Apparatus and method for performing microfluidic manipulations for chemical analysis

• US 6,342,142 B1
• Filed: 04/27/1999
• Issued: 01/29/2002
• Est. Priority Date: 08/01/1994
• Status: Expired due to Term

• Current Assignee: Lockheed Martin Energy Research Corporation (Martin Marietta Corporation)
• Original Assignee: UT-Battelle LLC
• Inventors: Ramsey, J. Michael
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): STARSIAK, JOHN S
• Application Number:
  US09/300,060
• Time in Patent Office: 1,008 Days
• Field of Search: 204/450, 204/451, 204/452, 204/453, 204/454, 204/455, 204/600, 204/601, 204/602, 204/603, 204/604, 204/605, 422/100
• US Class Current: 204/453
• CPC Class Codes: B01D 15/3842 Micellar chromatography
• CPC Class Codes: B01F 33/30 Micromixers
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00826 Quartz
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 Glass
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00889 Mixing
• CPC Class Codes: B01J 2219/00891 Feeding or evacuation
• CPC Class Codes: B01J 2219/00912 by electrophoresis
• CPC Class Codes: B01J 2219/00916 by chromatography
• CPC Class Codes: B01J 2219/00952 Sensing operations
• CPC Class Codes: B01J 2219/0097 Optical sensors
• CPC Class Codes: B01J 2219/00995 Mathematical modeling
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/0883 : Serpentine channels
• CPC Class Codes: B01L 2400/0415 : electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 : electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 : electrophoretic flow
• CPC Class Codes: B01L 3/5027 : by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502715 : characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
• CPC Class Codes: B01L 3/50273 : characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 : characterised by integrated valves microvalves F16K99/0001
• 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 3/502776 : specially adapted for focusing or laminating flows
• CPC Class Codes: B01L 3/502784 : specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: B29C 65/4895 : Solvent bonding, i.e. the surfaces of the parts to be joined being treated with solvents, swelling or softening agents, without adhesives
• CPC Class Codes: B29C 66/026 : Chemical pre-treatments B29C66/028 takes precedence
• CPC Class Codes: B29C 66/034 : Thermal after-treatments
• CPC Class Codes: B29C 66/54 : Joining several hollow-preforms, e.g. half-shells, to form hollow articles, e.g. for making balls, containers; Joining several hollow-preforms, e.g. half-cylinders, to form tubular articles
• CPC Class Codes: G01N 2030/027 : Liquid chromatography
• CPC Class Codes: G01N 2030/162 : electromigration
• CPC Class Codes: G01N 2030/285 : electrically driven carrier
• CPC Class Codes: G01N 2030/383 : by using auxiliary fluid
• CPC Class Codes: G01N 2030/8435 : for chemical reaction
• CPC Class Codes: G01N 27/44743 : Introducing samples
• CPC Class Codes: G01N 27/44791 : Microapparatus sample containers with integrated microfluidic structures B01L3/5027
• CPC Class Codes: G01N 30/02 : Column chromatography
• CPC Class Codes: G01N 30/16 : Injection G01N30/24 takes precedence
• CPC Class Codes: G01N 30/6095 : Micromachined or nanomachined, e.g. micro- or nanosize
• CPC Class Codes: Y10S 366/01 : Micromixers: continuous laminar flow with laminar boundary mixing in the linear direction parallel to the fluid propagation with or without conduit geometry influences from the pathway

Abstract

A microchip apparatus and method provide fluidic manipulations for a variety of applications, including sample injection for microchip liquid chromatography. The microchip is fabricated using standard photolitographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis is performed in channels formed in the substrate. Injections are made by electro-osmotically pumping sample through the injection channel that crosses the separation channel, followed by a switching of the potentials to force a plug into the separation channel.

Claims

1. A method of sample injection, comprising:

providing a microchip having first, second, third and fourth channel segments, the first, second, third and fourth channel segments communicating at an intersection;

moving a first material from a first channel segment into the intersection; and

subsequently moving the first material in the intersection into the second channel segment and simultaneously moving the first material in the first channel segment away from the intersection.

2. The method of claim 1, wherein the step of moving the first material into the intersection comprises moving the first material through the intersection into the third channel segment.

3. The method of claim 2, wherein the step of subsequently moving the portion of first material into the second channel segment comprises simultaneously moving the first material in the first channel segment and the first material in the third channel segment away from the intersection.

4. The method of claim 2, wherein the step of moving the first material through the intersection and into the third channel segment comprises moving a second material from the at least one of the second and fourth channel segments into the intersection.

5. The method of claim 2, wherein the step of moving the first material through the intersection and into the third channel segment comprises moving at least a second material from each of the second and fourth channel segments into the intersection.

6. The method of claim 5, wherein the step of moving the at least second material from the second and fourth channel segments into the intersection further comprises moving the second material through the intersection into the third channel segment.

7. The method of claim 1, wherein the step of moving the first material from the first channel segment into the intersection comprises applying an electric field between the first channel segment and the third channel segment, through the intersection.

8. The method of claim 7, wherein the step of moving the at least first material in the first channel segment away from the intersection comprises applying an electric field between the third channel segment and the first channel segment through the intersection.

9. The method of claim 1, wherein the second channel segment communicates with the intersection between the first channel segment and the third channel segment and the fourth channel segment communicates with the intersection between the third channel segment and the first channel segment.

10. The method of claim 9, wherein the first channel segment is directly across the intersection from the third channel segment.

11. The method of claim 1, wherein the intersection comprises a cross intersection.

12. The method of claim 1, wherein the first material comprises nucleic acids.

13. The method of claim 1, further comprising detecting at least a portion of the first material in the second channel segment.

14. The method of claim 13, wherein the first material comprises a detectable label associated therewith.

15. The method of claim 14, wherein the detectable label comprises a fluorescent label.

16. The method of claim 14, wherein the detecting step comprises exciting the fluorescent label, and detecting emitted fluorescence in the second channel segment.

17. The method of claim 16, wherein the fluorescent label is excited in the second channel segment using a laser.

18. The method of claim 16, wherein the fluorescent label is excited in the second channel segment using a laser diode.

19. The method of claim 16, wherein the fluorescent label is excited in the second channel segment using a LED.

20. A method of sample injection, comprising:

providing a substrate having first, second, third and fourth channel segments, the first, second, third and fourth channel segments communicating at a confluence region;

moving a first material from a first channel segment into the confluence region; and

subsequently moving the first material in the confluence region into the second channel segment and simultaneously moving the first material in the first channel segment away from the confluence region.

21. The method of claim 20, wherein the confluence region comprises a microscale channel segment, the first, second, third and fourth channel segments being in fluid communication with the microscale channel segment, and wherein the moving step comprises moving the first material from the first channel segment into the microscale channel segment.

22. The method of claim 21, wherein the step of moving the first material from the first channel segment into the confluence region comprises applying an electric field between the first channel segment and the third channel segment, through the confluence region.

23. The method of claim 22, wherein the step of moving the at least first material in the first channel segment away from the confluence region comprises applying an electric field between the third channel segment and the first channel segment through the confluence region.

24. The method of claim 21, wherein the second channel segment communicates with the confluence region between the first channel segment and the third channel segment and the fourth channel segment communicates with the confluence region between the third channel segment and the first channel segment.

25. The method of claim 21, wherein the confluence region comprises a channel intersection.

26. The method of claim 25, wherein the first channel segment is directly across the intersection from the third channel segment.

27. The method of claim 21, wherein the first material comprises nucleic acids.

28. The method of claim 21, further comprising detecting at least a portion of the first material in the second channel segment.

29. The method of claim 28, wherein the first material comprises a detectable label associated therewith.

30. The method of claim 29, wherein the detectable label comprises a fluorescent label.

31. The method of claim 30, wherein the detecting step comprises exciting the fluorescent label, and detecting emitted fluorescence in the second channel segment.

32. The method of claim 31, wherein the fluorescent label is excited in the second channel segment using a laser.

33. The method of claim 31, wherein the fluorescent label is excited in the second channel segment using a laser diode.

34. The method of claim 31, wherein the fluorescent label is excited in the second channel segment using a LED.

35. The method of claim 20, wherein in the providing step, the confluence region comprises a microscale channel segment, the first, second, third and fourth channel segments being in fluid communication with the microscale channel segment, and wherein the moving step comprises moving the first material from the first channel segment into the microscale channel segment and into the third channel segment.

36. The method of claim 35, wherein the first channel segment is in fluid communication with the microscale channel region at a point across from a point at which the third channel segment is in fluid communication with the microscale channel segment.

37. The method of claim 20, wherein the step of moving the first material into the confluence region comprises moving the first material through the confluence region into the third channel segment.

38. The method of claim 37, wherein the step of subsequently moving the portion of first material into the second channel segment comprises simultaneously moving the first material in the first channel segment and the first material in the third channel segment away from the confluence region.

39. The method of claim 37, wherein the step of moving the first material through the confluence region and into the third channel segment comprises moving a second material from the at least one of the second and fourth channel segments into the confluence region.

40. The method of claim 37, wherein the step of moving the first material through the confluence region and into the third channel segment comprises moving at least a second material from each of the second and fourth channel segments into the confluence region.

41. The method of claim 40, wherein the step of moving the at least second material from the second and fourth channel segments into the confluence region further comprises moving the second material through the confluence region into the third channel segment.

42. A method of sample injection, comprising:

providing a substrate having first, second, third and fourth channel segments, the first, second, third and fourth channel segments communicating at a first microscale channel region;

moving a first material from the first channel segment into the first microscale channel region; and

injecting the first material in the first microscale channel region into the second channel segment while simultaneously moving the first material in the first channel segment away from the first microscale channel region.

43. The method of claim 42, wherein the first material is electrokinetically moved from the first channel segment into the first microscale channel region.

44. The method of claim 42, wherein the first material in the first microscale channel region is electrokinetically injected into the second channel segment and the first material in the first channel segment is electrokinetically moved away from the first microscale channel region.

45. The method of claim 42, wherein the step of moving the first material into the first microscale channel region comprises moving the first material through the first microscale channel region into the third channel segment.

46. The method of claim 42, wherein the step of subsequently moving the portion of first material into the second channel segment comprises simultaneously moving the first material in the first channel segment and the first material in the third channel segment away from the first microscale channel region.

47. The method of claim 42, wherein the step of moving the first material through the first microscale channel region and into the third channel segment comprises moving a second material from the at least one of the second and fourth channel segments into the first microscale channel region.

48. The method of claim 42, wherein the step of moving the first material through the first microscale channel region and into the third channel segment comprises moving at least a second material from each of the second and fourth channel segments into the first microscale channel region.

49. The method of claim 48, wherein the step of moving the at least second material from the second and fourth channel segments into the first microscale channel region further comprises moving the second material through the first microscale channel region into the third channel segment.

50. The method of claim 42, wherein the second channel segment communicates with the first microscale channel region between the first channel segment and the third channel segment and the fourth channel segment communicates with the first microscale channel region between the third channel segment and the first channel segment.

51. The method of claim 50, wherein the first channel segment is directly across the first microscale channel region from the third channel segment.

52. The method of claim 42, wherein the first material comprises nucleic acids.

53. The method of claim 42, further comprising detecting at least a portion of the first material in the second channel segment.

54. The method of claim 53, wherein the first material comprises a detectable label associated therewith.

55. The method of claim 54, wherein the detectable label comprises a fluorescent label.

56. The method of claim 55, wherein the detecting step comprises exciting the fluorescent label, and detecting emitted fluorescence in the second channel segment.

57. The method of claim 56, wherein the fluorescent label is excited in the second channel segment using a laser.

58. The method of claim 56, wherein the fluorescent label is excited in the second channel segment using a laser diode.

59. The method of claim 56, wherein the fluorescent label is excited in the second channel segment using a LED.