Preparation method of silica-coated gold nanospheres and application thereof in surface-enhanced raman scattering detection

Abstract

The application discloses silica-coated gold nanospheres and application thereof in surface-enhanced Raman scattering detection. The method comprises the following steps: 1) preparing gold seeds with an average particle size of 25 nm; 2) preparing gold ball stock solution with a particle size of 50 nm by using the gold seeds; 3) taking the gold ball stock solution, concentrating, and adding a protective stabilizer; 4) adding APTMS solution and stirring; 5) adding sodium silicate solution, controlling the pH of the sodium silicate solution to be 5-7, adding NaCl, stirring, avoiding light, and reacting for 15-24 hours. The ultrathin shell layer of the gold nanospheres prepared by the method can effectively isolate the interference of complex matrix from outside, maximally retains the electromagnetic field enhancement effect generated by the local plasmon resonance of the gold core, avoids the problem that the enhancement factor is significantly reduced due to the over-thick shell layer in the traditional method, and thus the excellent SERS detection sensitivity is ensured.

Description

Technical Field

[0001] This invention relates to the field of biotechnology, specifically to silica-coated gold nanospheres and their application in surface-enhanced Raman scattering detection. Background Technology

[0002] SERS (Surface Plasmon Resonance Electromagnetic Field) relies on the localized surface plasmon resonance of noble metal nanoparticles to generate a strong electromagnetic field, amplifying the Raman signal of trace molecules by millions to hundreds of millions of times. It is widely used in the detection of environmental pollutants, small drug molecules, and trace biomarkers. Gold nanospheres exhibit superior chemical stability compared to silver nanoparticles, and gold cores with a particle size of approximately 50 nm possess the optimal SPR enhancement effect, making them the mainstream SERS substrate material.

[0003] However, bare gold nanospheres have two major drawbacks: ① Organic matter and salt ions are easily adsorbed on the gold surface in complex detection systems, changing the plasma peak position, introducing a large number of interfering peaks, and resulting in poor detection repeatability; ② High concentrations of analyte molecules can easily cause gold particles to agglomerate, leading to rapid substrate failure.

[0004] To address the aforementioned issues, the industry commonly employs the preparation of Au@SiO2. The inert silica shell isolates the gold core from the complex external matrix, enhancing colloidal stability. Simultaneously, the hydroxyl groups on the silica surface can be further functionalized, expanding detection application scenarios. Shell thickness is a core parameter determining SERS performance: the thicker the silica shell, the greater the electromagnetic field penetration loss, and the drastically reduced enhancement factor. Only 1–2 nm ultrathin, defect-free silica shells can balance isolation and protection with high Raman enhancement, representing the optimal structure for high-performance SERS substrates. Currently, the mainstream Au@SiO2 preparation route is the modified Stöber method: using sodium citrate to stabilize small gold particles as the core, and coating silica with an ethanol / water mixture and ammonia-catalyzed TEOS hydrolysis; APTES silane coupling agent is used to improve gold-silicon interface compatibility. Another method, the reverse microemulsion method, can prepare ultrathin silica shells. However, both methods typically do not provide ideal SERS enhancement results. The former reacts under alkaline conditions, and the shell thickness is difficult to control precisely within the ultrathin range of 1~2nm. An excessively thick shell will significantly weaken the electromagnetic field enhancement effect. Although the latter can produce a thin shell, the residual surfactants and oil phase impurities will interfere with the Raman signal and cause gold particles to agglomerate. Summary of the Invention

[0005] In view of the shortcomings of the prior art described above, the purpose of this invention is to provide silica-coated gold nanospheres and their application in surface-enhanced Raman scattering detection, so as to overcome the deficiencies of the prior art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: One aspect of the present invention provides a method for preparing gold nanoparticles coated with silica, the method comprising the following steps: 1) Preparation of gold seeds with an average particle size of 25 nm; 2) Prepare gold sphere stock solution with a particle size of 50 nm using gold seeds; 3) Take the gold ball stock solution, concentrate it, and add a protective stabilizer; 4) Add APTMS solution and stir; 5) Add sodium silicate solution, control the pH of sodium silicate solution to 5-7, add NaCl, stir, protect from light, and react for 15-24 hours.

[0007] APTMS, or 3-aminopropyltrimethoxysilane, is a commonly used silane coupling agent. Its CAS number is 13822-56-5.

[0008] Further, the method in step 1) is as follows: The HAuCl4 solution is heated and stirred until boiling, then sodium citrate solution is added, and the reaction continues for 10-20 minutes while maintaining boiling. The heating temperature can be 120-130°C, and the stirring speed is 450-510 rpm. Further, the molar ratio of HAuCl4 solution to sodium citrate solution is approximately 1:20.

[0009] Specifically, add 1000-1300 mL of 0.125 mM HAuCl4 solution to a flask, heat to 120-130 °C with stirring at 450-510 rpm until vigorous boiling, then quickly add 5-6.5 mL of 500 mM sodium citrate solution, maintain boiling and continue the reaction for 10-20 minutes to obtain gold seeds of approximately 25 nm. Allow the seed solution to cool naturally without purification, and store at low temperature for later use.

[0010] Further, step 2) involves taking a gold seed solution, heating it under reflux, and when the temperature reaches the reflux temperature of 120–130°C, adding HAuCl4 solution at a rate of 5–15 mL / min. After the addition is complete, heating is stopped, and the solution is kept stirred and cooled. The molar ratio of gold seeds to HAuCl4 is 1:4.

[0011] Specifically, the process is as follows: Place 500 mL of the seed culture in a double-necked flask and heat to reflux under stirring. When the temperature reaches the reflux temperature of 120–130 °C, slowly add 500 mL of 0.5 mM HAuCl4 solution at a rate of 5–15 mL / min. After the addition is complete, stop heating and allow the mixture to cool naturally to room temperature while stirring. This yields a stock solution of approximately 50 nm gold spheres. No purification is required; store at low temperature for later use.

[0012] Further, step 3) can be performed by centrifuging and concentrating the above-mentioned gold nanosphere sol by 1-2 times, adding a protective stabilizer after concentration, and stirring. The amount of gold nanoparticles to polyvinylpyrrolidone is in mass ratio, with gold nanoparticles:PVP = 20:1~50:1.

[0013] Specifically, the following steps can be taken: centrifuge the above gold nanosphere sol and concentrate it 1-2 times. After concentration, add 50-150 μL of 1wt% polyvinylpyrrolidone (PVP, K30) aqueous solution and stir gently.

[0014] Furthermore, the protective stabilizer may be selected from any one or more of PVP aqueous solution, polyethylene glycol PEG, polyethyleneimine PEI, sodium citrate, and phytic acid IP6.

[0015] Further, step 4) involves adding the concentrated gold nanoparticle solution to an APTMS solution and stirring. The amount of APTMS added is 0.03% to 0.04% of the total molar amount of the gold nanoparticles.

[0016] Specifically, the process involves adding 40–60 µL of 1 mM APTMS solution to the concentrated gold nanoparticle solution and stirring at 300–500 rpm for 15–40 min at room temperature. This allows APTMS to achieve modification via the interaction between amino groups and the gold surface.

[0017] Further, step 5) involves slowly adding a sodium silicate solution (pH 5-7) to the reaction system, followed by the addition of NaCl and stirring. After all the sodium silicate solution has been added, the reaction system is kept under light-protected conditions and stirred for 15-25 hours. The amount of sodium silicate added is 0.18%-0.45% of the total amount of gold nanoparticles, and the amount of NaCl added is 0.08%-0.20% of the total amount of gold nanoparticles.

[0018] Specifically, the reaction can be carried out by slowly adding 0.5-1.5 mL of 0.54 wt% sodium silicate solution to the above reaction system. The pH value of the sodium silicate solution should be controlled within the range of 5-7. 100-300 μL of 0.1 M NaCl is also added. The mixture is stirred at room temperature at 550-650 rpm throughout the process. After all the sodium silicate solution has been added, the reaction system is stirred and reacted at room temperature and in the dark for 15-25 h to obtain Au@SiO2 nanoparticles with a silica shell thickness of 1-2 nm.

[0019] Another aspect of the present invention provides gold nanoparticles prepared by the above method.

[0020] Another aspect of the present invention provides the application of the above-mentioned gold nanoparticles in surface-enhanced Raman scattering detection technology.

[0021] Another aspect of the present invention provides a product for detection in a surface-enhanced Raman scattering detection technique, the product comprising the aforementioned gold nanoparticles.

[0022] Compared with the prior art, the beneficial effects of the present invention are: This invention provides silica-coated gold nanospheres and their application in surface-enhanced Raman scattering (SERS) detection. The invention utilizes a sodium silicate system combined with PVP and APTMS interface modulation to uniformly coat the surface of gold nanospheres with an ultrathin silica shell of 1–2 nm thickness. This ultrathin shell effectively isolates interference from complex external matrices while maximally preserving the electromagnetic field enhancement effect generated by local plasmon resonance of the gold core. This avoids the problem of a significant decrease in the enhancement factor due to excessively thick shells in traditional methods, thus ensuring excellent SERS detection sensitivity. Attached Figure Description

[0023] Figure 1 This is a flowchart illustrating the method.

[0024] Figure 2 The SERS spectra of Example 1 are as follows: (a) Au@SiO2 blank substrate and spectrum after loading 4-MBA; (b) Au@SiO2 blank substrate and spectrum after loading phenytoin sodium.

[0025] Figure 3 The SERS spectra of Example 2 are as follows: (a) Au@SiO2 blank substrate and spectrum after loading 4-MBA; (b) Au@SiO2 blank substrate and spectrum after loading phenytoin sodium.

[0026] Figure 4 The SERS spectra of Example 3 are as follows: (a) Au@SiO2 blank substrate and spectrum after loading 4-MBA; (b) Au@SiO2 blank substrate and spectrum after loading phenytoin sodium.

[0027] Figure 5 The SERS spectra of Example 4 are as follows: (a) Au@SiO2 blank substrate and spectrum after loading 4-MBA; (b) Au@SiO2 blank substrate and spectrum after loading phenytoin sodium.

[0028] Figure 6 The SERS spectra of Example 5 are as follows: (a) Au@SiO2 blank substrate and spectrum after loading 4-MBA; (b) Au@SiO2 blank substrate and spectrum after loading phenytoin sodium.

[0029] Figure 7 The UV-Vis absorption spectra of 50 nm bare gold particles and Au@SiO2 colloid prepared in Example 3 are shown.

[0030] Figure 8 Transmission electron microscopy (TEM) images of the samples from Example 3; (a) 50 nm bare gold particles; (b) Au@SiO2 particles. Detailed Implementation

[0031] This invention provides a two-step seed growth method for preparing gold nanospheres, coating them with a 1-2 nm silica shell, and using them for surface-enhanced Raman scattering (SERS) detection. The method includes: I. Preparation of Au@SiO2 core-shell structured nanoparticles 1. Add 1000–1300 mL of 0.125 mM HAuCl4 solution to a round-bottom flask and heat to a vigorous boil at 120–130 °C with stirring at 450–510 rpm. Quickly add 5–6.5 mL of 500 mM sodium citrate solution and continue the reaction at a boil for 10–20 min to obtain gold seeds of approximately 25 nm. Allow the seed solution to cool naturally; no purification is required. Store at low temperature for later use.

[0032] 2. Place 500 mL of the above seed culture in a double-necked flask and heat to reflux with stirring. When the temperature reaches the reflux temperature of 120–130 °C, slowly add 500 mL of 0.5 mM HAuCl4 solution at a rate of 5–15 mL / min. After the addition is complete, stop heating and allow the mixture to cool naturally to room temperature while stirring. This yields the stock solution of gold spheres approximately 50 nm in size. No purification is required; store at low temperature for later use.

[0033] 3. Centrifuge the above gold nanosphere sol to concentrate it 1-2 times. After concentration, add 50-150 μL of 1wt% polyvinylpyrrolidone (PVP, K30) aqueous solution, stir gently for 5 min, and then carry out subsequent APTMS modification.

[0034] 4. Add 40-60 µL of 1 mM APTMS solution to the concentrated gold nanoparticle solution and stir at 300-500 rpm for 15-40 min at room temperature to allow APTMS to achieve modification through the interaction between amino groups and the gold surface.

[0035] 5. Slowly add 0.5–1.5 mL of 0.54 wt% sodium silicate solution to the above reaction system. The pH value of the sodium silicate solution should be controlled within the range of 5–7. Add 100–300 μL of 0.1 M NaCl, and stir at room temperature at 550–650 rpm throughout the process. After all the sodium silicate solution has been added, continue stirring the reaction system at room temperature and in the dark for 15–25 hours to obtain Au@SiO2 nanoparticles with a silica shell thickness of 1–2 nm.

[0036] II. Nanoparticle Characterization (I) Characterization by ultraviolet-visible absorption spectroscopy Pure gold nanoparticles (approximately 50 nm in diameter) and Au@SiO2 colloidal solution were used. An Agilent BioTek Epoch 2 microplate UV-Vis spectrophotometer was employed to scan the nanoparticles within the wavelength range of 200–800 nm, recording the positions and full width at half maximum (FWHM) of the local surface plasmon resonance absorption peaks. By comparing the changes in the plasmon resonance absorption peak positions of the gold nanospheres before and after coating, the coating condition of the silica shell was determined.

[0037] (II) Transmission electron microscopy characterization 50 nm pure gold nanoparticles and Au@SiO2 colloidal solution were dropped onto a copper mesh support film. After drying, the morphology, particle size distribution and silica shell thickness of the particles were observed using a transmission electron microscope.

[0038] III. SERS Detection Application of Au@SiO2 Core-Shell Nanoparticles A gold nanoparticle sol was mixed with the analyte solution at a 1:1 ratio and dropped onto a glass substrate for Raman spectroscopy. The SERS enhancement effect was assessed based on the intensity of the characteristic peak of the reporter molecule. The analyte included, but was not limited to, one of the reporter molecules: 4-mercaptobenzoic acid (4-MBA), rhodamine 6G (R6G), or p-mercaptoaniline (4-ATP); and included, but was not limited to, one of the complex drugs: phenytoin sodium, levetiracetam, or paroxetine.

[0039] The Raman spectrometer used for detection was an OTO Photonics EE2111, with a spectral response range of 180-1100 nm and an optical resolution of 0.2 nm to 13 nm. The Raman spectroscopy detection conditions included: using 785 nm excitation light as the light source, a laser power of 50–500 mW, and an integration time of 1–30 s.

[0040] The following specific examples illustrate the implementation of the present invention. Those skilled in the art can easily understand other advantages and effects of the present invention from the content disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and various details in this specification can also be modified or changed based on different viewpoints and applications without departing from the spirit of the present invention.

[0041] Example 1 1. Add 1000 mL of 0.125 mM HAuCl4 solution to a round-bottom flask and heat to 120 °C with stirring at 450 rpm until vigorous boiling. Quickly add 5 mL of 500 mM sodium citrate solution and continue the reaction at boiling for 10 min to obtain gold seeds of approximately 25 nm. Allow the seed solution to cool naturally without purification and store at low temperature for later use.

[0042] 2. Place 500 mL of the above seed culture in a double-necked flask and heat to reflux with stirring. When the temperature reaches the reflux temperature of 120°C, slowly add 500 mL of 0.5 mM HAuCl4 solution at a rate of 5 mL / min. After the addition is complete, stop heating and allow the mixture to cool naturally to room temperature while stirring. This yields the stock solution of gold spheres approximately 50 nm in size. No purification is required; store at low temperature for later use.

[0043] 3. Centrifuge the above gold nanosphere sol to concentrate it by 1 time. After concentration, add 50 μL of 1 wt% PVP aqueous solution, stir gently for 5 min, and then carry out subsequent APTMS modification.

[0044] 4. Take the concentrated gold nanoparticle solution and add 40µL of 1mM APTMS solution. Stir at 300rpm for 15min at room temperature to allow APTMS to achieve modification through the interaction between amino groups and the gold surface.

[0045] 5. Slowly add 0.5 mL of 0.54 wt% sodium silicate solution (pH value within 5) to the above reaction system, and add 100 μL of 0.1 M NaCl, stirring at room temperature and 550 rpm throughout the process. After all the sodium silicate solution has been added, continue stirring the reaction system at room temperature and in the dark for 15 hours to obtain Au@SiO2 nanoparticles.

[0046] Test results: Raman spectroscopy was performed on the obtained Au@SiO2. The analytes were 1 mg / mL 4-MBA and phenytoin sodium; the detection conditions were: laser power 300 mW, integration time 5 s. The detection results are as follows: Figure 2 As shown, the black curve represents the pure Au@SiO2 blank control. The blank substrate exhibits only a weak background signal with no obvious clutter interference. In Figure 2(a), after introducing 4-MBA, the signal at 1078 cm⁻¹... -1 1586cm -1 A very strong characteristic peak appears at this point, corresponding to the CS and C=C stretching vibrations of the benzene ring, indicating a significant signal enhancement effect. This suggests that the ultrathin SiO2 shell does not block the SERS enhancement effect of the gold core. Figure 2 (b) shows that after adsorption of phenytoin sodium, the complete set of characteristic fingerprint peaks of the drug molecule can be clearly obtained, with the main peak located at ~1030 cm⁻¹. -1 Each characteristic peak is clearly distinguishable from the blank signal on the substrate, enabling effective identification of drug molecules.

[0047] Example 2 1. Add 1243.45 mL of 0.125 mM HAuCl4 solution to a round-bottom flask and heat to 125 °C with stirring at 480 rpm until vigorous boiling. Quickly add 6.25 mL of 500 mM sodium citrate solution and continue the reaction at boiling for 15 min to obtain gold seeds of approximately 25 nm. Allow the seed solution to cool naturally without purification and store at low temperature for later use.

[0048] 2. Place 500 mL of the above seed culture in a double-necked flask and heat to reflux with stirring. When the temperature reaches the reflux temperature of 125°C, slowly add 500 mL of 0.5 mM HAuCl4 solution at a rate of 10 mL / min. After the addition is complete, stop heating and allow the mixture to cool naturally to room temperature while stirring. This yields the stock solution of gold spheres approximately 50 nm in size. No purification is required; store at low temperature for later use.

[0049] 3. Centrifuge the above gold nanosphere sol to concentrate it by 1.5 times. After concentration, add 100 μL of 1 wt% PVP aqueous solution, stir gently for 5 min, and then carry out subsequent APTMS modification.

[0050] 4. Take the concentrated gold nanoparticle solution and add 50µL of 1mM APTMS solution. Stir at 400rpm for 25min at room temperature to allow APTMS to achieve modification through the interaction between amino groups and the gold surface.

[0051] 5. Slowly add 1 mL of 0.54 wt% sodium silicate solution (pH 6) to the above reaction system, and add 200 μL of 0.1 M NaCl, stirring at room temperature and 600 rpm throughout the process. After all the sodium silicate solution has been added, continue stirring the reaction system at room temperature and in the dark for 20 hours to obtain Au@SiO2 nanoparticles.

[0052] Test results: Raman spectroscopy was performed on the obtained Au@SiO2. The analytes were 1 mg / mL 4-MBA and phenytoin sodium; the detection conditions were: laser power 300 mW, integration time 5 s. The detection results are as follows: Figure 3 As shown, the results indicate that the pure Au@SiO2 substrate exhibits a weak background Raman signal with no obvious interference from impurity peaks. After the introduction of 4-MBA and phenytoin sodium molecules, both analytes showed clear and highest-intensity characteristic fingerprint peaks, demonstrating the excellent SERS enhancement performance of the Au@SiO2 substrate. Simultaneously, UV and electron microscopy were performed on 50nm bare gold nanoparticles and the Au@SiO2 colloidal solution. The UV detection results are shown below. Figure 7As shown, compared to pure gold particles, the plasmon resonance absorption peak of Au@SiO2 exhibits a slight red shift and a significant increase in absorption intensity. This spectral change confirms that a thin layer of silica was successfully coated onto the surface of the gold particles. Transmission electron microscopy results are shown below. Figure 8 Further intuitive verification showed that the gold nanospheres were coated with a silica shell with a thickness of 1-2 nm.

[0053] Example 3 1. Add 1293.5 mL of 0.125 mM HAuCl4 solution to a round-bottom flask and heat to 130 °C with stirring at 510 rpm until vigorous boiling. Quickly add 6.5 mL of 500 mM sodium citrate solution and continue the reaction at boiling for 20 min to obtain gold seeds of approximately 25 nm. Allow the seed solution to cool naturally without purification and store at low temperature for later use.

[0054] 2. Place 500 mL of the above seed culture in a double-necked flask and heat to reflux with stirring. When the temperature reaches the reflux temperature of 130°C, slowly add 500 mL of 0.5 mM HAuCl4 solution at a rate of 15 mL / min. After the addition is complete, stop heating and allow the mixture to cool naturally to room temperature while stirring. This yields the stock solution of gold spheres approximately 50 nm in size. No purification is required; store at low temperature for later use.

[0055] 3. Centrifuge the above gold nanosphere sol to concentrate it twice. After concentration, add 150 μL of 1 wt% PVP aqueous solution, stir gently for 5 min, and then proceed with subsequent APTMS modification.

[0056] 4. Take the concentrated gold nanoparticle solution and add 60µL of 1mM APTMS solution. Stir at 400 rpm for 40 min at room temperature to allow APTMS to achieve modification through the interaction between amino groups and the gold surface.

[0057] 5. Slowly add 1.5 mL of 0.54 wt% sodium silicate solution (pH 7) to the above reaction system, and add 300 μL of 0.1 M NaCl, stirring at room temperature and 600 rpm throughout the process. After all the sodium silicate solution has been added, continue stirring the reaction system at room temperature and in the dark for 25 hours to obtain Au@SiO2 nanoparticles.

[0058] Test results: Raman spectroscopy was performed on the obtained Au@SiO2. The analytes were 1 mg / mL 4-MBA and phenytoin sodium. The detection conditions were: laser power 300 mW, integration time 5 s. The detection results are as follows: Figure 4As shown, the results indicate that the pure Au@SiO2 substrate exhibits a weak background Raman signal with no obvious interference from impurity peaks; the characteristic fingerprint peaks of the analytes 4-MBA and phenytoin sodium can be clearly detected, demonstrating that the Au@SiO2 substrate can effectively recognize drug molecules.

[0059] The above embodiments are for illustrating the implementation schemes disclosed in this invention and should not be construed as limiting the invention. Furthermore, various modifications listed herein, as well as variations in the methods and compositions of the invention, will be apparent to those skilled in the art without departing from the scope and spirit of the invention. Although the invention has been specifically described in conjunction with various specific preferred embodiments, it should be understood that the invention should not be limited to these specific embodiments. In fact, various modifications as described above that are obvious to those skilled in the art to obtain the invention should be included within the scope of this invention.

Claims

1. A method for preparing gold nanoparticles coated with silica, the method comprising the following steps: 1) Preparation of gold seeds with an average particle size of 25 nm; 2) Prepare gold sphere stock solution with a particle size of 50 nm using gold seeds; 3) Take the gold ball stock solution, concentrate it, and add a protective stabilizer; 4) Add APTMS solution and stir; 5) Add sodium silicate solution, control the pH of sodium silicate solution to 5-7, add NaCl, stir, protect from light, and react for 15-24 hours.

2. The method according to claim 1, characterized in that: The method for step 1) is as follows: heat the HAuCl4 solution while stirring until it boils, add sodium citrate solution, and continue the reaction for 10-20 minutes while maintaining the boiling state.

3. The method according to claim 1, characterized in that: Step 2) involves taking the gold seed solution, heating it to reflux, and when the temperature reaches the reflux temperature of 120-130℃, adding HAuCl4 solution at a rate of 5-15 mL / min. After the addition is complete, heating is stopped, and stirring is maintained while cooling.

4. The method according to claim 1, characterized in that: Step 3) involves centrifuging the above gold nanosphere sol to concentrate it 1-2 times, adding a protective stabilizer after concentration, and stirring.

5. The method according to claim 1, characterized in that: Step 4) involves adding the concentrated gold nanoparticle solution to APTMS solution and stirring.

6. The method according to claim 1, characterized in that: Step 5) involves slowly adding sodium silicate solution (pH 5-7) to the reaction system, along with NaCl, and stirring. After all the sodium silicate solution has been added, the reaction system is kept under light-protected conditions and stirred for 15-25 hours.

7. The method according to claim 1, characterized in that: The protective stabilizer may be selected from any one or more of PVP aqueous solution, polyethylene glycol PEG, polyethyleneimine PEI, sodium citrate, and phytic acid IP6.

8. Gold nanoparticles prepared by the method according to any one of claims 1-7.

9. The application of gold nanoparticles as described in claim 8 in surface-enhanced Raman scattering detection technology.

10. A product detection technique using surface-enhanced Raman scattering, characterized in that, The product comprises the gold nanoparticles as described in claim 8.

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