Redrawn capillary imaging reservoir

• US 6,884,626 B1
• Filed: 03/15/2000
• Issued: 04/26/2005
• Est. Priority Date: 04/27/1998
• Status: Expired due to Fees

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Root, David, Eid, Bernard, Borrelli, Nicholas F., Wusirika, Raja Rao, Dannoux, Thierry L. A., Carre, Alain R. E.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Gordon, Brian R
• Application Number:
  US09/525,920
• Time in Patent Office: 1,868 Days
• Field of Search: 422/99, 422/100, 422/102, 738/633.1, 738/638.1, 738/640.1, 738/643.1, 400/124.1, 101/93.37, 101/97, 101/98, 101/333, 436/180
• US Class Current: 436/180
• 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 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01J 2219/0031 the racks or blocks being mounted in stacked arrangements
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00648 : by the use of solid beads
• CPC Class Codes: B01J 2219/00659 : Two-dimensional arrays
• CPC Class Codes: B01J 2219/00673 : Slice arrays
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B01L 2200/021 : Adjust spacings in an array of wells, pipettes or holders, format transfer between arrays of different size or geometry
• CPC Class Codes: B01L 2300/0838 : Capillaries
• CPC Class Codes: B01L 3/0244 : using pins
• CPC Class Codes: B01L 3/50857 : using arrays or bundles of open capillaries for holding samples
• CPC Class Codes: B01L 3/563 : Joints or fittings in general F16L; Separable fluid transfer means to transfer fluids between at least two containers, e.g. connectors
• CPC Class Codes: C03B 19/06 : by sintering, e.g. by cold isostatic pressing of powders and subsequent sintering, by hot pressing of powders, by sintering slurries or dispersions not undergoing a liquid phase reaction
• CPC Class Codes: C03B 23/047 : by drawing C03B23/091 , C03B37/025 takes precedence
• CPC Class Codes: C03B 23/06 : by bending C03B23/096 takes precedence
• CPC Class Codes: C03B 37/028 : Drawing fibre bundles, e.g. for making fibre bundles of multifibres , image fibres; drawing multicore or photonic crystal fibres C03B37/027
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: C40B 70/00 : Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: G01N 1/16 : with provision for intake at several levels G01N1/2035 G01N1/12, G01N1/14 take precedence
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 2035/1069 : by adjusting the spacing between multiple probes of a single transferring head
• CPC Class Codes: G01N 33/54306 : Solid-phase reaction mechanisms
• CPC Class Codes: G01N 35/1065 : Multiple transfer devices
• CPC Class Codes: G01N 35/1067 : for transfer to or from containers having different spacing
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

Methods and apparatus for depositing a high density biological or chemical array onto a solid support. Specifically, the apparatus is made up of a plurality of open ended channels collectively forming a matrix. The matrix has been redrawn and cut such that the pitch of the channels on the loading end is larger than the pitch of the channels on the liquid delivery end. The upper portion of each channel serves as a reservoir, while the opposing end, which has been formed by the redrawing process, is diametrically sized such that liquid in the reservoir is retained by capillary pressure at the delivery end. At any point along the height of the capillary reservoir device, all cross-sectional dimensions and areas are uniformly reduced. In other words, the on-center orientation of any two channels, also referred to as the pitch between 2 channels, measured as a function of the diameter of any cross section, is constant throughout the structure. The liquid within the channels is either printed directly from the tool onto a substrate or transferred to a substrate by a typographical pin plate. In another embodiment, the device may be used in transferring sample between multiwell plates of different well density.

Claims

1. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a reservoir device having a plurality of individual passages, each passage having an input end and an output end of smaller cross sectional area than the input end;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate.

4. The method of any one of claims 1-3, wherein the contacting step includes moving the pins into contact with liquid from the corresponding passages.

5. The method as claimed in any one of claims 1-3, wherein the moving step includes moving the pins a sufficient distance such that the droplets of liquid directly contact the substrate.

6. The method as claimed in any one of claims 1-3, wherein the contacting step includes transferring droplets of liquid from the corresponding passages to tips of the pins.

7. The method as claimed in any one of claims 1-3, wherein the transfer device is a typographic pin plate.

8. The method as claimed in any one of claims 1-3, wherein the providing step includes providing a reservoir device in which a ratio of a cross sectional area of a passage relative to a cross sectional area of the reservoir device is substantially identical at a liquid-input end of the reservoir device and a liquid-output end of the reservoir device.

2. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a reservoir device having a plurality of individual passages, each passage having an output end and decreasing in cross sectional area along at least a portion of the passage in a direction toward the output end;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate.

3. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a rescrvoir device having a plurality of individual passages, each passage having an output end, a density of the passages in the reservoir device increasing along at least a portion thereof in a direction toward the output ends of the passages;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate.

9. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a reservoir device having a plurality of individual passages, each passage having an input end and an output end of smaller cross sectional area than the input end;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate,

wherein the providing step includes bundling a plurality of capillary tubes, and redrawing the bundled capillary tubes.

10. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a reservoir device having a plurality of individual passages, each passage having an input end and an output end of smaller cross sectional area than the input end;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate,

wherein the providing step includes extruding a material through a multi-cell die to create a multi-celled honeycomb structure, and redrawing at least a portion of the honeycomb structure.

11. The method of claim 10, wherein the providing step further includes cutting the redrawn portion in a direction perpendicular to a longitudinal direction of the passages to expose a face having a cross sectional area less than a cross sectional area of the extruded honeycomb structure.

12. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a reservoir device having a plurality of individual passages, each passage having an input end and an output end of smaller cross sectional area than the input end;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate,

wherein the providing step includes extruding material through a die thereby forming a block having the passages, and redrawing the block such that a circumference of the block is reduced.

13. A method for transferring individual droplets of liquid to a substrate, comprising:

providing a reservoir device having a plurality of individual passages, each passage having an input end and an output end of smaller cross sectional area than the input end;

positioning a transfer device having an array of pins extending therefrom such that the pins face the output ends of the passages;

contacting the pins with liquid from the corresponding passages to transfer droplets of liquid from the corresponding passages to the pins; and

moving the pins relative to the substrate to transfer the droplets of liquid onto the substrate,

wherein the positioning step includes positioning the pins opposite the output ends of the passages, and wherein the method further comprises the step of positioning the substrate between the pins and the output ends of the passages prior to moving the pins relative to the substrate.

14. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate.

17. The apparatus as claimed in any one of claims 14-16, wherein the reservoir device is a monolithic structure.

18. The apparatus as claimed in anyone of claims 14-16, further comprising a drive member adapted to move the pins relative to the corresponding passages.

19. The apparatus as claimed in any one of claims 14-16, wherein the pins are dimensioned to enter the corresponding passages.

20. The apparatus as claimed in any one of claims 14-16, wherein the passages are configured to prevent fluid communication therebetween.

21. The apparatus as claimed in any one of claims 14-16, wherein a ratio of a cross sectional area of a passage relative to a cross sectional area of the reservoir device is substantially identical at a liquid-inlet end of the reservoir device and at a liquid-output end of the reservoir device.

22. The apparatus as claimed in any one of claim 14-16, wherein the reservoir device has an input and an output in a different plane from the input.

23. The apparatus as claimed in claim 14, wherein the input end of each passage is in a different plane from the output end.

25. The apparatus as claimed in any one of claims 14-16, wherein the pins are dimensioned to extend into the output ends of the corresponding passages.

26. The apparatus as claimed in any one of claims 14-16, wherein the passages have interior walls having a wetting surface, and the output ends of the passages have a non-wetting end surface.

27. The apparatus as claimed in any one of claims 14-16, wherein the reservoir device is comprised of an organic polymer.

28. The apparatus as claimed in any one of claims 14-16, wherein the reservoir device is comprised of an inorganic polymer.

29. The apparatus as claimed in claim 28, wherein the inorganic polymer is glass.

30. The apparatus as claimed in any one of claims 14-16, wherein the reservoir device contains approximately 10,000 passages.

31. The apparatus as claimed in any one of claims 14-16, wherein the pins are adapted to receive liquid on tips of the pins.

32. The apparatus as claimed in any one of claims 14-16, wherein the transfer device is a typographic pin plate.

15. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each passage being isolated from each other passage, each passage having an output end and decreasing in cross sectional area along at least a portion of the passage in a direction toward the output end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages and to transfer individual droplets of liquid to the substrate.

24. The apparatus as claimed in any one of claims 15-16, wherein the passages of the reservoir device have an input end in a different plane from the output end.

16. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each passage having an output end, the density of the passages in the reservoir device increasing along at least a portion thereof in a direction toward the output ends of the passages; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate.

33. An apparatus for transferring individual droplets of liquid to a substrate, comprising;

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the reservoir device has an input and an output in the same plane as the input.

34. The apparatus as claimed in claim 33, wherein the reservoir device has a substantially U-shape.

37. The apparatus as claimed in any one of claims 33, 35, and wherein the reservoir device is approximately one inch square at the output ends of the passages.

38. The apparatus as claimed in any one of claims 33, 35, and 36, wherein the pins have a radius less than 50 μ

m.

39. The apparatus as claimed in any one of claims 33, 35, and 36, wherein the pins have a radius of about 40 μ

m.

40. The apparatus as claimed in any one of claims 33, 35, and 36, further comprising a boxed unit in which the reservoir device is mounted.

41. The apparatus as claimed in any one of claims 33, 35, and 36, wherein each passage is dimensioned to contain 5 to 500 microliters of liquid.

35. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the reservoir device has an input and an output in a different plane from the input, and

wherein the reservoir device has a substantially conical shape.

36. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the reservoir device has an input and an output in a different plane from the input, and

wherein the reservoir device has a substantially L-shape.

42. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the passages are defined by redrawn capillary tubes.

43. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the input end of each passage is in the same plane as the output end.

44. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each passage having an output end and decreasing in cross sectional area along at least a portion of the passage in a direction toward the output end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the passages of the reservoir device have an input end in the same plane as the output end.

45. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end; and

a transfer device having an array of pins extending therefrom;

the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the passages of the reservoir device form a substantially U-shape.

46. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each passage having an output end and decreasing in cross sectional area along at least a portion of the passage in a direction toward the output end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the passages of the reservoir device have an input end in a different plane from the output end, and

wherein the reservoir device has a substantially conical shape.

47. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each passage having an output end and decreasing in cross sectional area along at least a portion of the passage in a direction toward the output end; and

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate,

wherein the passages of the reservoir device have an input end in a different plane from, the output end, and

wherein the reservoir device has a substantially L-shape.

48. An apparatus for transferring individual droplets of liquid to a substrate, comprising:

a reservoir device having a plurality of individual passages, each of the passages having an input end and an output end of smaller cross sectional area than the input end;

a transfer device having an array of pins extending therefrom, the transfer device positionable such that the pins face the output ends of the passages, the pins being adapted to receive liquid from corresponding passages for transfer of individual droplets of liquid to the substrate; and

a drive member adapted to move the pins relative to the corresponding passages,

wherein the pins are mounted on a flexible mount, and the drive member is coupled to the flexible mount to flex the pins toward the output ends of the corresponding passages.

49. A reservoir device for use in transferring a high density biological or chemical array of individual droplets of liquid to a substrate, comprising:

a plurality of passages collectively foaming a matrix having a plurality of rows and columns, each of the passages having an input end and an output end, the passages being spaced apart by a center-to-center distance measured from the center of one passage to the center of an adjacent passage, the center-to-center distance between adjacent passages being larger between respective input ends than between respective output ends.

50. The reservoir device as claimed in claim 49, wherein, along at least a portion of the adjacent passages, the center-to-center distance between the adjacent passages decreases uniformly.

51. The reservoir device as claimed in claim 49, wherein the output end of each of the passages has a smaller cross sectional area than the input end.

52. The reservoir device as claimed in claim 49, wherein each of the passages decreases in cross sectional area along at least a portion of the passage in a direction toward the output end.

53. The reservoir device as claimed in claim 49, wherein a density of the passages in the reservoir device increases along at least a portion thereof in a direction toward the output ends of the passages.

54. The reservoir device as claimed in claim 49, wherein a ratio of a cross sectional area of a passage relative to a cross sectional area of the reservoir device is substantially identical at a liquid-input end of the reservoir device and a liquid-output end of the reservoir device.

55. The reservoir device as claimed in claim 49, wherein the passages are configured to prevent fluid communication therebetween.

56. The reservoir device as claimed in claim 54, wherein the reservoir device is approximately one inch square at the liquid-output end.

57. The reservoir device as claimed in claim 49, wherein the passages have interior walls having a wetting surface, and the output ends of the passages have a non-wetting end surface.

58. The reservoir device as claimed in claim 49, wherein the reservoir device is comprised of an organic polymer.

59. The reservoir device as claimed in claim 49, wherein the reservoir device is comprised of an inorganic polymer.

60. The reservoir device as claimed in claim 59, wherein the inorganic polymer is glass.

61. The reservoir device as claimed in claim 49, wherein the reservoir device contains approximately 10,000 passages.

62. The reservoir device as claimed in claim 49, wherein each passage is dimensioned to contain 5 to 500 microliters of liquid.

63. The reservoir device as claimed in claim 49, wherein the center-to-center distance is approximately 220 μ

m at the output ends of the passages.

64. The reservoir device as claimed in claim 49, wherein the center-to-center distance is approximately 350 μ

m at the output ends of the passages.

65. The reservoir device as claimed in claim 49, wherein the output end of each of the passages has a diameter of approximately 180 μ

m.

66. The reservoir device as claimed in claim 49, wherein the matrix is formed by a redrawn extruded material.

67. The reservoir device as claimed in claim 49, wherein the matrix is formed by bundled, redrawn capillary tubes.