 17, wherein the means for altering sedimentation velocity of the first particles includes means for adjusting tonicity of the liquid to osmotically change size of the first particles.

19. The apparatus of claim 17, wherein the means for altering sedimentation velocity of the first particles includes means for adjusting at least one of density and viscosity of the liquid.

20. The apparatus of claim 17, wherein the means for altering sedimentation velocity of the first particles includes means for linking together first particles to form a series of first particle groups.

21. The apparatus of claim 17, further comprising a fluid chamber in the holder and means for separating particles flowing from the outlet in the fluid chamber from liquid flowing from the outlet of the fluid chamber.

22. The apparatus of claim 21, wherein the means for separating particles includes a supplemental chamber having an inlet in fluid communication with the outlet of the fluid chamber.

23. The apparatus of claim 21, wherein the means for separating particles includes a separation channel having a collection well for retaining particles therein, the separation channel including an inlet, a particle concentrate outlet located in the collection well, and a liquid outlet located in a portion of the separation channel outside of the collection well, the inlet of the separation channel being flow connected to the outlet of the fluid chamber.

27. The apparatus of claim 17, comprising means for separating particles flowing from the outlet of the fluid chamber from liquid flowing from the outlet of the fluid chamber.

24. An apparatus for separating first particles from second particles, the apparatus comprising:

a motor;

a centrifuge rotor coupled to the motor for rotation about an axis of rotation;

a fluid chamber connected to the rotor, the fluid chamber having an inlet and an outlet;

means for supplying liquid and first and second particles to the inlet of the fluid chamber;

means for controlling at least one of the motor and the supplying means to maintain a saturated fluidized bed of first particles within the fluid chamber and to cause second particles to be retained in the fluid chamber; and

means for separating particles flowing from the outlet of the fluid chamber from liquid flowing from the outlet of the fluid chamber.

25. The apparatus of claim 24, wherein the means for separating particles includes a supplemental chamber having an inlet in fluid communication with the outlet of the fluid chamber.

26. The apparatus of claim 24, wherein the means for separating particles includes a separation channel having a collection well for retaining particles therein, the separation channel including an inlet, a particle concentrate outlet located in the collection well, and a liquid outlet located in a portion of the separation channel outside of the collection well, the inlet of the separation channel being flow connected to the outlet of the fluid chamber.

28. The apparatus of claim 24, further comprising a holder for holding the fluid chamber on the rotor.

29. The apparatus of claim 24, further comprising means for altering sedimentation velocity of the first particles.