JP2022509915A - 分子の構造および配座を決定するための電子回折イメージングシステム - Google Patents
分子の構造および配座を決定するための電子回折イメージングシステム Download PDFInfo
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Abstract
Description
ピクセルサイズ=(距離)(波長)/(2)(サンプルサイズ)
Claims (18)
- サンプルの単一のターゲット分子の3次元構造を画像化するための電子回折画像化システムであって、
前記サンプルに向かう第1の方向に、少なくとも15nmの横方向コヒーレンス長を有する電子ビームを放出する電子源と、
前記サンプルによって回折された電子を検出し、その空間分布を示す出力を生成する2次元電子検出器と、
前記サンプルが配置されているサンプル支持体であって、前記サンプルが配置されている前記支持体の領域内の電子に対して実質的に透明であり、および、少なくとも2つの垂直方向への前記サンプル支持体の並進を可能にするように、かつ、前記サンプルを異なる角度方向に回転させることを可能にするように構成された、前記サンプル支持体と、
前記ターゲット分子を前記電子ビームの中心となるように、前記検出器の出力に応じて前記サンプル支持体の前記並進を調整する調整装置と、
を備えたことを特徴とする電子回折画像化システム。 - 前記電子ビームは、5keVと30keVとの間の動作エネルギーを有することを特徴とする請求項1に記載の画像化システム。
- 前記電子源は、前記ビームの直径を、前記ターゲット分子のサイズの3倍以下に制限するビーム調整光学系を含むことを特徴とする請求項1又は2に記載の画像化システム。
- 前記ビーム調整光学系は、前記電子源によって放出された高度に発散する電子を遮断することを特徴とする請求項3に記載の画像化システム。
- 前記調整システムは、前記検出器によって検出された回折分布の重心を特定し、および、前記重心を前記電子ビームの中心に実質的に位置合わせするように前記サンプル支持体を調整することを特徴とする請求項1ないし4のいずれか1つに記載の画像化システム。
- 前記調整システムは、30nm未満の混同の球を維持するように制御されることを特徴とする請求項1ないし5のいずれか1つに記載の画像化システム。
- 電子源、電子検出器、およびサンプル支持体は、それぞれ真空環境に配置されていることを特徴とする請求項1ないし6のいずれか1つに記載の画像化システム。
- 前記電子源は、10-9mbar以下の真空内に配置されていることを特徴とする請求項1ないし7のいずれか1つに記載の画像化システム。
- 前記サンプル支持体は、10-6mbar以下の真空中に配置されることを特徴とする請求項1ないし8のいずれか1つに記載の画像化システム。
- 前記サンプル支持体は、電子に対して透明である基板と、前記基板が取り付けられている剛性の支持体構造とを含むことを特徴とする請求項1ないし9のいずれか1つに記載の画像化システム。
- 前記剛性の支持体構造は、前記サンプルが配置される前記基板の領域に隣接する開口部を有することを特徴とする請求項10に記載の画像化システム。
- 前記支持体構造の開口部のサイズに対する前記サンプル支持体の厚さは、前記サンプル支持体の360°回転中に、前記電子ビームが前記支持体構造によって遮られる角度が5度未満であるようにされたことを特徴とする請求項11に記載の画像化システム。
- サンプルの単一のターゲット分子の3次元構造を画像化するための方法であって、
前記サンプルを、前記サンプルが配置されているサンプル支持体の領域内の電子に対して実質的に透明である前記サンプル支持体上に配置することであって、前記サンプル支持体は、少なくとも2つの垂直方向への前記サンプル支持体の並進を可能にし、および、前記サンプルを異なる角度方向に回転させることを可能にするように構成され、
少なくとも15nmの横方向コヒーレンス長を有する電子ビームを、電子源から前記サンプルに向かって第1の方向に向けることと、
2次元電子検出器を用いて前記サンプルによって回折された電子を検出し、および、その空間分布を示す検出器出力を生成することと、
前記ターゲット分子を電子ビームの中心となるように、前記検出器の出力に応じて前記サンプル支持体の位置を調整する調整システムと
を含むことを特徴とする方法。 - 前記電子源は、5keVと30keVとの間の動作エネルギーを有することを特徴とする請求項13に記載の方法。
- 前記電子源は、前記ビームの直径を、前記ターゲット分子のサイズの3倍以下に制限するビーム調整光学系を含むことを特徴とする請求項13又は14に記載の方法。
- 前記調整システムが、前記検出器によって検出された回折分布の重心を特定し、および、その重心を前記電子ビームの中心に実質的に位置合わせするように前記サンプル支持体を調整することを特徴とする請求項13ないし15のいずれか1つに記載の方法。
- 前記調整システムは、30nm未満の混同の球を維持するように制御されることを特徴とする請求項13ないし16のいずれか1つに記載の方法。
- 前記サンプル支持体は、電子に対して透明である基板と、前記基板が取り付けられている剛性の支持体構造とを含み、前記剛性の支持体構造は、前記サンプルが配置される前記基板の領域に隣接する開口部を有し、前記サンプル支持体の360°回転中に、前記電子ビームが前記支持体構造によって遮られる角度が5度未満であるように、前記サンプル支持体の厚さに対して前記支持体構造の開口部のサイズが決められたことを特徴とする請求項13ないし17のいずれか1つに記載の方法。
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PCT/IB2019/059152 WO2020089751A1 (en) | 2018-10-31 | 2019-10-24 | Electron diffraction imaging system for determining molecular structure and conformation |
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EP2402976A1 (en) | 2010-06-30 | 2012-01-04 | Fei Company | Method of electron diffraction tomography |
JP6420835B2 (ja) | 2013-08-13 | 2018-11-07 | メディカル リサーチ カウンシルMedical Research Council | 多孔性の金属箔を備える電子顕微鏡試料支持体 |
US10515791B2 (en) * | 2016-01-08 | 2019-12-24 | Universitaet Zuerich | Method and apparatus for imaging single molecules |
US9978557B2 (en) * | 2016-04-21 | 2018-05-22 | Fei Company | System for orienting a sample using a diffraction pattern |
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