Parallel sequential reactor

• US 5,288,468 A
• Filed: 10/30/1992
• Issued: 02/22/1994
• Est. Priority Date: 05/24/1991
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Church, George M., Kieffer-Higgins, Stephen G.
• Primary Examiner(s): NOT, DEFINED
• Assistant Examiner(s): Trembley, T. A.
• Application Number:
  US07/970,650
• Time in Patent Office: 480 Days
• Field of Search: 422/63, 422/65, 422/67, 422/81, 422/110, 422/111, 422/116, 435/287, 435/288, 435/289, 436/47, 436/49, 436/527, 436/530, 935/88, 525/54.1, 525/54.11, 530/333, 530/334
• US Class Current: 422/116
• 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 2219/00412 In multiple arrangements
• CPC Class Codes: B01J 2219/00504 Pins
• 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 2219/00689 using computers
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: G01N 1/31 Apparatus therefor
• CPC Class Codes: G01N 2035/0434 in the form of a syringe or pipette tip
• CPC Class Codes: G01N 2035/1076 plurality or independently movable heads
• CPC Class Codes: G01N 35/1065 Multiple transfer devices
• CPC Class Codes: G01N 35/1072 with provision for selective pipetting of individual channels

Abstract

A reactor for sequentially modifying a molecule attached to a solid phase support, including: a plurality of substrate carriers, each substrate carrier capable of carrying a solid phase support to which a molecule to be modified can be attached; a plurality of reagent chambers, each capable of comprising a reagent for effecting a modification of the molecule; and means for individually bringing each of a plurality of chosen substrate carriers into a reagent-contact mode and a reagent-non-contact mode with each of a plurality of reagent chambers. Each of a plurality of the substrate carriers is capable of sequential contact with the contents of a plurality of the reagent chambers. The sequential contact is capable of resulting in the sequential modification of molecules attached to solid phase supports on the plurality of substrate carriers.

Claims

1. A reactor for sequentially modifying a molecule attached to a solid phase support, comprising

a plurality of substrate carriers, each substrate carrier capable of carrying a solid phase support to which a molecule to be modified can be attached,

a plurality of reagent chambers, each capable of comprising a reagent for effecting a modification of said molecule, and

means for individually bringing each of a plurality of chosen substrate carriers into a reagent-contact mode and a reagent-non-contact mode with each of a plurality of reagent chambers comprising means for individually positioning each of a plurality of chosen substrate carriers in a reagent-contact mode and in a reagent-non-contact mode, and means for positioning each of a plurality of chosen reagent chambers relative to a chosen substrate carrier such that when said chosen substrate carrier is in said reagent-contact mode said chosen substrate carrier is in contact with the contents of a chosen reagent chamber and when said chosen substrate carrier is in said reagent-non-contact mode said chosen substrate carrier is not in contact with said contents of said chosen reagent chamber and wherein said individual positioning means is positioned such that a first substrate carrier and a second substrate carrier can be simultaneously placed in the reagent-contact mode with respect to a first chosen reagent chamber,

each of a plurality of said substrate carriers being capable of sequential contact with the contents of a plurality of said reagent chambers said sequential contact being capable of resulting in the sequential modification of molecules attached to said solid phase supports on said plurality of substrate carriers.

2. The reactor of claim 1, further comprising means for controlling the sequence in which said plurality of reagent chambers and said plurality of substrate carriers are brought into the reagent-contact mode.

3. The reactor of claim 1, further comprising sufficient reagent chambers to perform a sequence of reactions resulting in the synthesis of a nucleic acid molecule on one of said plurality of substrate carriers.

4. The reactor of claim 1, further comprising sufficient reagent chambers to perform a sequence of reactions resulting in the synthesis of a protein molecule on one of said plurality of substrate carriers.

5. The reactor of claim 1, further comprising means for supplying reagent to and removing reagent from one of said reagent chambers.

6. The reactor of claim 1, further comprising,

a computer to control the positioning of a plurality of said substrate carriers and the positioning of a plurality of said reagent chambers.

7. The reactor of claim 6, wherein said computer is programmed to effect a sequence of positionings of a first substrate carrier relative to said plurality of reagent chambers said sequence being capable of effecting a desired sequence of modifications of a first polymeric molecule on said first substrate carrier.

8. The reactor of claim 7, wherein said computer is programmed to effect a sequence of positionings of a second substrate carrier relative to said plurality of reagent chambers said sequence being capable of effecting a desired sequence of modifications of a second polymeric molecule in said second substrate carrier.

9. The reactor of claim 8, wherein said computer is programmed such that said first polymeric molecule comprises a different sequence of monomeric subunits than does said second polymeric molecule.

10. The reactor of claim 9, wherein said computer is programmed such that at least one reaction in the modification of said first polymeric molecule and one reaction in the modification of said second polymeric molecule are performed simultaneously.

11. The reactor of claim 10, wherein said computer is programmed such that said simultaneous reactions are performed in different reagent chambers.

12. The reactor of claim 10, wherein said computer is programmed such that said simultaneous reaction are performed in the same reagent chamber.

13. The reactor of claim 1, wherein said means for individually bringing each of a plurality of reagent chambers comprises a moveable carrier which carries a plurality of reagent chambers, said individual positioning means are positioned relative to said moveable carrier such that the action of said individual positioning means causes the transition from the reagent-non-contacting mode to the reagent-contacting mode of a chosen substrate carrier with respect to a chosen one of said reagent chambers and movement of said moveable carrier establishes which of said plurality of reagent chambers is said chosen reagent chamber with respect to a chosen substrate carrier.

14. The reactor of claim 13, wherein said individual positioning means is positioned such that a first substrate carrier and a second substrate carrier can be simultaneously placed in the reagent-contact mode with respect to a first chosen reagent chamber.

15. The reactor of claim 13, further comprising,

a computer to control the positioning of a plurality of said substrate carriers and the positioning of a plurality of said reagent chambers.

16. The reactor of claim 15, wherein said computer is programmed to effect a sequence of positionings of a first substrate carrier relative to said plurality of reagent chambers said sequence being capable of effecting a desired sequence of modifications of a first polymeric molecule on a first substrate carrier.

17. The reactor of claim 16, wherein said computer is programmed to effect a sequence of positionings of a second substrate carrier relative to said plurality of reagent chambers said sequence being capable of effecting a desired sequence of modifications of a second polymeric molecule in a second substrate carrier.

18. The reactor of claim 17, wherein said computer is programmed such that said first polymeric molecule comprises a different sequence of monomeric subunits than does said second polymeric molecule.

19. The reactor of claim 18, wherein said computer is programmed such that at least one reaction in the modification of said first polymeric molecule and one reaction in the modification of said second polymeric molecule are performed simultaneously.

20. The reactor of claim 19, wherein said computer is programmed such that said simultaneous reactions are performed in different reagent chambers.

21. The reactor of claim 19, wherein said computer is programmed such that said simultaneous reaction are performed in the same reagent chamber.