Dynamic Raman detection device and detection method based on magnetic control cluster

Abstract

The invention provides a dynamic Raman detection device and method based on a magnetic control cluster. The device comprises a magnetic SERS probe, a magnetic field generation unit, a Raman detection unit and an imaging unit, wherein the magnetic field generation unit is used for generating a programmable time-varying magnetic field to drive the magnetic SERS probe to form a dynamic micro-nano motor cluster; the Raman detection unit is used for performing laser irradiation on a magnetic control cluster area and collecting Raman scattering signals; the imaging unit is used for monitoring and positioning the magnetic control cluster in real time; a control unit; the to-be-detected area is located in the effective working space of the magnetic field generation unit; and the control unit is electrically connected with the magnetic field generation unit, the Raman detection unit and the imaging unit and is used for adjusting magnetic field parameters, synchronously controlling a detection time sequence and processing imaging and spectral data. According to the technical scheme, the dynamic motion characteristic and the surface Raman enhancement effect of the micro-nano motor cluster are combined, the external magnetic field is used for driving the probe to form a reconfigurable dynamic cluster, and high-sensitivity and accurate positioning detection in a complex environment is achieved.

Description

Technical Field

[0001] This invention relates to the field of Raman detection technology, and in particular to a dynamic Raman detection device and method based on a magnetically controlled cluster. Background Technology

[0002] Micro-nanomotors (or micro-nanorobots) have attracted widespread attention in the biomedical field due to their small size and active motion capabilities. However, the tiny size of a single micro-nanomotor makes it difficult to support complex functional components. Therefore, controlling micro-nanomotors to form clusters using external physical fields (such as magnetic fields) to enhance environmental adaptability and functional performance has become a research hotspot. While controlling micro-nanomotors to form clusters using external physical fields (such as magnetic fields) can enhance their environmental adaptability and functional performance, existing magnetically controlled micro-nanomotors are mainly used for drug delivery and rarely used for dynamic SERS detection. Traditional SERS probes lack active motion capabilities, making it difficult to achieve efficient enrichment in complex fluids (such as blood), and they also face positioning difficulties.

[0003] Raman spectroscopy is widely used in the fields of substance detection and diagnosis due to its high sensitivity and specificity, but it still faces many challenges in practical applications. On the one hand, traditional surface-enhanced Raman scattering (SERS) probes are mostly static probes, relying solely on steady-state hotspots to achieve signal enhancement. This results in insufficient sensitivity and a high limit of detection (LOD) in complex environmental samples, making it difficult to meet the detection requirements of low-concentration targets. On the other hand, traditional probes lack active movement capabilities, only able to drift with the current, making it difficult to reach specific areas against the flow in blood vessels or microchannels with flow velocity, and also unable to achieve efficient enrichment in low-concentration samples. Furthermore, Raman probes are difficult to directly observe and locate with optical equipment in non-transparent environments (such as biological tissues and whole blood), leading to the problem of "invisibility and inaccuracy," severely limiting its application in the detection of deep tissues in vivo.

[0004] Therefore, developing a Raman detection technology that can solve the problems of insufficient signal enhancement, lack of active addressing capability, and difficulty in deep localization has become an urgent technical problem to be solved in this field. Summary of the Invention

[0005] To address the above technical problems, this invention discloses a dynamic Raman detection device and method based on a magnetically controlled cluster. By combining the dynamic motion characteristics of micro-nano motor clusters with the surface Raman enhancement effect, an external magnetic field is used to drive the probe to form a reconfigurable dynamic cluster. This solves the problems of insufficient signal enhancement, inability to actively address, and difficulty in deep detection and positioning in existing Raman detection technologies, and achieves high sensitivity and accurate positioning detection in complex environments.

[0006] The technical solution adopted by this invention is as follows:

[0007] A dynamic Raman detection device based on a magnetically controlled cluster includes a magnetic SERS probe, a magnetic field generating unit for generating a programmable time-varying magnetic field to drive the magnetic SERS probe to form a dynamic micro / nano motor cluster, a Raman detection unit for laser irradiation of the magnetically controlled cluster region and acquisition of Raman scattering signals, an imaging unit for real-time monitoring and positioning of the magnetically controlled cluster, and a control unit; the area to be measured is located within the effective working space of the magnetic field generating unit.

[0008] The magnetic SERS probe has both magnetic response characteristics and surface-enhanced Raman scattering activity, and can be a core-shell structure, yolk-shell structure, Janus structure, polymer structure, or magnetic microsphere structure with surface modified with noble metal satellites.

[0009] The magnetic field generating unit includes a permanent magnet generating unit, an electromagnetic generating unit, or a combination of both, and can output a rotating magnetic field, an oscillating magnetic field, a superimposed magnetic field, or a gradient magnetic field; the permanent magnet generating unit includes a fixed permanent magnet, a movable mechanical magnetic arm, a rotating magnetic field generator, or a Halbach array, wherein the permanent magnet is made of at least one of neodymium iron boron, samarium cobalt, or ferrite; the electromagnetic generating unit includes at least one of a DC electromagnet, an AC electromagnet, a solenoid, a Helmholtz coil, a Maxwell coil, a three-dimensional orthogonal coil system, or a photolithographic planar microcoil;

[0010] The imaging unit includes one or more of the following: ultrasound imaging unit, optical imaging unit, X-ray imaging unit, computed tomography imaging unit, magnetic resonance imaging unit, photoacoustic imaging unit, or thermal imaging unit.

[0011] The Raman detection unit includes one of the following: a microscopic confocal Raman spectrometer, a fiber optic Raman spectrometer, a handheld or portable Raman spectrometer, a Fourier transform Raman spectrometer, and a customized Raman signal reading module;

[0012] The control unit is electrically connected to the magnetic field generating unit, the Raman detection unit, and the imaging unit, respectively, and is used to adjust the magnetic field parameters, synchronously control the detection sequence, and process imaging and spectral data.

[0013] This technical approach involves injecting or introducing SERS-active magnetic SERS probes into the target fluid. An external magnetic field (without physical contact) drives the probes to overcome fluid resistance (flow velocity) and traverse complex channels or blood vessels to reach the lesion area. An imaging unit tracks the position of the probe cluster. Upon reaching the target area, the probes form dynamic clusters (vortices, strips, etc.) under the influence of the magnetic field, generating collision hotspots. The clusters disperse to capture pathogens or molecules and then re-aggregate. Maintaining the dynamic "vortex" or "oscillation" motion of the clusters utilizes high-frequency collisions between particles to generate numerous "transient hotspots," thereby achieving extremely high Raman signal sensitivity in complex environments. This enables highly sensitive and precise localization detection even in challenging conditions.

[0014] As a further improvement of the present invention, the imaging unit is an ultrasonic imaging unit. By controlling the cluster to rotate at a specific frequency, a unique high-echo bright spot is formed under the action of the ultrasonic imaging unit, achieving precise positioning in non-transparent environments. By utilizing a magnetic field driven at a specific frequency to rotate the magnetic SERS probe, it presents an enhanced Doppler signal or a high-echo bright spot in ultrasonic imaging, thereby achieving precise positioning in opaque media.

[0015] As a further improvement of the present invention, the magnetic SERS probe unit includes a magnetic core, a SERS active component, and a protective layer. The magnetic core is one of iron(II,III) oxide, iron(III) oxide, pure iron, cobalt, nickel, or an alloy thereof, or a ferrite material. The SERS active component is one of gold, silver, copper, platinum, palladium, or an alloy thereof, or a nanomaterial. The protective layer is a SiO2 layer with a thickness of 2-5 nm, which covers the surface of the SERS active component.

[0016] This invention discloses a dynamic Raman detection method based on a magnetically controlled cluster, which uses the dynamic Raman detection device based on a magnetically controlled cluster as described above for detection, and includes the following steps:

[0017] Step S1: Introduce the magnetic SERS probe into the fluid environment to be tested; wherein the fluid to be tested includes blood, water sample, food matrix or industrial fluid;

[0018] Step S2: The programmable time-varying magnetic field is generated by the magnetic field generating unit, which drives the magnetic SERS probes to aggregate through magnetic dipole interaction to form a dynamic micro-nano motor cluster with a specific geometric shape.

[0019] Step S3: The magnetic field parameters are adjusted by the control unit to maintain the cluster in a dynamic state, so that the magnetic SERS probes inside the cluster collide and move at high frequency, generating a large number of transient gap hotspots on the basis of the steady-state gap hotspots inside the magnetic flux.

[0020] Step S4: The cluster position is monitored in real time using the imaging unit, and the cluster area is irradiated with laser and Raman scattering signals are collected by the Raman detection unit.

[0021] After the test is completed, the cluster can be controlled by a magnetic field for recovery or directional discharge.

[0022] This technical solution utilizes a "dynamic motion state" controlled by a specific magnetic field to generate "transient gap hotspots." This differs from traditional static aggregation; it is a technical effect achieved by making particles move and collide, based on specific control logic.

[0023] Traditional SERS detection typically requires probes to be stationary or tightly clustered to form stable "hot spots." It is generally believed that vigorous probe movement disrupts this tight gap, leading to signal fluctuations or attenuation. The technical solution of this invention utilizes a magnetically controlled, statically dynamic state. In this state, the probe not only avoids signal attenuation due to movement but also generates additional "transient gap hot spots" through "high-frequency collisions." Furthermore, the signal in the dynamic state is significantly higher than in the static state, and the detection limit is significantly reduced, overcoming the contradiction between "motion stability" and "SERS signal strength." Additionally, Raman spectroscopy is optical, but light cannot penetrate whole blood or deep tissues, making it "invisible" to the probe. While imaging units such as ultrasound can penetrate, they struggle to distinguish between tiny nanoclusters and complex background tissue (low signal-to-noise ratio). This detection method establishes a magneto-acoustic linkage mechanism, controlling the cluster's rotational movement at a specific frequency, and artificially creating unique high-echo bright spots using ultrasound, solving the visualization challenge of micro / nano manipulation in macroscopically opaque environments.

[0024] As a further improvement of the present invention, in step S2, the magnetic field generated by the magnetic field generating unit includes a rotating magnetic field, an oscillating magnetic field, a composite magnetic field formed by the superposition of a rotating magnetic field and a static bias magnetic field, and a gradient magnetic field with a spatial gradient distribution. Furthermore, by adjusting the frequency, amplitude, phase difference, and direction of the magnetic field, the magnetic field generating unit can control the probe to form one or more of the following: a vortex-like cluster, a strip-like cluster, a chain-like cluster, a spherical cluster, a droplet-like cluster, or an alternating dispersion-reaggregation state.

[0025] As a further improvement of the present invention, in step S2, the magnetic field parameters of the magnetic field generating unit are adjusted to satisfy any of the following conditions:

[0026] When generating a rotating magnetic field, the magnetic field strength is set to 4mT, 6mT, or 8mT, the rotation frequency is set to 10~20Hz, and the magnetic field function is... A R This represents the maximum value of the rotating magnetic field strength, where ƒ is the frequency of the rotating magnetic field, and B... x and B yThese represent the components of the magnetic field along the x-axis and y-axis, respectively.

[0027] When generating an oscillating magnetic field, the magnetic field strength is set to 15 mT, the oscillation frequency is set to 10 Hz, 15 Hz, or 20 Hz, and the magnetic field function is: A O and C O All are constants, θ is the angle between the oscillation normal and the y-axis, ƒ is the oscillation frequency, and B is the constant. x and B y These represent the components of the magnetic field along the x-axis and y-axis, respectively.

[0028] When a dispersing magnetic field is generated, the magnetic field function is: A xy and A z These represent the maximum magnetic field strengths in the xy plane and the y plane, respectively. xy and ƒ z These are the frequencies of the rotating magnetic field in the xy plane and the oscillating magnetic field in the z direction, respectively. x B y B z These are the components of the magnetic field along the x-axis, y-axis, and z-axis, respectively.

[0029] As a further improvement of the present invention, the detection parameters of the Raman detection unit in step S4 satisfy the following: when detecting crystal violet, 532nm laser excitation is used, the laser energy intensity is set to 5%, the single acquisition time is 5s, the cumulative number of acquisitions is 2, and the characteristic peak is taken at 917cm. -1 When detecting Rhodamine 6G, a 633nm laser was used for excitation, the laser energy intensity was set to 10%, the single acquisition time was 10s, and the cumulative acquisition was 2 times. The characteristic peak was taken at 613cm. -1 .

[0030] This invention discloses the applications of the dynamic Raman detection method based on magnetron clusters described above, for food safety detection (such as melamine and pesticide residues in milk), water quality monitoring (such as heavy metal ions), biomedical detection, industrial fluid analysis, microfluidic chip point sampling, or the collection and recovery of trace samples in hazardous environments (such as radiation or strong acid environments). It can also be used for "localization of tiny objects in non-transparent media," for industrial flaw detection, or for tracing within closed systems.

[0031] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0032] First, the detection sensitivity is significantly improved by adopting the technical solution of this invention. Employing a "dynamic enhancement" strategy, transient hotspots are generated through high-frequency collisions within the magnetron cluster. These hotspots work synergistically with steady-state hotspots, resulting in Raman enhancement performance approximately 10 times higher than in the static aggregation state. This significantly reduces the detection limit (LOD) and can meet the detection requirements for low-concentration target analytes.

[0033] Secondly, it achieves deep visualization and precise positioning. By combining imaging technologies such as ultrasound imaging to establish a magneto-acoustic linkage mechanism, and controlling the cluster to rotate at a specific frequency to form a unique high-echo bright spot, it solves the problem of Raman probes being "invisible" in non-transparent environments (such as whole blood and deep tissues), and achieves precise positioning and real-time tracking of the cluster.

[0034] Third, it has strong environmental adaptability. The cluster morphology can be reconstructed by adjusting the magnetic field parameters. It can be deformed into a strip-like pattern in narrow microchannels or vascular branches, and can be converted into a vortex shape for efficient enrichment in open areas. It can adapt to different detection environments and fluid conditions, and has extremely strong environmental adaptability.

[0035] Fourth, it has the potential for active addressing against flow velocity. Breaking through the limitation of traditional probes that can only drift with the flow, the cluster can resist the impact of liquid at a certain flow velocity, enabling it to go against the flow to reach a specific area for targeted sampling and detection. After the detection is completed, it can be recovered under magnetic field control, possessing the potential for minimally invasive / non-invasive diagnosis and treatment, and is especially suitable for in vivo detection in the biomedical field. Attached Figure Description

[0036] Figure 1 This is a structural block diagram of the dynamic Raman detection device based on a magnetron cluster according to an embodiment of the present invention.

[0037] Figure 2 This is a flowchart illustrating the dynamic Raman enhancement detection method based on a magnetron cluster, according to an embodiment of the present invention.

[0038] Figure 3 This is a schematic diagram of the preparation process of magnetic SERS probe particles according to an embodiment of the present invention.

[0039] Figure 4 This is an embodiment of the present invention that uses Raman enhancement to detect the Raman spectra of crystal violet using dynamic and static clusters.

[0040] Figure 5 This is a schematic diagram of the formation of a vortex-shaped cluster according to an embodiment of the present invention; wherein, (a) is a schematic diagram of a three-dimensional rotating magnetic field; and (b) is a schematic diagram of the formation principle of the vortex-shaped cluster.

[0041] Figure 6 This is a schematic diagram of the formation of a strip-shaped cluster according to an embodiment of the present invention; wherein, (a) is a schematic diagram of a three-dimensional oscillating magnetic field; and (b) is a schematic diagram of the formation principle of the strip-shaped cluster.

[0042] Figure 7 This is a schematic diagram of the formation of a dispersed cluster according to an embodiment of the present invention; wherein, (a) is a schematic diagram of the dispersing magnetic field; and (b) is a schematic diagram of the principle of the formation of a dispersed cluster.

[0043] Figure 8 These are the Raman scattering spectra of different clusters of crystal violet solution under 532nm laser excitation in embodiments of the present invention.

[0044] Figure 9 These are the Raman scattering spectra of different clusters of Rhodamine 6G solution under 633nm laser excitation in embodiments of the present invention.

[0045] Figure 10 These are the whole-blood Raman test results under different cluster states in embodiments of the present invention.

[0046] Figure 11 This is a motion tracking diagram of the cluster in B-mode ultrasound imaging according to an embodiment of the present invention; wherein (a), (b) and (c) are images of the cluster on the motion path, respectively. Detailed Implementation

[0047] The preferred embodiments of the present invention will be described in further detail below.

[0048] Example 1

[0049] like Figure 1 As shown, a dynamic Raman detection device based on a magnetically controlled cluster includes a magnetic SERS probe, a magnetic field generating unit, a Raman detection unit, an imaging unit, and a control unit. The control unit is electrically connected to the magnetic field generating unit, the Raman detection unit, and the imaging unit, respectively, and is used to adjust the magnetic field parameters, synchronously control the detection timing, and process imaging and spectral data.

[0050] The magnetic SERS probe has both magnetic response characteristics and surface-enhanced Raman scattering activity, and can be a core-shell structure, yolk-shell structure, Janus structure, polymer structure, or magnetic microsphere structure with surface modified with noble metal satellites.

[0051] The magnetic field generating unit is used to generate a programmable time-varying magnetic field to drive the magnetic SERS probe to form a dynamic micro-nano motor cluster. The magnetic field generating unit includes a permanent magnet generating unit, an electromagnetic generating unit, or a combination of the two, and can output a rotating magnetic field, an oscillating magnetic field, a superimposed magnetic field, or a gradient magnetic field. The permanent magnet generating unit includes a fixed permanent magnet, a mobile mechanical magnetic arm, a rotating magnetic field generator, or a Halbach array, wherein the permanent magnet is made of at least one of neodymium iron boron, samarium cobalt, or ferrite. The electromagnetic generating unit includes at least one of a DC electromagnet, an AC electromagnet, a solenoid, a Helmholtz coil, a Maxwell coil, a three-dimensional orthogonal coil system, or a photolithographic planar microcoil.

[0052] The Raman detection unit is used to irradiate the magnetron cluster region with laser and collect Raman scattering signals. The Raman detection unit includes one of the following: a microconfocal Raman spectrometer, a fiber optic Raman spectrometer, a handheld or portable Raman spectrometer, a Fourier transform Raman spectrometer, and a customized Raman signal reading module.

[0053] The imaging unit is used for real-time monitoring and positioning of the magnetically controlled cluster; in this embodiment, the imaging unit is an ultrasonic imaging unit.

[0054] The area to be measured is located within the effective working space of the magnetic field generating unit. The control unit controls the magnetic field generating unit through the magnetic control unit.

[0055] like Figure 2 As shown, the detection method of this detection device includes:

[0056] Step 1: Probe Introduction. Introduce the magnetic SERS probe dispersion into the test fluid environment. The test fluid may include blood, water samples, food matrices, or industrial fluids, etc. The probe concentration is adjusted according to the detection requirements.

[0057] Step 2: Cluster Formation. A programmable time-varying magnetic field is generated by the magnetic field generating unit and applied to the magnetic SERS probe. This drives the probe to aggregate through magnetic dipole interactions, forming a dynamic micro / nano motor cluster with a specific geometric shape. The appropriate magnetic field type is selected based on the detection scenario. For example, in open areas, a vortex-like cluster can be formed for efficient enrichment, while in narrow microchannels or vascular branches, a strip-like cluster can be formed to travel through them.

[0058] Step 3: Dynamic Maintenance. The magnetic field parameters are adjusted by the control unit to maintain the cluster in a dynamic state, causing high-frequency collisions and relative motion between the probes within the cluster. This dynamic motion generates numerous "instantaneous gap hotspots" based on the steady-state gap hotspots within the magnetic flux linkage, significantly enhancing the Raman scattering signal.

[0059] Step 4: Location and Detection. The imaging unit monitors the cluster's position in real time to ensure accuracy in the detection area; simultaneously, a Raman detection unit irradiates the cluster area with laser, acquiring Raman scattering signals according to preset parameters. During detection, the cluster's dynamic motion is continuously maintained to ensure signal enhancement. Ultrasound or color Doppler ultrasound is used as the imaging unit to track the probe cluster's position (cluster rotation generates specific red / blue Doppler signals, allowing the probes to be "seen" in opaque blood / tissue). Upon reaching the target area, a magnetic field disperses the cluster to capture pathogens or molecules, then they re-aggregate. Maintaining the cluster's dynamic "vortex" or "oscillation" motion utilizes high-frequency collisions between particles to generate numerous "transient hotspots," thereby achieving extremely high Raman signal sensitivity in complex environments.

[0060] After the detection is completed, the magnetic field parameters are adjusted by the magnetic field generating unit to control the cluster to perform directional recovery or discharge, so as to avoid the impact of probe residue on the environment or sample.

[0061] In this embodiment, the magnetic SERS probe unit adopts a core-shell structure design, with superparamagnetic Fe3O4 nanoparticles as the magnetic core and an average particle size of about 400 nm. The middle layer is a polydopamine (PDA) coating layer with a thickness of about 30 nm, which is formed by reacting dopamine hydrochloride in Tris-HCl buffer (pH 8.5) for 3 hours. The SERS active layer is formed by electrostatically adsorbing and loading 15 nm gold nanoparticles (AuNPs) as seeds, and then growing a silver shell (Ag Shell) by reducing silver nitrate with ascorbic acid. The outermost layer is an ultrathin SiO2 protective layer with a thickness of 2-5 nm, which is prepared by hydrolyzing tetraethyl silicate (TEOS) or sodium silicate under alkaline conditions, which can prevent oxidation and improve biocompatibility.

[0062] The magnetron control unit can control the magnetic field generating unit to produce various programmable time-varying magnetic fields, including rotating magnetic fields, oscillating magnetic fields, superimposed magnetic fields, and gradient magnetic fields. A rotating magnetic field is a uniform magnetic field rotating at a specific frequency in two-dimensional or three-dimensional space; an oscillating magnetic field is an alternating magnetic field that changes in the form of a sine wave, square wave, or triangular wave in a specific direction; a superimposed magnetic field is a composite magnetic field formed by superimposing a rotating magnetic field with a static bias magnetic field, or by superimposing a rotating magnetic field with an oscillating magnetic field; and a gradient magnetic field is a magnetic field with a spatial gradient distribution used to drive the overall translation of the cluster. By adjusting the magnetic field frequency, amplitude, phase difference, and direction, the probe can be controlled to form vortex swarms, ribbon swarms, chains, globules, liquid-like clusters, or alternating dispersed-regrouping states, meeting the needs of different detection scenarios. For example, a rotating magnetic field can form a vortex swarm, an oscillating magnetic field (a rotating magnetic field in the plane superimposed with a vertical static magnetic field) can form a ribbon swarm, and a dispersed magnetic field (a rotating magnetic field in the XY plane + an oscillating magnetic field in the Z-axis) can form a dispersed cluster.

[0063] The magnetic field function of the rotating magnetic field is: , where A R This represents the maximum value of the rotating magnetic field strength, where ƒ is the frequency of the rotating magnetic field, and B... x and B y These represent the components of the magnetic field along the x-axis and y-axis, respectively.

[0064] The clustering control of the rotating magnetic field is as follows: Under high magnetic field rotation frequency parameters, the rotation of the magnetic flux cannot keep pace with the rotation of the magnetic field, and the shape of the cluster is elongated, forming an unstable vortex cluster. When the magnetic field strength is high and the rotation frequency is low, the magnetic flux formed by the magnetic particles is too long, and the particles rotate in spindle-shaped clusters, making it impossible to form a cluster. When the magnetic field parameters are within a certain range, the rotation of the magnetic flux is synchronized with the rotation of the magnetic field, and a stable vortex cluster can be formed. Therefore, the magnetic field strength was set to 4mT, 6mT, or 8mT in the experiment; the rotation frequency was set to 10~20Hz. It was found that the area of ​​the vortex cluster increased slightly with the increase of the magnetic field frequency. This is because with the increase of the rotation frequency, the centrifugal force on the magnetic particles increases, causing some diffusion of the cluster. At the same time, with the increase of the magnetic field strength, the magnetic force between the magnetic particles increases, inhibiting the diffusion of the cluster under centrifugal force. Therefore, with the strengthening of the magnetic field, the increase in cluster area with increasing frequency weakens.

[0065] Magnetic field function of oscillating magnetic field: , where A O and C O All are constants, θ is the angle between the oscillation normal and the y-axis, ƒ is the oscillation frequency, and B is the constant. x and B y These represent the components of the magnetic field along the x-axis and y-axis, respectively.

[0066] Cluster control of the oscillating magnetic field is as follows: at a large amplitude ratio and a high oscillation frequency, the strip-shaped clusters are elongated along their long axis, resulting in an excessively high aspect ratio, making effective control of the strip-shaped clusters impossible. When the magnetic field amplitude ratio is low, the magnetic particles oscillate in spindle-shaped clusters, making it impossible to form strip-shaped clusters. In the experiment, a magnetic field strength of 15 mT was selected; the oscillation frequency was set to 10 Hz, 15 Hz, or 20 Hz. By adjusting the amplitude ratio, the aspect ratio of the clusters can be controlled (for example, as the amplitude ratio increases from 2.0 to 4.0, the aspect ratio increases accordingly).

[0067] The magnetic field function that disperses the magnetic field: Among them, A xy and A z These represent the maximum magnetic field strengths in the xy plane and the y plane, respectively. xy and ƒ z These are the frequencies of the rotating magnetic field in the xy plane and the oscillating magnetic field in the z direction, respectively. x B y B z These are the components of the magnetic field along the x-axis, y-axis, and z-axis, respectively.

[0068] The cluster control of the dispersed magnetic field is as follows: Under the action of the magnetic field, magnetic particles connect with each other to form magnetic chains. The magnetic chains rotate under the action of the rotating magnetic field in the XY plane, and at the same time, they oscillate perpendicular to the XY plane under the action of the oscillating magnetic field in the Z direction. During the collision between the magnetic chains and the substrate, the long magnetic chains are divided into multiple segments. At the same time, the oscillation in the Z direction hinders the mutual attraction of the eddy current field caused by the rotation of the magnetic chains. Therefore, the spacing between the magnetic chains increases, thus forming a dispersed cluster.

[0069] The Raman detection unit selects appropriate excitation wavelengths and detection parameters based on the target, enabling precise illumination of the dynamic cluster area and acquisition of Raman scattering signals. The imaging and positioning unit prioritizes ultrasonic imaging technology, controlling the cluster to rotate at a specific frequency to create unique high-echo bright spots, solving the positioning challenge in non-transparent environments; it can also combine other imaging methods according to scene requirements to ensure real-time tracking of the cluster.

[0070] The control unit, as the core control module of the device, is responsible for adjusting the magnetic field parameters, synchronously controlling the Raman detection timing, and processing imaging and spectral data to achieve automation and precision in the detection process.

[0071] This device utilizes a three-dimensional magnetic field to drive SERS-active magnetic nanoprobes to form a dynamic cluster, achieving active navigation, precise positioning, and high-sensitivity detection in complex environments. In terms of motion control, propulsion is generated by adjusting magnetic field parameters (frequency and orientation angle), enabling the cluster to overcome environmental flow velocities and achieve active navigation and remote sampling against / within the flow. For positioning and tracking, ultrasonic technology is incorporated to solve the challenge of precise positioning and real-time tracking in opaque environments. Regarding signal enhancement, the dynamic magnetic field drives high-frequency motion and collisions of the magnetic flux within the cluster, generating numerous "instantaneous gap hotspots." These hotspots, in conjunction with the steady-state hotspots within the magnetic flux, significantly enhance the Raman scattering signal.

[0072] The following description uses specific examples to illustrate the point.

[0073] Example 2

[0074] like Figure 3 As shown, the preparation of a magnetic SERS probe particle includes the following steps, and this probe is used as a magnetic surface-enhanced Raman probe (Fe3O4@PDA@Au@Ag@SiO2) for all subsequent detections.

[0075] (1) Magnetic core: Superparamagnetic Fe3O4 nanoparticles with an average particle size of about 400 nm were synthesized by solvothermal method.

[0076] (2) Intermediate layer: Fe3O4 was dispersed in Tris-HCl buffer (pH 8.5), and dopamine hydrochloride was added and stirred for 3 hours to form a polydopamine (PDA) coating layer with a thickness of about 30 nm.

[0077] (3) SERS active layer: 15 nm gold nanoparticles (AuNPs) are loaded onto the PDA surface by electrostatic adsorption as seeds. Silver nitrate is reduced with ascorbic acid to grow an Ag shell on the surface of the gold seeds, forming a surface with a strong electromagnetic field enhancement effect.

[0078] (4) Protective layer: under alkaline conditions, tetraethyl silicate (TEOS) or sodium silicate is hydrolyzed to coat the surface of the silver shell with an ultrathin SiO2 layer of about 2-5 nm to prevent oxidation and improve biocompatibility.

[0079] Example 3

[0080] Using the magnetic SERS probe prepared in Example 2, a comparative experiment was conducted on the SERS signal enhancement performance of static clusters and dynamic clusters.

[0081] This embodiment verifies the enhancement effect of dynamic magnetron clustering on SERS signals by comparing the Raman signal intensities under static and dynamic states, at the same probe and analyte concentrations. In this embodiment, the magnetic SERS probe is dispersed in water to obtain a probe dispersion with a concentration of 10 mg / ml; the analyte (crystal violet (CV) or rhodamine 6G (R6G)) is dispersed in water at a concentration of 10 mg / ml. -4 mol / L; to obtain the analyte solution;

[0082] Spectral acquisition parameters: For crystal violet (CV): use 532nm laser excitation, laser energy intensity set to 5%, single acquisition time 5s, cumulative acquisition 2 times; For rhodamine 6G (R6G): use 633nm laser excitation, laser energy intensity set to 10%, single acquisition time 10s, cumulative acquisition 2 times.

[0083] Experimental procedure:

[0084] (1) Take 50µL of probe dispersion and 50µL of test solution and mix them in the 3M tape hole (9mm in diameter) on the glass slide, and cover with a coverslip.

[0085] (2) Static test: Apply a magnetic field to make the particles aggregate but not move, and record the intensity of the characteristic peak.

[0086] (3) Dynamic test: Apply a magnetic field to make the cluster move and record the intensity of the characteristic peak at the same position.

[0087] (4) Test results: For the same cluster, whether it is vortex-shaped or strip-shaped, the Raman signal intensity in the moving state is higher than that in the stationary state, as shown in the following results. Figure 4 As shown.

[0088] It is evident that, due to the movement of the cluster, in addition to the originally formed steady-state hotspots, a large number of instantaneous gap hotspots are generated during the collision of the magnetic links. These hotspots further enhance the Raman enhancement performance on the basis of the steady-state hotspots.

[0089] Example 4

[0090] Experiments on the detection of crystal violet and rhodamine 6G by dynamic clusters of different morphologies.

[0091] Based on Example 3, this example compares the enhancement effect of different cluster morphologies on SERS signals under the same probe concentration and analyte concentration.

[0092] Experimental procedure:

[0093] (1) Take 50µL of probe dispersion and 50µL of test solution and mix them in the 3M tape hole (9mm in diameter) on the glass slide, and cover with a coverslip.

[0094] (2) Different morphological cluster tests: different types of magnetic fields were applied to put the clusters in different motion states, and the intensity of characteristic peaks was recorded (CV was taken as 917 cm⁻¹). -1 R6G is 613cm -1 ).

[0095] Vortex-shaped clusters: such as Figure 5 As shown, a rotating magnetic field (magnetic field strength 8 mT, rotation frequency 20 Hz) is applied to form a vortex-like cluster, and the intensity of the characteristic peaks is recorded.

[0096] Strip-shaped clusters: such as Figure 6 As shown, an oscillating magnetic field (magnetic field strength 15mT, oscillation frequency 15Hz, amplitude ratio 3.0) was applied to form a strip-shaped cluster, and the intensity of the characteristic peaks was recorded.

[0097] Dispersed clusters: such as Figure 7 As shown, a dispersive magnetic field (XY plane rotation frequency 10Hz, Z-axis oscillation frequency 5Hz) is applied to form a dispersed cluster, and the intensity of the characteristic peak is recorded.

[0098] Test results are as follows Figure 8 and Figure 9 As shown, for two different Raman characteristic molecules, the Raman signal intensities of the vortex cluster and the strip cluster are similar and both are much higher than those of the dispersed cluster.

[0099] Conclusion: Raman enhancement performance is significantly better in clusters with aggregated states than in clusters with dispersed states.

[0100] Example 5

[0101] In vitro whole blood environmental testing experiment.

[0102] This embodiment verifies the whole blood environment detection capability of the dynamic detection system, including the following steps:

[0103] 100 μL of rabbit whole blood was added to a 3M thick adhesive tape sample reservoir, followed by 2 μL of a 10 mg / mL SERSprobe particle dispersion (using the probe dispersion from Example 2). A glass slide was then placed in a Helmholtz coil for Raman spectroscopy. Due to the high viscosity of whole blood, a strong magnetic field is required for manipulation; therefore, the sampling and detection of micro / nano particle clusters within whole blood was performed by fixing an N52 neodymium magnet to a servo motor to generate a high-intensity rotating magnetic field. The results are as follows: Figure 10 As shown, in rabbit whole blood, the Raman signal intensity of vortex (VS) and strip (RS) clusters is significantly higher than that of disassembled swarms, and much higher than that of pure whole blood background.

[0104] Example 6

[0105] Ultrasonic positioning capability test experiment.

[0106] This embodiment verifies the ultrasonic positioning capability under the dynamic detection system, including the following steps:

[0107] Rabbit whole blood was introduced into a 5 mm diameter silicone tubing, and the flow rate was controlled to approximately 1.5 cm / s using a syringe pump. 1 mL of SERS probe particle solution (using the probe dispersion from Example 2) was added, and a rotating neodymium magnet was used to control the formation of clusters within the tubing. The tubing was then immersed in water, using water as the ultrasound medium, for ultrasound imaging of the tubing and the probe particle clusters. The movement of the clusters was controlled by moving the rotating neodymium magnet, and the clusters were tracked under ultrasound imaging. The results are as follows: Figure 11 As shown, under ultrasound, the probe cluster appears as a hyperechoic white bright spot, enabling precise positioning in opaque blood. This demonstrates that the magneto-acoustic linkage mechanism of this invention can effectively solve the visualization challenges in deep tissues.

[0108] In summary, this invention achieves dynamic clustering of micro- and nano probes through precise magnetic field programming control, and provides a novel solution for high-sensitivity Raman detection in complex environments by utilizing its unique "dynamic hotspot" enhancement mechanism and "magnetic-acoustic" dual-mode positioning capability.

[0109] The above description, in conjunction with specific preferred embodiments, provides a further detailed explanation of the present invention. It should not be construed that the specific implementation of the present invention is limited to these descriptions. For those skilled in the art, various simple deductions or substitutions can be made without departing from the concept of the present invention, and all such modifications and substitutions should be considered within the scope of protection of the present invention.

Claims

1. A dynamic Raman detection device based on a magnetically controlled cluster, characterized in that: It includes a magnetic SERS probe, a magnetic field generating unit for generating a programmable time-varying magnetic field to drive the magnetic SERS probe to form a dynamic micro / nano motor cluster, a Raman detection unit for laser irradiation of the magnetically controlled cluster region and acquisition of Raman scattering signals, an imaging unit for real-time monitoring and positioning of the magnetically controlled cluster, and a control unit; the area to be tested is located within the effective working space of the magnetic field generating unit. The magnetic SERS probe has both magnetic response characteristics and surface-enhanced Raman scattering activity, and can be a core-shell structure, yolk-shell structure, Janus structure, polymer structure, or magnetic microsphere structure with surface modified with noble metal satellites. The magnetic field generating unit includes a permanent magnet generating unit, an electromagnetic generating unit, or a combination of both, and can output a rotating magnetic field, an oscillating magnetic field, a superimposed magnetic field, or a gradient magnetic field; the permanent magnet generating unit includes a fixed permanent magnet, a movable mechanical magnetic arm, a rotating magnetic field generator, or a Halbach array, wherein the permanent magnet is made of at least one of neodymium iron boron, samarium cobalt, or ferrite; the electromagnetic generating unit includes at least one of a DC electromagnet, an AC electromagnet, a solenoid, a Helmholtz coil, a Maxwell coil, a three-dimensional orthogonal coil system, or a photolithographic planar microcoil; The imaging unit includes one or more of the following: ultrasound imaging unit, optical imaging unit, X-ray imaging unit, computed tomography imaging unit, magnetic resonance imaging unit, photoacoustic imaging unit, or thermal imaging unit. The Raman detection unit includes one of the following: a microconfocal Raman spectrometer, a fiber optic Raman spectrometer, a handheld or portable Raman spectrometer, a Fourier transform Raman spectrometer, and a customized Raman signal reading module. The control unit is electrically connected to the magnetic field generating unit, the Raman detection unit, and the imaging unit, respectively, and is used to adjust the magnetic field parameters, synchronously control the detection sequence, and process imaging and spectral data.

2. The dynamic Raman detection device based on a magnetically controlled cluster according to claim 1, characterized in that: The imaging unit is an ultrasound imaging unit.

3. The dynamic Raman detection device based on a magnetically controlled cluster according to claim 1, characterized in that: The magnetic SERS probe unit includes a magnetic core, a SERS active component, and a protective layer. The magnetic core is one of iron(II,III) oxide, iron(III) oxide, pure iron, cobalt, nickel, or an alloy thereof, or a ferrite material. The SERS active component is one of gold, silver, copper, platinum, palladium, or an alloy thereof, or a nanomaterial. The protective layer is a 2-5 nm thick SiO2 layer covering the surface of the SERS active component.

4. A dynamic Raman detection method based on a magnetically controlled cluster, characterized in that: The detection is performed using the dynamic Raman detection device based on a magnetically controlled cluster as described in any one of claims 1 to 3, comprising the following steps: Step S1: Introduce the magnetic SERS probe into the fluid environment to be tested; Step S2: A programmable time-varying magnetic field is generated by the magnetic field generating unit, which drives the magnetic SERS probes to aggregate through magnetic dipole interaction to form a dynamic micro-nano motor cluster with a specific geometric shape. Step S3: The magnetic field parameters are adjusted by the control unit to maintain the cluster in a dynamic state, so that the magnetic SERS probes inside the cluster collide and move at high frequency, generating a large number of transient gap hotspots on the basis of the steady-state gap hotspots inside the magnetic flux. Step S4: The cluster position is monitored in real time using the imaging unit, and the cluster area is irradiated with laser and Raman scattering signals are collected by the Raman detection unit.

5. The dynamic Raman detection method based on a magnetically controlled cluster according to claim 4, characterized in that: In step S2, the magnetic field parameters of the magnetic field generating unit are adjusted to satisfy any of the following conditions: When generating a rotating magnetic field, the magnetic field strength is set to 4mT, 6mT, or 8mT, the rotation frequency is set to 10~20Hz, and the magnetic field function is... A R This represents the maximum value of the rotating magnetic field strength, where ƒ is the frequency of the rotating magnetic field, and B... x and B y These represent the components of the magnetic field along the x-axis and y-axis, respectively. When generating an oscillating magnetic field, the magnetic field strength is set to 15 mT, the oscillation frequency is set to 10 Hz, 15 Hz, or 20 Hz, and the magnetic field function is: A O and C O All are constants, θ is the angle between the oscillation direction and the y-axis, ƒ is the oscillation frequency, and B is a constant. x and B y These represent the components of the magnetic field along the x-axis and y-axis, respectively. When a dispersing magnetic field is generated, the magnetic field function is: A xy and A z These represent the maximum magnetic field strengths in the xy plane and the y plane, respectively. xy and ƒ z These are the frequencies of the rotating magnetic field in the xy plane and the oscillating magnetic field in the z direction, respectively. x B y B z These are the components of the magnetic field along the x-axis, y-axis, and z-axis, respectively.

6. The dynamic Raman detection method based on a magnetron cluster according to claim 4, characterized in that: The detection parameters of the Raman detection unit in step S4 meet the following requirements: when detecting crystal violet, a 532nm laser is used for excitation, the laser energy intensity is set to 5%, the single acquisition time is 5s, the cumulative number of acquisitions is 2, and the characteristic peak is taken at 917cm. -1 When detecting Rhodamine 6G, a 633nm laser was used for excitation, the laser energy intensity was set to 10%, the single acquisition time was 10s, and the cumulative acquisition was 2 times. The characteristic peak was taken at 613cm. -1 .

7. The application of the dynamic Raman detection method based on a magnetically controlled cluster as described in claim 4, characterized in that: Used for food safety testing, water quality monitoring, biomedical testing, industrial fluid analysis, microfluidic chip sampling, or collection and recovery of trace samples in hazardous environments.

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