Method of performing array-based hybridization assays using thermal inkjet deposition of sample fluids

• US 6,221,653 B1
• Filed: 04/27/1999
• Issued: 04/24/2001
• Est. Priority Date: 04/27/1999
• Status: Expired due to Fees

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Caren, Michael P., Luebke, Kevin J.
• Primary Examiner(s): Horlick, Kenneth R.
• Assistant Examiner(s): Siew, Jeffrey
• Application Number:
  US09/300,589
• Time in Patent Office: 728 Days
• Field of Search: 435/6, 435/7.1, 435/7.2, 435/91.1, 435/91.2, 435/287.2, 435/286.4, 435/287.9, 435/287.3, 536/22.1, 536/23.1, 536/24.3, 536/24.31, 536/24.32, 536/24.33, 347/1, 347/19, 347/68, 347/85, 422/50, 422/100, 422/68.1, 422/109
• US Class Current: 435/287.2
• 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 2219/00527 Sheets
• 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 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00608 DNA chips
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• 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 2219/00707 separated from the reactor apparatus
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01J 2219/0074 Biological products
• 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 60/14 : for creating libraries

Abstract

Methods are provided for depositing a quantity of fluid onto the surface of an array. In the subject methods, a thermal inkjet head loaded with the fluid is positioned in opposing relationship to, e.g. over, the array surface. Actuation of the thermal inkjet results in the expulsion of a quantity of fluid onto the array surface. The subject methods find particular use in array-based binding assays in which an array of binding agents is employed for the detection of an analyte(s), particularly array-based hybridization assays.

Claims

1. A method for depositing a quantity of fluid on a substrate surface having a plurality of binding agents stably associated therewith, said method comprising:

loading said fluid into a thermal inkjet head comprising an orifice and a firing chamber by contacting said orifice with said fluid 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 in opposing relation to said substrate surface; and

actuating said thermal inkjet head in a manner sufficient to expel said quantity of fluid back through said orifice onto said substrate surface;

whereby said quantity of fluid is deposited on said substrate surface.

2. The method according to claim 1, wherein said fluid is heated prior to said actuation.

3. The method according to claim 1, wherein said fluid comprises a biomolecule.

4. The method according to claim 3, wherein said biomolecule is a nucleic acid.

5. The method according to claim 1, wherein said fluid substrate surface is the surface of an array.

6. A method for depositing a quantity of fluid on an array surface having a plurality of biomolecules stably associated therewith, said method comprising:

loading said fluid into a thermal inkjet head comprising an orifice and a firing chamber by contacting said orifice with said fluid 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 in opposing relation to said array surface; and

actuating said thermal inkjet head in a manner sufficient to expel said quantity of fluid back through said orifice onto said array surface;

whereby said quantity of fluid is deposited on said array surface.

7. The method according to claim 6, wherein said method further comprises applying back pressure to said head during said contacting step.

8. The method according to claim 6, wherein said biomolecule is a nucleic acid.

9. A method for introducing a fluid sample to a binding agent, said method comprising:

loading said fluid into a thermal inkjet head comprising an orifice and a firing chamber by contacting said orifice with said fluid 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 sample in opposing relation to a surface of an array, wherein said array comprises a plurality of binding agents stably associated with said surface;

actuating said thermal inkjet head in a manner sufficient to expel a quantity of said fluid sample back through said orifice onto said array surface; and

allowing interaction between said fluid sample and said binding agent.

10. The method according to claim 9, wherein said fluid comprises a biomolecule.

11. The method according to claim 10, wherein said biomolecule is a nucleic acid.

12. A method for detecting the presence of an analyte in a fluid sample, said method comprising:

loading said fluid into a thermal inkjet head comprising an orifice and a firing chamber by contacting said orifice with said fluid 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 sample in opposing relation to a surface of an array, wherein said array comprises a plurality of binding agents stably associated with said surface and at least one of said binding agents specifically binds to said analyte;

actuating said thermal inkjet head in a manner sufficient to expel a quantity of said fluid sample back through said orifice onto said array surface; and

detecting the presence of any binding complexes between said at least one binding agent and said analyte on said array surface;

whereby the presence of said analyte in said fluid sample is detected.

13. The method according to claim 12, wherein said analyte is a biomolecule.

14. The method according to claim 13, wherein said analyte is a nucleic acid.

15. The method according to claim 12, wherein said method further comprises heating said fluid sample prior to said actuating.

16. The method according to claim 12, wherein said method further comprises washing said array prior to said detecting step.

17. A method for performing an array-based hybridization assay, said method comprising:

(a) loading a fluid target nucleic acid sample into a thermal inkjet head comprising an orifice and a firing chamber by contacting said orifice with said fluid sample in a manner sufficient for said fluid sample to flow through said orifice into said firing chamber;

(b) positioning said thermal inkjet head filled with said fluid sample in opposing relation to a surface of an array, wherein said array comprises a plurality of probe nucleic acids stably associated with said surface;

(c) actuating said thermal inkjet head in a manner sufficient to expel a quantity of said fluid sample back through said orifice onto said array surface to produce a sample contacted array;

(d) maintaining said sample contacted array under hybridization conditions for a period of time sufficient for any complementary nucleic acids to hybridize to each other;

(e) washing the surface of said array; and

(f) detecting the presence of any double-stranded nucleic acids on said array surface.

18. The method according to claim 17, wherein said method further comprises heating said fluid sample prior to said actuating.

19. The method according to claim 17, wherein said fluid target nucleic acid sample does not exceed 200 pico liters in quantity.