Multiple laminar flow-based particle and cellular separation with laser steering

• US 20070029257A1
• Filed: 10/06/2006
• Published: 02/08/2007
• Est. Priority Date: 09/04/2003
• Status: Active Grant

• Current Assignee: ABS Global, Inc. (Genus PLC)
• Original Assignee: Arryx, Inc. (Haemonetics Corporation)
• Inventors: Anderson, Amy, Shireman, Jessica, Plewa, Joseph, Mueth, Daniel, Gruber, Lewis, Rosenbaum, Neil
• Granted Patent: US 7,402,131 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: A61M 1/36 Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
• CPC Class Codes: A61M 1/3603 in the same direction
• CPC Class Codes: A61M 1/3681 by irradiation
• CPC Class Codes: A61M 1/3693 using separation based on different densities of components, e.g. centrifuging
• CPC Class Codes: A61M 1/38 Removing constituents from donor blood and storing or returning remainder to body , e.g. for transfusion
• CPC Class Codes: A61M 2206/11 Laminar flow
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B03C 1/28 Magnetic plugs and dipsticks
• CPC Class Codes: B03C 2201/02 Electrostatic separation of liquids from liquids
• CPC Class Codes: B03C 2201/18 Magnetic separation whereby the particles are suspended in a liquid
• CPC Class Codes: B03C 5/005 Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength
• CPC Class Codes: G01N 30/0005 Field flow fractionation
• CPC Class Codes: G03H 1/08 Synthesising holograms, i.e. holograms synthesized from objects or objects from hologramsusing electric digital computers G06F; G06T
• CPC Class Codes: G03H 1/2294 Addressing the hologram to an active spatial light modulator
• CPC Class Codes: G03H 2001/0077 for optical manipulation, e.g. holographic optical tweezers [HOT]
• CPC Class Codes: G03H 2001/085 Kinoform, i.e. phase only encoding wherein the computed field is processed into a distribution of phase differences
• CPC Class Codes: Y10T 436/25375 Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

The invention provides a method, apparatus and system for separating blood and other types of cellular components, and can be combined with holographic optical trapping manipulation or other forms of optical tweezing. One of the exemplary methods includes providing a first flow having a plurality of blood components; providing a second flow; contacting the first flow with the second flow to provide a first separation region; and differentially sedimenting a first blood cellular component of the plurality of blood components into the second flow while concurrently maintaining a second blood cellular component of the plurality of blood components in the first flow. The second flow having the first blood cellular component is then differentially removed from the first flow having the second blood cellular component. Holographic optical traps may also be utilized in conjunction with the various flows to move selected components from one flow to another, as part of or in addition to a separation stage.

Claims

1. A method of separating blood into components, the method comprising:

providing a first flow having a plurality of blood components;

providing a second flow;

contacting the first flow with the second flow to provide a first separation region; and

differentially sedimenting a first blood cellular component of the plurality of blood components into the second flow while concurrently maintaining a second blood cellular component of the plurality of blood components in the first flow.

2. The method of claim 1, further comprising:

differentially removing the second flow having the first blood cellular component from the first flow having the second blood cellular component.

3. The method of claim 1, wherein the first blood cellular component is a plurality of red blood cells and a plurality of white blood cells.

4. The method of claim 3, further comprising:

holographically separating the plurality of white blood cells from the plurality of red blood cells.

5. The method of claim 1, wherein the second blood cellular component is a plurality of platelets.

6. The method of claim 1, further comprising:

providing a third flow;

contacting the first flow with the third flow to provide a second separation region; and

differentially sedimenting the second blood cellular component of the plurality of blood components into the third flow while concurrently maintaining a third blood component of the plurality of blood components in the first flow.

7. The method of claim 6, further comprising:

holographically trapping the second blood cellular component.

8. The method of claim 6, wherein the second blood cellular component is a plurality of platelets and wherein the third blood component is plasma.

9. The method of claim 6, further comprising:

recirculating the first flow to form the second flow.

10. The method of claim 1, further comprising:

holographically separating a plurality of second blood cellular components from the first flow.

11. The method of claim 1, further comprising:

holographically removing a plurality of contaminants or biological debris from the first flow.

12. The method of claim 1, wherein the first flow substantially comprises whole blood from a donor and an anticoagulant, and the second flow substantially comprises plasma from the donor.

13. The method of claim 1, wherein the sedimentation step is rate zonal.

14. The method of claim 1, wherein the sedimentation step is isopycnic.

15. The method of claim 1, wherein the first flow and the second flow are substantially non-turbulent.

16. The method of claim 1, wherein the first flow and the second flow are substantially laminar.

17. The method of claim 1, wherein the separation region has a predetermined length substantially parallel to a direction of flow of the first and second flows and a predetermined depth substantially perpendicular to the direction of flow of the first and second flows, the predetermined length and predetermined depth having been determined from a first sedimentation rate of the first blood cellular component, from a second sedimentation rate of the second blood cellular component, from a first flow rate of the first flow, and from a second flow rate of the second flow.

18. The method of claim 1, wherein the first flow and the second flow have substantially the same flow rates.

19. The method of claim 1, wherein the first flow has a first flow rate and the second flow has a second flow rate, the second flow rate comparatively greater than the first flow rate.

20. The method of claim 1, wherein a first volume of the first flow in the separation region is comparatively less than a second volume of the second flow in the separation region.

21. An apparatus which performs the method of claim 1.

22. A method of separating a fluid mixture into constituent components, the method comprising:

providing a substantially laminar first flow having the fluid mixture, the fluid mixture having a plurality of components, the plurality of components having a corresponding plurality of sedimentation rates;

providing a substantially laminar second flow;

contacting the first flow with the second flow to provide a first separation region, the first flow and the second flow having a substantially non-turbulent interface within the separation region;

differentially sedimenting from the first flow a first component of the plurality of components into the second flow to form an enriched second flow and a depleted first flow, while concurrently maintaining a second component of the plurality of components in the first flow, the first component having a first sedimentation rate of the plurality of sedimentation rates and the second component having a second sedimentation rate of the plurality of sedimentation rates, wherein the first sedimentation rate is comparatively greater than the second sedimentation rate;

differentially removing the enriched second flow from the depleted first flow; and

holographically manipulating the second component in the depleted first flow.

23. The method of claim 22, wherein the fluid mixture is whole blood, wherein the first component is a plurality of red blood cells and white blood cells, and wherein the second component is a plurality of platelets.

24. The method of claim 22, wherein the fluid mixture is semen, wherein the first component is a plurality of non-motile or nonviable spermatozoa cells, and wherein the second component is a plurality of motile or viable spermatozoa cells.

25. The method of claim 22, wherein the optical manipulation step further comprises:

holographically trapping the second component to remove the second component from the depleted first flow.

26. The method of claim 22, further comprising:

holographically removing a plurality of contaminants or biological debris from the first flow.

27. The method of claim 22, further comprising:

providing a third flow;

contacting the depleted first flow with the third flow to provide a second separation region; and

holographically trapping the second component and moving the second component from the depleted first flow into the third flow while concurrently maintaining a third component of the plurality of components in the depleted first flow.

28. The method of claim 27, further comprising:

recirculating the depleted first flow to form the second flow.

29. An apparatus which performs the method of claim 22.

30. A method of separating a fluid mixture into constituent components, the method comprising:

providing a substantially laminar first flow having the fluid mixture, the fluid mixture having a plurality of components, the plurality of components having a corresponding plurality of sedimentation rates;

providing a substantially laminar second flow;

providing a substantially laminar third flow;

contacting the first flow with the second flow and with the third flow to provide a first separation region, the first flow and the second flow having a substantially non-turbulent first interface within the separation region, and the first flow and the third flow having a substantially non-turbulent second interface within the separation region;

differentially removing from the first flow a first component of the plurality of components into the second flow to form an enriched second flow and a depleted first flow;

differentially removing from the first flow a second component of the plurality of components into the third flow to form an enriched third flow and a further depleted first flow;

differentially removing the enriched second flow from the depleted first flow; and

differentially removing the enriched third flow from the depleted first flow.

31. The method of claim 30, wherein the first flow, the second flow, and the third flow each have a different density to provide a stepped density gradient in the first separation region.

32. The method of claim 30, wherein the removal of the first component and the second component from the first flow is performed by diffusion.

33. The method of claim 30, wherein the removal of the first component and the second component from the first flow is performed by isopycnic or rate zonal sedimentation.

34. The method of claim 30, wherein the removal of the second component from the first flow is performed by holographic optical trapping manipulation.

35. The method of claim 30, wherein the removal of the first component and the second component from the first flow is performed electromagnetically.

36. The method of claim 30, wherein the fluid mixture is whole blood, wherein the first component is a plurality of red blood cells and white blood cells, and wherein the second component is a plurality of platelets.

37. The method of claim 30, wherein the fluid mixture is semen, wherein the first component is a plurality of non-motile or nonviable spermatozoa cells, and wherein the second component is a plurality of motile or viable spermatozoa cells.

38. The method of claim 30, wherein the step of differentially removing from the first flow the second component further comprises:

holographically trapping the second component to remove the second component from the depleted first flow.

39. An apparatus for separating a fluid mixture into constituent components, the apparatus comprising:

means for providing a substantially laminar first flow having the fluid mixture, the fluid mixture having a plurality of components, the plurality of components having a corresponding plurality of sedimentation rates;

means for providing a substantially laminar second flow;

means for providing a substantially laminar third flow;

means for contacting the first flow with the second flow and with the third flow to provide a first separation region, the first flow and the second flow having a substantially non-turbulent first interface within the separation region, and the first flow and the third flow having a substantially non-turbulent second interface within the separation region;

means for differentially removing from the first flow a first component of the plurality of components into the second flow to form an enriched second flow and a depleted first flow;

means for differentially removing from the first flow a second component of the plurality of components into the third flow to form an enriched third flow and a further depleted first flow;

means for differentially removing the enriched second flow from the depleted first flow; and

means for differentially removing the enriched third flow from the depleted first flow.

40. The apparatus of claim 39, wherein the first flow, the second flow, and the third flow each have a different density to provide a stepped density gradient in the first separation region.

41. The apparatus of claim 39, wherein the means for removal of the first component and the second component from the first flow is diffusion.

42. The apparatus of claim 39, wherein the means for removal of the first component and the second component from the first flow is performed by isopycnic or rate zonal sedimentation.

43. The apparatus of claim 39, wherein the means for removal of the second component from the first flow is a holographic optical trap.

44. The apparatus of claim 39, wherein the fluid mixture is whole blood, wherein the first component is a plurality of red blood cells and white blood cells, and wherein the second component is a plurality of platelets.

45. The apparatus of claim 39, wherein the fluid mixture is semen, wherein the first component is a plurality of non-motile or nonviable spermatozoa cells, and wherein the second component is a plurality of motile or viable spermatozoa cells.

46. A method of separating blood into components, the method comprising:

providing a substantially laminar first flow having a plurality of blood components;

providing a substantially laminar second flow;

contacting the first flow with the second flow to provide a first separation region, a size of the first separation region having been predetermined based on a plurality of sedimentation rates of the plurality of blood components;

differentially rate zonal sedimenting a plurality of red blood cells and a plurality of white blood cells, of the plurality of blood components, into the second flow while concurrently maintaining a plurality of platelets and plasma, of the plurality of blood components, in the first flow;

differentially removing the second flow having the first blood cellular component from the first flow having the second blood cellular component;

providing a third flow;

contacting the first flow with the third flow to provide a second separation region;

differentially rate zonal sedimenting the plurality of platelets into the third flow while concurrently maintaining plasma in the first flow; and

recirculating the first flow to form the second flow.

47. An apparatus for separating a plurality of components in a fluid, the apparatus comprising:

an optically transparent sorting channel having a first inlet for a first flow and a second inlet for a second flow, the optically transparent sorting channel further having a first outlet for the first flow and a second outlet for the second flow; and

a holographic optical trap system coupled to the optically transparent sorting channel, the holographic optical trap system adapted to generate a holographic optical trap to select and move a first component in the first flow, of a plurality of components in the first flow, into the second flow to form an enriched second flow and a depleted first flow, while a second component of the plurality of components is concurrently maintained in the first flow.

48. An apparatus for separating a fluid mixture into constituent, non-motile components, the apparatus comprising:

a first sorting channel having a first inlet for a first flow and a second inlet for a second flow;

the first sorting channel further having a first outlet for the first flow and a second outlet for the second flow, the first sorting channel adapted to allow a first component in the first flow, of a plurality of components in the first flow, to sediment into the second flow to form an enriched second flow and a depleted first flow, while concurrently maintaining a second component of the plurality of components in the first flow;

a second, optically transparent sorting channel having a first optical inlet coupled to the first outlet for the first flow and having a first optical outlet, the second, optically transparent sorting channel further having a second optical inlet for a third flow and a second optical outlet for the third flow; and

a holographic optical trap system coupled to the second, optically transparent sorting channel, the holographic optical trap system adapted to generate a holographic optical trap to select and move the second component from the first flow into the third flow.

49. A method of separating a plurality of cells, the method comprising:

providing a first flow having the plurality of cells;

providing a second flow;

contacting the first flow with the second flow to provide a first separation region; and

differentially removing a first cell of the plurality of cells into the second flow while concurrently maintaining a second cell of the plurality of cells in the first flow.

50. The method of claim 49, further comprising:

differentially removing the second flow having the first cell from the first flow having the second cell.

51. The method of claim 49, further comprising:

providing a third flow;

contacting the first flow with the third flow to provide a second separation region; and

differentially removing the second cell of the plurality of cells into the third flow while concurrently maintaining a third cell of the plurality of cells in the first flow.

52. The method of claim 49, further comprising:

holographically separating a plurality of second cells from the first flow.

53. The method of claim 49, further comprising:

holographically removing a plurality of contaminants or biological debris from the first flow.

54. The method of claim 49, wherein the first flow and the second flow each have a different density to provide a stepped density gradient in the first separation region.

55. The method of claim 49, wherein the removal of the first cell from the first flow is performed by isopycnic or rate zonal sedimentation.

56. The method of claim 55, wherein the first cell is a nonviable or non-motile spermatozoa cell.

57. The method of claim 49, wherein the removal of the first cell from the first flow is performed by self-motility.

58. The method of claim 57, wherein the first cell is a viable or motile spermatozoa cell.

59. An apparatus for separating a plurality of cells, the method comprising:

means for providing a first flow having the plurality of cells;

means for providing a second flow;

means for contacting the first flow with the second flow to provide a first separation region; and

means for differentially removing a first cell of the plurality of cells into the second flow while concurrently maintaining a second cell of the plurality of cells in the first flow.

60. The apparatus of claim 59, further comprising:

means for differentially removing the second flow having the first cell from the first flow having the second cell.

61. The apparatus of claim 59, further comprising:

means for providing a third flow;

means for contacting the first flow with the third flow to provide a second separation region; and

means for differentially removing the second cell of the plurality of cells into the third flow while concurrently maintaining a third cell of the plurality of cells in the first flow.

62. The apparatus of claim 59, further comprising:

means for holographically separating a plurality of second cells from the first flow.

63. The apparatus of claim 59, wherein the first flow and the second flow each have a different density to provide a stepped density gradient in the first separation region.

64. The apparatus of claim 59, wherein the means for removal of the first cell from the first flow is isopycnic or rate zonal sedimentation.

65. The apparatus of claim 64, wherein the first cell is a nonviable or non-motile spermatozoa cell.

66. The apparatus of claim 59, wherein the means for removal of the first cell from the first flow is self-motility.

67. The apparatus of claim 66, wherein the first cell is a viable or motile spermatozoa cell.

68. An apparatus for separating a component from a plurality of components in a fluid, the apparatus having an aspect ratio of length to width, the apparatus comprising:

a first sorting channel having a first inlet for a first flow and a second inlet for a second flow;

the first and second flows each having a flow direction along the length of the apparatus, the first sorting channel further having a first outlet for the first flow and a second outlet for the second flow, the first sorting channel adapted to allow a first component in the first flow, of a plurality of components in the first flow, to be selectively removed into the second flow to form an enriched second flow and a depleted first flow, while concurrently maintaining a second component of the plurality of components in the first flow; and

wherein the aspect ratio of length to width is less than about 2;

1.

69. The apparatus of claim 68, wherein the aspect ratio of length to width is from about 2:

1 to 1;

2.

70. The apparatus of claim 68, further comprising:

a second, optically transparent sorting channel having a first optical inlet coupled to the first outlet for the first flow and having a first optical outlet, the second, optically transparent sorting channel further having a second optical inlet for a third flow and a second optical outlet for the third flow; and

a holographic optical trap system coupled to the second, optically transparent sorting channel, the holographic optical trap system adapted to generate a holographic optical trap to select and move the second component from the first flow into the third flow.

71. (canceled)