Capillary pins for high-efficiency microarray printing device

• US 8,283,181 B2
• Filed: 07/09/2008
• Issued: 10/09/2012
• Est. Priority Date: 06/27/2001
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Pinkel, Daniel, Albertson, Donna G., Hamilton, Greg, Brown, Nils W., Nordmeyer, Robert
• Primary Examiner(s): Gordon, Brian R
• Application Number:
  US12/169,863
• Publication Number:
  US 20090029876A1
• Time in Patent Office: 1,553 Days
• Field of Search: 422501-504, 422520-522, 738/633.2, 738/64, 738/640.1, 738/641.1, 738/641.3, 738/641.6, 738/642.4, 436/180, 436/54, 436/807
• US Class Current: 436/180
• CPC Class Codes: B41J 2/005 characterised by bringing liquid or particles selectively into contact with a printing material printing by selective application of impact or pressure on a printing or impression-transfer material B41J2/22
• CPC Class Codes: B41J 2/25 Print wires
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2565/507 characterised by the density of the capture oligonucleotide
• CPC Class Codes: Y10T 436/119163 with aspirator of claimed structure
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/2575 Volumetric liquid transfer

Abstract

This invention provides improved components (e.g. array “pins”, print head, substrate platen, print head platen, and the like) for microarray printing devices as well as microarray printing devices incorporating such components. In one embodiment, this invention provides a microarray print head comprising a plurality of glass or quartz spotting capillaries disposed in a support that maintains a fixed spacing between the spotting capillaries and that permits the spotting capillaries to move in a direction parallel to the long axis of the capillaries.

Claims

1. A method of printing a microarray, said method comprising:

providing an array substrate in a microarray printing device, said printing device comprising;

a microarray substrate holder attached to a platen wherein said substrate holder contains said array substrate; and

a microarray print head, said print head comprising;

a plurality of spotting capillaries disposed in a support that permits the spotting capillaries to move in a direction parallel to the long axis of said capillaries, wherein said capillaries are coupled to pistons;

a vacuum chamber comprising an upper wall and a lower wall through which the capillaries and the pistons are disposed; and

a port in said chamber to which a vacuum can be applied;

wherein said pistons and capillaries are disposed such that increasing the vacuum in said chamber increases a force holding the pistons into the chamber and thereby increases the resistance of said capillaries to deflection away from a printing substrate;

providing a series of solutions comprising reagents that will form features of said microarray; and

operating said microarray printing device to print said micro array on the array substrate.

2. The method of claim 1, wherein said microarray printing device prints a microarray comprising at least 1,000 different array elements.

3. The method of claim 1, wherein said microarray printing device prints a microarray comprising having an average inter-feature spacing of no more than about 130 μ

m.

4. The method of claim 1, wherein said microarray is a nucleic acid microarray.

5. The method of claim 1, wherein said microarray is a protein microarray.

6. The method of claim 1, wherein said microarray is a small an organic molecule microarray.

7. The method of claim 1, wherein said substrate is a glass substrate.

8. The method of claim 1, wherein said substrate is a metal-coated glass substrate.

9. The method of claim 1, wherein said microarray printing device comprises a manifold in fluid communication with said capillaries.

10. The method of claim 9, wherein said microarray printing device applies vacuum to said manifold to load a spotting capillary.

11. The method of claim 9, wherein the vacuum is applied as one or more pulses.

12. The method of claim 9, wherein said microarray printing device applies positive pressure to the manifold when dispensing from a spotting capillary to the substrate.

13. The method of claim 1, wherein said method comprises loading feature-forming reagents from a microtiter plate comprising at least about 864 wells.

14. The method of claim 11, wherein the duration of each of said one or more pulses is less than about 0.5 sec.

15. The method of claim 1, wherein each capillary is coupled to a single piston.

16. The method of claim 1, wherein one or more capillaries are coupled to a single piston.

17. The method of claim 1, wherein said print head further comprises a means for adjusting the vacuum in said chamber.

18. The method of claim 1, wherein the lower wall of said chamber comprises a plurality of tapered guide holes in which said capillaries are disposed.

19. The method of claim 1, wherein the lower wall of said chamber comprises two or more guide plates such that lateral movement of said capillaries is constrained at two or more positions.

20. The method of claim 1, wherein the lower wall of said chamber comprises two guide plates such that lateral movement of said capillaries is constrained at two positions.

21. The method of claim 1, wherein said spotting capillaries pass through an upper end of the pistons.

22. The method of claim 1, wherein said spotting capillaries are attached to an upper portion of the pistons at an upper portion of the capillaries.

23. The method of claim 1, wherein said capillaries are spaced to accommodate a standard 864 well microtiter plate.

24. The method of claim 1, wherein said capillaries are spaced to accommodate a standard 1536 well microtiter plate.

25. The method of claim 1, wherein the distance between adjacent spotting capillaries is about 3 mm or less, center to center.

26. The method of claim 1, wherein said spotting capillaries are glass or quartz.

27. The method of claim 1, wherein said spotting capillaries have a beveled tip.

28. The method of claim 27, wherein said beveled tip is ground.

29. The method of claim 1, wherein a capillary in said print head has maximum load volume of about 0.5 μ

L.

30. The method of claim 1, wherein a capillary in said print head has a minimum load volume of about 0.05 μ

L.

31. The method of claim 1, wherein a capillary in said print head has a load volume of about 0.2 μ

L.

32. The method of claim 1, wherein said print head comprises at least 4 spotting capillaries.

33. The method of claim 1, wherein said print head comprises at least 16 spotting capillaries.

34. The method of claim 1, wherein said print head comprises from 16 to about 256 capillaries.

35. The method of claim 1, wherein said capillaries are in fluid communication with a manifold.

36. The method of claim 35, wherein said manifold comprises at least one common port and individual ports wherein an aperture into an individual port is disposed inward of the inside wall of said manifold.

37. The method of claim 1, wherein said printing device prints at least 5,000 array elements per spotting capillary per load.

38. The method of claim 1, wherein said printing device prints array elements with a precision of at least 30 μ

m.

39. The method of claim 1, wherein said printing device prints array elements with an average inter-element spacing 130 μ

m or less.

40. The method of claim 9, wherein said microarray printer utilizes pressure and vacuum to control reagent loading or dispensing.

41. The method of claim 1, wherein said device prints more than 200 microarray substrates in a run.

42. The method of claim 1, wherein said device loads reagents from a microtiter plate comprising at least about 864 wells.

43. The method of claim 1, wherein said device loads reagents from a microtiter plate comprising at least about 1536 wells.

44. The method of claim 1, wherein said device comprises means for applying positive or negative pressure to the spotting capillaries and/or to the chamber in the print head.