Microfluidic transfer pin

• US 8,277,753 B2
• Filed: 08/23/2002
• Issued: 10/02/2012
• Est. Priority Date: 08/23/2002
• Status: Active Grant

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Hasan, Leila, Linton, John, Brenan, Colin J. H.
• Primary Examiner(s): Nagpaul, Jyoti
• Application Number:
  US10/227,179
• Publication Number:
  US 20040037748A1
• Time in Patent Office: 3,693 Days
• Field of Search: 422 99-101, 422/50, 422500-503, 436/180, 347/84
• US Class Current: 422/500
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01L 2200/025 Align devices or objects to ensure defined positions relative to each other
• CPC Class Codes: B01L 2200/0642 Filling fluids into wells by specific techniques
• CPC Class Codes: B01L 2200/141 Preventing contamination, tampering
• CPC Class Codes: B01L 2200/142 Preventing evaporation
• CPC Class Codes: B01L 2400/027 electrostatic forces between substrate and tip
• CPC Class Codes: B01L 3/021 Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

A liquid dispenser for a microfluidic assay system is described. The dispenser includes at least one transfer pin for transferring a microfluidic sample of liquid to a target receptacle. A pin tip at one end of the transfer pin is structured to cooperate with an opening in the target receptacle. The tip uses a high voltage potential to transfer the sample from the pin to the receptacle.

Claims

1. A microfluidic liquid dispenser assay system comprising:

a target receptacle comprising a platen, the platen comprising a first planar surface, a first opening on the first planar surface, an opposing planar surface, and a second opening on the opposing planar surface, wherein the target receptacle is a through-hole;

at least one transfer pin for transferring a microfluidic sample of liquid to the target receptacle, the at least one transfer pin having a slot for holding the microfluidic sample; and

a pin tip at an end of the transfer pin structured to cooperate with the first opening in the target receptacle, the pin tip having a high voltage potential for transferring the sample from the at least one transfer pin to the target receptacle; and

a voltage control module configured to apply the high voltage potential to the pin tip to encourage wetting of a liquid bridge between the pin tip and the through-hole;

wherein the through-hole extends from the first opening on the first planar surface of the platen to the second opening on the opposing planar surface of the platen, and wherein the through-hole is submersed in a liquid that is immiscible with the microfluidic sample.

2. A liquid dispenser system according to claim 1, wherein the target receptacle includes hydrophilic walls regions that attract the sample.

3. A liquid dispenser system according to claim 1, wherein the target receptacle includes an opening hydrophilic region surrounded by hydrophobic material.

4. A liquid dispenser system according to claim 1, further comprising:

a transfer pin array including a plurality of transfer pins for transferring a plurality of samples to a corresponding plurality of target receptacles.

5. A liquid dispenser system according to claim 4, wherein individual transfer pins in the array are sequentially actuable.

6. A liquid dispenser system according to claim 4, wherein at least one transfer pin in the array is independently positionable for alignment with respect to the first opening of a target receptacle.

7. A liquid dispenser system according to claim 4, wherein at least one individual transfer pin in the array is gravity-fed floating.

8. A liquid dispenser system according to claim 1, wherein the microfluidic sample is from 0.2 to 100 nanoliters.

9. A liquid dispenser system according to claim 1, wherein the transfer pin has a diameter greater than the first opening of the target receptacle.

10. A liquid dispenser system according to claim 1, wherein the sample is a polar liquid.

11. A liquid dispenser system according to claim 10, wherein the polar liquid is an aqueous, DMSO, dimethylformamide (DMF), or acetonitrile solution.

12. A liquid dispenser system according to claim 1, wherein the high voltage potential is between 100V and 5 kV.

13. A liquid dispenser system according to claim 1, wherein the voltage control module is configured to apply the high voltage potential to the pin tip before the transfer pin is positioned at the target receptacle, and to remove the high voltage potential after the transfer pin is moved away from the target receptacle.

14. A liquid dispenser system according to claim 1, wherein the voltage control module includes a resistor network.

15. A liquid dispenser system according to claim 1, wherein the voltage control module includes a controllable switch in series with the transfer pin.

16. A liquid dispenser system according to claim 1, wherein the at least one transfer pin is able to dispense multiple samples without replenishment.

17. A liquid dispenser system according to claim 1, wherein the target receptacle is comprised by one or more wells in an array of through-hole wells.

18. A liquid dispenser system according to claim 1, wherein the target receptacle is a through-hole well in a platen array of wells.

19. A liquid dispenser system according to claim 1, wherein the second opening is not bonded to a substrate at the time of loading.

20. A method for use in dispensing a microfluidic sample of a liquid, the method comprising:

providing at least one transfer pin for transferring a microfluidic sample of liquid to a target receptacle, one end of the transfer pin having a slot holding the microfluidic sample and a pin tip structured to cooperate with an opening in the target receptacle;

initiating transfer of the sample from the at least one transfer pin tip and the target receptacle when the sample contacts the target receptacle; and

applying a high voltage potential between the pin tip and the target receptacle to transfer the sample from the at least one transfer pin to the target receptacle, wherein the target receptacle is a through-hole and

submersing the target receptacle in a liquid that is immiscible with the microfluidic sample.

21. A method according to claim 20, wherein the high voltage potential is applied to the transfer pin.

22. A method according to claim 20, wherein the high voltage potential is applied to the target receptacle.

23. A method according to claim 20, wherein the target receptacle includes hydrophilic walls that attract the sample.

24. A method according to claim 20, wherein the target receptacle includes an opening surrounded by hydrophobic material.

25. A method according to claim 20, further comprising:

providing a transfer pin array including a plurality of transfer pins for transferring a plurality of samples to a corresponding plurality of target receptacles.

26. A method according to claim 25, wherein individual transfer pins in the array are sequentially actuable.

27. A method according to claim 25, wherein at least one transfer pin in the array is independently positionable for alignment with respect to the opening of a target receptacle.

28. A method according to claim 25, wherein at least one transfer pin in the array is gravity-fed floating.

29. A method according to claim 20, wherein the microfluidic sample is from 0.2 to 100 nanoliters.

30. A method according to claim 20, wherein the transfer pin has a diameter greater than the opening of the target receptacle.

31. A method according to claim 20, wherein the sample is a polar liquid.

32. A method according to claim 31, wherein the polar liquid is an aqueous, DMSO, dimethylformamide (DMF), or acetonitrile solution.

33. A method according to claim 20, wherein the high voltage potential is between 100V and 5 kV.

34. A method according to claim 20, further comprising:

controlling when the high voltage potential is applied to and removed.

35. A method according to claim 34, wherein the controlling step includes applying the high voltage potential before the transfer pin is positioned at the target receptacle, and removing the high voltage potential after the transfer pin is moved away from the target receptacle.

36. A method according to claim 34, wherein the controlling step uses a resistor network.

37. A method according to claim 34, wherein the controlling step uses a controllable switch in series with the transfer pin.

38. A method according to claim 20, further comprising:

applying evaporation control measures to the target receptacle.

39. A method according to claim 38, wherein the applying step includes immersing the target receptacle in an immiscible liquid.

40. A method according to claim 39, wherein the immiscible liquid is a perfluorinated hydrocarbon, hydrocarbon, or silicone fluid.

41. A method according to claim 38, wherein the applying step uses at least one of humidity control, fluid pressure, and receptacle cooling.

42. A method according to claim 20, wherein the applying step includes positioning the transfer pin in direct contact with target receptacle.

43. A method according to claim 20, wherein the applying step includes positioning the transfer pin near the target receptacle without direct contact.

44. A method according to claim 20, further comprising:

sequentially transferring multiple samples to the target receptacle to produce a layered pattern of samples.

45. A method according to claim 20, wherein the at least one transfer pin is able to dispense multiple samples without replenishment.

46. A method according to claim 20, wherein the target receptacle is one or more wells in an array of through-hole wells.

47. A method according to claim 20, wherein the target receptacle is a through-hole well in a platen array of wells.

48. A microfluidic assay system comprising:

at least one liquid sample storage device including a plurality of target receptacles, the at least one liquid sample storage device comprising a platen, the platen comprising a first planar surface, a first opening on the first planar surface, an opposing planar surface, and a second opening on the opposing planar surface, wherein a least one of the plurality of target receptacles is a through-hole; and

a microfluidic liquid dispenser having;

i. a high voltage supply that develops a high voltage potential;

ii. at least one transfer pin for transferring a microfluidic sample of liquid to the first opening on the first planar surface, the at least one transfer pin having a slot for holding the microfluidic sample, one end of the transfer pin having a pin tip structured to cooperate with an opening in the target receptacle;

iii. a voltage controller configured to apply the high voltage potential to the pin tip to encourage the wetting of a liquid bridge between the pin tip and the through-hole; and

iv. a dispenser positioning module that positions the liquid dispenser to enable the transfer pin to cooperate with one of the target receptacles for transferring the sample,

wherein the through-hole extends from the first opening on the first planar surface of the platen to the second opening on the opposing planar surface of the platen, and wherein at least one of the plurality of target receptacles is submersed in a liquid that is immiscible with the microfluidic sample.

49. An assay system according to claim 48, wherein the voltage controller applies the high voltage potential to the transfer pin.

50. An assay system according to claim 48, wherein the voltage controller applies the high voltage potential to the target storage receptacle.

51. An assay system according to claim 48, wherein the target storage receptacle includes hydrophilic walls that attract the sample.

52. An assay system according to claim 48, wherein the target storage receptacle includes an opening surrounded by hydrophobic material.

53. An assay system according to claim 48, wherein the liquid dispenser includes a transfer pin array including a plurality of transfer pins for transferring a plurality of samples to a corresponding plurality of target storage receptacles.

54. An assay system according to claim 53, wherein individual transfer pins in the array are sequentially actuable.

55. An assay system according to claim 53, wherein at least one transfer pin in the array is independently positionable for alignment with respect to the first opening of a target storage receptacle.

56. An assay system according to claim 53, wherein at least one transfer pin in the array is gravity-fed floating.

57. An assay system according to claim 48, wherein the microfluidic sample is from 0.2 to 100 nanoliters.

58. An assay system according to claim 48, wherein the transfer pin has a diameter greater than the first opening of the target storage receptacle.

59. An assay system according to claim 48, wherein the sample is a polar liquid.

60. An assay system according to claim 59, wherein the polar liquid is an aqueous, DMSO, dimethylformamide (DMF), or acetonitrile solution.

61. An assay system according to claim 48, wherein the high voltage potential is between 100V and 5 kV.

62. An assay system according to claim 48, wherein the voltage controller applies the high voltage potential to the pin tip before the transfer pin is positioned at the target storage receptacle, and removes the high voltage potential after the transfer pin is moved away from the target storage receptacle.

63. An assay system according to claim 48, wherein the voltage controller uses a resistor network.

64. An assay system according to claim 48, wherein the voltage controller uses a controllable switch in series with the transfer pin.

65. An assay system according to claim 48, wherein the storage device uses evaporation control measures to control evaporation of samples from the storage receptacles.

66. An assay system according to claim 65, wherein the evaporation control measures include immersing the storage receptacles in an immiscible liquid.

67. An assay system according to claim 66, wherein the immiscible liquid is a perfluorinated hydrocarbon, hydrocarbon, or silicone fluid.

68. An assay system according to claim 65, wherein the evaporation control measures include at least one of humidity control, fluid pressure, and receptacle cooling.

69. An assay system according to claim 48, wherein the positioning module positions the dispenser so that the at least one transfer pin makes direct contact with target storage receptacle for transferring the sample.

70. An assay system according to claim 48, wherein the positioning module positions the dispenser so that the at least one transfer pin is near the target storage receptacle without direct contact for transferring the sample.

71. An assay system according to claim 48, wherein the liquid dispenser operates to sequentially transfer multiple samples to the target storage receptacle to produce a layered pattern of samples.

72. An assay system according to claim 48, wherein the at least one transfer pin is able to dispense multiple samples without replenishment.

73. An assay system according to claim 48, wherein the target receptacle is one or more wells in an array of through-hole wells.

74. An assay system according to claim 48, wherein the target receptacle is a through-hole well in a platen array of wells.

75. A liquid dispenser according to claim 48, wherein the second opening is not bonded to a substrate at the time of loading.

76. A method for use in dispensing a microfluidic sample of a liquid into a target receptacle wherein the target receptacle is a through-hole, the through-hole extending from a first opening on a first planar surface of a platen to a second opening on an opposing planar surface of the platen, the method comprising:

providing a microfluidic liquid dispenser, the dispenser including;

at least one transfer pin for transferring a microfluidic sample of liquid to the target receptacle, the at least one transfer pin having a slot for holding the microfluidic sample;

a pin tip at one end of the transfer pin structured to cooperate with the first opening in the target receptacle, the pin tip having a high voltage potential for transferring the sample from the at least one transfer pin to the target receptacle; and

a voltage control module configured to apply the high voltage potential to the pin tip to encourage the wetting of a liquid bridge between the pin tip and the through-hole;

applying the high voltage potential to encourage the wetting of the liquid bridge between the pin tip and the through-hole to thereby dispense the microfluidic sample; and

submersing the target receptacle in a liquid that is immiscible with the microfluidic sample.

77. The method of claim 76, further comprising:

initiating transfer of the sample from the at least one transfer pin tip and the target receptacle when the sample contacts the target receptacle.

78. A method of claim 76, wherein the immiscible liquid is a perfluorinated hydrocarbon, hydrocarbon, or silicone fluid.

79. A method for use in dispensing a microfluidic sample of a liquid into a target receptacle wherein the target receptacle is a through-hole, the through-hole extending from the first opening on one planar surface of a platen to a second opening on an opposing planar surface of the platen, the method comprising:

providing a microfluidic assay system including;

at least one liquid sample storage device including a plurality of target receptacles; and

a microfluidic liquid dispenser having;

i. a high voltage supply that develops a high voltage potential;

ii. at least one transfer pin for transferring a microfluidic sample of liquid to a first opening on a target receptacle, the at least one transfer pin having a slot for holding the microfluidic sample, one end of the transfer pin having a pin tip structured to cooperate with an opening in the target receptacle;

iii. a voltage controller configured to apply the high voltage potential to the pin tip to encourage wetting of a liquid bridge between the pin tip and the through-hole; and

iv. a dispenser positioning module that positions the liquid dispenser to enable the transfer pin to cooperate with the target receptacle for transferring the sample; and

applying the high voltage potential to encourage the wetting of the liquid bridge between the pin tip and the through-hole, thereby dispensing the microfluidic sample; and

submersing the plurality of target receptacles in a liquid that is immiscible with the microfluidic sample.

80. The method of claim 79, further comprising:

initiating transfer of the sample from the at least one transfer pin tip to the target receptacle when the sample contacts the target receptacle.

81. A method of claim 79, wherein the immiscible liquid is a perfluorinated hydrocarbon, hydrocarbon, or silicone fluid.

82. A method for use in dispensing a microfluidic sample of a liquid, the method comprising:

submersing a target receptacle in a liquid that is immiscible with the microfluidic sample to form a submersed target receptacle;

providing at least one transfer pin for transferring a microfluidic sample of liquid to the submersed target receptacle, one end of the transfer pin having a pin tip structured to cooperate with an opening in the submersed target receptacle;

initiating transfer of the sample from the at least one transfer pin tip to the target receptacle when the sample contacts the submersed target receptacle; and

applying a high voltage potential between the pin tip and the submersed target receptacle for transferring the sample from the at least one transfer pin to the submersed target receptacle,

wherein the target receptacle is a through-hole.

83. A method of claim 82, wherein the immiscible liquid is a perfluorinated hydrocarbon, a hydrocarbon, or a silicone fluid.