CN111044960B - Solid nuclear magnetic resonance quantitative detection method and device based on successive cross polarization - Google Patents

Solid nuclear magnetic resonance quantitative detection method and device based on successive cross polarization Download PDF

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CN111044960B
CN111044960B CN201911410819.4A CN201911410819A CN111044960B CN 111044960 B CN111044960 B CN 111044960B CN 201911410819 A CN201911410819 A CN 201911410819A CN 111044960 B CN111044960 B CN 111044960B
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CN111044960A (en
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舒婕
唐丹丹
王宁
张志兰
闫春辉
唐明华
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Suzhou University
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    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
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    • G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
    • G01R33/00—Arrangements or instruments for measuring magnetic variables
    • G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
    • G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
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Abstract

The application provides a solid nuclear magnetic resonance quantitative detection method and a solid nuclear magnetic resonance quantitative detection device based on successive cross polarization, wherein a sample to be detected is detected on a solid nuclear magnetic resonance spectrometer based on a preset pulse sequence, and a spectrogram of the sample to be detected is obtained; the pulse sequence comprises a plurality of first pulse units and a second pulse unit, wherein the first pulse units are used for increasing different groups in a sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13and C, performing cross polarization on the C nucleus, and calculating the proportion of each group in the sample to be detected according to the spectrogram of the sample to be detected. In the scheme, the second pulse unit is used for measuring the content of the sample to be measured1The magnetization vector of the H-nucleus is fixed in the magic angle direction, thereby prolonging the length of the sample to be measured1T of H nucleus1ρ HAnd the effect of improving the accuracy of quantitative detection is achieved.

Description

Solid nuclear magnetic resonance quantitative detection method and device based on successive cross polarization
Technical Field
The invention relates to the technical field of nuclear magnetic resonance, in particular to a solid nuclear magnetic resonance quantitative detection method and device based on successive cross polarization.
Background
The solid nuclear magnetic resonance quantitative detection technology is used for quantitatively analyzing the structure and components of a solid sample. The technology is mainly characterized in that a preset pulse sequence is transmitted to a solid sample to be analyzed to determine an initial spectrogram of the sample to be analyzed, the initial spectrogram is subjected to Fourier transform, phase correction and baseline correction to obtain a processed spectrogram, and finally, the spectral peaks of all groups in the processed spectrogram are integrated, so that the proportion of all groups or components in the sample to be analyzed can be determined.
In the existing solid nuclear magnetic resonance quantitative detection technology, the most convenient and fast technology is to measure a sample to be analyzed by using a pulse sequence (Multiple-CP) consisting of a plurality of cross-polarized pulse units. However, when the measurement is performed based on such a pulse sequence, if it is in the sample to be analyzed1Spin lattice relaxation time (T) under spin-locking field of H-nuclei1ρ H) Shorter, the accuracy of the results obtained from the final measurement can be significantly affected.
Disclosure of Invention
Based on the defects of the prior art, the invention provides a solid nuclear magnetic resonance quantitative detection method and a solid nuclear magnetic resonance quantitative detection device based on successive cross polarization, so as to solve the problem that the prior detection technology detects T1ρ HThe accuracy is poor when the sample is short.
The invention provides a solid nuclear magnetic resonance quantitative detection method based on successive cross polarization, which comprises the following steps:
determining a sample to be detected on the basis of a preset pulse sequence in a solid nuclear magnetic resonance spectrometer to obtain a spectrogram of the sample to be detected; the preset pulse sequence comprises a plurality of first pulse units and a second pulse unit which are sequentially arranged, wherein the first pulse units are used for increasing the number of groups which are positioned in different groups in the sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus;
sequentially carrying out Fourier transform, phase correction and baseline correction on the spectrogram of the sample to be detected to obtain a processed spectrogram;
and integrating the spectral peaks respectively corresponding to different groups of the sample to be detected in the processed spectrogram, thereby determining the proportion of each group or component in the sample to be detected.
Optionally, the determining a sample to be detected on the basis of a preset pulse sequence in a solid-state nuclear magnetic resonance spectrometer to obtain a spectrogram of the sample to be detected includes:
increasing different groups in the sample to be detected by using first pulse units in the pulse sequence one by one13Enhancement coefficient of signal of the C-nucleus;
the magnetization vector of the 1H nucleus of the sample to be detected is locked in the magic angle direction by utilizing the spin locking field generated by the second pulse unit, and the magnetization vector of the sample to be detected is locked in the magic angle direction13C core and1h nucleus is cross-polarized; wherein the effective field direction of the spin locking field is the magic angle direction;
collecting different groups in the sample to be tested13And C, obtaining a spectrogram of the sample to be detected by using the signal of the core C.
Optionally, the spin locking field generated by the second pulse unit is used for locking the spin of the sample to be tested1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1the H nucleus is cross-polarized, and comprises:
in that1The H channel applies a first RF pulse to1The magnetization vector of the H nucleus is parallel to the xy plane; wherein the first radio frequency pulse is a 90 ° radio frequency pulse;
applying a second RF pulse to the sample to be measured1The magnetization vector of the H nucleus is in the magic angle direction which deviates 54.7 degrees from the z axis; wherein the second radio frequency pulse is a 35.3 ° radio frequency pulse;
applying a third RF pulse to1The effective field direction of H is magic angle direction and is along the direction of spin locking field1H nucleus and13c, performing cross polarization on the nucleus; wherein the third RF pulse comprises1H spin-locked field RF pulse and13c, said spin-locked field radio frequency pulse of1The off-resonance frequency of the spin-lock field RF pulse of H is equal to the spin-lock field RF pulse power of 1H divided by
Figure BDA0002349916750000021
The second aspect of the present invention provides a solid-state nuclear magnetic resonance quantitative detection apparatus based on sequential cross polarization, comprising:
the measuring unit is used for measuring a sample to be measured on the basis of a preset pulse sequence in a solid nuclear magnetic resonance spectrometer to obtain a spectrogram of the sample to be measured; the preset pulse sequence comprises a plurality of first pulse units and a second pulse unit which are sequentially arranged, wherein the first pulse units are used for increasing the number of groups which are positioned in different groups in the sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus;
the processing unit is used for sequentially carrying out Fourier transform, phase correction and baseline correction on the spectrogram of the sample to be detected to obtain a processed spectrogram;
and the integration unit is used for integrating the spectral peaks of different groups respectively corresponding to the sample to be detected in the processed spectrogram, so as to determine the proportion of each group in the sample to be detected.
Optionally, the determining unit is configured to determine, based on a preset pulse sequence, a sample to be detected on a solid nuclear magnetic resonance spectrometer, and when obtaining a spectrogram of the sample to be detected, the determining unit is specifically configured to:
increasing different groups in the sample to be detected by using first pulse units in the pulse sequence one by one13Enhancement coefficient of signal of the C-nucleus;
the spin locking field generated by the second pulse unit is used for locking the sample to be measured1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1h nucleus is cross-polarized; wherein the effective field direction of the spin locking field is the magic angle direction;
collecting different groups in the sample to be tested13And C, obtaining a spectrogram of the sample to be detected by using the signal of the core C.
Optionally, the measuring unit generates using the second pulse unitThe spin lock field of1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1when the H nucleus is cross-polarized, the method is specifically used for:
in that1The H channel applies a first RF pulse to1The magnetization vector of the H nucleus is parallel to the xy plane; wherein the first radio frequency pulse is a 90 ° radio frequency pulse;
applying a second RF pulse to the sample to be measured1The magnetization vector of the H nucleus is in the magic angle direction which deviates 54.7 degrees from the z axis; wherein the second radio frequency pulse is a 35.3 ° radio frequency pulse;
applying a third RF pulse to1The effective field direction of H is magic angle direction and is along the direction of spin locking field1H nucleus and13c, performing cross polarization on the nucleus; wherein the third RF pulse comprises1H spin-locked field RF pulse and13c, said spin-locked field radio frequency pulse of1The off-resonance frequency of the spin-locked field RF pulse of H is equal to the1Spin-locked field RF pulse power of H divided by
Figure BDA0002349916750000031
The application provides a solid nuclear magnetic resonance quantitative detection method and a solid nuclear magnetic resonance quantitative detection device based on successive cross polarization, wherein a sample to be detected is detected on a solid nuclear magnetic resonance spectrometer based on a preset pulse sequence, and a spectrogram of the sample to be detected is obtained; the pulse sequence comprises a plurality of first pulse units and a second pulse unit, wherein the first pulse units are used for increasing different groups in a sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus; carrying out Fourier transform, phase correction and baseline correction on a spectrogram of a sample to be detected in sequence to obtain a processed spectrogram; finally, integrating the spectral peaks of different groups respectively corresponding to the sample to be detected in the spectrogram, thereby determining the sample to be detectedThe ratio of each group or component in (a). The scheme is to detect the content of the sample1The magnetization vector of the H-nucleus is fixed in the magic angle direction, thereby prolonging the length of the sample to be measured1T of H nucleus1ρ HAnd the effect of improving the accuracy of quantitative detection is achieved.
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In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
FIG. 1 is a schematic diagram of a pulse sequence used in analyzing a sample by a conventional cross-polarization method;
FIG. 2 is a schematic diagram showing a pulse sequence used in the measurement of a sample by a conventional sequential cross-polarization (Multiple-CP) method;
FIG. 3 is a flow chart of a successive cross polarization based solid NMR quantitative detection method provided by the present application;
FIG. 4 is a schematic diagram of a pulse sequence and a phase cycle used in the method for the quantitative detection of solid NMR based on successive cross polarization provided in the present application;
FIG. 5a is a graph showing the relationship between the contact time and the relative intensity of the peak of each group when alanine solid powder was detected by the CP method;
FIG. 5b is a graph showing the relationship between the contact time and the relative intensity of the peak of each group when alanine solid powder was detected by the Multiple-CP method;
FIG. 5c is a graph showing the relationship between the contact time and the relative intensity of the peaks of the respective groups when alanine solid powder is detected by the successive cross polarization based solid NMR quantitative determination method provided herein;
fig. 6 is a schematic structural diagram of a successive cross polarization based solid-state nmr quantitative detection apparatus according to an embodiment of the present application.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
First, to facilitate understanding of the protocol provided herein, two solid-state nmr detection methods are briefly described below.
The first solid-state nuclear magnetic resonance detection method is proposed based on Cross Polarization (CP) phenomenon, and is a Cross Polarization detection method (CP method for short) implemented by using a single Cross Polarization pulse unit. The technology utilizes a single cross polarization pulse unit to measure the atlas of the sample to be measured, and has the advantages of short time consumption and high sensitivity. However, the CP method has no quantification property, and cannot accurately calculate the ratio of each group in the sample to be measured.
The pulse sequence of a single cross-polarized pulse unit is shown in fig. 1, where the black rectangles represent 90 ° rf pulses and the white rectangles represent cross-polarized spin-lock field pulses.
The second solid nuclear magnetic resonance detection method is to form a pulse unit sequence by a plurality of cross polarization pulse units, and to perform a plurality of cross polarization on a sample to be detected by using the pulse unit sequence, thereby determining the spectrogram of the sample to be detected. This method may be referred to as a successive cross-polarization (Multiple-CP) method. The spectrum of the sample to be detected obtained by the measurement of the Multiple-CP method can determine the proportion of each group in the sample to be detected by calculating the integral of each spectrum peak in the spectrum, namely, the Multiple-CP method can realize the quantitative detection of the solid sample.
Specifically, the Multiple-CP method utilizes a plurality of cross-polarization pulse units to carry out cross-polarization processes of corresponding times on a sample to be detected, so that different groups in the sample to be detected are subjected to cross-polarization processes13The enhancement coefficient eta of the signal of the C core is continuously increased, so that the enhancement coefficient finally tends toConsistent and close to ideal values: etaideal＝γH/γCThereby realizing the purpose of quantitatively detecting each group in the sample to be detected.
Wherein eta isidealAfter cross polarization in an ideal state13Enhancement factor of C nucleus, gammaHIs composed of1Gyromagnetic ratio of H nucleus, gammaCIs composed of13Gyromagnetic ratio of the C nucleus.
However, the Multiple-CP method cannot inhibit the content of the sample to be detected1Spin lattice relaxation time under spin-locking field of H-nuclei (i.e. T)1ρ H) For T1ρ HShort samples or groups, and the quantitative detection results measured using the Multiple-CP method tend to be less accurate.
The pulse sequence used for determining the profile of the sample to be tested in the Multiple-CP method is shown in FIG. 2, in which Loop represents the number of cycles of the cross-polarization process.
Based on the defects of the Multiple-CP method, the application provides a novel pulse sequence and a solid nuclear magnetic resonance quantitative detection method based on the novel pulse sequence so as to provide a method for more accurately detecting T1ρ HA method for quantitative detection of shorter samples or groups.
Referring to fig. 3, the method includes the following steps:
s301, determining the sample to be detected on the basis of the preset pulse sequence on a solid nuclear magnetic resonance spectrometer, and obtaining a spectrogram of the sample to be detected.
The preset pulse sequence comprises a plurality of first pulse units and a second pulse unit, wherein the first pulse units are used for increasing different groups in a sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13the C nuclei were cross-polarized.
Specifically, the first pulse unit in step S301 may be a Cross-polarized pulse unit (i.e., CP unit) as described above, and the second pulse unit is an LGCP (Lee-Goldbury Cross Polarization) unit.
That is, the pulse sequence used in the present application to determine the spectrum of the sample to be measured, the pulse sequence consisting of a plurality of CP units and one LGCP unit, may be referred to as a Multiple-LGCP pulse sequence. The solid nuclear magnetic resonance quantitative detection method based on the Multiple-LGCP pulse sequence can be correspondingly marked as a Multiple-LGCP method.
An alternative schematic of the Multiple-LGCP pulse sequence is shown in fig. 4, where the gray rectangles represent 35.3 ° pulses and the gray shaded rectangles represent LGCP processes. The phase cycle related to the pulse sequence is phi 1 ═ y, -y; 2 is-y, y; x, x, -x, -x, y, y, -y, -y; phi 4 is x; Φ 6 ═ y, y, y, -y, x, -x, -x, x; phi 7 is-y, y; Φ 8 ═ y, -y, -y, y, -x, x, x, -x; and (x, x, y) where 2 is 35.3 ° of the phase cycle for the pulse (each pulse corresponds to the phase cycle as indicated by the label in fig. 4).
It is understood that, on the basis of the pulse sequence (referred to as Multiple-CP pulse sequence) used in the existing Multiple-CP method, the last CP unit of the Multiple-CP pulse sequence may be replaced with the LGCP unit, so as to obtain the Multiple-LGCP pulse sequence used in the present application.
The specific process for determining the spectrogram of the sample to be detected by using the Multiple-LGCP pulse sequence comprises the following steps of:
increasing the CP units in the Multiple-LGCP pulse sequence one by one to be positioned at different groups in the sample to be tested13Enhancement factor of the signal of the C-nucleus.
The spin locking field generated by the LGCP unit in the Multiple-LGCP pulse sequence is used for locking the spin of the sample to be tested1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1the H nuclei were cross-polarized.
Wherein, the effective field direction of the spin locking field is magic angle direction.
Collecting different radicals in a sample to be tested13And C, obtaining a spectrogram of the sample to be detected by using the signal of the core C.
Using LGCP in Multiple-LGCP pulse sequencesThe spin-locked field generated by the unit will be of the sample to be measured1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1the specific process of cross-polarization of H nucleus is:
in that1The H channel applies a first RF pulse to1The magnetization vector of the H nucleus is parallel to the xy plane; wherein the first radio frequency pulse is a 90 ° radio frequency pulse.
Applying a second RF pulse to the sample to be measured1The magnetization vector of the H-nuclei is in the magic angle direction of 54.7 ° off the z-axis. Wherein the second rf pulse is a 35.3 ° rf pulse.
Applying a third RF pulse to1The effective field direction of H is magic angle direction and is along the direction of spin locking field1H nucleus and13the C nuclei were cross-polarized.
Wherein the third RF pulse comprises1H spin-locked field RF pulse and13the spin-lock field radio frequency pulse of C,1the off-resonance frequency Δ LG of the spin-locked field rf pulse of H satisfies the following condition:
Figure BDA0002349916750000071
wherein, ω is1To represent1The power of the spin-lock field radio frequency pulse of H.
The solid nuclear magnetic resonance detection method provided by the application can accurately detect T1ρ HShorter samples or groups were quantitatively detected because:
will be provided with1The magnetization vector of the H nucleus is locked in the magic angle direction, and the dipole coupling effect between hydrogen nuclei can be inhibited, so that the magnetization vector can be effectively prolonged in the sample or the group1T of H nucleus1ρ HThereby obtaining more accurate quantitative detection results.
S302, Fourier transform, phase correction and baseline correction are sequentially carried out on the spectrogram of the sample to be detected, and the processed spectrogram is obtained.
And S303, integrating the spectral peaks respectively corresponding to different groups of the sample to be detected in the processed spectrogram, so as to determine the proportion of each group in the sample to be detected.
The specific operation process of the solid nuclear magnetic resonance quantitative detection method provided by the application is as follows:
and (3) filling solid powder of a sample to be detected into the solid nuclear magnetic tube and placing the solid nuclear magnetic tube into the probe, calling a Multiple-LGCP pulse sequence file, setting optimized experimental parameters, and collecting a spectrogram of the sample to be detected, which is obtained by measuring the Multiple-LGCP pulse sequence. After the acquisition is finished, Fourier transform, phase correction and baseline correction are carried out on the acquired spectrogram to obtain a processed spectrogram, then, integration is carried out on the spectral peaks of all the groups in the processed spectrogram respectively to obtain the integral value of each group, namely the final quantitative data.
During the above procedure, the cross-polarization kinetic curve was plotted using origine 7.5 software, revealing the dependence of the relative intensity of the corresponding spectral peak of each group on the cross-polarization contact time.
The application provides a solid nuclear magnetic resonance quantitative detection method based on successive cross polarization, which is characterized in that a sample to be detected is detected on a solid nuclear magnetic resonance spectrometer based on a preset pulse sequence, and a spectrogram of the sample to be detected is obtained; the pulse sequence comprises a plurality of first pulse units and a second pulse unit, wherein the first pulse units are used for increasing different groups in a sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus; carrying out Fourier transform, phase correction and baseline correction on a spectrogram of a sample to be detected in sequence to obtain a processed spectrogram; and finally, integrating the spectral peaks of different groups respectively corresponding to the sample to be detected in the spectrogram, thereby determining the proportion of each group or component in the sample to be detected. The scheme is to detect the content of the sample1The magnetization vector of the H-nucleus is fixed in the magic angle direction, thereby prolonging the length of the sample to be measured1T of H nucleus1ρ HTo achieve improved quantitative detectionThe effect of accuracy.
The following describes the process and results of detecting a specific sample by using the method provided by the present application, and also provides the results of detecting a sample by using the existing CP method and Multiple-CP method as a comparison for intuitively understanding the beneficial effects of the method provided by the present application.
In this example, the test was carried out using alanine solid powder as a sample to be tested. Alanine was chosen as the reason for the quantitative analysis: the signal-to-noise ratio of the CP spectrum of alanine is high, and the method is commonly used for a standard sample optimized by a solid nuclear magnetic method. Furthermore, T of alanine1ρ HShorter, T at a spin-lock field strength of 62.5kHz1ρ HIs 1.67 ms.
The parameters of the instrument used in determining the alanine profile were as follows:
the apparatus used for quantitative determination of alanine was an Avance III HD 400 solid NMR spectrometer with a magic angle of 5kHz, using a DVT H/X probe, supporting a 3.2mm solid sample tube.
In the process of acquiring the spectrogram, the parameters used by the Multiple-LGCP pulse sequence are as follows:1the 90 ° pulse width for the H channel was set to 3.2 μ s and the power was 78.1 kHz. In LGCP Process1The pulse power of the H channel was 62.5 kHz.13The 90 ° pulse width for C was set at 3.2 μ s and the power was 78.1 kHz. The waiting time for each sampling is 6s, and the number n of CP process cycles is 3. The cross-polarization pulses used in the experiments were all Ramp-shaped pulses. The contact time during LGCP was 0.8 ms. The CP contact time of the cross-polarization kinetic curve is 1-2ms with 1ms interval.
The specific experimental operation steps comprise: and (3) filling solid alanine powder into a solid nuclear magnetic tube and placing the solid nuclear magnetic tube into a probe, calling a Multiple-LGCP pulse sequence file, setting optimized experimental parameters, and collecting a spectrogram of alanine. And after the acquisition is finished, Fourier transform, phase correction and baseline correction are carried out. And integrating three groups of CH3, CH and COOH in the alanine spectrogram to obtain corresponding integral values, namely the final quantitative data. The cross-polarization kinetic curve was plotted using origine 7.5 software to reveal the dependence of the relative intensity of the spectral peaks of each group on the cross-polarization contact time.
Table 1 below shows experimental error data obtained by examining alanine solid powder by the CP method, the Multiple-CP method, and the Multiple-LGCP method, respectively.
TABLE 1
Figure BDA0002349916750000091
Figure BDA0002349916750000101
With reference to table 1 and fig. 5a, 5b and 5c, which show graphs of the relative intensity relationship between the contact time and the peak spectrum of each group in different detection methods, wherein the abscissa of fig. 5a, 5b and 5c is the contact time, the ordinate is the relative intensity, as indicated in the graph, the square coordinate points indicate the relative intensity of COOH groups, the circular coordinate points indicate the relative intensity of CH groups, and the triangular coordinate points indicate CH groups3Relative strength of the groups.
It can be found that:
as shown in FIG. 5a, for the CP method, the relative strength of each group of alanine is obviously different under the same contact time, the deviation is large compared with the theoretical ratio of the groups, and the deviation is between 18 and 78 percent, which indicates that the CP is not quantitative.
As shown in FIG. 5b, the relative intensity of each group of alanine detected by the Multiple-CP method is close to the theoretical value compared with the CP method, but the deviation of the test result gradually increases with the increase of the contact time of the cross-polarized pulse unit and the sample, which shows that the accuracy of the quantitative detection of Multiple-CP is influenced by the T of the sample to be detected1ρ HThe influence of (c). As can be seen from the data in Table 1, when alanine was detected by the Multiple-CP method, the T of alanine was detected1ρ HThe influence is obvious, and the error is 5 percent when the quantitative results of the CH3, CH and COOH groups of the alanine are compared with the standard values within 0.4-0.7 ms of the contact timeThe following; however, as the contact time increases, the error increases gradually and exceeds 5%, up to 22%. Therefore, for the Multiple-CP method, the contact time of the cross-polarized pulse unit needs to be set within the range of 0.4-0.7 ms, and the requirement of parameter conditions is severe.
The Multiple-LGCP method provided by the application can inhibit T of alanine1ρ HUnder the same contact time of the cross polarization pulse unit, the relative intensities of the spectrum peaks of all the groups basically tend to be consistent, when the contact time is 0.4-1.8 ms, the error of the quantitative detection result of the three groups is less than 3%, the accuracy is high, and the range of the allowed contact time parameter setting is wide.
With reference to fig. 6, the apparatus includes the following structure:
the determination unit 601 is configured to determine, on the basis of a preset pulse sequence, a sample to be detected on a solid nuclear magnetic resonance spectrometer, so as to obtain a spectrogram of the sample to be detected.
The preset pulse sequence comprises a plurality of first pulse units and a second pulse unit which are sequentially arranged, wherein the first pulse units are used for increasing different groups in a sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13the C nuclei were cross-polarized.
The processing unit 602 is configured to perform fourier transform, phase correction, and baseline correction on a spectrogram of a sample to be detected in sequence, so as to obtain a processed spectrogram.
An integrating unit 603, configured to integrate spectral peaks, in the processed spectrogram, corresponding to different groups of the sample to be detected, respectively, so as to determine a proportion of each group in the sample to be detected.
The determination unit 601 is configured to determine a sample to be detected on the basis of a preset pulse sequence in a solid nuclear magnetic resonance spectrometer, and when obtaining a spectrogram of the sample to be detected, the determination unit is specifically configured to:
increasing the number of different groups in the sample to be tested by using the first pulse unit in the pulse sequence one by one13Enhancement coefficient of signal of the C-nucleus;
using the spin-lock field generated by the second pulse unit to hold the sample to be measured1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1h nucleus is cross-polarized;
wherein, the effective field direction of the spin locking field is a magic angle direction;
collecting different radicals in a sample to be tested13And C, obtaining a spectrogram of the sample to be detected by using the signal of the core C.
The measuring unit 601 uses the spin-lock field generated by the second pulse unit to measure the sample1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1when the H nucleus is cross-polarized, the method is specifically used for:
in that1The H channel applies a first RF pulse to1The magnetization vector of the H nucleus is parallel to the xy plane; wherein the first radio frequency pulse is a 90 ° radio frequency pulse.
Applying a second RF pulse to the sample to be measured1The magnetization vector of the H-nuclei is in the magic angle direction of 54.7 ° off the z-axis. Wherein the second rf pulse is a 35.3 ° rf pulse.
Applying a third RF pulse to1The effective field direction of H is magic angle direction and is along the direction of spin locking field1H nucleus and13the C nuclei were cross-polarized.
Wherein the third RF pulse comprises1H spin-locked field RF pulse and13the spin-lock field radio frequency pulse of C,1the off-resonance frequency Δ LG of the spin-locked field rf pulse of H satisfies the following condition:
Figure BDA0002349916750000111
wherein, ω is1To represent1The power of the spin-lock field radio frequency pulse of H.
The application provides a solid nuclear magnetic resonance quantitative detection device based on successive cross polarization, a determination unit 601 determines a sample to be detected on a solid nuclear magnetic resonance spectrometer based on a preset pulse sequence to obtain a spectrogram of the sample to be detected; the pulse sequence comprises a plurality of first pulse units and a second pulse unit, wherein the first pulse units are used for increasing different groups in a sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus; the processing unit 602 performs fourier transform, phase correction and baseline correction on the spectrogram of the sample to be detected in sequence to obtain a processed spectrogram; the integration unit 603 integrates spectral peaks of the processed spectrogram corresponding to different groups of the sample to be detected, so as to determine the proportion of each group in the sample to be detected. The scheme is to detect the content of the sample1The magnetization vector of the H-nucleus is fixed in the magic angle direction, thereby prolonging the length of the sample to be measured1T of H nucleus1ρ HAnd the effect of improving the accuracy of quantitative detection is achieved.
Those skilled in the art can make or use the present application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the application. Thus, the present application is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims (6)

1. A solid nuclear magnetic resonance quantitative detection method based on successive cross polarization is characterized in that,
determining a sample to be detected on the basis of a preset pulse sequence in a solid nuclear magnetic resonance spectrometer to obtain a spectrogram of the sample to be detected; whereinThe preset pulse sequence comprises a plurality of first pulse units and a second pulse unit which are sequentially arranged, wherein each first pulse unit is used for increasing the number of groups which are positioned in different groups in the sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus;
sequentially carrying out Fourier transform, phase correction and baseline correction on the spectrogram of the sample to be detected to obtain a processed spectrogram;
and integrating the spectral peaks respectively corresponding to different groups of the sample to be detected in the processed spectrogram, thereby determining the proportion of each group in the sample to be detected.
2. The detection method according to claim 1, wherein the step of determining a sample to be detected on the basis of a preset pulse sequence in a solid-state nuclear magnetic resonance spectrometer to obtain a spectrum of the sample to be detected comprises:
increasing different groups in the sample to be detected by using first pulse units in the pulse sequence one by one13Enhancement coefficient of signal of the C-nucleus;
the spin locking field generated by the second pulse unit is used for locking the sample to be measured1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1h nucleus is cross-polarized; wherein the effective field direction of the spin locking field is the magic angle direction;
collecting different groups in the sample to be tested13And C, obtaining a spectrogram of the sample to be detected by using the signal of the core C.
3. The detection method according to claim 2, wherein the spin-lock field generated by the second pulse unit is used to lock the spin of the sample to be detected1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1the H nucleus is cross-polarized, and comprises:
in that1The H channel applies a first RF pulse to1The magnetization vector of the H nucleus is parallel to the xy plane; wherein the first radio frequency pulse is a 90 ° radio frequency pulse;
applying a second RF pulse to the sample to be measured1The magnetization vector of the H nucleus is in the magic angle direction which deviates 54.7 degrees from the z axis; wherein the second radio frequency pulse is a 35.3 ° radio frequency pulse;
applying a third RF pulse to1The effective field direction of H is magic angle direction and is along the direction of spin locking field1H nucleus and13c, performing cross polarization on the nucleus; wherein the third RF pulse comprises1H spin-locked field RF pulse and13c, said spin-locked field radio frequency pulse of1The off-resonance frequency of the spin-locked field RF pulse of H is equal to the1Spin-locked field RF pulse power of H divided by
Figure FDA0002767698770000021
4. A solid nuclear magnetic resonance quantitative detection device based on successive cross polarization is characterized by comprising:
the measuring unit is used for measuring a sample to be measured on the basis of a preset pulse sequence in a solid nuclear magnetic resonance spectrometer to obtain a spectrogram of the sample to be measured; the preset pulse sequence comprises a plurality of first pulse units and a second pulse unit which are sequentially arranged, wherein each first pulse unit is used for increasing the number of groups which are positioned in different groups in the sample to be detected13Enhancement coefficient of signal of the C-nucleus; the second pulse unit is used for sampling the sample to be measured1The magnetization vector of the H nucleus being fixed in the magic angle direction and being used for the sample to be measured1H nucleus and13c, performing cross polarization on the nucleus;
the processing unit is used for sequentially carrying out Fourier transform, phase correction and baseline correction on the spectrogram of the sample to be detected to obtain a processed spectrogram;
and the integration unit is used for integrating the spectral peaks of different groups respectively corresponding to the sample to be detected in the processed spectrogram, so as to determine the proportion of each group in the sample to be detected.
5. The detection apparatus according to claim 4, wherein the determination unit is configured to perform determination on a sample to be detected by a solid-state nuclear magnetic resonance spectrometer based on a preset pulse sequence, and when obtaining a spectrum of the sample to be detected, the determination unit is specifically configured to:
increasing different groups in the sample to be detected by using first pulse units in the pulse sequence one by one13Enhancement coefficient of signal of the C-nucleus;
the spin locking field generated by the second pulse unit is used for locking the sample to be measured1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1h nucleus is cross-polarized; wherein the effective field direction of the spin locking field is the magic angle direction;
collecting different groups in the sample to be tested13And C, obtaining a spectrogram of the sample to be detected by using the signal of the core C.
6. The detecting device according to claim 5, wherein the measuring unit uses the spin-lock field generated by the second pulse unit to lock the spin of the sample to be measured1The magnetization vector of the H nucleus is locked in the magic angle direction and is used for the sample to be measured13C core and1when the H nucleus is cross-polarized, the method is specifically used for:
in that1The H channel applies a first RF pulse to1The magnetization vector of the H nucleus is parallel to the xy plane; wherein the first radio frequency pulse is a 90 ° radio frequency pulse;
applying a second RF pulse to the sample to be measured1The magnetization vector of the H nucleus is in the magic angle direction which deviates 54.7 degrees from the z axis; wherein the second radio frequency pulse is a 35.3 ° radio frequency pulse;
applying a third radio frequencyPulse of1The effective field direction of H is magic angle direction and is along the direction of spin locking field1H nucleus and13c, performing cross polarization on the nucleus; wherein the third RF pulse comprises1H spin-locked field RF pulse and13c, said spin-locked field radio frequency pulse of1The off-resonance frequency of the spin-locked field RF pulse of H is equal to the1Spin-locked field RF pulse power of H divided by
Figure FDA0002767698770000031
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