JP4234685B2 - Nuclear magnetic resonance measurement method and system - Google Patents

Nuclear magnetic resonance measurement method and system Download PDF

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JP4234685B2
JP4234685B2 JP2005014092A JP2005014092A JP4234685B2 JP 4234685 B2 JP4234685 B2 JP 4234685B2 JP 2005014092 A JP2005014092 A JP 2005014092A JP 2005014092 A JP2005014092 A JP 2005014092A JP 4234685 B2 JP4234685 B2 JP 4234685B2
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金也 小林
ミンソク 朴
秀太 羽原
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Hitachi Ltd
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本発明は核磁気共鳴計測システムに関し、特に多量な試料を効率よく計測する核磁気共鳴計測方法の制御方式に関する。   The present invention relates to a nuclear magnetic resonance measurement system, and more particularly to a control method of a nuclear magnetic resonance measurement method for efficiently measuring a large amount of samples.

創薬開発では、多量試料の蛋白質の構造、あるいは蛋白質と薬との相互作用を迅速に同定、高スループットで計測する必要がある。   In drug development, it is necessary to quickly identify the protein structure of a large amount of sample or the interaction between the protein and the drug and measure it with high throughput.

これらの同定や計測は核磁気共鳴法（ＮＭＲ）により評価可能である。ＮＭＲ測定に関しては非特許文献１が知られている。   These identifications and measurements can be evaluated by nuclear magnetic resonance (NMR). Regarding NMR measurement, Non-Patent Document 1 is known.

蛋白質の時代−構造・物性・機能研究の新展開（共立出版株式会社；1274〜1282頁、著者：阿久津秀雄）The Age of Protein-New Developments in Structural, Physical, and Functional Research (Kyoritsu Publishing Co., Ltd .; 1274-1282, Author: Hideo Akutsu)

従来の核磁気共鳴計測は質量分析などに比べ、計測時間やデータ後処理が長期化する。また、試料内に混入した不純物や、温度変化による成分変化した物を計測した場合、これらの計測結果は無駄になってしまう。さらに、試料内の少数種の成分比率が非常に多い場合は、同一種を何度も測定することとなり、得られる情報が少ない割には、計測時間が長期化する可能性がある。これらを除外するために、現状は計測者が手作業にて実施している。しかし、これではユーザーに大きな負担を与える事になる。   Conventional nuclear magnetic resonance measurement requires longer measurement time and data post-processing than mass spectrometry. In addition, when measuring impurities mixed in the sample or components whose components have changed due to temperature changes, these measurement results are wasted. Furthermore, when the component ratio of a small number of species in the sample is very large, the same species is measured many times, and there is a possibility that the measurement time may be prolonged for less information to be obtained. In order to exclude them, the measurer is currently carrying out manually. However, this places a heavy burden on the user.

本発明の目的は、上記従来技術の問題点に鑑み、試料内の不純物や試料の変質、あるいは同一種を何度も計測するような場合に、自動的に計測を停止して次の計測をスタートできる核磁気共鳴計測方法およびシステムを提供することにある。   In view of the above-mentioned problems of the prior art, the object of the present invention is to automatically stop the measurement when the impurities in the sample, the sample alteration, or the same species are measured many times. It is to provide a nuclear magnetic resonance measurement method and system that can be started.

上記目的を達成するための本発明は、核磁気共鳴（ＮＭＲ）測定に基づいて試料の（物質の）構造を分析する核磁気共鳴計測方法において、複数の試料の中から選定された試料についてＮＭＲ測定を実施し、所定時間経過後に測定データを分析し、（１）質の低いデータか、（２）不純物有りか、（３）同一試料の測定回数がしきい値以上か判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、何れかに該当する場合は当該試料の測定を終了して次の試料の測定に移ることを特徴とする。   In order to achieve the above object, the present invention provides a nuclear magnetic resonance measurement method for analyzing a (material) structure of a sample based on nuclear magnetic resonance (NMR) measurement. Measure and analyze the measurement data after a lapse of a predetermined time, and determine whether (1) low quality data, (2) impurities, or (3) whether the same sample is measured more than the threshold If the above is not applicable, the NMR measurement is continued. If any of the above is satisfied, the measurement of the sample is terminated and the measurement of the next sample is started.

あるいは、複数の試料の中から選定された試料についてＮＭＲ測定を実施し、所定時間経過後に外場を与えて該外場の測定データを分析し、（１）質の低いデータか、（２）不純物有りか判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、何れかに該当する場合は当該試料の測定を終了して次の試料の測定に移ることを特徴とする。   Alternatively, NMR measurement is performed on a sample selected from a plurality of samples, an external field is applied after a predetermined time has elapsed, and the measurement data of the external field is analyzed, and (1) low-quality data or (2) It is characterized in that it is determined whether or not there is an impurity. If none of the above is applicable, the NMR measurement is continued. If any of the impurities is applicable, the measurement of the sample is terminated and the measurement of the next sample is started.

本発明の核磁気共鳴計測システムは、試料の構造を示すデータを測定する核磁気共鳴（ＮＭＲ）測定装置と、測定データに基づいて試料の構造を分析し、同定するデータ後処理装置と、測定を制御する制御装置を備えるものにおいて、前記制御装置は、複数の試料の中から選定された試料について前記核磁気共鳴（ＮＭＲ）測定装置にＮＭＲ測定を実施させ、所定時間経過後に測定データを分析し、（１）質の低いデータか、（２）不純物有りか、（３）同一試料の測定回数がしきい値以上か判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、何れかに該当する場合は当該試料の測定を終了して次の試料の測定に移るように構成したことを特徴とする。   The nuclear magnetic resonance measurement system of the present invention includes a nuclear magnetic resonance (NMR) measurement device that measures data indicating the structure of a sample, a data post-processing device that analyzes and identifies the structure of the sample based on the measurement data, and a measurement The control device causes the nuclear magnetic resonance (NMR) measurement device to perform NMR measurement on a sample selected from a plurality of samples, and analyzes the measurement data after a predetermined time has elapsed. (1) Whether the data is low quality, (2) Impurity, (3) Whether the number of measurements of the same sample is equal to or greater than a threshold value, In such a case, the measurement of the sample is finished and the measurement of the next sample is started.

本発明によれば、核磁気共鳴測定による測定データを実時間で自動分析すると共に、不要な測定を回避するようにしている。これにより、試料内に混入した不純物や、温度変化による成分が変化した場合、ＮＭＲ測定が停止する。さらに、試料内の少数種の成分比率が非常に多い場合に、同一試料の計測を回避する。この結果、ユーザーに新たな負担を加える事になしにＮＭＲ計測を高スループット化することができる。   According to the present invention, measurement data obtained by nuclear magnetic resonance measurement is automatically analyzed in real time, and unnecessary measurement is avoided. Thereby, when impurities mixed in the sample or components due to temperature change are changed, NMR measurement is stopped. Furthermore, measurement of the same sample is avoided when the component ratio of minority species in the sample is very large. As a result, it is possible to increase the NMR measurement without adding a new burden on the user.

以下に、本発明の複数の実施形態について図面を参照しながら詳細に説明する。
（実施例１）
図２は核磁気共鳴測定システムの構成図である。試料を前処理する前処理装置301、核磁気共鳴測定装置302、核磁気共鳴測定装置を制御する制御装置303、測定データを処理するデータ後処理装置304、入力及び出力結果を表示する入出力端末305からなる。 Hereinafter, a plurality of embodiments of the present invention will be described in detail with reference to the drawings.
Example 1
FIG. 2 is a configuration diagram of a nuclear magnetic resonance measurement system. Pre-processing device 301 for pre-processing a sample, nuclear magnetic resonance measuring device 302, control device 303 for controlling the nuclear magnetic resonance measuring device, data post-processing device 304 for processing measurement data, input / output terminal for displaying input and output results 305.

図３は核磁気共鳴測定の処理フローを示す。まず、試料を前処理し(401)、それを核磁気共鳴測定し(402)、測定されたデータを後処理し(403)、測定試料の構造を同定する(404)。   FIG. 3 shows a processing flow of nuclear magnetic resonance measurement. First, the sample is pretreated (401), it is subjected to nuclear magnetic resonance measurement (402), the measured data is postprocessed (403), and the structure of the measurement sample is identified (404).

核磁気共鳴測定（４０２）では、磁場発生装置、高周波プローブ、パルスゼネレーター、ＲＦトランスミッター、レシーバーなどを活用し、核磁気共鳴スペクトルを測定する。後処理（４０３）では核磁気共鳴スペクトルから、１Ｈ信号−１Ｈ信号間の相関や、１Ｈ信号−１3Ｃ信号間の相関などを解析する。同定（４０４）では、後処理（４０３）から得られた水素−水素間の距離等と、分子動力学計算、蛋白質の構造が格納されているデータベース検索などから測定試料の３次元構造を同定する。 In the nuclear magnetic resonance measurement (402), a magnetic magnetic resonance spectrum is measured using a magnetic field generator, a high-frequency probe, a pulse generator, an RF transmitter, a receiver, and the like. From the post-processing (403) the nuclear magnetic resonance spectra, 1 H signal - 1 correlations and between H signal, 1 H signal - 13 to analyze the correlation and between C signal. In the identification (404), the three-dimensional structure of the measurement sample is identified from the hydrogen-hydrogen distance obtained from the post-processing (403), the molecular dynamics calculation, the database search storing the protein structure, and the like. .

図４は核磁気共鳴装置の各構成要素の配置を示す模式図である。試料溶液４が入った試料のサンプル管３の周囲に核磁気共鳴プローブコイル５が巻かれ、その周囲に静磁場発生用マグネット６が設置される。マグネット６のボア７を通してプローブコイル５の引き出し線８が引き出れる。９はサンプル管３の導入用のガイドである。これにより、試料内のターゲットである蛋白質などの磁気共鳴スペクトルを測定し、蛋白質などの構造を同定可能にしている。   FIG. 4 is a schematic diagram showing the arrangement of each component of the nuclear magnetic resonance apparatus. A nuclear magnetic resonance probe coil 5 is wound around the sample tube 3 of the sample containing the sample solution 4, and a static magnetic field generating magnet 6 is installed around the sample. The lead wire 8 of the probe coil 5 is drawn out through the bore 7 of the magnet 6. Reference numeral 9 denotes a guide for introducing the sample tube 3. As a result, the magnetic resonance spectrum of the protein as the target in the sample is measured, and the structure of the protein can be identified.

図５に、図４の構造とは異なる核磁気共鳴装置の模式図を示す。図５では、静磁場発生用のマグネットの配置がドーナツ状となっている。   FIG. 5 shows a schematic diagram of a nuclear magnetic resonance apparatus different from the structure of FIG. In FIG. 5, the arrangement of the magnets for generating a static magnetic field has a donut shape.

図１は本実施例によるNMR計測の処理フローを示す。まず、試料を前処理装置で試料Ａ、Ｂ、Ｃ、・・・を作成し(101)、たとえば試料Ａを選択する（102）。選択した試料を図４または図５のNMR装置にて計測する（103）。試料は、予め複数個、作成されており、ある試料の計測が終了すると、自動的に次の試料が測定されるシステムである。   FIG. 1 shows a processing flow of NMR measurement according to this example. First, samples A, B, C,... Are prepared using a pretreatment apparatus (101), and for example, sample A is selected (102). The selected sample is measured with the NMR apparatus of FIG. 4 or 5 (103). A plurality of samples are prepared in advance, and when measurement of a certain sample is completed, the next sample is automatically measured.

このとき、NMRの生データ計測（103）を実施することと並行して、処理104による判定を実時間で実施する。処理104の判定は制御装置303により下記（１）、（２）、（３）について行われる。ここではＮＭＲ計測の生データか、あるいは周波数変換などでデータ処理後のデータを、データ後処理装置304により、測定試料の構造を同定することにより行われる。なお、測定データ後処理や制御装置の処理は、実時間で評価することが望ましいので、並列計算機の利用もあり得る。
（１）質の低い実験データの測定（測定途中で試料が変質する）。同一試料の測定途中に、構成元素の比率が１％以上変化する場合。
（２）試料に混入されている不純物を測定。蛋白質をターゲットとしていて、アミノ酸が検出されない場合。
（３）既に何回も測定した試料で測定回避したいデータの測定。同一試料のＮＭＲの測定積算回数が設定しきい値以上となった場合。しきい値は、測定データ後処理404で試料の構造を同定できるのに十分な測定積算回数とする。なお、同一物の判定は、しきい値を超えた試料の核磁気共鳴スペクトルデータを、制御装置303内のメモリーにデータベースとして格納し、その後の測定結果をデータベースと比較して判断する。 At this time, in parallel with performing the raw data measurement (103) of NMR, the determination by the processing 104 is performed in real time. The determination of the process 104 is performed for the following (1), (2), and (3) by the control device 303. Here, it is performed by identifying raw data of NMR measurement or data after data processing by frequency conversion or the like by using the data post-processing device 304 to identify the structure of the measurement sample. In addition, since it is desirable to evaluate the measurement data post-processing and the control device processing in real time, a parallel computer may be used.
(1) Measurement of low-quality experimental data (sample changes during measurement). When the ratio of constituent elements changes by 1% or more during measurement of the same sample.
(2) Measure impurities mixed in the sample. When protein is targeted and no amino acids are detected.
(3) Measurement of data to be avoided in a sample that has already been measured many times. When the cumulative number of NMR measurements on the same sample exceeds the set threshold. The threshold is set to a sufficient number of measurement integrations so that the structure of the sample can be identified by the measurement data post-processing 404. The same thing is determined by storing the nuclear magnetic resonance spectrum data of the sample exceeding the threshold value as a database in the memory in the control device 303 and comparing the subsequent measurement result with the database.

処理104による判定の結果、（１）−（３）の何れにも該当しない場合は同一試料の測定を継続する。処理104による判定の結果、（１）−（３）の何れかに該当する場合は、制御装置303で、NMR装置302の測定を終了するか判断（105）する。   As a result of the determination by the processing 104, when none of (1) to (3) is applicable, the measurement of the same sample is continued. As a result of the determination by the processing 104, if any of (1) to (3) is satisfied, the control device 303 determines whether or not the measurement of the NMR device 302 is finished (105).

ここで、（１）は、温度変化により試料の成分が変化する場合に起こる。特に、生体内の有機物であれば、成分変化が生じる可能性が大きい。（２）は、試料を融解するための媒質内の不純物が計測される場合を想定している。（３）は、多量な試料で計測時間を短縮でき、微量な試料で十分な測定時間を確保できる。   Here, (1) occurs when the components of the sample change due to temperature changes. Particularly, in the case of an organic substance in a living body, there is a high possibility that a component change occurs. (2) assumes a case where impurities in the medium for melting the sample are measured. In (3), the measurement time can be shortened with a large amount of sample, and sufficient measurement time can be secured with a small amount of sample.

処理105で測定を終了しない場合，測定時間、入力パルス波形、測定対象などの測定パラメータを変更（107）してＮＭＲ測定103を継続する。測定終了の場合は、測定データを入出力端末305に出力（108）し、次の試料の選定に移る（109）。   If the measurement is not terminated in the process 105, the measurement parameters such as the measurement time, the input pulse waveform, and the measurement target are changed (107) and the NMR measurement 103 is continued. When the measurement is completed, the measurement data is output to the input / output terminal 305 (108), and the next sample is selected (109).

図６に本実施例の時間チャートを示す。まず、試料ＡのＮＭＲ測定中の一定時間経過後に、測定データを判定（104）し、上記（１）〜（３）の何れにも該当しないのでＮＭＲ測定を継続する。さらに一定時間経過後、上記判定（104）を繰り返し、この結果が（１）と判断されると、ＮＭＲ測定を中断し、次の試料Ｂを再測定する。試料ＢのＮＭＲ測定中の一定時間経過後に、測定データを判定（104）し、上記（２）と判断されると、ＮＭＲ測定を中断する。次に、試料ＣのNMR測定を実施し、一定時間経過後に、（１）と判断されたため、測定対象を炭素上の水素から、窒素上の水素に変更し、ＮＭＲ測定を再開する。   FIG. 6 shows a time chart of this embodiment. First, measurement data is judged (104) after a lapse of a certain time during the NMR measurement of sample A, and the NMR measurement is continued because none of the above (1) to (3) is applicable. Further, after a predetermined time has elapsed, the above determination (104) is repeated. When this result is determined as (1), the NMR measurement is interrupted and the next sample B is measured again. After a certain period of time during the NMR measurement of the sample B, the measurement data is determined (104). If it is determined as (2) above, the NMR measurement is interrupted. Next, the NMR measurement of Sample C is performed, and after a certain time has elapsed, it is determined as (1). Therefore, the measurement target is changed from hydrogen on carbon to hydrogen on nitrogen, and NMR measurement is resumed.

図７に別の時間チャートを示す。本例は、測定データの判定を、ＮＭＲ測定と並列に実施している。これにより、図６にくらべ、NMR計測時間を短縮できる。   FIG. 7 shows another time chart. In this example, determination of measurement data is performed in parallel with NMR measurement. Thereby, compared with FIG. 6, NMR measurement time can be shortened.

以上のように、本実施例によればユーザーに新たな負担を加える事になしに、NMR計測を高スループット化することができる。
（実施例２）
本発明の実施例２を説明する。実施例１では、測定継続か否かの判定（１０４）を、ＮＭＲ計測のみで実施した。本実施例では、外場を与えて、この計測結果を判定条件とするものである。外場には、光として赤外，可視光、電磁場としてＵＶ、テラヘルツ（THz）あるいは熱や超音波がある。分光法としては、赤外分光、ラマン分光などがある。さらには、外場の影響を、外場の導入前後でのＮＭＲ計測データの差、例えば、化学シフトの差から見積もることもできる。 As described above, according to the present embodiment, it is possible to increase the throughput of NMR measurement without adding a new burden on the user.
(Example 2)
A second embodiment of the present invention will be described. In Example 1, the determination (104) as to whether or not the measurement was continued was performed only by NMR measurement. In this embodiment, an external field is given and this measurement result is used as a determination condition. In the external field, there are infrared, visible light as light, UV, terahertz (THz), heat and ultrasonic waves as electromagnetic fields. Spectroscopy includes infrared spectroscopy, Raman spectroscopy, and the like. Furthermore, the influence of an external field can also be estimated from a difference in NMR measurement data before and after the introduction of the external field, for example, a chemical shift difference.

図９は実施例２による核磁気共鳴装置の構成要素配置の模式図で、実施例１の図４に対応するものである。外場発信部１から光あるいは電磁場を導入し、反対側の外場検出部２からの透過光を計測している。あるいは、外場導入口側で反射光を計測するようにしてもよい。   FIG. 9 is a schematic diagram of component arrangement of the nuclear magnetic resonance apparatus according to the second embodiment, and corresponds to FIG. 4 of the first embodiment. Light or electromagnetic field is introduced from the external field transmitter 1 and the transmitted light from the external field detector 2 on the opposite side is measured. Alternatively, the reflected light may be measured on the outside field introduction port side.

図１０は実施例２における測定を示す説明図である。計測１はＮＭＲ測定を示す。計測２は外場111を与えたときのＮＭＲ測定を示す。本実施例では外場を与えた時の透過光を計測し、この計測結果を判定条件としている。113は溶液４中の標的が蛋白質のみの試料である。   FIG. 10 is an explanatory diagram showing measurement in Example 2. Measurement 1 shows NMR measurement. Measurement 2 shows the NMR measurement when the external field 111 is given. In this embodiment, transmitted light when an external field is applied is measured, and the measurement result is used as a determination condition. 113 is a sample in which the target in the solution 4 is only a protein.

図８は外場を利用した測定フローである。実施例１と異なるのは、ＮＭＲ測定と並列に、外場を測定し（201）、外場の計測結果から、下記（１）、（２）が判定（202）された場合に、測定を中断するか、測定パラメータを変更する。   FIG. 8 is a measurement flow using an external field. The difference from Example 1 is that the external field is measured in parallel with the NMR measurement (201), and when the following (1) and (2) are determined (202) from the measurement result of the external field, the measurement is performed. Stop or change measurement parameters.

同一試料の測定途中に構成元素の比率が１％以上変化する場合は、外場の着目する構成元素に関する計測スペクトルの変化から判定する。また、不純物に関しては、予め、外場による不純物の計測スペクトルデータを303の制御装置のメモリーに格納しておき、計測途中で、外場計測データと比較することにより、判定する。
（１）質の低い実験データの測定：測定途中で試料が変質する場合（同一試料の測定途中に構成元素の比率が１％以上変化する）。
（２）試料に混入されている不純物を測定した場合（蛋白質をターゲットし、アミノ酸が検出されない）。 When the ratio of the constituent elements changes by 1% or more during the measurement of the same sample, the determination is made from the change in the measurement spectrum related to the constituent elements of interest in the external field. In addition, impurities are determined by storing measured spectrum data of impurities in the external field in advance in the memory of the control device 303 and comparing the measured spectrum data with the external field measurement data during the measurement.
(1) Measurement of low-quality experimental data: When the sample changes in the middle of measurement (the ratio of the constituent elements changes by 1% or more during the measurement of the same sample).
(2) When impurities contained in the sample are measured (proteins are targeted and amino acids are not detected).

実施例２は外場を導入するため、実施例１にくらべ情報量が増え、NMRに比較して、短期間で（１）、（２）を判定することできる利点がある。   Since Example 2 introduces an external field, the amount of information increases compared to Example 1, and there is an advantage that (1) and (2) can be determined in a short period of time compared to NMR.

本実施例によれば、ユーザーに新たな負担を加える事になしにNMR計測を高スループット化することができる。   According to the present embodiment, it is possible to increase the NMR measurement without adding a new burden on the user.

なお、上記の実施例１においては、試料として、蛋白質、糖鎖または薬化合物としている。このとき、前処理として、ＬＣ（液体クロマト）により、試料が分離され、自動的にＮＭＲにて計測される。   In Example 1 above, the sample is a protein, sugar chain or drug compound. At this time, as a pretreatment, the sample is separated by LC (liquid chromatography) and automatically measured by NMR.

このとき、上記（１）−（３）の判定条件のうち、特に、既に何回も測定した試料であるかを判定する際に、試料のＬＣ保持時間（リテンションタイム）がある裕度で一致するかどうか調べるようにしてもよい。これにより、試料に関する情報が増え、計測変更の判定の精度を向上できる。   At this time, among the determination conditions (1) to (3) above, particularly when determining whether the sample has already been measured many times, the LC retention time (retention time) of the sample matches with a certain margin. You may make it check whether to do. Thereby, the information regarding a sample increases and the precision of determination of a measurement change can be improved.

本発明の実施例１における核磁気共鳴の計測処理を示すフロー図。The flowchart which shows the measurement process of the nuclear magnetic resonance in Example 1 of this invention. 本発明を実施するに好適な核磁気共鳴測定システム構成図。1 is a configuration diagram of a nuclear magnetic resonance measurement system suitable for carrying out the present invention. 本発明を実施するに好適な核磁気共鳴測定のフロー図。FIG. 3 is a flow chart of nuclear magnetic resonance measurement suitable for carrying out the present invention. 実施例１の核磁気共鳴装置の各構成要素の配置を模式図。FIG. 3 is a schematic diagram showing the arrangement of each component of the nuclear magnetic resonance apparatus of the first embodiment. 核磁気共鳴装置の各構成要素の他の配置を模式図。The schematic diagram of other arrangement | positioning of each component of a nuclear magnetic resonance apparatus. 実施例１による核磁気共鳴測定のタイムチャート図。FIG. 3 is a time chart of nuclear magnetic resonance measurement according to the first embodiment. 実施例１による他の核磁気共鳴測定のタイムチャート図。FIG. 6 is a time chart of another nuclear magnetic resonance measurement according to the first embodiment. 本発明の実施例２における核磁気共鳴の計測処理を示すフロー図。The flowchart which shows the measurement process of the nuclear magnetic resonance in Example 2 of this invention. 実施例２の核磁気共鳴装置の各構成要素の配置を模式図。FIG. 6 is a schematic diagram showing the arrangement of each component of the nuclear magnetic resonance apparatus of the second embodiment. 実施例２における測定を示す説明図。Explanatory drawing which shows the measurement in Example 2. FIG.

符号の説明Explanation of symbols

１…外場発信部、２…外場検出部、３…試料のサンプル管、４…試料溶液、５…核磁気共鳴プローブコイル、６…静磁場発生用マグネット、７…マグネットのボア、８…核磁気共鳴プローブコイルの引き出し線、９…試料保持管の導入用のガイド、１０…シールド部、１１１…外場、１１３…標的蛋白質のみの試料。   DESCRIPTION OF SYMBOLS 1 ... External field transmission part, 2 ... External field detection part, 3 ... Sample tube of sample, 4 ... Sample solution, 5 ... Nuclear magnetic resonance probe coil, 6 ... Magnet for static magnetic field generation, 7 ... Bore of magnet, 8 ... Lead wire of nuclear magnetic resonance probe coil, 9 ... guide for introducing sample holding tube, 10 ... shield portion, 111 ... external field, 113 ... sample of only target protein.

Claims (8)

核磁気共鳴（ＮＭＲ）測定に基づいて試料の構造を分析する核磁気共鳴計測方法において、
複数の試料の中から選定された試料についてＮＭＲ測定を実施し、所定時間経過後に測定データを分析し、（１）質の低いデータか、（２）不純物有りか、（３）同一試料の測定回数がしきい値以上か判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、何れかに該当する場合は当該試料の測定を終了して次の試料の測定に移ることを特徴とする核磁気共鳴計測方法。 In a nuclear magnetic resonance measurement method for analyzing the structure of a sample based on nuclear magnetic resonance (NMR) measurement,
NMR measurement is performed on a sample selected from a plurality of samples, and the measurement data is analyzed after a predetermined period of time. (1) Whether the data is low quality, (2) Impurity exists, (3) Measurement of the same sample It is determined whether the number of times is greater than or equal to a threshold value, and if none of the above is true, the NMR measurement is continued, and if any of them is true, the measurement of the sample is terminated and the measurement of the next sample is started. Nuclear magnetic resonance measurement method. 請求項１において、前記（１）−（３）の何れかに該当する場合は、測定パラメータを再設定することを特徴とする核磁気共鳴計測方法。   The nuclear magnetic resonance measurement method according to claim 1, wherein when any of (1) to (3) is satisfied, the measurement parameter is reset. 核磁気共鳴（ＮＭＲ）測定と外場に基づいて試料の物質の構造を分析する核磁気共鳴計測方法において、
複数の試料の中から選定された試料についてＮＭＲ測定を実施し、所定時間経過後に外場を与えて該外場の測定データを分析し、（１）質の低いデータか、（２）不純物有りか判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、（１）または（２）に該当する場合は当該試料の測定を終了して次の試料の測定に移ることを特徴とする核磁気共鳴計測方法。 In a nuclear magnetic resonance measurement method for analyzing the structure of a sample material based on nuclear magnetic resonance (NMR) measurement and an external field,
NMR measurement is performed on a sample selected from a plurality of samples, and an external field is applied after a predetermined period of time to analyze the measurement data of the external field. (1) Low quality data or (2) Impurities The above-described NMR measurement is continued if none of the above applies, and the measurement of the sample is terminated and the measurement is transferred to the next sample if the measurement corresponds to (1) or (2). Nuclear magnetic resonance measurement method. 請求項３において、外場として光、電磁場、テラヘルツ、熱超音波の何れかを導入することを特徴とする核磁気共鳴計測方法。   4. The nuclear magnetic resonance measurement method according to claim 3, wherein any one of light, electromagnetic field, terahertz, and thermal ultrasonic waves is introduced as an external field. 試料の構造を示すデータを測定する核磁気共鳴測定装置と、測定データに基づいて試料の構造を分析し、同定するデータ後処理装置と、測定を制御する制御装置を備える核磁気共鳴計測システムにおいて、
前記制御装置は、複数の試料の中から選定された試料について前記核磁気共鳴測定装置にＮＭＲ測定を実施させ、所定時間経過後に測定データを分析し、（１）質の低いデータか、（２）不純物有りか、（３）同一試料の測定回数がしきい値以上か判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、何れかに該当する場合は当該試料の測定を終了して次の試料の測定に移るように構成したことを特徴とする核磁気共鳴計測システム。 In a nuclear magnetic resonance measuring system including a nuclear magnetic resonance measuring apparatus that measures data indicating the structure of a sample, a data post-processing apparatus that analyzes and identifies the structure of the sample based on the measurement data, and a control device that controls the measurement ,
The control device causes the nuclear magnetic resonance measurement apparatus to perform NMR measurement on a sample selected from a plurality of samples, and analyzes the measurement data after a predetermined time elapses. (1) Low quality data or (2 ) Determine whether there is an impurity, or (3) If the number of measurements of the same sample is greater than or equal to the threshold value, if none of them is met, continue the NMR measurement. A nuclear magnetic resonance measurement system configured to move to the next sample measurement. 試料の構造を示すデータを測定する核磁気共鳴測定装置と、試料に外場を与えて測定する外場測定装置と、測定データに基づいて試料の構造を分析し、同定するデータ後処理装置と、測定を制御する制御装置を備える核磁気共鳴計測システムにおいて、
前記制御装置は、複数の試料の中から選定された試料について前記核磁気共鳴測定装置にＮＭＲ測定を実施させ、所定時間経過後に外場を与えて外場測定データを分析し、（１）質の低いデータか、（２）不純物有りか判定し、何れにも該当しない場合は前記ＮＭＲ測定を継続し、何れかに該当する場合は当該試料の測定を終了して次の試料の測定に移るように構成したことを特徴とする核磁気共鳴計測システム。 A nuclear magnetic resonance measuring apparatus for measuring data indicating the structure of the sample, an external field measuring apparatus for measuring by applying an external field to the sample, a data post-processing apparatus for analyzing and identifying the structure of the sample based on the measurement data, and In a nuclear magnetic resonance measurement system comprising a control device for controlling the measurement,
The control device causes the nuclear magnetic resonance measurement apparatus to perform NMR measurement on a sample selected from a plurality of samples, gives an external field after a predetermined time, and analyzes external field measurement data. (2) Impurities are determined. If none of the data is applicable, the NMR measurement is continued. If any of the data is applicable, the measurement of the sample is terminated and the measurement of the next sample is started. A nuclear magnetic resonance measurement system characterized by being configured as described above. 請求項５において、前処理として試料を分離する液体クロマトを設け、該液体クロマトで測定された過去の試料のＬＣ保持時間をデータベースに格納し、前記ＮＭＲ測定の前処理として測定されたＬＣ保持時間をデータベースの値と比較し、一致する測定を回避することを特徴とする核磁気共鳴計測システム。   6. The LC retention time measured as a pretreatment of the NMR measurement according to claim 5, wherein a liquid chromatograph for separating the sample is provided as a pretreatment, the LC retention time of the past sample measured by the liquid chromatography is stored in a database, A nuclear magnetic resonance measurement system characterized by comparing the value with the value in the database and avoiding the coincident measurement. 請求項５、６または７において、前記ＮＭＲ測定の測定結果をリアルタイムに格納するデータベースを設けることを特徴とする核磁気共鳴計測システム。   8. The nuclear magnetic resonance measurement system according to claim 5, wherein a database for storing the measurement result of the NMR measurement in real time is provided.
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