JP6884130B2 - 生体分子分析用のナノプラズモンセンサー、キット、及びこれを用いた生体分子の分析方法 - Google Patents
生体分子分析用のナノプラズモンセンサー、キット、及びこれを用いた生体分子の分析方法 Download PDFInfo
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- JP6884130B2 JP6884130B2 JP2018221108A JP2018221108A JP6884130B2 JP 6884130 B2 JP6884130 B2 JP 6884130B2 JP 2018221108 A JP2018221108 A JP 2018221108A JP 2018221108 A JP2018221108 A JP 2018221108A JP 6884130 B2 JP6884130 B2 JP 6884130B2
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Description
図1は例示的な実施例によるナノプラズモンセンサーの概略的な断面図である。
ナノプラズモンセンサー10のセンシング部100は、次のような工程により製造することができる。
図2A〜図2Eは例示的な実施例によるナノプラズモンセンサーを用いた生体分子の分析方法を説明するための図である。また、図3A及び図3Bは例示的な実施例によるセンシング部を示す概略的な斜視図である。
以下、本発明の一実施例を図1〜図2Eを併せて参照して詳細に説明する。但し、下記実施例は、本発明を例示するものであり、本発明が下記実施例に限定されるものではない。
20 第1プローブ分子
30 分析対象物
40 第2プローブ分子
50 酵素
60 沈殿物
101 ベース層
110 誘電体グレーティング
120 金属構造物
121 第1水平部
122 垂直部
123 第2水平部
150 井戸型チャンバー
200 測定部
210 光源部
220 受光部
300 物質提供部
Claims (18)
- 一方向に延びる誘電体グレーティング、及び前記誘電体グレーティングの上面と一側面を覆い、少なくとも一つの折曲部を有するように配置される金属構造物を含むナノプラズモンセンサーを提供する段階と、
前記金属構造物の表面に第1プローブ分子を固定させる段階と、
前記第1プローブ分子と相補的な塩基配列を有する分析対象物を導入し、前記第1プローブ分子と前記分析対象物をハイブリッド化する段階と、
前記第1プローブ分子とハイブリッド化する第2プローブ分子を前記分析対象物に結合させる段階と、
前記第2プローブ分子に酵素を結合させる段階と、
前記酵素と反応する基質を導入し、酵素反応による沈殿物を生成する段階と、
前記金属構造物における局所表面プラズモン共鳴現象を測定する段階と、を含む、ナノプラズモンセンサーを用いた生体分子の分析方法。 - 前記第1プローブ分子を固定させる段階で、前記第1プローブ分子はヘアピン構造をなす、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記分析対象物をハイブリッド化する段階で、前記分析対象物は、前記第1プローブ分子よりも短い長さを有し、溶解(melting)された前記第1プローブ分子の下端に結合する、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記分析対象物はマイクロRNA(miRNA)であり、前記第1プローブ分子はLNA(locked nucleic acid)である、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記分析対象物をハイブリッド化する段階は、前記第1プローブ分子の物質に応じて、60℃以上の温度でハイブリッド化する段階と、10℃以下の温度に冷却させる段階と、を含む、請求項4に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記金属構造物は金(Au)を含み、前記第1プローブ分子は前記金属構造物と結合するチオール基を有する、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記第2プローブ分子は前記酵素と結合する分子団を有する、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記第2プローブ分子はビオチン分子団を有し、前記酵素はストレプトアビジン(streptavidin)分子団を有する、請求項7に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記基質は、4−クロロナフトール(4−chloronaphthol)、DAB(3,3'−diaminobenzidine)、AEC(3−amino−9−ethylcarbazole)、TMB(3,3'、5,5'−Tetramethylbenzidine)、BCIP(5−bromo−4−chloro−3−indolyl phosphate)/NBT(nitro blue tetrazolium)、TR/Naphthol AS−MX(4−Chloro−2 methylbenzenediazonium/3−Hydroxy−2−naphthoic acid 2,4−dimethylanilide phosphate)、X−gal(5−Bromo−4−chloro−3−indolyl β−D−galactopyranoside)、S−gal(3,4−Cyclohexenoesculetin β−D−galactopyranoside)、Bluo−gal(5−Bromo−3−indolyl β−D−galactopyranoside)、及びRed−gal(6−Chloro−3−indolyl−β−D−galactopyranoside)のうち少なくとも一つである、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記ナノプラズモンセンサーは前記誘電体グレーティングが位置するベース層をさらに含み、
前記金属構造物は、
前記誘電体グレーティングの上面に配置される第1水平部と、
前記第1水平部から折り曲げられて、前記誘電体グレーティングの側面に沿って配置される垂直部と、
前記垂直部から折り曲げられて、前記ベース層の上面に沿って配置される第2水平部と、を含む、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。 - 前記第2水平部は、前記垂直部から前記第1水平部と反対方向に折り曲げられる、請求項10に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記金属構造物の全体の幅は10nm〜500nmの範囲である、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- 前記金属構造物の厚さは1nm〜200nmの範囲である、請求項1に記載のナノプラズモンセンサーを用いた生体分子の分析方法。
- ベース層上に一方向に延びるように配置される少なくとも一つの誘電体グレーティング、及び前記誘電体グレーティングの上面と一側面を覆い、少なくとも一つの折曲部を有するように配置される金属構造物を含むセンシング部と、
前記金属構造物上に、第1プローブ分子、前記第1プローブ分子と相補的な塩基配列を有する分析対象物、前記第1プローブ分子とハイブリッド化する第2プローブ分子、前記第2プローブ分子と結合する酵素、及び前記酵素と反応して沈殿物を形成する基質を順に提供する物質提供部と、
前記ベース層の上部に配置され、前記金属構造物に入射する入射光を発生させる光源部、及び前記ベース層の下部に配置され、前記金属構造物における光特性の変化を検出する受光部を含み、前記金属構造物における局所表面プラズモン共鳴現象を測定する測定部と、を含む、生体分子分析用のナノプラズモンセンサー。 - 前記センシング部は、前記金属構造物を複数の領域に区分する複数の井戸型チャンバーをさらに含む、請求項14に記載の生体分子分析用のナノプラズモンセンサー。
- ベース層上に一方向に延びるように配置される少なくとも一つの誘電体グレーティングと、
前記誘電体グレーティングの上面と一側面を覆い、少なくとも一つの折曲部を有するように配置される金属構造物と、
分析対象物とハイブリッド化し、前記金属構造物の表面に結合する第1プローブ分子と、
前記分析対象物と結合していない末端で前記第1プローブ分子とハイブリッド化する第2プローブ分子と、
前記第2プローブ分子と結合する酵素と、
前記酵素と反応して前記金属構造物の表面に沈殿物を形成する基質と、を含む、生体分子分析用のキット。 - 前記第1プローブ分子は、LNA(locked nucleic acid)である、請求項16に記載の生体分子分析用のキット。
- 前記第1プローブ分子と相補的な塩基配列を有する前記分析対象物を検出する、請求項16に記載の生体分子分析用のキット。
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