Methods for manufacturing arrays

• US 6,649,348 B2
• Filed: 06/29/2001
• Issued: 11/18/2003
• Est. Priority Date: 06/29/2001
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Bass, Jay K., McEntee, John F., Mobed-Miremadi, Maryam, Lazaruk, Tim J.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US09/896,572
• Publication Number:
  US 20030003222A1
• Time in Patent Office: 872 Days
• Field of Search: 536/25.3, 536/23.1, 536/24.3, 536/25.31, 422/68.1, 435/7.1, 435/174, 435/6, 435/283.1, 435/287.2, 435/288.5, 530/333, 530/334, 530/335
• US Class Current: 435/6.19
• 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 2219/00286 Reactor vessels with top and bottom openings
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00662 Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00675 In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00689 using computers
• CPC Class Codes: B01J 2219/00691 using robots
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 60/14 for creating libraries
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

Apparatus and methods are disclosed for synthesizing a plurality of compounds on the surface of supports. Biopolymer features are attached to the surfaces of the supports. The synthesis generally comprises a plurality of steps. In the present invention at least two of the steps are performed by placing a support having a functionalized surface into a chamber of a flow cell and subjecting the surface to a step of the synthesis and placing the support into a chamber of another flow cell and subjecting the surface to another step of the synthesis. An apparatus generally comprises a plurality of flow cells and one or more fluid dispensing stations are mounted on the platform and are in fluid communication with one or more of the plurality of flow cells. A station for monomer addition to the surface of the support is mounted on the platform. The apparatus further comprises a mechanism for moving a support to and from the station for monomer addition and a flow cell and from one flow cell to another flow cell.

Claims

1. A method for synthesizing an array of chemical compounds on the surface of a support, said method comprising:

(a) contacting a surface of said support with a fluid reagent for synthesizing said chemical compounds,

(b) mounting said support in a chamber of a flow cell and subjecting said surface to one step of said synthesis and

(c) mounting said support in a chamber of another flow cell and subjecting said surface to another step of said synthesis wherein (a)-(c) are repeated until said array of chemical compounds is synthesized on said surface and wherein each of said flow cells comprises a housing with a chamber and an inlet and an outlet for introduction and removal of fluids in the chamber in which the support is mounted wherein said support is selected from the group consisting of a strip, a plate or a flat glass.

2. A method according to claim 1 further comprising mounting said support after step (c) of said synthesis into a chamber of another flow cell and subjecting said surface to another step of said synthesis.

3. A method according to claim 1 wherein said synthesis comprises “

n”

number of steps including (b) and (C) and said method comprises independently mounting a support into a chamber of one of “

n”

number of flow cells and subjecting said surface to a different step of said synthesis in each of said flow cells.

4. A method according to claim 1 wherein reagents for step (b) of said synthesis are in fluid communication with said how cell of step (b) and reagents for step (c) of said synthesis are in fluid communication with said flow cell of step (C) and wherein the fluid communication of the flow cell of step (b) is separate from the fluid communication of the flow cell of step (c).

5. A method according to claim 1 wherein at least one of said steps of said synthesis comprises washing said surface.

6. A method according to claim 1 wherein said chemical compounds are polymers.

7. A method according to claim 6 wherein said polymers are biopolymers.

8. A method according to claim 1 wherein said flow cells comprise a holder for said support.

9. A method according to claim 1 wherein said flow cells comprise at least one inlet and an outlet.

10. A method according to claim 9 wherein a condition of fluid exiting said outlet is determined and based on said determination at least a portion of said fluid is directed to said inlet or to a waste container for said fluid.

11. A method according to claim 9 wherein fluid exiting said outlet is subjected to purification and a condition of said fluid is determined and based on said determination at least a portion of said fluid is directed to said inlet or to a waste container for said fluid.

12. A method according to claim 9 wherein a wash solution and a reagent for said synthesis are independently directed to said inlet.

13. A method for synthesizing an array of biopolymers on the surface of a support wherein said synthesis comprises a plurality of monomer additions, said method comprising:

(a) depositing droplets of monomer addition reagents on a surface of said support,

(b) placing said support into a chamber of a flow cell and subjecting said surface to a step of said synthesis that is subsequent to a monomer addition and

(c) placing said support into a chamber of another flow cell and subjecting said surface to another step of said synthesis that is subsequent to step (b) wherein said steps are repeated until said array of biopolymers is synthesized on said surface and wherein each of said flow cells comprises a housing with a chamber and an inlet and an outlet for introduction and removal of fluids in the chamber in which the support is placed and wherein said flow cell of (b) is dedicated to said step (b) and said flow cell of (c) is dedicated to step (c).

14. A method according to claim 13 wherein one of said steps (b) and (c) comprises a wash.

15. A method according to claim 13 wherein said biopolymers are polynucleotides.

16. A method according to claim 13 wherein step (b) comprises subjecting said surface to an oxidizing agent.

17. A method according to claim 13 wherein step (c) comprises subjecting said surface to an agent for removing a protecting group.

18. A method according to claim 13 wherein said flow cells comprise at least one inlet and an outlet and a holder for said support.

19. A method according to claim 18 wherein fluid exiting said flow cell is subjected to purification and a condition of said fluid is determined and based on said determination at least a portion of said fluid is directed to said flow cell or to a waste container for said fluid.

20. A method according to claim 18 wherein a wash solution and a reagent for said synthesis are independently directed to said inlet.

21. A method according to claim 13 wherein a condition of fluid exiting said flow cell is determined and based on said determination at least a portion of said fluid is directed to said flow cell or to a waste container for said fluid.

22. A method according to claim 21 wherein said fluid is an organic solvent.

23. A method according to claim 13 wherein said biopolymers are peptides.

24. A method according to claim 13 wherein said biopolymers are synthesized on said surface in multiple arrays and said support is subsequently diced into individual arrays of biopolymers on a support.

25. A method according to claim 13 wherein reagents for said first step of said synthesis are in separate fluid communication with said first flow cell and reagents for said second step of said synthesis are in separate fluid communication with said second flow cell.

26. A method according to claim 13 further comprising exposing the array to a sample and reading the array.

27. A method according to claim 26 comprising forwarding data comprising a result obtained from a reading of the array.

28. A method according to claim 27 wherein the data is transmitted to a remote location.

29. A method according to claim 26 comprising receiving data comprising a result of an interrogation obtained by the reading of the array.