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

• US 7,699,767 B2
• Filed: 06/13/2008
• Issued: 04/20/2010
• Est. Priority Date: 07/31/2002
• Status: Expired due to Term

• Current Assignee: ABS Global, Inc. (Genus PLC)
• Original Assignee: Arryx, Inc. (Haemonetics Corporation)
• Inventors: Anderson, Amy, Mueth, Daniel, Rosenbaum, Neil Harris, Shireman, Jessica, Plewa, Joseph, Gruber, Lewis
• Primary Examiner(s): NGUYEN, KIET TUAN
• Application Number:
  US12/213,109
• Publication Number:
  US 20090032449A1
• Time in Patent Office: 676 Days
• Field of Search: 494/3, 494/5, 494/36, 494/37, 494/38, 494/45, 250/251, 210/782, 210/786, 210/787, 210/252, 210/259, 210/360.1, 435/2, 435/7, 435/173.1, 435/372, 435/372.3, 422/72, 422/82.05, 422/82.06, 422/82.11, 422/101, 422/104, 436/177
• US Class Current: 494/36
• CPC Class Codes: A61L 2/08 Radiation
• CPC Class Codes: B01D 21/0009 Settling tanks making use of electricity or magnetism electric ultra filters B01D61/425; filters making use of electricity or magnetism B01D35/06; magnetic or electrostatic separation B03C
• CPC Class Codes: B01D 21/01 using flocculating agents for purifying water C02F1/52; for liquid radioactive waste G21F9/10
• CPC Class Codes: B01D 21/262 by using a centrifuge
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0864 comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• 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 1/00 Magnetic separation
• CPC Class Codes: B03C 1/002 High gradient magnetic separation
• CPC Class Codes: B03C 1/288 disposed at the outer circumference of a recipient
• CPC Class Codes: B03C 2201/26 for use in medical applications
• CPC Class Codes: B03C 5/005 Dielectrophoresis, i.e. dielectric particles migrating towards the region of highest field strength B03C5/02 takes precedence; electrophoresis B01D57/02
• CPC Class Codes: B04B 13/00 Control arrangements specially designed for centrifuges; Programme control of centrifuges control arrangements for feed, charge, or discharge B04B11/00
• CPC Class Codes: G01N 15/0205 by optical means
• CPC Class Codes: G01N 15/0227 using imaging; using holography
• CPC Class Codes: G01N 15/04 Investigating sedimentation of particle suspensions
• CPC Class Codes: G01N 15/042 by centrifuging and investigating centrifugates centrifuges per se B04B
• CPC Class Codes: G01N 15/05 in blood
• CPC Class Codes: G01N 15/0631 : Separation of liquids, e.g. by absorption, wicking
• CPC Class Codes: G01N 15/0656 : using electric, e.g. electrostatic methods or magnetic methods by investigating individual particles G01N15/1031, G01N15/12
• CPC Class Codes: G01N 15/14 : Optical investigation techniques, e.g. flow cytometry
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/0053 : in liquids, e.g. trouble
• CPC Class Codes: G01N 2015/0233 : using holography
• CPC Class Codes: G01N 2015/0288 : Sorting the particles
• CPC Class Codes: G01N 2015/035 : the optical arrangement forming an integrated apparatus with the sample container
• CPC Class Codes: G01N 2015/045 : by optical analysis
• CPC Class Codes: G01N 2015/1016 : Particle flow simulating, e.g. liquid crystal cell
• CPC Class Codes: G01N 2015/1028 : Sorting particles
• CPC Class Codes: G01N 21/6486 : Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence
• CPC Class Codes: G01N 2201/061 : Sources
• CPC Class Codes: G01N 2458/00 : Labels used in chemical analysis of biological material
• CPC Class Codes: G01N 27/447 : using electrophoresis
• CPC Class Codes: G01N 27/44756 : Apparatus specially adapted therefor
• CPC Class Codes: G01N 33/487 : of liquid biological material
• CPC Class Codes: G01N 33/491 : by separating the blood components G01N15/05 takes precedence
• CPC Class Codes: G01N 33/4915 : using flow cells flow cytometry G01N15/14
• CPC Class Codes: G01N 33/5091 : for testing the pathological state of an organism
• CPC Class Codes: G02B 21/32 : Micromanipulators structurally combined with microscopes
• CPC Class Codes: G03H 1/0005 : Adaptation of holography to specific applications holographic optical element G02B5/32; holographic scanner G02B26/106; recognition using holographic mask G06V10/88; holographic memories G11B7/0065, G11C13/042
• 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: G03H 2225/32 : Phase only
• CPC Class Codes: G21K 5/08 : Holders for targets or for other objects to be irradiated
• CPC Class Codes: H05H 3/04 : Acceleration by electromagnetic wave pressure

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 sorting a mixture comprising:

providing an input solution, including a plurality of components, through an input channel into a sorting region as a substantially laminar first flow;

providing a buffer solution through a buffer channel into said sorting region as a substantially laminar second flow;

contacting said first flow with said second flow in said sorting region, said first flow and said second flow having a substantially non-turbulent, laminar flow separation interface within said sorting region; and

sorting said plurality of components from said input channel in said sorting region using holographic optical trapping, such that selected components from said plurality of components are optically trapped and removed from said sorting region via a selected channel into a selected solution, and unselected components from said plurality of components are removed from said sorting region via a waste channel.

2. The method according to claim 1, further comprising:

pumping said input solution and said buffer solution into said sorting region.

3. The method according to claim 2, further comprising:

maintaining a constant flow rate and pressure during said pumping.

4. The method according to claim 3, further comprising:

incorporating bubble traps at said input channel or said buffer channel.

5. The method according to claim 1, wherein the mixture is blood, and said plurality of components include red blood cells, white blood cells, contaminants, platelets and cellular debris.

6. The method according to claim 5, wherein said selected components are one of red blood cells and platelets, and said unselected components are white blood cells, contaminants and cellular debris.

7. The method according to claim 1, further comprising:

creaming said selected components from said plurality of components from said input channel, in said sorting region, to exit through said selection channel.

8. The method according to claim 1, further comprising:

sedimenting said selected components from said plurality of components from said input channel, in said sorting region, to exit through said selection channel.

9. The method according to claim 1, further comprising:

pumping said input solution into said input channel, and said selected components in said selection channel to a selected solution reservoir, and said unselected components in said waste channel to a waste solution reservoir.

10. An apparatus for sorting a mixture, comprising:

an input reservoir which holds an input solution including a plurality of components;

a buffer reservoir which holds a buffer solution;

a sorter having an input channel for input of said input solution, and a buffer channel for input of said buffer solution, and a selection channel for removal of selected components of said plurality of components, and a waste channel for removal of unselected components of said plurality of components;

wherein said input solution and said buffer solution enter said sorter as a first flow and second flow, respectively, as substantially laminar flows, and said first flow and said second flow contact each other in a sorting region of said sorter, said first flow and said second flow having a substantially non-turbulent, laminar flow separation interface within said sorting region; and

a holographic optical trapping system which optically traps said selected components of said plurality of components in said sorting region, and moves said selected components to said selection channel, whereas unselected components exit through said waste channel.

11. The apparatus according to claim 10, further comprising:

a pumping system, to pump said input solution and said buffer solution into said sorter.

12. The apparatus according to claim 11, wherein a constant flow rate and pressure are maintaining during pumping by said pumping system.

13. The apparatus according to claim 12, further comprising:

at least one bubble trap incorporated at said input channel or said buffer channel.

14. The apparatus according to claim 10, wherein the mixture is blood, and said plurality of components include red blood cells, white blood cells, contaminants, platelets and cellular debris.

15. The apparatus according to claim 14, wherein said selected components are one of red blood cells and platelets, and said unselected components are white blood cells, contaminants and cellular debris.

16. The apparatus according to claim 10, wherein said selected components from said plurality of components are creamed from said input channel, in said sorting region, to exit through said selection channel, and forwarded to a selected solution reservoir.

17. The apparatus according to claim 16, wherein said sorter is a multi-layer laminar flow sorter, said multi-layer laminar flow sorter comprising:

a plurality of buffer channels introducing buffer solution into said sorting region, as a top layer and a bottom layer;

a plurality of input channels introducing input solutions as substantially laminar flows into said sorting region;

a plurality of selection channels for removal of said selected components from said sorting region; and

a plurality of sorting stages forming a layer between said input channels and said selection channels, in said sorting region;

wherein said selected components are separated from said unselected components in said sorting stages.

18. The apparatus according to claim 17, wherein said sorting stages include tortuous channel configurations.

19. The apparatus according to claim 17, further comprising:

a plurality of flow control posts in said sorting stages, to regulate fluid flow within the channel configurations.

20. The apparatus according to claim 10, wherein said selected components are sedimented from said plurality of components from said input channel, in said sorting region, to exit through said selection channel, and forwarded to a selected solution reservoir.

21. The apparatus according to claim 10, wherein said unselected components from said plurality of components exit through said waste channel to a waste solution reservoir.

22. The apparatus according to claim 10, further comprising:

a pumping system to pump said input solution into said input channel, and said selected components in said selection channel to a selected solution reservoir, and said unselected components in said waste channel to a waste solution reservoir.

23. The apparatus according to claim 10, wherein said sorter is a high-aspect flat sorter.

24. The apparatus according to claim 23, further comprising:

a pair of dividers, which divide said sorter into three regions, an input region, said sorting region, and an output region.

25. The apparatus according to claim 23, further comprising a plurality of flat sorters, each connected to said input solution reservoir, buffer solution reservoir, selected solution reservoir, and waste solution reservoir.

26. The apparatus according to claim 23, further comprising:

a plurality of buffer channels having substantially laminar second flows, said second flows which form more than one non-turbulent, laminar flow interface with at least said first flow, and a plurality of selection channels for receiving selected components, such that of said plurality of selection channels has a different selected component.

27. The apparatus according to claim 26, wherein said first flow and said second flows are flowing at different rates.

28. The apparatus according to claim 26, wherein said sorting region is constricted.

29. The apparatus according to claim 23, further comprising:

a plurality of selection channels, such that different selected components are removed from the sorting region.