Capillary pins for high-efficiency microarray printing device

• US 20050169808A1
• Filed: 12/15/2004
• Published: 08/04/2005
• 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., Brown, Nils W., Hamilton, Greg, Nordmeyer, Robert
• Granted Patent: US 7,402,286 B2
• Time in Patent Office: Days
• US Class Current: 422/100
• 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

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 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;

a vacuum chamber through which the capillaries and the pistons are disposed;

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 the force holding the pistons into the chamber and thereby increases the resistance of said capillaries to deflection away from a printing substrate.

2. The print head of claim 1, wherein each capillary is coupled to a single piston.

3. The print head of claim 1, wherein one or more capillaries are coupled to a single piston.

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

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

6. The print head 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.

7. The print head of claim 6, wherein the lower wall of said chamber comprises two guide plates such that lateral movement of said capillaries is constrained at two positions.

8. The print head of claim 1, wherein said spotting capillaries pass through the upper end of the pistons.

9. The print head of claim 1, wherein said spotting capillaries are attached to the upper portion of the pistons at the upper portion of the capillaries.

10. The print head of claim 1, wherein the spacing of said capillaries accommodates a standard 864 well microtiter plate.

11. The print head of claim 1, wherein the spacing of said capillaries accommodates a standard1536 well microtiter plate.

12. The print head of claim 1, wherein the spacing between two adjacent spotting capillaries is about 3 mm or less, center to center.

13. The print head of claim 1, wherein said spotting capillaries are glass or quartz.

14. The print head of claim 1, wherein said spotting capillaries have a beveled tip.

15. The print head of claim 13, wherein said beveled tip is ground.

16. The print head of claim 1, wherein a capillary comprising said print head has maximum load volume of about 0.5 μ

L.

17. The print head of claim 1, wherein a capillary comprising said print head has a minimum load volume of about 0.05 μ

L.

18. The print head of claim 1, wherein a capillary comprising said print head has a load volume of about 0.2 μ

L.

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

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

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

22. The print head of claim 1, wherein said print head is in a microarray printing device.

23. The print head of claim 1, wherein said capillaries are in fluid communication with a manifold.

24. The print head of claim 23, 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.

25. A microarray printing device, said microarray printing device comprising:

a microarray print head according to any of claims 1 through 24; and

a microarray substrate holder attached to a platen.

26. The microarray printing device of claim 25, wherein said microarray substrate holder comprises one or more vacuum ports under the substrate when the substrate is place on the platen.

27. The microarray printing device of claim 25, wherein said microarray substrate holder comprises locating pins to position each substrate.

28. The microarray printing device of claim 25, wherein said microarray substrate holder comprises a spring loaded retainer.

29. The microarray printing device of claim 25, wherein said printing device can print at least about 1500 to about 2000 array elements per spotting capillary per load.

30. The microarray printing device of claim 25, wherein said printing device can print array elements with a precision of at least 30 μ

m.

31. The microarray printing device of claim 25, wherein said printing device can print array elements with a precision of at least 10 μ

m precision.

32. The microarray printing device of claim 25, wherein said printing device can print array elements with a precision of at least 5 μ

m precision.

33. The microarray printing device of claim 25, wherein said printing device can print array elements with an average inter-element spacing of 130 μ

m or less.

34. The microarray printing device of claim 25, wherein said printing device can print array elements with an average inter-element spacing of 100 μ

m or less.

35. The microarray printing device of claim 25, wherein said printing device can print array elements with an average inter-element spacing of 90 μ

m or less.

36. The microarray printing device of claim 25, wherein said printing device can print array elements with an average inter-element spacing of 70 μ

m or less.

37. The microarray printing device of claim 25, wherein said microarray printer utilizes pressure and vacuum to control reagent loading or dispensing.

38. The microarray printing device of claim 25, wherein the spotting capillaries are in fluid communication with a manifold thereby permitting liquids to be drawn through said capillaries into said manifold.

39. The microarray printing device of claim 38, wherein said manifold comprises a common port and individual ports wherein an aperture into an individual port is disposed inward of the inside wall of said manifold.

40. The microarray printing device of claim 25, wherein said device can print more than 200 microarray substrates in a run.

41. The microarray printing device of claim 25, wherein said device loads reagents from a microtiter plate comprising at least about 864 wells.

42. The microarray printing device of claim 25, wherein said device loads reagents from a microtiter plate comprising at least about 1536 wells.

43. The microarray printing device of claim 25, wherein said device comprises means for applying positive or negative pressure to the spotting capillaries and/or to the vacuum chamber in the print head.

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

providing an array substrate in a microarray printing device of any one of claims 25 through 44;

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

operating said microarray printing device to print said microarray.

45. The method of claim 44, wherein said microarray printing device prints a microarray comprising at least 1,000 different array elements.

46. The method of claim 44, wherein said microarray printing device prints a microarray comprising having an average inter-feature spacing of no more than about 130 μ

m.

47. The method of claim 44, wherein said microarray is a nucleic acid microarray.

48. The method of claim 44, wherein said microarray is a protein microarray.

49. The method of claim 44, wherein said microarray is a small organic molecule microarray.

50. The method of claim 44, wherein said substrate is a glass substrate.

51. The method of claim 44, wherein said substrate is a metal-coated glass substrate.

52. The method of claim 44, wherein said microarray printing device applies vacuum to the manifold to load a spotting capillary.

53. The method of claim 52, wherein the vacuum is applied as one or more pulses.

54. The method of claim 53, wherein the pulses are less than about 0.5 sec in duration.

55. The method of claim 44, wherein said microarray printing device applies positive pressure to the manifold when dispensing from a spotting capillary to the substrate.

56. The method of claim 44, wherein said method comprises loading feature-forming reagents from a microtiter plate comprising at least about 864 wells.