Automated oligomer synthesis

• US 20050169816A1
• Filed: 12/15/2004
• Published: 08/04/2005
• Est. Priority Date: 12/15/2003
• Status: Abandoned Application

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Kirshner, Brian M.
• Application Number:
  US11/013,940
• Publication Number:
  US 20050169816A1
• Time in Patent Office: Days
• US Class Current: 422/130
• 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 2219/00279 Features relating to reactor vessels
• CPC Class Codes: B01J 2219/00283 Reactor vessels with top opening
• CPC Class Codes: B01J 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/00326 Movement by rotation
• CPC Class Codes: B01J 2219/00328 Movement by linear translation
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/00369 in multiple or parallel arrangements
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00418 using pressure
• CPC Class Codes: B01J 2219/00423 using filtration, e.g. through porous frits
• CPC Class Codes: B01J 2219/00454 by chemical cleavage from the solid support
• CPC Class Codes: B01J 2219/00549 2-dimensional
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00599 Solution-phase processes
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00698 Measurement and control of process parameters
• CPC Class Codes: B01J 2219/00704 : integrated with the reactor apparatus
• 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: C40B 60/06 : Integrated apparatus specially adapted for both creating libraries and identifying library members

Abstract

Systems, including apparatus and methods, for automated synthesis of oligomers.

Claims

1. A system for automated oligomer synthesis, comprising:

a synthesis station including a dispenser configured to dispense reagents for oligomer synthesis to reaction vessels, the synthesis station having an entrance and an exit;

a conveyor device including a plurality of receivers configured to hold the reaction vessels, the conveyor device being configured to drive the receivers through a closed loop that passes through the synthesis station; and

a controller configured to operate the synthesis station and the conveyor device so that oligomers are synthesized automatically as reaction vessels held by the receivers pass through the synthesis station from the entrance to the exit.

2. The system of claim 1, wherein the dispenser is configured to dispense the reagents to the reaction vessels with the reaction vessels in motion within the synthesis station.

3. The system of claim 1, the reaction vessels being columns having an inlet through which reagents are received and an outlet through which fluid is removed, wherein the conveyor device defines a plurality of discrete holders configured to receive the columns.

4. The system of claim 1, wherein the receivers and their reaction vessels follow a path through the synthesis station, and wherein the synthesis station includes a driver configured to move the dispenser at least substantially horizontally.

5. The system of claim 1, wherein the synthesis station includes a plurality of discrete sub-stations at which individual subunits or subunit multimers of the oligomers are added.

6. The system of claim 1, wherein the synthesis station includes a fluid removal mechanism configured to remove fluid from the reaction vessels, and wherein the fluid removal mechanism includes a plurality of removal mechanisms configured to remove fluid independently from subsets of one or more reaction vessels in the synthesis station.

7. The system of claim 6, wherein the synthesis station includes a driver coupled to the fluid removal mechanism, and wherein the driver is configured to move the fluid removal mechanism along a path parallel to a portion of the closed loop disposed within the synthesis station to selectively engage reaction vessels.

8. The system of claim 1, wherein the conveyor device is configured to have an adjustable speed along the closed loop.

9. The system of claim 1, further comprising a robotic transfer device configured to at least one of (1) add reaction vessels to and (2) remove reaction vessels from the conveyor device.

10. The system of claim 9, wherein the robotic transfer device can remove reaction vessels during their transit through the synthesis station.

11. The system of claim 1, wherein the dispenser is configured to add reagents to the reaction vessels without contacting the reaction vessels.

12. The system of claim 1, the reaction vessels including indicia that permit identification of each reaction vessel, the system further comprising a sensor in communication with the controller and configured to sense the indicia so that the controller can identify each reaction vessel.

13. The system of claim 1, wherein the synthesis station further includes reservoirs that supply the dispenser with reagents for oligomer synthesis, and wherein the reservoirs are configured to be replenished during operation of the dispenser.

14. A system for automated oligomer synthesis, comprising:

a synthesis station including a dispenser configured to dispense reagents for oligomer synthesis to columns, the synthesis station having an entrance and an exit;

a conveyor device including a plurality of re-usable holders configured to support the columns, the conveyor device being configured to drive the holders through a closed loop that passes through the synthesis station; and

a controller configured to receive data defining sequences of subunits of oligomers to be synthesized and to operate the synthesis station and the conveyor device so that the oligomers are synthesized automatically as reaction columns disposed in the holders pass through the synthesis station from the entrance to the exit.

15. A method of automated oligomer synthesis, comprising:

driving a plurality of receivers in a closed loop that passes through a synthesis station including a dispenser configured to dispense reagents for oligomer synthesis to reaction vessels held by the receivers; and

operating the synthesis station and the conveyor device so that the oligomers are synthesized automatically as the reaction vessels pass through the synthesis station.

16. The method of claim 15, further comprising a step of receiving data defining sequences of oligomer products to be synthesized, wherein the step of operating synthesizes oligomers corresponding to the oligomer products based on the data.

17. The method of claim 16, wherein the oligomers have structures that are chemically distinct from the oligomer products, the method further comprising a step of processing the oligomers to create the oligomer products after the step of operating.

18. The method of claim 15, further comprising steps of (1) placing the reaction vessels automatically in the receivers before the reaction vessels pass through the synthesis station, and (2) removing the reaction vessels automatically from the receivers after the reaction vessels pass through the synthesis station.

19. The method of claim 15, wherein the step of operating includes a step of moving a dispenser within the synthesis station in a direction generally parallel to driven movement of the reaction vessels in the synthesis station so that the dispenser can selectively dispense reagents for oligomer synthesis to reaction vessels.

20. The method of claim 15, wherein the step of operating includes a step of removing fluid selectively from a subset of the reaction vessels disposed in the synthesis station.

21. The method of claim 15, wherein the step of driving includes a step of stopping movement of the receivers at a plurality of predefined positions.