CN111643683A - Composite Raman probe and preparation method and application thereof - Google Patents
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Abstract
The invention relates to a composite Raman probe and a preparation method and application thereof. The preparation method of the composite Raman probe comprises the following steps: modifying the enhanced Raman nanoparticles to enable the charges on the surfaces of the enhanced Raman nanoparticles to be neutral or the charges to be the same as the electrical property of the tracer, so as to obtain modified enhanced Raman nanoparticles; and mixing the modified enhanced Raman nano-particles with the tracer to obtain the composite Raman probe. According to the composite Raman probe and the preparation method and application thereof, the Raman signal of the enhanced Raman nanoparticle has specificity and cannot be interfered by tracer molecules, meanwhile, the enhanced Raman nanoparticle cannot interfere the detection of the tracer, and therefore the obtained composite Raman probe can realize accurate Raman positioning and tracer positioning functions, and the purpose of double tracing is achieved. The preparation method has simple process and is suitable for mass production.
Description
Technical Field
The invention relates to the technical field of nano materials, in particular to a composite Raman probe and a preparation method and application thereof.
Background
Cancer is a serious threat to human health and life safety and is one of the diseases with high mortality rate. Surgical resection is currently one of the most effective methods for treating cancer. Sentinel Lymph Node (SLN) is the first node of lymph metastasis in malignant tumor, and has important significance for lymph node metastasis in malignant tumor region and guidance of lymph node cleaning. Sentinel lymph node biopsy technique is considered "the most influential contribution and change of tumor surgery over the past 10 years". The sentinel lymph node biopsy can ensure the safety of the tumor, effectively avoid unnecessary large-scale lymph cleaning and reduce a plurality of complications such as hemorrhage, nerve injury, lymphedema and the like.
Therefore, accurate location of the sentinel lymph nodes is an essential step for performing sentinel lymph node biopsies. Currently, sentinel lymph node tracers have been used in large numbers in breast cancer surgery. The tracer which is widely applied to sentinel lymph node tracing in clinic mainly comprises the following components according to action methods: dye method tracer, fluorescent tracer, radionuclide tracer.
The clinically commonly used dye lymph node tracers are mainly: methylene Blue (Methylene Blue), nanocarbon (Carban Nano Particle), isothio Blue (Isosulfan Blue), Patent Blue (Patent Blue), and the like. However, methylene blue has poor targeting, easily stains secondary lymph nodes in a shorter time and risks increasing background interference, and therefore the time window of operation left to the physician in the operation is relatively short. There is also the possibility of blue staining and necrosis of the skin and other adverse effects. However, nanocarbon does not have SLN targeting, has poor visibility due to shallow lymphatic vessel ink staining, lacks a large sample prospective study, has a value to be further verified as a tracer, and is not suggested by experts to be clinically applied.
The fluorescent lymph node tracer comprises indocyanine green, methylene blue and the like. The method has the defects of low detection rate caused by easy migration to a secondary lymph node in a short time, background interference caused by autofluorescence of biological tissues, poor stability of fluorescent materials, fluorescence bleaching phenomenon, difficult development of deep lymph vessels and lymph nodes, limited penetration (usually less than 1mm), lack of long-term follow-up data and the like.
The radionuclide lymph node imaging agent is mainly colloid obstructing 99 labeling, and includes sulfur colloid, dextran, tin colloid, serum protein colloid, etc. The radionuclide lymph node imaging technology is a method for selectively imaging the draining lymphatic system by using a SPECT-CT machine to examine after local injection around tumors by using radionuclide to mark a water-soluble colloidal substance which is easy to be absorbed by the lymphatic system. The radionuclide lymph node imaging technology is used for gathering in a tumor regional lymph node by means of a radionuclide-labeled colloid and imaging the lymph node, so that clinical treatment is guided. The radionuclides commonly used are 99mTc, 125I, 131I, etc. The radioactive imaging agent mainly comprises 99 mTc-labeled sulfur colloid, 99 mTc-labeled dextran, 99 mTc-labeled albumin and the like, and the 99 mTc-labeled sulfur colloid or dextran is clinically used at present. The nuclide tracer has good targeting and visibility, is simple and convenient to operate and moderate in price, but adds a quality control link in the practical application process, needs to check the phenomena of reagent preparation of medical science and injection-grade large-scale ECT equipment, and also has the problems of iatrogenic nuclide pollution, safety and the like.
Each of these single methods, when used, has different disadvantages, resulting in inaccurate sentinel node location. Therefore, the use of dual-tracer technology-nuclide plus dye methods-to provide sentinel lymph node localization accuracy-is strongly recommended in current clinical guidelines for breast cancer surgery (us 2017 version, eu 2015 version, china 2017 version). However, the current double tracer technology still depends on a nuclide method, and the two tracers need to be injected separately and independently at the same time, which is easy to consume more operation time.
Disclosure of Invention
Therefore, it is necessary to provide a composite raman probe, a preparation method and an application thereof for solving the problems of how to improve positioning accuracy, convenience in use and the like.
A preparation method of a composite Raman probe comprises the following steps:
modifying the enhanced Raman nanoparticles to enable the charges on the surfaces of the enhanced Raman nanoparticles to be neutral or the charges to be the same as the electrical property of the tracer, so as to obtain modified enhanced Raman nanoparticles;
and mixing the modified enhanced Raman nano-particles with the tracer to obtain the composite Raman probe.
In one embodiment, the modified enhanced raman nanoparticles, the tracer and the adjuvant are mixed to obtain the composite raman probe.
In one embodiment, the adjuvant comprises a solubilizing agent, a cosolvent, a suspending agent, an emulsifier, a bacteriostatic agent, a pH adjusting agent, an antioxidant, and/or an osmotic pressure adjusting agent.
In one embodiment, the mixing means comprises stirring, shaking, sonication, homogenization, or emulsification.
In one embodiment, the enhanced raman nanoparticles are modified by surface physical modification or surface chemical modification.
In one embodiment, the surface physical modification method is adsorption, encapsulation, ultraviolet light or plasma; surface chemical modification is carried out by a coupling agent.
In one embodiment, the tracer is a dye tracer, a fluorescent tracer or a superparamagnetic tracer.
In one embodiment, the modified enhanced raman nanoparticles are mixed with the tracer in the following parts by mass: 0.01-100 parts of modified enhanced Raman nano particles and 0.01-100 parts of tracer.
In one embodiment, the modified enhanced raman nanoparticles have a size of 1 to 1000 nm.
A composite Raman probe comprises a modified enhanced Raman nanoparticle and a tracer, wherein the charge of the surface of the modified enhanced Raman nanoparticle is neutral or the same as the electrical property of the tracer.
An application of the composite Raman probe in medical imaging.
Compared with the prior art, the invention has the beneficial effects that: modifying the enhanced Raman nanoparticles to enable the charges on the surfaces of the enhanced Raman nanoparticles to be neutral or the charges to be the same as the electrical property of the tracer, so as to obtain modified enhanced Raman nanoparticles, thereby avoiding the enhanced Raman nanoparticles and the tracer from agglomerating, ensuring the independence of the enhanced Raman nanoparticles and the tracer on the detection method, ensuring that the detection signals of the enhanced Raman nanoparticles and the tracer do not interfere with each other, namely, the enhanced Raman nanoparticles can carry out signal detection through a Raman spectrometer and the tracer can be detected through naked eye observation or other instruments, then mixing the modified enhanced Raman nanoparticles with the tracer to obtain the composite Raman probe, wherein the enhanced Raman nanoparticles in the obtained composite Raman probe have specificity and cannot be interfered by the tracer molecules when the enhanced Raman nanoparticles are detected through the Raman spectrometer, and simultaneously, the enhanced Raman nanoparticles are light in color and free of fluorescence signals and magnetism, the enhanced Raman nanoparticles and the tracer are mutually independent, and cannot be interfered by the enhanced Raman nanoparticles when the tracer is detected, so that the obtained composite Raman probe can realize accurate Raman positioning and tracer positioning functions, and the purpose of double tracing is achieved. In addition, the obtained composite Raman probe has no problems of fluorescence quenching, radioactive nuclear pollution, safety and the like, and can be stored for a long time. The preparation method has simple process and is suitable for mass production.
Drawings
FIG. 1 is an electron micrograph of a composite Raman probe obtained in example 1;
fig. 2 is an electron micrograph of the composite raman probe obtained in the comparative example.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
The preparation method of the composite raman probe of the embodiment includes the following steps:
s1: and modifying the enhanced Raman nanoparticles to enable the electric charge on the surface of the enhanced Raman nanoparticles to be neutral or the electric charge of the surface of the enhanced Raman nanoparticles to be the same as that of the tracer, so as to obtain the modified enhanced Raman nanoparticles.
Specifically, the surface of the enhanced raman nanoparticle is modified such that the surface of the enhanced raman nanoparticle is neutral in charge or such that the electrical property of the enhanced raman nanoparticle is the same as the electrical property of the tracer. For example: if the electrical property of the tracer is negative, the enhanced raman nanoparticles need to be modified to have the negative electrical property, or the surface charge is neutral.
The enhanced Raman nanoparticles can be modified by a surface physical modification method or a surface chemical modification method. Further, in one embodiment, the surface physical modification is mainly through physical actions such as adsorption, encapsulation and the like, and the surface of the particle is modified by means of ultraviolet rays, plasma and the like; the surface chemical modification mainly utilizes a coupling agent to modify, and utilizes the interaction between organic functional groups contained in the coupling agent and the enhanced Raman nano-particles to realize the modification or functionalization of the enhanced Raman nano-particles. Wherein, the coupling agent can be polyalcohol and/or silane coupling agent. Further, the coupling agent is polyethylene glycol or a silane coupling agent.
Further, the enhanced raman nanoparticle comprises a metal nanoparticle, a raman signal molecular layer coated on the metal nanoparticle, and a protective layer coated on the raman signal molecular layer. The enhanced Raman nanoparticles have the advantages of strong and stable signals, high specificity, strong tissue penetrating power, good biological safety, convenience in operation and the like, and have very wide application prospects in the field of biomedicine.
Further, the metal nanoparticles may be gold nanoparticles, silver nanoparticles, copper nanoparticles, aluminum nanoparticles, or platinum nanoparticles. In this embodiment, the metal nanoparticles are gold nanoparticles.
In one embodiment, the shape of the metal nanoparticles includes, but is not limited to, spheres, rods, cubes, triangular platelets, stars, dimers, trimers, multimers, core-shell structures, and the like.
Wherein the Raman molecule can be one or more of dimercaptobenzene, p-toluene thiophenol, p-aminophenol, p-nitrobenzothiophenol and 2-naphthalene thiol. The thickness of the protective layer can be 0-300nm, and the material adopted by the protective layer can be organic or inorganic molecules such as silicon dioxide, aluminum oxide, polydopamine, polyaniline and the like.
Further, in one embodiment, the modified enhanced raman nanoparticles have a size of 1-1000 nm. By adopting the modified enhanced Raman nanoparticles with the size, the detection accuracy of Raman signals is ensured, the agglomeration and the like caused by overlarge nanoparticles are avoided, and the modified enhanced Raman nanoparticles and the tracer can be uniformly dispersed. Further, the size of the modified enhanced Raman nano-particles is 5-50nm, so that the dispersibility is further improved.
In one embodiment, the tracer is a dye tracer, a fluorescent tracer or a superparamagnetic tracer. The superparamagnetic tracer may be a superparamagnetic iron oxide-cored nanoparticle.
In one embodiment, the dye tracer includes, but is not limited to, methylene blue, nanocarbon, isothio blue, and patent blue, and the like, and is not limited thereto.
S2: and mixing the modified enhanced Raman nanoparticles with a dye tracer to obtain the composite Raman probe.
Specifically, the modified enhanced raman nanoparticles can be mixed with a tracer by stirring, oscillation, ultrasound, homogenization, emulsification, and the like, to obtain the composite raman probe. In one embodiment, the modified enhanced raman nanoparticles are mixed with the tracer in the following parts by mass: 0.01-100 parts of modified enhanced Raman nano particles and 0.01-100 parts of tracer. Further, 30-70 parts of modified enhanced Raman nano particles and 20-60 parts of a tracer.
In one embodiment, step S2 includes: and mixing the modified enhanced Raman nano-particles, the tracer and the auxiliary materials to obtain the composite Raman probe. The stability of the composite Raman probe is further improved through auxiliary materials. Wherein the auxiliary materials comprise solubilizer, cosolvent, suspending agent, emulsifier, bacteriostatic agent, pH regulator, antioxidant and/or osmotic pressure regulator.
The preparation method of the composite Raman probe comprises the following steps: modifying the enhanced Raman nanoparticles to enable the charges on the surfaces of the enhanced Raman nanoparticles to be neutral or the charges to be the same as the electrical property of the tracer, so as to obtain modified enhanced Raman nanoparticles, thereby avoiding the enhanced Raman nanoparticles and the tracer from agglomerating, ensuring the independence of the enhanced Raman nanoparticles and the tracer on the detection method, ensuring that the detection signals of the enhanced Raman nanoparticles and the tracer do not interfere with each other, namely, the enhanced Raman nanoparticles can carry out signal detection through a Raman spectrometer and the tracer can be detected through naked eye observation or other instruments, then mixing the modified enhanced Raman nanoparticles with the tracer to obtain the composite Raman probe, wherein the enhanced Raman nanoparticles in the obtained composite Raman probe have specificity and cannot be interfered by the tracer molecules when the enhanced Raman nanoparticles are detected through the Raman spectrometer, and simultaneously, the enhanced Raman nanoparticles are light in color and free of fluorescence signals and magnetism, the enhanced Raman nanoparticles and the tracer are mutually independent, and cannot be interfered by the enhanced Raman nanoparticles when the tracer is detected, so that the obtained composite Raman probe can realize accurate Raman positioning and tracer positioning functions, and the purpose of double tracing is achieved. In addition, the obtained composite Raman probe has no problems of fluorescence quenching, radioactive nuclear pollution, safety and the like, and can be stored for a long time. The preparation method has simple process and is suitable for mass production.
It should be noted that, when the tracer is a dye tracer, the raman signal of the enhanced raman nanoparticle has specificity and is not interfered by dye molecules; meanwhile, the color of the enhanced Raman nano-particles is lighter, so that the interference on the color of dye molecules is avoided, and double tracing is realized. When the tracer is the fluorescence tracer, through modifying reinforcing raman nanoparticle for it does not interfere with each other with the fluorescence tracer, can not receive the interference of fluorescence tracer when detecting through the raman spectroscopy appearance, and simultaneously, reinforcing raman nanoparticle does not have fluorescence signal, can not receive the interference of reinforcing raman nanoparticle when adopting fluorescence detection instrument to detect the fluorescence tracer. Moreover, when the tracer is a superparamagnetic tracer, the enhanced Raman nanoparticles and the superparamagnetic nanoparticles can stably coexist, are not aggregated and do not interfere with each other, and the enhanced Raman nanoparticles are not magnetic, so that when the composite Raman probe is detected, a Raman signal and a magnetic signal are detected, and the positioning accuracy is improved.
It should be noted that not both lymph node tracers may be mixed to give a composite tracer and double-traced. For example, when the isothio blue in the dye tracer and the indocyanine green in the fluorescent tracer are mixed, both tracers generate fluorescent signals, and generate mutual interference of the signals, so that the double-tracing effect cannot be achieved.
In addition, the obtained composite Raman probe can be in the forms of suspension, freeze-dried preparation and the like. Therefore, the composite Raman probe is convenient to use and can be injected once, the injection mode is similar to that of the existing sentinel lymph node developer, the false positive and the false negative caused by a single tracer can be rapidly mastered and solved, the accurate positioning of the lymph node is guaranteed, and the visualization effect is realized in the operation process, so that a doctor can find the sentinel lymph node more quickly, and the higher detection success rate is obtained.
In the using process, after the composite probe is injected around areola or tumor, under the action of lymphatic tropism, the composite probe is diffused to lymph nodes through a lymphatic system and dyes sentinel lymph nodes, and then a Raman spectrometer is used for detecting and positioning the sentinel lymph nodes. Because the migration speed of the tracer molecules in the composite probe is different from that of the enhanced Raman nanoparticles, only the lymph which detects the tracer and the Raman signal can be identified as sentinel lymph nodes, and the dual-tracing function is realized.
The composite raman probe of an embodiment includes a modified enhanced raman nanoparticle and a dye tracer, and the surface of the modified enhanced raman nanoparticle is neutral in charge or the same in electrical property as the tracer. It should be noted that the structure of the composite raman probe is as described in the above embodiment, and is not described herein again. The composite Raman probe can realize the dual-tracing function.
The composite Raman probe is applied to medical imaging.
The raw materials used are all commercially available.
In addition, the enhanced raman nanoparticles of this embodiment can be prepared by using an existing method. The enhanced Raman nanoparticles can be core-shell structure gold nanoparticles wrapping mesoporous silica layers and the like.
It should be noted that, in the following description of specific embodiments, the core-shell structure gold nanoparticles wrapping the mesoporous silica layer are all prepared by the above method, and will not be described again.
The invention is further illustrated by the following specific examples.
Example 1
(1) Preparing core-shell structure gold nanoparticles wrapping the mesoporous silica layer;
(2) adding 3-aminopropyltriethoxysilane (namely: silane coupling agent KH-550) with the concentration of 5% (volume percentage) into the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer obtained in the step (1), magnetically stirring for 30 minutes at the rotating speed of 500rpm, centrifuging and washing, and modifying the obtained core-shell structure gold nanoparticles wrapped with the mesoporous silica layer to ensure that the surface charge of the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer is electropositive;
(3) and (3) ultrasonically mixing the modified core-shell structure gold nanoparticles wrapped with the mesoporous silica layer in the step (2) and methylene blue in a volume ratio of 5:5, and uniformly mixing after ultrasonic treatment for 1 minute to obtain the composite Raman probe. Wherein, the technological parameters of the ultrasound are as follows: power 600w, frequency 40 KHz.
Example 2
(1) Preparing core-shell structure gold nanoparticles wrapping the mesoporous silica layer;
(2) adding 2-triethoxysilylacetic acid with the concentration of 5% (volume percentage) into the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer obtained in the step (1) by adopting a surface chemical modification method, magnetically stirring for 30 minutes at the rotating speed of 500rpm, and carrying out centrifugal washing to modify the obtained core-shell structure gold nanoparticles wrapped with the mesoporous silica layer so that the surface charge of the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer is electronegative;
(3) and (3) ultrasonically mixing the modified gold nanoparticles wrapped with the mesoporous silica layer in the step (2) and the nanocarbon according to the volume ratio of 3:7, and uniformly mixing after ultrasonic treatment for 1 minute to obtain the composite Raman probe. Wherein, the technological parameters of the ultrasound are as follows: power 600w, frequency 40 KHz.
Example 3
(1) Preparing core-shell structure gold nanoparticles wrapping the mesoporous silica layer;
(2) adding 3-aminopropyltriethoxysilane (namely: silane coupling agent KH-550) with the concentration of 5% (volume percentage) into the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer obtained in the step (1), magnetically stirring for 30 minutes at the rotating speed of 500rpm, centrifuging and washing, and modifying the obtained core-shell structure gold nanoparticles wrapped with the mesoporous silica layer to ensure that the surface charge of the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer is electropositive;
(3) and (3) mechanically stirring and uniformly mixing the modified nano-particles obtained in the step (2) and the patent blue in a volume ratio of 3:7 for 10 minutes to obtain the composite Raman probe.
Example 4
(1) Preparing core-shell structure gold nanoparticles wrapping the mesoporous silica layer;
(2) adding 35% (mass percentage) of poly (diallyldimethylammonium chloride) solution into the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer obtained in the step (1) by adopting an electrostatic adsorption modification method, magnetically stirring the mixture for 30 minutes at the rotating speed of 500rpm, and performing centrifugal washing to modify the obtained core-shell structure gold nanoparticles wrapped with the mesoporous silica layer so that the surface charge of the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer is electropositive;
(3) and (2) magnetically stirring the modified nano-particles obtained in the step (1) and isothioblue for 15 minutes at a volume ratio of 6:4 at a rotating speed of 500rpm to obtain the composite Raman probe.
Example 5
(1) Preparing core-shell structure gold nanoparticles wrapping the mesoporous silica layer;
(2) adding 3-aminopropyltriethoxysilane (namely: silane coupling agent KH-550) with the concentration of 5% (volume percentage) into the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer obtained in the step (1), magnetically stirring for 30 minutes at the rotating speed of 500rpm, centrifuging and washing, and modifying the obtained core-shell structure gold nanoparticles wrapped with the mesoporous silica layer to ensure that the surface charge of the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer is electropositive;
and (3) ultrasonically mixing the modified gold nanoparticles with the core-shell structure and the indocyanine green, which wrap the mesoporous silica layer, in the step (2) according to the volume ratio of 5:5, and uniformly mixing after performing ultrasonic treatment for 1 minute to obtain the composite Raman probe. Wherein, the technological parameters of the ultrasound are as follows: power 600w, frequency 40 KHz.
Example 6
(1) Preparing core-shell structure gold nanoparticles wrapping the mesoporous silica layer;
(2) adding 3-aminopropyltriethoxysilane (namely: silane coupling agent KH-550) with the concentration of 5% (volume percentage) into the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer obtained in the step (1), magnetically stirring for 30 minutes at the rotating speed of 500rpm, centrifuging and washing, and modifying the obtained core-shell structure gold nanoparticles wrapped with the mesoporous silica layer to ensure that the surface charge of the core-shell structure gold nanoparticles wrapped with the mesoporous silica layer is electropositive;
and (3) ultrasonically mixing the modified core-shell structure gold nanoparticles wrapped with the mesoporous silica layer in the step (2) and the superparamagnetic iron oxide nanoparticles according to the volume ratio of 5:5, and uniformly mixing after ultrasonic treatment for 1 minute to obtain the composite Raman probe. Wherein, the technological parameters of the ultrasound are as follows: power 600w, frequency 40 KHz.
Comparative example 1
And (2) magnetically stirring the core-shell structure gold nanoparticles which are not subjected to surface chemical modification and wrapped with the mesoporous silica layer and are obtained in the step (1) and methylene blue for 15 minutes at the volume ratio of 5:5 at the rotating speed of 500rpm, so that the obtained composite Raman probe can generate an obvious agglomeration phenomenon and cannot be used for sentinel lymph node tracing.
The technical features of the embodiments described above may be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the embodiments described above are not described, but should be considered as being within the scope of the present specification as long as there is no contradiction between the combinations of the technical features.
The above-mentioned embodiments only express several embodiments of the present invention, and the description thereof is more specific and detailed, but not construed as limiting the scope of the invention. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the inventive concept, which falls within the scope of the present invention. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (11)
1. The preparation method of the composite Raman probe is characterized by comprising the following steps:
modifying the enhanced Raman nanoparticles to enable the charges on the surfaces of the enhanced Raman nanoparticles to be neutral or the charges to be the same as the electrical property of the tracer, so as to obtain modified enhanced Raman nanoparticles;
and mixing the modified enhanced Raman nano-particles with the tracer to obtain the composite Raman probe.
2. The method of claim 1, wherein the modified enhanced Raman nanoparticles, the tracer and an adjuvant are mixed to obtain the composite Raman probe.
3. The method for preparing a composite raman probe according to claim 2, wherein the auxiliary materials include a solubilizing agent, a cosolvent, a suspending agent, an emulsifier, a bacteriostatic agent, a pH adjusting agent, an antioxidant and/or an osmotic pressure adjusting agent.
4. The method of any one of claims 1-3, wherein the mixing comprises stirring, shaking, sonication, homogenizing, or emulsification.
5. The method for preparing a composite raman probe according to any one of claims 1 to 3, wherein the enhanced raman nanoparticle is modified by a surface physical modification method or a surface chemical modification method.
6. The method for preparing the composite Raman probe according to claim 5, wherein the surface physical modification method is adsorption, encapsulation, ultraviolet light or plasma; surface chemical modification is carried out by a coupling agent.
7. The method for preparing a composite raman probe according to claims 1 to 3, wherein the tracer is a dye tracer, a fluorescent tracer or a superparamagnetic tracer.
8. The method for preparing a composite raman probe according to any one of claims 1 to 3, wherein the modified enhanced raman nanoparticle and the tracer are mixed in parts by mass as follows: 0.01-100 parts of modified enhanced Raman nano particles and 0.01-100 parts of tracer.
9. The method of any one of claims 1-3, wherein the modified enhanced Raman nanoparticles have a size of 1-1000 nm.
10. A composite raman probe comprising a modified enhanced raman nanoparticle tracer, wherein the surface of the modified enhanced raman nanoparticle is neutrally charged or has the same electrical property as the tracer.
11. Use of a composite raman probe according to claim 10 in medical imaging.
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|---|---|---|---|---|
| CN114815428A (en) * | 2021-01-28 | 2022-07-29 | 惠州市华阳光学技术有限公司 | Photochromic material |
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