Multiple Capillary Device and Method for Synthesis and Dispensing

• US 20080269076A1
• Filed: 05/04/2006
• Published: 10/30/2008
• Est. Priority Date: 05/06/2005
• Status: Abandoned Application

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applera Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Ermakov, Sergey V.
• Application Number:
  US11/919,965
• Publication Number:
  US 20080269076A1
• Time in Patent Office: Days
• US Class Current: 506/32
• 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 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00308 interchangeably mounted in racks or blocks
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• CPC Class Codes: B01J 2219/00524 in the shape of fiber bundles
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0829 Multi-well plates; Microtitration plates
• CPC Class Codes: B01L 2300/0838 Capillaries
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: G01N 35/1074 arranged in a two-dimensional array

Abstract

A system and method for synthesizing a peptide, a nucleic acid sequence, an oligonucleotide, a DNA sequence, an RNA sequence, or the like, inside an array of capillary tubes, is provided. The system can comprise an array of capillary tubes. Each of the capillary tubes in the array of capillary tubes can comprise a first end, a second end, an inner wall, and a sequence linker bonded to the inner wall. The system can comprise a pressure control source that can be in fluid communication with each of the first ends of the array of capillary tubes. The system can comprise a reagent container support, wherein the second end of each of the capillary tubes can be adapted to move towards and/or away from the reagent container support.

Claims

1. A system comprising:

an array of capillary tubes, each capillary tube in the array of capillary tubes comprising a first end, a second end, an inner wall, and a sequence linker bonded to the inner wall;

a pressure control source in fluid communication with each of the first ends; and

a reagent container support;

wherein the second end of each capillary tube is adapted to individually move towards and away from the reagent container support.

2. The system of claim 1, further comprising at least one of a waste reservoir or reagent container in fluid communication with at least one of the first ends.

3. The system of claim 1, further comprising a first interface arranged to hold the array of capillary tubes operatively within the pressure control source.

4. The system of claim 1, wherein the pressure control source comprises a pressure control block.

5. The system of claim 1, further comprising a microfluidic device located proximate the second ends of the array of capillary tubes.

6. The system of claim 5, further comprising a second interface arranged to hold the second ends of the capillary tubes in the microfluidic device.

7. The system of claim 6, wherein the second ends of the array of capillary tubes pass through and extend beyond the second interface by at least about 0.1 cm.

8. The system of claim 1, further comprising a reagent container supported by the reagent container support, wherein the reagent container comprises at least one multi-well plate comprising a plurality of wells.

9. The system of claim 8, further comprising at least one dispensing unit adapted to at least partially fill at least one of the plurality of wells with one or more reagents.

10. The system of claim 1, further comprising a cleaving reagent adapted to be in fluid communication with at least one of the first ends.

11. The system of claim 1, wherein the reagent container support further comprises a rotating platen adapted to support a plurality of reagent plates.

12. The system of claim 1, wherein the pressure control source 15 is capable of providing a positive pressure and a negative pressure individually to each capillary tube.

13. The system of claim 1, wherein the array of capillary tubes comprises 24 or more capillary tubes.

25. The system of claim 1, wherein said sequence linker is a nucleotide linker.

26. The system of claim 1, wherein said sequence linker is an amino acid linker.

27. The system of claim 1, wherein the linker comprises a protected oligonucleotide.

28. The system of claim 1, wherein the first reagent comprises a deprotectant.

29. The system of claim 1, wherein the second reagent comprises a protected nucleotide.

30. The system of claim 1, wherein the first sequence comprises an oligonucleotide.

31. The system of claim 1, wherein the first sequence comprises a ribonucleic acid sequence.

32. The system of claim 1, wherein the first sequence comprises a deoxyribonucleic acid sequence.

33. The system of claim 1, wherein the first sequence comprises a peptide sequence.

14. A system comprising:

an array of capillary tubes, each capillary tube comprising a first end, a second end, and an inner wall;

a pressure control source in fluid communication with each of the first ends; and

a reagent container support comprising a rotating platen adapted to hold a plurality of reagent containers;

wherein the second end of each capillary tube is adapted to individually move toward and away from the reagent container support.

15. The system of claim 14, further comprising at least one of a waste reservoir or a reagent container in fluid communication with at least one of the first ends.

16. The system of claim 14, further comprising a first interface arranged to hold the array of capillary tubes operatively within the pressure control source.

17. The system of claim 14, wherein the pressure control source comprises a pressure control block.

18. The system of claim 14, further comprising a microfluidic device located proximate the second ends of the array of capillary tubes.

19. The system of claim 18, further comprising a second interface arranged to hold the second ends of the capillary tubes in the microfluidic device.

20. The system of claim 19, wherein the second ends of the array of capillary tubes pass through and extend beyond the second interface by at least about 0.1 cm.

21. The system of claim 14, further comprising a reagent container supported by the reagent container support, wherein the reagent container comprises at least one multi-well plate comprising a plurality of wells.

22. The system of claim 21, further comprising at least one dispensing unit adapted to at least partially fill at least one of the plurality of wells with one or more reagents.

23. The system of claim 14, further comprising a cleaving reagent adapted to be in fluid communication with at least one of the first ends.

24. The system of claim 14, wherein the pressure control source is capable of providing a positive pressure and a negative pressure individually to each capillary tube.

34. A method comprising:

providing an array of capillary tubes, each capillary tube including a first end, a second end, an inner wall, and a linker bonded to the inner wall;

connecting a pressure control source to the first ends, wherein the pressure control source is capable of providing a pressure differential to each of the capillary tubes;

moving one or more of the second ends into communication with a first reagent in a first container;

drawing the first reagent through the one or more second ends into the one or more respective capillary tubes;

reacting the first reagent with the linker in the one or more respective capillary tubes to form a first activated sequence;

removing excess first reagent from the one or more respective capillary tubes;

moving the one or more second ends into communication with a second reagent in a second container;

drawing the second reagent through the one or more second ends and into the one or more respective capillary tubes; and

reacting the second reagent with the first activated sequence to form a first sequence.

35. The method of claim 34, wherein the first container comprises a first multi-well plate.

36. The method of claim 35, wherein the second container comprises a second multi-well plate that differs from the first multi-well plate.

37. The method of claim 34, wherein the linker comprises a protected oligonucleotide.

38. The method of claim 34, wherein the first reagent comprises a deprotectant.

39. The method of claim 34, wherein the second reagent comprises a protected nucleotide.

40. The method of claim 34, wherein the first sequence comprises an oligonucleotide.

41. The method of claim 34, wherein the first sequence comprises a ribonucleic acid sequence.

42. The method of claim 34, wherein the first sequence comprises a deoxyribonucleic acid sequence.

43. The method of claim 34, wherein the first sequence comprises a peptide sequence.

44. The method of claim 34, further comprising removing excess second reagent from the one or more capillary tubes.

45. The method of claim 44, further comprising moving the one or more second ends into communication with a third reagent in a third container;

drawing the third reagent through the one or more second ends and into the one or more respective capillary tubes; and

reacting the third reagent with the first sequence.

46. The method of claim 45, wherein the third reagent comprises a deprotectant and reacting the third reagent with the first sequence forms a second activated sequence.

47. The method of claim 46, further comprising removing excess third reagent from the one or more capillary tubes.

48. The method of claim 47, further comprising moving the one or more second ends into communication with a fourth reagent in a fourth container;

drawing the fourth reagent through the one or more second ends and into the one or more respective capillary tubes; and

reacting the fourth reagent with the second activated sequence.

49. The method of claim 48, wherein the fourth reagent comprises a protected nucleotide.

50. The method of claim 34, wherein the array of capillary tubes comprises a first subset and a second subset, and the method further comprises moving the second ends of the second subset into communication with a third reagent in a third container, wherein the second subset at least partially differs from the first subset;

drawing the third reagent through the second ends of the second subset and into the second subset of capillary tubes; and

reacting the third reagent with at least one of the linker or the first sequence to form an activated sequence in the second subset of the array of capillary tubes.

51. The method of claim 50, comprising drawing different reagents into different ones of the second subset of capillary tubes to form different sequences in the different ones of the second subset of capillary tubes.

52. The method of claim 34, wherein the second container comprises a multi-well plate, that comprises at least one first well that contains the second reagent and at least one well that does not contain the second reagent.

53. The method of claim 52, wherein a count of wells in the multi-well plate equals a count of capillary tubes in the array of capillary tubes.

54. The method of claim 34, further comprising cleaving the first sequence or a derivative thereof, from the inner wall.

55. The method of claim 34, wherein the pressure control source comprises a pressure control block.

56. A method comprising:

loading a first reagent into an array of capillaries, each capillary comprising an inner wall and a linker bonded to the inner wall;

reacting the first reagent with the linker to form an activated sequence;

loading a second reagent into the array of capillaries; and

reacting the first activated sequence to form a first sequence.