Nuclear magnetic resonance sensing apparatus and nuclear magnetic resonance sensing method

Abstract

When performing nuclear magnetic resonance sensing on an object that exhibits chemical shifts, the specific molecular structure contained within the object is quantitatively and accurately identified. [Solution] After unwanted band components are removed from the IF demodulated signal obtained by intermediate frequency (IF) demodulation of the nuclear magnetic resonance observation signal, the digitizing device 21 generates a magnetic field, etc., corresponding to the IF demodulated signal. The optical quantum sensor unit generates light corresponding to the magnetic field, etc., using a sensing element. This light is converted into a sensor signal by a photoelectric element. The A / D converter digitizes the sensor signal to generate a digital IF demodulated signal. The optical quantum sensor unit has an inconsistent output intensity characteristic in a predetermined frequency range. The correction processing unit 22b corrects the IF demodulated signal in accordance with the frequency of the magnetic field, etc., so that the frequency characteristics of the IF demodulated signal in the above frequency range become closer to constant.

Description

[Technical Field]

[0001] The present invention relates to a nuclear magnetic resonance sensing device and a nuclear magnetic resonance sensing method. [Background technology]

[0002] Generally, a measurement device utilizing nuclear magnetic resonance (NMR) applies a high-frequency magnetic field based on an RF (Radio Frequency) signal with a frequency close to the precession frequency to the object being measured using a high-frequency coil, causing the nuclear magnetization to resonate. This resonant nuclear magnetization is then detected by a receiving coil to generate an observation signal that includes a nuclear magnetic resonance (NMR) signal.

[0003] A certain nuclear magnetic resonance sensing device (a) applies a high-frequency magnetic field based on an RF signal to a target object and generates an observation signal with a frequency shifted from the frequency of the RF signal by the frequency of the NMR signal, (b) generates an IF demodulated signal including the NMR signal in a mixer, (c) extracts the low-frequency band component of the IF demodulated signal in a low-pass filter, (d) further generates a magnetic field etc. corresponding to the IF demodulated signal that has passed through the low-pass filter in a digitizing device, (e) generates light corresponding to the magnetic field etc. in an optical quantum sensor unit using a sensing member and converts that light into a sensor signal using a photoelectric element, and (f) digitizes the sensor signal in an analog / digital converter (see, for example, Patent Documents 1 and 2). This optical quantum sensor unit performs quantum operations on the sensing member described above to generate light corresponding to the magnetic field etc. in the sensing member. [Prior art documents] [Patent Documents]

[0004] [Patent Document 1] International Publication No. 2023 / 089883 [Patent Document 2] International Publication No. 2024 / 224587 [Overview of the Initiative] [Problems that the invention aims to solve]

[0005] On the other hand, as an application of nuclear magnetic resonance sensing, the shift in the frequency of the NMR signal (Larmor frequency) depending on the molecular structure surrounding the atom containing the atomic nucleus being observed (i.e., chemical shift) is used to identify compounds and determine molecular structures. In this process, the amount of frequency shift and relative intensity (integral value of the peak waveform, etc.) of the peak corresponding to the chemical shift of a specific atomic nucleus within the molecular structure relative to a standard sample are identified in the NMR signal spectrum. Based on this amount of shift and relative intensity, a specific molecular structure (functional group, etc.) and its quantity contained in the target object are identified. The specific atomic nucleus mentioned above is, 1 H 13 These include C, and tetramethylsilane (TMS) is used as a standard sample, for example.

[0006] Therefore, when performing the aforementioned nuclear magnetic resonance sensing on an object having a chemical shift, if the aforementioned optical quantum sensor does not have a certain sensitivity to the frequency of the magnetic field applied to the aforementioned optical quantum sensor, it may not be possible to accurately evaluate specific molecules contained in the target substance quantitatively and stoichiometrically.

[0007] The present invention has been made in view of the above problems, and aims to provide a nuclear magnetic resonance sensing device and a nuclear magnetic resonance sensing method that can accurately evaluate the abundance of specific molecules contained in a target object when performing nuclear magnetic resonance sensing on a target object having a chemical shift. [Means for solving the problem]

[0008] The nuclear magnetic resonance sensing device according to the present invention comprises: a nuclear magnetic resonance sensing unit that applies a high-frequency magnetic field based on an RF signal to a target object and generates an observation signal with a frequency shifted from the frequency of the RF signal by the frequency of the nuclear magnetic resonance signal; a mixer unit that performs intermediate frequency demodulation of the observation signal to generate an intermediate frequency demodulated signal including the nuclear magnetic resonance signal; a low-pass filter that transmits a frequency component in the intermediate frequency demodulated signal that is shifted from the intermediate frequency of the intermediate frequency demodulation by the frequency of the nuclear magnetic resonance signal; a digitizing device that digitizes the intermediate frequency demodulated signal that has passed through the low-pass filter; and a correction processing unit that performs correction processing on the sensor signal after digitization. The digitizing device comprises a physical field generator that generates a magnetic field or electric field corresponding to the intermediate frequency demodulated signal that has passed through the low-pass filter; an optical quantum sensor unit that generates light corresponding to the magnetic field or electric field using a sensing member and converts the light into an electrical signal as a sensor signal using a photoelectric element; and an analog / digital converter that digitizes the sensor signal to generate a digital intermediate frequency demodulated signal. The optical quantum sensor unit (a) performs quantum operations on the sensing member to generate the aforementioned light corresponding to the aforementioned magnetic field or electric field on the sensing member, and (b) has inconsistent sensitivity characteristics and non-uniform output intensity characteristics in a predetermined frequency range. The correction processing unit, in the correction process, corrects the intermediate frequency demodulated signal in accordance with the frequency of the aforementioned magnetic field or electric field so that the frequency characteristics of the intermediate frequency demodulated signal in the aforementioned frequency range become closer to constant in accordance with the aforementioned output intensity characteristics.

[0009] The nuclear magnetic resonance sensing method according to the present invention comprises the steps of: applying a high-frequency magnetic field based on an RF signal to a target object and generating an observation signal with a frequency shifted from the frequency of the RF signal by the frequency of the nuclear magnetic resonance signal; performing intermediate frequency demodulation of the observation signal to generate an intermediate frequency demodulated signal including the nuclear magnetic resonance signal; using a low-pass filter to transmit frequency components in the intermediate frequency demodulated signal that are shifted from the intermediate frequency of the intermediate frequency demodulation by the frequency of the nuclear magnetic resonance signal; digitizing the intermediate frequency demodulated signal that has passed through the low-pass filter; and performing correction processing on the intermediate frequency demodulated signal after digitization. In the digitizing step, (a) a magnetic field or electric field corresponding to the intermediate frequency demodulated signal that has passed through the low-pass filter is generated; (b) an optical quantum sensor unit generates light corresponding to the above-mentioned magnetic field or electric field in a sensing member, and the light is converted into an electrical signal as a sensor signal by a photoelectric element; and (c) an analog / digital converter digitizes the sensor signal to generate a digital intermediate frequency demodulated signal. The optical quantum sensor unit (a) performs quantum operations on the sensing member to generate the aforementioned light corresponding to the aforementioned magnetic field or electric field on the sensing member, and (b) has inconsistent sensitivity characteristics and non-uniform output intensity characteristics in a predetermined frequency range. Then, in the correction process, the intermediate frequency demodulated signal is corrected in accordance with the frequency of the magnetic field or electric field so that the frequency characteristics of the intermediate frequency demodulated signal in the aforementioned frequency range become closer to constant in accordance with the aforementioned output intensity characteristics. [Effects of the Invention]

[0010] According to the present invention, a nuclear magnetic resonance sensing apparatus and nuclear magnetic resonance sensing method are obtained that can quantitatively and accurately identify specific molecular structures contained in a target object when performing nuclear magnetic resonance sensing on a target object having a chemical shift. [Brief explanation of the drawing]

[0011] [Figure 1] Figure 1 is a block diagram showing the configuration of a nuclear magnetic resonance sensing device according to Embodiment 1 of the present invention. [Figure 2]Figure 2 is a block diagram showing the configuration of the digitizing device 21 in Figure 1. [Figure 3] Figure 3 shows the configuration of the sensor body 51 in the digitizing device according to Embodiment 1. [Figure 4] Figure 4 illustrates a specific phase in a pseudo-IF signal. [Figure 5] Figure 5 shows an example of a measurement sequence. [Figure 6] Figure 6 illustrates the relationship between the spinlock frequency fLOCK, the frequency fAC of the AC field under test, the intensity S of the sensor signal, and the maximum value max|dS / dB| of the derivative (dS / dB) of the sensor signal intensity S with respect to the magnetic flux density B of the AC field under test. [Figure 7] Figure 7 illustrates the distribution of sensor signal strength S (relative value) with respect to the frequency fAC and phase shift of the AC field under measurement. [Figure 8] Figure 8 illustrates the maximum slope value max|dS / dB| of the measured AC field with respect to frequency fAC in Embodiment 1. [Figure 9] Figure 9 illustrates the sampling of sensor signals. [Figure 10] Figure 10 illustrates the sensor signals appearing in the observable bandwidth. [Figure 11] Figure 11 illustrates the case where the filtering process described above attenuates the bandwidth corresponding to the range from half the sampling frequency fs (fs / 2) to the sampling frequency fs. [Figure 12] Figure 12 illustrates the case where the filtering process described above attenuates the bandwidth corresponding to the range from 0 to half the sampling frequency (fs / 2). [Figure 13] Figure 13 illustrates the correction process based on calibration data and the derivation of the NMR spectrum. [Figure 14] Figure 14 shows the NMR spectrum of ethylbenzene with respect to 1H. [Figure 15]Figure 15 illustrates the identification of calibration data in Embodiment 2. [Figure 16] Figure 16 illustrates the setting of the intermediate frequency in Embodiment 3. [Figure 17] Figure 17 illustrates the setting of the intermediate frequency in Embodiment 4. [Figure 18] Figure 18 illustrates the setting of the spinlock frequency in Embodiment 5. [Figure 19] Figure 19 illustrates the measurement sequence (dynamic decoupling) in Embodiment 6. [Figure 20] Figure 20 illustrates the maximum slope value max|dS / dB| of the measured AC field with respect to frequency fAC in Embodiment 6. [Modes for carrying out the invention]

[0012] Embodiments of the present invention will be described below with reference to the figures.

[0013] Embodiment 1.

[0014] Figure 1 is a block diagram showing the configuration of a nuclear magnetic resonance sensing device according to Embodiment 1 of the present invention. This nuclear magnetic resonance sensing device is used for molecular structure analysis of target objects using chemical shifts.

[0015] The nuclear magnetic resonance sensing device shown in Figure 1 comprises a nuclear magnetic resonance sensing unit 1, reference signal generators 2 and 3, a switching unit 4, a matching and tuning circuit 5, a mixer unit 6, and a low-pass filter 7.

[0016] The nuclear magnetic resonance sensing unit 1 applies an RF signal (described later) to the target object, and the frequency f of the RF signal is measured. RF From the frequency f of the nuclear magnetic resonance (NMR) signal NMR The frequency shifted by (f RF +f NMR It generates an observation signal (analog electrical signal) of ).

[0017] Specifically, the nuclear magnetic resonance sensing unit 1 includes a coil 11 and a magnet unit 12. The coil 11 applies a high-frequency magnetic field based on an RF signal to the target object 101, senses a magnetic field change based on the movement of nuclear magnetization in the target object 101, and outputs an observation signal. The magnet unit 12 is a permanent magnet or an electromagnet, and applies a static magnetic field or a gradient magnetic field to the target object 101. This observation signal includes an NMR signal and has a frequency that is the sum of the frequency f NMR and the RF signal frequency f RF and is (f RF + f NMR ).

[0018] The reference signal generation device 2 generates and outputs an RF signal. The reference signal generation device 3 generates and outputs a local oscillation (LO) signal. The LO signal has a frequency that is lower by a single intermediate frequency f RF from the RF signal frequency f IF . The RF signal is branched by a coupler 2a, and the LO signal is branched by a splitter 3a so that they have the same level after branching.

[0019] The switching unit 4 switches the connection destination of the nuclear magnetic resonance sensing unit 1 side (the nuclear magnetic resonance sensing unit via the matching and tuning circuit 5) from one of the transmission system of the RF signal (the reference signal generation device 2) and the reception system of the observation signal (the reference signal generation devices 2 and 3, the mixer unit 6, and the low-pass filter 7) to the other. Specifically, when transmitting the RF signal, the switching unit 4 electrically connects the transmission system to the nuclear magnetic resonance sensing unit 1 side, and when receiving the observation signal, the switching unit 4 electrically connects the reception system to the nuclear magnetic resonance sensing unit 1 side.

[0020] The matching and tuning circuit 5 is a circuit that performs impedance matching to suppress reflection of the RF signal in the nuclear magnetic resonance sensing unit 1 and frequency tuning so that the level of the NMR signal is improved.

[0021] The mixer unit 6 performs intermediate frequency demodulation of the observed signal based on the LO signal to generate an intermediate frequency demodulated signal (IF demodulated signal) that includes the nuclear magnetic resonance signal. Specifically, the mixer unit 6 mixes the observed signal and the LO signal and performs intermediate frequency (IF) demodulation to obtain two frequency components (2f RF -f IF -f NMR ),(f IF +f NMR It generates and outputs an IF demodulated signal having ). For example, the mixer section 6 is a DBM (Double Balanced Mixer) consisting of a diode and a phase divider, and does not include active elements such as transistors.

[0022] The low-pass filter 7 attenuates unwanted band components in the IF demodulated signal described above, and modulates the intermediate frequency f of the intermediate frequency demodulation. IF From the frequency f of the nuclear magnetic resonance signal NMR It allows the frequency components that have been shifted by only a certain amount to pass through. Specifically, the low-pass filter 7 allows the two bandwidth components (2f) obtained from the IF demodulation of the IF demodulated signal in the mixer section 6 to pass through. RF -f IF -f NMR ),(f IF +f NMR ) the high-frequency band component (2f RF -f IF -f NMR ) is attenuated, and the lower frequency band component (f) of the two band components is attenuated. IF +f NMR This is a filter that allows ) to pass through. Note that the low-pass filter 7 is an analog filter composed only of passive elements such as capacitors, inductors, and resistors.

[0023] Furthermore, the nuclear magnetic resonance sensing device shown in Figure 1 includes a mixer unit 8 and a phase detection unit 9.

[0024] The mixer section 8 generates a pseudo-intermediate frequency signal (frequency f) from the LO signal and the RF signal. IF This generates a pseudo-IF signal. Here, in order to suppress the delay between the IF demodulated signal and the pseudo-IF signal, it is preferable to use the same mixer unit 8 as the mixer unit 6.

[0025] The phase detection unit 9 detects a specific phase in the waveform of the pseudo-IF signal and generates and outputs a synchronization signal indicating the specific phase. The phase detection unit 9 may detect the specific phase using a comparator (such as a zero-crossing comparator), or it may convert the pseudo-IF signal into a digital signal using an analog-to-digital converter and perform signal processing on that digital signal using a DSP (Digital Signal Processor) or the like to detect the specific phase.

[0026] Furthermore, the nuclear magnetic resonance sensing device shown in Figure 1 includes a digitizing device 21 and a control device 22.

[0027] The digitizing device 21 outputs the IF demodulated signal (frequency component (f) from the low-pass filter 7. IF +f NMR Converts an analog signal to a digital signal.

[0028] The control device 22 includes a non-volatile storage device 22a such as flash memory, and a computer that operates according to a control program. This computer includes a CPU (Central Processing Unit), ROM (Read Only Memory), RAM (Random Access Memory), etc. It loads the control program from ROM or storage device 22a into RAM and executes it with the CPU to perform the operations described later, and also operates as a correction processing unit 22b and an identification processing unit 22c. The storage device 22a stores the calibration data described later.

[0029] Specifically, the control device 22 controls the nuclear magnetic resonance sensing unit 1 and the switching unit 4 to apply the above-mentioned high-frequency magnetic field to the nuclear magnetic resonance sensing unit 1 and output the above-mentioned observation signal. Furthermore, the control device 22 outputs the IF demodulated signal (frequency component (f) as a digital signal. IF +f NMR The signal is input from the digitizing device 21 and undergoes predetermined signal processing (frequency component f NMR(For example, extraction of the frequency components (f)) is performed, and the IF demodulated signal (frequency components (f) IF +f NMR )) from frequency f NMR Extract the components (i.e., the NMR signal). IF is, f NMR It is a sufficiently high frequency compared to f RF is, f IF This is a significantly higher frequency compared to [another frequency].

[0030] The correction processing unit 22b performs correction processing on the digitized IF demodulated signal (specifically, the digitized sensor signal described later).

[0031] The identification processing unit 22c derives the NMR spectrum of the target object 101 based on the IF demodulated signal corrected by the correction processing unit 22b, and identifies the molecular structure (functional groups, etc.) and the quantity (number) of that molecular structure (functional groups, etc.) from the NMR spectrum.

[0032] Figure 2 is a block diagram showing the configuration of the digitizing device 21 in Figure 1. As shown in Figure 2, the digitizing device 21 comprises a physical field generator 41, an optical quantum sensor unit 42, and an analog-to-digital converter (A / D converter, ADC) 43.

[0033] The physical field generator 41 generates a magnetic field corresponding to the input signal (i.e., the analog IF demodulated signal that has passed through the low-pass filter 7) input via the input terminal 41a of the physical field generator 41. For example, the physical field generator 41 generates this magnetic field using conductive coils or wiring. This generated magnetic field corresponds to the frequency of the IF demodulated signal (here, f IF +f NMR ) has the same frequency f AC It has.

[0034] The optical quantum sensor unit 42 comprises a sensor body 51 and a photoelectric element 52. In the sensor body 51, a sensing member generates light (observation light) corresponding to the magnetic field generated by the physical field generator 41, and the photoelectric element 52 converts this light into an electrical signal as a sensor signal. The photoelectric element 52 is a photodiode or phototransistor, and generates a sensor signal corresponding to the intensity of the incident observation light.

[0035] Specifically, the optical quantum sensor unit 42 (specifically the sensor body 51) performs quantum operations (in this case, quantum operations using microwaves and laser light) on the sensing member at a specific phase timing specified by the synchronization signal, causing light corresponding to the magnetic field generated by the physical field generator 41 to be generated on the sensing member.

[0036] In Embodiment 1, the optical quantum sensor unit 42 (specifically the sensor body 51) performs quantum operations on the sensing member according to optically detected magnetic resonance (ODMR) to generate the aforementioned observation light on the sensing member.

[0037] Preferably, the phase detection unit 9 detects a specific phase in the waveform of the pseudo-IF signal immediately after the start of free induction decay, and the optical quantum sensor unit 42 performs the above-mentioned quantum operation on the sensing member 1 by applying microwaves to the sensing member 1 at the timing of that specific phase.

[0038] Figure 3 shows the configuration of the sensor body 51 in the digitizing device according to Embodiment 1. In Embodiment 1, for ODMR, as shown in Figure 3, for example, the sensor body 51 includes a magnetic resonance member 61 as a sensing member, a high-frequency magnetic field generator 62, and a magnet 63, a high-frequency power supply 64, a light-emitting device 65, and a controller 66.

[0039] The magnetic resonance member 61 has a crystalline structure, and its electron spin quantum state changes in response to the magnetic field generated by the physical field generator 41. It is also a member capable of electron spin quantum manipulation (based on Rabi oscillations) using microwaves of a frequency corresponding to the alignment direction of defects and impurities in the crystal lattice. In other words, the magnetic resonance member 61 is placed within the aforementioned magnetic field.

[0040] In this embodiment, the magnetic resonance member 61 is a photodetector magnetic resonance member having a plurality (i.e., an ensemble) of specific color centers. These specific color centers have energy levels that can be Zeeman split, and can take on multiple orientations in which the shift width of the energy levels during Zeeman splitting is different from that of the others.

[0041] Here, the magnetic resonance member 61 is a material such as diamond containing multiple NV (Nitrogen Vacancy) centers as a single type of specific color center. In the case of NV centers, the ground state is a triplet state with ms=0, +1, -1, and the ms=+1 and ms=-1 levels undergo Zeeman splitting. When NV centers transition from the excited state at the ms=+1 and ms=-1 levels to the ground state, a predetermined proportion fluoresce, while the remaining proportion of NV centers transition non-radiatively from the excited state (ms=+1 or ms=-1) to the ground state (ms=0). Note that the color centers included in the magnetic resonance member 61 may be color centers other than NV centers.

[0042] The high-frequency magnetic field generator 62 applies microwaves to the magnetic resonance member 61 to perform quantum manipulation of the electron spin of the magnetic resonance member 61. For example, the high-frequency magnetic field generator 62 comprises a substantially circular coil section that emits microwaves and terminal sections extending from both ends of the coil section and fixed to a substrate. The high-frequency power supply 64 generates its microwave current and conducts it to the high-frequency magnetic field generator 62. The coil section conducts two parallel currents at a predetermined interval so as to sandwich the magnetic resonance member 61, and emits the microwaves described above. The coil section is, for example, a plate-shaped coil, and due to the skin effect, the microwave current flows through the end face of the coil section, thus forming the two currents described above. The coil section may also be formed of two conductors corresponding to the two currents described above. As a result, microwaves of substantially uniform intensity are applied to the magnetic resonance member 61.

[0043] In the case of NV centers, color centers are formed in a diamond crystal by defects (vacancies) (V) and nitrogen (N) as impurities. There are four possible positions for adjacent nitrogen (N) atoms relative to a defect (vacancy) (V) in the diamond crystal (i.e., the alignment direction of pairs of vacancies and nitrogen atoms), and the sub-levels after Zeeman splitting (i.e., energy levels from the ground) corresponding to each of these alignment directions are different. Therefore, in the characteristics of fluorescence intensity after Zeeman splitting due to a static magnetic field with respect to microwave frequency, four different dip frequency pairs (fi+, fi-) appear, corresponding to each direction i (i=1,2,3,4). Here, the microwave frequency (wavelength) is set corresponding to one of these four dip frequency pairs.

[0044] Furthermore, the magnet 63 applies a static magnetic field (DC magnetic field) to the magnetic resonance member 61, causing Zeeman splitting of the energy levels of multiple specific color centers (in this case, multiple NV centers) within the magnetic resonance member 61. Here, the magnet 63 is a ring-shaped permanent magnet, such as a ferrite magnet, alnico magnet, or samarium-cobalt magnet. Note that the magnet 63 may also be an electromagnet.

[0045] Furthermore, in the magnetic resonance member 61, the crystal of the magnetic resonance member 61 is formed and the orientation of the magnetic resonance member 61 is set such that the arrangement direction of the defects and impurities described above substantially coincides with the direction of the static magnetic field (and the direction of the applied magnetic field) described above.

[0046] Furthermore, in this embodiment, an optical system (not shown) is provided from the light-emitting device 65 to the magnetic resonance member 61 in order to irradiate the magnetic resonance member 41 with excitation light, and an optical system (not shown) is provided from the magnetic resonance member 61 to the photoelectric element 52 in order to detect fluorescence (observation light) from the magnetic resonance member 61.

[0047] The observed light is focused toward the photoelectric element 52 by an optical system, such as a composite parabolic focuser (CPC). For example, a magnetic resonance member 61 is placed on the CPC, and of the fluorescence emitted in all directions from the color center within the magnetic resonance member 61, the fluorescence emitted over a wide solid angle (for example, a predetermined proportion or more of all directions) is focused by this optical system.

[0048] The light-emitting device 65 is equipped with a laser diode or the like as a light source, and emits laser light of a predetermined wavelength as excitation light to be irradiated onto the magnetic resonance member 61.

[0049] The controller 66 controls (a) the high-frequency power supply 64 and the light-emitting device 65 according to a predetermined measurement sequence (e.g., Hahn echo sequence) to perform quantum operations with the microwave and laser light described above, generating observation light in the sensor body 51 and generating a sensor signal in the photoelectric element 52. For example, the controller 66 includes a computer that operates according to a control program, and this computer includes a CPU, ROM, RAM (Random Access Memory), etc., and performs the above operations by loading the control program into RAM and executing it with the CPU. The controller 66 may be built into the control device 22, or the control device 22 may be configured to operate as the controller 66.

[0050] Figure 4 illustrates specific phases in a pseudo-IF signal. In this embodiment, for example, as shown in Figure 4, the phase detection unit 9 detects consecutive 0-degree, 180-degree, and 360-degree phases as specific phases in the waveform of the pseudo-IF signal, and the optical quantum sensor unit 42 performs the above-mentioned quantum operation on the sensing member 1 by applying microwaves to the sensing member 1 at timings T1, T2, and T3 of the detected specific phases, according to the Hahn echo sequence. According to the Hahn echo sequence, π / 2 pulse microwaves are applied at timings T1 and T3, and π pulse microwaves are applied at timing T2.

[0051] Note that the frequency f of the pseudo-IF signal IF and the frequency (f) of the IF demodulated signal IF +f NMR The difference between (=f) and ) NMR ) has, f NMR ga f IF Because it is sufficiently small, the pseudo-IF signal is almost synchronized with the IF demodulated signal (especially in the initial stages of observation), as shown in Figure 4, for example. Therefore, based on the synchronization signal described above, the quantum operations described above are performed at the appropriate timing in the IF demodulated signal.

[0052] The measurement sequence is not limited to the Hahn echo sequence; it can be selected according to the frequency of the magnetic field being measured. For example, if the period of the magnetic field is greater than or equal to the T2 relaxation time, the magnetic field measurement is performed using multiple Ramsey pulse sequences as described above. If the period of the magnetic field is shorter than the T2 relaxation time, a spin echo pulse sequence (such as the Hahn echo sequence) may be applied. Furthermore, if the period of the magnetic field is shorter than half of the T2 relaxation time, the magnetic field measurement may be performed according to the Qdyne method.

[0053] Returning to Figure 2, the A / D converter 43 digitizes the aforementioned sensor signal (without directly digitizing the input signal from the low-pass filter 7), thereby generating a digital IF demodulated signal corresponding to the input signal (analog IF demodulated signal), which is output via the output terminal 43a of the A / D converter 43.

[0054] In this embodiment, the optical quantum sensor unit 42 (specifically the sensor body 51) generates the aforementioned observation light on the sensing member (magnetic resonance member 61) such that the level of the sensor signal exceeds the noise floor of the A / D converter 43.

[0055] Here, the level (amplitude) of the sensor signal changes depending on factors such as the efficiency of the sensing member (in Embodiment 1, the type and number of color centers in the magnetic resonance member 61, etc.), the light collection efficiency of the observed light (in Embodiment 1, the amount of incident light to the photoelectric element 52 relative to the amount of light emitted by the color center), and the conversion efficiency of the photoelectric element 52 (the level of the sensor signal relative to the amount of incident light). Therefore, the values ​​of these factors are determined so that the level of the sensor signal exceeds the noise floor of the A / D converter 43, according to the noise floor (known) of the A / D converter 43. As a result, for example, the sensitivity of the optical quantum sensor unit 42 is 1.5 pT / Hz. 1 / 2 That is considered to be the case.

[0056] Furthermore, generally speaking, the noise of an A / D converter includes quantization noise and thermal noise, and in high-resolution A / D converters, thermal noise is dominant over quantization noise. In this embodiment, the A / D converter 43 is a high-resolution A / D converter, and the values ​​of the above-mentioned factors are determined so that the level of the sensor signal exceeds the noise level of the thermal noise.

[0057] Furthermore, the reference voltage of the A / D converter 43 is set according to the range of the sensor signal (minimum level and maximum level). Note that lowering the reference voltage of the A / D converter reduces quantization noise, but does not reduce thermal noise.

[0058] The level (or range) of the input IF demodulated signal and the electromagnetic conversion efficiency of the physical field generator 41 are known.

[0059] Furthermore, in this embodiment, the digitizing device 21 does not have an amplification circuit between the photoelectric element 52 and the A / D converter 43 to electrically increase the sensor signal. Moreover, in this embodiment, there is no amplification circuit between the input signal source and the physical field generator 41 to electrically increase the input signal. In other words, in this embodiment, there is no electrical amplification circuit upstream of the A / D converter 43 that would be a source of noise. In such an amplification circuit, thermal noise is generated and amplified, similar to the A / D converter 43, so noise is superimposed on the signal input to the A / D converter 43. Therefore, it is preferable that such an amplification circuit is not provided.

[0060] Furthermore, the high-frequency power supply 64 and controller 66 are electrically isolated from the A / D converter 43, so that electrical noise generated by the high-frequency power supply 64 and controller 66 does not enter the A / D converter 43.

[0061] Furthermore, in this embodiment 1, the optical quantum sensor unit 42 (controller 66) periodically and repeatedly performs quantum operations on the sensing member according to the synchronization signal to generate light corresponding to the magnetic field on the sensing member, thereby causing the digitizing device 21 to output a digital IF demodulated signal synchronized with the synchronization signal. Then, the control device 22, based on this digital IF demodulated signal, accurately determines the frequency f of the NMR signal according to the Qdyne method. NMR Identify it.

[0062] In this embodiment 1, neither an amplification circuit nor a buffer is provided between the nuclear magnetic resonance sensing unit 1 and the digitizing device 21. In other words, only passive elements are used in the circuit from the nuclear magnetic resonance sensing unit 1 to the digitizing device 21, thereby suppressing the generation of thermal noise.

[0063] Furthermore, when controlling the high-frequency power supply 64 and light-emitting device 65 to apply microwaves and excitation light to the magnetic resonance member 1 in a predetermined measurement sequence, in a normal Hahn echo pulse sequence (spin echo pulse sequence) or a normal dynamic decoupling, the reciprocal of the spin lock frequency of the microwave pulse sequence is 1 / f. LOCK ) is the period of the measured AC field (1 / f AC ) is matched, but the controller 66 sets the reciprocal of the spinlock frequency of the microwave pulse sequence in the measurement sequence (1 / f LOCK ) is the period of the measured AC field (1 / f AC Microwaves and excitation light are applied to the magnetic resonance member 1 in a manner different from that described above. Here, f LOCK This is the spin lock frequency, and f AC f is the frequency of the AC field under measurement, and the AC field under measurement is the AC magnetic field or AC electric field applied to the sensing member (magnetic resonance member 61), and here, as described above, it is the frequency f generated by the physical field generator 41. AC It is the magnetic field.

[0064] Figure 5 shows an example of a measurement sequence. Figure 5 shows the timing of the microwave pulse relative to the AC magnetic field under measurement, and the timing of the excitation light irradiation (twice, for initialization and measurement) in the measurement sequence of Embodiment 1. As shown in Figure 5, fluorescence is detected during the excitation light irradiation period for each measurement.

[0065] In particular, the controller 66 applies a microwave pulse sequence based on a Hahn echo pulse sequence or dynamic decoupling to the magnetic resonance member 1. At that time, the reciprocal of the spinlock frequency of the microwave pulse sequence (1 / f) is applied. LOCK ) is the period of the measured AC field (1 / f AC This is different from the previous example. In Embodiment 1, a microwave pulse sequence based on a Hahn echo sequence (spin echo pulse sequence) is applied to the magnetic resonance member 1.

[0066] The reciprocal of the spinlock frequency (1 / f) in the case of a Hahn echo pulse sequence LOCK ) is the time length from the end of the first π / 2 pulse to the tip of the second π / 2 pulse, as shown in Figure 5, for example. In Embodiment 1, the controller 66 applies a microwave pulse sequence based on the Hahn echo pulse sequence to the magnetic resonance member 1 in the measurement sequence. However, the reciprocal of the spinlock frequency of the microwave pulse sequence (1 / f) LOCK ) is the period of the measured AC field (1 / f AC Shorter than ).

[0067] Figure 6 shows the spin lock frequency f. LOCK and the frequency f of the AC field under measurement AC This figure illustrates the relationship between the intensity S of the sensor signal and the maximum value max|dS / dB| of the derivative (dS / dB) of the intensity S of the sensor signal with respect to the magnetic flux density B of the AC field being measured.

[0068] As shown in Figure 6, the intensity S of the sensor signal is B, f AC , and f LOCK It is a function of and max|dS / dB| is f AC and f LOCK It is a function of the above. In the equation shown in Figure 6, γ is the gyromagnetic ratio (constant), and φ0 is the phase difference between the microwave pulse sequence and the AC field being measured.

[0069] Here, as shown in Figure 6 for example, dS / dB represents the slope, and the larger dS / dB, the higher the sensitivity. Therefore, under the condition that max|dS / dB| is maximized, f AC and f LOCK It is preferable that this is set.

[0070] Figure 7 shows the frequency f of the AC field under measurement. AC This figure illustrates the distribution of sensor signal strength S (relative value) with respect to phase shift. In Figure 7, the sensor signal strength S (relative value) is represented by contour lines. Figure 8 shows the frequency f of the AC field under measurement in Embodiment 1. ACThis diagram illustrates the maximum value of the slope, max|dS / dB|, relative to .

[0071] For example, as shown in Figure 7, the sensor signal strength S changes depending on the magnitude of the phase shift between the AC field under measurement and the measurement sequence, but for example, as shown in Figures 7 and 8, the maximum value of the sensor signal strength S is f AC ga f LOCK If it is the same as f AC ga f LOCK The value becomes larger when the value is lower. Note that Figure 8 shows f without considering phase shift. AC This shows the maximum slope value max|dS / dB| for each value.

[0072] In other words, the maximum value (max|dS / dB|) of the derivative (dS / dB) of the intensity S of the sensor signal with respect to the magnetic flux density B of the AC field being measured is equal to the spin lock frequency f of the microwave pulse sequence. LOCK The frequency f of the AC field being measured AC The spin lock frequency f is set to be larger than when it matches LOCK and the frequency f of the AC field under measurement AC The setting is configured. Note that the frequency f of the AC field being measured is AC It is preferable to set this to the peak frequency (or its vicinity) of the characteristic curve in Figure 8.

[0073] Also, the frequency f of the AC field being measured AC If there is a possibility of fluctuations or deviations within a predetermined range, the spinlock frequency can be set so that the measurement bandwidth of a predetermined range, including the peak frequency of the characteristic curve in Figure 8, is within the frequency band of interest. This allows measurements to be performed under conditions where the maximum slope (max|dS / dB|) (i.e., sensitivity) is good.

[0074] As described above, the optical quantum sensor unit 42 operates within a predetermined frequency range (the frequency f of the applied AC field). AC It has inconsistent sensitivity characteristics and non-uniform output strength characteristics in the range of ( ). Here, as described above, the reciprocal of the spinlock frequency is the period (1 / f) of the magnetic or electric field applied to the sensing member.AC ) is variable within the above frequency range due to being different from the above. In the above correction processing unit 22b, in the correction processing, the frequency characteristics of the IF demodulation signal within that frequency range are made to approach a constant (that is, the gain of each frequency becomes constant), and the frequency f of the magnetic field or electric field applied to the sensing member AC is used to correct the IF demodulation signal. That is, the value of the IF demodulation signal is corrected by the correction coefficient corresponding to the frequency f AC .

[0075] In this embodiment, calibration data corresponding to the output intensity characteristics is stored in the storage device 22a, and the correction processing unit 22b performs the above correction processing by referring to the calibration data. For example, the calibration data includes, for each frequency f AC , the signal intensity at that frequency f AC and the correction coefficient obtained from the signal intensity. The correction processing unit 22b performs the above correction processing by referring to the calibration data and multiplying the correction coefficient corresponding to the frequency of the above magnetic field or electric field by the value of the sensor signal

[0076] Also, the above frequency range is set according to the chemical shift of one or more specific molecular structures. Here, the above frequency range is set to include the range where the appearance range of the chemical shift of one or more specific molecular structures is included

[0077] Note that the relationship between the chemical shift (ppm) and the frequency f of the NMR signal NMR is as follows

[0078] f NMR = f RF × chemical shift (ppm)

[0079] Also, since the frequency f of the alternating field (magnetic field or electric field) applied to the magnetic resonance member 61 AC has the relationship of f AC = f IF + f NMR (described later), f IFThe frequency range described above, when f is kept constant, corresponds to the chemical shift of one or more specific molecular structures. AC It is set to include all of the above.

[0080] For example, the target nucleus of NMR 1 H (proton) is the frequency of the RF signal f RF When the NMR resonance frequency is 43 MHz, and the range of chemical shifts to be detected is set to -2 ppm to 18 ppm, the frequency of the NMR signal f NMR The range is -86Hz to 774Hz, and the above f AC The frequency range (i.e., the frequency range in which the IF demodulated signal should be corrected) is the intermediate frequency f IF Based on this, the frequency f of the NMR signal NMR It is set according to the range.

[0081] Furthermore, if the molecular structure of the target is unknown, the above-mentioned frequency range may be set by the user as appropriate.

[0082] Figure 9 illustrates the sampling of a sensor signal. For example, as shown in Figure 9, when the A / D converter 43 samples and digitizes the sensor signal at a predetermined sampling frequency fs under undersampling conditions, the observable bandwidth of the digitized sensor signal will be from 0 to fs / 2.

[0083] Figure 10 illustrates the sensor signal appearing in the observable bandwidth. For example, as shown in Figure 10, if the sensor signal contains unwanted components in addition to the components of the AC field being measured, aliasing may cause these unwanted components to enter the observable bandwidth. Therefore, to attenuate such unwanted components, filtering is performed on the sensor signal to attenuate bandwidths other than the predetermined measurement bandwidth. This measurement bandwidth is set corresponding to the sampling frequency fs. This filtering may be performed by an analog circuit for the sensor signal as an analog signal, or by a digital signal processor or the control device 22 described above for the sensor signal as a digital signal.

[0084] Figure 11 illustrates the case where the filtering process described above attenuates the bandwidth corresponding to the range from half the sampling frequency fs (fs / 2) to the sampling frequency fs. For example, the spinlock frequency f is set such that the above measurement bandwidth corresponds to the range from 0 to half the sampling frequency fs and includes the peak frequency which is the maximum value (max|dS / dB|) of the derivative of the intensity of the sensor signal with respect to the magnetic flux density of the AC field under measurement. LOCK This is set. In this case, aliasing is suppressed, and as shown in Figure 11, for example, the measurement bandwidth is set to a range between a frequency that is an integer (n-1) multiple of the sampling frequency fs ((n-1)fs) and a frequency that is an integer (n-1) multiple of the sampling frequency fs plus half of the sampling frequency fs ((n-1)fs + fs / 2), thereby enabling the detection of the sensor signal with good sensitivity in the observable bandwidth.

[0085] Figure 12 illustrates the case where the filtering process described above attenuates the bandwidth corresponding to the range from 0 to half the sampling frequency (fs / 2). For example, the spinlock frequency f is set such that the measurement bandwidth corresponds to the range from half the sampling frequency fs to the sampling frequency fs, and includes the peak frequency which is the maximum value of the derivative of the intensity of the sensor signal with respect to the magnetic flux density of the AC field under measurement. LOCKThis is set. In this case, assuming aliasing is used, for example as shown in Figure 12, the measurement bandwidth is set to the range between the frequency obtained by adding half of the sampling frequency fs to an integer (n-1) multiple of the sampling frequency fs ((n-1)fs+fs / 2) and the frequency which is an integer n multiple of the sampling frequency fs (nfs), thereby enabling the detection of the sensor signal with good sensitivity in the observable bandwidth. In this case, due to aliasing, the sensor signal is detected at a frequency symmetric to (n-1 / 2)×fs.

[0086] Next, the operation of the nuclear magnetic resonance sensing device according to Embodiment 1 will be described.

[0087] The control device 22 controls the nuclear magnetic resonance sensing unit 1 and the switching unit 4 to apply a high-frequency magnetic field based on the RF signal from the transmitting system to the target object 101 in the nuclear magnetic resonance sensing unit 1, and controls the switching unit 4 to conduct the observation signal from the nuclear magnetic resonance sensing unit 1 to the receiving system.

[0088] As shown in Figure 1, the observed signal is converted into an IF demodulated signal based on the LO signal by the mixer unit 6, and the IF demodulated signal, from which the high-frequency band components have been removed by the low-pass filter 7, is input to the digitizer 21.

[0089] Furthermore, the mixer unit 8 generates a pseudo-IF signal from the RF signal and the LO signal, and the phase detection unit 9 generates a synchronization signal indicating a specific phase from the pseudo-IF signal.

[0090] In the digitizing device 21, when the IF demodulated signal is applied to the physical field generator 41, the physical field generator 41 generates a magnetic field of an intensity corresponding to the level of the input signal, which is applied to the sensor body 51 of the optical quantum sensor unit 42.

[0091] In the sensor body 51, the measurement sequence is executed in synchronization with the synchronization signal as described above, and light is generated with an intensity corresponding to the strength of the magnetic field. In Embodiment 1, according to ODMR, the magnetic resonance member 61 generates light with an intensity corresponding to the strength of the magnetic field.

[0092] Specifically, the controller 66 executes a measurement sequence continuously, as shown in Figure 5, for example, and each measurement sequence (in Embodiment 1, f AC higher f LOCK In the Hahn echo sequence, the light-emitting device 12 emits excitation light, and the high-frequency magnetic field generator 62 emits microwaves.

[0093] Then, the photoelectric element 52 receives the light generated by the sensor body 51, generates a sensor signal with a level corresponding to the amount of light received, and outputs it to the A / D converter 43.

[0094] The A / D converter 43 digitizes the sensor signal, generates a digital IF demodulated signal corresponding to the analog IF demodulated signal, and outputs it to the control device 22.

[0095] In the control device 22, the correction processing unit 22b continuously and repeatedly acquires the value of the digital IF demodulated signal and corrects the value of the digital IF demodulated signal based on the calibration data as described above. The identification processing unit 22c then derives an NMR signal and an NMR spectrum from the corrected IF demodulated signal through signal processing and performs molecular structure analysis of the target object 101 based on the NMR spectrum.

[0096] Figure 13 illustrates the correction process based on calibration data and the derivation of the NMR spectrum. For example, as shown in Figure 13, the output intensity characteristics are identified as calibration data within the calibration range (the frequency range described above), and the intensity of the IF demodulated signal (i.e., the sensor signal described above) is corrected based on the calibration data. Specifically, for each frequency in the output intensity characteristics, the ratio of the signal intensity S at that frequency to the signal intensity So at the reference frequency (S / So) is used as the correction coefficient, and the intensity of the IF demodulated signal obtained at that frequency is multiplied by this coefficient to correct the intensity of the IF demodulated signal. The reference frequency is the frequency f of the IF demodulated signal obtained for a standard sample (here, TMS). AC Therefore, as shown in Figure 13, for example, the NMR spectrum is obtained as the frequency shift and relative intensity relative to the frequency (reference frequency) and intensity of the standard sample.

[0097] Here, the identification processing unit 22c derives an NMR spectrum based on the corrected IF demodulated signal, and identifies the molecular structure (such as functional groups) and its quantity contained in the target object based on the peak position and peak shape in the NMR spectrum.

[0098] The NMR spectrum shows the relative frequency (ppm) and relative intensity relative to the frequency and intensity of the standard sample (in this case, TMS).

[0099] Figure 14 shows 1 This figure shows the NMR spectrum of ethylbenzene with respect to H. For example, as shown in Figure 14, in the case of ethylbenzene, peaks for methyl, methylene, and phenyl groups appear in the NMR spectrum. In other words, if the identification processing unit 22c detects peaks like those shown in Figure 14 in the NMR spectrum, it determines that the target object contains methyl, methylene, and phenyl groups, and determines that it contains ethylbenzene based on the ratio of the number of methyl, methylene, and phenyl groups.

[0100] As described above, according to Embodiment 1, the nuclear magnetic resonance sensing unit 1 applies a high-frequency magnetic field based on the RF signal to the target object, and the frequency f of the RF signal RF From the frequency f of the nuclear magnetic resonance signal NMR The system generates an observation signal with a frequency shifted by a certain amount. The mixer section 6 performs intermediate frequency demodulation of the observation signal to generate an intermediate frequency demodulated signal that includes the nuclear magnetic resonance signal. The low-pass filter 7 attenuates unwanted band components in the intermediate frequency demodulated signal, and the intermediate frequency f of the intermediate frequency demodulation IF From the frequency f of the nuclear magnetic resonance signal NMR The frequency components shifted by only a certain amount are transmitted. The digitizing device 21 digitizes the intermediate frequency demodulated signal that has passed through the low-pass filter 7. The correction processing unit 22b performs correction processing on the sensor signal after digitization. The digitizing device 21 comprises a physical field generator 41 that generates a magnetic field or electric field corresponding to the intermediate frequency demodulated signal that has passed through the low-pass filter 7, an optical quantum sensor unit 42 that generates light corresponding to the magnetic field or electric field with a sensing member and converts the light into an electrical signal as a sensor signal with a photoelectric element, and an A / D converter 43 that digitizes the sensor signal and generates a digital intermediate frequency demodulated signal. The optical quantum sensor unit 42 (a) performs quantum operations on the sensing member to generate the light corresponding to the magnetic field or electric field with the sensing member, and (b) has non-uniform output intensity characteristics in a predetermined frequency range. Then, in the correction processing, the correction processing unit 22b adjusts the frequency f of the magnetic field or electric field to bring the frequency characteristics of the intermediate frequency demodulated signal in the above frequency range closer to constant, corresponding to its output intensity characteristics. AC The intermediate frequency demodulated signal is corrected accordingly.

[0101] As a result, the intensity of the intermediate frequency demodulated signal, which fluctuates due to sensitivity variations of the optical quantum sensor unit 42 that depend on the frequency of the applied magnetic field, is compensated for. Therefore, when performing nuclear magnetic resonance sensing on an object that has a chemical shift, specific molecular structures contained in the object can be quantitatively and accurately identified.

[0102] Embodiment 2.

[0103] Figure 15 is a diagram illustrating the identification of calibration data in Embodiment 2. In Embodiment 2, the above-mentioned calibration data is the intermediate frequency f of intermediate frequency demodulation for a specific target object. IF By changing the frequency f of multiple magnetic or electric fields in the aforementioned frequency range, for example, as shown in Figure 15, AC This is set based on the intensity distribution of the sensor signal obtained. The specific target object may be the standard sample mentioned above or other substances. The calibration data may be its intensity distribution or the distribution of the ratio S / So (correction coefficient) mentioned above. If the calibration data is an intensity distribution, the correction coefficient is derived from the intensity values ​​in the calibration data during the correction process.

[0104] Furthermore, the other configurations and operations of the nuclear magnetic resonance sensing device according to Embodiment 2 are the same as those of any of the other embodiments, so their description will be omitted.

[0105] Embodiment 3.

[0106] In Embodiment 3, the above-mentioned calibration data is obtained in a predetermined frequency range (i.e., the range in which calibration should be performed), and includes the spin lock frequency and the magnetic field frequency f. AC It is calculated based on the following. Specifically, for example, the signal strength S shown in Figure 6 is used for each frequency f. AC Calibration data is derived by deriving the following. The calibration data may be the intensity distribution or the distribution of the ratio S / So described above. In Embodiment 3, the calibration data may be calculated in advance and stored in the storage device 22a, or it may be calculated during the correction process.

[0107] Figure 16 is a diagram illustrating the setting of the intermediate frequency in Embodiment 3. In Embodiment 3, the intermediate frequency f described above is IF As shown in Figure 16, for example, the frequency f corresponds to the median of the range of chemical shifts (chemical shift range) for multiple specific molecular structures. AC This is set to match the peak frequency of the sensitivity characteristic (i.e., the frequency at which sensitivity is maximum).

[0108] For example, the spinlock frequency f LOCK When f is 20kHz and the peak frequency of the sensitivity characteristic is 15kHz, RF When the frequency is 43 MHz and the target range for chemical shift is -2 to 18 ppm, f NMR The range is -86Hz to 774Hz.

[0109] In this case, f NMR Since the median of the range is 344Hz, f NMR f at =344Hz AC The intermediate frequency f is set so that the peak frequency matches 15kHz. IF This is considered to be 14.656kHz (=15kHz-344Hz). Therefore, in this case, f AC The frequency range is 14.57kHz to 15.43kHz.

[0110] Furthermore, in this way, f AC When the frequency range is 14.57kHz to 15.43kHz, and digitization is performed with a sampling frequency fs of 13kHz, an undersampling condition is met. As described above, within the observable bandwidth of 0 to 6.5kHz, the peak of the IF demodulated signal is observed at a frequency of one of 1.57kHz to 2.43kHz. In the case of an undersampling condition, the original f is obtained from the frequency of the peak observed within the observable range. AC The frequency, and therefore f NMR The frequency and chemical shift are derived.

[0111] The other configurations and operations of the nuclear magnetic resonance sensing device according to Embodiment 3 are the same as those of any of the other embodiments, so their description will be omitted.

[0112] Embodiment 4.

[0113] Figure 17 is a diagram illustrating the setting of the intermediate frequency in Embodiment 4. In Embodiment 4, if the molecular structure to be detected in the target object is specified, the intermediate frequency f IF This is the frequency f corresponding to the frequency of the chemical shift of that particular molecular structure. AC This is set to match the peak frequency of the sensitivity characteristics.

[0114] For example, the spinlock frequency f LOCK When f is 20kHz and the peak frequency of the sensitivity characteristic is 15kHz, RF When the frequency is 43 MHz and the chemical shift of the target molecular structure is 10 ppm, f NMR This becomes 430Hz. In this case, f AC The intermediate frequency f is set so that the peak frequency matches 15kHz. IF This frequency is said to be 14.57 kHz (= 15 kHz - 430 Hz).

[0115] Note that the frequency f of the IF demodulated signal is as described above. AC When the frequency is 15kHz, and digitization is performed with a sampling frequency fs of 12kHz, an undersampling condition occurs. As described above, in the observable bandwidth of 0-6kHz, the peak of the digital IF demodulated signal is observed at 3kHz (=15kHz-12kHz). In the case of an undersampling condition, the original f is obtained from the frequency of the peak observed in the observable range. AC The frequency, and therefore f NMR The frequency and chemical shift are derived.

[0116] Furthermore, the other configurations and operations of the nuclear magnetic resonance sensing device according to Embodiment 4 are the same as those of any of the other embodiments, so their description will be omitted.

[0117] Embodiment 5.

[0118] Figure 18 is a diagram illustrating the setting of the spinlock frequency in Embodiment 5. In Embodiment 5, if the molecular structure to be detected in the target object is specified, the spinlock frequency f LOCK This is the frequency f corresponding to the frequency of the chemical shift of that particular molecular structure. AC This is set to match the peak frequency of the sensitivity characteristic. In other words, the spin lock frequency f LOCK When this changes, the sensitivity characteristics change, and the peak frequency of the sensitivity characteristics also changes. Therefore, the peak frequency of the sensitivity characteristics corresponds to the frequency f of the chemical shift of that particular molecular structure. AC It will be adjusted to match.

[0119] For example, f RF If the frequency is 43 MHz and the chemical shift of the target molecular structure is 5 ppm, then f NMR This becomes 215Hz, and the intermediate frequency f IF If it is set to 13kHz, the frequency f of the IF demodulated signal will AC This corresponds to 13.215kHz.

[0120] Therefore, to ensure that the peak frequency of the sensitivity characteristic is 13.215 kHz, the spin lock frequency f is determined based on the relationship shown in Figure 6, for example. LOCK The spin lock frequency f is set. LOCK This is set to 17.62kHz.

[0121] Furthermore, f AC When the frequency is 13.215kHz, and digitization is performed with a sampling frequency fs of 12kHz, an undersampling condition is met. As described above, in the observable bandwidth of 0-6kHz, the peak of the digital IF demodulated signal is observed at 1.215kHz (=13.215kHz-12kHz). In the case of undersampling, the original f is obtained from the frequency of the peak observed in the observable range. AC The frequency, and therefore f NMR The frequency and chemical shift are derived.

[0122] The other configurations and operations of the nuclear magnetic resonance sensing device according to Embodiment 5 are the same as those of any of the other embodiments, so their description will be omitted.

[0123] Embodiment 6.

[0124] Figure 19 is a diagram illustrating the measurement sequence (dynamic decoupling) in Embodiment 6. In Embodiment 6, dynamic decoupling is used as the measurement sequence, for example, as shown in Figure 19. Examples of dynamic decoupling include XY8-k and CPMG (Carr-Purcell-Meiboom-Gill).

[0125] In the optical quantum sensor unit 42, the controller 66 applies a microwave pulse sequence based on dynamic decoupling to the magnetic resonance member 1 during this measurement sequence. However, the reciprocal of the spinlock frequency of the microwave pulse sequence (1 / f) is used. LOCK ) is the period of the measured AC field (1 / f AC It is longer than ). Note that in the case of dynamic decoupling, the reciprocal of the spin lock frequency (1 / f) LOCK ) is the time length from the center of the first π pulse to the center of the last π pulse in a sequence of N π pulses, as shown in Figure 19, for example.

[0126] Figure 20 shows the frequency f of the AC field under measurement in Embodiment 6. AC This diagram illustrates the maximum value of the slope, max|dS / dB|, relative to .

[0127] In the case of dynamic decoupling, for example, as shown in Figure 20, the frequency f of the AC field under measurement AC The characteristic of the maximum slope max|dS / dB| with respect to changes depending on the number of pulses N, but the peak frequency is the spinlock frequency f LOCK It is higher. Therefore, the frequency f of the AC field being measured AC However, the spin lock frequency f LOCKIt is set higher. In other words, the reciprocal of the spinlock frequency of the microwave pulse sequence (1 / f LOCK ) is the period of the measured AC field (1 / f AC It will be set to be longer than ).

[0128] The other configurations and operations of the nuclear magnetic resonance sensing device according to Embodiment 6 are the same as those of any of the other embodiments, so their description will be omitted.

[0129] Furthermore, various changes and modifications to the embodiments described above will be obvious to those skilled in the art. Such changes and modifications may be made without deviating from the spirit and scope of the subject matter and without diminishing the intended advantages. In other words, such changes and modifications are intended to be included in the claims.

[0130] For example, in the above embodiment, quadrature phase detection may be performed. In that case, specifically, the above-described LO signal and the LO signal after a 90-degree phase shift are used, and the above-described signal processing is performed on each, thereby demodulating each IF demodulated signal to obtain the demodulated signal I and the demodulated signal Q (frequency component f). NMR Each of these is generated, and predetermined signal processing is performed to obtain the NMR signal (frequency component f NMR Extract the following:

[0131] Furthermore, in the above embodiment, the measurement method in the sensor body 51 is not limited to the ODMR described above, and any other measurement method is acceptable as long as it uses a sensing member corresponding to a physical field such as an electric field, performs quantum operations on the sensing member, and can detect observed light corresponding to the physical field intensity.

[0132] Furthermore, in the above embodiment, the control device 22 may perform predetermined calculation processing on the output signal of the digitizing device 21 so that the value of the output signal (digital value) matches the level of the analog IF demodulated signal.

[0133] Furthermore, in the above embodiment, a low-noise buffer (voltage amplification = 1) that satisfies the noise level requirement may be provided between the low-pass filter 7 and the digitizing device 21, if necessary.

[0134] Furthermore, although digitization is performed under undersampling conditions in the above embodiment, the sampling conditions are not limited to undersampling conditions.

[0135] Furthermore, in the above embodiment, for the identification of molecular structure based on chemical shift 1 The NMR spectrum of H has been derived, but instead, 13 The NMR spectra of other atomic nuclei, such as 13C, may also be derived.

[0136] Furthermore, in the above embodiment, the spin lock frequency f LOCK and the frequency f of the IF demodulated signal AC Although the sensitivity characteristics and output intensity characteristics are inconsistent due to this, even if the output intensity characteristics are inconsistent due to other factors (e.g., frequency (wavelength) characteristics of the optical system), the same correction as described above compensates for the intensity of the IF demodulated signal that fluctuates due to the inconsistency of the output intensity characteristics.

[0137] Furthermore, the part that generates the analog IF demodulated signal in the above embodiment is not limited to what is described above, but may also be the one described in International Publication No. 2023 / 089883, International Publication No. 2024 / 224587, etc. In other words, unwanted frequency band components are removed and the intermediate frequency f IF From the frequency f of the NMR signal NMR All that is needed is an IF demodulated signal with a frequency shifted by that amount. [Industrial applicability]

[0138] The present invention can be applied, for example, to various measurements and imaging using nuclear magnetic resonance. [Explanation of symbols]

[0139] 1. Nuclear Magnetic Resonance Sensing Unit 6. Mixer section 7. Low-pass filter 21 Digitizing device 22a Storage device 22b Correction Processing Unit 41 Physical field generator 42 Optical quantum sensor section 43 A / D converters 51 Sensor body 52 Photoelectric elements 61 Magnetic resonance member (an example of a sensing member) 62 High-frequency magnetic field generator 63 Magnets 64 High frequency power supply 65 Light-emitting device 66 Controllers

Claims

1. A nuclear magnetic resonance sensing unit applies a high-frequency magnetic field based on an RF signal to a target object and generates an observation signal with a frequency shifted from the frequency of the RF signal by the frequency of the nuclear magnetic resonance signal, A mixer unit that performs intermediate frequency demodulation of the observed signal to generate an intermediate frequency demodulated signal including the nuclear magnetic resonance signal, In the intermediate frequency demodulated signal, a low-pass filter is provided that transmits frequency components shifted from the intermediate frequency of the intermediate frequency demodulation by the frequency of the nuclear magnetic resonance signal, A digitizing device that digitizes the intermediate frequency demodulated signal that has passed through the low-pass filter, The system includes a correction processing unit that performs correction processing on the intermediate frequency demodulated signal after digitization, The digitizing device comprises a physical field generator that generates a magnetic field or electric field corresponding to the intermediate frequency demodulated signal transmitted through the low-pass filter; an optical quantum sensor unit that generates light corresponding to the magnetic field or electric field using a sensing member and converts the light into an electrical signal as a sensor signal using a photoelectric element; and an analog-to-digital converter that digitizes the sensor signal to generate a digital intermediate frequency demodulated signal. The optical quantum sensor unit (a) performs quantum operations on the sensing member to generate light corresponding to the magnetic field or electric field on the sensing member, and (b) has an inconsistent output intensity characteristic in a predetermined frequency range. The correction processing unit, in the correction processing, corrects the intermediate frequency demodulated signal in accordance with the frequency of the magnetic field or electric field so that the frequency characteristics of the intermediate frequency demodulated signal in the frequency range are brought closer to a constant value in accordance with the output intensity characteristics. A nuclear magnetic resonance sensing device characterized by [feature].

2. The sensing member is a magnetic resonance member in which the electron spin quantum state changes in response to the magnetic field and in which electron spin quantum manipulation can be performed using microwaves. The optical quantum sensor unit comprises the sensing member, a high-frequency magnetic field generator that performs electron spin quantum manipulation of the magnetic resonance member with microwaves, a high-frequency power supply that generates microwaves in the high-frequency magnetic field generator, a light-emitting device that emits excitation light to be irradiated onto the magnetic resonance member, a light-receiving device that receives fluorescence emitted by the magnetic resonance member in response to the excitation light and generates a sensor signal corresponding to the intensity of the fluorescence, and a controller that controls the high-frequency power supply and the light-emitting device to apply the microwaves and excitation light to the magnetic resonance member in a predetermined measurement sequence. The controller applies the microwave pulse sequence based on a Hahn echo pulse sequence or dynamic decoupling to the magnetic resonance member. The reciprocal of the spin-lock frequency of the microwave pulse sequence is different from the period of the magnetic field. The output strength characteristics are inconsistent within the frequency range because the reciprocal of the spinlock frequency is different from the period of the magnetic field. A nuclear magnetic resonance sensing device according to claim 1, characterized by the following:

3. The device further includes a storage device that stores calibration data corresponding to the output intensity characteristics, The correction processing unit performs the correction process by referring to the calibration data. The calibration data is set based on the distribution of the intensity of the sensor signal obtained at multiple magnetic field frequencies within the frequency range by changing the intermediate frequency of the intermediate frequency demodulation for a specific target object. A nuclear magnetic resonance sensing device according to claim 1 or claim 2, characterized by the above.

4. The correction processing unit performs the correction process by referring to the calibration data. The calibration data is calculated based on the spin lock frequency and the frequency of the magnetic field or electric field. A nuclear magnetic resonance sensing device according to claim 2, characterized by the following:

5. The nuclear magnetic resonance sensing apparatus according to any one of claims 1 to 4, characterized in that the intermediate frequency of the intermediate frequency demodulation is set such that the frequency of the magnetic field or electric field corresponding to the median of the appearance range of chemical shifts of a plurality of specific molecular structures matches the peak frequency of the sensitivity characteristics of the optical quantum sensor unit.

6. The nuclear magnetic resonance sensing apparatus according to any one of claims 1 to 4, characterized in that the intermediate frequency of the intermediate frequency demodulation is set such that the frequency of the magnetic field or electric field corresponding to the frequency of the chemical shift of one specific molecular structure matches the peak frequency of the sensitivity characteristics of the optical quantum sensor.

7. The nuclear magnetic resonance sensing device according to claim 2, characterized in that the spin lock frequency is set such that the frequency of the magnetic field or electric field corresponding to the frequency of the chemical shift of one specific molecular structure matches the peak frequency of the sensitivity characteristics of the optical quantum sensor unit.

8. The nuclear magnetic resonance sensing device according to claim 1, characterized in that the frequency range is set according to the range of appearance of chemical shifts of one or more specific molecular structures.

9. The steps include: applying a high-frequency magnetic field based on an RF signal to a target object and generating an observation signal with a frequency shifted from the frequency of the RF signal by the frequency of the nuclear magnetic resonance signal; The steps include performing intermediate frequency demodulation of the observed signal to generate an intermediate frequency demodulated signal including the nuclear magnetic resonance signal, A low-pass filter is used to transmit a frequency component in the intermediate frequency demodulated signal that is shifted from the intermediate frequency of the intermediate frequency demodulation by the frequency of the nuclear magnetic resonance signal. A digitizing step in which the intermediate frequency demodulated signal that has passed through the low-pass filter is digitized, The step of performing a correction process on the intermediate frequency demodulated signal after digitization is also included. In the digitizing step, (a) a magnetic field or electric field corresponding to the intermediate frequency demodulated signal that has passed through the low-pass filter is generated; (b) an optical quantum sensor unit generates light corresponding to the magnetic field or electric field in a sensing member, and the light is converted into an electrical signal as a sensor signal by a photoelectric element; and (c) an analog-to-digital converter digitizes the sensor signal to generate a digital intermediate frequency demodulated signal. The optical quantum sensor unit (a) performs quantum operations on the sensing member to generate light corresponding to the magnetic field or electric field on the sensing member, and (b) has an inconsistent output intensity characteristic in a predetermined frequency range. In the correction process, the intermediate frequency demodulated signal is corrected in accordance with the frequency of the magnetic field or electric field so that the frequency characteristics of the intermediate frequency demodulated signal in the frequency range are brought closer to a constant value in accordance with the output intensity characteristics. A nuclear magnetic resonance sensing method characterized by the following.

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