Chemical reaction apparatus for performing multiple reaction on a surface and collecting the product

• US 5,925,732 A
• Filed: 01/02/1997
• Issued: 07/20/1999
• 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): Achutamurthy, Ponnathapura
• Assistant Examiner(s): Ricigliano, Joseph W.
• Application Number:
  US08/778,876
• Time in Patent Office: 929 Days
• Field of Search: 422/131, 422/134, 422/100, 423/659, 435/6, 435/7.1, 436/518, 530/334, 536/25.3
• US Class Current: 506/40
• 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 method for chemical synthesis comprising:

a. providing a reaction support having a first and second surfaces, said first surface having a plurality of selected sites for chemical synthesis, said second surface located adjacent to a collection plate having a plurality of collection wells such that one or more of said selected sites for chemical synthesis are associated with a collection well throughout said synthesis;

b. providing one or more droplet generators actuated through a piezoelectric device, each connected to one or more chemical reservoirs for jetting chemical reagents;

c. delivering by way of said droplet generator or generators to said selected sites on the first surface of said reaction support a plurality of chemical reagents, the chemical nature, amount and sequence of which is predetermined and under the control of a control means to effect synthesis of at least one chemical species;

d. upon complete synthesis of said chemical species on said reaction support at selected sites transporting said chemical species through the reaction support to said collection wells associated with said selected sites of said reaction support such that at least one chemical species is collected in said collection well or wells.

2. The method of claim 1 further comprising challenging said chemical species in an assay.

3. The method of claim 1 wherein said delivery of chemical reagents is performed iteratively to effect the synthesis of an oligomer.

4. The method of claim 3 wherein said oligomer is an oligonucleotide.

5. The method of claim 3 wherein said oligomer is a polypeptide.

6. The method of claim 3 wherein said oligomer is a peptide nucleic acid.

7. The method of claim 1 wherein said jetting droplet generator is a continuous droplet generator.

8. The method of claim 1 wherein said jetting droplet generator is a droplet on demand generator.

9. The method of claim 1 wherein said reaction support has a porosity such that liquid is capable of passing from said first surface to said second surface.

10. The method of claim 9 wherein said reaction support is selected from the group consisting of permeable and semipermeable membranes, polymeric membranes, and porated membranes and glasses.

11. The method of claim 10 wherein said reaction support is control pore glass.