Method and device for producing oligonucleotide arrays

• US 20030068621A1
• Filed: 10/04/2001
• Published: 04/10/2003
• Est. Priority Date: 10/04/2001
• Status: Abandoned Application

• Current Assignee: Jonathan Briggs
• Original Assignee: Jonathan Briggs
• Inventors: Briggs, Jonathan
• Application Number:
  US09/969,887
• Publication Number:
  US 20030068621A1
• Time in Patent Office: Days
• US Class Current: 435/6
• 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 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00364 Pipettes
• CPC Class Codes: B01J 2219/00367 capillary
• CPC Class Codes: B01J 2219/00376 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential 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 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00644 the porous medium being present in discrete locations, e.g. gel pads
• CPC Class Codes: B01J 2219/00648 by the use of solid beads
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 : using computers
• CPC Class Codes: B01J 2219/00691 : using robots
• CPC Class Codes: B01J 2219/00722 : Nucleotides
• CPC Class Codes: B82Y 30/00 : Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/14 : Libraries containing macromolecular compounds and not covered by groups C40B40/06 - C40B40/12
• CPC Class Codes: C40B 50/14 : Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 : for creating libraries

Abstract

The present invention relates to a method for producing a nucleic acid, polynucleotide, oligonucleotide, or polymer array and device therefore, wherein the method includes synthesizing a plurality of positionally addressable nucleic acids, polynucleotides, oligonucleotides, or polymers in a reaction array, and transferring these positionally addressable substances from the reaction array directly to a substrate to form the desired product array.

Claims

1. A method for producing nucleic acid, polymer, oligomer or oligonucleotide array comprising:

a) synthesizing a set of positionally addressable nucleic acids, polymers, oligomers or oligonucleotides in a reaction array; and

b) transferring said positionally addressable nucleic acids, polymers, oligomers or oligonucleotides from said reaction array directly to a product array to form said nucleic acid, polymer, oligomer or oligonucleotide array.

2. A method for producing an nucleic acid, polymer, oligomer or oligonucleotide array comprising:

a) synthesizing a set of positionally addressable nucleic acids, polymers, oligomers or oligonucleotides on solid reaction supports in a reaction array;

b) cleaving said positionally addressable nucleic acids, polymers, oligomers or oligonucleotides from said solid reaction supports; and

c) transferring said cleaved positionally addressable nucleic acids, polymers, oligomers or oligonucleotides from said reaction array directly to a product array to form said nucleic acid, polymer, oligomer or oligonucleotide array;

wherein said reaction array comprises a plate with a plurality reaction wells.

3. The method of claim 2 wherein said solid reaction support is comprised of a material selected from the group consisting of controlled pore glass, a polymer, and a polymer suspension.

4. The method of claim 2 wherein said plate of said reaction array is comprised of plastic.

5. The method of claim 2 wherein said plate of said reaction array is comprised of a fluoropolymer resin.

6. The method of claim 2 wherein said plate of said reaction array is between about 0.1 and about 10.0 mm in thickness.

7. The method of claim 2 wherein said reaction wells have a maximum diameter of between about 50 and about 500 microns.

8. The method of claim 2 wherein said reaction wells are spaced between about 100 and about 1000 microns apart from their respective centers.

9. The method of claim 2 wherein said plate of said reaction array has a reaction well density greater than 900 holes per cm².

10. The method of claim 2 wherein said plate of said reaction array has a reaction well density greater than 1000 holes per cm².

11. The method of claim 2 wherein said plate of said reaction array has a reaction well density greater than 1100 holes per cm².

12. The method of claim 2 wherein said nucleic acids, polymers, oligomers or oligonucleotides are synthesized by sequential introduction of reagents from an automated dispensing system.

13. The method of claim 12 wherein said automatic dispensing system is comprised of four syringes.

14. The method of claim 12 wherein said reagents are amidites.

15. The method of claim 12 wherein said automated dispensing system is comprised of an ink-jet emitter.

16. The method of claim 2 wherein said nucleic acids, polymers, oligomers or oligonucleotides are transferred from said reaction array directly to said product array via robotically controlled transfer pins.

17. The method of claim 2 wherein said nucleic acids, polymers, oligomers or oligonucleotides are transferred from said reaction array directly to said product array via direct contact between the product array and the reaction array.

18. The method of claim 17 wherein the said transfer is facilitated by the use of a pressurized inert gas.

19. A device for producing an nucleic acid, polymer, oligomer or oligonucleotide array comprising:

a) a reaction array for nucleic acid, polymer, oligomer or oligonucleotide synthesis comprising a plate with a plurality of reaction wells;

b) a reagent delivery module;

c) an nucleic acid, polymer, oligomer or oligonucleotide transfer module; and

d) a product array comprising a solid substrate.

20. The device of claim 19 wherein said plurality of reaction wells further comprises solid reaction supports.

21. The device of claim 20 wherein said solid reaction support is comprised of a material selected from the group consisting of controlled pore glass a polymer, and a polymer suspension.

22. The device of claim 19 wherein said plate of said reaction array is comprised of plastic.

23. The device of claim 19 wherein said plate of said reaction array is comprised of a fluoropolymer resin.

24. The device of claim 19 wherein said plate of said reaction array is between about 0.1 and about 10.0 mm in thickness.

25. The device of claim 19 wherein said reaction wells have a maximum diameter of between about 500 and about 500 microns.

26. The device of claim 19 wherein said reaction wells are spaced between about 100 and about 1000 microns apart from their respective centers.

27. The device of claim 19 wherein said plate of said reaction array has a reaction well density greater than 900 holes per cm².

28. The device of claim 19 wherein said plate of said reaction array has a reaction well density greater than 1000 holes per cm².

29. The device of claim 19 wherein said plate of said reaction array has a reaction well density greater than 1100 holes per cm².

30. The device of claim 19 further comprising an automated synthesis reagent dispensing system.

31. The device of claim 30 wherein said automated synthesis reagent dispensing system comprises four syringes.

32. The device of claim 30 wherein said automated synthesis reagent dispensing system comprises an ink-jet emitter.

33. The device of claim 19 wherein said nucleic acid, polymer, oligomer or oligonucleotide transfer module comprises an array of transfer pins.

34. The device of claim 33 further comprising a robotic control module for controlling said transfer pins.

35. The device of claim 19 wherein said nucleic acid, polymer, oligomer or oligonucleotide transfer module comprises a clamp attaching said product array to the bottom of said reaction array.

36. The device of claim 19 wherein said nucleic acid, polymer, oligomer or oligonucleotide transfer module comprises a bolt attaching said product array to the bottom of said reaction array.

37. The device of claim 19 wherein said nucleic acid, polymer, oligomer or oligonucleotide transfer module comprises a pressurized inert gas dispenser for facilitating transfer of the nucleic acids, polymers, oligomers and oligonucleotides from the reaction array to the product array.

38. A method for producing a polymer array comprising:

a) synthesizing a set of positionally addressable polymers in a reaction array; and

b) transferring said positionally addressable polymers from said reaction array directly to a product array to form said polymer array.

39. A method for producing an polynucleotide array comprising:

a) synthesizing a set of positionally addressable polynucleotides in a reaction array; and

b) transferring said positionally addressable polynucleotides from said reaction array directly to a product array to form said polynucleotide array.