Synthesis of oligomers in arrays

• US 20060024713A1
• Filed: 06/30/2005
• Published: 02/02/2006
• Est. Priority Date: 06/30/2004
• Status: Abandoned Application

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Butler, John H.
• Application Number:
  US11/172,753
• Publication Number:
  US 20060024713A1
• 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 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00511 Walls of reactor vessels
• 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 2219/00689 using computers
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides

Abstract

Systems, including apparatus and methods, for synthesis of oligomers in arrays.

Claims

1. A device for synthesis of oligomers in an array, comprising:

a porous member including an array of islands and a spacer joined to the array of islands and separating the islands, the islands and the spacer having different surface energies, the porous member including opposing surfaces, each island defining a plurality of pores configured to receive a fluid and to permit passage of the fluid between the opposing surfaces; and

one or more reaction surfaces associated with each island of the array, the one or more reaction surfaces being configured to support synthesis of at least one oligomer using reagents received from the plurality of pores of the island.

2. The device of claim 1, wherein the porous member is formed at least substantially of silicon.

3. The device of claim 1, wherein the islands of the array are more hydrophilic than the spacer.

4. The device of claim 1, wherein the porous member includes interior walls that define the plurality of pores of each island, and wherein the interior walls overlap the one or more reaction surfaces associated with each island.

5. The device of claim 4, wherein the interior walls at least substantially include the one or more reaction surfaces associated with each island.

6. The device of claim 1, wherein at least one of the one or more reaction surfaces associated with each island is separate from the porous member.

7. The device of claim 6, which further comprises a channel layer disposed adjacent the porous member, the channel layer defining a plurality of channels disposed in one-to-one correspondence with the array of islands, each channel being in fluid communication with the island with which the channel is disposed in correspondence.

8. The device of claim 7, wherein the channel layer includes a plurality of channel walls, each channel wall defining one of the plurality of channels disposed in correspondence with one of the islands of the array, and wherein the channel wall includes at least one of the one or more reaction surfaces.

9. The device of claim 7, which further comprises sets of particles disposed in each of the plurality of channels, each set of particles disposed in one of the channels including at least one of the one or more reaction surfaces.

10. The device of claim 9, further comprising a permeable layer adjoining the channel layer and spaced from the porous member, the porous member and the permeable layer being configured to permit movement of fluid through the plurality of channels and to restrict movement of the sets of particles out of the channels.

11. The device of claim 1, wherein the one or more reaction surfaces include a moiety configured to react with an oligomer component and held in place on the reaction surface by at least one of a covalent bond and a noncovalent interaction.

12. The device of claim 11, wherein the at least one oligomer is at least one nucleic acid oligomer, and wherein the oligomer component is configured to form a portion of the at least one nucleic acid oligomer.

13. The device of claim 1, wherein each island includes interior walls that define the pores, and wherein the surface energy of the island is defined substantially by the interior walls.

14. The device of claim 1, wherein the plurality of pores have a random distribution within the porous member.

15. The device of claim 1, wherein the porous member is one piece.

16. A device for parallel synthesis of oligomers, comprising:

a porous member including an array of islands and a spacer joined to the array of islands and separating the islands, the array of islands being more hydrophilic than the spacer, each island defining a plurality of pores permitting reagents to pass through such island; and

a channel structure disposed adjacent the porous member and at least partially defining a plurality of reaction compartments disposed in one-to-one correspondence with the array of islands, each reaction compartment being configured to support synthesis of at least one oligomer using the reagents that pass through the corresponding island of the array.

17. The device of claim 16, wherein each reaction compartment includes a set of particles having a reaction surface configured to support synthesis of the at least one oligomer.

18. The device of claim 17, wherein each reaction compartment has a pair of generally opposing walls that are porous so that the reaction compartment permits passage of the reagents and restrict passages of the set of particles.

19. The device of claim 16, wherein the channel structure includes interior walls, each interior wall at least partially defining one of the reaction compartments and being configured to support synthesis of the at least one oligomer of the one reaction compartment.

20. The device of claim 16, further comprising a frame configured to support the porous member and channel structure, the frame defining a chamber and disposed in fluid communication with the array of islands and configured to create a pressure drop between the porous member and chamber to urge fluids through the reaction compartments.

21. A method of synthesizing oligomers in an array, comprising:

selecting a porous member including an array of porous islands joined to a spacer region that separates the hydrophilic porous islands, the array of porous islands and the spacer region having different surface energies; and

passing one or more oligomer components through each porous island of the array in fluid isolation so that the one or more oligomer components contact a reaction surface associated with such porous island and separated from other porous islands of the plurality.

22. A method of fabricating a synthesis support device, comprising:

selecting a porous member having an array of porous islands joined to a spacer region that separates the porous islands of the array, the porous islands and the spacer region having different surface energies; and

placing a plurality of reaction compartments adjacent the porous member and in one-to-one correspondence with the array of porous islands, each reaction compartment being disposed in fluid communication a corresponding porous island of the array.

23. The method of claim 22, wherein the step of selecting a porous member includes (1) a step of selecting a porous member having a first surface energy, and (2) a step of modifying the porous member selectively at positions corresponding to the array of porous islands so that the positions have a second surface energy.

24. The method of claim 23, wherein the step of modifying the porous member includes (1) a step of disposing a mask adjacent the porous member, and (2) a step of exposing the porous member to a condition so that the mask restricts exposure to the condition.

25. The method of claim 23, wherein the step of selecting a porous member having a first surface energy includes (1) a step of selecting a silicon member, (2) a step of forming pores in the silicon member, and (3) a step of exposing the silicon member to a condition that creates the first surface energy.

26. The method of claim 22, further comprising a step of retaining a set of particles in each reaction compartment.