# US 10,371,774 B2 · Method for two field nuclear magnetic resonance measurements

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- Number: US 10,371,774 B2
- Document ID: US10371774B2
- Status: Granted
- Kind: B2
- Application number: 15/096,287
- Filed: 2016-04-12
- Published: 2016-10-13
- Granted: 2019-08-06
- Earliest claimed: 2015-04-13
- Assignees: Bruker AG; Ecole Normale Superieur; Centre National De La Recherche Scientifique; Universite Pierre Et Marie Curie (Paris 6)
- Applicants: Bruker BioSpin S.A.S.; Ecole normale supérieure; Centre National de la Recherche Scientifique; Université Pierre et Marie Curie (Paris 6)
- Inventors: Samuel Cousin; Cyril Charlier; Fabien Ferrage; Jean-Max Tyburn; Thorsten Marquardsen
- Web page: https://patentgrep.com/patent/US10371774B2

## CPC

- G01R 33/4616: {using specific RF pulses or specific modulation schemes, e.g. stochastic excitation, adiabatic RF pulses, composite pulses, binomial pulses, Shinnar-le-Roux pulses, spectrally selective pulses not being used for spatial selection}
- G01R 33/387: Compensation of inhomogeneities
- G01R 33/445: {MR involving a non-standard magnetic field B0, e.g. of low magnitude as in the earth's magnetic field or in nanoTesla spectroscopy, comprising a polarizing magnetic field for pre-polarisation, B0 with a temporal variation of its magnitude or direction such as field cycling of B0 or rotation of the direction of B0, or spatially inhomogeneous B0 like in fringe-field MR or in stray-field imaging}
- G01R 33/4633: {Sequences for multi-dimensional NMR}
- G01R 33/307: {specially adapted for moving the sample relative to the MR system, e.g. spinning mechanisms, flow cells or means for positioning the sample inside a spectrometer}
- G01R 33/3635: {Multi-frequency operation}
- G01R: MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES (indicating correct tuning of resonant circuits H03J3/12)

## Abstract

A method for carrying out two-field nuclear magnetic resonance (=2FNMR) measurements involves preparing a sample (9a) in a first working volume (5) of a highly homogeneous magnetic field with a first field strength; transferring the sample (9a) to a second working volume (7) with a magnetic field having lower homogeneity and having a second field strength, wherein the first field strength is at least 2 Tesla larger than the second field strength; manipulating the sample (9a) at the second working volume (7) by applying a sequence of radio-frequency (=RF) and/or field gradient pulses; transferring the sample (9a) back to the first working volume (5); and detecting an NMR signal of the sample (9a) in the first working volume (5). The method allows for NMR experiments with which more and/or improved quality information about an investigated sample can be obtained.

## Claims

### Claim 1

A method for carrying out two-field nuclear magnetic resonance (=2FNMR) measurements on a sample, the method comprising the steps of:
a) preparing the sample during a preparation period in a first working volume of a first magnetic field with a first field strength and having a homogeneity better than 0.01 ppm;
b) transferring, during a first transfer period, the sample to a second working volume with a second magnetic field having a homogeneity of 100 ppm or better or in a range between 2 ppm and 100 ppm, and having a second field strength of 0.05 Tesla or larger or of 0.1 Tesla or larger, wherein the first field strength is at least 2 Tesla larger than the second field strength;
c) manipulating, during a manipulation period, the sample at the second working volume by applying a sequence of radio-frequency (=RF) and/or field gradient pulses, wherein the sequence is insensitive to or minimizes effects of an inhomogeneity of the second magnetic field in the second working volume;
d) transferring the sample back to the first working volume during a second transfer period; and
e) detecting an NMR signal of the sample in the first working volume.

### Claim 2 (depends on 1)

The method of claim 1, wherein in step c), the RF and/or field gradient pulse sequence is insensitive to or minimizes the effects of the inhomogeneity of the magnetic field in the second working volume by exciting and/or filtering nuclear spin transitions with energy differences independent of local variations of a strength of the magnetic field in the second working volume.

### Claim 3 (depends on 1)

The method of claim 1, wherein in step c), the RF and/or field gradient pulse sequence excites zero- or multiple-quantum coherences of nuclear spins of the sample in the second working volume.

### Claim 4 (depends on 1)

The method of claim 1, wherein the steps a) through e) are repeated with the sample several times, for obtaining a multidimensional NMR measurement which displays at least one dimension based on a development and/or manipulation of nuclear spins of the sample in the second working volume and at least one dimension based on a development and/or manipulation of nuclear spins of the sample in the first working volume.

### Claim 5 (depends on 4)

The method of claim 4, wherein, in each step c), at least one time parameter of the sequence of RF and/or field gradient pulses is set to a different value.

### Claim 6 (depends on 1)

The method of claim 1, wherein the 2FNMR measurement includes a two-field zero-quantum NMR spectroscopy experiment, with building-up and preparing polarization of nuclei of a specific type during step a), with a sequence of RF pulses, delays and field gradient pulses generating and filtering zero-quantum coherences of a specific type during step c), and with detecting single-quantum coherences during step e).

### Claim 7 (depends on 6)

The method of claim 6, wherein the nuclei of a specific type comprises 13C nuclei.

### Claim 8 (depends on 1)

The method of claim 1, wherein a total duration of the first and second transfer periods and the manipulation period is less than a spin-lattice relaxation time of nuclear spins of the sample manipulated in the second working volume during step c).

### Claim 9 (depends on 1)

The method of claim 1, wherein the first and the second transfer period each have a duration of less than 100 ms.

### Claim 10 (depends on 1)

The method of claim 1, wherein a sequence of RF and/or field gradient pulses is applied to the sample in the first working volume during step a).

### Claim 11 (depends on 1)

The method of claim 1, wherein step e) includes applying a single or a sequence of RF and/or field gradient pulses to the sample in the first working volume before starting NMR signal acquisition.

### Claim 12 (depends on 1)

The method of claim 1, wherein step c) is triggered by position sensors sensing a position of the sample in the second working volume and/or that step e) is triggered by position sensors sensing a position of the sample in the first working volume.

### Claim 13 (depends on 1)

The method of claim 1, wherein NMR probes at the first and second working volume are synchronized.

### Claim 14 (depends on 1)

The method of claim 1, wherein the preparation period of step a) is longer than a spin relaxation time in the first working volume of the nuclear spins of the sample manipulated during step c).

### Claim 15 (depends on 1)

The method of claim 1, wherein, during step a) and/or step c) and/or step e), RF and/or field gradient pulses are applied to different types of nuclei of the sample.

### Claim 16 (depends on 15)

The method of claim 15, wherein nuclear spins of the different nuclei are manipulated at different working volumes.

### Claim 17 (depends on 1)

The method of claim 1, wherein, during step a) and/or step c) and/or step e), RF and/or field gradient pulses are applied only to nuclei of the sample which have an electric quadrupole moment of zero.

### Claim 18 (depends on 17)

The method of claim 17, wherein the nuclei of the sample are 1 H, 13C and/or 15N.

### Claim 19 (depends on 1)

The method of claim 1, wherein during step c), a pulse sequence performs a transfer of polarization in networks of nuclei through scalar coupling interactions or a transfer of polarization by isotropic mixing.