OPM-based superparamagnetic nanoparticle relaxation signal detection system and method

By designing a superparamagnetic nanoparticle relaxation signal detection system based on OPM, the problem of interfering relaxation detection during particle magnetization and lack of quantitative detection of fixed source of spatial magnetic particles is solved, and efficient relaxation signal detection and quantitative detection of spatial fixed source of particle in extremely weak magnetic environments are realized.

CN119667565AActive Publication Date: 2025-03-21BEIHANG UNIV
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Patent Information

Application Number
CN202411893354.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-12-20
Publication Date
2025-03-21
Estimated Expiration
2044-12-20

AI Technical Summary

Technical Problem

There are two main problems in the existing magnetic relaxation detection of superparamagnetic nanoparticles in OPM detection: one is that the particle magnetization process interferes with the relaxation field detection, and the other is that the detection system for spatial magnetic particles is lacking.

Method used

A superparamagnetic nanoparticle relaxation signal detection system based on OPM is designed, including a particle magnetization module and a relaxation signal synchronization detection module. The system generates a uniform magnetic field through multi-planar magnetic moment-free coils, and synchronously collects signals using OPM arrays and data acquisition modules, effectively suppressing the interference of the magnetization process on relaxation detection, and realizing quantitative detection of spatial magnetic particles in fixed source.

Benefits of technology

The system can effectively detect the relaxation signal of superparamagnetic nanoparticles in an extremely weak magnetic environment, reduce the interference of the magnetization process on detection, and achieve more accurate quantitative estimation of the spatial fixed source of particles.

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Abstract

The invention discloses a superparamagnetic nanoparticle relaxation signal detection system and method based on OPM. The detection system comprises a magnetic nanoparticle module, an OPM array and a magnetic field generation module in a magnetic shielding environment, and a magnetic field control module and a data acquisition module which are connected with the magnetic nanoparticle module, the OPM array and the magnetic field generation module and outside the magnetic shielding environment. The magnetic nanoparticle module is placed in a controllable magnetic field area of the magnetic field generation module to wait for magnetization, the OPM array receives relaxation signals generated after particle magnetization, and the magnetic field generation module is used for generating a particle magnetization field and a background field inside; the magnetic field control module receives a magnetic field module instruction of the upper computer and supplies power to the magnetic field generation module through the constant-voltage power supply; and the data acquisition module is connected with the OPM array to acquire the relaxation signal, receives the magnetic field mode signal generated by the magnetic field control module, and transmits the data back to the upper computer. According to the invention, a particle magnetization device is improved, and magnetization background noise is suppressed from hardware.
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Description

Technical Field

[0001] The invention belongs to the field of biomedical engineering, and particularly relates to a superparamagnetic nanoparticle relaxation signal detection system and method based on OPM. Background Art

[0002] In recent years, various bioimaging methods for superparamagnetic nanoparticles have been proposed. In particular, superparamagnetic nanoparticles of ferroferric oxide or iron oxide are widely used in cell tissue imaging as a contrast agent with excellent magnetic properties and good biocompatibility. At present, enhanced magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) are commonly used methods to study the spatial distribution of superparamagnetic nanoparticles, and are also hot topics in nanomedicine. Their common point is that they obtain spatial imaging information of particles by magnetizing particles with high-frequency alternating magnetic fields, which has important applications in the detection of tumor and other lesion cell tissues and magnetic hyperthermia.

[0003] With the development and maturity of superconducting quantum interference device (SQUID) and optical pumping magnetometer (OPM), biological extremely weak magnetic field detection has received extensive attention and research. OPM has the advantages of flexible layout, multi-axis measurement, high sensitivity and low cost, so it has developed rapidly in the field of brain magnetometry and heart magnetometry imaging.

[0004] Ordinary tumor and other cell tissues cannot spontaneously generate potential and displacement, and the current ultra-high sensitivity magnetometers such as SQUID and OPM cannot reach the detection limit of the magnetic field of cell tissues, so superparamagnetic nanoparticles are needed as a medium to detect tumor cells. The superparamagnetic nanoparticle relaxation detection method based on OPM can fully combine the magnetic properties of superparamagnetic nanoparticles and the layout and sensitivity advantages of OPM, which can have great advantages in small cell and low dose imaging.

[0005] Superparamagnetic nanoparticles are macroscopically non-magnetic and need to be magnetized by an external magnetic field to generate specific characterization signals. Due to the bandwidth limitation and time resolution characteristics of ultra-high sensitivity magnetic sensors, the particles can be magnetized by DC field to detect relaxation decay signals. However, the current magnetic relaxation detection for superparamagnetic nanoparticles in OPM has the following problems: (1) The magnetization and relaxation detection of particles are carried out under the same conditions. The magnetization process of particles will affect the magnetic shielding environment of the relaxation detection device, interfere with the detection of the relaxation field, and the coil inductance effect and the recovery time of the magnetic sensor are not conducive to signal recovery; (2) There is a lack of spatial magnetic particle source determination and quantitative detection system for OPM. Summary of the invention

[0006] In order to solve the above technical problems, the present invention proposes a superparamagnetic nanoparticle relaxation signal detection system and method based on OPM to realize spatial magnetic particle detection in an extremely weak magnetic environment.

[0007] To achieve the above purpose, the technical solution adopted by the present invention is:

[0008] On the one hand, the present invention provides a superparamagnetic nanoparticle relaxation signal detection system based on OPM, comprising a particle magnetization module and a relaxation signal synchronization detection module, wherein:

[0009] The particle magnetization module includes a magnetic nanoparticle module, a magnetic field generation module and a magnetic field control module, and the relaxation signal synchronization detection module includes an OPM array and a data acquisition module;

[0010] The magnetic nanoparticle module includes ferroferric oxide or iron oxide superparamagnetic nanoparticles in a fixed state, and is placed in a controllable magnetic field region generated by a magnetic field generation module;

[0011] The magnetic field generating module comprises a background field generating module composed of a coil without magnetic moment and a magnetizing field generating module composed of a one-dimensional Helmholtz coil. The coil without magnetic moment and the one-dimensional Helmholtz coil adopt a non-magnetic skeleton to generate a magnetic field in the area where the magnetic nanoparticle module is placed. The magnetic field generating module is connected to a constant voltage power supply to supply power to the background field generating module and the magnetizing field generating module.

[0012] The magnetic field control module includes a circuit control panel capable of setting a magnetization mode, and the circuit control panel is detachably arranged between the magnetic moment-free coil and the constant voltage power supply, and controls the magnetization field generation module to generate a pulsed magnetic field through the host computer, and simultaneously controls the background field generation module to generate a constant magnetic field;

[0013] The OPM array is used to receive the magnetic field generated by the magnetic field generation module and act on the magnetic nanoparticle module to generate a relaxation signal, and the OPM array outputs multiple sets of simulation data of over-range magnetization field and particle Neel relaxation signal;

[0014] The data acquisition module includes an analog-to-digital conversion data acquisition card connected to the OPM array and the circuit control panel, which synchronously acquires the analog data output by the OPM array and the pulse electrical signal representing the magnetic field mode and transmits them to the host computer.

[0015] Furthermore, the one-dimensional Helmholtz coil is a group of symmetrical single-plane coils, the group of symmetrical single-plane coils includes two mutually symmetrical annular coils, the two mutually symmetrical annular coils have the same number of turns, the same coil winding method and the coil radius is equal to the coil spacing, the magnetic moment-free coil includes at least one group of dual-plane coils, the group of dual-plane coils is two mutually parallel one-dimensional Helmholtz coil structures with overlapping symmetry centers and opposite winding directions.

[0016] Furthermore, the background field generating module uses at least one group of dual-plane coils to generate a controllable near-zero magnetic field, and the magnetization field generating module uses a group of one-dimensional Helmholtz coils with the same winding direction to generate a controllable uniform pulsed square wave excitation magnetic field. The magnetization field generating module is placed in the near-zero magnetic field area of ​​the background field generating module.

[0017] Furthermore, the circuit control module includes a mode setting module and a mode acquisition module. The mode setting module includes a mode control circuit, which is connected to the constant voltage power supply to provide a controllable DC current for the background field generation module, and is connected to the electromagnetic relay to provide a pulse current with an adjustable duty cycle for the magnetization field generation module; the mode acquisition module outputs a pulse electrical signal representing the switching of the electromagnetic relay.

[0018] Furthermore, the near-zero magnetic field generated by the background field generating module is a fixed uniform constant magnetic field of the order of nT to pT, and the magnetic field range covers the magnetization field generating module and the OPM array area.

[0019] Furthermore, the OPM array is arranged on an OPM array platform, and the OPM array platform includes a card slot plane arranged in a square or a ring, and the OPM magnetic sensitive axes on all the card slot planes are parallel to the center direction of the uniform magnetic field of the magnetization field generating module. The OPM array platform is a flat plate that can move horizontally and vertically and has a measurable scale. The OPM array and the OPM array platform are parallel to the one-dimensional Helmholtz coil of the magnetization field generating module and the magnetic moment-free coil plane of the background field generating module.

[0020] Furthermore, the host computer is connected to the magnetic field control module to output control instructions, and is also connected to the data acquisition module to receive analog data output by the OPM array and pulse electrical signal data representing the magnetic field pattern, and processes and analyzes the received data.

[0021] Furthermore, the magnetic nanoparticle module, magnetic field generating module and OPM array are all placed in a magnetic shielding barrel or a magnetic shielding room, and the host computer, constant voltage power supply, magnetic field control module and data acquisition module are all placed outside the magnetic shielding barrel or the magnetic shielding room, and the inner and outer parts are connected by a coaxial cable or twisted pair cable with a shielding effect for coil power supply and information transmission.

[0022] On the other hand, the present invention also provides a superparamagnetic nanoparticle relaxation signal detection method based on OPM, which is applied to the aforementioned superparamagnetic nanoparticle relaxation signal detection system based on OPM, comprising the following steps:

[0023] Step 1, placing the superparamagnetic nanoparticles to be tested at a position to be tested in the magnetic field generating module, wherein the position to be tested is the center of the internal uniform magnetic field generated by the magnetic field generating module;

[0024] Step 2, turn on the constant voltage power supply, and set the circuit control block connected to the magnetization field generation module through the host computer to a pulse output mode with a high level time in the range of (1s, 2s) and a low level time in the range of (5s, 20s);

[0025] Step 3, setting and connecting the background field generation module to a fixed DC output mode through the constant voltage power supply and the circuit control panel and starting it, so that the background field generation module generates an adjustable fixed uniform magnetic field;

[0026] Step 4: Turn on the OPM array, perform air chamber heating, magnetic compensation and calibration, and start measuring and collecting data;

[0027] Step 5, the start-up circuit control module outputs voltage to the magnetization field generation module, so that a uniform pulse DC field sequence is generated in the center of the magnetization field generation module to magnetize the sample, the OPM array always remains in the open and data collection state, and the switch control signal in the pulse output mode of the circuit control module is synchronously collected;

[0028] Step 6: Turn off the circuit control board and the OPM array, stop data acquisition, and transmit the measured data to the host computer as the original particle signal;

[0029] Step 7, remove or replace the superparamagnetic nanoparticles to be tested in step 1 with pure water, repeat steps 2 to 5, and collect the data measured by the OPM array as the background attenuation signal;

[0030] Step 8: Filter and cancel the original particle signal data collected in step 6 and the background attenuation signal data collected in step 7 to obtain the spatial detection signal of the particle.

[0031] The beneficial effects of the present invention are:

[0032] The present invention provides a relaxation signal detection device and a measurement method for superparamagnetic nanoparticles that can be used under OPM atomic magnetometer measurement conditions. The device can effectively suppress the influence of background decay generated by the magnetization process on the OPM working state and particle relaxation detection, and can effectively restore the relaxation signal generated by the particles to obtain a more accurate particle source quantitative estimation in space. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Schematic diagram of the superparamagnetic nanoparticle relaxation signal detection system based on OPM of the present invention;

[0034] Figure 2 A schematic diagram of the arrangement of coils in a magnetic field generating module according to an embodiment of the present invention;

[0035] Figure 3 Schematic diagram of the OPM array and detection platform layout of an embodiment of the present invention.

[0036] Reference numerals:

[0037] 1. Background field generation module, 11. The first group of planar coils without magnetic moment, 12. The second group of planar coils without magnetic moment; 2. Magnetization field generation module; 3. Measurement platform, 31. OPM array platform, 32. Particle placement platform, 33. Slide platform, 34. Longitudinal slide, 35. OPM atomic magnetometer. DETAILED DESCRIPTION

[0038] The present invention is described in detail below with reference to the accompanying drawings and embodiments. The specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0039] The working principle of the superparamagnetic nanoparticle relaxation signal detection system based on OPM of the present invention is as follows: superparamagnetic nanoparticles with magnetization and relaxation time of milliseconds and seconds are selected, such as ferroferric oxide or iron oxide nanoparticles with a core diameter of about 23-27nm; a multi-plane magnetic moment-free coil is used to replace a single-plane Helmholtz coil as a magnetic field generation module, and an adjustable near-zero background magnetic field of nT to pT order and a uniform directional pulse magnetic field of mT order are generated internally, and the magnetic field decays rapidly externally; a relay is used to control the output of pulsed square wave current, so that the particles are rapidly magnetized and then relax and the whole signal is collected, and in addition, the background decay signal without particles or pure water under the same magnetization condition is collected, and the above two signals are synchronously collected by a data acquisition module and transmitted back to a host computer for subsequent analysis and processing.

[0040] In a first aspect, the present invention provides an OPM-based superparamagnetic particle magnetization module, comprising a magnetic nanoparticle module, a magnetic field generation module and a magnetic field control module.

[0041] Specifically, the particles used in the magnetic nanoparticle module specifically refer to spherical or quasi-spherical nanoparticles of ferroferric oxide or iron oxide with biocompatible coating materials, with a diameter of about 23-27nm and a narrow particle size distribution. When the particles are in a fixed state, including targeted binding, particle aggregation, freeze drying, etc., the particles will undergo a relaxation process dominated by Neel relaxation during the relaxation process, and its relaxation time ,in, is the particle core volume, is the characteristic damping time constant, usually 10 -9 s, k B =1.38×10 -23 JK -1 is the Boltzmann constant, K[J / m 3 ] is magnetic anisotropy, and T[K] is temperature. The Brownian relaxation process that enables the particle to physically rotate will be suppressed, and its relaxation time , is the viscosity of the local environment, is the hydrodynamic volume of the particle. Therefore, the effective relaxation time of the particle is Under the above conditions, the effective relaxation time of particles is in the range of milliseconds to seconds and can be effectively detected by OPM.

[0042] Particles need to be magnetized by an external magnetic field before relaxation occurs. Multi-plane coils without magnetic moment can generate a uniform magnetic field in a large range in the center, so that most particles can be magnetized within a few hundred milliseconds to a few seconds. The magnetization process of particles can be described by the Langevin function:

[0043] ,

[0044] ,

[0045] in, represents the net magnetization intensity of the particle after magnetization, represents the saturation magnetization, is the applied magnetizing field strength, µ0=4π×10 -7 N / A 2 is the magnetic permeability of free space, is the Langevin function that characterizes the magnetization process, and the intermediate parameter , Coth(·) represents the hyperbolic cotangent function. The ratio of magnetization can be expressed as According to simulation calculations, the magnitude of the magnetic field required to complete magnetization is in the order of mT (millitesla), or tens of G (gauss).

[0046] The magnetic field generating module is a coil group composed of two or more parallel planar windings, which are used for the background field generating module 1 and the magnetization field generating module 2 respectively. A group of planar coils without magnetic moment includes four winding planes with central symmetry, and one side of the center has two winding planes with different radii and a total magnetic moment of zero. Assuming that there are m groups of coils without magnetic moment, all planar coil groups should meet the following requirements:

[0047] ,

[0048] in, and Indicates the number of winding turns on two planes on one side, and Represents the winding radius of two planes on one side. For the coil without magnetic moment used in the background field generation module 1, the winding directions of the adjacent planes on one side are opposite, and the winding directions of the two symmetrical planes are the same; for the Helmholtz coil used in the magnetization field generation module 2, the winding directions of the two symmetrical planes are the same. The direction of the current passing through the coil is consistent with the winding direction. The position of each group of coil planes from the center point is adjusted according to the optimization method to meet the requirements that the background field generation module 1 can generate nT to pT magnetic fields within the range of the OPM array and the magnetization field generation module, the magnetization field generation module 2 can generate mT magnetic fields within the cm range at the center, and the external magnetic field of the background field generation module 1 decays rapidly to meet the magnetic shielding requirements.

[0049] The magnetic field control module includes a circuit control panel composed of a mode setting module and a mode acquisition module, which is connected to a constant voltage power supply for powering the circuit control panel, and is connected to a host computer to control the constant voltage power supply to output voltage to the magnetic field generation module, and is also connected to a data acquisition module to output a pulse electrical signal. The constant voltage power supply provides the power required for driving the circuit control panel and powers the magnetic field generation module, outputs a low-noise constant voltage, and provides a branch for powering the circuit control panel, and the other branch is directly connected to the magnetic field generation module and is disconnected by the mode setting module. The mode setting module is a pulse control circuit integrated on the circuit control panel, and the host computer accesses the circuit control panel through a communication interface to interact with the MCU and manipulate the pulse control circuit. The main components of the pulse control circuit are mainly electromagnetic relays, and the disconnection time can be controlled by the host computer setting, so that the circuit board block outputs a pulse voltage sequence. The mode acquisition module is a potential measurement circuit integrated on the circuit control panel, which collects the disconnection signal of the electromagnetic relay and outputs a pulse electrical signal with a maximum value of 3.3V. The interface for outputting the signal is set on the circuit board and connected to the data acquisition module.

[0050] In the second aspect, the present invention provides a particle relaxation detection and acquisition scheme. First, the center of the OPM array plane is placed on the central axis of each coil, about 5 cm or less from the center of the magnetizing field, and the OPM measurement axis is set to align with the direction of the magnetizing field, and the number of OPMs is M. Then, the background attenuation signal is collected under the magnetic field excitation condition of no particles or pure water. The pulse high level is recorded as the excitation time , the pulse low level section, i.e. the disconnection time, is recorded as , use multiple groups of pulse square waves to excite the Helmholtz coil of the magnetizing field generation module, the number of pulses is recorded as N, the OPM output signal and the switch control signal of the relay are collected synchronously, and the sampling rate is set to , then the collected background attenuation signal is recorded as , is a set of size While collecting the OPM signal, the relay disconnection signal is collected synchronously, recorded as The sampling rate is consistent with the OPM signal, and it is a matrix of the same size. Next, the excitation and magnetization signals of the magnetic nanoparticles placed under the same conditions are collected in the same way as above. The obtained particle original signal and the synchronous relay disconnection signal are recorded as and .

[0051] Through the signal processing module, using the synchronous disconnect signal and The background attenuation signal and the original particle signal collected are respectively and The segmented processing is performed, and the background attenuation signal after segmented averaging is filtered and cancelled with the original particle signal to finally obtain the spatial detection signal of the particle.

[0052] The superparamagnetic particle magnetization module based on OPM provided in the first aspect is applied to the present invention, such as Figure 1 As shown, the superparamagnetic nanoparticle relaxation signal detection system based on OPM of the present invention includes: a particle magnetization module and a relaxation signal synchronization detection module, and the particle magnetization module includes a magnetic nanoparticle module, a magnetic field generation module, and a magnetic field control module.

[0053] The magnetic nanoparticle module is a selected fixed state of ferroferric oxide or iron oxide superparamagnetic nanoparticles, which mainly undergo Neel relaxation after magnetization;

[0054] The magnetic field generating module is a non-magnetic moment coil and a Helmholtz coil with a non-magnetic frame and a low-inductance multi-turn winding, and the coil is connected to a constant voltage power supply, and the constant voltage power supply is used to supply power to the magnetizing coil so that it generates a uniform background field and a pulsed magnetizing field in the central area to magnetize the magnetic nanoparticle module;

[0055] The magnetic field control module is a circuit control module that can set the magnetization mode. It is detachably arranged between the no-magnetic-moment coil and the constant-voltage power supply. By opening and closing it, the magnetization field generation module 2 generates a pulsed magnetic field, so that the magnetic nanoparticle module has a suitable magnetization process and a sufficient relaxation process.

[0056] The relaxation signal synchronous detection module includes an OPM array and a data acquisition module, the magnetic sensitive axis of the OPM array is parallel to the uniform magnetic field direction of the center of the Helmholtz coil of the magnetization field generation module, the data acquisition module includes an analog-to-digital conversion data acquisition card connecting the OPM array and the circuit control panel, which can realize the synchronous acquisition of the particle signal detected by the magnetometer and the pulse electrical signal representing the magnetic field mode, the OPM array outputs multiple groups of analog data of the over-range magnetization field and particle Neil relaxation signal, the circuit control panel outputs 3.3V TTL conversion square wave signal data, and the analog-to-digital conversion data acquisition card synchronously collects and saves the two signals at the same sampling rate. The magnetic nanoparticle module, the magnetic field generation module and the OPM array are all placed in a magnetic shielding environment that enables the OPM array to perform extremely weak magnetic detection, and the constant voltage power supply, the magnetic field control module and the data acquisition module are placed outside the magnetic shielding environment. The connection between each module from the magnetic shielding environment to the non-magnetic shielding environment adopts a coaxial cable or a twisted pair cable to reduce electromagnetic interference.

[0057] like Figure 2 As shown, a configuration of a non-magnetic moment coil of a background field generating module and a Helmholtz coil of a magnetizing field generating module in a magnetic field generating module of the present invention, in which the background field generating module 1 includes two groups of interconnected non-magnetic moment planar coil groups: a first group of non-magnetic moment planar coils 11 and a second group of non-magnetic moment planar coils 12. One group of planar coil groups is four planar windings symmetrical about the measuring platform 3, and the radius and number of winding turns of the four planar coils of the first group of non-magnetic moment planar coils 11 from left to right are respectively expressed as , , , The radius and number of turns of the four planar coils from left to right of the second group of planar coils without magnetic moment 12 are respectively expressed as , , , The winding directions of adjacent planes on one side are opposite, the winding directions of the two symmetrical planes are the same, the winding inlets and outlets of all planes are connected in series, and the coil group without magnetic moment meets the following conditions:

[0058] ,

[0059] The magnetization field generation module 2 is a set of Helmholtz coils on both sides of the measurement platform, with the number of turns being , the distance between the two coils is equal to the coil radius , the uniform magnetic field in the center covers the entire measurement platform. Assume that the current is I, and the magnetic field generated in the center Size:

[0060] ,

[0061] Where, µ0=4π×10 -7 N / A 2 is the magnetic permeability of free space, It is the background magnetic field generated by the background field generation module 1 in the measurement platform area.

[0062] The distance between each coil in the magnetic field generating module is determined by an optimization method so that it can generate a uniform pulsed magnetic field of the order of mT in the measurement platform 3 area, and can generate a controllable uniform extremely weak background magnetic field of the order of nT to pT. The magnetic field decays rapidly outside the range of the magnetic field generating module 2. The number of planar coil groups in the background field generating module 1 can be increased or decreased according to the optimization results.

[0063] like Figure 3 As shown, a design mode of the OPM array measurement platform of the present invention. There are three platforms from top to bottom, namely OPM array platform 31, particle placement platform 32 and slide rail platform 33. OPM array platform 31 and slide rail platform 33 are interconnected by longitudinal slide rail 34, and particle placement platform 32 is connected with slide rail platform 33 by transverse slide rail. Particle placement platform 32 can be moved in plane by slide rail platform 33 to change the particle position in space, and longitudinal slide rail 34 can be disassembled. When particle placement platform 32 moves in plane, two longitudinal slide rails 34 on one side of the moving direction can be removed, and two longitudinal slide rails 34 on the other side are locked and fixed, and then moved by transverse slide rail. When it is necessary to change the longitudinal movement, the transverse slide rail between particle placement platform 32 and slide rail platform 33 is locked, and particle placement platform 32 and slide rail platform 33 are kept relatively still, and moved by longitudinal slide rail 34. Scales are marked at the slide rail, and the position of particles in space is controllable. During the measurement process, the OPM array platform 31 and the magnetization field generation module 2 are kept relatively still, and the amount of information of the spatial measurement is increased by moving the particles. The OPM array platform 31 is used to place multiple OPM atomic magnetometers 35, which have a variety of arrangements and can be set in the form of rings and rectangular arrays. The particle placement platform 32 can be set with a porous structure, which can increase the amount of spatial information by placing particles in different holes, and can also perform multi-particle source measurement.

[0064] The specific embodiments described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific embodiment of the present invention and is 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 in the scope of protection of the present invention.

Claims

1. A superparamagnetic nanoparticle relaxation signal detection system based on OPM, characterized in that: It includes a particle magnetization module and a relaxation signal synchronous detection module, wherein: The particle magnetization module includes a magnetic nanoparticle module, a magnetic field generation module and a magnetic field control module, and the relaxation signal synchronization detection module includes an OPM array and a data acquisition module; The magnetic nanoparticle module includes ferroferric oxide or iron oxide superparamagnetic nanoparticles in a fixed state, and is placed in a controllable magnetic field region generated by a magnetic field generation module; The magnetic field generating module comprises a background field generating module composed of a coil without magnetic moment and a magnetizing field generating module composed of a one-dimensional Helmholtz coil. The coil without magnetic moment and the one-dimensional Helmholtz coil adopt a non-magnetic skeleton to generate a magnetic field in the area where the magnetic nanoparticle module is placed. The magnetic field generating module is connected to a constant voltage power supply to supply power to the background field generating module and the magnetizing field generating module. The magnetic field control module includes a circuit control panel capable of setting a magnetization mode, and the circuit control panel is detachably arranged between the magnetic moment-free coil and the constant voltage power supply, and controls the magnetization field generation module to generate a pulsed magnetic field through the host computer, and simultaneously controls the background field generation module to generate a constant magnetic field; The OPM array is used to receive the magnetic field generated by the magnetic field generation module and act on the magnetic nanoparticle module to generate a relaxation signal, and the OPM array outputs multiple sets of simulation data of over-range magnetization field and particle Neel relaxation signal; The data acquisition module includes an analog-to-digital conversion data acquisition card connected to the OPM array and the circuit control panel, which synchronously acquires the analog data output by the OPM array and the pulse electrical signal representing the magnetic field mode and transmits them to the host computer.

2. The superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claim 1, characterized in that: The one-dimensional Helmholtz coil is a group of symmetrical single-plane coils, the group of symmetrical single-plane coils includes two mutually symmetrical annular coils, the two mutually symmetrical annular coils have the same number of turns, the same coil winding method, and the coil radius is equal to the coil spacing, the magnetic moment-free coil includes at least one group of dual-plane coils, and the group of dual-plane coils is a one-dimensional Helmholtz coil structure with two mutually parallel and opposite winding directions with overlapping symmetry centers.

3. The superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claim 1, characterized in that: The background field generation module uses at least one group of dual-plane coils to generate a controllable near-zero magnetic field. The magnetization field generation module uses a group of one-dimensional Helmholtz coils with the same winding direction to generate a controllable uniform pulse square wave excitation magnetic field. The magnetization field generation module is placed in the near-zero magnetic field area of ​​the background field generation module.

4. The superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claim 1, characterized in that: The circuit control module includes a mode setting module and a mode acquisition module. The mode setting module includes a mode control circuit, which is connected to the constant voltage power supply to provide a controllable DC current for the background field generation module, and connected to the electromagnetic relay to provide a pulse current with an adjustable duty cycle for the magnetization field generation module; The mode acquisition module outputs a pulse electrical signal representing the switching of the electromagnetic relay.

5. The superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claim 1, characterized in that: The near-zero magnetic field generated by the background field generation module is a fixed uniform constant magnetic field of nT to pT order, and the magnetic field range covers the magnetization field generation module and the OPM array area.

6. The superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claim 1, characterized in that: The OPM array is arranged on an OPM array platform, and the OPM array platform includes card slot planes arranged in a square or annular manner. The OPM magnetic sensitive axes on all card slot planes are parallel to the center direction of the uniform magnetic field of the magnetization field generating module. The OPM array platform is a flat plate that can move horizontally and vertically and has a measurable scale. The OPM array and the OPM array platform are parallel to the one-dimensional Helmholtz coil of the magnetization field generating module and the magnetic moment-free coil plane of the background field generating module.

7. The superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claim 1, characterized in that: The host computer is connected to the magnetic field control module to output control instructions, and is also connected to the data acquisition module to receive the analog data output by the OPM array and the pulse electrical signal data representing the magnetic field mode, and to process and analyze the received data.

8. A superparamagnetic nanoparticle relaxation signal detection system based on OPM according to claims 1-7, characterized in that: The magnetic nanoparticle module, magnetic field generating module and OPM array are all placed in a magnetic shielding barrel or a magnetic shielding room, and the host computer, constant voltage power supply, magnetic field control module and data acquisition module are all placed outside the magnetic shielding barrel or the magnetic shielding room. The inner and outer parts are connected by a coaxial cable or twisted pair cable with a shielding effect for coil power supply and information transmission.

9. A superparamagnetic nanoparticle relaxation signal detection method based on OPM, applied to the superparamagnetic nanoparticle relaxation signal detection system based on OPM according to any one of claims 1 to 8, characterized in that: The following steps are involved: Step 1, placing the superparamagnetic nanoparticles to be tested at a position to be tested in the magnetic field generating module, wherein the position to be tested is the center of the internal uniform magnetic field generated by the magnetic field generating module; Step 2, turn on the constant voltage power supply, and set the circuit control block connected to the magnetization field generation module through the host computer to a pulse output mode with a high level time in the range of (1s, 2s) and a low level time in the range of (5s, 20s); Step 3, setting and connecting the background field generation module to a fixed DC output mode through the constant voltage power supply and the circuit control panel and starting it, so that the background field generation module generates an adjustable fixed uniform magnetic field; Step 4: Turn on the OPM array, perform air chamber heating, magnetic compensation and calibration, and start measuring and collecting data; Step 5, the start-up circuit control module outputs voltage to the magnetization field generation module, so that a uniform pulse DC field sequence is generated in the center of the magnetization field generation module to magnetize the sample, the OPM array always remains in the open and data collection state, and the switch control signal in the pulse output mode of the circuit control module is synchronously collected; Step 6: Turn off the circuit control board and the OPM array, stop data acquisition, and transmit the measured data to the host computer as the original particle signal; Step 7, remove or replace the superparamagnetic nanoparticles to be tested in step 1 with pure water, repeat steps 2 to 5, and collect the data measured by the OPM array as the background attenuation signal; Step 8: Filter and cancel the original particle signal data collected in step 6 and the background attenuation signal data collected in step 7 to obtain the spatial detection signal of the particle.

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