Small volume chambers

• US 6,790,620 B2
• Filed: 12/24/2001
• Issued: 09/14/2004
• Est. Priority Date: 12/24/2001
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Tolosko, Brent T., Bass, Jay K., McEntee, John F., Mobed-Miremadi, Maryam, Lazaruk, Tim J.
• Primary Examiner(s): Forman, BJ
• Application Number:
  US10/035,787
• Publication Number:
  US 20030118716A1
• Time in Patent Office: 995 Days
• Field of Search: 435/4, 435/6, 435/7.1, 435/174, 435/283.1, 435/288.5, 422/50, 422/129, 422/134, 536/25.3, 536/23.1
• US Class Current: 435/6.11
• 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 2219/00333 Closures attached to the reactor vessels
• CPC Class Codes: B01J 2219/00353 Pumps
• CPC Class Codes: B01J 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00387 Applications using probes
• CPC Class Codes: B01J 2219/00389 Feeding through valves
• CPC Class Codes: B01J 2219/00414 using suction
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00495 Means for heating or cooling the reaction vessels
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00518 in the shape of tapes
• CPC Class Codes: B01J 2219/0052 in the shape of elongated tubes
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00536 in the shape of disks
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00657 One-dimensional arrays
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00662 : Two-dimensional arrays within two-dimensional arrays
• CPC Class Codes: B01J 2219/00664 : Three-dimensional arrays
• CPC Class Codes: B01J 2219/00675 : In-situ synthesis on the substrate
• CPC Class Codes: B01J 2219/00677 : Ex-situ synthesis followed by deposition 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: B01J 2219/00725 : Peptides
• CPC Class Codes: B01J 2219/00729 : Peptide nucleic acids [PNA]
• CPC Class Codes: B01J 2219/00731 : Saccharides
• 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 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 40/12 : Libraries containing saccharides or polysaccharides, 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

Abstract

Apparatus and methods are disclosed for forming a reaction chamber having relatively small volumes. An apparatus comprises two elements and a mechanism for introducing a gas to form a movable aerodynamic seal between the elements. In this manner a chamber having a controllable interior environment is formed. One of the elements may have at least a portion of a device for dispensing reagents sealingly affixed therein. The other element may be adapted for introduction of a support into the interior of the chamber formed by the top and the bottom element. The apparatus may be used in methods for synthesizing biopolymers on a support.

Claims

1. A method for synthesizing an array of biopolymers on a support, said method comprising:

(a) performing a step in the synthesis of an array of biopolymers on a support in a reaction chamber formed between two elements disposed relative to one another in a sealed, movable relationship, wherein said support and one of said elements is moved relative to the other of said elements during said performing,

(b) removing said support from said reaction chamber, and

(c) optionally repeating steps (a) through (b) until said array of biopolymers is formed.

2. A method according to claim 1 wherein said reaction chamber is formed by disposing two elements relative to one another to form a gap therebetween;

and introducing a gas into said gap to form a sealed reaction chamber comprising said two elements.

3. A method for synthesizing an array of biopolymers on a support, said method comprising:

(a) introducing a support into a reaction chamber formed between a separate top element and a separate bottom element disposed relative to one another to form a gap therebetween, said a top element having sealingly affixed therein at least a portion of a device for dispensing reagents, said bottom element being adapted for introduction of a support therethrough, wherein a gas is introduced into said gap, a pressure of said gas being sufficient to form an aerodynamic seal between said top element and said bottom element thereby forming said chamber, and wherein said top element or said bottom element is movable with respect to the other during said aerodynamic seal

(b) bringing said support and a dispensing system for dispensing reagents for the synthesis of said biopolymers into a dispensing position relative to discrete sites on said surface of said support by moving said support and said bottom element relative to said top element,

(c) activating said support if said support is not already activated and dispensing said reagents to said discrete sites to perform a step of said synthesis,

(d) removing said support and/or said dispensing system from said relative dispensing position, and

(e) optionally repeating steps (a) through (d) until said array of biopolymers is formed.

4. A method according to claim 3 wherein said gas is introduced adjacent a perimeter of said top element and a perimeter of said bottom element.

5. A method according to claim 3 wherein said gas is introduced through openings in side walls of said bottom element.

6. A method according to claim 3 wherein said gas is introduced at a pressure of about 20 to about 50 psi.

7. A method according to claim 3 comprising introducing a second gas into an interior of said chamber after step (b).

8. A method according to claim 7 wherein a flow of said second gas through the interior of said chamber is substantially uniform.

9. A method according to claim 7 wherein a flow of said second gas within the interior of said chamber is dispersed.

10. A method according to claim 7 wherein said second gas is selected from the group consisting of nitrogen, argon, neon and helium.

11. A method according to claim 3 wherein said reagents are monomer addition reagents.

12. A method according to claim 3 wherein an array of said biopolymers is synthesized on said support.

13. A method according to claim 3 wherein said biopolymers are polynucleotides or polypeptides.

14. A method according to claim 3 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.

15. A method according to claim 3 for synthesizing an array of biopolymers on a surface of a support, said method comprising adding one or more polymer subunits at each of multiple feature locations on said support during each of multiple rounds of subunit additions wherein each round of subunit additions comprises:

(a) introducing said support into said reaction chamber,

(b) bringing said support and a dispensing system for dispensing said polymer subunits for the synthesis of said biopolymers into a dispensing position relative to said discrete sites on said surface,

(c) dispensing said polymer subunits to said discrete sites, and

(d) removing said support and/or said dispensing system from said dispensing position.

16. A method according to claim 3 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.

17. A method according to claim 3 further comprising exposing the array to a sample and reading the array.

18. A method according to claim 17 comprising forwarding data representing a result obtained from a reading of the array.

19. A method according to claim 18 wherein the data is transmitted to a remote location.

20. A method according to claim 17 comprising receiving data representing a result of an interrogation obtained by the reading of the array.

21. A method according to claim 3 wherein said top element is stationary and said bottom element is moved relative to said top element to bring said support and said dispensing system for dispensing reagents for the synthesis of said biopolymers into a dispensing position relative to discrete sites on said surface of said support.