Nucleic acid array in situ fabrication methods and arrays produced using the same

• US 7,534,561 B2
• Filed: 04/02/2003
• Issued: 05/19/2009
• Est. Priority Date: 04/02/2003
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Leproust, Eric M., Perbost, Michel G. M., Wolber, Paul K., Sana, Theodore R.
• Primary Examiner(s): FORMAN, BETTY J
• Application Number:
  US10/407,080
• Publication Number:
  US 20040197781A1
• Time in Patent Office: 2,239 Days
• Field of Search: None
• 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 2219/0036 Nozzles
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• 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 2219/00596 Solid-phase 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 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 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 2219/00693 Means for quality control
• CPC Class Codes: B01J 2219/00695 Synthesis control routines, e.g. using computer programs
• CPC Class Codes: B01J 2219/00707 separated from the reactor apparatus
• 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: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C12Q 2545/101 : with an internal standard/control
• CPC Class Codes: C12Q 2565/513 : characterised by the pattern of the arrayed oligonucleotides
• 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

Abstract

Methods and devices for producing a nucleic acid arrays using in situ nucleic acid array synthesis protocols are provided. A feature of certain embodiments of the invention is that control probes are produced in collections of features, e.g., columns, of the arrays that have been selected according to a particular efficient control probe feature/column selection protocol. A feature of certain other embodiments of the invention is that an “all-bases-all-layers” probe set is produced in at least one of column of the arrays. Also provided are devices configured for use in the subject methods, as well as arrays produced using the subject methods and devices as well as methods for using such arrays.

Claims

1. A method of producing a nucleic acid microarray comprising two or more different nucleic acids immobilized at different locations on a surface, said method comprising:

(a) identifying a collection of feature locations of the nucleic acid microarray in which to produce control probes during synthesis of the nucleic acid microarray using an in situ microarray synthesis protocol, wherein said protocol utilizes a pulse-jet fluid deposition device having a total number of nozzle groups Y that traverse an entire array surface in one or more passes during said protocol, wherein each pass of said protocol is made up of a total number of swaths Z, and wherein said collection of feature locations samples less than all of said nozzle groups Y in any given swath but all of said nozzle groups Y in said total number of swaths Z of any given pass; and

(b) producing said nucleic acid microarray using said in situ microarray synthesis protocol, wherein said control probes are produced in said collection of feature locations.

2. The method according to claim 1, wherein said collection of feature locations is made up of a collection of columns.

3. The method according to claim 1, wherein said collection of feature locations make up a regular pattern.

4. The method according to claim 1, wherein said collection of feature locations make up a random pattern.

5. The method according to claim 1, wherein less than about 50% of the total number of groups Y is sampled in any given swath.

6. The method according to claim 1, wherein the same collection of feature locations is employed for printing control probes in each pass of said protocol.

7. A method for producing a nucleic acid microarray having a nucleic acid microarray layout, wherein said nucleic acid microarray comprises test probes and control probes, and wherein said method comprises:

(a) selecting a collection of columns of said nucleic acid microarray layout in which to produce said control probes during synthesis of said nucleic acid microarray using an in situ microarray synthesis protocol, wherein said nucleic acid microarray layout has a total number of columns X and said in situ microarray synthesis protocol utilizes a pulse-jet fluid deposition device having a total number of nozzle groups Y, and wherein said selecting comprises

identifying a column pattern period that either;

(i) shares no prime factors with Y and when multiplied by Y produces a product that does not exceed X;

or

(ii) shares a single prime factor of 2 with Y and when multiplied by Y produces a product that does not exceed X;

employing said column pattern period to select said collection of columns of said nucleic acid microarray layout in which to produce said control probes; and

(b) producing said nucleic acid microarray using said in situ microarray synthesis protocol, wherein said control probes are produced in said collection of columns.

8. The method according to claim 7, wherein said pattern period shares no prime factors with Y.

9. The method according to claim 7, wherein said method further comprises selecting an initial column in which to print control probes that results in control probes being printed in substantially the same number of replicate columns per nozzle group.

10. The method according to claim 7, wherein said pattern period shares a single prime factor of 2 with Y.

11. The method according to claim 10, wherein said employing comprises selecting a first collection of columns in which to print control probes and then a second collection of columns in which to print control probes, wherein said second collection of columns has an initial column that is adjacent to the initial column of said first collection of columns.

12. The method according to claim 7, wherein Y is an integer ranging from about 5 to about 50.

13. The method according to claim 7, wherein X is an integer ranging from about 50 to about 1024.

14. The method according to claim 7, wherein each nozzle group making up said total number Y is made up of 6 individual nozzles.