Gene pen devices for array printing

• US 6,235,473 B1
• Filed: 07/02/1998
• Issued: 05/22/2001
• Est. Priority Date: 07/02/1998
• Status: Expired due to Term

• Current Assignee: Beckman Coulter Incorporated (Danaher Corporation)
• Original Assignee: Orchid Biosciences Incorporated (Laboratory Corporation Of America Holdings)
• Inventors: Friedman, Mitchell, Rogers, Yu-Hui, Boyce-Jacino, Michael
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Siew, Jeffrey
• Application Number:
  US09/109,915
• Time in Patent Office: 1,055 Days
• Field of Search: 435/6, 435/286.4, 422/131, 422/130, 422/116
• US Class Current: 435/6.19
• 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 2219/00364 Pipettes
• 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 2219/00382 Stamping
• CPC Class Codes: B01J 2219/00385 Printing
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• 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 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• 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 2219/0063 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: B01L 3/0258 : using stamps
• CPC Class Codes: B01L 3/0262 : using touch-off at substrate or container
• CPC Class Codes: B01L 3/0265 : using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
• CPC Class Codes: C07B 61/00 : Other general methods
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 2035/1023 : using a valve in the tip or nozzle
• CPC Class Codes: G01N 2035/1037 : Using surface tension, e.g. pins or wires
• CPC Class Codes: G01N 35/1074 : arranged in a two-dimensional array

Abstract

The invention concerns an apparatus for printing arrays of molecules and methods for printing these arrays. More particularly, the invention relates to a gene pen apparatus that may be used for delivering arrays of oligonucleotides on solid supports from a multiplicity of reagent reservoirs through flow controlling means. The flow controlling means may for example, be either a pin valve means or a wicking means.

Claims

1. A gene pen apparatus for delivering arrays of oligonucleotides on an array support comprising:

(A) an array-forming printhead, said printhead comprising a body, a printing face, and a flow controlling means, said body having, a multiplicity of bores therethrough, said printing face comprising a multiplicity of fluid orifices, each of said fluid orifices being contiguous with at least one of said bores, said fluid orifices being spatially arranged in an array, and said flow controlling means is either a pin valve means or wicking member means, wherein the flow controlling means is located at the fluid orifices; and

(B) a multiplicity of reagent reservoirs, each of said reagent reservoirs being fluidly connected to at least one of said bores at an end, each of said reagent reservoir being of sufficient volume to enable the printing of a multiplicity of said arrays.

2. The gene pen apparatus of claim 1, comprising at least 5 fluid reservoirs.

3. The gene pen apparatus of claim 1, comprising at least 10 fluid reservoirs.

4. The gene pen apparatus of claim 1, comprising at least 100 fluid reservoirs.

5. The gene pen apparatus of claim 1, comprising at least 1000 fluid reservoirs.

6. The gene pen apparatus of claim 1, comprising at least 10,000 fluid reservoirs.

7. The gene pen apparatus of claim 1, comprising at least 100,000 fluid reservoirs.

8. The array-forming printhead of claim 1, wherein said printing face is hydrophobic.

9. The array-forming printhead of claim 1, wherein said printing face is hydrophilic.

10. The array-forming printhead of claim 1, wherein the flow controlling means is a pin valve positioned internally within the bore of each of said fluid orifices, said pin valve extending inwardly into the body of said printhead and extending outwardly beyond the printing face of said array-forming printhead, such that contacting said printing face of said printhead with an array support causes said pin valve to be pushed further into said orifice, opening said pin valve and allowing reagent fluid flow.

11. The array-forming printhead of claim 9, wherein the flow controlling means is a pin valve positioned internally within the bore of each of said fluid orifices, said pin valve extending inwardly into the body of said printhead and extending outwardly beyond the printing face of said array-forming printhead, such that contacting said printing face of said printhead with an array support causes said pin valve to be pushed further into said orifice, opening said pin valve and allowing reagent fluid flow.

12. The array-forming printhead of claim 1, wherein the flow controlling means is a wicking means, said wicking member means comprising a felt tip positioned internally within the bore of each of said orifices, such that said felt tip extends outwardly beyond the printing face of said array-forming printhead.

13. The array-forming printhead of claim 9, wherein the flow controlling means is a wicking means, said wicking member means comprising a felt tip positioned internally within the bore of each of said orifices, such that said felt tip extends outwardly beyond the printing face of said array-forming printhead.

14. The array-forming printhead of claim 1, additionally comprising a wicking member positioned internally within the bore of each of said orifices.

15. The gene pen apparatus of claim 1, wherein said fluid connection is mediated by reagent-carrying tubes.

16. The gene pen apparatus of claim 15, wherein said printing face comprises said reagent-carrying tubes.

17. The gene pen apparatus of claim 15, wherein said reagent-carrying tubes are said reagent reservoirs.

18. The array-forming printhead of claim 16, additionally comprising an outer retaining member, said reagent-carrying tubes being tightly packed within said outer retaining member.

19. The array-forming printhead of claim 18, wherein said outer retaining member is a tube of circular cross-section.

20. The array-forming printhead of claim 18, wherein said outer retaining member is a tube of rectangular cross-section.

21. The gene pen apparatus of claim 16, additionally comprising a wicking member positioned internally within the each of said reagent-carrying tubes.

22. The gene pen apparatus of claim 16, additionally comprising a wicking member positioned internally within each of said reagent reservoirs.

23. The gene pen apparatus of claim 16, additionally comprising a wicking member positioned internally within the each of said fluid orifices.

24. A method for printing an array of molecules on an array support, comprising the step of contacting at least one array-forming printhead of at least one pen apparatus, with an array support, thereby transferring an amount of a multiplicity of reagent solutions to the array support so as to form an array on said support, said gene pen apparatus comprising:

(A) an array-forming printhead, said printhead comprising a body, and a printing face, said body having a multiplicity of bores therethrough, said printing face comprising a multiplicity of fluid orifices, each of said fluid orifices being contiguous with at least one of said bores, said fluid orifices being spatially arranged in an array, and

(B) a multiplicity of reagent reservoirs, each of said reagent reservoirs having a reagent flow controlling means, said reagent flow controlling means being comprised of either a pin valve means or a wicking means, said reagent reservoirs being fluidly connected to at least one of said bores at an end, each of said reagent reservoirs being of sufficient volume to enable the printing of a multiplicity of said arrays.

25. The method of claim 24, wherein a multiplicity of gene pens are contacted with the array support.

26. The method of claim 24, wherein said array support is a solid support.

27. The method of claim 24, wherein said array support is a semi-solid support.

28. The method of claim 24, wherein said array support is hydrophobic.

29. The method of claim 24, wherein said array support is hydrophilic.

30. The method of claim 24, wherein said array support comprises array receptacles, said receptacles being hydrophilic and at least an area surrounding each of said array receptacles is hydrophobic.

31. The method of claim 24, wherein said array support comprises array receptacles, said receptacles being hydrophobic and at least an area surrounding each of said array receptacles is hydrophilic.

32. The method of claim 30, wherein said hydrophobicity results from treatment of at least a portion of said array support with a hydrophobic silane and said hydrophilicity results from treatment of said array receptacles with a hydrophilic silane.

33. The method of claim 31, wherein said hydrophobicity results from treatment of at least a portion of said array support with a hydrophobic silane and said hydrophilicity results from treatment of said array receptacles with a hydrophilic silane.

34. The method of claim 31, wherein said hydrophobicity results from treatment of at least a portion of said array support with hydrophobic silane and said hydrophilicity results from treatment of said array receptacles with protein.

35. The method of claim 34, wherein said protein is an antibody.

36. The method of claim 34, wherein said protein is streptavidin.

40. The method of claim 24, wherein said printhead has at least one fluid orifices per cm².

41. The method of claim 24, wherein said printhead has at least ten fluid orifices per cm².

42. The method of claim 24, wherein said printhead has at least one hundred fluid orifices per cm².

43. The method of claim 24, wherein said printhead has at least one thousand fluid orifices per cm².

37. A method for printing an array of molecules on an array support, comprising the steps of:

(A) contacting at least one array-forming printhead of at least one gene pen apparatus, with a transfer pad, thereby transferring a sufficient amount of a multiplicity of reagent solutions to said transfer pad, said gene pen apparatus comprising a printing head and a reagent reservoirs, said reagent reservoir having a reagent flow controlling means; and

(B) contacting said transfer pad with an array support, thereby transferring a sufficient amount of said reagent solutions from said transfer pad to the array support so as to form an array on said array support.

38. The method of claim 37, wherein said gene pen apparatus comprises:

(A) an array-forming printhead, said printhead comprising a body, and a printing face, said body having a multiplicity of bores therethrough, said printing face comprising a multiplicity of fluid orifices, each of said fluid orifices being contiguous with at least one of said bores, said fluid orifices being spatially arranged in an array, and

(B) a multiplicity of reagent reservoirs, each of said reagent reservoirs being fluidly connected to at least one of said bores at an end, each of said reagent reservoirs being of sufficient volume to enable the printing of a multiplicity of said arrays.

39. The method of claim 38, wherein said transfer pad of claim 37 is a lithography transfer pad.