Apparatus and method for spotting a substrate

• US 6,579,367 B2
• Filed: 07/30/2002
• Issued: 06/17/2003
• Est. Priority Date: 03/15/1999
• Status: Expired due to Fees

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Vann, Charles S., Bryning, Zbigniew
• Primary Examiner(s): SELLS, JAMES D
• Application Number:
  US10/209,565
• Publication Number:
  US 20020174831A1
• Time in Patent Office: 322 Days
• Field of Search: 118/401, 118/407, 118/410, 118/411, 118/412, 222/420
• US Class Current: 118/401
• 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 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00376 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00527 Sheets
• 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 2219/00626 Covalent
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2400/028 Pin is moved through a ring which is filled with a fluid
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 3/0244 using pins
• CPC Class Codes: B01L 3/0251 : Pin and ring type or pin in tube type dispenser
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/00237 : Handling microquantities of analyte, e.g. microvalves, capillary networks
• CPC Class Codes: G01N 2035/1034 : Transferring microquantities of liquid
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 2035/1039 : Micropipettes, e.g. microcapillary tubes
• CPC Class Codes: G01N 2035/1069 : by adjusting the spacing between multiple probes of a single transferring head
• CPC Class Codes: G01N 35/1016 : Control of the volume dispensed or introduced
• CPC Class Codes: G01N 35/1067 : for transfer to or from containers having different spacing
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention provides a method and apparatus for dispensing a small volume of a selected liquid, such as a biological sample or reagent, onto a substrate. The device includes a tube adapted to contain the liquid. An elongate fiber is disposed within the tube for axial movement therein between raised and lowered positions. Upon shifting or oscillating the fiber between its raised and lowered positions, a liquid spot can be formed at a selected position on the substrate. The device is readily adaptable for the production of micro-arrays having a great number of individual spots.

Claims

1. An apparatus for manipulating liquid reagents, comprising:

a manifold including a plurality of capillary channels, each adapted to hold a selected liquid, said channels including opposite upper-end and lower-end openings, with said lower openings defining a first array and said upper openings defining a second array,

a support movable between raised and lowered positions with respect to said manifold, and

a plurality of tips, coupled to said support for movement therewith, each tip being adapted to move longitudinally within an associated channel, as the support is moved between its raised and lowered positions.

2. The apparatus of claim 1, wherein each of said channels includes an interior region that is hydrophilic.

3. The apparatus of claim 1, wherein an exterior surface, adjacent each of said channels, exhibits hydrophobic characteristics.

4. The apparatus of claim 1, which further includes shifting means operatively connected to the support for shifting the same between its raised and lowered positions.

5. The apparatus of claim 1, wherein the diameter of the channels at their lower ends is less than about 200 μ

m.

6. The apparatus of claim 1, wherein each channel has a substantially uniform diameter extending along a lower end region thereof that terminates at the channel'"'"'s lower end.

7. The apparatus of claim 1, further comprising a plurality of fibers held by said support, with a distal end of each fiber defining one of said tips.

8. The apparatus of claim 1, wherein the center-to-center spacing of the openings of the first array differs from the center-to-center spacing of the openings of the second array.

9. The apparatus of claim 1, wherein the center-to-center spacing of the openings of the first array is substantially equal to the center-to-center spacing of the openings of the second array.

10. An apparatus for manipulating liquid reagents, comprising:

a manifold including a plurality of capillary channels, each adapted to hold a selected liquid, said channels including opposite upper-end and lower-end openings, with said lower openings defining a first array and said upper openings defining a second array, and

a plurality of tips movable between raised and lowered positions with respect to said manifold, each tip being adapted to move longitudinally within an associated channel, as it is moved between its raised and lowered positions.

11. The apparatus of claim 10, wherein each of said channels includes an interior region that is hydrophilic.

12. The apparatus of claim 10, wherein an exterior surface, adjacent each of said channels, exhibits hydrophobic characteristics.

13. The apparatus of claim 10, wherein the diameter of the channels at their lower ends is less than about 200 μ

m.

14. The apparatus of claim 10, wherein each channel has a substantially uniform diameter extending along a lower end region thereof that terminates at the channel'"'"'s lower end.

15. The apparatus of claim 10, further comprising a plurality of fibers, with a distal end of each fiber defining one of said tips.

16. The apparatus of claim 10, wherein the center-to-center spacing of the openings of the first array differs from the center-to-center spacing of the openings of the second array.

17. The apparatus of claim 10, wherein the center-to-center spacing of the openings of the first array is substantially equal to the center-to-center spacing of the openings of the second array.

18. An apparatus for the manipulation of liquid reagents, comprising:

a manifold including first and second substantially parallel, planar surfaces and a plurality of channels extending between said surfaces, said channels including opposite upper-end and lower-end openings, with said lower openings defining a first array and said upper openings defining a second array,

wherein a region of each channel extending from a respective one of the lower-end openings is of capillary size, such that a liquid placed in the channel will normally be maintained therein,

and wherein the center-to-center spacing of the openings of the first array differs from the center-to-center spacing of the openings of the second array.

19. The apparatus of claim 18, wherein each of said channels includes an interior region that is hydrophilic.

20. The apparatus of claim 18, wherein an exterior surface, adjacent each of said channels, exhibits hydrophobic characteristics.

21. The apparatus of claim 18, wherein each of said channels has an inner diameter that changes on progressing from the upper- to lower-end openings.

22. The apparatus of claim 18, further comprising a plurality of tips movable between raised and lowered positions with respect to said manifold, each tip being adapted to move longitudinally within an associated channel, as it is moved between its raised and lowered positions.

23. The apparatus of claim 22, further comprising a plurality of fibers, with a distal end of each fiber defining one of said tips.

24. The apparatus of claim 18, further comprising a plurality of fibers, each fiber being adapted to move longitudinally within a respective one of said channels.

25. The apparatus of claim 24, wherein said fibers are optical fibers.

26. An apparatus for the manipulation of liquid reagents, comprising:

a manifold including first and second substantially parallel, planar surfaces and a plurality of channels extending between said surfaces, said channels including opposite upper-end and lower-end openings, with said lower openings defining a first array and said upper openings defining a second array,

wherein a region of each channel extending from a respective one of the lower-end openings is of capillary size, such that a liquid placed in the channel will normally be maintained therein,

and wherein each of said channels has an inner diameter that changes on progressing from the upper- to lower-end openings.

27. The apparatus of claim 26, wherein each of said channels includes an interior region that is hydrophilic.

28. The apparatus of claim 26, wherein an exterior surface, adjacent each of said channels, exhibits hydrophobic characteristics.

29. The apparatus of claim 26, wherein the center-to-center spacing of the openings of the first array differs from the center-to-center spacing of the openings of the second array.

30. The apparatus of claim 26, further comprising a plurality of tips movable between raised and lowered positions with respect to said manifold, each tip being adapted to move longitudinally within an associated channel, as it is moved between its raised and lowered positions.

31. The apparatus of claim 30, further comprising a plurality of fibers, with a distal end of each fiber defining one of said tips.

32. The apparatus of claim 26, further comprising a plurality of fibers, each fiber being adapted to move longitudinally within a respective one of said channels.

33. The apparatus of claim 32, wherein said fibers are optical fibers.

34. An apparatus for the manipulation of liquid reagents, comprising:

a manifold including a plurality of channels, said channels including opposite upper-end and lower-end openings, with said lower openings defining a first array and said upper openings defining a second array,

a substrate positioned under said manifold, and

a plurality of protuberances extending from said substrate, with said protuberances being disposed in an array like said first array;

wherein a region of each channel extending from a respective one of the lower-end openings is of capillary size, such that a liquid placed in the channel will normally be maintained therein,

and further wherein said manifold is adapted for movement toward and away from said substrate.