Combinatorial synthesis system

• US 6,508,988 B1
• Filed: 10/03/2000
• Issued: 01/21/2003
• Est. Priority Date: 10/03/2000
• Status: Expired due to Term

• Current Assignee: California Institute of Technology
• Original Assignee: California Institute of Technology
• Inventors: Van Dam, R. Michael, Unger, Marc A., Quake, Stephen R.
• Primary Examiner(s): Warden, Jill
• Assistant Examiner(s): Handy, Dwayne K.
• Application Number:
  US09/679,432
• Time in Patent Office: 840 Days
• Field of Search: 422/68.1, 422/99, 422/100, 422/103, 436/174, 436/179, 436/180, 435/283.1, 435/287.8, 435/287.9, 435/288.3, 435/288.5, 204/193, 204/600
• US Class Current: 422/130
• 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 2219/00355 peristaltic
• CPC Class Codes: B01J 2219/00398 in multiple arrangements
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00427 using masks
• 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 2219/0059 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 2219/00612 the surface being inorganic
• 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 2219/00637 by coating it with another layer
• 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 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00729 Peptide nucleic acids [PNA]
• 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 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• 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
• CPC Class Codes: Y10T 436/25 : including sample preparation
• CPC Class Codes: Y10T 436/2575 : Volumetric liquid transfer

Abstract

The present invention provides a chemical reaction apparatus for synthesizing an array of compounds and methods for using the same. In particular, the chemical reaction apparatus of the present invention comprises a solid support base, a first elastic member attached to the solid support base, and a first plurality of flow channels between the solid support base and the first elastic member. In addition, the solid support base comprises a functional group within at least a portion of the first plurality of flow channels for attaching compounds thereto. Optionally, the chemical reaction apparatus may further comprise a second plurality of flow channels which are in a different direction than the first plurality of flow channels. Moreover, the chemical reaction apparatus of the present invention can also include a second elastic member attached to the first elastic member. A plurality of pressure channels present in between the first and the second elastic members allows control of fluid flow within the first plurality of flow channels and/or the second plurality of flow channels.

Claims

1. A chemical reaction apparatus for synthesizing compounds, said reaction apparatus comprising a solid support base, a first elastic member interconnected to said solid support base, a first plurality of flow channels between said solid support base and said first elastic member, a second elastic member interconnected to said first elastic member, a plurality of pressure channels between said first elastic member and said second elastic member, and an elastomeric film that is disposed in between said flow channel and said pressure channel to regulate fluid flow through said flow channel, wherein said elastomeric film is deflectable into said flow channel in response to an actuation force applied to said pressure channel, said elastomeric film when positioned in said flow channel restricting fluid flow therethrough, wherein said solid support base comprises a functional group within at least a portion of said first plurality of flow channels for attaching compounds thereto.

2. The chemical reaction apparatus of claim 1, wherein said first elastic member is removably attached to said solid support base.

3. The chemical reaction apparatus of claim 1, wherein each of said first flow channels is substantially parallel to each other.

4. The chemical reaction apparatus of claim 1 further comprising a second plurality of flow channels between said first elastic member and said solid support base.

5. The chemical reaction apparatus of claim 4, wherein said second plurality of flow channels are substantially perpendicular to said first plurality of flow channels.

6. The chemical reaction apparatus of claim 1, wherein said plurality of pressure channels are substantially parallel to said first plurality of flow channels.

7. The chemical reaction apparatus of claim 6, wherein at least a portion of said plurality of pressure channels are aligned in between said first plurality of flow channels.

8. The chemical reaction apparatus of claim 7, wherein at least a portion of said plurality of pressure channels are aligned on top of said first plurality of flow channels.

9. The chemical reaction apparatus of claim 8, wherein said plurality of pressure channels aligned on top of said first plurality of flow channels comprise a varying channel widths within each pressure channels.

10. The chemical reaction apparatus of claim 1, wherein the cross-section of said channels are substantially arcuate.

11. The chemical reaction apparatus of claim 1, wherein said solid support base is selected from the group consisting of glass, polystyrene, polystyrene-divinylbenzene copolymer, silicone rubber, quartz, latex, polyurethane, gold and other derivatizable transition metals, silicon dioxide, silicon nitride, gallium arsenide, and the like.

12. The chemical reaction apparatus of claim 11, wherein said first elastic member is selected from the group consisting of polyacrylates, polyisoprene, polybutadiene, polychloroprene, polyisobutylene, poly(styrene-butadiene-styrene), polyurethanes, silicone rubbers, poly(bis(fluoroalkoxy)phosphazene), poly(carboranesiloxanes), poly(acrylonitrile-butadiene), poly(1-butene), poly(chlorotrifluoroethylenevinylidene fluoride) copolymers, poly(ethyl vinyl ether), poly(vinylidene fluoride), poly(vinylidene fluoride-hexafluoropropylene) copolymer, polyvinylchloride, polysulfone, polycarbonate, polymethacrylates, and fluoroelatomers.

13. The chemical reaction apparatus of claim 1, wherein said functional group provides covalent linkage between said solid support base and compounds.

14. The chemical reaction apparatus of claim 1, wherein said solid support further comprises a linker interconnected to said functional group, and wherein said linker further comprises a linking group for attaching compounds thereto.

15. The chemical reaction apparatus of claim 1, wherein the interior of said flow channels comprise chemical resistant coating.

16. A chemical reaction apparatus for synthesizing compounds, said chemical reaction apparatus comprising:

(a) a solid support base;

(b) a first elastic member attached to said solid support base;

(c) a first plurality of flow channels between said solid support base and said elastic member;

(d) a second elastic member attached to said first elastic member;

(e) a plurality of pressure channels between said first elastic member and said second elastic member; and

(f) an elastomeric segment disposed in between said flow channel and said pressure channel to regulate fluid flow through said flow channel,

wherein said solid support base comprises a functional group within at least a portion of said first plurality of flow channel for attaching compounds thereto.

17. The chemical reaction apparatus of claim 16, wherein said first plurality of flow channels are substantially parallel to each other.

18. The chemical reaction apparatus of claim 16, wherein said plurality of pressure channels are substantially parallel to said first plurality of flow channels.

19. The chemical reaction apparatus of claim 18, wherein at least a portion of said plurality of pressure channels are aligned in between said first plurality of flow channels.

20. The chemical reaction apparatus of claim 19, wherein at least a portion of said plurality of pressure channels are aligned on top of said first plurality of flow channels.

21. The chemical reaction apparatus of claim 20, wherein said plurality of pressure channels aligned on top of said first plurality of flow channels comprise a varying channel widths within each pressure channels.

22. The chemical reaction apparatus of claim 16, wherein the cross-section of said channels are curved.

23. The chemical reaction apparatus of claim 16, wherein said solid support base is selected from the group consisting of glass, polystyrene, polystyrene-divinylbenzene copolymer, silicone rubber, quartz, latex, polyurethane, gold and other derivatizable transition metals, silicon dioxide, silicon nitride, gallium arsenide, and the like.

24. The chemical reaction apparatus of claim 16, further comprising a second plurality of flow channels between said first elastic member and said solid support base.

25. The chemical reaction apparatus of claim 24, wherein said second plurality of flow channels are substantially perpendicular to said first plurality of flow channels.

26. The chemical reaction apparatus of claim 16, wherein each of said first elastic member and said second elastic member comprise a first component and a second component.

27. The chemical reaction apparatus of claim 26, wherein said first elastic member comprises excess of said first component and said second elastic member comprises excess said second component.

28. The chemical reaction apparatus of claim 16, wherein each of said first elastic member and said second elastic member is independently selected from the group consisting of polyacrylates, polyisoprene, polybutadiene, polychloroprene, polyisobutylene, poly(styrene-butadiene-styrene), polyurethanes, silicone rubbers, poly(bis(fluoroalkoxy)phosphazene), poly(carborane-siloxanes), poly(acrylonitrile-butadiene), poly(1-butene), poly(chlorotrifluoroethylene-vinylidene fluoride) copolymers, poly(ethyl vinyl ether), poly(vinylidene fluoride), poly(vinylidene fluoride-hexafluoropropylene) copolymer, polyvinylchloride, polysulfone, polycarbonate, polymethacrylates, and fluoroelatomers.

29. The chemical reaction apparatus of claim 16, wherein said functional group provides covalent linkage between said solid support base and said compounds.

30. The chemical reaction apparatus of claim 16, wherein said solid support further comprises a linker interconnected to said functional group, and wherein said linker further comprises a linking group for attaching said compounds thereto.

31. The chemical reaction apparatus of claim 16, further comprising an elastomeric segment that is disposed in between said flow channel and said pressure channel, wherein said elastomeric segment is deflectable into said flow channel in response to an actuation force applied to said pressure channel, said elastomeric segment when positioned in said flow channel restricting fluid flow therethrough.

32. A method for synthesizing a plurality of compounds comprising the steps of:

(a) pressurizing a chemical reaction apparatus, wherein said chemical apparatus comprises;

(i) a solid support base;

(ii) a first elastic member attached to said solid support base;

(iii) a first.plurality of flow channels and a second plurality of flow channels between the interface of said solid support base and said first elastic member, wherein said first plurality of flow channels intersects said second plurality of flow channels, and wherein at least a portion of said solid support base within the intersections of said first plurality of flow channels and said second plurality of flow channels comprises a functional group for attaching compounds thereto;

(iv) a second elastic member interconnected to said first elastic member;

(v) a first plurality of pressure channels between said first elastic member and said second elastic member, wherein said first plurality of pressure channels are aligned in between said first plurality of flow channels, and wherein said first plurality of pressure channels are capable of sealing at least a portion of said second plurality of flow channels when said first plurality of pressure channels are pressurized; and

(vi) a second plurality of pressure channels between said first elastic member and said second elastic member, wherein said second plurality of pressure channels are capable of sealing at least a portion of said first plurality of flow channels when at least a portion of said second plurality of pressure channels are pressurized,

wherein said first plurality of pressure channels are pressurized to seal at least a portion of said second plurality of flow channels;

(b) adding a set of compounds to said first plurality of flow channels, whereby at least a portion of said set of compounds are attached to said solid support base to produce a solid-support bound compounds;

(c) removing substantially all non-attached compounds from said first plurality of flow channels;

(d) pressurizing said second plurality of pressure channels to seal at least a portion of said first plurality of flow channels;

(e) adding another set of compounds to said second plurality of flow channels, whereby at least a portion of said set of compounds are attached to said solid-support bound compounds; and

(f) removing substantially all non-attached compounds from said second plurality of flow channels.

33. The method of claim 32, wherein said first plurality of flow channels and said second plurality of flow channels are substantially perpendicular.

34. The method of claim 32 further comprising repeating said steps (a) to (c), said steps (d) to (f), or combinations thereof.

35. The method of claim 32, wherein said set of compounds comprises at least two different compounds.

36. The method of claim 35, wherein only one compound from said set of compounds is introduced to each of said first plurality of flow channels.

37. The method of claim 32, wherein said another set of compounds comprises at least two different compounds.

38. The method of claim 37, wherein only one compound from said another set of compounds is introduced to each of said second plurality of flow channels.

39. The method of claim 32, wherein said set of compounds is introduced by injection of a set of solutions comprising said compounds, wherein each solution comprises only one compound from said set of compounds.