Method and apparatus for making nucleic acid arrays

• US 6,458,583 B1
• Filed: 09/09/1998
• Issued: 10/01/2002
• Est. Priority Date: 09/09/1998
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Bruhn, Laurakay, Schleifer, Arthur, Caren, Michael P., Schembri, Carol T.
• Primary Examiner(s): Sisson, Bradley L.
• Application Number:
  US09/150,504
• Time in Patent Office: 1,483 Days
• Field of Search: 435/6, 435/91.1, 435/287.2, 436/94, 436/518, 536/23.1, 536/25.3, 422/100
• US Class Current: 506/16
• 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 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00529 DNA chips
• CPC Class Codes: B01J 2219/0059 Sequential processes
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01L 2400/0442 thermal energy, e.g. vaporisation, bubble jet
• CPC Class Codes: B01L 3/0268 using pulse dispensing or spraying, eg. inkjet type, piezo actuated ejection of droplets from capillaries
• 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 60/14 for creating libraries
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

Abstract

Methods and devices for depositing a nucleic acid on a substrate surface are provided. In the subject methods, a thermal inkjet head loaded with nucleic acid fluid composition is positioned in opposing relationship to, e.g. over, a substrate surface. Actuation of the thermal inkjet results in the expulsion of volume of the nucleic acid composition onto the substrate surface. The subject methods and devices find use in a variety of applications, particularly in the preparation of nucleic acid arrays, and more particular arrays of oligonucleotides or polynucleotides, e.g. cDNAs.

Claims

1. A method for depositing a pre-made nucleic acid onto a substrate surface wherein said deposited nucleic acid is capable of hybridizing to its complement, said method comprising:

loading an aqueous fluid composition of said pre-made nucleic acid into thermal inkjet head comnprising an orifice and a firing chamber by contacting said orifice with said fluid composition in a manner sufficient for said fluid composition to flow through said orifice into said firing chamber;

positioning said thermal inkjet head filled with said fluid composition of said pre-made nucleic acid in opposing relation to said substrate surface, and

actuating said thermal inkjet head in a maniner sufficient to expel a volume of said composition onto said substrate surface,

whereby said pre-made nucleic acid is deposited on said substrate surface, wherein

said deposited nucleic acid is capable of hybridizing to its complement.

2. The method according to claim 1, wherein said method further comprises applying back pressure to said head during said contacting step.

3. A method for depositing a pre-made nucleic acid onto a substrate surface wherein said deposited nucleic acid is capable of hybridizing to its complement, said method comprising:

(a) loading an aqueous fluid composition orsaid pre-made nucleic acid into a thermal inkjet head comprising;

(i) an orifice;

(ii) a firing chamber; and

(iii) a heating element;

by contacting said orifice with said fluid composition in a manner sufficent for said fluid composition to flow through said orifice into said firing chamber;

(b) positioning said loaded thermal inkjet head in opposing relationship to a substrate surface; and

(c) raising the temperature of said heating element in a manner sufficient to expel a volume of said pre-made nucleic acid fluid through said orifice onto said substrate surface;

whereby said pre-made nucleic acid is deposited on a substrate surface, wherein said deposited nucleic acid is capable of hybridizing to its complement.

4. The method according to claim 3, wherein said nucleic acid is an oligonucleotide.

5. The method according to claim 3, wherein said nucleic acid is a polynucleotide.

6. The method according to claim 5, wherein said polynucleotide is a cDNA.

7. The method according to claim 3, wherein said method further comprises applying back pressure to said firing chamber during said contacting step.

8. The method according to claim 3, wherein said method comprises depositing nucleic acids in a plurality of discreet regions on said substrate surface.

9. A method for producing a eDNA array, said method comprising:

(a) loading an aqueous fluid pre-made cDNA composition into a Thermal inkjet head comprising;

(i) an orifice;

(ii) a firing chamber; and

(iii) a heating clement;

by contacting said orifice with said fluid composition in a manner sufficient lor said fluid composition to flow through said orifice into said firing chamber;

(b) positioning said loaded inkjet head in opposing relationship to a substrate surface;

(c) raising the temperature of said heating clement in a manner sufficient to expel a volume of DNA composition through said orifice onto said substrate surface; and

(d) repeating steps (a) to (c) at least one additional time,

whereby said array is produced, wherein cDNAs present on said array are capable of hybridizing to their complemnents.

10. The method according to claim 9, wherein said method further comprises applying back pressure to said firing chamber during said contacting step.