Preparation method and application of a spatial type surface enhanced raman probe

Abstract

The application provides a preparation method and application of a spatial type surface enhanced Raman probe, and belongs to the technical field of preparation of the surface enhanced Raman probe. The hot spot of the probe takes a dielectric material-metal combination as a core, takes cetyltrimethylammonium bromide (CTAB) as a hard template on the surface of the core, synthesizes a mesoporous silica layer through one-pot wet chemical method, realizes a double-layer spatial type structure by chemical plating of metal particles on the surface again, the number of layers of the structure can be adjusted, the preparation of a more efficient 'hot spot' is realized, and the prepared enhanced Raman probe can be used for trace detection of cannabinoids.

Description

Technical Field

[0001] This invention belongs to the field of surface-enhanced Raman probe preparation technology, specifically relating to a method for preparing and applying a spatial surface-enhanced Raman probe. Background Technology

[0002] Surface-enhanced Raman scattering (SERS) is an emerging analytical technique developed based on the optical enhancement phenomenon of localized surface plasmon resonance (LSPR). With its unique technological advantages, it has shown broad application prospects in multiple fields. SERS technology has three core advantages: first, high detection sensitivity, simple sample preparation, and accurate capture of trace substances; second, high detection efficiency, enabling rapid analysis and supporting quantification, balancing speed and accuracy; and third, molecular recognition capability, achieving precise identification by collecting molecular energy level data, avoiding false positives or false negatives. Based on these advantages, SERS technology is currently widely used in key areas such as food safety analysis, biomedical analysis, and environmental monitoring, providing important technical support for quality control and safety assurance in various industries.

[0003] The core of SERS detection performance depends on the enhancement effect of the probe, and the composition, size and surface morphology of the probe directly determine whether the SERS effect can be generated and the intensity of the SERS signal. In the probe action mechanism, the "hot spot" is the key core - it refers to the region on the surface of the nanostructure where the local electromagnetic field is significantly enhanced. Its enhancement effect is mainly based on local surface plasmon resonance (LSPR). These regions are also the most significant parts of electromagnetic field enhancement on the SERS probe. The commonly used surface-enhanced Raman probe types currently include: (1) single noble metal and two-dimensional noble metal nanomaterials, such as gold, silver and copper; (2) magnetic nanocomposite materials, such as Fe3O4 composite materials; (3) metal-dielectric nanocomposite materials made with noble metal as the base and dielectric materials as the auxiliary. In single noble metal and two-dimensional noble metal nanomaterials, the probe performance depends only on the interparticle gap. However, without surface protection, these noble metal nanoparticles are prone to agglomeration under thermodynamic action due to their extremely high surface energy, which makes the detection signal unstable. The preparation and surface modification process of magnetic nanoparticles is relatively complex, and the stability of the magnetic substrate needs to be further improved. Metal-dielectric nanocomposites can be used to detect a variety of analytes in complex systems. The preparation process may be relatively complex, requiring precise control of the composite ratio and structure of noble metals and semiconductors. At the same time, the efficiency and testing accuracy of current probe single "hot spots" still need to be further improved.

[0004] Against this backdrop, the design and fabrication of efficient and stable surface-enhanced Raman (SERS) probes to achieve accurate detection of trace analytes, such as synthetic cannabinoids, has become an urgent need in the field of surface-enhanced Raman detection. Summary of the Invention

[0005] To address the problems existing in the background technology, the present invention aims to provide a method for preparing and applying a spatial surface-enhanced Raman probe. The probe's inner layer is a combination of dielectric material and metal. A mesoporous silica layer is synthesized on its surface using a one-pot wet chemical method with hexadecyltrimethylammonium bromide (CTAB) as a hard template. Metal particles are then chemically plated onto the surface to achieve a double-layer spatial structure, and the number of layers can be adjusted. This structure enables more efficient preparation of "hot spots," and the enhanced Raman probe prepared by this invention can be used for trace detection of synthetic cannabinoids.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows:

[0007] A method for preparing a spatial surface-enhanced Raman probe includes the following steps:

[0008] Step 1. Preparation of dielectric microspheres@metal nanoparticles:

[0009] Dielectric microspheres with a particle size of not less than 500 nm are added to a sensitization solution. After stirring evenly, the solution is allowed to stand for sensitization. The sensitized dielectric microspheres are then washed by centrifugation with pure water and dispersed in pure water. The sensitized dielectric microspheres are then added to a silver ammonia solution and stirred in the dark for reaction. A sodium citrate-glucose mixed solution is then added for reaction. After the reaction, the solution is centrifuged and washed to obtain dielectric microspheres@metal nanoparticles.

[0010] Step 2. A mesoporous silica layer is grown on the surface of dielectric microspheres@metal nanoparticles. The specific process is as follows:

[0011] Step 2.1. Perform weak alkaline surface activation treatment on dielectric microspheres@metal nanoparticles at room temperature, and then wash them by centrifugation with ethanol-water solution; the specific process of weak alkaline surface activation treatment is as follows: disperse dielectric microspheres@metal nanoparticles in ammonia solution and stir to activate at room temperature;

[0012] Step 2.2. Add hexadecyltrimethylammonium bromide and diethanolamine to pure water, heat and stir to dissolve, then add the dielectric microspheres@metal nanoparticles obtained in step 2.1, then add ethoxysilane, heat and stir; after the reaction is complete, wash with pure water by centrifugation, disperse the precipitate in pure water to obtain a suspension;

[0013] Step 2.3. Add the suspension to an ethanol-hydrochloric acid mixed solution, reflux and wash, then centrifuge and wash to obtain a mesoporous silica layer on the surface of dielectric microspheres@metal nanoparticles.

[0014] Step 3. Repeat step 1 to deposit metal nanoparticles on the surface of the mesoporous silica layer to obtain a bilayer spatial structure;

[0015] Step 4. Repeat steps 2 and 3 several times to obtain a multi-layered spatial structure.

[0016] Further, in step 1, the dielectric microspheres are SiO2 or TiO2 with a particle size range of 500~1000 nm; the metal nanoparticles are Ag with a particle size of 5~25 nm.

[0017] Further, in step 1, the sensitization solution is obtained by mixing and stirring trifluoroacetic acid (TFAE) and tin dichloride (SnCl2) until homogeneous; the sodium citrate-glucose mixed solution is obtained by mixing and stirring glucose and sodium citrate until homogeneous.

[0018] Furthermore, the silver ammonia solution is obtained by mixing potassium hydroxide (KOH) and silver nitrate (AgNO3), stirring until homogeneous, and then adding ammonia water dropwise.

[0019] Furthermore, in step 1, the centrifugation rate for centrifugal washing is 3000~4000 rpm, and the washing time is 4~5 min.

[0020] Furthermore, in step 2.2, after adding ethoxysilane (TEOS), the reaction temperature is heated to 80~90 ℃, and the reaction time is 2~6 h.

[0021] Furthermore, in step 2.3, the volume percentage of hydrochloric acid in the ethanol-hydrochloric acid mixed solution is 1% to 5%; the centrifugation rate for centrifugation washing is 1500 to 2000 rpm, and the washing time is 3 min.

[0022] Furthermore, the mesoporous silica obtained in step 2 provides attachment points for silver particles to support the framework. The thickness of the pore layer is 20~60 nm. The greater the thickness, the lower the surface energy and the better the anti-agglomeration performance; the smaller the thickness, the denser the contact between the metallic silver particles and the higher the "hot spot" efficiency. The selection should be made according to the test environment.

[0023] Furthermore, in step 4, the number of repetitions is determined according to the requirements, and the number of repetitions is a natural number.

[0024] The present invention also provides the application of the spatial surface-enhanced Raman probe prepared by the above method in the detection of synthetic cannabinoids. The specific detection process is as follows: the synthetic cannabinoid to be tested is dropped onto a silicon wafer, and then the spatial surface-enhanced Raman probe of the present invention is dropped onto the synthetic cannabinoid. The probe and the cannabinoid solution are mixed evenly by stirring, and the adsorption is completed by standing. Then, it is dried, and the test is performed after drying and cooling.

[0025] The mechanism of this invention is as follows:

[0026] This invention relates to a spatial surface-enhanced Raman probe, the core of which is a SiO2@Ag composite structure formed by silver plating on the surface of silica (SiO2) spheres with a diameter of not less than 500 nm, and the outer shell is a supporting framework composed of mesoporous silica. This structure utilizes the specific combination of the SiO2 sphere core and the mesoporous SiO2 sphere shell, two materials with high dielectric constants, to synergistically generate a significant near-field focusing effect. In this structure, the mesoporous channels and their outer surfaces provide abundant attachment sites for noble metal nanoparticles. The mesoporous silica layer not only acts as a spacer to prevent direct physical contact and short-circuiting between the inner and outer silver nanoparticles, but its high specific surface area and porous structure also adsorb and enrich the target analyte, allowing the target molecules to more easily enter the "hot spot" region formed by the nano-interstices, thereby further improving the detection sensitivity. Introducing metallic silver nanoparticles onto a mesoporous SiO2 spherical shell allows the mesoporous SiO2 to effectively isolate the inner and outer layers of metallic silver nanostructures, forming 1–20 nm nanometer gaps. This, in turn, generates numerous "hot spots" between the inner and outer layers of the silver nanoparticles, as well as between the outer layers. This ability to design and effectively superimpose the number of hot spots on a single microsphere significantly enhances the detection sensitivity of the Raman signal.

[0027] In summary, due to the adoption of the above technical solution, the beneficial effects of the present invention are:

[0028] 1. This invention utilizes a one-pot method to prepare enhanced Raman probes with spatial structures. The thickness of the pore layer is controlled by adjusting the amount of silicon source, and the distribution of silver particles is controlled by adjusting the concentration of silver ammonia solution. The preparation method is simple, convenient, low-cost, and allows for easy on-site sample preparation.

[0029] 2. A silica core of at least 500 nm is used, whose size matches the visible-near-infrared band, providing a superior optical scattering background. This core, together with the mesoporous silica layer, serves as a support and control layer. By adjusting the thickness of the mesoporous silica layer, the gap between the two layers of silver nanoparticles is controlled, thereby effectively regulating the distribution and intensity of the local electromagnetic field and producing a synergistic enhancement effect.

[0030] 3. The probe of this invention possesses an innovative core-satellite structure. The core of this invention lies in the combination of multilayered silver nanoparticles and a silica core with mesoporous silica. A mesoporous silica layer of a certain thickness forms a controllable nano-gap between the first and second silver layers, constituting an ideal three-dimensional electromagnetic field "hot spot" region. Compared with a core-shell structure with only one layer of metal, the electromagnetic field in the structure of this invention not only exists in the outermost layer of the particles but is also greatly confined and enhanced in the nano-gap within the mesoporous silica layer in the thickness direction. This gives each composite particle itself extremely strong near-field enhancement capabilities. The probe of this invention also exhibits good anti-agglomeration properties and stability, and demonstrates good detection performance for analytes that are easily soluble in water or alcohol.

[0031] 4. The enhanced Raman probe prepared by this invention was found through finite element simulation to have high efficiency of single probe "hot spots" and high sensitivity analysis effect on the analyte molecules. Attached Figure Description

[0032] Figure 1 This is a schematic diagram of the double-layer spatial structure enhanced Raman probe prepared in Example 1 of the present invention.

[0033] Figure 2 These are transmission electron micrographs of products at different stages during the preparation of the double-layer spatial structure enhanced Raman probe in Example 1 of this invention.

[0034] Among them, (a) is SiO2, (b) is SiO2@Ag, (c) is SiO2@Ag@mSiO2, and (d) is SiO2@Ag@mSiO2@Ag.

[0035] Figure 3 Finite element simulation diagrams of the SiO2@Ag@mSiO2 precursor and SiO2@Ag@mSiO2@Ag prepared in Example 1 of the present invention.

[0036] Figure 4 This is the Raman spectrum of the double-layer spatial structure enhanced Raman probe of the present invention for the detection of synthetic cannabinoids. Detailed Implementation

[0037] To make the objectives, technical solutions, and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments and accompanying drawings.

[0038] Example 1

[0039] A method for preparing a spatial surface-enhanced Raman probe includes the following steps:

[0040] Step 1. Preparation of SiO2@Ag, the specific process is as follows:

[0041] Step 1.1. Preparation of sensitization solution: Mix 72 mmol of trifluoroacetic acid (TFAE) and 29 mmol of tin dichloride (SnCl2) and stir until homogeneous;

[0042] Step 1.2. Add silica microspheres with a diameter of 500 nm to the prepared sensitization solution, stir evenly, and let stand for sensitization for 30 min. Wash the sensitized silica with pure water by centrifugation at a speed of 3000 rpm for 4 min, and disperse it in 1 mL of pure water to obtain a suspension. The sensitization solution forms catalytically active sites on the silica surface, which can adsorb and activate silver ions.

[0043] Step 1.3. Add the suspension to the silver ammonia solution, stir and react in the dark for 5 min; the silver ammonia solution is obtained by mixing 12 mmol / L potassium hydroxide (KOH) and 30 mmol / L silver nitrate (AgNO3), stirring evenly, and then adding ammonia water (NH3•H2O) dropwise.

[0044] Step 1.4. After the reaction is complete, add sodium citrate-glucose mixed solution and react. Centrifuge and wash to obtain SiO2@Ag; the sodium citrate-glucose mixed solution is obtained by mixing 50 mmol of glucose and 50 mmol of sodium citrate and stirring evenly.

[0045] Step 2. Grow a mesoporous silica layer on the SiO2@Ag surface. The specific process is as follows:

[0046] Step 2.1. Disperse SiO2@Ag in an ammonia solution (0.1% v / v), stir and activate at room temperature for 40 min, then wash with aqueous solution by centrifugation to obtain activated SiO2@Ag;

[0047] Step 2.2. Add 10 mmol of hexadecyltrimethylammonium bromide (CTAB) and 13 mmol of diethanolamine (DEA) to pure water, where CTAB is a dispersant and DEA is a surfactant. After heating and stirring to dissolve, add activated SiO2@Ag, and then add 10 mmol of ethoxysilane (TEOS) as a silicon source. Stir and react at 80°C. After the reaction is complete, wash with pure water by centrifugation, and disperse the precipitate in 1 mL of pure water to obtain a SiO2@Ag suspension with a mesoporous silica layer.

[0048] Step 2.3. Add the suspension obtained in Step 2.2 to an ethanol-hydrochloric acid mixed solution, reflux and wash, then centrifuge at 1500 rpm for 3 min to thoroughly clean the pores, and then disperse in 1 mL of pure water to obtain the SiO2@Ag@mSiO2 precursor; where ethanol can dissolve CTAB better than water and can disperse product particles, while hydrochloric acid can destroy the cationic structure of CTAB, promote CTAB decomposition, and open up the pores of the mesoporous silica layer;

[0049] Step 3. Repeat step 1 and deposit silver on the surface of the SiO2@Ag@mSiO2 precursor prepared in step 2 to obtain a surface-enhanced Raman probe with a double-layer spatial structure of SiO2@Ag@mSiO2@Ag.

[0050] This invention utilizes a specific combination of two high-dielectric-constant materials, SiO2 spherical cores and mesoporous SiO2 spherical shells, to synergistically generate a significant near-field focusing effect. The near-field focusing effect of silica refers to the silica microspheres acting as "optical antennas." When a beam of light shines on the microspheres, due to their spherical lens effect, the light is refracted and focused at the spherical surface. The incident light also excites whispering-gallery modes on the surface of the microspheres, which propagate along the surface. On the backlit side, these surface waves constructively interfere with the directly transmitted propagating waves, thereby generating a highly localized focal point in the near-field region, thus enhancing the local electromagnetic field. Solid silica microspheres, due to their uniform refractive index and spherical symmetry, can generate powerful photonic nanojets (PNJs), ensuring that the incident light wavefront can be refracted, reflected, and interfered with with a precisely controllable phase relationship within and on the surface of the sphere, thus forming a coherently superimposed, tightly focused light spot on the backlit side.

[0051] To generate a strong near-field jig (PNJ), the optimal diameter is generally between 1 and 10 vacuum wavelengths. Since the vacuum wavelength of visible light is around 532 nm, the optimal particle size is generally between 500 nm and 5 μm. If the particle size is too small, the scattering ability of the particles is too weak, making it impossible to effectively converge light waves and modulate the phase, making it difficult to excite the backpropagating surface waves required to form a PNJ, resulting in a negligible near-field enhancement effect. If the particle size is too large, the light undergoes multiple reflections and interferences within the sphere, complicating the mode. The PNJ may split into multiple side lobes, or the focal point may be elongated and moved away from the sphere, leading to a decrease in the quality of the focused spot and a deterioration in localization.

[0052] To achieve significant near-field enhancement, standalone mesoporous silica often requires the use of whispering-gallery modes or Fabry-Perot resonances, necessitating a perimeter of the entire shell or microsphere that is an integer multiple of the wavelength, approximately 1-10 μm. This invention, through a combination of solid silica with a core of at least 500 nm and a mesoporous silica shell, uses the solid core as a converging element. This achieves near-field focusing of the aforementioned solid silica microspheres and also guides and "injects" some light energy into the mesoporous shell, increasing the base light intensity within the shell. This results in numerous random, nanoscale local light intensity enhancement points forming within the many pores and at their intersections.

[0053] Figure 1 This is a schematic diagram of the double-layer spatial structure enhanced Raman probe prepared in Example 1 of this invention. As shown in the diagram, the inner layer of the probe is SiO2@Ag, and the outer layer is a mesoporous silica support framework, providing large-area silver attachment sites in the outer layer and channels. The surface is then silver-plated again, causing the silver nanoparticles to form numerous "hot spots" between inner-inner layers, inner-outer layers, and outer layers, resulting in a superposition of hot spots on a single microsphere. Silver nanoparticles can focus light into a very small space around them. When two or more silver nanoparticles approach each other or when a particle approaches a metal film / interface, a synergistic effect occurs, and their converged light fields superimpose and are amplified sharply, forming "hot spots." The formation of "hot spots" exists in two forms, the most common being metal-to-metal coupling: each photoexcited silver particle can be considered an oscillating dipole. When two dipoles are very close, the oscillating electric field of one particle strongly polarizes the other particle, inducing another dipole. Coherent coupling occurs between these two dipoles. Within the narrow gap between them, the electric fields of the two dipoles superimpose in phase, generating a local electric field of extremely high intensity. Another form involves a single silver particle attached to a silicon dioxide surface; if there is a metal layer beneath or opposite the silicon dioxide, a "hot spot" can also form. The ideal range for this gap is 2-20 nm. Within this range, silver nanoparticles exhibit strong near-field coupling, and the dipoles coherently superimpose, generating a very strong hot spot. If the metal nanoparticles are too far apart, there is no coupling, and they scatter independently, resulting in no hot spot formation. If the distance is too close, electrons can flow directly between the particles through quantum tunneling, disrupting the charge spatial separation required for plasmon oscillation. This causes the local surface plasmon resonance mode to be "short-circuited" or strongly damped, and energy is mainly dissipated in a non-radiative form rather than being converted into a local electromagnetic field, thus preventing hot spot formation.

[0054] Figure 2The images show transmission electron microscopy (TEM) images of the products at different stages during the preparation of the double-layer spatial structure enhanced Raman probe in Example 1 of this invention; where (a) is SiO2 with an average particle size of 500 nm, (b) is SiO2@Ag obtained by silver plating on the surface of silicon dioxide, (c) is SiO2@Ag@mSiO2 obtained by growing mesoporous silicon dioxide on the surface of SiO2@Ag, and (d) is SiO2@Ag@mSiO2 obtained by silver plating on the surface of SiO2@Ag@mSiO2.

[0055] Figure 3 Finite element simulation diagrams of the SiO2@Ag@mSiO2 precursor and SiO2@Ag@mSiO2@Ag prepared in Example 1 of this invention are shown. The left diagram shows the finite element simulation diagram of the SiO2@Ag@mSiO2 precursor, and the right diagram shows the finite element simulation diagram of SiO2@Ag@mSiO2@Ag. In the diagrams, the bright spot region at the bottom is the main region of electric field enhancement. At these bright spot locations, the incident light excites a strong local electromagnetic field, which is a manifestation of the local surface plasmon resonance effect. The brighter and wider the bright spot region, the better the enhancement effect represented by the simulation. In the left diagram, the maximum electric field strength is 5.7, and the percentage of regions with an intensity exceeding 2 is 6.8%. In the right diagram, the maximum electric field strength is 6.5, and the percentage of regions with an intensity exceeding 2 is 8.0%. Generally, regions with an electric field strength greater than 2 are considered "hot spot" regions, which can achieve Raman enhancement. In the right image, the bright spot area of ​​SiO2@Ag@mSiO2@Ag is more numerous and brighter than that of the precursor in the left image. This indicates that the double-layer structure of the present invention produces a stronger and larger "hot spot" enhancement effect in the region. In other words, the probe of the present invention effectively improves the "hot spot" efficiency and enhances the "hot spot" effect, which is more conducive to the detection of trace substances.

[0056] The double-layered spatial structure enhanced Raman probe prepared in this embodiment is used for trace detection of synthetic cannabinoids. The specific detection process is as follows:

[0057] Five μL of 10 nmol / L synthetic cannabinoid was dropped onto a silicon wafer, followed by five μL of the bilayer spatial structure enhanced Raman probe of this invention. The probe and cannabinoid solution were stirred until homogeneous, and allowed to stand for 1 min to complete adsorption. The wafer was then dried in an oven at 60 °C and cooled before testing. Raman spectral data were acquired using a 785 nm laser.

[0058] Meanwhile, the double-layer spatial structure enhanced Raman probe of this invention was replaced with conventional gold nanorods for the detection of synthetic cannabinoids.

[0059] Raman spectra of both for the detection of synthetic cannabinoids are as follows: Figure 4As shown in the figure, the characteristic peak positions of synthetic cannabinoids detected by the enhanced Raman probe of this invention and those detected by gold nanoparticles are almost identical, indicating the reliability of the enhanced Raman probe of this invention. Furthermore, it can be observed that the peak intensities of the characteristic peaks in the spectrum measured by the enhanced Raman probe of this invention are significantly higher than those of the gold nanoparticles, demonstrating the superior detection performance of the enhanced Raman probe of this invention.

[0060] In summary, the spatial surface-enhanced Raman probe of this invention is more conducive to the adsorption of analytes, can generate more "hot spots" in environments prone to aggregation, and has good stability and anti-aggregation properties. Even if they aggregate, due to their large volume and mass and low surface energy, individual probes can be separated by mechanical manipulation such as ultrasound, enabling highly sensitive analysis of analytes and facilitating trace detection. In contrast, conventional probes using metal nanoparticles are extremely prone to aggregation, which negates the effect of surface-enhanced Raman spectroscopy and cannot be dispersed by mechanical manipulation.

[0061] The above description is merely a specific embodiment of the present invention. Any feature disclosed in this specification may be replaced by other equivalent or similar features unless otherwise specified. All disclosed features, or steps in all methods or processes, may be combined in any way except for mutually exclusive features and / or steps.

Claims

1. A method for preparing a spatial surface-enhanced Raman probe, characterized in that, Includes the following steps: Step 1. Preparation of dielectric microspheres@metal nanoparticles: Dielectric microspheres with a particle size of not less than 500 nm are added to a sensitization solution. After stirring evenly, the solution is allowed to stand for sensitization. The sensitized dielectric microspheres are then washed by centrifugation with pure water and dispersed in pure water. The sensitized dielectric microspheres are then added to a silver ammonia solution and stirred in the dark for reaction. A sodium citrate-glucose mixed solution is then added for reaction. After the reaction, the solution is centrifuged and washed to obtain dielectric microspheres@metal nanoparticles. Step 2. Growing a mesoporous silica layer on the surface, the specific process is as follows: Step 2.

1. The dielectric microspheres@metal nanoparticles were subjected to weak alkaline surface activation treatment at room temperature, and then washed by centrifugation with ethanol-water solution; Step 2.

2. Add hexadecyltrimethylammonium bromide and diethanolamine to pure water, heat and stir to dissolve, then add the dielectric microspheres@metal nanoparticles obtained in step 2.1, then add ethoxysilane, heat and stir; after the reaction is complete, wash with pure water by centrifugation, disperse the precipitate in pure water to obtain a suspension; Step 2.

3. Add the suspension to an ethanol-hydrochloric acid mixed solution, reflux and wash, then centrifuge and wash to obtain a mesoporous silica layer on the surface of dielectric microspheres@metal nanoparticles. The mesoporous silica provides attachment sites for silver particles to support the framework. The thickness of the pore layer is 20~60 nm. The greater the thickness, the lower the surface energy and the better the anti-agglomeration performance; the smaller the thickness, the denser the contact between the silver particles and the higher the hot spot efficiency. The choice should be made according to the test environment. Step 3. Repeat step 1 to deposit metal nanoparticles on the surface of the mesoporous silica layer to obtain a bilayer spatial structure; Step 4. Repeat steps 2 and 3 at least once to obtain a multi-layered spatial structure.

2. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, In step 1, the dielectric microspheres are SiO2 or TiO2 with a particle size range of 500~1000 nm; the metal nanoparticles are Ag with a particle size of 5~25 nm.

3. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, In step 1, the sensitization solution is obtained by mixing trifluoroacetic acid and tin dichloride and stirring until homogeneous; the silver ammonia solution is obtained by mixing potassium hydroxide and silver nitrate, stirring until homogeneous, and then adding ammonia water dropwise.

4. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, The sodium citrate-glucose mixed solution is prepared by mixing and stirring glucose and sodium citrate until homogeneous.

5. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, In step 1, the centrifugation rate for centrifugal washing is 3000~4000 rpm, and the washing time is 4~5 min.

6. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, In step 2.2, after adding ethoxysilane, the reaction temperature is heated to 80~90 ℃ and the reaction time is 2~6 h.

7. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, In step 2.3, the volume percentage of hydrochloric acid in the ethanol-hydrochloric acid mixed solution is 1%~5%; the centrifugation rate for washing is 1500~2000 rpm, and the washing time is 3 min.

8. The method for preparing a spatial surface-enhanced Raman probe as described in claim 1, characterized in that, In step 4, the number of repetitions is determined according to the requirements.

9. The application of a spatial surface-enhanced Raman probe prepared according to the method of any one of claims 1-8 in the detection of synthetic cannabinoids, characterized in that, The specific testing process is as follows: the synthetic cannabinoid to be tested is dropped onto a silicon wafer, and then the spatial surface-enhanced Raman probe is dropped into the synthetic cannabinoid. The probe and cannabinoid solution are mixed evenly by stirring, allowed to stand to complete the adsorption, and then dried. After drying and cooling, the test is performed.

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