Generation of combinatorial libraries

• US 5,449,754 A
• Filed: 04/22/1994
• Issued: 09/12/1995
• Est. Priority Date: 08/07/1991
• Status: Expired due to Term

• Current Assignee: H & N Instruments Incorporated
• Original Assignee: H & N Instruments Incorporated
• Inventors: Nishioka, Gary M.
• Primary Examiner(s): Niebling, John
• Assistant Examiner(s): DELACROIX MUIRHEI, CYBILLE
• Application Number:
  US08/231,494
• Time in Patent Office: 508 Days
• Field of Search: 436/518, 436/527, 530/334
• US Class Current: 506/18
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00436 Maskless processes
• CPC Class Codes: B01J 2219/00441 using lasers
• CPC Class Codes: B01J 2219/00475 Sheets
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00533 essentially rectangular
• 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 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00686 Automatic
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00711 Light-directed synthesis
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C07C 231/02 from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
• CPC Class Codes: C07C 237/12 : having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups peptides C07K
• CPC Class Codes: C07K 1/047 : Simultaneous synthesis of different peptide species; Peptide libraries
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries

Abstract

Ink-jet printing technology is applied to the creation of multi unit chemical compound libraries. Ink-jet type nozzles are used to inject multiple droplets onto the surface an appropriate support, such droplets consisting of solutions containing units of the chemical compound that will attach to the support surface. Droplets are then injected, by such nozzles, onto the support attached unit droplets that contain units that will attach to such support attached units. The second step is repeated to create multiple varying unit chemical compounds. Ink-jet printing technology allows the deposition of small droplets that do not overlap or splatter. The system is particularly useful in the creation of libraries of multiple peptide compounds where the units are amino acids.

Claims

1. A method of making chemical compounds of preselected varying sequenced chemical units attached to the surface of a solid support comprising:

a) injecting droplets of a first liquid solution containing one of said units that is disposed to attach to said surface from nozzles constructed in the manner of an ink-jet printing head positioned to deposit said droplets onto said surface in separate selective locations on said surface so that such units attach to the surface of said support; and

b) injecting droplets of a second liquid solution containing one of said units that is disposed to attach to the units of said first liquid coupling solution from said nozzles positioned to cause said second droplets to impinge onto the selective locations so that the units of said second liquid attach to the units of said first liquid coupling solution attached to said support.

2. The method of claim 1 including:

c) injecting droplets of a third liquid solution containing one of said units that is disposed to attach to the units of said first or second liquid solution from said nozzles position to cause said droplets to impinge on preselected droplets of said second liquid solution droplets so that the units of said third liquid attach to the units of said first or second liquid solutions.

3. The method of claim 2 wherein step c) is repeated with solutions containing varying preselected units disposed to attach to the units of one or more of the preceding injected solutions to create multiple unit chemical compounds.

4. The method of claim 1 wherein the support in step a) is sequentially moved relative to said nozzles and droplets of said first liquid coupling solution are injected onto said surface in multiple separate selective locations prior to step b) and wherein said support in step b) is sequentially moved relative to said nozzles so that droplets of said second liquid coupling solutions are injected to impinge onto the droplets of said of said first liquid solution in such multiple separate selective locations.

5. The method of claim 4 including:

d) sequentially moving the support, relative to said nozzles and injecting droplets of a third liquid solution containing one of said units that;

are disposed to attach to the units of said first or second liquid solution to impinge onto the units of said preselected droplets of said first or second liquid solutions in such multiple separate selective locations.

6. The method of claim 5 wherein step d) is repeated with solutions containing varying preselected units disposed to attach to the units of one or more of the preceding injected solutions to create multiple unit chemical compounds.

7. The method of claim 6 wherein, said chemical compounds are peptides and said unit are amino acids.

8. The method of claim 7 wherein said printing head contains a minimum of 20 nozzle orifices and each orifice is disposed to inject separate preselected amino acid units onto the support.