JP4741499B2 - 表面への分子の結合 - Google Patents
表面への分子の結合 Download PDFInfo
- Publication number
- JP4741499B2 JP4741499B2 JP2006534165A JP2006534165A JP4741499B2 JP 4741499 B2 JP4741499 B2 JP 4741499B2 JP 2006534165 A JP2006534165 A JP 2006534165A JP 2006534165 A JP2006534165 A JP 2006534165A JP 4741499 B2 JP4741499 B2 JP 4741499B2
- Authority
- JP
- Japan
- Prior art keywords
- polymer
- acrylamide
- reactive groups
- methacrylamide
- mixtures
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 230000009149 molecular binding Effects 0.000 title 1
- 229920000642 polymer Polymers 0.000 claims abstract description 156
- 238000000034 method Methods 0.000 claims abstract description 60
- 239000000758 substrate Substances 0.000 claims abstract description 47
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 25
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 23
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 23
- 239000000203 mixture Substances 0.000 claims description 100
- -1 N-substituted acrylamide Chemical class 0.000 claims description 67
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 26
- 238000002493 microarray Methods 0.000 claims description 16
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 claims description 14
- 125000000524 functional group Chemical group 0.000 claims description 14
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 claims description 13
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 12
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 claims description 11
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical group CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 claims description 11
- 239000011521 glass Substances 0.000 claims description 10
- 239000000463 material Substances 0.000 claims description 9
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims description 8
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 8
- 239000012965 benzophenone Substances 0.000 claims description 8
- 238000009739 binding Methods 0.000 claims description 8
- 229920003023 plastic Polymers 0.000 claims description 8
- 239000004033 plastic Substances 0.000 claims description 8
- XLPJNCYCZORXHG-UHFFFAOYSA-N 1-morpholin-4-ylprop-2-en-1-one Chemical compound C=CC(=O)N1CCOCC1 XLPJNCYCZORXHG-UHFFFAOYSA-N 0.000 claims description 7
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 7
- RJGDLRCDCYRQOQ-UHFFFAOYSA-N anthrone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3CC2=C1 RJGDLRCDCYRQOQ-UHFFFAOYSA-N 0.000 claims description 7
- 230000027455 binding Effects 0.000 claims description 7
- 239000010703 silicon Substances 0.000 claims description 7
- 229910052710 silicon Inorganic materials 0.000 claims description 7
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 claims description 6
- 150000004056 anthraquinones Chemical class 0.000 claims description 6
- QRWZCJXEAOZAAW-UHFFFAOYSA-N n,n,2-trimethylprop-2-enamide Chemical compound CN(C)C(=O)C(C)=C QRWZCJXEAOZAAW-UHFFFAOYSA-N 0.000 claims description 5
- JMCVCHBBHPFWBF-UHFFFAOYSA-N n,n-diethyl-2-methylprop-2-enamide Chemical compound CCN(CC)C(=O)C(C)=C JMCVCHBBHPFWBF-UHFFFAOYSA-N 0.000 claims description 5
- OVHHHVAVHBHXAK-UHFFFAOYSA-N n,n-diethylprop-2-enamide Chemical compound CCN(CC)C(=O)C=C OVHHHVAVHBHXAK-UHFFFAOYSA-N 0.000 claims description 5
- OHLHOLGYGRKZMU-UHFFFAOYSA-N n-benzylprop-2-enamide Chemical compound C=CC(=O)NCC1=CC=CC=C1 OHLHOLGYGRKZMU-UHFFFAOYSA-N 0.000 claims description 5
- PMJFVKWBSWWAKT-UHFFFAOYSA-N n-cyclohexylprop-2-enamide Chemical compound C=CC(=O)NC1CCCCC1 PMJFVKWBSWWAKT-UHFFFAOYSA-N 0.000 claims description 5
- ZIWDVJPPVMGJGR-UHFFFAOYSA-N n-ethyl-2-methylprop-2-enamide Chemical compound CCNC(=O)C(C)=C ZIWDVJPPVMGJGR-UHFFFAOYSA-N 0.000 claims description 5
- AWGZKFQMWZYCHF-UHFFFAOYSA-N n-octylprop-2-enamide Chemical compound CCCCCCCCNC(=O)C=C AWGZKFQMWZYCHF-UHFFFAOYSA-N 0.000 claims description 5
- BPCNEKWROYSOLT-UHFFFAOYSA-N n-phenylprop-2-enamide Chemical compound C=CC(=O)NC1=CC=CC=C1 BPCNEKWROYSOLT-UHFFFAOYSA-N 0.000 claims description 5
- QNILTEGFHQSKFF-UHFFFAOYSA-N n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C=C QNILTEGFHQSKFF-UHFFFAOYSA-N 0.000 claims description 5
- 229910052990 silicon hydride Inorganic materials 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- AKVUWTYSNLGBJY-UHFFFAOYSA-N 2-methyl-1-morpholin-4-ylprop-2-en-1-one Chemical compound CC(=C)C(=O)N1CCOCC1 AKVUWTYSNLGBJY-UHFFFAOYSA-N 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- WFKDPJRCBCBQNT-UHFFFAOYSA-N n,2-dimethylprop-2-enamide Chemical compound CNC(=O)C(C)=C WFKDPJRCBCBQNT-UHFFFAOYSA-N 0.000 claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 4
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 3
- 238000012545 processing Methods 0.000 claims description 2
- 150000003961 organosilicon compounds Chemical class 0.000 claims 3
- 150000002118 epoxides Chemical class 0.000 claims 2
- 150000002540 isothiocyanates Chemical class 0.000 claims 2
- 239000002023 wood Substances 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 14
- 102000004169 proteins and genes Human genes 0.000 abstract description 5
- 108091005461 Nucleic proteins Proteins 0.000 abstract description 4
- 230000003100 immobilizing effect Effects 0.000 abstract description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 239000000178 monomer Substances 0.000 description 51
- 150000003140 primary amides Chemical class 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
- 150000001875 compounds Chemical class 0.000 description 32
- 239000000047 product Substances 0.000 description 31
- 239000000243 solution Substances 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 229920001577 copolymer Polymers 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 108020004414 DNA Proteins 0.000 description 12
- 102000053602 DNA Human genes 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 150000001408 amides Chemical group 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 108091034117 Oligonucleotide Proteins 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 238000000576 coating method Methods 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 8
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 description 7
- 238000007792 addition Methods 0.000 description 7
- 239000011248 coating agent Substances 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 229950000688 phenothiazine Drugs 0.000 description 7
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 230000009257 reactivity Effects 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 5
- 150000002924 oxiranes Chemical class 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 5
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 4
- FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- VOZRXNHHFUQHIL-UHFFFAOYSA-N glycidyl methacrylate Chemical compound CC(=C)C(=O)OCC1CO1 VOZRXNHHFUQHIL-UHFFFAOYSA-N 0.000 description 4
- 238000009396 hybridization Methods 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 229920001451 polypropylene glycol Polymers 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- BACYUWVYYTXETD-UHFFFAOYSA-N N-Lauroylsarcosine Chemical compound CCCCCCCCCCCC(=O)N(C)CC(O)=O BACYUWVYYTXETD-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 238000007605 air drying Methods 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 210000003050 axon Anatomy 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- ZLZGHBNDPINFKG-UHFFFAOYSA-N chloro-decyl-dimethylsilane Chemical compound CCCCCCCCCC[Si](C)(C)Cl ZLZGHBNDPINFKG-UHFFFAOYSA-N 0.000 description 3
- UTMBOOWVJPCANU-UHFFFAOYSA-N chloro-dimethyl-(4-methylphenyl)silane Chemical compound CC1=CC=C([Si](C)(C)Cl)C=C1 UTMBOOWVJPCANU-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 239000012065 filter cake Substances 0.000 description 3
- 229920001477 hydrophilic polymer Polymers 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 229910000077 silane Inorganic materials 0.000 description 3
- 239000005361 soda-lime glass Substances 0.000 description 3
- 239000012064 sodium phosphate buffer Substances 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 229920001169 thermoplastic Polymers 0.000 description 3
- 239000004416 thermosoftening plastic Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 2
- FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 2
- WUIJTQZXUURFQU-UHFFFAOYSA-N 1-methylsulfonylethene Chemical compound CS(=O)(=O)C=C WUIJTQZXUURFQU-UHFFFAOYSA-N 0.000 description 2
- XWRBMHSLXKNRJX-UHFFFAOYSA-N 2-ethenyl-1-oxidopyridin-1-ium Chemical compound [O-][N+]1=CC=CC=C1C=C XWRBMHSLXKNRJX-UHFFFAOYSA-N 0.000 description 2
- RCEJCSULJQNRQQ-UHFFFAOYSA-N 2-methylbutanenitrile Chemical compound CCC(C)C#N RCEJCSULJQNRQQ-UHFFFAOYSA-N 0.000 description 2
- MXRGSJAOLKBZLU-UHFFFAOYSA-N 3-ethenylazepan-2-one Chemical compound C=CC1CCCCNC1=O MXRGSJAOLKBZLU-UHFFFAOYSA-N 0.000 description 2
- LTQUNXZZRXILFZ-UHFFFAOYSA-N 4-(2-ethoxyethoxy)-2-methylidenebutanoic acid Chemical compound CCOCCOCCC(=C)C(O)=O LTQUNXZZRXILFZ-UHFFFAOYSA-N 0.000 description 2
- IFQUPKAISSPFTE-UHFFFAOYSA-N 4-benzoylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C(=O)C1=CC=CC=C1 IFQUPKAISSPFTE-UHFFFAOYSA-N 0.000 description 2
- WOJKKJKETHYEAC-UHFFFAOYSA-N 6-Maleimidocaproic acid Chemical compound OC(=O)CCCCCN1C(=O)C=CC1=O WOJKKJKETHYEAC-UHFFFAOYSA-N 0.000 description 2
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 108091028043 Nucleic acid sequence Proteins 0.000 description 2
- 229920000604 Polyethylene Glycol 200 Polymers 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229960002684 aminocaproic acid Drugs 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical compound O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000001307 helium Substances 0.000 description 2
- 229910052734 helium Inorganic materials 0.000 description 2
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 229920001480 hydrophilic copolymer Polymers 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 238000007834 ligase chain reaction Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 2
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 2
- PNLUGRYDUHRLOF-UHFFFAOYSA-N n-ethenyl-n-methylacetamide Chemical compound C=CN(C)C(C)=O PNLUGRYDUHRLOF-UHFFFAOYSA-N 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229920002939 poly(N,N-dimethylacrylamides) Polymers 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 229920000570 polyether Polymers 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 239000004926 polymethyl methacrylate Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000010526 radical polymerization reaction Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000007420 reactivation Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 125000006850 spacer group Chemical group 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- QLWQBUVPOLBDCD-UHFFFAOYSA-N tert-butyl n-[3-(2-methylprop-2-enoylamino)propyl]carbamate Chemical compound CC(=C)C(=O)NCCCNC(=O)OC(C)(C)C QLWQBUVPOLBDCD-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ABZLKHKQJHEPAX-UHFFFAOYSA-N tetramethylrhodamine Chemical compound C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C([O-])=O ABZLKHKQJHEPAX-UHFFFAOYSA-N 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
- VLARLSIGSPVYHX-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 6-(2,5-dioxopyrrol-1-yl)hexanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCCCCN1C(=O)C=CC1=O VLARLSIGSPVYHX-UHFFFAOYSA-N 0.000 description 1
- DWHJJLTXBKSHJG-HWKANZROSA-N (e)-5-hydroxy-2-methylpent-2-enoic acid Chemical compound OC(=O)C(/C)=C/CCO DWHJJLTXBKSHJG-HWKANZROSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- UUORGSXWPOMXJJ-UHFFFAOYSA-N 1-[azido(ethyl)phosphoryl]ethane Chemical compound CCP(=O)(CC)N=[N+]=[N-] UUORGSXWPOMXJJ-UHFFFAOYSA-N 0.000 description 1
- UDJZTGMLYITLIQ-UHFFFAOYSA-N 1-ethenylpyrrolidine Chemical compound C=CN1CCCC1 UDJZTGMLYITLIQ-UHFFFAOYSA-N 0.000 description 1
- QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
- IEJPPSMHUUQABK-UHFFFAOYSA-N 2,4-diphenyl-4h-1,3-oxazol-5-one Chemical compound O=C1OC(C=2C=CC=CC=2)=NC1C1=CC=CC=C1 IEJPPSMHUUQABK-UHFFFAOYSA-N 0.000 description 1
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical group N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- HQNSWBRZIOYGAW-UHFFFAOYSA-N 2-chloro-n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC(Cl)=C1 HQNSWBRZIOYGAW-UHFFFAOYSA-N 0.000 description 1
- FRGPNSFCLLXLJR-UHFFFAOYSA-N 2-diazonio-1-[(2-methylpropan-2-yl)oxy]-3-oxobut-1-en-1-olate Chemical compound CC(=O)C(=[N+]=[N-])C(=O)OC(C)(C)C FRGPNSFCLLXLJR-UHFFFAOYSA-N 0.000 description 1
- JBVSBLLOZVDAAZ-UHFFFAOYSA-N 2-diazonio-1-[(2-methylpropan-2-yl)oxy]ethenolate Chemical compound CC(C)(C)OC([O-])=C[N+]#N JBVSBLLOZVDAAZ-UHFFFAOYSA-N 0.000 description 1
- UWBALSPTLHOGFE-UHFFFAOYSA-N 2-diazonio-1-phenoxyethenolate Chemical compound [N-]=[N+]=CC(=O)OC1=CC=CC=C1 UWBALSPTLHOGFE-UHFFFAOYSA-N 0.000 description 1
- ZSTBZBURMWJKSQ-UHFFFAOYSA-N 2-diazonio-1-phenylethenolate Chemical compound N#[N+]C=C([O-])C1=CC=CC=C1 ZSTBZBURMWJKSQ-UHFFFAOYSA-N 0.000 description 1
- MRLXSYXBKLYMCK-UHFFFAOYSA-N 2-ethyl-5h-1,2-oxazole Chemical compound CCN1OCC=C1 MRLXSYXBKLYMCK-UHFFFAOYSA-N 0.000 description 1
- HAUVRGZOEXGUJS-UHFFFAOYSA-N 2-methyl-4-(oxiran-2-yl)but-2-enoic acid Chemical compound OC(=O)C(C)=CCC1CO1 HAUVRGZOEXGUJS-UHFFFAOYSA-N 0.000 description 1
- IXEVBKYJNFWMPR-UHFFFAOYSA-N 3-phenyl-3-(trifluoromethyl)diazirine Chemical compound C=1C=CC=CC=1C1(C(F)(F)F)N=N1 IXEVBKYJNFWMPR-UHFFFAOYSA-N 0.000 description 1
- VCTBSHQJICJJFV-UHFFFAOYSA-N 4-azido-1-fluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(N=[N+]=[N-])=CC=C1F VCTBSHQJICJJFV-UHFFFAOYSA-N 0.000 description 1
- KKGFAULLJCULTN-UHFFFAOYSA-N 4-benzoyl-n-[3-(2-methylprop-2-enoylamino)propyl]benzamide Chemical compound C1=CC(C(=O)NCCCNC(=O)C(=C)C)=CC=C1C(=O)C1=CC=CC=C1 KKGFAULLJCULTN-UHFFFAOYSA-N 0.000 description 1
- NJMYQRVWBCSLEU-UHFFFAOYSA-N 4-hydroxy-2-methylidenebutanoic acid Chemical compound OCCC(=C)C(O)=O NJMYQRVWBCSLEU-UHFFFAOYSA-N 0.000 description 1
- RTUYNYSPUHQITK-UHFFFAOYSA-N 4-methylbenzoyl azide Chemical compound CC1=CC=C(C(=O)N=[N+]=[N-])C=C1 RTUYNYSPUHQITK-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 238000000018 DNA microarray Methods 0.000 description 1
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- BXEFQPCKQSTMKA-UHFFFAOYSA-N OC(=O)C=[N+]=[N-] Chemical compound OC(=O)C=[N+]=[N-] BXEFQPCKQSTMKA-UHFFFAOYSA-N 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004721 Polyphenylene oxide Chemical group 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- ITLHXEGAYQFOHJ-UHFFFAOYSA-N [diazo(phenyl)methyl]benzene Chemical compound C=1C=CC=CC=1C(=[N+]=[N-])C1=CC=CC=C1 ITLHXEGAYQFOHJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000011354 acetal resin Substances 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 238000012644 addition polymerization Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 150000004982 aromatic amines Chemical class 0.000 description 1
- 238000003491 array Methods 0.000 description 1
- WXNULMMARANRBV-UHFFFAOYSA-N azidoethane formic acid Chemical compound OC=O.CCN=[N+]=[N-] WXNULMMARANRBV-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 1
- 150000008366 benzophenones Chemical class 0.000 description 1
- PJHUABJTDFXYRQ-UHFFFAOYSA-N benzoyl azide Chemical compound [N-]=[N+]=NC(=O)C1=CC=CC=C1 PJHUABJTDFXYRQ-UHFFFAOYSA-N 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- JRZBPELLUMBLQU-UHFFFAOYSA-N carbonazidic acid Chemical compound OC(=O)N=[N+]=[N-] JRZBPELLUMBLQU-UHFFFAOYSA-N 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000002508 contact lithography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 150000003950 cyclic amides Chemical class 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004845 diazirines Chemical class 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- ZWJPCOALBPMBIC-UHFFFAOYSA-N diphenylketene Chemical compound C=1C=CC=CC=1C(=C=O)C1=CC=CC=C1 ZWJPCOALBPMBIC-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000005670 electromagnetic radiation Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
- 229920001903 high density polyethylene Polymers 0.000 description 1
- 239000004700 high-density polyethylene Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000005660 hydrophilic surface Effects 0.000 description 1
- 230000005661 hydrophobic surface Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229920001684 low density polyethylene Polymers 0.000 description 1
- 239000004702 low-density polyethylene Substances 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- DCUFMVPCXCSVNP-UHFFFAOYSA-N methacrylic anhydride Chemical compound CC(=C)C(=O)OC(=O)C(C)=C DCUFMVPCXCSVNP-UHFFFAOYSA-N 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- XHIRWEVPYCTARV-UHFFFAOYSA-N n-(3-aminopropyl)-2-methylprop-2-enamide;hydrochloride Chemical compound Cl.CC(=C)C(=O)NCCCN XHIRWEVPYCTARV-UHFFFAOYSA-N 0.000 description 1
- LNJYHYJGJOCYCH-UHFFFAOYSA-N n-(3-isothiocyanatopropyl)-2-methylprop-2-enamide Chemical compound CC(=C)C(=O)NCCCN=C=S LNJYHYJGJOCYCH-UHFFFAOYSA-N 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- CTRLRINCMYICJO-UHFFFAOYSA-N phenyl azide Chemical compound [N-]=[N+]=NC1=CC=CC=C1 CTRLRINCMYICJO-UHFFFAOYSA-N 0.000 description 1
- 125000006187 phenyl benzyl group Chemical group 0.000 description 1
- CPGRMGOILBSUQC-UHFFFAOYSA-N phosphoryl azide Chemical compound [N-]=[N+]=NP(=O)(N=[N+]=[N-])N=[N+]=[N-] CPGRMGOILBSUQC-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920000768 polyamine Chemical group 0.000 description 1
- 238000012643 polycondensation polymerization Methods 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005597 polymer membrane Polymers 0.000 description 1
- 238000001955 polymer synthesis method Methods 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000000197 pyrolysis Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- HSVFKFNNMLUVEY-UHFFFAOYSA-N sulfuryl diazide Chemical class [N-]=[N+]=NS(=O)(=O)N=[N+]=[N-] HSVFKFNNMLUVEY-UHFFFAOYSA-N 0.000 description 1
- 238000006557 surface reaction Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- UXWVQHXKKOGTSY-UHFFFAOYSA-N tert-butyl phenyl carbonate Chemical compound CC(C)(C)OC(=O)OC1=CC=CC=C1 UXWVQHXKKOGTSY-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- NONOKGVFTBWRLD-UHFFFAOYSA-N thioisocyanate group Chemical group S(N=C=O)N=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54353—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals with ligand attached to the carrier via a chemical coupling agent
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00351—Means for dispensing and evacuation of reagents
- B01J2219/00387—Applications using probes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00608—DNA chips
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00623—Immobilisation or binding
- B01J2219/00626—Covalent
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00632—Introduction of reactive groups to the surface
- B01J2219/00637—Introduction of reactive groups to the surface by coating it with another layer
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2800/00—Copolymer characterised by the proportions of the comonomers expressed
- C08F2800/10—Copolymer characterised by the proportions of the comonomers expressed as molar percentages
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F2800/00—Copolymer characterised by the proportions of the comonomers expressed
- C08F2800/20—Copolymer characterised by the proportions of the comonomers expressed as weight or mass percentages
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
- C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/31504—Composite [nonstructural laminate]
- Y10T428/31855—Of addition polymer from unsaturated monomers
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Food Science & Technology (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Genetics & Genomics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
- Laminated Bodies (AREA)
- Peptides Or Proteins (AREA)
- Paints Or Removers (AREA)
Description
本発明は、例えば、生体分子、例えば核酸及びタンパク質を固定するために用いることができる方法、試薬及び基材に関する。1実施態様では、本発明は、本発明に従うポリマーでコーティングされた表面に関する。1実施態様では、本発明は、表面に分子を高密度で熱化学的及び/又は光化学的に結合する方法に関する。
デオキシリボ核酸(DNA)の基材への固定は、DNA型アッセイ系の開発において及びDNA解析用のマイクロ加工アレイの開発を含む他の目的のために重要な局面となっている。
固定のための基材は、マイクロウェルプレート、試験管、ビーズ、顕微鏡スライド、シリコン・ウエハー又は膜を含む。
本発明は、例えば、生体分子例えば核酸及びタンパク質を固定するために用いられる方法、組成物及び基材に関する。本発明は、第一アミド以外の非荷電極性部分を含有するモノマー(複数)の相当量を含むポリマー例えば、N-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド又はそれらの混合物、を含む又は採用することができる。
定義
本明細書で用いる語句「第一アミド」とは、式-CONH2によって表されるアミド部分を言う。第一アミドは無置換アミドとも言われる。それは、アミドの窒素原子上の置換を含まない。それは、アミドの窒素原子に結合した2つの水素原子を含む。
本発明は、例えば、生体分子例えば核酸及びタンパク質を固定するために用いることができる方法、試薬及び基材に関する。本発明の方法、試薬及び基材は、第一アミド以外の非荷電極性部分を含むモノマー(複数)の相当量を含むポリマーを含む。1実施態様では、本ポリマーは、小スポットサイズを有利に提供し及び/又は表面上にスポットされる物質の大きな接触角を有利に提供する基材上で採用することができる。本発明を限定するものではないが、1実施態様では、本ポリマーは、より高いスポット密度を提供することができ、同時に、液相反応速度論を与える水溶性環境において親水性を維持することができる。
本ポリマーは、合成ポリマー、例えば付加、縮合又はフリーラジカルポリマー化から得られるコポリマーでよい。本発明に従うポリマーは、1以上の反応性基、例えば熱化学的反応性、光化学的反応性等の反応性基、又はそれらの混合物を有する、1以上のモノマーを含んでもよい。好適な追加のモノマー及び反応性基は、米国特許第5,858,653号及び同6,465,178号、及び米国特許出願第20030113792(シリアル番号09/521,545号)に記載されている。これらは参考文献として本明細書に組み込まれている。
1実施態様では、本発明は、生体分子例えば核酸を固定するために好適な表面を提供することができる。生体分子の固定は、反応性基、例えばポリマーの熱化学的反応性基を採用することができる。例えば、コーティングされる材料表面は、1以上の熱化学的反応性基を含むことができる。これは、1以上の熱化学的反応性基を含む本ポリマーの実施態様を固定するために使用することができる。好適な熱化学的反応性基は、活性化エステル(例えばNOS)、エポキシド、アズラクトン、活性化ヒドロキシル及びマレイミド基を含む。
4-ベンゾイル安息香酸(BBA) 1.0 kg (4.42 moles)を、リフラックスコンデンサー及びオーバーヘッドスターラーを備えた乾燥5リットルフラスコに加えた後、645 ml (8.84 moles)の塩化チオニル及び725 mlのトルエンを加えた。次いで、ジメチルホルムアミド 3.5 mlを加え、混合物を4時間リフラックス温度で加熱した。冷却後、溶媒を減圧下で留去し、残渣の塩化チオニルを3 x 500 mlのトルエンを用いて3回の濃縮により除いた。生成物を1:4のトルエン:ヘキサンから再結晶し、真空オーブンで乾燥後、988 g (収率91 %)を得た。生成物の融点は92〜94℃であった。核磁気共鳴(NMR)分析(1H NMR(CDCl3))は、所望の生成物と一致した:芳香族プロトン7.20-8.25 (m, 9H)。全ての化学シフト値は、テトラメチルシラン内部標準からppmでダウンフィールドした。最終化合物は、化合物IIIの合成に使用するモノマーの調製の使用のために保存した。
1,3-ジアミノプロパン 1910 g (25.77 moles)の1000 ml CH2Cl2溶液を、12リットルモートンフラスコに加え、氷浴で冷却した。次いで、t-ブチルフェニルカーボネート1000 g (5.15 moles)の250 ml CH2C12溶液を滴下速度で加え、反応温度を15℃未満に保持した。添加後、混合物を室温まで暖め、2時間攪拌した。反応混合物を900 mlのCH2C12及び500 gの氷で希釈し、2500 mlの2.2 N NaOHをゆっくりと加えた。溶液が塩基性になったのを確認するために試験した後、生成物を分液漏斗に移し、有機層を除き、抽出物#1として取っておいた。水層を次いで、3 x 1250 mlのCH2C12で抽出し、各抽出物を別分画として取っておいた。次いで、4つの有機抽出物を分画#1〜分画#4まで、連続的に、一回1250 mlの0.6 N NaOHで洗浄した。この洗浄操作を1250 mlの0.6 N NaOHで二回繰り返した。次に、有機抽出物を併せ、Na2SO4で乾燥した。濾過及び一定の重量までの溶媒の濃縮により、825 gのN-モノ-t-BOC-1,3-ジアミノプロパンを得た。これは更に精製することなく使用した。
実施例2に記載の一般的方法に従って調製し化合物II 120 g (0.672 moles)を、オーバーヘッドスターラーを付けた乾燥リットル3口丸底フラスコに加えた。フェノチアジン 23〜25 mgをインヒビターとして加えた後、800 mlのクロロホルムを加えた。懸濁液を氷浴で10℃未満に冷却し、実施例1に記載の一般的方法に従って調製した172.5 g (0.705 moles)の化合物Iを固体で加えた。トリエチルアミン 207 ml (1.485 moles)の50 mlクロロホルムを1〜1.5時間かけて滴下した。氷浴を除き、周囲温度で2.5時間攪拌した。次いで、生成物を600 mlの0.3 N HCl及び2 x 300 mlの0.07 N HCIで洗浄した。硫酸ナトリウムで乾燥後、クロロホルムを減圧下で除き、そして、ポリマー化を防ぐために各再結晶化に23〜25 mgのフェノチアジンを用いて、生成物を4:1のトルエン:クロロホルムから2回再結晶した。化合物IIIの典型的収率は90 %であり、融点は147〜151℃であった。NMR分光計による分析は、所望の生成物と一致した:1H NMR (CDC13) 芳香族プロトン 7.20-7 95 (m,9H)、アミドNH 6.55 (broad t, 1H)、ビニルプロトン 5.65, 5.25(m, 2H)、アミドNに隣接するメチレン 3.20-3.60 (m, 4H)、メチル 1.95 (s, 3H)、及び残メチレン 1.50-2.00 (m, 2H)。最終化合物を例えば実施例5及び6に記載の光活性ポリマーの合成に使用するために保存した。
官能基化モノマーを以下の方法で調製し、実施例5及び6に記載のように使用し、ポリマー骨格に活性エステル基を導入した。オーバーへッドスターラー及び乾燥チューブを付けた3口の3リットルフラスコ中で、6-アミノヘキサン酸 100 g (0.762 moles)を300 mlの酢酸に溶解した。無水マレイン酸 78.5 g (0.801 moles)を200mlの酢酸に溶解し、6-アミノへキサン酸溶液に加えた。沸騰水浴で加熱しながら混合物を1時間攪拌し、白色固体を得た。室温で終夜冷却した後で、固体を濾過によって回収し、2 x 50 mlのヘキサンで洗浄した。乾燥後、(Z)-4-オキソ-5-アザウンデク-2-エンジオイックアシッドの典型的収率は158〜165 g (90〜95%)であり、融点は160〜165℃であった。NMR分光計による分析は所望の生成物と一致した:1H NMR (DMSO-d6) アミドプロトン 8.65-9.05 (m, 1H)、ビニルプロトン 6.10, 6.30 (d, 2H)、窒素に隣接するメチレン 2.85-3.25 (m, 2H)、カルボニルに隣接するメチレン 2.15 (t, 2H)、及び残メチレン 1.00-1.75 (m, 6H)。
光活性コポリマーを以下の方法により調製した。DMA41.46 g(416 mmol)、実施例3に記載の一般的方法に従って調製した化合物III 1.56 g(4.5mmol)、実施例4に記載の一般的方法に従って調製した化合物IV 6.88 g(22.3 mmol)及びアゾビス(2-メチル-ブチロニトリル)(Vazo-67)1.4 g(7.3 mmol)を200 mlのテトラヒドロフラン(THF)に溶解した。THF溶液を不活性雰囲気下で、Vazo 67 0.34 g(1.8 mmol)のTHF(50 ml)の第二攪拌リフラックス溶液に1時間に渡って加えた。THF溶液の激しく攪拌したヘキサン(2500 ml)へのゆっくりした添加により、ポリマーを単離した。沈殿したポリマー生成物を濾過により単離し、フィルタケーキを200 mlのヘキサンで洗浄した。生成物を30℃で減圧下に乾燥し、51.7 gの白色固体を得た。
光活性コポリマーを以下の方法で調製した。DMA 38.65 g (390 mmole);実施例3に記載の一般的方法に従って調製した化合物III 1.5 g (4.3 mmol); 実施例4に記載の一般的方法に従って調製した化合物IV 9.9 g (32.1 mmol); 及びベンゾイルペルオキシド 3.1 g (13.0 mmol)をTHF (200 ml)に溶解した。THF溶液を不活性雰囲気下で、1.9 g(13.0 mmol)のN,N-ジエチルアニリンを含むTHF(50 ml)の第二攪拌リフラックス溶液に1時間に渡って加えた。この溶液を不活性ガス雰囲気下で室温で終夜攪拌した。THF溶液の激しく攪拌したヘキサン(2500 ml)へのゆっくりした添加により、ポリマーを単離した。沈殿したポリマー生成物を濾過により単離し、フィルタケーキを200 mlのヘキサンで洗浄した。生成物を30℃で減圧下に乾燥し、43 gのグレイ固体を得た。
N-デシルジメチルクロロシラン及びp-トリルジメチルクロロシラン(United Chemical Technologies, Bristol, Pennsylvania)の各1 %アセトンの混合物中に1分間浸漬することにより、ソーダ石灰ガラススライド(Erie Scientific, Portsmouth, NH)をシランで処理した。風乾後、スライドを最小30分間、110℃のオーブンで養生した。スライドを次いで、アセトンで洗浄し、脱イオン(DI)水中に浸漬した。最後に、スライドを更に110℃で10分間、オーブン中で更に乾燥させた。
オーバーヘッドスターラー、熱電対、乾燥チューブ及び滴下漏斗を付けた500 ml丸底フラスコ中に、APMA-HCl (20.0 g, 112 mmole; 化合物II)及びクロロホルム(100 ml; CHCl3)を入れた。次いで、二硫化炭素(9.84 g [7.46 ml], 19.2 mmole; CS2)を約5分で加えた後、トリエチルアミン(11.32 g [15.6 ml], 111.8 mmole)を加えた。反応を氷浴で3〜8℃に冷却した。この冷溶液に、ジシクロヘキシルカルボジイミド(25.8 g, 125.0 mmole ; DCC)のCHC13 (40 ml)溶液を滴下漏斗を使って30分かけて加えた。添加が完了した後、反応を1時間氷浴中で攪拌した。次いで、反応を終夜室温で攪拌した。溶媒をエア抜きしながら、回転エバポレータで除いた。75.6 g残渣を、直径76.2 mm (3インチ)、長さ215.9 mm (8.5インチ)の長いシリカカラムを用い、アセトン/クロロホルム-4/96〜6/94で溶出し、2回フラッシュ精製した。各カラムから92〜50 ml分画を集めた。
20 mlのバイアルに、APMA-NCS (化合物VI) 1.93 g, 10.5 mmole; (2,2-ジメトキシエチル)アミン 1.06 g, 10.0 mmole; 及びクロロホルム7 mlを入れた。反応は室温で終夜攪拌した。TLCは、出発物質の存在を示した。反応は50℃で4時間加熱した。反応はほとんど終了し、50℃で終夜攪拌した。溶媒を濃縮し、3.07 gの白色固体を得た。粗生成物を、直径41.3 mm (15/8)で152 mm (6インチ)長のシリカゲルカラムでフラッシュ精製した。カラムを3Lのアセトン/クロロホルム-30/70で、33 ml分画で溶出した。分画26〜78を併せ、濃縮し、2.73 g (理論値94 %)化合物VIIを得た。400 MHz NMR分光計による分析は、所望のジメトキシエチル-APMAに一致した:1H NMR(CDCl3) アミドプロトン 7.23, 7.02及び6.5 (broads, 3H); ビニルプロトン 5.81 (s, 1H)及び5.37 (s, 1H); メチンプロトン 4.47 (t, 1H); メチレンプロトン 3.7 (m, 2H), 3.62 (m, 2H)及び3.36 (m, 2H); メトキシプロトン 3.42 (s, 6H); メチルプロトン 1.99 (m, 3H); 及び中央のメチレン 1.75 (m, 2H)。化合物VIIは、比較化合物XII及び化合物XIIIを調製するために使用した。
光活性コポリマーは以下の方法で調製した。アクリルアミド 0.42 g (5.92 mmol)、実施例3に記載の一般的方法に従って調製した化合物III 0.016 g (0.046 mmol)、化合物VI 0.064 g (0.347 mmol)及びVazo-67 0.014 g (0.073 mmol)を5.5 mlのテトラヒドロフラン(THF)に溶解した。THF溶液をヘリウムで4分間噴霧し、次いで、反応溶液を窒素でシールし、50〜55℃で終夜オーブン内に置いた。ポリマーを濾過により単離した。固体を2 x 5 mlのTHFで洗浄した。生成物を30℃で減圧下に乾燥し、0.44 gの白色固体(比較化合物VIII)を得た。上記と同様な方法を使用して、以下の表4に示す比較化合物XIIを調製した。
光活性コポリマーを以下の方法で調製した。アクリルアミド 14.1 g (199mmol)、実施例3に記載の一般的方法に従い調製した化合物III 0.829 g (2.37 mmol)、GMA 5.04 g (35.5 mmol)及びVazo-67 0.43 g (2.24 mmol)を200 mlのテトラヒドロフラン(THF)に溶解した。THF溶液を、不活性雰囲気下で1時間かけて、Vazo-67 0.116g (0.60 mmol)のTHF (50 ml)の第二攪拌リフラックス溶液に加えた。溶液を不活性雰囲気下で攪拌しながら4時間リフラックスした。ポリマーを濾過により単離した。固体を2 x 80 mlのTHFで洗浄した。生成物を30℃で減圧下に乾燥し、19.6 gの白色固体(比較化合物IX)を得た。
光活性コポリマーを以下の方法で調製した。DMA 7.70 g (77.7mmol)、実施例3に記載の一般的方法に従って調製した化合物III 0.324 g (0.925 mmol)、GMA (Sigma, St. Louis, MO) 1.97 g (13.9 mmol)、Vazo-67 0.189 g (0.983 mmol)を68. mlのTHFに溶解した。THF溶液をヘリウムで4分間噴霧し、次いで、反応溶液を窒素でシールし、50〜55℃で終夜オーブン内に置いた。THF溶液を激しく攪拌したジエチルエーテル(500 ml)にゆっくりと添加することにより、ポリマーを濾過により単離した。沈殿ポリマー生成物を濾過により単離し、フィルタケーキを2 x 50 mlのエーテルで洗浄した。生成物を30℃で減圧で乾燥し、9.6 gの白色固体(化合物X)を得た。上記と同様の方法を用いて、以下の表4及び5に示す、化合物XI、化合物XIII及び化合物XIV(アクリロイルモルホリンはSigma Aldrich, St. Louis, MOから購入可能)を調製した。
N-デシルジメチルクロロシラン及びp-トリルジメチルクロロシラン(United Chemical Technologies, Bristol, Pennsylvania)の各1 %アセトンの混合物中に1分間浸漬することにより、ソーダ石灰ガラススライド(Erie Scientific, Portsmouth, NH)をシランで処理した。風乾後、スライドを最小30分間、110℃のオーブンで養生した。スライドを次いで、アセトンで洗浄し、DI水中に浸漬した。最後に、スライドを更に110℃で10分間、オーブン中で更に乾燥させた。
N-デシルジメチルクロロシラン及びp-トリルジメチルクロロシラン(United Chemical Technologies, Bristol, Pennsylvania)の各1 %アセトンの混合物中に1分間浸漬することにより、ソーダ石灰ガラススライド(Erie Scientific, Portsmouth, NH)をシランで処理した。風乾後、スライドを最小30分間、110℃のオーブンで養生した。スライドを次いで、アセトンで洗浄し、DI水中に浸漬した。最後に、スライドを更に110℃で10分間、オーブン中で更に乾燥させた。
Claims (21)
- 表面及びポリマーを含む基材であって、当該ポリマーは当該表面の少なくとも一部分をコーティングし及び当該表面に結合し、そして
当該ポリマーは、
少なくとも40 mol%のN-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド、又はそれらの混合物;及び、
1以上のペンダント反応性基、ここで1以上のペンダント反応性基は、熱化学的反応性基、光化学的反応性基又はそれらの混合物を含み、当該ポリマーは、1以上の熱化学的反応性基、1以上の光化学的反応性基又はそれらの混合物の残基を介して当該表面に共有結合的に結合され、1以上のペンダント反応性基は生体分子と共有結合を形成するように構成され、1以上の光化学的反応性基は、アセトフェノン、ベンゾフェノン、キノン、アントラキノン、アントロン、アントロンヘテロ環状アナローグ又はそれらの混合物から選ばれる、
を含む、前記基材。 - 前記ポリマーが、N,N-ジメチルアクリルアミド、N,N-ジエチルアクリルアミド、N-イソプロピルアクリルアミド、N-t-ブチルアクリルアミド、N-オクチルアクリルアミド、N-シクロヘキシルアクリルアミド、N-フェニルアクリルアミド、N-ベンジルアクリルアミド、N-(CH20C4H9)アクリルアミド、N-(CH2CH2OH)アクリルアミド、N-(CH20H)アクリルアミド、N-(CH2CH2CH20H)アクリルアミド、N-メチルメタクリルアミド、N-エチルメタクリルアミド、N,N-ジメチルメタクリルアミド、N,N-ジエチルメタクリルアミド、N-アクリロイルモルホリン、N-メタクリロイルモルホリン、N-(CH20C4H9)メタクリルアミド、N-(CH2CH2OH)メタクリルアミド、N-(CH20H)メタクリルアミド又はそれらの混合物を含む、請求項1記載の基材。
- 前記ポリマーが、N,N-ジメチルアクリルアミドを含む、請求項2記載の基材。
- 前記ポリマーが、85〜95 mol%のN-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド又はそれらの混合物を含む、請求項1記載の基材。
- 前記熱化学的反応性基が、NOS、エポキシド、アルデヒド、イソチオシアネート又はそれらの混合物を含む、請求項1記載の基材。
- 前記光化学的反応性基が、光反応性アリールケトンを含み、そして前記生体分子が核酸を含む、請求項1記載の基材。
- 前記基材が活性化スライドを含む、請求項1記載の基材。
- 前記スライドはマイクロアレイを加工するために構成され;
前記生体分子は核酸を含み;そして
前記表面はプラスチック、水素化ケイ素、又は有機ケイ素化合物で予備処理されたガラスもしくはシリコンスライドを含む、請求項7記載の基材。 - 前記スライドが、20ナノリットル以下の量で試料を受けるよう構成される、請求項7記載の基材。
- 前記生体分子がポリペプチド又は核酸を含む、請求項1記載の基材。
- 前記生体分子が核酸を含み、そして、当該核酸がアミン基、スルフヒドリル基又はそれらの混合物を含む、請求項10記載の基材。
- ポリマーを含む組成物であって、当該ポリマーは、
少なくとも40 mol%のN-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド又はそれらの混合物;及び
生体分子上の対応する官能基と共有結合を形成するように構成される1以上のペンダント反応性基、ここで1以上のペンダント反応性基は、熱化学的反応性基、光化学的反応性基又はそれらの混合物を含み、当該ポリマーは、1以上の熱化学的反応性基、1以上の光化学的反応性基又はそれらの混合物の残基を介して当該表面に共有結合的に結合され、1以上の光化学的反応性基は、アセトフェノン、ベンゾフェノン、キノン、アントラキノン、アントロン、アントロンヘテロ環状アナローグ又はそれらの混合物から選ばれる、
を含む、前記組成物。 - 前記ポリマーが、N,N-ジメチルアクリルアミド、N,N-ジエチルアクリルアミド、N-イソプロピルアクリルアミド、N-t-ブチルアクリルアミド、N-オクチルアクリルアミド、N-シクロヘキシルアクリルアミド、N-フェニルアクリルアミド、N-ベンジルアクリルアミド、N-(CH20C4H9)アクリルアミド、N-(CH2CH2OH)アクリルアミド、N-(CH20H)アクリルアミド、N-(CH2CH2CH20H)アクリルアミド、N-メチルメタクリルアミド、N-エチルメタクリルアミド、N,N-ジメチルメタクリルアミド、N,N-ジエチルメタクリルアミド、N-アクリロイルモルホリン、N-メタクリロイルモルホリン、N-(CH20C4H9)メタクリルアミド、N-(CH2CH2OH)メタクリルアミド、N-(CH20H)メタクリルアミド又はそれらの混合物を含む請求項12記載の組成物。
- 前記ポリマーが、N,N-ジメチルアクリルアミドを含む、請求項12記載の組成物。
- 前記ポリマーが、85〜95 mol%のN-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド又はそれらの混合物を含む、請求項12記載の組成物。
- 前記熱化学的反応性基が、NOS、エポキシド、アルデヒド、イソチオシアネート又はそれらの混合物を含む、請求項12記載の組成物。
- 前記光化学的反応性基が、光反応性アリールケトンを含み、そして前記生体分子が核酸を含む、請求項12記載の組成物。
- 前記生体分子が核酸を含み、そして、前記表面が、有機ケイ素化合物で予備処理されたガラス、有機ケイ素化合物で予備処理されたシリコン、水素化ケイ素又はプラスチックを含む、請求項12記載の組成物。
- 基材表面に生体分子を結合する方法であって、
ポリマーを含む組成物を提供するステップ、
ここで、当該ポリマーは、
少なくとも40 mol%のN-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド又はそれらの混合物、及び
生体分子上の対応する官能基と共有結合を形成するように構成される1以上のペンダント反応性基、ここで1以上のペンダント反応性基は、熱化学的反応性基、光化学的反応性基又はそれらの混合物を含み、当該ポリマーは、1以上の熱化学的反応性基、1以上の光化学的反応性基又はそれらの混合物の残基を介して当該表面に共有結合的に結合され、1以上の光化学的反応性基は、アセトフェノン、ベンゾフェノン、キノン、アントラキノン、アントロン、アントロンヘテロ環状アナローグ又はそれらの混合物から選ばれる、
を含み、
当該反応性基と反応する1以上の官能基を含む生体分子を含む溶液を提供するステップ;
当該溶液のアリコートを基材表面に適用するステップ;並びに
生体分子の反応性基と官能基との共有結合を形成するステップ、
を含む、前記方法。 - 支持体表面;
支持体表面に共有結合したポリマー、
ここで、当該ポリマーは、
少なくとも40 mol%のN-置換アクリルアミド、N,N-二置換アクリルアミド、N-置換メタクリルアミド、N,N-二置換メタクリルアミド又はそれらの混合物、及び
1以上のペンダント反応性基、ここで1以上のペンダント反応性基は、熱化学的反応性基、光化学的反応性基又はそれらの混合物を含み、当該ポリマーは、1以上の熱化学的反応性基、1以上の光化学的反応性基又はそれらの混合物の残基を介して当該表面に共有結合的に結合され、1以上の光化学的反応性基は、アセトフェノン、ベンゾフェノン、キノン、アントラキノン、アントロン、アントロンヘテロ環状アナローグ又はそれらの混合物から選ばれる、
を含む;並びに
当該支持体表面上に離れたスポットを形成するために当該ポリマーの1以上のペンダント反応性基に共有結合する生体分子、
を含む、マイクロアレイ。 - 前記スポットが、一般的に円形状であり、20ミクロン〜100ミクロンの直径を有し、そして中心から中心までが40ミクロン〜120ミクロンの間隔で、アレイ上の他のスポットと離れている、請求項20記載のマイクロアレイ。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/677,022 | 2003-10-01 | ||
US10/677,022 US7309593B2 (en) | 2003-10-01 | 2003-10-01 | Attachment of molecules to surfaces |
PCT/US2004/032443 WO2005033158A2 (en) | 2003-10-01 | 2004-09-30 | Attachment of molecules to surfaces |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2007510889A JP2007510889A (ja) | 2007-04-26 |
JP2007510889A5 JP2007510889A5 (ja) | 2007-11-01 |
JP4741499B2 true JP4741499B2 (ja) | 2011-08-03 |
Family
ID=34393654
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2006534165A Active JP4741499B2 (ja) | 2003-10-01 | 2004-09-30 | 表面への分子の結合 |
Country Status (8)
Country | Link |
---|---|
US (3) | US7309593B2 (ja) |
EP (1) | EP1668050B1 (ja) |
JP (1) | JP4741499B2 (ja) |
AT (1) | ATE448258T1 (ja) |
AU (1) | AU2004278408B2 (ja) |
CA (1) | CA2536303C (ja) |
DE (1) | DE602004024095D1 (ja) |
WO (1) | WO2005033158A2 (ja) |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6433154B1 (en) * | 1997-06-12 | 2002-08-13 | Bristol-Myers Squibb Company | Functional receptor/kinase chimera in yeast cells |
CN1830536A (zh) | 2000-05-16 | 2006-09-13 | 明尼苏达大学评议会 | 采用多喷嘴喷射产生大批生产量的颗粒 |
US7247338B2 (en) * | 2001-05-16 | 2007-07-24 | Regents Of The University Of Minnesota | Coating medical devices |
JP4630817B2 (ja) * | 2003-03-31 | 2011-02-09 | 独立行政法人理化学研究所 | 物質固定化剤、それを用いた物質固定化方法及びそれを用いた物質固定化基体 |
US7309593B2 (en) * | 2003-10-01 | 2007-12-18 | Surmodics, Inc. | Attachment of molecules to surfaces |
EP2168975A3 (en) | 2004-05-24 | 2012-01-11 | Genvault Corporation | Method of stably storing biomolecules in recoverable form |
US7935479B2 (en) | 2004-07-19 | 2011-05-03 | Cell Biosciences, Inc. | Methods and devices for analyte detection |
US7846676B2 (en) * | 2004-07-19 | 2010-12-07 | Cell Biosciences, Inc. | Methods and devices for analyte detection |
US7935489B2 (en) * | 2004-07-19 | 2011-05-03 | Cell Biosciences, Inc. | Methods and devices for analyte detection |
EP1872139A2 (en) | 2005-04-09 | 2008-01-02 | Cell Biosciences, Inc. | Automated micro-volume assay system |
US8945361B2 (en) | 2005-09-20 | 2015-02-03 | ProteinSimple | Electrophoresis standards, methods and kits |
US8117902B2 (en) * | 2005-11-03 | 2012-02-21 | University Of Massachusetts | Nanopatterned surfaces and related methods for selective adhesion, sensing and separation |
CN1962155A (zh) * | 2005-11-10 | 2007-05-16 | 鸿富锦精密工业(深圳)有限公司 | 一种二氧化碳激光焊接装置 |
EP2529761B1 (en) * | 2006-01-31 | 2017-06-14 | Nanocopoeia, Inc. | Nanoparticle coating of surfaces |
US7951428B2 (en) * | 2006-01-31 | 2011-05-31 | Regents Of The University Of Minnesota | Electrospray coating of objects |
US9108217B2 (en) | 2006-01-31 | 2015-08-18 | Nanocopoeia, Inc. | Nanoparticle coating of surfaces |
US20080017512A1 (en) * | 2006-07-24 | 2008-01-24 | Bordunov Andrei V | Coatings for capillaries capable of capturing analytes |
US9040816B2 (en) * | 2006-12-08 | 2015-05-26 | Nanocopoeia, Inc. | Methods and apparatus for forming photovoltaic cells using electrospray |
JP5423965B2 (ja) * | 2007-05-30 | 2014-02-19 | Jsr株式会社 | 非特異吸着防止剤 |
WO2009005718A1 (en) * | 2007-06-28 | 2009-01-08 | Surmodics, Inc. | Polypeptide microparticles having sustained release characteristics, methods and uses |
WO2009155612A2 (en) * | 2008-06-20 | 2009-12-23 | Genvault Corporation | Sample collection and storage devices and methods of use thereof |
US8382858B2 (en) | 2008-06-25 | 2013-02-26 | University Of Massachusetts | Nanoparticle-textured surfaces and related methods for selective adhesion, sensing and separation |
WO2010031007A2 (en) * | 2008-09-12 | 2010-03-18 | Genvault Corporation | Matrices and media for storage and stabilization of biomolecules |
WO2010129328A2 (en) | 2009-04-28 | 2010-11-11 | Surmodics, Inc. | Devices and methods for delivery of bioactive agents |
WO2011072199A2 (en) * | 2009-12-10 | 2011-06-16 | Surmodics, Inc. | Water-soluble degradable photo-crosslinker |
US10315987B2 (en) | 2010-12-13 | 2019-06-11 | Surmodics, Inc. | Photo-crosslinker |
US9861814B2 (en) | 2010-12-23 | 2018-01-09 | Medtronic, Inc. | Medical electrical lead having biological surface and methods of making and using same |
AU2012218007B2 (en) | 2011-02-15 | 2015-08-06 | Elanco Us Inc. | Methods for controlling pain in canines using a transdermal solution of fentanyl |
US9757497B2 (en) | 2011-05-20 | 2017-09-12 | Surmodics, Inc. | Delivery of coated hydrophobic active agent particles |
US9861727B2 (en) | 2011-05-20 | 2018-01-09 | Surmodics, Inc. | Delivery of hydrophobic active agent particles |
US10213529B2 (en) | 2011-05-20 | 2019-02-26 | Surmodics, Inc. | Delivery of coated hydrophobic active agent particles |
WO2012177940A2 (en) | 2011-06-24 | 2012-12-27 | The Regents Of The University Of California | Microfluidic devices and methods for separating and detecting constituents in a fluid sample |
SG11201404892UA (en) * | 2012-02-17 | 2014-09-26 | Nvs Technologies Inc | Polymer scaffolds for assay applications |
US9012022B2 (en) | 2012-06-08 | 2015-04-21 | Illumina, Inc. | Polymer coatings |
CN104854152A (zh) * | 2012-10-12 | 2015-08-19 | Nvs技术股份有限公司 | 具有正交反应基团的聚合物及其用途 |
US11246963B2 (en) | 2012-11-05 | 2022-02-15 | Surmodics, Inc. | Compositions and methods for delivery of hydrophobic active agents |
WO2014071387A1 (en) | 2012-11-05 | 2014-05-08 | Surmodics, Inc. | Composition and method for delivery of hydrophobic active agents |
EP2965083B1 (en) | 2013-03-07 | 2019-07-03 | The Regents of The University of California | Electrophoretic separation devices and methods for using the same |
MX2015012204A (es) * | 2013-03-14 | 2016-01-14 | Nvs Technologies Inc | Oxidacion superficial para secuestrar biomoleculas y metodos relacionados. |
BR112017016342B1 (pt) | 2015-01-29 | 2021-05-11 | Surmodics, Inc | revestimento de entrega de fármacos |
US10478546B2 (en) | 2015-09-15 | 2019-11-19 | Surmodics, Inc. | Hemodialysis catheter sleeve |
US10377928B2 (en) | 2015-12-10 | 2019-08-13 | Ppg Industries Ohio, Inc. | Structural adhesive compositions |
US10806904B2 (en) | 2016-03-31 | 2020-10-20 | Surmodics, Inc. | Two-part insertion tool and methods |
US10918835B2 (en) | 2016-03-31 | 2021-02-16 | Surmodics, Inc. | Delivery system for active agent coated balloon |
US20170281914A1 (en) | 2016-03-31 | 2017-10-05 | Surmodics, Inc. | Localized treatment of tissues through transcatheter delivery of active agents |
US10391292B2 (en) | 2016-06-15 | 2019-08-27 | Surmodics, Inc. | Hemostasis sealing device with constriction ring |
CA3036822A1 (en) | 2016-09-16 | 2018-03-22 | Surmodics, Inc. | Lubricious insertion tools for medical devices and methods for using |
US10758719B2 (en) | 2016-12-15 | 2020-09-01 | Surmodics, Inc. | Low-friction sealing devices |
US10898446B2 (en) | 2016-12-20 | 2021-01-26 | Surmodics, Inc. | Delivery of hydrophobic active agents from hydrophilic polyether block amide copolymer surfaces |
TW202203964A (zh) * | 2020-04-17 | 2022-02-01 | 小利蘭史丹佛大學董事會 | 用於生物醫藥調配物之聚合物賦形劑 |
EP4271509A1 (en) | 2020-12-30 | 2023-11-08 | 10X Genomics, Inc. | Molecular arrays and methods for generating and using the arrays |
WO2022147139A1 (en) | 2020-12-30 | 2022-07-07 | 10X Genomics, Inc. | Methods and compositions for light-controlled surface patterning using a polymer |
WO2022147140A1 (en) | 2020-12-30 | 2022-07-07 | 10X Genomics, Inc. | Molecular array generation using photoresist |
US20230338623A1 (en) | 2022-04-25 | 2023-10-26 | Surmodics, Inc. | Medical device coatings with microcrystalline active agents |
WO2024006798A1 (en) | 2022-06-29 | 2024-01-04 | 10X Genomics, Inc. | High definition molecular array feature generation using photoresist |
US20240167077A1 (en) | 2022-06-29 | 2024-05-23 | 10X Genomics, Inc. | Covalent attachment of splint oligonucleotides for molecular array generation using ligation |
US20240060127A1 (en) | 2022-06-29 | 2024-02-22 | 10X Genomics, Inc. | Methods and systems for light-controlled surface patterning using photomasks |
Family Cites Families (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5073484A (en) * | 1982-03-09 | 1991-12-17 | Bio-Metric Systems, Inc. | Quantitative analysis apparatus and method |
US5512329A (en) * | 1982-09-29 | 1996-04-30 | Bsi Corporation | Substrate surface preparation |
US4722906A (en) * | 1982-09-29 | 1988-02-02 | Bio-Metric Systems, Inc. | Binding reagents and methods |
US5002582A (en) * | 1982-09-29 | 1991-03-26 | Bio-Metric Systems, Inc. | Preparation of polymeric surfaces via covalently attaching polymers |
US4973493A (en) * | 1982-09-29 | 1990-11-27 | Bio-Metric Systems, Inc. | Method of improving the biocompatibility of solid surfaces |
US5217492A (en) * | 1982-09-29 | 1993-06-08 | Bio-Metric Systems, Inc. | Biomolecule attachment to hydrophobic surfaces |
US4542102A (en) * | 1983-07-05 | 1985-09-17 | Molecular Diagnostics, Inc. | Coupling of nucleic acids to solid support by photochemical methods |
US4582860A (en) * | 1983-12-15 | 1986-04-15 | Rohm And Haas Company | Oxirane resins for enzyme immobilization |
US4979959A (en) * | 1986-10-17 | 1990-12-25 | Bio-Metric Systems, Inc. | Biocompatible coating for solid surfaces |
WO1991016425A1 (de) | 1990-04-12 | 1991-10-31 | Hans Sigrist | Verfahren zur lichtinduzierten immobilisierung von biomolekülen an chemisch 'inerten' oberflächen |
FR2679255B1 (fr) * | 1991-07-17 | 1993-10-22 | Bio Merieux | Procede d'immobilisation d'un fragment nucleique par fixation passive sur un support solide, support solide ainsi obtenu et son utilisation. |
ATE192487T1 (de) * | 1992-02-13 | 2000-05-15 | Surmodics Inc | Immobilisierung eines chemischen spezies in einer vernetzten matrix |
US5512474A (en) * | 1992-05-29 | 1996-04-30 | Bsi Corporation | Cell culture support containing a cell adhesion factor and a positively-charged molecule |
US5414075A (en) * | 1992-11-06 | 1995-05-09 | Bsi Corporation | Restrained multifunctional reagent for surface modification |
WO1994017447A1 (en) * | 1993-01-21 | 1994-08-04 | The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Chemical functionalization of surfaces |
US5610287A (en) * | 1993-12-06 | 1997-03-11 | Molecular Tool, Inc. | Method for immobilizing nucleic acid molecules |
US5643580A (en) * | 1994-10-17 | 1997-07-01 | Surface Genesis, Inc. | Biocompatible coating, medical device using the same and methods |
US5707818A (en) * | 1994-12-13 | 1998-01-13 | Bsi Corporation | Device and method for simultaneously performing multiple competitive immunoassays |
WO1996037165A1 (en) * | 1995-05-26 | 1996-11-28 | Bsi Corporation | Method and implantable article for promoting endothelialization |
US5783502A (en) * | 1995-06-07 | 1998-07-21 | Bsi Corporation | Virus inactivating coatings |
DE19533682A1 (de) * | 1995-09-12 | 1997-03-13 | Biotronik Mess & Therapieg | Verfahren zum Anlagern und Immobilisieren von Heparin auf anorganischen Substratoberflächen von kardiovaskulären Implantanten |
US5714360A (en) | 1995-11-03 | 1998-02-03 | Bsi Corporation | Photoactivatable water soluble cross-linking agents containing an onium group |
US5942555A (en) * | 1996-03-21 | 1999-08-24 | Surmodics, Inc. | Photoactivatable chain transfer agents and semi-telechelic photoactivatable polymers prepared therefrom |
AU3568897A (en) * | 1996-06-07 | 1998-01-05 | Eos Biotechnology, Inc. | Immobilised linear oligonucleotide arrays |
US5981734A (en) * | 1997-07-17 | 1999-11-09 | University Of Chicago | Methods for immobilizing nucleic acids on a gel substrate |
US5858653A (en) * | 1997-09-30 | 1999-01-12 | Surmodics, Inc. | Reagent and method for attaching target molecules to a surface |
US6465178B2 (en) | 1997-09-30 | 2002-10-15 | Surmodics, Inc. | Target molecule attachment to surfaces |
DE19804518C2 (de) | 1998-02-05 | 2000-10-05 | Roehm Gmbh | Verfahren zur Herstellung von perlförmigen Mischpolymerisaten auf Acrylatbasis, danach hergestellte Trägerpolymermaterialien und deren Verwendung |
US6410044B1 (en) * | 1998-03-19 | 2002-06-25 | Surmodics, Inc. | Crosslinkable macromers |
US6376619B1 (en) | 1998-04-13 | 2002-04-23 | 3M Innovative Properties Company | High density, miniaturized arrays and methods of manufacturing same |
WO1999058716A1 (fr) | 1998-05-08 | 1999-11-18 | Kyowa Medex Co., Ltd. | Procede servant a quantifier une sequence specifique de genes et reactif de quantification |
US6254634B1 (en) * | 1998-06-10 | 2001-07-03 | Surmodics, Inc. | Coating compositions |
JP4560260B2 (ja) * | 1999-07-01 | 2010-10-13 | 旭化成ケミカルズ株式会社 | 低分子量オキシメチレン重合体及びその組成物 |
CA2377739A1 (en) | 1999-07-02 | 2001-01-11 | Symyx Technologies, Inc. | Polymer brushes for immobilizing molecules to a surface or substrate, where the polymers have water-soluble or water-dispersible segments and probes bonded thereto |
US6250044B1 (en) * | 2000-01-13 | 2001-06-26 | Kohler Co. | Shower door bar with recessed grip |
US6410643B1 (en) * | 2000-03-09 | 2002-06-25 | Surmodics, Inc. | Solid phase synthesis method and reagent |
DE60227845D1 (de) | 2002-11-29 | 2008-09-04 | Marcella Chiari | Verfahren zur immobilisierung biologischer moleküle an feste oberflächen |
US7820158B2 (en) | 2003-04-10 | 2010-10-26 | Surmodics, Inc. | Ligand-coupled initiator polymers and methods of use |
US7309593B2 (en) * | 2003-10-01 | 2007-12-18 | Surmodics, Inc. | Attachment of molecules to surfaces |
-
2003
- 2003-10-01 US US10/677,022 patent/US7309593B2/en active Active
-
2004
- 2004-09-30 DE DE200460024095 patent/DE602004024095D1/de active Active
- 2004-09-30 AU AU2004278408A patent/AU2004278408B2/en active Active
- 2004-09-30 EP EP04789464A patent/EP1668050B1/en active Active
- 2004-09-30 AT AT04789464T patent/ATE448258T1/de not_active IP Right Cessation
- 2004-09-30 WO PCT/US2004/032443 patent/WO2005033158A2/en active Application Filing
- 2004-09-30 JP JP2006534165A patent/JP4741499B2/ja active Active
- 2004-09-30 CA CA 2536303 patent/CA2536303C/en active Active
-
2007
- 2007-09-14 US US11/901,033 patent/US7829317B2/en not_active Expired - Lifetime
-
2010
- 2010-09-09 US US12/878,236 patent/US8129159B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
CA2536303A1 (en) | 2005-04-14 |
AU2004278408A1 (en) | 2005-04-14 |
US8129159B2 (en) | 2012-03-06 |
CA2536303C (en) | 2014-11-18 |
JP2007510889A (ja) | 2007-04-26 |
US20110009292A1 (en) | 2011-01-13 |
EP1668050B1 (en) | 2009-11-11 |
WO2005033158A2 (en) | 2005-04-14 |
US20050074478A1 (en) | 2005-04-07 |
US7309593B2 (en) | 2007-12-18 |
US7829317B2 (en) | 2010-11-09 |
DE602004024095D1 (de) | 2009-12-24 |
US20090042742A1 (en) | 2009-02-12 |
WO2005033158A3 (en) | 2005-06-02 |
EP1668050A2 (en) | 2006-06-14 |
AU2004278408B2 (en) | 2009-12-03 |
ATE448258T1 (de) | 2009-11-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4741499B2 (ja) | 表面への分子の結合 | |
JP5005869B2 (ja) | エポキシドポリマーの表面 | |
JP4768130B2 (ja) | 表面への標的分子の付着 | |
US5919523A (en) | Derivatization of solid supports and methods for oligomer synthesis | |
US20030082604A1 (en) | High density arrays | |
US20030148360A1 (en) | Replicable probe array | |
EP1349956A2 (en) | Replicable probe array | |
MXPA01006935A (es) | Union de moleculas de blanco a las superficies |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070911 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070911 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20091201 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20100226 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20100305 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100531 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100928 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20101227 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20110107 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20110405 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20110506 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 4741499 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20140513 Year of fee payment: 3 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |