NMR measurement method and apparatus

Patent metadata

Field	Value
Publication number	US-11067518-B2
Application number	US-201715837215-A
Country	US
Kind code	B2
Filing date	Dec 11, 2017
Priority date	Dec 12, 2016
Publication date	Jul 20, 2021
Grant date	Jul 20, 2021

Abstract

A whole measurement process includes a plurality of step combinations. Each of the step combinations is composed of a solution-state measurement step and a solid-state measurement step. In the solution-state measurement step, solution-state NMR measurement is performed such that magnetization that is to be used in the solid-state measurement step remains. In the solid-state measurement step, solid-state NMR measurement is performed by using the magnetization that remains. No waiting time for recovering magnetization is provided between the solution-state measurement step and the solid-state measurement step. The solid-state measurement step may be performed earlier, and the solution-state measurement step may be performed later. Alternatively, the two steps may be performed simultaneously.

First claim

The invention claimed is:

1. A time-resolved measurement method for intermittently observing a chemical reaction process or a crystallization process comprising:
repeatedly performing an observation process, the observation process comprising:
(a) providing a magnetization recovery waiting time;
(b) a first measurement step of performing one of solution-state NMR measurement and solid-state NMR measurement on a sample that includes a liquid and a solid;
(c) a second measurement step of performing the other of the solution-state NMR measurement and the solid-state NMR measurement on the sample; and
(d) repeating steps (a)-(c),

wherein the first measurement step performs NMR measurement of nuclei A such that magnetization of nuclei B remains when the second measurement step starts,
wherein the second measurement step performs NMR measurement of nuclei C by using the magnetization that remains in the nuclei B,
wherein the second measurement step is either performed subsequent to the first measurement step without magnetization recovery waiting time after the first measurement step, or performed concurrently with the first measurement step, and
wherein solution-state spectra are obtained at regular time intervals by repetition of the solution-state NMR measurements and solid-state spectra are obtained at the same regular time intervals by repetition of the solid-state NMR measurements.

2. The method according to claim 1 ,
wherein the nuclei C are nuclei that are the same as the nuclei A, nuclei that are the same as the nuclei B, or nuclei that are different from both the nuclei A and the nuclei B.

3. The method according to claim 1 ,
wherein the second measurement step includes a magnetization transfer step of transferring the magnetization that remains in the nuclei B to the nuclei C.

4. The method according to claim 3 ,
wherein the magnetization transfer step uses dipole-dipole interaction between the nuclei B and the nuclei C.

5. The method according to claim 1 ,
wherein the first measurement step is a solution-state NMR measurement step whose observation target is the nuclei A present in the liquid, and
wherein the second measurement step is performed subsequent to the first measurement step, and is a solid-state NMR measurement step whose observation target is the nuclei C present in the solid.

6. The method according to claim 5 ,
wherein the solid-state NMR measurement step comprises:
a magnetization transfer step of using dipole-dipole interaction that transfers the magnetization of the nuclei B to the nuclei C; and
after the magnetization transfer step, a detection step of detecting an FID signal coming from the nuclei C.

7. An NMR measurement apparatus comprising:
a sample container for containing a sample that includes a liquid and a solid, the sample container being placed in a static magnetic field;
measurement means for irradiating the sample with an RF wave and detecting an NMR signal coming from the sample;
transmission and reception means for supplying a transmission signal to the measurement means and processing a reception signal output from the measurement means; and
control means for setting a pulse sequence that is to be performed by the transmission and reception means,
wherein the pulse sequence includes a first subsequence and a second subsequence,
wherein the first subsequence is a subsequence for performing NMR measurement of nuclei A such that magnetization of nuclei B remains when the second subsequence starts and comprises performing of one of solution-state NMR measurement and solid-state NMR measurement on the sample,
wherein the second subsequence is a subsequence for performing NMR measurement of nuclei C by using the magnetization that remains in the nuclei B and comprises performing the other of the solution-state NMR measurement and the solid-state NMR measurement on the sample,
wherein the second subsequence is either performed subsequent to the first subsequence without magnetization recovery waiting time after the first subsequence, or performed concurrently with the first subsequence, and
wherein an observation process for intermittently observing a chemical reaction process or a crystallization process is repeatedly performed, the observation process comprises providing a magnetization recovery waiting time prior to performing the first subsequence, and
wherein the NMR measurement of nuclei A is obtained at regular time intervals by repetition of the first subsequence and the NMR measurement of nuclei C is obtained at the same regular time intervals by repetition of the second subsequence.

Assignees

• Riken
• Jeol Ltd

Inventors

• Nishiyama Yusuke

Classifications

• G01N24/08 Primary

  by using nuclear magnetic resonance (G01N24/12 takes precedence) · CPC title

• G01N24/088

  Assessment or manipulation of a chemical or biochemical reaction, e.g. verification whether a chemical reaction occurred or whether a ligand binds to a receptor in drug screening or assessing reaction kinetics · CPC title

• G01R33/44

  using nuclear magnetic resonance [NMR] (G01R33/24, G01R33/62 take precedence) · CPC title

• G01R33/4641

  Sequences for NMR spectroscopy of samples with ultrashort relaxation times such as solid samples · CPC title

• G01R33/50

  based on the determination of relaxation times {, e.g. T1 measurement by IR sequences; T2 measurement by multiple-echo sequences} · CPC title