Ink jet method of spotting a probe and manufacturing a probe array

• US 6,476,215 B1
• Filed: 07/31/1998
• Issued: 11/05/2002
• Est. Priority Date: 08/01/1997
• Status: Expired due to Fees

• Current Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Original Assignee: Canon Kabushiki Kaisha (Canon Inc.)
• Inventors: Suzuki, Tomohiro, Okamoto, Tadashi, Yamamoto, Nobuko
• Primary Examiner(s): Marschel, Ardin H.
• Application Number:
  US09/126,851
• Time in Patent Office: 1,558 Days
• Field of Search: 435/6, 435/7.1, 436/501, 536/25.3, 530/333, 422/50, 422/68.1
• US Class Current: 536/25.3
• 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 2219/00274 Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
• CPC Class Codes: B01J 2219/00315 Microtiter plates
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00378 Piezoelectric or ink jet dispensers
• CPC Class Codes: B01J 2219/00432 Photolithographic masks
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel 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 2219/00612 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 2219/00626 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 2219/00677 Ex-situ synthesis followed by deposition on the substrate
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• 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: B01L 2200/143 : Quality control, feedback systems
• 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: C07B 2200/11 : Compounds covalently bound to a solid support
• CPC Class Codes: C07H 21/00 : Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12N 11/14 : Enzymes or microbial cells immobilised on or in an inorganic carrier
• CPC Class Codes: C12N 15/11 : DNA or RNA fragments; Modified forms thereof DNA or RNA not used in recombinant technology, C07H21/00; Non-coding nucleic acids having a biological activity
• CPC Class Codes: C12N 2310/351 : Conjugate
• CPC Class Codes: C12Q 1/00 : Measuring or testing processes involving enzymes, nucleic acids or microorganisms measuring or testing apparatus with condition measuring or sensing means, e.g. colony counters, C12M1/34; Compositions therefor; Processes of preparing such compositions
• CPC Class Codes: C12Q 1/6837 : using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: C40B 30/04 : by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• 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 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: G01N 2035/00158 : Elements containing microarrays, i.e. "biochip"
• CPC Class Codes: G01N 33/54366 : Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/68 : involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6845 : Methods of identifying protein-protein interactions in protein mixtures

Abstract

Provided is a method of spotting a probe densely and efficiently on a surface of a solid support. A liquid containing a probe is attached to a solid support as droplets to form spots containing the probe on the solid support by an ink jet method.

Claims

1. A method of spotting to a solid support a probe which can bind specifically to a target comprising the steps of:

providing a solid support having a first functional epoxy group on the surface thereof by applying to the solid support polyglycidyl methacrylate having an epoxy group;

providing a single-stranded nucleic acid probe having a second functional amino group;

supplying and attaching a liquid containing the single-stranded nucleic acid probe on a selected portion of the surface of the solid support; and

forming a spot of the probe on the surface of the solid support.

2. A method of spotting a probe which can bind specifically to a target to a solid support comprising the steps of:

supplying and attaching a liquid containing a single-stranded nucleic acid probe on a selected portion of the surface of said solid support; and

forming a spot of the probe on the surface of the solid support,

wherein the liquid contains urea at 5-10 wt %, glycerine at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 0.5-1 wt %, wherein each said weight % is based on the total weight of the liquid.

3. The method according to claim 2, wherein the acetylene alcohol has a structure represented by the following general formula (I):

wherein R₁, R₂, R₃ and R₄ are each an alkyl group, each m and n represents an integer, and m=0 and n=0 or 1≦

m+n≦

30, and when m+n=1, m or n is 0.

4. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

providing a solid support having a first functional epoxy group on the surface thereof;

providing a single-stranded nucleic acid probe having a second functional amino group which reacts with the first functional epoxy group upon contact;

ejecting droplets of a liquid containing the single-stranded nucleic acid probe to selected different spot sites on the surface of said solid support, wherein the epoxy group is introduced by applying polyglycidyl methacrylate having an epoxy group to the solid support.

5. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

supplying and attaching a liquid containing a single-stranded nucleic acid probe on a selected portion of the surface of the solid support; and

forming spots of the probe at predetermined sites on the surface of the solid support,

wherein the liquid contains urea at 5-10 wt %, glycerine at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 0.5-1 wt %, each said wt % based on the total weight of the liquid.

6. The method according to claim 5, wherein the acetylene alcohol has a structure represented by the following general formula (I):

wherein R₁, R₂, R₃ and R₄ are each an alkyl group, each m and n represents an integer, and m=0 and n=0 or 1≦

m+n≦

30, and when m+n=1, m or n is 0.

7. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

(a) providing a solid support having a surface partitioned by a matrix arranged in a pattern on the surface and having a plurality of wells, the surface of the solid support being exposed at a bottom of the well;

(b) supplying and attaching a liquid containing the probe in the respective wells by ejecting the liquid; and

(c) forming spots of the probe in the respective wells;

wherein the matrix pattern is formed by photolithography, wherein the photolithography comprises the steps of forming a photosensitive resin layer on the surface of the solid support, exposing the photosensitive resin layer to light in a pattern corresponding to the matrix pattern, and developing; and

wherein the photosensitive resin layer is a UV resist selected from the group consisting of a cyclized polyisoprene-aromatic bisazide resist, a phenol resin-aromatic azide compound resist and a novolak resin-diazonaphtoquinone resist.

8. A method of manufacturing a probe array having a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

(a) providing a solid support having a surface partitioned by a matrix arranged in a pattern on the surface and having a plurality of wells, the surface of the solid support being exposed at a bottom of the well;

(b) supplying and attaching a liquid containing the probe in the respective wells by ejecting the liquid; and

(c) forming spots of the probe in the respective wells;

wherein the matrix pattern is formed by photolithography, said photolithography comprises the steps of forming a photosensitive resin layer on the surface of the solid support, exposing the photosensitive resin layer to light in a pattern corresponding to the matrix pattern, and developing, wherein the photosensitive resin layer is a DEEP-UV resist, wherein the DEEP-UV resist is a radiolysable polymer resist or a dissolution suppressant resist.

9. The method of manufacturing according to claim 8, wherein the radiolysable polymer resist is at least one selected from the group consisting of polymethyl methacrylate, polymethylene sulfone, polyhexafluorobutyl methacrylate, polymethylisopropenyl ketone, and poly-1-trimethylsilyl propyne bromide.

10. The method of manufacturing according to claim 8, wherein the dissolution suppressant resist is o-nitrobenzyl cholate ester.

11. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

(a) providing a solid support having a surface partitioned by a matrix arranged in a pattern on the surface and having a plurality of wells, the surface of the solid support being exposed at a bottom of the well;

(b) supplying and attaching a liquid containing the probe in the respective wells by ejecting the liquid; and

(c) forming spots of the probe in the respective wells, wherein the matrix pattern is formed by photolithography, said photolithography comprises the steps of forming a photosensitive resin layer on the surface of the solid support, exposing the photosensitive resin layer to light in a pattern corresponding to the matrix pattern, and developing, wherein the photosensitive resin layer is a polyvinylphenol-3,3′

-diazidediphenyl sulfone or polyglycidyl polymethacrylate DEEP-UV resist.

12. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

(a) providing a solid support having a surface partitioned by a matrix arranged in a pattern on the surface and having a plurality of wells, the surface of the solid support being exposed at a bottom of the well;

(b) supplying and attaching a liquid containing the probe in the respective wells by ejecting the liquid; and

(c) forming spots of the probe in the respective wells, wherein the matrix pattern is formed by photolithography, said photolithography comprises the steps of forming a photosensitive resin layer on the surface of the solid support, exposing the photosensitive resin layer to light in a pattern corresponding to the matrix pattern, and developing, wherein water repellency of the matrix pattern is further improved by postbaking of the matrix pattern.

13. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, each spot containing a probe, comprising the steps of:

providing a solid support having a maleimido group derived from N-(6-maleimidocaproyloxy) succinimide on the surface thereof,

providing a nucleic acid probe having a thiol group which reacts with the maleimido group upon contact; and

ejecting droplets of a liquid of the nucleic acid probe having the thiol group onto the sites having the maleimido group, wherein the liquid contains urea at 5-10 wt %, glycerine at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 0.5-1 wt % based on the total weight of the liquid.

14. The method according to claim 13, wherein the acetylene alcohol has a structure represented by the following general formula (I):

wherein R₁, R₂, R₃ and R₄ independently represent an alkyl group, m and n independently represent an integer, and 0≦

m+n≦

30.

15. A method of manufacturing a probe array having a plurality of spots arranged independently at a plurality of sites on a surface of a solid support, the spots containing a probe which can bind specifically to a target substance, comprising the steps of:

(a) providing a probe having a thiol group;

(b) providing a solid support having maleimido groups on its entire surface, each maleimido group being an active site capable of reacting with a thiol group; and

(c) ejecting droplets of a liquid containing the probe of step (a) on the solid support resulting from the step (b) wherein the liquid contains urea at 5-10 wt %, glycerine at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 0.5-1 wt %, based on the total weight of the liquid.

16. The method according to claim 15, wherein the acetylene alcohol has a structure represented by the following general formula (I):

wherein R₁, R₂, R₃ and R₄ independently represent an alkyl group, m and n independently represent an integer, and 0≦

m+n≦

30.