Laminar Flow-Based Separations of Colloidal and Cellular Particles

• US 20030159999A1
• Filed: 02/04/2003
• Published: 08/28/2003
• Est. Priority Date: 02/04/2002
• Status: Active Grant

• Current Assignee: Colorado School of Mines
• Original Assignee: Colorado School of Mines
• Inventors: Marr, David W.M., Oakey, John
• Granted Patent: US 7,318,902 B2
• Time in Patent Office: Days
• US Class Current: 210/695
• CPC Class Codes: B01D 57/02 by electrophoresis treatment of water, waste water, sewage or sludge by electrophoresis C02F1/469; electrophoretic production of compounds or non-metals C25B7/00; investigating or analysing materials by using electrophoresis G01N27/26
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0647 Handling flowable solids, e.g. microscopic beads, cells, particles
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0439 ultrasonic vibrations, vibrating piezo elements
• CPC Class Codes: B01L 2400/0454 radiation pressure, optical tweezers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502715 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/502753 characterised by bulk separation arrangements on lab-on-a-chip devices, e.g. for filtration or centrifugation separation in general B01D; microapparatus for analysis using electrophoresis G01N27/44791; sample preparation G01N1/28
• 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: B07C 5/06 measured mechanically sorting of cartridges F42B35/02
• CPC Class Codes: G01N 15/1023 Microstructural devices for non-optical measurement
• CPC Class Codes: G01N 15/1031 by measuring electrical or magnetic effects
• CPC Class Codes: G01N 15/1433 using image recognition
• CPC Class Codes: G01N 15/1459 the analysis being performed on a sample stream
• CPC Class Codes: G01N 15/1484 microstructural devices
• CPC Class Codes: G01N 15/149 : specially adapted for sorting particles, e.g. by their size or optical properties
• CPC Class Codes: G01N 2015/1406 : Control of droplet point
• CPC Class Codes: G01N 2015/1486 : Counting the particles
• CPC Class Codes: G01N 2030/009 : Extraction
• CPC Class Codes: G01N 30/00 : Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation G01N3/00, G01N5/00, G01N7/00, G01N9/00, G01N11/00, G01N13/00, G01N15/00, G01N17/00, G01N19/00, G01N21/00, G01N22/00, G01N23/00, G01N24/00, G01N25/00, G01N27/00, G01N29/00 take precedence
• CPC Class Codes: G01N 30/0005 : Field flow fractionation
• CPC Class Codes: G01N 30/10 : using a splitter
• CPC Class Codes: G01N 30/6052 : body
• CPC Class Codes: Y10T 436/25375 : Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]

Abstract

A system, method and apparatus employing the laminar nature of fluid flows in microfluidic flow devices in separating, sorting or filtering colloidal and/or cellular particles from a suspension in a microfluidic flow device is disclosed. The microfluidic flow device provides for separating a particle within a suspension flow in a microfluidic flow chamber. The chamber includes a microfluidic channel comprising at least one inlet port for receiving a suspension flow under laminar conditions, a first outlet port and a second outlet port. The chamber further includes an interface for translating a particle within the channel. The first outlet port receives a first portion of the suspension exiting the said channel and the second outlet port receives the particle in a second portion of the suspension exiting the channel.

Claims

1. A microfluidic flow device for separating a particle within a suspension flow, the microfluidic flow device comprising:

a microfluidic channel comprising an inlet port for receiving the suspension flow under laminar conditions, a first outlet port and a second outlet port; and

an interface for translating the particle within said channel, wherein said first outlet port is adapted to receive a first portion of the suspension exiting said channel and said second outlet port is adapted to receive the particle in a second portion of the suspension exiting the channel.

2. The microfluidic flow device of claim 1, wherein said interface comprises an optically transparent portion of said channel.

3. The microfluidic flow device of claim 1, wherein said interface comprises two or more electrodes to provide an electric field in the central channel.

4. The microfluidic flow device of claim 3, wherein said interface further comprises an electrical interconnect for receiving electrical energy from the system and providing the electrical energy to said two or more electrodes.

5. The microfluidic flow device of claim 1, wherein said interface further comprises a magnet for providing a magnetic field extending into said channel.

6. The microfluidic flow device of claim 1, wherein said channel is adapted such that an electric field may extend into said channel for translating the particle within the suspension flow.

7. The microfluidic flow device of claim 6, wherein said field comprises at least one or more of an optical trap, an electrical field and a magnetic field.

8. The microfluidic flow device of claim 1, where in said interface comprises a channel geometry for sorting the particle within the channel.

9. The microfluidic flow device of claim 1, wherein said laminar conditions comprise a Reynolds number of less than about 1000.

10. The microfluidic flow device of claim 1, wherein said channel comprises a cartridge.

11. The microfluidic flow device of claim 1, wherein said channel comprises a disposable cartridge.

12. The microfluidic flow device of claim 1 further comprising a pressure differential generator for providing fluid flow in said channel.

13. The microfluidic flow device of claim 12, wherein said pressure differential generator comprises one or more of the group comprising:

a pump, a capillary force generator, a gravity feed generator, an electro-osmosis system, a syringes, a valve, a suction generator, and a vacuum generator.

14. A microfluidic flow device for separating a particle from a suspension flow into a second fluid flow, the microfluidic flow device comprising:

a microfluidic channel comprising a first inlet port for receiving the suspension flow, a second inlet port for receiving the second fluid flow, a first outlet port and a second outlet port, wherein said channel is adapted to receive the suspension flow and the second fluid flow under laminar conditions; and

an interface for translating the particle from the suspension flow to the second fluid flow, wherein said first outlet port is adapted to receive at least a portion of the suspension flow exiting said channel and said second outlet port is adapted to receive the particle in at least a portion of the second fluid flow exiting said channel.

15. The microfluidic flow device of claim 14, wherein said interface comprises an optically transparent portion of said channel.

16. The microfluidic flow device of claim 14, wherein said interface comprises two or more electrodes to provide an electric field in the central channel.

17. The microfluidic flow device of claim 16, wherein said interface further comprises an electrical interconnect for receiving electrical energy from the system and providing the electrical energy to said two or more electrodes.

18. The microfluidic flow device of claim 14, wherein said interface further comprises a magnet for providing a magnetic field extending into said channel.

19. The microfluidic flow device of claim 14, wherein said channel is adapted such that an electric field may extend into said channel for translating the particle within the suspension flow.

20. The microfluidic flow device of claim 19, wherein said field comprises at least one or more of an optical trap, an electrical field and a magnetic field.

21. The microfluidic flow device of claim 14, where in said interface comprises a channel geometry for sorting the particle within the channel.

22. The microfluidic flow device of claim 14, wherein said laminar conditions comprise a Reynolds number of less than about 1000.

23. The microfluidic flow device of claim 14, further comprising a third inlet port.

24. The microfluidic flow device of claim 23, wherein said second and third inlet ports are adapted for providing a modulated flow rate.

25. The microfluidic flow device of claim 14, wherein said channel is adapted to receive the suspension flow and the second fluid flow in parallel flows in the same direction.

26. The microfluidic flow device of claim 14, wherein said channel is adapted to receive the suspension flow and the second fluid flow in parallel flows in the opposite direction.

27. The microfluidic flow device of claim 14, wherein said channel comprises a cartridge.

28. The microfluidic flow device of claim 27, wherein said channel comprises a disposable cartridge.

29. The microfluidic flow device of claim 14 further comprising a pressure differential generator for providing fluid flow in said channel.

30. The microfluidic flow device of claim 29, wherein said pressure differential generator comprises one or more of the group comprising:

a pump, a capillary force generator, a gravity feed generator, an electro-osmosis system, a syringes, a valve, a suction generator, and a vacuum generator.

31. The microfluidic flow device of claim 14, further comprising a third inlet port for receiving a third fluid flow.

32. The microfluidic flow device of claim 31, wherein said second inlet port enters said channel at a first angle to said first inlet port and said third inlet port enters said channel at a second angle to said first inlet port.

33. The microfluidic flow device of claim 32, wherein said second inlet port and said third inlet port provide a means for orienting the suspension flow in the channel.

34. The microfluidic flow device of claim 33, wherein said means for orienting the suspension flow is adapted to orient the suspension flow linearly.

35. The microfluidic flow device of claim 33, where in said means for orienting the suspension flow is adapted to modulate the position of the suspension flow within said channel.

36. A method of separating a particle within a suspension comprising:

receiving a suspension flow in a microfluidic channel, the suspension flowing under laminar conditions;

translating a particle within the suspension flow;

exiting a first portion of the suspension flow through a first outlet port, and

exiting the particle along with a second portion of the suspension flow through a second outlet port.

37. The method of claim 36, wherein the translating of the particle includes the application of a field.

38. The method of claim 37, wherein the translating of the particle includes the application of one or more of the group comprising:

an electric field, an optical field and a magnetic field.

39. The method of claim 36, wherein the translating of the particle comprises using a channel geometry for sorting the particle within the channel.

40. The method of claim 36, wherein the laminar conditions comprise a Reynolds number of less than about 1000.

41. The method of claim 36 further providing a pressure differential for providing fluid flow in the channel.

42. The method of claim 41, wherein the pressure differential is provided by one or more of the group comprising:

a pump, a capillary force generator, a gravity feed generator, an electro-osmosis system, a syringes, a valve, a suction generator, and a vacuum generator.

43. A method of separating a particle from a suspension flow comprising:

receiving a suspension flow in a microfluidic channel, the suspension flowing under laminar conditions;

receiving a second fluid flow in the channel, the suspension and the second fluid flowing under laminar conditions in the channel;

separating a particle from the suspension flow into the second fluid flow;

exiting at least a portion of the suspension flow through a first outlet port; and

exiting the particle in at least a portion of the second fluid flow through a second outlet port.

44. The method of claim 43, wherein the translating of the particle includes the application of a field.

45. The method of claim 44, wherein the translating of the particle includes the application of one or more of the group comprising:

an electric field, an optical field and a magnetic field.

46. The method of claim 43, wherein the translating of the particle comprises using a channel geometry for sorting the particle within the channel.

47. The method of claim 43, wherein the laminar conditions comprise a Reynolds number of less than about 1000.

48. The method of claim 43 further providing a pressure differential for providing fluid flow in the channel.

49. The method of claim 48, wherein the pressure differential is provided by one or more of the group comprising:

a pump, a capillary force generator, a gravity feed generator, an electro-osmosis system, a syringes, a valve, a suction generator, and a vacuum generator.

50. A cartridge for use in system to separate a particle from a suspension flow, the cartridge comprising:

a microfluidic channel comprising an inlet port for receiving a suspension flow under laminar conditions, a first outlet port and a second outlet port; and

an interconnect for connecting the cartridge to the system,

wherein said microfluidic channel is adapted to receive the suspension flow and provide an environment for translating the particle within the suspension flow, said first outlet port is adapted to receive a first portion of the suspension flow, and said second outlet port is adapted to receive the particle in a second portion of the suspension flow.

51. The cartridge of claim 50 further comprising an interface for translating the particle within said channel.

52. The cartridge of claim 51, wherein said interface comprises an optically transparent portion.

53. The cartridge of claim 51, wherein said interface comprises two or more electrodes to provide an electric field in the central channel.

54. The cartridge of claim 51, wherein said interface further comprises an electrical interconnect for receiving electrical energy from the system and providing the electrical energy to said two or more electrodes.

55. The cartridge of claim 51, wherein said interface further comprises an magnet for providing a magnetic field extending into said channel.

56. The cartridge of claim 50, wherein said channel is adapted such that a field may extend into said channel for translating the particle within the suspension flow.

57. The cartridge of claim 56, wherein said field comprises at least one or more of an optical trap, an electrical field and a magnetic field.

58. A microfluidic flow separator comprising:

a channel means for receiving a suspension flow under laminar conditions;

a translating means for translating a particle within the suspension flow; and

a first output means for exiting a first portion of the suspension flow; and

a second output means for exiting the particle in a second portion of the suspension flow.

59. A cartridge for use in system to separate a particle from a suspension flow into a second fluid flow, the cartridge comprising:

a microfluidic channel comprising a first inlet port for receiving the suspension flow, a second inlet port for receiving the second fluid flow, a first outlet port and a second outlet port, wherein said channel is adapted to receive the suspension flow and the second fluid flow under laminar conditions,

an interconnect for connecting the cartridge to the system,

wherein said microfluidic channel is adapted to provide an environment for translating the particle from the suspension flow to the second fluid flow, said first outlet port is adapted to receive at least a portion of the suspension flow, and said second outlet port is adapted to receive the particle in at least a portion of the second fluid flow.

60. The cartridge of claim 59 further comprising an interface for translating the particle within said channel.

61. The cartridge of claim 60, wherein said interface comprises an optically transparent portion.

62. The cartridge of claim 60, wherein said interface comprises two or more electrodes to provide an electric field in the central channel.

63. The cartridge of claim 60, wherein said interface further comprises an electrical interconnect for receiving electrical energy from the system and providing the electrical energy to said two or more electrodes.

64. The cartridge of claim 60, wherein said interface further comprises an magnet for providing a magnetic field extending into said channel.

65. The cartridge of claim 59, wherein said channel is adapted such that a field may extend into said channel for translating the particle within the suspension flow.

66. The cartridge of claim 65, wherein said field comprises at least one or more of an optical trap, an electrical field and a magnetic field.

67. A microfluidic flow separator comprising:

a channel means for receiving a suspension flow and a second fluid flow, the suspension flow and the second fluid flow under laminar conditions;

a separator means for separating a particle from the suspension flow into the second fluid flow; and

a first output means for exiting at least a portion of the suspension flow; and

a second output means for exiting the particle in at least a portion of the second fluid flow.

68. A microfluidic chemical dispenser for dispensing a first fluid flow into a plurality of receptacles comprising:

a first inlet port for receiving the first fluid flow;

a second inlet port for receiving a second fluid flow at a first angle to the first fluid flow;

a third inlet port for receiving a third fluid flow at a second angle to the first fluid flow;

a central channel for receiving the first fluid flow, the second fluid flow and the third fluid flow under laminar conditions;

a plurality of outlet ports for receiving fluid flow from the central channel;

a modulator means for modulating the relative flow rates of the second fluid stream and the third stream to dispense the first fluid flow into said plurality of outlet ports.

69. The microfluidic dispenser of claim 68, wherein the first fluid flow comprises a buffer fluid flow.

70. The microfluidic dispenser of claim 68, wherein the first fluid flow comprises a solvent fluid flow.

71. A system for separating a particle from a solution in a microfluidic flow device, the system comprising:

a microfluidic channel comprising an input port, a first output port and a second output port, said channel being adapted to receive the suspension via the input port under laminar conditions;

a detector for monitoring said channel and providing an output;

an information processor for receiving said output and determining if the particle is present in said channel; and

an actuator for translating the particle within said channel, wherein said information processor triggers said actuator if the particle is detected.