One-dimensional nuclear magnetic resonance total correlation spectrum generation method based on singlet filtering technology

Abstract

The invention discloses a one-dimensional nuclear magnetic resonance total correlation spectrum generation method based on a singlet filtering technology, and relates to the field of nuclear magnetic resonance spectroscopy detection, and longitudinal magnetization of a target coupling atom pair is converted into a nuclear spin singlet signal by adopting adiabatic pulses designed according to specific atomic nucleus coupling relation information; after tau waiting time, the singlet signal is converted into a traditional zero quantum signal, and the target singlet signal is converted into an observable signal by adopting a hard pulse zero quantum filtering module. Obtaining complete coupling network information of the target signal through J coupling evolution by adopting a total correlation spectrum module of zero quantum filtering, and generating a one-dimensional nuclear magnetic resonance total correlation spectrum; two acting frequency points of adiabatic pulses are arranged on the left side and the right side of the middle frequency point of the target coupling atom pair, two obtained spectrograms are subtracted, and the sensitivity and the selectivity are further improved. The method is suitable for various different sample systems, and has strong robustness and high sensitivity.

Description

Technical Field

[0001] This invention relates to the field of nuclear magnetic resonance spectroscopy detection, specifically to a method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology. Background Technology

[0002] Nuclear magnetic resonance (NMR) spectroscopy is a non-invasive detection technique commonly used for the compositional analysis and structural determination of complex compounds. In NMR spectroscopy, the most sensitive and frequently studied nucleus is (⁻¹)H. However, due to chemical shift dispersion and multiple peaks caused by J-coupling splitting, information about mixed compositions can be masked, and (⁻¹)H NMR spectra face the challenge of spectral overlap.

[0003] To address this issue, various nuclear magnetic resonance (NMR) methods have been proposed to achieve high-resolution detection of complex mixtures, such as DOSY, multidimensional spectroscopy, selective excitation techniques, and the SCACPEL method. Selective excitation techniques targeting the signal of interest largely depend on the selectivity of the radio frequency pulse used and the congestion of the NMR signal. Such techniques are generally unsuitable for complex samples with severe signal overlap. Most filtering methods for separating these substances suffer from poor selectivity, insufficient filtering efficiency, excessively long sampling times, or narrow applicability. Summary of the Invention

[0004] The purpose of this invention is to solve the problems in the prior art and propose a universal, highly selective, concise, efficient, and easy-to-operate method for extracting one-dimensional nuclear magnetic resonance (NMR) fully correlated spectrum signals to obtain the fully correlated spectrum of the complete coupling network of a specific signal. This method is of great significance for the separation and component identification of mixtures in complex chemical and biological environments and can further broaden the application scope of NMR technology.

[0005] The technical solution adopted by this invention to solve its technical problem is: to provide a method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology, comprising the following steps:

[0006] The signal of the target coupled proton pair with a coupling relationship is used as the target signal. The proton pair includes a first proton and a second proton. The time width of the 90° hard pulse required to excite the target signal is measured. The 90° hard pulse is applied to the sample to be tested to obtain the one-dimensional proton spectrum of the sample to be tested. The chemical shift information of the first proton, the two chemical shift information of the second proton, and the coupling constant J are determined.

[0007] An adiabatic pulse is generated to excite the target signal based on the chemical shift information and coupling constant information. Two observable signals of the target proton pair are obtained using the adiabatic pulse, namely the first spectrum and the second spectrum.

[0008] The two observable signals are used as input signals to the ZQF-TOCSY module after a waiting time of τ1.

[0009] The ZQF-TOCSY fully correlated spectrum module extends two observable signals through J-coupling evolution to obtain two one-dimensional nuclear magnetic resonance fully correlated spectra.

[0010] Subtracting the two one-dimensional NMR correlation spectra yields the final one-dimensional NMR correlation spectrum.

[0011] Preferably, the step of applying a 90° hard pulse to the sample to obtain a one-dimensional proton spectrum of the sample is performed using a single pulse consisting of a 90° radio frequency hard pulse and a signal sampling period.

[0012] Preferably, the step of generating an adiabatic pulse to excite the target signal based on chemical shift information and coupling constant information, and obtaining two observable signals of the target proton pair, namely a first spectrum and a second spectrum, using the adiabatic pulse includes the following steps:

[0013] Using MATLAB software, an adiabatic pulse is generated based on the chemical shift difference and coupling constant J of two chemical shift information.

[0014] Using the average of the frequencies of the first proton signal and the second signal as the center frequency, the frequency of the adiabatic pulse is set on both sides of the center frequency to obtain two singlet state signals. The singlet state signals are filtered by the hard pulse zero quantum filter module, and the two singlet state signals are converted into two observable single quantum signals as the first spectrum and the second spectrum.

[0015] Preferably, the hard pulse zero quantum filter module employs two sets of hard pulses and a dual gradient field, combined for use on singlet state signals;

[0016] The filtering process of the hard pulse zero quantum filter module includes the following steps:

[0017] The singlet state signal evolved over period τ is used as the input signal, and the singlet state signal is expressed as:

[0018] I + S - +I - S + +2I z S z ;

[0019] Among them, I + S represents the first-order positive-first-order single quantum density operator for the proton. - I represents the negative first-order single quantum density operator of the second proton. z S represents the density operator in the z-direction of the first proton.z Represents the density operator in the z-direction of the second proton;

[0020] The singlet state signal that evolves over period τ is represented as:

[0021] I + S - exp[i(ω S -ω I )τ]+I - S + [-i(ω S -ω I )τ]+2I z S z ;

[0022] Where, ω I With ω S The chemical shifts of the selected target signals are respectively, when At that time, the target singlet state signal strength is at its maximum; I - S represents the first proton negative first-order single quantum density operator. + represents the first-order positive quantum density operator of the second proton, and i represents the imaginary unit;

[0023] The first hard pulse is applied to the input signal, which is then converted into a two-quantum signal, represented as:

[0024] I + S + +I - S - ;

[0025] Applying a second hard pulse with an action angle of θ and a double gradient field to the two quantum signal transforms it into an observable single quantum signal, as follows:

[0026]

[0027] Preferably, the first set of hard pulses has an application angle of 90°, the second set of hard pulses has an application angle of 60°, and the intensity ratio of the dual gradient fields is -1:2, which is used to select the correct coherent path; the waiting time ω is inversely proportional to the chemical shift difference between the two chemical shift information.

[0028] Preferably, the observable signal is a pair of opposite magnetization signals that evolve into a co-magnetization signal after a waiting time of ω1.

[0029] Preferably, the fully correlated spectrum module uses a combination of a 90° hard pulse and a z-filter module, and a spin-locking module and a combination of a 90° hard pulse and a z-filter module to act on the input signal in sequence.

[0030] Preferably, the two z-filter modules are each applied to the sample under test by two different chirp pulses in conjunction with two different weak gradient fields.

[0031] Preferably, the chirp pulse is a 180° sweep pulse, and WURST0 is used as the waveform of the chirp pulse.

[0032] Preferably, the spin-locking module is a DIPSI3 spin-locking sequence.

[0033] The present invention has the following beneficial effects:

[0034] (1) The one-dimensional nuclear magnetic resonance full correlation spectrum generation method based on singlet state filtering technology proposed in this invention excites singlet state signals with adiabatic pulses and effectively filters interference signals using zero quantum filtering method, and is applicable to all coupling systems (both strong and weak).

[0035] (2) The one-dimensional nuclear magnetic resonance total correlation spectrum generation method based on singlet state filtering technology proposed in this invention uses a simple pulse sequence structure, has a high signal-to-noise ratio, a wide range of applications, strong robustness, and excellent selectivity. It can achieve complete extraction of specific substance signals in systems with complex compositions without causing damage to organisms. It can separate specific molecular signals in complex chemical and biological samples on various commercial nuclear magnetic resonance spectrometers and can be used for signal filtering in any coupled system. When using it, the complete coupling network coupling signal of any molecule can be selected for extraction. Compared with traditional selective total correlation spectroscopy, it has stronger selectivity, better suppression ratio, and a wider range of applications.

[0036] (3) The one-dimensional nuclear magnetic resonance total correlation spectrum generation method based on selective excitation of nuclear magnetic resonance singlet state signal proposed in this invention has the advantages of high experimental efficiency, accuracy and universality. It can accurately extract the complete signal of a specific substance in a system with complex composition (when the spectral peaks are crowded) and suppress other interference signals to finally obtain the one-dimensional nuclear magnetic resonance total correlation spectrum of the target molecule. It has important application significance for the structural analysis of chemical and biological complex samples in the field of nuclear magnetic resonance spectroscopy detection.

[0037] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments, but the present invention is not limited to the embodiments. Attached Figure Description

[0038] Figure 1 This is a diagram illustrating the method steps of an embodiment of the present invention;

[0039] Figure 2 This is a schematic diagram of the pulse sequence used in an embodiment of the present invention;

[0040] Figure 3This is a schematic diagram of the relevant signals in the processing procedure of an embodiment of the present invention; Figure 3 (a) in the image is a traditional one-dimensional hydrogen spectrum. Figure 3 In the above, (b) and (c) are the singlet filtered spectra obtained by applying an adiabatic pulse to the left and right sides of the intermediate frequency point of a pair of target coupled protons at +10Hz and -10Hz, respectively. Figure 3 In the diagram, (d) is the singlet filtered spectrum obtained by subtracting (b) and (c) from the two singlet filtered spectra, which further improves the signal-to-noise ratio; Figure 3 In the diagram, (e) and (f) are the singlet filtered full correlation spectra obtained by applying an adiabatic pulse to the left and right sides of the intermediate frequency point of a pair of target coupled protons at +10Hz and -10Hz, respectively. Figure 3 In this context, (g) represents the one-dimensional singlet filtered total correlation spectrum obtained by subtracting (e) from (f), which further improves the signal-to-noise ratio.

[0041] Figure 4 This is a diagram showing the experimental results of testing pig brain samples according to an embodiment of the present invention; wherein... Figure 4 (a) in the image is the one-dimensional proton NMR spectrum of a pig brain sample. The pig brain sample has a complex composition and there is severe signal congestion and overlap in the chemical shift region of 1-4.5 ppm. Figure 4 In the figure, (b)-(g) are the one-dimensional singlet filtered full correlation spectra of six important metabolites obtained by sampling using the method proposed in this invention. Detailed Implementation

[0042] See Figure 1 and Figure 2 The diagram shows the steps of a method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to an embodiment of the present invention, and a schematic diagram of the pulses used. The method includes the following steps:

[0043] S101, using the signal of the target coupled proton pair with a coupling relationship as the target signal, the proton pair including the first proton and the second proton; measuring the time width of the 90° hard pulse required to excite the target signal, applying the 90° hard pulse to the sample to be tested to obtain the one-dimensional proton spectrum of the sample to be tested, and determining the chemical shift information of the first proton, the two chemical shift information of the second proton, and the coupling constant J;

[0044] S102, generate an adiabatic pulse to excite the target signal based on the chemical shift information and coupling constant information, and use the adiabatic pulse to obtain two observable signals of the target proton pair, namely the first spectrum and the second spectrum;

[0045] S103, the two observable signals are used as the input signals of the ZQF-TOCSY module after waiting for τ1 time;

[0046] S104, the ZQF-TOCSY fully correlated spectrum module extends two observable signals through J-coupling evolution to obtain two one-dimensional nuclear magnetic resonance fully correlated spectra respectively;

[0047] S105, subtract the two one-dimensional NMR correlation spectra to obtain the final one-dimensional NMR correlation spectrum.

[0048] Specifically, the acquisition of a one-dimensional hydrogen spectrum is accomplished through a 90° radio frequency hard pulse and a signal sampling period.

[0049] Specifically, the sample to be tested and the target signal to be extracted are selected. The chemical shift and coupling constant of the target signal to be extracted are determined by literature search or one-dimensional proton spectrum of pure solution. The sample to be tested is placed, the one-dimensional proton spectrum of the sample is acquired, and the time width pw of the 90° hard pulse required to excite the target signal is measured.

[0050] Specifically, the two sides of the center frequency are set to +10Hz and -10Hz, and the final observable signals received are the first spectrum (+10Hz spectrum) and the second spectrum (-10Hz spectrum).

[0051] In a specific embodiment, the adiabatic pulse is a shaped pulse with increasing pulse amplitude but unchanged phase.

[0052] For details, please refer to Figure 2 Based on the chemical shift and coupling constant information of the target signal to be extracted, an adiabatic pulse required to excite the singlet state signal is generated. This generated adiabatic pulse is applied to the sample to excite the coupled target signal into the singlet state. The waiting time τ is inversely proportional to the chemical shift difference of the selected target coupling nuclei, primarily to convert the singlet state signal into a zero-quantum signal. The subsequent zero-quantum filtering module then filters and extracts the zero-quantum signal.

[0053] In a specific embodiment, generating the adiabatic pulse required to excite the target signal based on chemical shift information and coupling constant specifically includes:

[0054] By inputting the chemical shift difference and scalar coupling constant, the signal is generated using MATLAB code combined with adiabatic conditions. When applied to a specific frequency, it excites specific coupled hydrogen nuclei into a singlet state. By applying adiabatic pulses to the left and right sides of the mid-frequency point, two singlet state filtered spectra with different phases can be obtained. Subtracting the two spectra can further improve the signal-to-noise ratio of the spectrum.

[0055] In a specific embodiment, the hard pulse zero quantum filter module uses a 90° hard pulse, a hard pulse with an action angle of 60°, and two gradient fields to act on the sample to be tested.

[0056] In a specific embodiment, the hard pulse zero-quantum filter module filters the target signal and converts the target singlet state signal into an observable signal, specifically including:

[0057] After the density operator derivation, the simplified target singlet state signal model after the adiabatic pulse is as follows:

[0058] I + S - +I - S + +2I z S z ;

[0059] After evolution over period τ, the target singlet state signal model is:

[0060] I + S - exp[i(ω S -ω I )ω]+I - S + [-i(ω S -ω I )ω]+2I z S z ;

[0061] Where, ω I With ω S The chemical shifts of the selected target signals are respectively, when At that time, the target singlet signal strength is at its maximum;

[0062] After the first 90° hard pulse in the hard pulse zero-quantum filter module, the target singlet state signal is transformed into a two-quantum signal model as follows:

[0063] I + S + +I - S - ;

[0064] After the second hard pulse with an angle of θ and the interaction of the double gradient field in the hard pulse zero quantum filter module, the two-quantum signal model is transformed into an observable single-quantum signal model as follows:

[0065] I - S z +I z S - .

[0066] Specifically, the ratio of the gradient field intensities after the two hard pulses is -1:2.

[0067] Specifically, the fully correlated spectrum module uses two 90° hard pulses and two z-filter modules placed on both sides of the spin-locked module.

[0068] Specifically, the two z-filter modules are each applied to the sample by two different chirp pulses in conjunction with two different weak gradient fields. The chirp pulses are 180° swept pulses, using WURST0 as the waveform. The spin-locking module is a DIPSI3 spin lock.

[0069] For details, please refer to Figure 3 The diagram illustrates the relevant signals during the processing of this embodiment of the invention. The sample used is a butyl methacrylate (BMA) solution. An adiabatic pulse is applied to both sides of the mid-frequency point of the target coupled signal to obtain two singlet-state filtered spectra, the first and second spectra. The phases of the target signal in the two singlet-state filtered spectra are completely opposite, while the phases of other related signals are the same. Subtracting the two singlet-state filtered spectra enhances the signal-to-noise ratio, eliminates other related signals, and retains only the target singlet signal.

[0070] The above method will be verified by specific experiments.

[0071] Pig brain tissue biosamples contain a large number of complex metabolites and strong water peaks, and their magnetic field is inhomogeneous due to the non-uniform mixing of solid, liquid, and gas states. Under these unfavorable conditions, the sample's spectrum is completely dominated by increased peak width, complex spectral congestion, and strong background signals, producing a large number of crowded peaks between 1.0 ppm and 4.5 ppm, making it almost impossible to extract any useful information. It is difficult to separate relevant metabolites from one-dimensional proton spectra, which limits the widespread application of nuclear magnetic resonance spectroscopy in tissue samples. Therefore, this method was used to extract six typical metabolite signals from pig brain tissue biosamples. These are important indicators of many diseases. The instrument used in this embodiment was a Varian 500MHz nuclear magnetic resonance spectrometer.

[0072] Step 1: Place the pig brain tissue in a 5 mm NMR tube and add 600 μL of heavy water (D2O) as the sample. Place the sample into the NMR chamber, and after performing tuning, field locking, and shimming operations in the NMR spectrometer software interface, apply a 90° hard pulse to obtain the desired results. Figure 4 (a) shows the one-dimensional 1H NMR spectrum of pig brain tissue. Based on prior knowledge, the intramolecular coupling relationships of some components in the pig brain tissue and their chemical shift positions in the 1H NMR spectrum can be understood. Here, six compounds—choline, γ-aminobutyric acid, glutamic acid, lactic acid, inositol, and aspartic acid—were selected from the pig brain tissue for separation.

[0073] Step 2: Reference Figure 4(a) The adiabatic pulses were set to the center frequencies of the target signal pair (+10Hz and -10Hz) around the center frequencies, respectively. Two experiments were conducted, one at +10Hz and the other at -10Hz (resulting in two spectra; subtracting these spectra further improves the signal-to-noise ratio). The adiabatic pulses were designed based on the chemical shift difference and coupling constant of the target coupled proton pair. The waiting time τ after the adiabatic pulse was set according to the chemical shift difference between the two signals. The chirp pulse duration in the fully correlated spectrum module was set according to the 90° hard pulse pw. The spin-locking module duration was optimized based on the size of the molecular coupling network (a larger molecular coupling network requires a longer duration to allow the signal to reach more distant protons). Simultaneously, a four-step phase cycling strategy was employed, involving four samplings, each using a different pulse and receiver phase. The signals were then accumulated to improve the signal-to-noise ratio and optimize the filtering effect. The phases of the adiabatic pulse, the 60° hard pulse, and the receiver are (x,-x,x,-x), (x,x,-x,-x), and (x,x,-x,-x), respectively. A schematic diagram of the final designed pulse sequence is shown below. Figure 2 As shown, executing this pulse sequence yields the singlet-state filtered one-dimensional fully correlated spectrum of the selected substance. Figure 2 The difference between the adiabatic pulses +10Hz and -10Hz can further improve the signal-to-noise ratio, resulting in the final spectrum.

[0074] In this embodiment, the pulse sequence used ( Figure 2 The specific parameters are as follows: the power of the 90° hard pulse is 58dB, the duration is 13.5μs, the duration of the adiabatic pulse is 300ms, and the powers of the adiabatic pulses for the selected coupling signals of choline, γ-aminobutyric acid, glutamic acid, lactic acid, inositol, and aspartic acid are 35dB, 32dB, 23dB, 47dB, 18dB, and 28dB, respectively, with waiting times τ set to 1.70ms, 1.40ms, 4.40ms, 0.38ms, 9.6ms, and 7.8ms, respectively. The duration of the first chirp pulse is 50ms, and the duration of the second chirp pulse is 30ms. The inconsistent durations of the two chirp pulses are to prevent zero-quantum signal re-aggregation.

[0075] pass Figure 4As shown in the experimental results (b)-(g), the embodiments of this application can successfully extract the complete coupling network information of specific coupling pairs in selected components from the complex overlapping NMR spectra of biological tissues. However, the ZQF-TOCSY fully correlated module cannot transmit the signal to uncoupled single peaks, and the signal cannot be transmitted when the fully coupled network is truncated, resulting in the loss of some single-peak signals. This experimental result is consistent with previous literature reports. This demonstrates that the method proposed in the embodiments of this application has the ability to efficiently extract signals of specific substances from complex chemical and biological samples and identify those substances, further broadening the applicability of NMR spectroscopy and laying the foundation for the application of singlet state filtering technology in biological tissue samples.

[0076] In summary, the sample used in this embodiment is a representative sample selected by the present invention. One-dimensional singlet filtered nuclear magnetic resonance full correlation spectrum can also be obtained by using other samples and the method proposed in the embodiments of this application.

[0077] It is evident that the method proposed in this invention is applicable to a variety of different sample systems, possesses strong robustness, high sensitivity, and good selectivity, and can be used for the extraction of specific component signals from complex chemical and biological sample systems. This is of great significance for nuclear magnetic resonance spectroscopy in the separation of substances and the study of biological metabolites.

[0078] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology, characterized in that, Includes the following steps: The signal of the target coupled proton pair with a coupling relationship is used as the target signal. The proton pair includes a first proton and a second proton. The time width of the 90° hard pulse required to excite the target signal is measured. The 90° hard pulse is applied to the sample to be tested to obtain the one-dimensional proton spectrum of the sample to be tested. The chemical shift information of the first proton, the two chemical shift information of the second proton, and the coupling constant J are determined. An adiabatic pulse is generated to excite the target signal based on the chemical shift information and coupling constant information. Two observable signals of the target proton pair are obtained using the adiabatic pulse, namely the first spectrum and the second spectrum. The two observable signals are used as input signals to the ZQF-TOCSY module after a waiting time of τ1. The ZQF-TOCSY fully correlated spectrum module extends two observable signals through J-coupling evolution to obtain two one-dimensional nuclear magnetic resonance fully correlated spectra. Subtracting the two one-dimensional NMR correlation spectra yields the final one-dimensional NMR correlation spectrum.

2. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 1, characterized in that, The process of applying a 90° hard pulse to the sample to obtain a one-dimensional proton spectrum of the sample involves a single pulse consisting of a 90° radio frequency hard pulse and a signal sampling period.

3. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 1, characterized in that, The process of generating an adiabatic pulse to excite the target signal based on chemical shift information and coupling constant information, and obtaining two observable signals of the target proton pair, namely a first spectrum and a second spectrum, using the adiabatic pulse includes the following steps: Using MATLAB software, an adiabatic pulse is generated based on the chemical shift difference and coupling constant J of two chemical shift information. Using the average of the frequencies of the first proton signal and the second signal as the center frequency, the frequency of the adiabatic pulse is set on both sides of the center frequency to obtain two singlet state signals. The singlet state signals are filtered by the hard pulse zero quantum filter module, and the two singlet state signals are converted into two observable single quantum signals as the first spectrum and the second spectrum.

4. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 1, characterized in that, The hard pulse zero quantum filter module described above uses two sets of hard pulses and a dual gradient field, combined to be applied to singlet state signals; The filtering process of the hard pulse zero quantum filter module includes the following steps: The singlet state signal evolved over period τ is used as the input signal, and the singlet state signal is expressed as: AND + S - +I - S + +2I z S z ; Among them, I + S represents the first-order positive-first-order single quantum density operator for the proton. - I represents the negative first-order single quantum density operator of the second proton. z S represents the density operator in the z-direction of the first proton. z Represents the density operator in the z-direction of the second proton; The singlet state signal that evolves over period τ is represented as: I + S - exp[i(ω S -oh I )τ]+I - S + [-i(ω S -oh I )τ]+2I z S z ; Where, ω I With ω S The chemical shifts of the selected target signals are respectively, when At that time, the target singlet state signal strength is at its maximum; I - S represents the first proton negative first-order single quantum density operator. + represents the first-order positive quantum density operator of the second proton, and i represents the imaginary unit; The first hard pulse is applied to the input signal, which is then converted into a two-quantum signal, represented as: I + S + +I - S - ; Applying a second hard pulse with an action angle of θ and a double gradient field to the two quantum signal transforms it into an observable single quantum signal, as follows:

5. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 4, characterized in that, The first set of hard pulses has an application angle of 90°, the second set of hard pulses has an application angle of 60°, and the intensity ratio of the dual gradient fields is -1:2, which is used to select the correct coherent path; the waiting time τ is inversely proportional to the chemical shift difference between the two chemical shift information.

6. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 2, characterized in that, The observable signals are a pair of opposite magnetization signals that evolve into same-direction magnetization signals after a waiting time of τ1.

7. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 1, characterized in that, The fully correlated spectrum module uses a combination of 90° hard pulse and z-filter module, and a spin-locking module and a combination of 90° hard pulse and z-filter module to act on the input signal in sequence.

8. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 7, characterized in that, The two z-filter modules are respectively subjected to the sample under test by two different chirp pulses and two different weak gradient fields.

9. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 7, characterized in that, The chirp pulse is a 180° sweep pulse, and WURST0 is used as the waveform of the chirp pulse.

10. The method for generating a one-dimensional nuclear magnetic resonance fully correlated spectrum based on singlet state filtering technology according to claim 7, characterized in that, The spin-locking module is specifically a DIPSI3 spin-locking sequence.

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