Apparatus and method for spotting a substrate

• US 7,211,148 B2
• Filed: 01/18/2005
• Issued: 05/01/2007
• Est. Priority Date: 03/15/1999
• Status: Expired due to Fees

• Current Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Vann, Charles S., Bryning, Zbigniew T.
• Primary Examiner(s): SELLS, JAMES D
• Application Number:
  US11/038,334
• Publication Number:
  US 20050120949A1
• Time in Patent Office: 833 Days
• Field of Search: 118/401, 118/407, 118/410, 118/411, 118/412, 422/81, 422/100, 222/420, 427/2.11
• 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 elongated 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. A method for the manipulation of liquid, comprising:

(a) providing a system comprising (i) a device comprising first and second opposing surfaces and at least 1024 channels extending between said surfaces, said channels including opposite upper-end and lower-end openings, with said openings defining upper and lower opening arrays;

wherein at least a region of each channel is of capillary size, and wherein each of said channels includes an interior region that is hydrophilic; and

(ii) a multi-well tray;

(b) introducing a selected liquid comprising a biological sample or reagent into said channels, with the liquid being retained in the channels by surface tension forces;

(c) placing said device adjacent said multi-well tray, such that each of said channels is in alignment with a respective well of said tray; and

(d) transferring the selected liquid from each channel into its respective well.

2. The method of claim 1, wherein said device is of a monolithic construction.

3. The method of claim 1, wherein the center-to-center spacing of the openings of the upper opening array is substantially equal to the center-to-center spacing of the openings of the lower opening array.

4. The method of claim 1, wherein the device includes at least 1536 channels.

5. A method for the manipulation of liquid, comprising:

(a) providing a system comprising (i) a device comprising first and second opposing surfaces and at least 1024 channels extending between said surfaces, said channels including opposite upper-end and lower-end openings, with said openings defining upper and lower opening arrays;

wherein at least a region of each channel is of capillary size, such that a liquid placed in the channel will normally be maintained therein;

(ii) a multi-well tray;

(iii) a liquid-transfer tip, movable between said channels and said tray;

(iv) an actuator operatively connected to the tip for moving the tip; and

(v) a control unit operatively connected to the actuator for controlling the actuator; and

(b) using said tips, moving a selected liquid comprising a biological sample or reagent between said channels and said tray.

6. The method of claim 5, wherein in step (b), said liquid is moved from a plurality of the channels into a plurality of wells of the tray.

7. The method of claim 5, wherein each of said channels includes an interior region that is hydrophilic.

8. The method of claim 5, wherein said actuator is a piezoelectric actuator.

9. A system for the manipulation of liquid, comprising:

a device comprising first and second opposing surfaces and at least 1024 channels extending between said surfaces, said channels including opposite upper-end and lower-end openings, with said upper-end and lower-end openings defining respective opening arrays;

wherein at least a region of each channel is of capillary size, such that a liquid placed in the channel will normally be maintained therein;

a plurality of liquid-transfer tips disposed in an array;

wherein said tips are adapted for movement toward and away from one of said surfaces;

an actuator operatively connected to the tip for moving the tip; and

a control unit operatively connected to the actuator for controlling the actuator.

10. The system of claim 9, wherein said array of tips is alignable with at least a subset of said channels.

11. The system of claim 9, wherein each of said tips is comprised of a distal end region of an elongated member.

12. The system of claim 9, wherein each of said channels includes an interior region that is hydrophilic.

13. The system of claim 9, further comprising a multi-well tray, with said tips being adapted for movement between said channels and said tray.

14. The system of claim 9, wherein said actuator is a piezoelectric actuator.

15. A system for manipulation of liquid, comprising:

a device comprising at least 1536 channels in fixed, spaced relation;

with the channels including opposite upper-end and lower-end openings;

wherein at least a region of each channel is of capillary size, such that an aqueous liquid placed in the channel will normally be maintained therein;

a liquid-transfer tip;

an actuator operably coupled to said tip, and adapted to move said tip toward and away from said channels; and

a control unit operatively connected to the actuator for controlling the actuator.

16. The system of claim 15, wherein each of said channels includes an interior region that is hydrophilic.

17. The system of claim 15, wherein each of said tips is comprised of a distal end region of an elongated member.

18. The system of claim 15, wherein said channels are defined by through-holes formed in a block.

19. The system of claim 15, wherein said actuator is a piezoelectric actuator.

20. The system of claim 15, wherein the longitudinal axis of at least some of said channels comprises a curve.

21. The system of claim 15, further comprising a conveyer disposed under said device.

22. The system of claim 21, further comprising a multi-well plate disposed on said conveyor.