SYSTEMS AND METHODS FOR PARTICLE FOCUSING IN MICROCHANNELS

• US 20090014360A1
• Filed: 04/16/2008
• Published: 01/15/2009
• Est. Priority Date: 04/16/2007
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: DiCarlo, Dino, Edd, Jon, Toner, Mehmet, Irimia, Daniel
• Granted Patent: US 8,186,913 B2
• Time in Patent Office: Days
• US Class Current: 209/208
• CPC Class Codes: B01D 21/0087 Settling tanks provided with means for ensuring a special flow pattern, e.g. even inflow or outflow B01D21/2411 takes precedence
• CPC Class Codes: B01D 21/265 by using a vortex inducer or vortex guide, e.g. coil B01D21/0054 takes precedence
• CPC Class Codes: B01D 45/04 by utilising inertia B01D45/12 takes precedence
• CPC Class Codes: B01D 45/12 by centrifugal forces centrifuges B04B; cyclones B04C
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0883 Serpentine channels
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0433 vibrational forces
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 2400/0622 distribution valves, valves having multiple inlets and/or outlets, e.g. metering valves, multi-way valves
• CPC Class Codes: B01L 2400/084 Passive control of flow resistance
• CPC Class Codes: B01L 3/502746 characterised by the means for controlling flow resistance, e.g. flow controllers, baffles B01L3/502738 takes precedence
• 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: B01L 3/502776 specially adapted for focusing or laminating flows
• CPC Class Codes: B33Y 80/00 Products made by additive manufacturing
• CPC Class Codes: C12M 23/16 Microfluidic devices; Capillary tubes integrated microfluidic structures B01L3/5027; microreactors B01J19/0093
• CPC Class Codes: C12M 41/36 of biomass, e.g. colony counters or by turbidity measurements electrooptical investigation of individual particles G01N15/14, flow cytometers G01N15/1404
• CPC Class Codes: C12M 47/04 Cell isolation or sorting purging biological preparations of unwanted cells C12N5/0081, determining the presence or kind of microorganism C12Q1/04
• CPC Class Codes: F16L 41/02 : Branch units, e.g. made in one piece, welded, riveted
• CPC Class Codes: F17D 1/00 : Pipe-line systems conveying articles or materials through a pipe- line by means of a fluid carrier B65G51/00, B65G53/00; liquids B67D; special devices for transferring liquids from bulk storage containers into vehicles or boats or vice versa, e.g. loading or unloading vehicles or portable containers B67D7/00; conveying material which has been excavated by a dredger or soil shifter through a pipe-line E02F7/10; sewer pipe-line systems E03F3/00; thermal insulation of pipe-lines F16L59/00; central heating systems F24D
• CPC Class Codes: G01N 15/0255 : with mechanical, e.g. inertial, classification, and investigation of sorted collections with centrifuges G01N15/042
• CPC Class Codes: G01N 15/10 : Investigating individual particles
• CPC Class Codes: G01N 2015/0288 : Sorting the particles
• CPC Class Codes: G01N 2015/1006 : for cytology
• CPC Class Codes: G01N 2015/1028 : Sorting particles
• CPC Class Codes: G01N 2015/1081 : Sorting the particles
• CPC Class Codes: Y10T 137/85938 : Non-valved flow dividers
• CPC Class Codes: Y10T 137/85978 : With pump
• CPC Class Codes: Y10T 436/117497 : with a continuously flowing sample or carrier stream
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

Claims

1. A system for focusing particles suspended within a moving fluid into one or more localized stream lines, comprising:

a substrate;

at least one channel provided on the substrate, the at least one channel having an inlet and an outlet;

a fluid moving along the at least one channel in a laminar flow and including suspended particles;

a pumping element driving the laminar flow of the fluid;

wherein the fluid, the channel, and the pumping element are configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.

2. The system of claim 1, wherein moving the fluid suspension focuses the particles into four localized streams.

3. The system of claim 1, wherein moving the fluid suspension focuses the particles into two localized streams.

4. The system of claim 1, wherein moving the fluid suspension focuses the particles into a single localized stream.

5. The system of claim 1, wherein the at least one channel has a hydraulic diameter and a ratio of a size of the particles focused to the hydraulic diameter is greater than or equal to about 0.07.

6. The system of claim 5, wherein the ratio of particle size to hydraulic diameter is less than or equal to about 0.5.

7. The system of claim 1, wherein a Reynolds Number of the fluid flow during focusing is greater than or equal to about 1 and less than or equal to about 250.

8. The system of claim 1, wherein the one or more focused stream lines have a width that is less than or equal to about five times a size of the focused particles.

9. The system of claim 1, wherein the one or more focused stream lines have a width that is less than or equal to about four times a size of the particles focused.

10. The system of claim 1, wherein the one or more focused stream lines have a width that is less than or equal to about three times a size of the particles focused.

11. The system of claim 1, wherein the one or more focused stream lines have a width that is less than or equal to about two times a size of the particles focused.

12. The system of claim 1, wherein the one or more focused stream lines have a width that is equal to about 1.05 times a size of the particles focused.

13. The system of claim 1, wherein at least first and second outlet branches are formed at an outlet portion of the at least one channel, at least one of the first and second outlet branches being located on the substrate so as to receive the particles from a focused stream line.

14. The system of claim 13, wherein the system increases the concentration of particles in solution.

15. The system of claim 4, wherein at least first and second outlet branches are formed at an outlet portion of the at least one channel, at least one of the first and second outlet branches being located on the substrate so as to receive the particles from the single localized stream.

16. The system of claim 15, wherein the system increases the concentration of particles in solution.

17. The system of claim 1, wherein the at least one channel has a rectangular cross-section.

18. The system of claim 17, wherein the at least one rectangular channel has a width of less than or equal to about 1000 micrometers.

19. The system of claim 17, wherein the at least one rectangular channel has a width of less than or equal to about 650 micrometers.

20. The system of claim 17, wherein the at least one rectangular channel has a width of less than or equal to about 100 micrometers.

21. The system of claim 17, wherein the at least one rectangular channel has a width of less than or equal to about 80 micrometers.

22. The system of claim 17, wherein the at least one rectangular channel has a width of less than or equal to about 65 micrometers.

23. The system of claim 17, wherein the at least one rectangular channel has a width of less than or equal to about 50 micrometers.

24. The system of claim 17, wherein a size of the particles focused is less than or equal to about 20 micrometers.

25. The system of claim 17, wherein a size of the particles focused is less than or equal to about 10 micrometers.

26. The system of claim 17, wherein the particles are cells.

27. The system of claim 26, wherein the cells are mammalian cells.

28. The system of claim 27, wherein the cells are blood cells.

29. The system of claim 27, wherein the cells are tumor cells.

30. The system of claim 26, wherein the cells are bacteria cells.

31. The system of claim 17, wherein the aspect ratio of the rectangular cross-section results in the focusing of particles into two streams.

32. The system of claim 31, wherein the focusing of particles into one or more localized stream lines spaces the particles approximately evenly longitudinally.

33. The system of claim 31, wherein the aspect ratio of a first rectangle dimension to a second rectangle dimension is between approximately 0.3 and 0.8.

34. The system of claim 33, wherein the aspect ratio is approximately 1 to 2.

35. The system of claim 32, wherein a particle Reynolds number for the fluid suspension moving through the channel is greater than or equal to about 0.2.

36. The system of claim 17, wherein the at least one channel curves.

37. The system of claim 36, wherein the location of the at least one focused stream depends upon inertial forces and Dean drag forces acting on the particles.

38. The system of claim 37, wherein the location further depends upon centrifugal forces acting on the particles.

39. The system of claim 36, wherein a Dean number for flow through the channel is less than or equal to about 20.

40. The system of claim 36, wherein the curve is symmetric and sigmoidal.

41. The system of claim 36, wherein the curve is asymmetric and sigmoidal.

42. The system of claim 41, wherein the radius of curvature varies.

43. The system of claim 42, wherein the radius of curvature changes after each inflection of the curve.

44. The system of claim 43, wherein a cross sectional dimension of the channel varies.

45. The system of claim 44, wherein the cross sectional dimension of the channel changes after each inflection of the curve.

47. The system of claim 1, wherein a plurality of channels are provided on the substrate and are configured to allow parallel flow.

48. The system of claim 1, wherein a plurality of channels are provided on the substrate, and at least some of the channels are configured to allow serial flow.

49. The system of claim 1, wherein a plurality of channels are provided on the substrate and a first channel has first and second output branches leading to second and third channels respectively.

50. The system of claim 49, wherein at least two of the channels are configured to focus particles of different predetermined diameters.

51. The system of claim 1, further comprising a detector for detecting and enumerating particles in the one or more focused stream lines.

52. The system of claim 4, further comprising a detector for detecting and enumerating particles in the single localized stream.

53. The system of claim 51, further comprising a tagging system for tagging selected particles with a tag that can be detected by the detector, the detector thereby detecting and enumerating the selected particles.

46. (canceled)

54-196. -196. (canceled)