JP4568175B2 - バイオセンサー及び生理活性物質の固定化方法 - Google Patents
バイオセンサー及び生理活性物質の固定化方法 Download PDFInfo
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- JP4568175B2 JP4568175B2 JP2005163456A JP2005163456A JP4568175B2 JP 4568175 B2 JP4568175 B2 JP 4568175B2 JP 2005163456 A JP2005163456 A JP 2005163456A JP 2005163456 A JP2005163456 A JP 2005163456A JP 4568175 B2 JP4568175 B2 JP 4568175B2
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Description
好ましくは、カチオン性基はオニウム又はその前駆体である。
好ましくは、金属は金、銀、銅、白金またはアルミニウムのいずれかである。
好ましくは、本発明のバイオセンサーは、非電気化学的検出に使用される。
好ましくは、本発明のバイオセンサーは、表面プラズモン共鳴分析に使用される。
好ましくは、生理活性物質と相互作用する物質を表面プラズモン共鳴分析により検出または測定する。
核酸としては、測定の対象とする核酸と相補的にハイブリダイズするものを使用することができる。核酸は、DNA(cDNAを含む)、RNAのいずれも使用できる。DNAの種類は特に限定されず、天然由来のDNA、遺伝子組換え技術により調製した組換えDNA、又は化学合成DNAの何れでもよい。
低分子有機化合物としては通常の有機化学合成の方法で合成することができる任意の化合物が挙げられる。
免疫グロブリン結合性蛋白質としては、例えばプロテインAあるいはプロテインG、リウマチ因子(RF)等を使用することができる。
糖結合性蛋白質としては、レクチン等が挙げられる。
脂肪酸あるいは脂肪酸エステルとしては、ステアリン酸、アラキジン酸、ベヘン酸、ステアリン酸エチル、アラキジン酸エチル、ベヘン酸エチル等が挙げられる。
以下の実施例により本発明を更に具体的に説明するが、本発明の範囲はこれらの実施例に限定されるものではない。
攪拌機、温度計、および塩化カルシウム管を付した三口フラスコに、蒸留水350mLと亜硫酸ナトリウム56部から成る溶液に、炭酸水素ナトリウム65部を加えて、懸濁液を調製した。この懸濁液に2−クロロエタンスルホニルクロリド65部を4〜10℃の範囲で滴下し、滴下後同温度でさらに75分間攪拌した。その後、この反応液に49%硫酸水溶液を4〜10℃の範囲で滴下し、滴下後同温度でさらに1時間反応させた。得られた反応液を濾過し、結晶を蒸留水100mLで洗浄した。得られた濾液に、N,N’−メチレンビスアクリルアミド62部とエタノール370mLと蒸留水120mLを70℃に加熱してほぼ均一に溶解した溶液を、冷却した前記濾液に5〜10℃の範囲で滴下し、同温度で2時間攪拌した。得られた反応液を冷蔵庫で一晩放置した。濾過して得られた粘性個体を蒸留水1.5Lで洗浄した後、蒸留水/エタノール=1/1 1Lで再結晶した。得られた結晶を50℃で2時間減圧乾燥して、2−クロロエタンスルホン基を有するモノマー42部(収率:37%)を得た。
2−クロロエタンスルホン基を有するモノマー 1部、(3−アクリルアミドプロピル)トリメチルアンモニウムクロリドの75%水溶液 4.4部、ジメチルホルムアミド25部、ジメチル2,2’−アゾビスイソブチレート0.08部をフラスコ中に仕込み、2分間窒素パージを行った後、密栓して、65℃で3時間重合を行った。得られたポリマー溶液の温度を15℃に降温し、トリエチルエミン0.36部を加えて30分攪拌した。その後、透析膜でポリマーを精製し、凍結乾燥した。得られたポリマーは2部であった。得られたポリマーP-1のNMRチャートを図1に示す。
本実施例は、タンパク質を固定するためのセンサーチップの作製に関するものである。
(1)試料1(比較例)の作成
カルボキシメチルデキストランが結合した表面として、Biacore社センサーチップCM-5(research grade)を、そのまま用いた。
センサーチップ上に金膜のみが形成されている表面として、Biacore社センサーチップAuを用いて実験を行った。センサーチップAuを12分間、UVオゾン処理を行った後、4.0mMの8−ヒドロキシオクタンチオール(同仁化学製)および1.0mMの11−アミノウンデカンチオール(同仁化学製)を溶解したエタノール/水(80/20)混合溶媒中で、40℃16時間反応させた。表面を5×50mlの水、50mlのエタノール/水(80/20)、及び5×50mlの水で洗浄した。さらに本センサーチップを、ポリマー(P-1)を10質量%溶解した水溶液中で60℃16時間反応させた。表面を5×50mlの水で洗浄することで、試料2を得た。
本実施例は、実施例1で得られたセンサーチップに対する等電点以上のpHにおけるタンパク質のプレコンセントレーションに関するものである。タンパク質としては、CA(Carbonic Anhydrase:SIGMA社製)を用いた。用いたCAは、ATTO社のAE-8150を用いた電気泳動実験で、同時測定したマーカー(Broad pI Kit, pH 3.5-9.3:Amersham Biosciences社製)との比較から、等電点が5.8程度であることを確認した。1mgのCAを1mlのHBS-EPバッファー(ビアコア社製、pH7.4)に溶解した溶液を10μl秤量し、90μlの炭酸バッファー(PIERCE社製、pH9.4)を加えることで、0.1mg/mlのCA溶液(pH9.4, 0.1mg/ml)を調整した。なお、HBS-EPバッファーの組成は、HEPES(N-2-Hydroxyethylpiperazine-N'-2-ethanesulfonicAcid)0.01mol/l(pH7.4)、NaCl0.15mol/l、EDTA 0.003mol/l、Surfactant P20 0.005質量%である。
タンパク質としてペプシン(和光純薬社製)を用いた以外は、実施例2と同様の検討を行った。測定されたペプシンの等電点は4.0程度であった。
1mgのペプシンを1mlのHBS-EPバッファー(ビアコア社製、pH7.4)に溶解した溶液を10μl秤量し、90μlの酢酸バッファー(Biacore社製、pH5.0)を加えることで、0.1mg/mlのペプシン溶液(pH5.0, 0.1mg/ml)を調整した。
実施例1で作製した試料1、2をBiacore社製の表面プラズモン共鳴装置であるBiacore3000にセットし、ペプシン溶液(pH5.0, 0.1mg/ml)を5分間流した後、10mMNaOHを1分間×2回流した場合のプレコンセントレーションについて検討した。得られたセンサーグラムを図3に示す。
Claims (12)
- 生理活性物質を化学的に固定化できる反応性基とカチオン性基とを併せ持つ測定チップ表面に、等電点以上のpHを有する生理活性物質含有液を接触させることを含む生理活性物質の固定化方法において、前記生理活性物質が酸性タンパク質である方法。
- 生理活性物質を化学的に固定化できる反応性基が、生理活性物質を共有結合により固定化することができる、請求項1に記載の生理活性物質の固定化方法。
- 生理活性物質を化学的に固定化できる反応性基とカチオン性基とを併せ持つ表面が、水溶性高分子が結合している表面、疎水性高分子が結合している表面、又は自己組織化単分子膜が形成されている表面の何れかである、請求項1又は2の何れか1項に記載の生理活性物質の固定化方法。
- 生理活性物質を化学的に固定化できる反応性基が、ビニルスルホン基又はその前駆体、ハロトリアジン基、エポキシ基、カルボン酸活性エステル基、アルデヒド基、イソシアネート基、又はアセトアセチル基のいずれかである、請求項1から3の何れか1項に記載の生理活性物質の固定化方法。
- カチオン性基がオニウム又はその前駆体である、請求項1から4の何れか1項に記載の生理活性物質の固定化方法。
- 生理活性物質を化学的に固定化できる反応性基とカチオン性基を併せ持つ表面が金属上に形成されている、請求項1から5の何れか1項に記載の生理活性物質の固定化方法。
- 金属が金、銀、銅、白金またはアルミニウムのいずれかである、請求項6に記載の生理活性物質の固定化方法。
- 生理活性物質を化学的に固定化できる反応性基とカチオン性基とを併せ持つ表面が、バイオセンサーの表面である、請求項1から7の何れか1項に記載の生理活性物質の固定化方法。
- 請求項1から8の何れか1項に記載の生理活性物質の固定化方法により生理活性物質が固定された測定チップと、被験物質とを接触させる工程を含む、該生理活性物質と相互作用する物質を検出または測定する方法。
- 前記生理活性物質が、前記生理活性物質を化学的に固定化できる反応性基と共有結合により結合している請求項9に記載の方法。
- 生理活性物質と相互作用する物質を非電気化学的方法により検出または測定する、請求項9又は10の何れか1項に記載の方法。
- 生理活性物質と相互作用する物質を表面プラズモン共鳴分析により検出または測定する、請求項9から11の何れか1項に記載の方法。
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EP06003590A EP1696235B1 (en) | 2005-02-23 | 2006-02-22 | Biosensor |
DE602006009980T DE602006009980D1 (de) | 2005-02-23 | 2006-02-22 | Biosensor |
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Citations (4)
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JP2001521625A (ja) * | 1997-04-16 | 2001-11-06 | ベーイーオー メリュー | 標的生物学的物質を単離するための方法、捕獲相、検出相、及び試薬 |
JP2002060671A (ja) * | 2000-08-11 | 2002-02-26 | Mitsubishi Chemicals Corp | 新規コーティング樹脂板 |
JP2003075448A (ja) * | 2001-09-03 | 2003-03-12 | Fuji Photo Film Co Ltd | バイオセンサー用表面 |
JP2005062074A (ja) * | 2003-08-19 | 2005-03-10 | National Institute Of Advanced Industrial & Technology | Dnaチップおよび標的dnaの検出方法。 |
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JP2001521625A (ja) * | 1997-04-16 | 2001-11-06 | ベーイーオー メリュー | 標的生物学的物質を単離するための方法、捕獲相、検出相、及び試薬 |
JP2002060671A (ja) * | 2000-08-11 | 2002-02-26 | Mitsubishi Chemicals Corp | 新規コーティング樹脂板 |
JP2003075448A (ja) * | 2001-09-03 | 2003-03-12 | Fuji Photo Film Co Ltd | バイオセンサー用表面 |
JP2005062074A (ja) * | 2003-08-19 | 2005-03-10 | National Institute Of Advanced Industrial & Technology | Dnaチップおよび標的dnaの検出方法。 |
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