Fluidic methods and devices for parallel chemical reactions

• US 20030118486A1
• Filed: 09/16/2002
• Published: 06/26/2003
• Est. Priority Date: 07/03/2000
• Status: Abandoned Application

• Current Assignee: Cogene Biotechn Ventures, L.P., Genesis Park LP, Life Technologies Corporation (Thermo Fisher Scientific Incorporated), Vanguard VII Accredited Affiliates Fund LP (Vanguard Fund VII), Vanguard VII-A LP (Vanguard Fund VII), Vanguard VII LP (Vanguard Fund VII), Vanguard VII Qualified Affiliates Fund LP (Vanguard Fund VII)
• Original Assignee: Xeotron Corp. (Thermo Fisher Scientific Incorporated)
• Inventors: Zhou, Xiaochuan, Gulari, Erdogan
• Application Number:
  US10/245,801
• Publication Number:
  US 20030118486A1
• Time in Patent Office: Days
• US Class Current: 422/102
• 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 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00279 Features relating to reactor vessels
• CPC Class Codes: B01J 2219/00306 Reactor vessels in a multiple arrangement
• CPC Class Codes: B01J 2219/00313 the reactor vessels being formed by arrays of wells in blocks
• CPC Class Codes: B01J 2219/00322 the individual reactor vessels being arranged serially in stacks
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/00731 Saccharides
• CPC Class Codes: B01J 2219/00734 Lipids
• CPC Class Codes: B01J 2219/00783 Laminate assemblies, i.e. the reactor comprising a stack of plates
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00831 : Glass
• CPC Class Codes: B01J 2219/00833 : Plastic
• CPC Class Codes: B01J 2219/0086 : Dimensions of the flow channels
• CPC Class Codes: B01J 2219/00936 : UV-radiations
• CPC Class Codes: B01J 2219/00943 : Visible light, e.g. sunlight
• CPC Class Codes: B01L 3/5025 : for parallel transport of multiple samples
• 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 40/12 : Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries

Abstract

Fluidic methods and devices for conducting parallel chemical reactions are disclosed. The methods are based on the use of in situ photogenerated reagents such as photogenerated acids, photogenerated bases, or any other suitable chemical compounds that produce active reagents upon light radiation. The present invention describes devices and methods for performing a large number of parallel chemical reactions without the use of a large number of valves, pumps, and other complicated fluidic components. The present invention provides microfluidic devices that contain a plurality of microscopic vessels for carrying out discrete chemical reactions. Other applications may include the preparation of microarrays of DNA and RNA oligonucleotides, peptides, oligosacchrides, phospholipids and other biopolymers on a substrate surface for assessing gene sequence information, screening for biological and chemical activities, identifying intermolecular complex formations, and determining structural features of molecular complexes.

Claims

1. A microfluidic reactor comprising a plurality of flow-through reaction cells for parallel chemical reactions, wherein the reactor comprises one or more inlet channels, one or more outlet channels and a plurality of reaction cells, wherein each reaction cell is in fluid communication with an inlet channel and an outlet channel, and further wherein the fluid connection narrows between the inlet channel and the reaction cell and between the reaction cell and the outlet channel effective to inhibit backflow of fluid from the reaction cell to the inlet channel and from the outlet channel to the reaction cell.

2. The microfluidic reactor of claim 1, wherein the reaction cells are connected to inlet and outlet channels by inlet and outlet conduits, wherein the width of the conduits is less than the width of the reaction cells.

3. The microfluidic reactor of claim 2, wherein the cross sectional shape of the reaction cells is round, square, rectangular, octagonal or polygonal.

4. The microfluidic reactor of claim 2, wherein the inlet conduits, the outlet conduits or the inlet and outlet conduits are substantially straight.

5. The microfluidic reactor of claim 2, wherein the inlet conduits, the outlet conduits or the inlet and outlet conduits are curved.

6. The microfluidic reactor of claim 2, wherein the inlet conduits, the outlet conduits or the inlet and outlet conduits are serpentine.

7. The microfluidic reactor of claim 2, wherein the inlet channel enters the inlet conduit at a right angle.

8. The microfluidic reactor of claim 2, wherein the inlet channel enters the inlet conduit at less than a right angle.

9. The microfluidic reactor of claim 1, comprising an inlet restriction gap disposed between the inlet channel and the reaction cell and an outlet restriction gap disposed between the reaction cell and the outlet channel.

10. The microfluidic reactor of claim 9, wherein the restriction gaps are formed between a ridge of the microfluidic template and the inner surface of the window plate.

11. The microfluidic reactor of claim 1, wherein the reactor comprises at least 10 reaction cells.

12. The microfluidic reactor of claim 1, wherein the reactor comprises at least 100 reaction cells.

13. The microfluidic reactor of claim 1, wherein the reactor comprises at least 1,000 reaction cells.

14. The microfluidic reactor of claim 1, wherein the reactor comprises at least 10,000 reaction cells.

15. The microfluidic reactor of claim 1, wherein the reactor comprises from 900 to 10,000 reaction cells.

16. The microfluidic reactor of claim 1, wherein the reaction cells are adapted for use of in situ generated chemical reagents which are generated in the reaction chamber.

17. The microfluidic reactor of claim 1, wherein the reactor comprises a silicon microfluidic template.

18. The microfluidic reactor of claim 1, wherein the reactor comprises a plastic microfluidic template.

19. The microfluidic reactor of claim 1, wherein the distance between adjacent reaction cells is from 10 to 5,000 microns.

20. The microfluidic reactor of claim 1, wherein the reactor further comprises one common inlet channel, branch inlet channels, branch outlet channels, and one common outlet channel.

21. The microfluidic reactor of claim 1, wherein the reactor further comprises immobilized molecules in the reaction chamber.

22. The microfluidic reactor of claim 21, wherein the immobilized molecules are biopolymers.

23. The microfluidic reactor of claim 21, wherein the immobilized molecules are immobilized with use of linker molecules.

24. The microfluidic reactor of claim 21, wherein the immobilized molecules are DNA, RNA, DNA oligonucleotides, RNA oligonucleotides, peptides, oligosaccharides, or phospholipids.

25. The microfluidic reactor of claim 21, wherein the immobilized molecules are oligonucleotides.

26. The microfluidic reactor of claim 1, wherein the reactor further comprises DNA, RNA, DNA oligonucleotides, RNA oligonucleotides, peptides, oligosaccharides, phospholipids, or combinations thereof adsorbed to the reaction chamber.

27. The microfluidic reactor of claim 1, wherein the reactor further comprises immobilized molecules in a double-layer configuration in the reaction chamber.

28. The microfluidic reactor of claim 1, wherein the reactor further comprises a three-dimensional attachment of immobilized molecules in the reaction chamber.

29. The microfluidic reactor of claim 1, further comprising porous films in the reaction chamber.

30. The microfluidic reactor of claim 29, wherein the porous films are porous glass films.

31. The microfluidic reactor of claim 1, wherein the reactor is in the form of an array device chip comprising fluid channels to distribute fluid to a plurality of reaction cells for parallel chemical reaction.

32. The microfluidic reactor of claim 2, wherein the width of the conduit is from 5 microns to 50 microns.

33. The microfluidic reactor of claim 1, wherein the reaction chambers contain beads.

34. The microfluidic reactor of claim 1, wherein the reaction chambers contain resin pads.

35. The microfluidic reactor of claim 1, wherein the reaction cells are adapted for use of in situ generated chemical reagents which are photo-generated in solution.

36. The microfluidic reactor of claim 1, wherein each reaction cell has a separate outlet channel which allows for individual collection of effluent from each reaction cell.

37. A chip comprising a plurality of microfluidic reactors according to claim 1.

38. The microfluidic reactor of claim 37, wherein the device chip has a configuration with one or more levels.

39. A microfluidic reactor comprising a plurality of flow-through reaction cells for parallel chemical reactions, wherein the reactor comprises one or more inlet channels, one or more outlet channels and a plurality of reaction cells, wherein each reaction cell is in fluid communication with an inlet channel and an outlet channel, and further wherein the reaction cells are connected to inlet and outlet channels by inlet and outlet conduits, wherein the width of the conduits is less than the width of the reaction cells, effective to inhibit backflow of fluid from the reaction cell to the inlet channel and from the outlet channel to the reaction cell.

40. The microfluidic reactor of claim 39, wherein the cross sectional shape of the reaction cells is round, square, rectangular, octagonal or polygonal.

41. The microfluidic reactor of claim 39, wherein the inlet conduits, the outlet conduits or the inlet and outlet conduits are substantially straight, curved or serpentine.

42. The microfluidic reactor of claim 39, wherein the inlet channel enters the inlet conduit at a right angle.

43. The microfluidic reactor of claim 39, wherein the inlet channel enters the inlet conduit at less than a right angle.