Microcolumn-based, high-throughput microfluidic device

• US 20030049862A1
• Filed: 05/24/2002
• Published: 03/13/2003
• Est. Priority Date: 09/07/2001
• Status: Active Grant

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Shi, Youchun, Peng, Jinlin, Yuen, Po Ki, He, Lin, Webb, Brian L.
• Granted Patent: US 7,390,463 B2
• Time in Patent Office: Days
• US Class Current: 436/180
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/026 Fluid interfacing between devices or objects, e.g. connectors, inlet details
• CPC Class Codes: B01L 2300/046 Function or devices integrated in the closure
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 3/5025 for parallel transport of multiple samples
• CPC Class Codes: B01L 3/50853 with covers or lids
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 35/028 having reaction cells in the form of microtitration plates
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A biological assay device for use in molecular biology, pharmaceutical research, genomic analysis, combinatorial chemistry, and in the general field of the analysis of molecules that may be deposited on supports of various kinds is provided. Specifically, the present invention includes a fluidic or microfluidic device, which integrates fluidic capability into existing multi-well plates of standard configuration, for performing either single or continuous fluidic manipulations in a high-throughout format. Methods for the use and manufacture of these devices are also provided.

Claims

1. A fluidic device for high-throughput biological or chemical assays, the device comprising:

a support structure with a first surface;

a number of fluidic modules extending from said first surface;

each of said fluidic modules having a three-dimensional body with a surface remotely located relative to said first surface and a set of at least a first fluidic channel formed in said body; and

said first fluidic channel having an inlet port and extending through said body of said fluidic module to said remote surface.

2. The fluidic device according to claim 1, the device further comprising a second fluidic channel, which extends at least partially through said support structure or fluidic module from said remote surface to an outlet portal.

3. The fluidic device according to claim 2, wherein said outlet portal exits into waste passages located in said support structure.

4. The fluidic device according to claim 2, wherein said outlet portal exits onto said second surface of said support structure.

5. The fluidic device according to claim 3, wherein said waste passages form a common reservoir.

6. The fluidic device according to claim 1, wherein said fluidic module has at least one sidewall.

7. The fluidic device according to claim 1, wherein each fluidic module is sized to be introduced into a corresponding well of a plate with an industry-standard format.

8. The fluidic device according to claim 7, wherein said fluidic module is positioned a predetermined distance above a bottom wall of said corresponding well.

9. The fluidic device according to claim 7, wherein said fluidic module has a sealing mechanism that engages with either a bottom wall or a sidewall of said well, or a top surface of said plate to form a fluid-tight space, which functions as a reaction chamber.

10. The fluidic device according to claim 7, wherein said sealing mechanism is a gasket, an O-ring, a rib or flange on said distal surface.

11. The fluidic device according to claim 7, wherein said fluidic modules are arrayed in a matrix.

12. The fluidic device according to claim 11, wherein said matrix is in a 24-, 48-, 96-, 192, 384, or 576-well format.

13. The fluidic device according to claim 1, wherein said fluidic modules are arrayed on a strip.

14. The fluidic device according to claim 13, wherein said strip is in a 6, 8, 12-well format.

15. The fluidic device according to claim 9, wherein said fluidic channels enable continuous flow of fluids in through one fluidic channel into said reaction chamber and out through another fluidic channel.

16. The fluidic device according to claim 1, wherein at least a part of said remote surface of said fluidic module is configured with a porous substrate.

17. The fluidic device according to claim 16, wherein said porous substrate is a membrane, filter, polymer, or glass-frit wafer.

18. The fluidic device according to claim 1, wherein said remote surface of said fluidic module has a recess that is larger than the cross-section of a fluidic channel.

19. The fluidic device according to claim 1, wherein said inlet port is sized to permit a pipette tip, syringe, or other conduit to be introduced within.

20. The fluidic device according to claim 2, wherein when said second fluidic channel extends to an outlet port on the second planar surface, said outlet port is configured to receive a conduit for fluids.

21. The fluidic device according to claim 1, wherein an array of biological or chemical analytes is disposed on said remote surface.

22. The fluidic device according to claim 21, wherein said biological analytes include DNA, RNA, proteins, cells, and cellular components.

23. The fluidic device according to claim 1, wherein said device further includes an electrochemical sensor.

24. The fluidic device according to claim 1, wherein an optical grating is disposed on said remote surface.

25. The fluidic device according to claim 24, wherein said optical grating is an optical waveguide.

26. The fluidic device according to claim 1, wherein said device further comprises an optical detection device for monitoring assays.

33. The upper plate according to claim 1, wherein said plate further includes an electrochemical sensor.

27. A multiplexed microfluidic device comprising:

a plurality of three-dimensional fluidic modules;

a common plate from which each module extends;

wherein each of said modules has a surface remote from said common plate, and a set of at least a first fluidic channel and a second fluidic channel formed therein.

29. The upper plate according to claim 27, wherein said fluidic module further comprises a second fluidic channel, which extends at least partially through the plate structure and body of the fluidic module from the remote major surface to an outlet portal.

30. The upper plate according to claim 27, wherein an array of biological or chemical analytes is disposed on said remote major surface.

31. The upper plate according to claim 27, wherein at least a part of said remote surface of said fluidic module is configured with a porous substrate.

32. The upper plate according to claim 27, wherein each fluidic module is sized to be introduced into a corresponding well of a lower plate.

28. An upper plate of a microfluidic device, said plate comprising:

a structure with at least one fluidic module, said fluidic module comprises a three-dimensional body with a set of at least one fluidic channel extending from a first surface of said plate through the body to a surface remote from the plate structure.

34. A method for performing high-throughput biological or chemical assays in a microfluidic system, the method including:

providing an array of three-dimensional fluidic modules, each comprising a body with a set of at least one fluidic channel formed therein, of which at least a first channel has an inlet port located in a surface of a support structure and extending through said support structure and fluidic module to a surface thereof remote to said support structure;

providing analytes on either said remote surface or a bottom of a well in a plate, or both;

creating a reaction zone between each fluidic module and a corresponding well in said plate; and

introducing an assay solution through said first fluidic channel.

35. The method according to claim 34, further comprising:

providing a second fluidic channel, which extends at least partially through said support structure or fluidic module from said remote surface thereof to an outlet portal; and

exiting said assay solution through said second fluidic channel after interaction with said analytes.

36. The method according to claim 34, wherein assay solution is pumped continuously through said fluidic channels and said reaction zone.

37. The method according to claim 34, wherein said assay solution is pumped back and forth through said fluidic channels.

38. A kit for high-throughput biological or chemical assays in a microfluidic system, the kit includes:

a fluidic device and a well plate, wherein said fluidic device has a three-dimensional fluidic module with at least one fluidic channel formed therein terminating at a remote surface, said three-dimensional body is capable of being inserted a well, and each well in said plate has a bottom wall.

39. The kit according to claim 38, further comprising biological or chemical analytes on said remote surface, a bottom of a well in a plate, or both.

40. The kit according to claim 38, wherein the bottom wall of the plate has a depression at the center of the bottom.

41. The kit according to claim 38, wherein said fluidic device further comprises a second fluidic channel in said fluidic module.

42. The kit according to claim 38, wherein said fluidic device or well plate further includes an electrochemical sensor.

43. The kit according to claim 38, wherein gratings are formed on said remote surface.

44. The kit according to claim 38, wherein a grating is disposed on the bottom wall of the plate.

45. The kit according to claim 38, wherein a grating is disposed on both said remote surface and the bottom wall of the plate.

46. The kit according to claim 38, wherein a number of said fluidic modules is arranged in a 24-, 48-, 96-, 384-, or 576-unit format.

47. The kit according to claim 38, wherein a number of said fluidic modules is arrayed in an 8- or 12-unit strip.

48. The kit according to claim 38, wherein a gap distance between said remote surface and said bottom wall ranges from ˜

1 microns to ˜

5 mm.

49. The kit according to claim 48, wherein said gap distance ranges from ˜

1-500 microns.

50. The kit according to claim 49, wherein said gap distance ranges from ˜

5-150 microns.

51. A high-throughput fluidic device comprising:

a well plate having a number of wells, each well having a sidewall and a bottom surface;

a plurality of three-dimensional fluidic modules;

a common structure from which each module extends;

wherein each of said modules has a surface remote from said common structure, and a set of at least a first fluidic channel formed therein.

52. The device according to claim 51, wherein said device further comprises a second fluidic channel in said fluidic module.

53. The device according to claim 51, wherein said fluidic device or well plate further includes an electrochemical sensor.

54. The device according to claim 51, wherein gratings are formed on said remote surface.

55. The device according to claim 51, wherein a grating is disposed on the bottom wall of the plate.

56. The device according to claim 51, wherein a grating is disposed on both said remote surface and the bottom wall of the plate.

57. The device according to claim 51, wherein biological or chemical analytes are located on said remote surface, a bottom of a well in a plate, or both.

58. The device according to claim 57, wherein said analytes include DNA, RNA, oligonucleotides, proteins, peptides, cells, cellular components, small chemical molecules, and drugs.

59. The device according to claim 51, wherein a number of said fluidic modules is arranged in a 24-, 48-, 96-, 384-, or 576-unit format.

60. The device according to claim 51, wherein a number of said fluidic modules is arrayed in an 8- or 12-unit strip.

61. The device according to claim 51, wherein said fluidic modules have a size that can be inserted into each well.

62. The device according to claim 51, wherein either said remote surface or said bottom surface of said well plate has a spacer element to provide a gap between said remote surface and said bottom surface.

63. The device according to claim 62, wherein said gap distance between said remote surface and said bottom surface ranges from ˜

1 microns to ˜

5 mm.

64. The device according to claim 63, wherein said gap distance ranges from ˜

1-500 microns.

65. The device according to claim 64, wherein said gap distance ranges from ˜

5-150 microns.