Synthesis of oligomers in arrays

• US 9,283,535 B2
• Filed: 11/06/2012
• Issued: 03/15/2016
• Est. Priority Date: 06/30/2004
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Butler, John H.
• Primary Examiner(s): HANEY, AMANDA MARIE
• Application Number:
  US13/669,604
• Publication Number:
  US 20130165349A1
• Time in Patent Office: 1,225 Days
• US Class Current: 1/1
• 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 method of placing reagents in reaction compartments of an array of reaction compartments comprising:

dispensing a first reagent to one or more porous islands in an array of porous islands, wherein each porous island is in fluid communication with at least one reaction compartment disposed adjacent to said porous island, and wherein each porous island is configured to restrict said first reagent from flowing laterally beyond each of said one or more porous islands, wherein said porous island defines an upper layer of said reaction compartment, and wherein a retainer layer is disposed adjacent to said reaction compartment and said retainer layer defines a lower layer of said reaction compartment, wherein the reaction compartment is configured as a channel between said porous island and said retainer layer, wherein the channel walls comprise a reaction surface, and wherein said porous island is separable from said reaction compartment;

dispensing a second reagent to said one or more porous islands; and

removing said first and second reagents from said reaction compartment.

2. The method according to claim 1, further comprising:

removing said first reagent from said reaction compartment before dispensing said second reagent.

3. The method according to claim 1, further comprising:

dispensing said second reagent to said one or more porous islands before removing said first reagent from said reaction compartment.

4. The method of claim 1, wherein said second reagent is dispensed to contact concurrently a plurality of said porous islands.

5. The method of claim 1, wherein each porous island is surrounded by a spacer,

wherein said each porous island and its surrounding spacer have different surface energies, and

whereby said first reagent in a given porous island is restricted from flowing laterally over said surrounding spacer by said difference in surface energy.

6. The method of claim 1, wherein said first reagent is received in said each porous island,

whereby said first reagent in a given porous island is restricted from flowing laterally between adjacent porous islands by capillary action between said first reagent and said porous island.

7. The method of claim 1, wherein said removing step is achieved by exerting a positive pressure to said reaction compartment to push fluid through said reaction compartment, thereby removing said first and second reagents from said reaction compartment.

8. The method of claim 1, wherein said removing step is achieved by exerting a negative pressure to said reaction compartment to pull fluid from said reaction compartment, thereby removing said first and second reagents from said reaction compartment.

9. The method of claim 1, wherein said retainer layer is a permeable retainer layer.

10. The method of claim 1, wherein said retainer layer is separable from said reaction compartment.

11. The method of claim 1, wherein said reaction surface comprises a reactive moiety covalently coupled to the channel wall.

12. A method of placing reagents in reaction compartments of an array of reaction compartments comprising:

dispensing a first reagent to one or more porous islands in an array of porous islands, wherein each porous island is in fluid communication with at least one reaction compartment disposed adjacent to said porous island, and wherein each porous island is configured to restrict said first reagent from flowing laterally beyond each of said one or more porous islands, wherein said porous island defines an upper layer of said reaction compartment, and wherein a retainer layer is disposed adjacent to said reaction compartment and said retainer layer defines a lower layer of said reaction compartment, wherein the reaction compartment is configured as a channel between said porous island and said retainer layer, wherein the channel walls comprise a reaction surface, and wherein said retainer layer is separable from said reaction compartment;

dispensing a second reagent to said one or more porous islands; and

removing said first and second reagents from said reaction compartment.

13. The method according to claim 12, further comprising:

removing said first reagent from said reaction compartment before dispensing said second reagent.

14. The method according to claim 12, further comprising:

dispensing said second reagent to said one or more porous islands before removing said first reagent from said reaction compartment.

15. The method of claim 12, wherein said second reagent is dispensed to contact concurrently a plurality of said porous islands.

16. The method of claim 12, wherein each porous island is surrounded by a spacer, wherein said each porous island and its surrounding spacer have different surface energies, and whereby said first reagent in a given porous island is restricted from flowing laterally over said surrounding spacer by said difference in surface energy.

17. The method of claim 12, wherein said first reagent is received in said each porous island, whereby said first reagent in a given porous island is restricted from flowing laterally between adjacent porous islands by capillary action between said first reagent and said porous island.

18. The method of claim 12, wherein said removing step is achieved by exerting a positive pressure to said reaction compartment to push fluid through said reaction compartment, thereby removing said first and second reagents from said reaction compartment.

19. The method of claim 12, wherein said removing step is achieved by exerting a negative pressure to said reaction compartment to pull fluid from said reaction compartment, thereby removing said first and second reagents from said reaction compartment.

20. The method of claim 12, wherein said retainer layer is a permeable retainer layer.

21. The method of claim 20, wherein said porous island is separable from said reaction compartment.