Chemical synthesis apparatus employing a droplet generator

• US 6,277,334 B1
• Filed: 05/18/1999
• Issued: 08/21/2001
• Est. Priority Date: 09/21/1994
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: Ecker, David J., Wyatt, Jacqueline R., Hebert, Normand, Kiely, John S., Acevedo, Oscar, Davis, Peter W.
• Primary Examiner(s): TRAN, HIEN THI
• Application Number:
  US09/313,403
• Time in Patent Office: 826 Days
• Field of Search: 422/131, 422/100, 422/134, 422/102, 422/62, 422/104, 422/942, 422/946-948, 436/43, 436/54, 436/808, 436/178, 436/44, 436/47, 435/286.4
• US Class Current: 422/131
• 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 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00333 Closures attached to the reactor vessels
• CPC Class Codes: B01J 2219/00351 Means for dispensing and evacuation of reagents
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• 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 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00641 the porous medium being continuous, e.g. porous oxide substrates
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/0072 Organic compounds
• 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: B01L 3/0268 : using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• CPC Class Codes: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C12P 19/34 : Polynucleotides, e.g. nucleic acids, oligoribonucleotides
• 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 60/14 : for creating libraries

Abstract

Chemical reaction apparatus, materials and methods are provided for the automatable, efficient synthesis of chemical species and libraries. In accordance with preferred embodiments, chemical droplet generation and direction techniques are employed to prepare oligomers and libraries of chemical species. Reaction assemblies adapted for efficient synthetic employment and for improved collection are also disclosed.

Claims

1. A chemical reaction apparatus comprising

a. a porous reaction support having a plurality of reaction sites upon a first surface thereof and a second surface substantially parallel with the first surface, the support being capable of transporting fluid contacting the first surface to the second surface of the support in a direction substantially normal to the first surface;

b. a first droplet generator for jetting first reactant droplets upon the first surface;

c. a second droplet generator for jetting second reactant droplets upon the first surface; and

d. control means for causing the droplets from each of the droplet generators, to impact upon sets of said reaction sites; and

a plurality of collection wells adjacent to said second surface of the reaction support for collecting chemical species therefrom.

2. The apparatus of claim 1 wherein the porous support comprises controlled pore glass.

3. The apparatus of claim 1 wherein the porous support comprises a porated solid.

4. The apparatus of claim 1 wherein the porous support comprises fibers having a substantially common axis normal to the first surface.

5. The apparatus of claim 1 wherein the porous is an anisotropic membrane.

6. The apparatus of claim 1 further comprising additional droplet generators for jetting chemical reactant upon said first surface.

7. The apparatus of claim 1 wherein said control means is a digital computer.

8. The apparatus of claim 1 wherein at least one droplet generator is adapted for traversing over the first surface of the reaction support.

9. A chemical reaction apparatus comprising

a. a porous reaction support having a plurality of reaction sites upon a first surface thereof and a second surface substantially parallel with the first surface, the support being capable of transporting fluid contacting the first surface to the second surface of the support in a direction substantially normal to the first surface;

b. a droplet generator for jetting droplets of chemical reactant upon the first surface;

c. a plurality of reactant reservoirs in fluid communication with said droplet generator;

d. control means for causing chemical reactants from selected ones of said plurality of reactant reservoirs to be jetted by said droplet generator upon sets of said reaction sites; and

a plurality of collection wells adjacent to said second surface of the reaction support for collecting chemical species therefrom.

10. The apparatus of claim 9 further comprising valve means for directing chemical reactants from said reactant reservoirs to the droplet generator in response to control signals from said control means.

11. The apparatus of claim 9 wherein the porous support comprises controlled pore glass.

12. The apparatus of claim 9 wherein the porous support comprises a porated solid.

13. The apparatus of claim 9 wherein the porous support comprises fibers having a substantially common axis normal to the first surface.

14. The apparatus of claim 9 wherein the porous support is an anisotropic membrane.

15. The apparatus of claim 9 further comprising additional droplet generators for jetting chemical reactant upon said first surface.

16. The apparatus of claim 9 wherein said control means is a digital computer.

17. The apparatus of claim 9 wherein the droplet generator is adapted for traversing over the first surface of the reaction support.