JP4967104B2 - バイオセンサーチップ - Google Patents
バイオセンサーチップ Download PDFInfo
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- JP4967104B2 JP4967104B2 JP2007089850A JP2007089850A JP4967104B2 JP 4967104 B2 JP4967104 B2 JP 4967104B2 JP 2007089850 A JP2007089850 A JP 2007089850A JP 2007089850 A JP2007089850 A JP 2007089850A JP 4967104 B2 JP4967104 B2 JP 4967104B2
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- biosensor chip
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- 229920000642 polymer Polymers 0.000 claims description 60
- 229920006254 polymer film Polymers 0.000 claims description 48
- 230000002209 hydrophobic effect Effects 0.000 claims description 37
- 229910052751 metal Inorganic materials 0.000 claims description 31
- 239000002184 metal Substances 0.000 claims description 31
- 239000000758 substrate Substances 0.000 claims description 31
- 239000003960 organic solvent Substances 0.000 claims description 28
- 125000000524 functional group Chemical group 0.000 claims description 25
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims description 22
- 229920001600 hydrophobic polymer Polymers 0.000 claims description 21
- 230000003647 oxidation Effects 0.000 claims description 16
- 238000007254 oxidation reaction Methods 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 229920005597 polymer membrane Polymers 0.000 claims description 11
- 239000006087 Silane Coupling Agent Substances 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 238000004381 surface treatment Methods 0.000 claims description 9
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 claims description 7
- 238000005266 casting Methods 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 3
- 239000010408 film Substances 0.000 description 45
- 239000000243 solution Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000011148 porous material Substances 0.000 description 20
- 238000000034 method Methods 0.000 description 14
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 11
- 229910052737 gold Inorganic materials 0.000 description 11
- 239000010931 gold Substances 0.000 description 11
- -1 polyethylene terephthalate Polymers 0.000 description 11
- 239000013543 active substance Substances 0.000 description 10
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 description 10
- 239000007789 gas Substances 0.000 description 9
- 238000006068 polycondensation reaction Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000010409 thin film Substances 0.000 description 7
- 150000003573 thiols Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000001338 self-assembly Methods 0.000 description 5
- 230000035945 sensitivity Effects 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000006059 cover glass Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
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- IBRQUKZZBXZOBA-UHFFFAOYSA-N 1-chloro-3-(3-chlorophenyl)sulfonylbenzene Chemical compound ClC1=CC=CC(S(=O)(=O)C=2C=C(Cl)C=CC=2)=C1 IBRQUKZZBXZOBA-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
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- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 2
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- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 2
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- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- ARCGXLSVLAOJQL-UHFFFAOYSA-N trimellitic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C(C(O)=O)=C1 ARCGXLSVLAOJQL-UHFFFAOYSA-N 0.000 description 2
- GWOLZNVIRIHJHB-UHFFFAOYSA-N 11-mercaptoundecanoic acid Chemical compound OC(=O)CCCCCCCCCCS GWOLZNVIRIHJHB-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-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
- MXPYJVUYLVNEBB-UHFFFAOYSA-N 2-[2-(2-carboxybenzoyl)oxycarbonylbenzoyl]oxycarbonylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)OC(=O)C1=CC=CC=C1C(=O)OC(=O)C1=CC=CC=C1C(O)=O MXPYJVUYLVNEBB-UHFFFAOYSA-N 0.000 description 1
- UUEWCQRISZBELL-UHFFFAOYSA-N 3-trimethoxysilylpropane-1-thiol Chemical compound CO[Si](OC)(OC)CCCS UUEWCQRISZBELL-UHFFFAOYSA-N 0.000 description 1
- SAQWCPXBLNGTCC-UHFFFAOYSA-N 6-(prop-2-enoylamino)hexanoic acid Chemical compound OC(=O)CCCCCNC(=O)C=C SAQWCPXBLNGTCC-UHFFFAOYSA-N 0.000 description 1
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
- TZZSWAXSIGWXOS-UHFFFAOYSA-N CC(NCCCCC(O)=O)=O Chemical compound CC(NCCCCC(O)=O)=O TZZSWAXSIGWXOS-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920000089 Cyclic olefin copolymer Polymers 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 238000012696 Interfacial polycondensation Methods 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 239000004696 Poly ether ether ketone Substances 0.000 description 1
- 229920002319 Poly(methyl acrylate) Polymers 0.000 description 1
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- 229920001328 Polyvinylidene chloride Polymers 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
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- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
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- 229920005603 alternating copolymer Polymers 0.000 description 1
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- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
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- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
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- IKJFYINYNJYDTA-UHFFFAOYSA-N dibenzothiophene sulfone Chemical group C1=CC=C2S(=O)(=O)C3=CC=CC=C3C2=C1 IKJFYINYNJYDTA-UHFFFAOYSA-N 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
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- ANSXAPJVJOKRDJ-UHFFFAOYSA-N furo[3,4-f][2]benzofuran-1,3,5,7-tetrone Chemical compound C1=C2C(=O)OC(=O)C2=CC2=C1C(=O)OC2=O ANSXAPJVJOKRDJ-UHFFFAOYSA-N 0.000 description 1
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- XQPVIMDDIXCFFS-UHFFFAOYSA-N n-dodecylprop-2-enamide Chemical compound CCCCCCCCCCCCNC(=O)C=C XQPVIMDDIXCFFS-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
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Description
まず、基板として16mm×16mmのカバーグラスを用い、この上に厚さが45nmの金薄膜を設けた。そして、このように金薄膜を有する基板を、濃度が1.0%となる3−メルカプト−プロピル−トリメトキシシランの1%酢酸水溶液に60分間浸漬し、金薄膜をカップリング処理した。
実施例と同様に、厚さが45nmの金薄膜を有する、16mm×16mmのカバーグラスを、濃度1mmol/Lとなる10−カルボキシ−1−デカンチオールのエタノール溶液に24時間浸漬し、その後エタノールで洗浄して、アルカンチオールの単分子層を作製した。
以上のように作製した実施例、比較例のバイオセンサーチップをSPR測定装置のプリズム上に固定して、専用の測定マウントをセットしてフロー式で次の操作を行った。
この結果、実施例の微細多孔質高分子膜を設けたバイオセンサーチップを用いたSPRセンサーの出力としての共鳴角度の変化は、従来技術にかかる比較例のアルカンチオールを用いたバイオセンサーチップ基材のものに比べて優れていることがわかった。
12 金属膜
13 微細多孔質高分子膜
Claims (13)
- 基板と、この表面に設けられた金属膜と、この金属膜上にチオール系シランカップリング剤を介して固定され且つ表面に親水性の官能基を有する微細多孔質高分子膜とを具備し、前記微細多孔質高分子膜が、両親媒性高分子を含む疎水性有機溶媒溶液を相対湿度50〜95%の高湿度条件下でキャスティングすることにより形成された膜であることを特徴とするバイオセンサーチップ。
- 請求項1に記載のバイオセンサーチップにおいて、前記疎水性有機溶媒溶液が疎水性高分子を含むことを特徴とするバイオセンサーチップ。
- 請求項2に記載のバイオセンサーチップにおいて、前記疎水性有機溶媒溶液が、疎水性高分子と両親媒性高分子とを質量比50:50〜99:1の割合で含むものであることを特徴とするバイオセンサーチップ。
- 請求項1〜3の何れかに記載のバイオセンサーチップにおいて、前記親水性の官能基が、前記両親媒性高分子の親水性部位に起因するものを含むことを特徴とするバイオセンサーチップ。
- 請求項1〜4の何れかに記載のバイオセンサーチップにおいて、前記微細多孔質高分子膜は、プラズマ酸化処理又はオゾン酸化処理による表面処理が施されたものであることを特徴とするバイオセンサーチップ。
- 請求項5に記載のバイオセンサーチップにおいて、前記親水性の官能基が、前記表面処理により形成されたものを含むことを特徴とするバイオセンサーチップ。
- 請求項1〜6の何れかに記載のバイオセンサーチップにおいて、前記親水性の官能基がカルボキシル基であることを特徴とするバイオセンサーチップ。
- 請求項1〜7の何れかに記載のバイオセンサーチップにおいて、表面プラズモン共鳴バイオセンサーに使用されるものであることを特徴とするバイオセンサーチップ。
- 請求項1〜8の何れかに記載のバイオセンサーチップにおいて、前記微細多孔質高分子膜の表面が化学修飾されていることを特徴とするバイオセンサーチップ。
- 基板の表面に金属膜を設ける工程と、この金属膜の表面をチオール系シランカップリング剤で処理する工程と、両親媒性高分子を含む疎水性有機溶媒溶液を前記金属膜上に相対湿度50〜95%の高湿度条件下でキャスティングすることにより微細多孔質高分子膜を形成する工程とを具備することを特徴とするバイオセンサーチップの製造方法。
- 請求項10に記載のバイオセンサーチップの製造方法において、前記疎水性有機溶媒溶液が疎水性高分子を含むことを特徴とするバイオセンサーチップの製造方法。
- 請求項11に記載のバイオセンサーチップの製造方法において、前記疎水性有機溶媒溶液が、疎水性高分子と両親媒性高分子とを質量比50:50〜99:1の割合で含むものであることを特徴とするバイオセンサーチップの製造方法。
- 請求項10〜12の何れかに記載のバイオセンサーチップの製造方法において、前記微細多孔質高分子膜の表面に、プラズマ酸化処理又はオゾン酸化処理による表面処理を施すことを特徴とするバイオセンサーチップの製造方法。
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