Ink jet method of spotting probe, probe array and indentification methods

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.

What is claimed is:  
     
         1 . A method of spotting a probe which can bind specifically to a target to a solid support comprising the steps of: 
 supplying a liquid containing a probe on a surface of a solid support by an ink jet method and attaching the liquid, and    forming a spot of probe on the surface of the solid support.    
     
     
         2 . The method of spotting according to  claim 1  wherein the probe is a single-stranded nucleic acid probe.  
     
     
         3 . The method of spotting according to  claim 2  wherein the single-stranded nucleic acid probe includes a single-stranded DNA probe.  
     
     
         4 . The method of spotting according to  claim 2  wherein the single-stranded nucleic acid probe includes an RNA probe.  
     
     
         5 . The method of spotting according to  claim 2  wherein the single-stranded nucleic acid probe includes a single-stranded PNA probe.  
     
     
         6 . The method of spotting according to  claim 2  wherein the surface of the solid support has a first functional group and the single-stranded nucleic acid probe has a second functional group, and the first and second functional groups react each other by contact.  
     
     
         7 . The method of spotting according to  claim 6  wherein the first functional group on the surface of the solid support is a maleimido group and the second functional group of the single-stranded nucleic acid probe is a thiol (SH) group.  
     
     
         8 . The method of spotting according to  claim 7  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with N-(6-maleimidocaproyloxy) succinimide.  
     
     
         9 . The method of spotting according to  claim 7  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with succinimidyl-4-(maleimido phenyl) butyrate.  
     
     
         10 . The method of spotting according to  claim 7  wherein the maleimido group is reacted with the thiol group for at least 30 minutes.  
     
     
         11 . The method of spotting according to  claim 10  wherein the single-stranded nucleic acid comprises a single-stranded PNA probe, at the terminus of which the thiol group exists, and the maleimido group is reacted with the thiol group for at least 2 hours.  
     
     
         12 . The method of spotting according to  claim 11  wherein the thiol group at the terminus of the single-stranded PNA probe is introduced by binding cysteine group to the N-terminus of the single-stranded PNA probe.  
     
     
         13 . The method of spotting according to  claim 6  wherein the first functional group on the surface of the solid support is an epoxy group and the second functional group of the single-stranded nucleic acid probe is an amino group.  
     
     
         14 . The method of spotting according to  claim 13  wherein the solid support is a glass plate and the epoxy group is introduced by applying a silane compound having an epoxy group in the molecule thereof on the surface of the glass plate and reacting the compound with the glass plate.  
     
     
         15 . The method of spotting according to  claim 13  wherein the epoxy group is introduced by applying polyglycidyl methacrylate having an epoxy group on the solid support.  
     
     
         16 . The method of spotting according to  claim 1  wherein the liquid contains urea at 5-10 wt %, glycerin at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 1 wt % of the liquid.  
     
     
         17 . The method of spotting according to  claim 16  wherein the acetylene alcohol has a structure represented by the following general formula (I):  
       
         
           
           
               
               
           
         
       
       (wherein, R 1 , R 2 , R 3 , and R 4  represent an alkyl group, each m and n represent an integral, and m=0 and n=0 or 1≦m+n≦30, and when m+n=1, m or n is 0.)  
     
     
         18 . The method of spotting according to  claim 2  wherein a concentration of the single-stranded nucleic acid probe in the liquid is 0.05-500 μM.  
     
     
         19 . The method of spotting according to  claim 18  wherein a concentration of the single-stranded nucleic acid probe in the liquid is 2-50 μM.  
     
     
         20 . The method of spotting according to  claim 2  wherein a length of the single-stranded nucleic acid probe is 2-5,000 bases.  
     
     
         21 . The method of spotting according to  claim 20  wherein a length of the single-stranded nucleic acid probe is 2-60 bases.  
     
     
         22 . The method of spotting according to  claim 1  wherein the ink jet method is a bubble jet method.  
     
     
         23 . The method of spotting according to  claim 1  wherein the probe is an oligopeptide or a polypeptide with a specific amino acid sequence.  
     
     
         24 . The method of spotting according to  claim 1  wherein the probe is a protein.  
     
     
         25 . The method of spotting according to  claim 24  wherein the protein is an antibody.  
     
     
         26 . The method of spotting according to  claim 24  wherein the protein is an enzyme.  
     
     
         27 . The method of spotting according to  claim 1  wherein the probe is an enzyme.  
     
     
         28 . The method of spotting according to  claim 1  wherein the liquid is supplied so as to form independent spots in a density of 10,000 spots per square inch on the solid support.  
     
     
         29 . The method of spotting according to  claim 1  wherein the solid support has a flat surface and homogenous surface properties.  
     
     
         30 . The method of spotting according to  claim 29  wherein the liquid is supplied on the surface of the solid support so as to obtain a distance between the adjacent spots not smaller than the maximum width of the spot.  
     
     
         31 . The method of spotting according to  claim 30  wherein blocking is performed on the surface of the solid support to prevent a sample from attaching to the surface other than spots of the surface of the solid support.  
     
     
         32 . The method of spotting according to  claim 31  wherein the blocking is achieved by using bovine serum albumin.  
     
     
         33 . The method of spotting according to  claim 1  wherein the solid support is partitioned by a matrix arranged in a pattern on the surface, a plurality of wells whose bottom is the surface of the solid support exposed in the pattern are provided, and the liquid is supplied to the respective wells.  
     
     
         34 . The method of spotting according to  claim 33  wherein the solid support is optically transparent and the matrix is opaque.  
     
     
         35 . The method of spotting according to  claim 33  wherein the matrix comprises a resin.  
     
     
         36 . The method of spotting according to  claim 33  wherein the surface of the matrix is hydrophobic.  
     
     
         37 . The method of spotting according to  claim 33  wherein the bottom of the wells is hydrophilic.  
     
     
         38 . The method of spotting according to  claim 33  wherein the matrix has a thickness of 1-20 μm.  
     
     
         39 . The method of spotting according to  claim 33  wherein the wells have a maximum width of 200 μm.  
     
     
         40 . The method of spotting according to  claim 33  wherein the matrix has a width 1/2-2 times the maximum width of the wells.  
     
     
         41 . A probe array comprising a plurality of spots of a probe, the spots being provided independently at a plurality of sites of a surface of a solid support in a density of 10,000 spots per square inch or higher.  
     
     
         42 . The probe array according to  claim 41  wherein the solid support has a flat surface and homogenous surface properties.  
     
     
         43 . The probe array according to  claim 42  wherein the probe is a single-stranded nucleic acid probe.  
     
     
         44 . The probe array according to  claim 43  wherein the single-stranded nucleic acid probe includes a single-stranded DNA probe.  
     
     
         45 . The probe array according to  claim 43  wherein the single-stranded nucleic acid includes a single-stranded RNA probe.  
     
     
         46 . The probe array according to  claim 43  wherein the single-stranded nucleic acid includes a single-strand ed PNA probe.  
     
     
         47 . The probe array according to  claim 43  wherein the single-stranded nucleic acid is covalently bound to the surface of the solid support by a reaction between a first functional group on the surface of the solid surface and a second functional group of the single-stranded nucleic acid probe.  
     
     
         48 . The probe array according to  claim 47  wherein the first functional group on the surface of the solid support is a maleimido group and the second functional group of the single-stranded nucleic acid probe is a thiol (SH) group.  
     
     
         49 . The probe array according to  claim 48  wherein the single-stranded nucleic acid probe is a single-stranded PNA probe and contains a cysteine residue on an N-terminus side.  
     
     
         50 . The probe array according to  claim 47  wherein the first functional group on the surface of the solid support is an epoxy group and the second functional group of the single-stranded nucleic acid probe is an amino group.  
     
     
         51 . The probe array according to  claim 42  wherein the spots are formed by supplying a liquid containing the probe on the solid support.  
     
     
         52 . The probe array according to  claim 42  wherein the probe is an oligopeptide or a polypeptide with a specific amino acid sequence.  
     
     
         53 . The probe array according to  claim 42  wherein the probe is a protein.  
     
     
         54 . The probe array according to  claim 53  wherein the protein is an antibody.  
     
     
         55 . The probe array according to  claim 53  wherein the protein is an enzyme.  
     
     
         56 . The probe array according to  claim 42  wherein the probe is an antigen.  
     
     
         57 . The probe array according to  claim 42  wherein a distance between the adjacent spots is not smaller than a maximum width of the spot.  
     
     
         58 . The probe array according to  claim 41  wherein the solid support is partitioned by a matrix arranged in a pattern on the surface, a plurality of wells whose bottom is the surface of the solid support exposed in a pattern are provided, and the liquid is supplied to the respective wells.  
     
     
         59 . The probe array according to  claim 58  wherein the probe is a single-stranded nucleic acid probe.  
     
     
         60 . The probe array according to  claim 59  wherein the single-stranded nucleic acid probe includes a single-stranded DNA probe.  
     
     
         61 . The probe array according to  claim 59  wherein the single-stranded nucleic acid includes a RNA probe.  
     
     
         62 . The probe array according to  claim 59  wherein the single-stranded nucleic acid includes a single-stranded PNA probe.  
     
     
         63 . The probe array according to  claim 62  wherein the single-stranded nucleic acid is covalently bound to the surface of the solid support by a reaction between the first functional group of the surface of the solid surface and the second functional group on the single-stranded nucleic acid probe.  
     
     
         64 . The probe array according to  claim 63  wherein the first functional group on the surface of the solid support is a maleimido group and the second functional group of the single-stranded nucleic acid probe is a thiol (SH) group.  
     
     
         65 . The probe array according to  claim 64  wherein the single-stranded nucleic acid probe is a single-stranded PNA probe and contains a cysteine residue on an N-terminal side.  
     
     
         66 . The probe array according to  claim 63  wherein the first functional group on the surface of the solid support is an epoxy group and the second functional group of the single-stranded nucleic acid probe is an amino group.  
     
     
         67 . The probe array according to  claim 58  wherein the spots are formed by supplying a liquid containing a probe on the solid support.  
     
     
         68 . The probe array according to  claim 58  wherein the probe is an oligopeptide or a polypeptide with a specific amino acid sequence.  
     
     
         69 . The probe array according to  claim 58  wherein the probe is a protein.  
     
     
         70 . The probe array according to  claim 69  wherein the protein is an antibody.  
     
     
         71 . The probe array according to  claim 69  wherein the protein is an enzyme.  
     
     
         72 . The probe array according to  claim 58  wherein the probe is an antigen.  
     
     
         73 . The probe array according to  claim 58  wherein the matrix is opaque.  
     
     
         74 . The probe array according to  claim 73  wherein the solid support is optically transparent.  
     
     
         75 . The probe array according to  claim 58  wherein the matrix comprises a resin.  
     
     
         76 . The probe array according to  claim 58  wherein the probe is attached only to the wells.  
     
     
         77 . The probe array according to  claim 58  wherein the matrix has a thickness of 1-20 μm.  
     
     
         78 . The probe array according to  claim 58  wherein the wells have a maximum width of 200 μm.  
     
     
         79 . The probe array according to  claim 58  wherein a distance between the wells is 1/2-2 times the maximum width of the wells.  
     
     
         80 . The probe array according to  claim 41  wherein the probe array comprises at least 2 spots each of which comprises a different kind of probe.  
     
     
         81 . A method of manufacturing a probe array having a plurality of spots arranged independently in 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 a step of supplying a liquid containing the probe and attaching the liquid to a predetermined site on the surface of the solid support by means of an ink jet method to form the spots.  
     
     
         82 . The method of manufacturing according to  claim 81  wherein the probe is a single-stranded nucleic acid probe.  
     
     
         83 . The method of manufacturing according to  claim 82  wherein the single-stranded nucleic acid probe is a single-stranded DNA probe.  
     
     
         84 . The method of manufacturing according to  claim 82  wherein the single-stranded nucleic acid probe is an RNA probe.  
     
     
         85 . The method of manufacturing according to  claim 82  wherein the single-stranded nucleic acid probe is a single-stranded PNA probe.  
     
     
         86 . The method of manufacturing according to  claim 82  wherein the surface of the solid surface has a first functional group and the single-stranded nucleic acid probe has a second functional group, and the first and the second functional groups react each other by contact.  
     
     
         87 . The method of manufacturing according to  claim 86  wherein the first functional group on the surface of the solid support is a maleimido group and the second functional group of the single-stranded nucleic acid probe is a thiol (SH) group.  
     
     
         88 . The method of manufacturing according to  claim 87  wherein the solid support is a glass plate and a maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with N-(6-maleimidocaproyloxy) succinimide.  
     
     
         89 . The method of manufacturing according to  claim 87  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with succinimidyl-4-(maleimido phenyl) butyrate.  
     
     
         90 . The method of manufacturing according to  claim 87  wherein the maleimido group is reacted with the thiol group for at least 30 minutes.  
     
     
         91 . The method of manufacturing according to  claim 90  wherein the single-stranded nucleic acid is a single-stranded PNA probe, at the terminus of which the thiol group exists, the maleimido group is reacted with the thiol group for at least 2 hours.  
     
     
         92 . The method of manufacturing according to  claim 91  wherein the thiol group at the terminus of the single-stranded PNA probe is introduced by binding cysteine group to an N-terminal of the single-stranded PNA probe.  
     
     
         93 . The method of manufacturing according to  claim 86  wherein the first functional group on the surface of the solid support is an epoxy group and the second functional group of the single-stranded nucleic acid probe has is an amino group.  
     
     
         94 . The method of manufacturing according to  claim 93  wherein the solid support is a glass plate and the epoxy group is introduced by applying a silane compound having an epoxy group in the molecule thereof on the surface of the glass plate and reacting the compound with the glass plate.  
     
     
         95 . The method of manufacturing according to  claim 93  wherein the epoxy group is introduced by applying polyglycidyl methacrylate having an epoxy group on the solid support.  
     
     
         96 . The method of manufacturing according to  claim 93  wherein the liquid contains urea at 5-10 wt %, glycerin at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 1 wt % of the liquid.  
     
     
         97 . The method of manufacturing according to  claim 96  wherein the acetylene alcohol has a structure represented by the following general formula (I):  
       
         
           
           
               
               
           
         
       
       (wherein, R 1 , R 2 , R 3 , and R 4  represent an alkyl group, each m and n represent an integral, and m=0 and n=0, or 1≦m+n≦30, and when m+n=1, m or n is 0.)  
     
     
         98 . The method of manufacturing according to  claim 82  wherein a concentration of the single-stranded nucleic acid probe in the liquid is 0.05-500 μM.  
     
     
         99 . The method of manufacturing according to  claim 98  wherein the concentration of the single-stranded nucleic acid probe in the liquid is 2-50 μM.  
     
     
         100 . The method of manufacturing according to  claim 82  wherein a length of the single-stranded nucleic acid probe is 2-5,000 bases.  
     
     
         101 . The method of manufacturing according to  claim 100  wherein the length of the single-stranded nucleic acid probe is 2-60 bases.  
     
     
         102 . The method of manufacturing according to  claim 81  wherein the ink jet method is a bubble jet method.  
     
     
         103 . The method of manufacturing according to  claim 81  wherein the liquid is supplied so as to form independent spots in a density of 10,000 spots per square inch on the solid support of higher.  
     
     
         104 . The method of manufacturing according to  claim 81  wherein the probe is an oligopeptide or a polypeptide with a specific amino acid sequence.  
     
     
         105 . The method of manufacturing according to  claim 81  wherein the probe is a protein.  
     
     
         106 . The method of manufacturing according to  claim 105  wherein the protein is an antibody.  
     
     
         107 . The method of manufacturing according to  claim 105  wherein the protein is an enzyme.  
     
     
         108 . The method of manufacturing according to  claim 81  wherein the probe is an antigen.  
     
     
         109 . The method of manufacturing according to  claim 81  wherein the solid support has a flat surface and homogenous surface properties.  
     
     
         110 . The method of manufacturing according to  claim 109  wherein blocking is performed, following spotting of the probe to the solid support, to prevent a sample from attaching to the surface other than the spots.  
     
     
         111 . The method of manufacturing according to  claim 110  wherein the blocking comprises a step of immersing the solid support to which the spots have been formed in an aqueous solution of bovine serum albumin.  
     
     
         112 . The method of manufacturing according to  claim 111  wherein a concentration of the aqueous solution of bovine serum albumin is 0.1-5%.  
     
     
         113 . The method of manufacturing according to  claim 111  wherein the solid support is immersed in an aqueous solution of bovine serum albumin for at least 2 hours.  
     
     
         114 . The method of manufacturing according to  claim 109  wherein the liquid is supplied on the surface of the solid support so as to obtain a distance between the adjacent spots not smaller than a maximum width of the spot.  
     
     
         115 . The method of manufacturing according to  claim 81  wherein the solid support is partitioned by a matrix arranged in a pattern on the surface, a plurality of wells whose bottom is the surface of the solid support exposed in a pattern are provided, and the liquid is supplied to the respective wells.  
     
     
         116 . The method of manufacturing according to  claim 115  wherein the solid support is optically transparent and the matrix is opaque.  
     
     
         117 . The method of manufacturing according to  claim 115  wherein the matrix comprises a resin.  
     
     
         118 . The method of manufacturing according to  claim 115  wherein the surface of the matrix is hydrophobic.  
     
     
         119 . The method of manufacturing according to  claim 115  wherein the bottom of the wells is hydrophilic.  
     
     
         120 . The method of manufacturing according to  claim 115  wherein the wells have a maximum width of 200 μm.  
     
     
         121 . The method of manufacturing according to  claim 115  wherein the matrix has a width 1/2-2 times the maximum width of the wells.  
     
     
         122 . The method of manufacturing according to  claim 115  wherein a thickness of the matrix is 1-20 μm.  
     
     
         123 . The method of manufacturing according to  claim 115  wherein the matrix pattern is formed by photolithography.  
     
     
         124 . The method of manufacturing according to  claim 123  wherein the photolithography comprises a step of forming a resin layer on the surface of the solid support, forming a photoresist layer on the resin layer, exposing the photoresist layer to light in a pattern corresponding to the matrix pattern, and developing to form the pattern of the photoresist on the resin layer; and a step of patterning the resin layer using the pattern of the photoresist as a mask and then removing the pattern of the photoresists.  
     
     
         125 . The method of manufacturing according to  claim 123  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.  
     
     
         126 . The method of manufacturing according to  claim 125  wherein the photosensitive resin layer is selected from the group consisted of a UV resist, a DEEP-UV resist, or an ultraviolet cure resin.  
     
     
         127 . The method of manufacturing according to  claim 126  wherein the UV resist is selected from the group consisted of a cyclized polyisoprene-aromatic bisazide resist, a phenol resin-aromatic azide compound resist, or a novolak resin-diazonaphtoquinone resist.  
     
     
         128 . The method of manufacturing according to  claim 126  wherein the DEEP-UV resin is a radiolysable polymer resist or a dissolution suppressant resist.  
     
     
         129 . The method of manufacturing according to  claim 128  wherein the radiation decomposition polymer resist is at least one selected from a group consisting of polymethyl methacrylate, polymethylene sulfone, polyhexafluorobutyl methacrylate, polymethylisopropenyl ketone, and poly-1-trimethylsilyl propyne bromide.  
     
     
         130 . The method of manufacturing according to  claim 128  wherein the dissolution suppressant resist is o-nitrobenzyl cholate ester.  
     
     
         131 . The method of manufacturing according to  claim 126  wherein the DEEP-UV resist is polyvinylphenol-3,3′-diazidediphenyl sulfone or polyglycidyl polymethacrylate.  
     
     
         132 . The method of manufacturing according to  claim 125  wherein water repellency of the matrix pattern formed by patterning of the photosensitive resin layer is further improved by postbaking of the matrix pattern.  
     
     
         133 . The method of manufacturing according to  claim 115  wherein a first functional group which can form a covalent bond with a second functional group of the probe is introduced on the surface of the solid support prior to formation of the wells.  
     
     
         134 . The method of manufacturing according to  claim 115  wherein a first functional group which can form a covalent bond with a second functional group of the probe is introduced on the surface of the solid support following formation of the wells.  
     
     
         135 . The method of manufacturing according to  claim 134  wherein a solution containing a compound for introducing the first functional group to the surface of the solid support is supplied to the wells.  
     
     
         136 . The method of manufacturing according to  claim 135  wherein the solution is supplied to the wells by means of the ink jet method.  
     
     
         137 . The method of manufacturing according to  claim 136  wherein the solution is a silane coupling agent containing a silane compound having an epoxy group or an amino group in its molecule.  
     
     
         138 . The method of manufacturing according to  claim 136  wherein the solution contains a compound which can react with an amino group on a glass substrate to introduce a maleimido group on the glass substrate.  
     
     
         139 . The method of manufacturing according to  claim 138  wherein the compound is N-maleimidocaproyloxy succinimide or succinimidyl-4-(maleimidophenyl) butyrate.  
     
     
         140 . A method for detecting whether a target substance is contained in a sample, comprising the steps of: 
 providing a probe array comprising a plurality of spots each containing a probe which specifically binds to the target substance, the spots being arranged independently on a solid support;    contacting the sample with each of the spots; and    detecting presence or absence of a reacted product between the target substance and the probe, wherein the respective spots are formed by spotting a liquid containing the probe on the solid support by an ink jet method.    
     
     
         141 . The method according to  claim 140  wherein the target substance is a single-stranded nucleic acid having a first base sequence and the probe is a single-stranded nucleic acid probe having a second base sequence complementary to the first base sequence.  
     
     
         142 . The method according to  claim 141  wherein the single-stranded nucleic acid probe is a single-stranded DNA probe.  
     
     
         143 . The method according to  claim 141  wherein the single-stranded nucleic acid probe is an RNA probe.  
     
     
         144 . The method according to  claim 141  wherein the single-stranded nucleic acid probe is a single-stranded PNA probe.  
     
     
         145 . The method according to  claim 141  wherein the surface of the solid surface has a first functional group and the single-stranded nucleic acid probe has a second functional group, respectively, and the functional groups react each other by contact.  
     
     
         146 . The method according to  claim 145  wherein the first functional group on the surface of the solid support is a maleimido group and the second functional group of the single-stranded nucleic acid probe is a thiol (SH) group.  
     
     
         147 . The method according to  claim 146  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with N-(6-maleimidocaproyloxy) succinimide.  
     
     
         148 . The method according to  claim 146  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with succinimidyl-4-(maleimidophenyl) butyrate.  
     
     
         149 . The method according to  claim 146  wherein the maleimido group is reacted with the thiol group for at least 30 minutes.  
     
     
         150 . The method according to  claim 149  wherein the single-stranded nucleic acid comprises a single-stranded PNA probe having a thiol group on the terminus and the maleimido group is reacted with the thiol group for at least 2 hours.  
     
     
         151 . The method according to  claim 146  wherein the thiol group at a terminus of the single-stranded PNA probe is introduced by binding cysteine group to an N-terminus of the single-stranded PNA probe.  
     
     
         152 . The method according to  claim 145  wherein the first functional group on the surface of the solid support is an epoxy group and the second functional group of the single-stranded nucleic acid probe is an amino group.  
     
     
         153 . The method according to  claim 152  wherein the solid support is a glass plate and the epoxy group is introduced by applying a silane compound having an epoxy group in the molecule thereof on the surface of the glass plate and reacting the compound with the glass plate.  
     
     
         154 . The method according to  claim 152  wherein the epoxy group is introduced by applying polyglycidyl methacrylate having an epoxy group on the solid support.  
     
     
         155 . The method according to  claim 141  wherein the liquid contains urea at 5-10 wt %, glycerin at 5-10 wt %, thiodiglycol at 5-10 wt %, and an acetylene alcohol at 1 wt % of the liquid.  
     
     
         156 . The method according to  claim 155  wherein the acetylene alcohol has a structure represented by the following general formula (I):  
       
         
           
           
               
               
           
         
       
       (wherein, R 1 , R 2 , R 3 , and R 4  represent an alkyl group, each m and n represent an integral, and m=0 and n=0 or 1≦m+n≦30, and when m+n=1, m or n is 0.)  
     
     
         157 . The method according to  claim 155  wherein a concentration of the single-stranded nucleic acid probe in the liquid is 0.05-500 μM.  
     
     
         158 . The method according to  claim 157  wherein a concentration of the single-stranded nucleic acid probe in the liquid is 2-50 μM.  
     
     
         159 . The method according to  claim 155  wherein a length of the single-stranded nucleic acid probe is 2-5,000 bases.  
     
     
         160 . The method according to  claim 159  wherein a length of the single-stranded nucleic acid probe is 2-60 bases.  
     
     
         161 . The method according to  claim 141  wherein the ink jet method is a bubble jet method.  
     
     
         162 . The method according to  claim 140  wherein the probe is an oligopeptide or a polypeptide with a specific amino acid sequence.  
     
     
         163 . The method according to  claim 140  wherein the probe is a protein.  
     
     
         164 . The method according to  claim 163  wherein the protein is an antibody.  
     
     
         165 . The method according to  claim 163  wherein the protein is an enzyme.  
     
     
         166 . The method according to  claim 140  wherein the probe is an antigen.  
     
     
         167 . The method according to  claim 140  wherein the liquid is supplied so as to form independent spots in a density of 10,000 spots per square inch on the solid support.  
     
     
         168 . The method according to  claim 140  wherein the solid support has a flat surface and homogenous surface properties.  
     
     
         169 . The method according to  claim 168  wherein the liquid is supplied on the surface of the solid support so as to obtain a distance between the adjacent spots not smaller than the maximum width of the spots.  
     
     
         170 . The method according to  claim 168  wherein blocking is performed on the surface of the solid support to prevent the sample from attaching to the surface other than the spots of the surface of the solid support.  
     
     
         171 . The method according to  claim 170  wherein blocking is achieved by using bovine serum albumin.  
     
     
         172 . The method according to  claim 140  wherein the solid support is partitioned by a matrix arranged in a pattern on the surface, a plurality of wells whose bottom is the surface of the solid support exposed in the pattern are provided, and the liquid is supplied to the respective wells.  
     
     
         173 . The method according to  claim 172  wherein the solid support is optically transparent and the matrix is opaque.  
     
     
         174 . The method according to  claim 172  wherein the matrix comprises a resin.  
     
     
         175 . The method according to  claim 172  wherein the surface of the matrix is hydrophobic.  
     
     
         176 . The method according to  claim 172  wherein the bottom of the wells is hydrophilic.  
     
     
         177 . The method according to  claim 172  wherein the matrix has a thickness of 1-20 μm.  
     
     
         178 . The method according to  claim 172  wherein the wells have a maximum width of 200 μm.  
     
     
         179 . The method according to  claim 172  wherein the matrix has a width 1/2-2 times the maximum width of the wells.  
     
     
         180 . A method of identifying a structure of a target substance contained in a sample comprising the steps of: 
 preparing a probe array provided with spots of a probe, the probe being able to bind specifically to the target substance, on a surface of a solid support;    contacting the sample to the spots; and    detecting binding between the target substance and the probe.    
     
     
         181 . The method of identification according to  claim 180  wherein the target substance is a single-stranded nucleic acid, the structure to be identified is a base sequence of the single-stranded nucleic acid as the target substance, 
 the probe array is provided with a plurality of spots each of which contains single-stranded nucleic acids with different base sequences on a solid support, at least one of the spots contain a single-stranded nucleic acid with a base sequence complementary to that anticipated for the single-stranded nucleic acid as the target substance, and the plurality of spots are formed by attaching a liquid containing the respective single-stranded nucleic acids on the solid support by means of an ink jet method.  
 
     
     
         182 . The method of identification according to  claim 181  wherein the single-stranded nucleic acid probe is a single-stranded DNA probe.  
     
     
         183 . The method of identification according to  claim 181  wherein the single-stranded nucleic acid probe is an RNA probe.  
     
     
         184 . The method of identification according to  claim 181  wherein the single-stranded nucleic acid probe is a single-stranded PNA probe.  
     
     
         185 . The method of identification according to  claim 181  wherein the surface of the solid surface and the single-stranded nucleic acid probe have a first and a second functional groups, respectively, and the functional groups react each other by contact.  
     
     
         186 . The method of identification according to  claim 181  wherein the first functional group on the surface of the solid support is a maleimido group and the second functional group of the single-stranded nucleic acid probe is a thiol (SH) group.  
     
     
         187 . The method of identification according to  claim 186  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with N-(6-maleimidocaproyloxy) succinimide.  
     
     
         188 . The method of identification according to  claim 186  wherein the solid support is a glass plate and the maleimido group is introduced by introducing an amino group on the surface of the glass plate and then reacting the amino group with succinimidyl-4-(maleimido phenyl) butyrate.  
     
     
         189 . The method of identification according to  claim 186  wherein the maleimido group is reacted with the thiol group for at least 30 minutes.  
     
     
         190 . The method of identification according to  claim 189  wherein the single-stranded nucleic acid is a single-stranded PNA probe having a thiol group on the terminus thereof and the maleimido group is reacted with the thiol group for at least 2 hours.  
     
     
         191 . The method of identification according to  claim 186  wherein the thiol group at the terminus of the single-stranded PNA probe is introduced by binding cysteine group to an N-terminus of the single-stranded PNA probe.  
     
     
         192 . The method of identification according to  claim 185  wherein the first functional group on the surface of the solid support is an epoxy group and the second functional group of the single-stranded nucleic acid probe is an amino group.  
     
     
         193 . The method of identification according to  claim 192  wherein the solid support is a glass plate and the epoxy group is introduced by applying a silane compound having an epoxy group in the molecule on the surface of the glass plate and reacting the compound with the glass plate.  
     
     
         194 . The method of identification according to  claim 192  wherein the epoxy group is introduced by applying polyglycidyl methacrylate having an epoxy group on the solid support.  
     
     
         195 . The method of identification according to  claim 181  wherein the liquid contains urea at 5-10 wt %, glycerin at 5-10 wt %, thiodiglycol at 5-10 wt %, and acetylene alcohol at 1 wt % of the liquid.  
     
     
         196 . The method of identification according to  claim 195  wherein the acetylene alcohol has a structure represented by the following general formula (I):  
       
         
           
           
               
               
           
         
       
       (wherein, R 1 , R 2 , R 3 , and R 4  represent an alkyl group, each m and n represent an integral, and m=0 and n=0 or 1≦m+n≦30, and when m+n=1, m or n is 0.)  
     
     
         197 . The method of identification according to  claim 195  wherein a concentration of the single-stranded nucleic acid probe in the liquid is 0.05-500 μM.  
     
     
         198 . The method of identification according to  claim 197  wherein the concentration of the single-stranded nucleic acid probe in the liquid is 2-50 μM.  
     
     
         199 . The method of identification according to  claim 197  wherein a length of the single-stranded nucleic acid probe is 2-5,000 bases.  
     
     
         200 . The method of identification according to  claim 199  wherein a length of the single-stranded nucleic acid probe is 2-60 bases.  
     
     
         201 . The method of identification according to  claim 181  wherein the ink jet method is a bubble jet method.  
     
     
         202 . The method of identification according to  claim 180  wherein the probe is an oligopeptide or a polypeptide with a specific amino acid sequence.  
     
     
         203 . The method of identification according to  claim 180  wherein the probe is a protein.  
     
     
         204 . The method of identification according to claim  203  wherein the protein is an antibody.  
     
     
         205 . The method of identification according to claim  203  wherein the protein is an enzyme.  
     
     
         206 . The method of identification according to  claim 180  wherein the probe is an antigen.  
     
     
         207 . The method of identification according to  claim 180  wherein the liquid is supplied so as to form independent spots in a density of 10,000 spots per square inch on the solid support.  
     
     
         208 . The method of identification according to  claim 180  wherein the solid support has a flat surface and homogenous surface properties.  
     
     
         209 . The method of identification according to claim  208  wherein the liquid is supplied on the surface of the solid support so as to obtain a distance between the adjacent spots not smaller than the maximum width of the spots.  
     
     
         210 . The method of identification according to claim  208  wherein blocking is performed on the surface of the solid support to prevent the sample from attaching to the surface other than spots of the surface of the solid support.  
     
     
         211 . The method of identification according to claim  210  wherein blocking is achieved by using bovine serum albumin.  
     
     
         212 . The method of identification according to  claim 180  wherein the solid support is partitioned by a matrix arranged in a pattern on the surface, a plurality of wells whose bottom is the surface of the solid support exposed in the pattern are provided, and the liquid is supplied to the respective wells.  
     
     
         213 . The method of identification according to claim  212  wherein the solid support is optically transparent and the matrix is opaque.  
     
     
         214 . The method of identification according to claim  212  wherein the matrix comprises a resin.  
     
     
         215 . The method of identification according to claim  212  wherein the surface of the matrix is hydrophobic.  
     
     
         216 . The method of identification according to claim  212  wherein the bottom of the wells is hydrophilic.  
     
     
         217 . The method of identification according to claim  212  wherein the matrix has a thickness of 1-20 μm.  
     
     
         218 . The method of identification according to claim  212  wherein the wells have a maximum width of 200 μm.  
     
     
         219 . The method of identification according to claim  212  wherein the matrix has a width 1/2-2 times a maximum width of the wells.