WO2013022152A1 - Method for manufacturing metal nanoparticles having surface-enhanced raman scattering activity using cyclodextrin, and biosensor including the metal nanoparticles manufactured using the method - Google Patents

Abstract

The present invention relates to a method for manufacturing metal nanoparticles having surface-enhanced Raman scattering (SERS) activity, which is characterized in that the method comprises a step of mixing an aqueous metal salt solution, an aqueous cyclodextrin solution, and an aqueous sodium hydroxide solution. In the method for manufacturing the metal nanoparticles according to the present invention, metal salts are reduced through a one-pot process using cyclodextrin in an aqueous solution at room temperature, thereby simplifying the process and achieving superior processing efficiency. In addition, since the cyclodextrin functions as a reducing agent and as a protecting agent in the aqueous solution, making a separate organic reducing agent unnecessary, the manufacturing process is environmentally-friendly. The metal nanoparticles can be obtained in various shapes and sizes, such as a sphere, a polygon, a nanorod, a nanowire, a nanoflower, etc., simply by controlling the concentrations of reactants and the reaction temperature. Further, the thus-obtained various kinds of metal nanoparticles have superior SERS activity and can therefore be applied in a biosensor for detecting biomaterials in the field of biomedicine.

Description

Method for producing metal nanoparticles having surface enhanced Raman scattering activity using a cyclodextrin and biosensor comprising metal nanoparticles prepared accordingly

The present invention relates to a method for producing metal nanoparticles having surface enhanced Raman scattering activity, and more particularly, by using a cyclodextrin that simultaneously acts as a reducing agent and a protective agent in the process of one-pot process, the metal nanoparticles from the metal salt simply It relates to a manufacturing method.

Precious metal nanoparticles such as gold or silver have special electronic, optical, and mechanical properties, and as a result, researches for synthesizing precious metal nanoparticles in various sizes and shapes are possible in various applications in microelectronics, chemical sensors, catalysts, and medical fields. Actively done.

Among them, silver nanoparticles are of particular interest due to their unique physical and chemical properties. Surface plasmon resonance and light scattering of silver nanoparticles can be used to recognize molecules or molecular labels, and the size and shape of nanoparticles play a very important role in determining their properties. The shape and the like are reported to vary depending on the manufacturing method and the conditions thereof.

Silver nanoparticles are chemically reduced, thermally decomposed, ultrasonically irradiated with ultrasonic waves, sonochemical methods, photo-induced reactions, electrochemical reduction methods, template methods, biochemical reduction methods in aqueous and organic solutions. It is manufactured by various methods, and the chemical reduction method is a method that can produce a large amount of nanoparticles in a relatively short time. However, organic solvents and reducing agents used in such chemical reduction methods have strong toxicity and may be harmful to the human body and may cause environmental pollution.

Therefore, there is an urgent need to develop a method of synthesizing silver nanoparticles in a one-pot process using a non-toxic and biocompatible material, and acting as a reducing agent, without going through several steps in an aqueous solution. to be.

In particular, it is necessary to develop a manufacturing method that can improve the purity of the final material as well as cost reduction during manufacturing, while preventing the human and environmental hazards described above. It is necessary to provide an optical nanodevice that can be modified by biological detection.

In the prior art, Korean Patent No. 10-1029138 describes a method for producing gold or silver nanoparticle films having surface enhanced Raman scattering activity, and Korean Patent No. 10-0838254 describes a method for preparing silver colloids.

Therefore, the first problem to be solved by the present invention is to use a cyclodextrin in room temperature, aqueous solution without using additional reducing agent, using a silver nitrate in a simple one-pot reaction to produce silver nanoparticles The present invention also provides a method for preparing silver nanoparticles having various shapes and sizes.

The second problem to be solved by the present invention is to provide a biosensor using the silver nanoparticles prepared by the manufacturing method as a substrate for surface-enhanced Raman scattering (SERS).

The present invention to achieve the first object,

Metal salt aqueous solution; Cyclodextrin aqueous solution; And it provides a method for producing metal nanoparticles comprising the step of mixing ;.

According to one embodiment of the invention, the cyclodextrin may be any one selected from α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, the base is any selected from sodium hydroxide, calcium hydroxide and magnesium hydroxide It can be one.

According to another embodiment of the present invention, the metal salt may be a metal salt including any one metal selected from Au, Ag, Pt, Pd, Ru, Rh, Fe, Co, Ni, Cu, Zn and Ti. .

According to another embodiment of the present invention, the metal salt is _{AgNO 3, AgCl, AgBr, AgI} , CH 3 COOAg, AgBF 4, KAuCl 4, NaAuCl 4 · xH 2 O, NaAuBr 4 · xH 2 O, AuCl 3, AuBr ₃ , AuCl and mixtures thereof.

According to another embodiment of the present invention, the metal nanoparticles are characterized in that they are capped with cyclodextrin.

According to another embodiment of the present invention, by adjusting one or more of the concentration of the cyclodextrin, the concentration of the base and the reaction temperature during the reaction can be adjusted to the size and shape of the metal nanoparticles, respectively.

According to another embodiment of the present invention, the concentration of the metal salt is 2-10 mM, the concentration of the cyclodextrin is 2-10 mM, the concentration of the base is 2-60 mM, and the reaction temperature is 4-80 ° C. Independently adjusting the size and shape of the metal nanoparticles can be adjusted respectively.

According to another embodiment of the present invention, the diameter of the metal nanoparticles may be 1 nm-1 μm.

The present invention to achieve the second object,

A surface-enhanced Raman scattering (SERS) substrate comprising metal nanoparticles capped with cyclodextrin prepared according to the preparation method; Raman probes; laser; And it provides a bio sensor comprising a Raman detector.

According to an embodiment of the present invention, the Raman probe may be P-aminothiophenol.

The method for preparing metal nanoparticles according to the present invention can be easily prepared in a one-pot process by reducing metal salts using cyclodextrins at room temperature and in aqueous solution, and thus has excellent process efficiency, and cyclodextrins are reducing agents and It is an environmentally friendly process because it does not need to add other organic reducing agents as a protective agent, and it is a metal nano having various shapes and sizes such as spheres, polygons, nanorods, nanowires, and nanoflowers by only controlling the concentration and reaction temperature of the reactants. Allows the preparation of the particles. In addition, the various metal nanoparticles thus prepared have excellent surface-enhanced Raman scattering (SERS) activity, it can be used as a biosensor for detecting biomaterials in the biomedical field.

1A is a UV-vis absorption spectrum of silver nanoparticles prepared according to Synthesis Example 1, FIG. 1B is a graph showing the average size of silver nanoparticles, and FIG. 1C is an XRD diffraction pattern.

2 is a UV-vis spectrum of silver nanoparticles prepared according to Synthesis Examples 5, 4, 1, 6 ( NaOH concentration 5, 10, 20, 40 mM, respectively) of the present invention.

3 is a UV-vis spectrum of silver nanoparticles prepared according to Synthesis Examples 2 and 3. FIG.

4 is a UV-vis spectrum of silver nanoparticles prepared according to Synthesis Examples 7, 8.

5 is the FT-IR spectrum (a) of the CD itself, FT-IR spectrum (b) of the CD capping silver nanoparticles according to Synthesis Example 1 of the present invention.

FIG. 6 is a PATP Raman spectrum and a PATP Raman spectrum on a silver substrate. FIG. 6A is a synthesis example 5, FIG. 6B is a synthesis example 4, FIG. 6C is a synthesis example 1, and FIG. 6D is a Raman spectrum of the synthesis example 6. FIG.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The present invention is to prepare a metal nanoparticles by mixing a metal salt aqueous solution and a cyclodextrin aqueous solution, and mixed with a sodium hydroxide aqueous solution to the mixture solution at room temperature, without adding a separate reducing agent or protective agent, one-pot in an aqueous solution It is characterized in that the manufacturing simply.

The present invention uses a dimethyl formamide, ethanol, methanol, ethylene glycol, sodium citrate and the like as a reducing agent in the prior art, the human body that occurs when the metal nanoparticles are produced by reducing the reaction by heating at 60 ℃ or more in an aqueous solution, As an improvement in environmental hazards and an increase in process cost, the metal nanoparticles having different shapes and sizes are prepared using cyclodextrins which simultaneously act as reducing agents and stabilizers at room temperature.

Cyclodextrin used in the present invention is a water-soluble, non-toxic organic macrocyclic material, consisting of D-(+)-glucopyranose bound by α-1,4-linkage ( Α-, β-, and γ-cyclodextrins are usually composed of 6-8 units) to form complexes containing various guest molecular materials, followed by host-guest interactions, molecular sieve detection, drug carriers, and catalysts. Used in foods, cosmetics, pesticides, etc.

In the present invention, any one selected from α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin was used, and preferably, metal nanoparticles can be prepared using β-cyclodextrin.

Metal nanoparticles can be used in various fields depending on their shape and size. For example, polygonal and spherical nanoparticles can be used as SERS spectroscopy, flower forms as catalysts, and nanorod forms can be utilized in flexible devices. have. As described above, the metal nanoparticles should be manufactured in various sizes and shapes. The present invention can independently control one or more of the concentration of cyclodextrin, the concentration of sodium hydroxide, and the reaction temperature, respectively, to control the size and shape of the metal nanoparticles. It is characterized by being.

According to the present invention, cyclodextrins can be used to prepare stable metal nanoparticles, in particular silver nanoparticles at room temperature without the use of additional reducing agents and without the consumption of additional energy, and also by using cyclodextrin at room temperature. Silver nanoparticles can be produced in various shapes and sizes.

In particular, the synthesis of the nanoparticles according to the present invention can be easily prepared by the one-pot reaction of silver nitrate (AgNO ₃ ) using cyclodextrin (CD) in room temperature, alkali aqueous solution. CD is a non-toxic, biocompatible, water-soluble macrocycle organic material and prepared in a positive aqueous solution, making the reaction process simpler and more environmentally friendly. Furthermore, in the present invention, silver nanoparticles of various sizes and shapes may be prepared by changing reaction conditions such as concentration of reactants and reaction temperature. That is, spherical, polygonal, rod, flower, and wire-shaped nanoparticles may be prepared in an aqueous alkali solution using β-cyclodextrin not separately treated under different reaction conditions.

In addition, in the present invention, when silver nanoparticles are used as a substrate for surface-enhanced Raman scattering (SERS), and p-amino-thiophenol (PATP) is used as a Raman probe, the silver nanoparticles are bonded by silver nanoparticles in the composite of the silver nanoparticles. It can induce enhanced Raman scattering effect than individual silver nanoparticles, which can be utilized in biosensors capable of detecting biomaterials in the biomedical field.

Hereinafter, the present invention will be described in more detail with reference to preferred examples. However, these examples are intended to illustrate the present invention in more detail, it will be apparent to those skilled in the art that the scope of the present invention is not limited thereby.

<Example>

The cyclodextrin (β-Cyclodextrin), silver nitrate (AgNO ₃ ), and PATP (p-aminothiophenol) used in the present invention were purchased from Aldrich and used without further purification, and NaOH was purchased from DC Chemical and used without any treatment.

Synthesis Example 1. Synthesis of Silver Nanoparticles (Ag-1)

1 mL of an aqueous solution of silver nitrate (AgNO ₃ , 5 mM) and 1 mL of an aqueous solution of cyclodextrin (CD, 5 mM) were mixed at room temperature, followed by mixing 2 mL of an aqueous NaOH solution (20 mM). After shaking gently for 1 minute for homogenization, it was left at room temperature for one day. The first dark brown solution turned to a yellow solution after 12 hours, indicating that silver nanoparticles were formed in the solution.

Synthesis Examples 2 to 8. Synthesis of Silver Nanoparticles (Ag-2 to Ag-8)

It was prepared in the same manner as in Synthesis example 1, except that nitric acid was prepared by varying the concentration, the concentration of CD, and the reaction temperature as shown in Table 1 below.

Reaction conditions and physical properties thereof for each synthesis example are shown in the following [Table 1].

Table 1

division	Silver Nitrate / CD Concentration (mM)	NaOH concentration (mM)	Reaction temperature (℃)	Average diameter (nm)	shape
Synthesis Example 1 (Ag-1)	5/5	20	25	34.50 ± 5.69	polygon
Synthesis Example 2 (Ag-2)	2.5 / 5	20	25	9.23 ± 1.35	rectangle
Synthesis Example 3 (Ag-3)	5 / 2.5	20	25	32.24 ± 7.66	wire
Synthesis Example 4 (Ag-4)	5/5	10	25	54.46 ± 12.94	Flower form
Synthesis Example 5 (Ag-5)	5/5	5	25	146.49 ± 28.73	Ant-like
Synthesis Example 6 (Ag-6)	5/5	40	25	24.79 ± 5.14	Flower-form
Synthesis Example 7 (Ag-7)	5/5	20	4	19.22 ± 4.34	Rod or spherical
Synthesis Example 8 (Ag-8)	5/5	20	65	12.80 ± 0.99	rectangle

Synthesis Example 9 Synthesis of Gold Nanoparticles

It was prepared in the same manner as the preparation of the silver nanoparticles, using KAuCl ₄ as a precursor, 4 mL NaOH aqueous solution (40 mM) was mixed, and after one week it was red wine red. It was found that gold nanoparticles were formed by this.

As such, various metal nanoparticles as well as silver and gold nanoparticles can be synthesized by the production method of the present invention synthesized at room temperature and aqueous solution using cyclodextrin without using a separate toxic organic reducing agent and a protecting agent.

Example 1 Preparation of Silver Nanoparticles (PATP-coated AgNPs) Coated with PATP

The CD-capped-AgNPs colloidal solution capped with CD obtained in Synthesis Example 1 was centrifuged at 4000 rpm for 15 minutes, the supernatant was discarded and the remaining residue was dispersed in 1 mL of ionized water. 500 uL of PTAP ethanol solution (0.1 M) was mixed and left at room temperature for 3 hours. The surface of the silver nanoparticles capped with CD was coated with PTAP to form silver nanoparticles coated with PATP. It was centrifuged at 4000 rpm for 10 minutes, and excess CD and PTAP were removed to separate silver nanoparticles coated with PATP.

The separated PTAP-AgNP was mounted on a SERS glass substrate to measure SERS.

Experimental Example 1. Confirmation of physical properties of silver nanoparticles

The physical properties of the silver nanoparticles obtained according to Synthesis Example 1 were confirmed. 1A shows UV-vis absorption spectra representing surface plasmon resonance bands of AgNPs at 414 nm, and TEM images of silver nanoparticles show that most of the nanoparticles have a polygonal shape and are self-assembled. It can be seen that the silver nanoparticles are face-centred cubic structure (face-centred cubic structure). In addition, as shown in Figure 1b, the size of the silver nanoparticles was 28.81-40.19 nm. Figure 1c is a result of analyzing the XRD diffraction for the silver nanoparticles, it can be seen that the shape of the silver nanoparticles is a single face-centered structure.

Experimental Example 2. Confirmation of physical properties of silver nanoparticles prepared by varying NaOH concentration

UV-vis absorption spectra for the Ag-5, Ag-4, Ag-1, and Ag-6 prepared by varying NaOH concentrations of 5, 10, 20, and 40 mM, respectively, are shown in FIG. 2. That is, when the NaOH concentration was changed from 40 mM to 5 mM, the absorption peak of the silver nanoparticles shifted from 410 nm to 420 nm. This is due to the increase in particle size and dispersion.

In addition, as a result of analyzing the TEM image, when the NaOH concentration was 5 mM, the silver nanoparticles were self-assembled to have a polygonal or ant-like shape, and when the concentration was 10 mM, the nanoflower form was shown. In addition, in the case of 20 mM, a well-dispersed polygonal form was shown, and in the case of 40 mM, a flower form was shown. However, it can be seen that the flower shape is also a shape in which several polygonal nanoparticles are self-assembled when viewed in a higher resolution TEM image.

At 40, 20, 10, and 5 mM NaOH concentrations, the nanoparticles were 24.79 ± 5.14, 34.50 ± 5.69, 54.46 ± 12.94 and 146.49 ± 28.73 nm, respectively. As the NaOH concentration decreased, the particle size decreased, and the peak shifted to a red color in the UV-vis absorption spectrum. This is because the nanoparticles aggregate at low concentrations to form a complex form or a branched form.

CD structurally has a truncated cone-like structure with a hollow, truncated cone-like structure and has a unique structure in which -OH groups on the surface are bonded to -OH groups on adjacent torus structures. It is also a substance with water-soluble properties and non-toxic. Because of these properties, CD enables the adsorption, reduction and growth of metal particles at the nanoscale. The CD has a -OH group, which enables reduction of Ag ⁺ in an aqueous alkali solution.

NaOH serves to deprotonate the OH group of the CD and thereby stabilize it while increasing the reactivity of the nanoparticles. Reaction with only CD material without NaOH cannot reduce the silver salt to silver nanoparticles. It can be seen that the CD material reduces silver salts to silver nanoparticles in the presence of NaOH, and serves as a capping material of silver nanoparticles. In addition, silver nanoparticles do not form upon reaction with the CD material under acidic conditions.

Thus, CD functions as a reducing and protecting agent under basic conditions, and basic conditions deprotonate the OH group of the CD. As the concentration of NaOH decreases, the reduction by CD material and the stabilization of nanoparticles decrease, and the size of the particles increases due to the aggregation of nanoparticles. However, as the concentration of NaOH increased, the CD was less strongly coated on the silver nanoparticles, resulting in agglomeration of nanoparticles.

Experimental Example 3. Confirmation of physical properties of silver nanoparticles according to metal salt and CD concentration

In FIG. 3, UV-vis spectra of silver nanoparticles are shown for the case where the concentration of CD is 5 mM (Synthesis Example 2) and 2.5 mM (Synthesis Example 2). As the concentration of CD was changed from 5 mM to 2.5 mM, the peak of the silver nanoparticles shifted from 414 nm (FIG. 1A) to 417 nm (FIG. 3). This is due to the change in particle size and dispersibility. In contrast, the peak of surface plasmon resonance was lower in intensity as the concentration of silver nitrate was changed from 5 mM to 2.5 mM. This is because the size of the particles is smaller and there is a change in dispersibility.

This can also be confirmed in the TEM image. Synthesis Example 3 shows that the silver nanoparticles are self-assembled to show the nanowire shape, and the wire shape is well maintained by the CD. The size of the self-assembled nanoparticles is 32.24 ±. At 7.66 nm, the wire form constitutes a pack in which polygonal nanoparticles are closely coupled.

As the concentration of CD decreases, the silver nanoparticles do not aggregate to form one large particle, and each nanoparticle shows a shape in which wires are aligned. This is because secondary bonding occurs between the -OH groups on the surface of the CD-coated particles, and therefore, it can be seen that CD can act as a binder with the molecular sieve.

In Synthesis Example 2, the concentration of silver salt is low, whereas on the other hand, when the concentration of CD is high, the particles show a spherical shape, and the size also decreases to 9.23 ± 1.35 nm. That is, as the concentration of CD increases, the binding of silver and CD increases, and CD plays a role of protecting silver nanoparticles during the growth of nanoparticles, thereby inhibiting the growth of particles and decreasing their size.

Experimental Example 4. Confirmation of physical properties of silver nanoparticles according to reaction temperature

Physical properties of silver nanoparticles according to the reaction temperature, dispersibility, etc. were confirmed. To this end, Synthesis Examples 1, 7, 8 were all prepared by varying the temperature at room temperature (25 ° C), 4 ° C, 65 ° C under the same conditions of AgNO ₃ 5 mM, CD 5 mM, NaOH 20 mM, respectively.

Ag-8 prepared at 65 ° C. had a size of 12.80 ± 0.99 nm, which was smaller than that produced at room temperature. This is because the activity between the silver salt and the CD increases at high temperature, so crystal nuclei are formed quickly and smaller spherical particles are formed, and CD is well protected from the silver nanoparticles, thereby inhibiting the growth of the particles. In contrast, in the case of AG-7 manufactured at 4 ° C., small spherical particles are bonded to each other to form a rod-shaped structure (size 19.22 ± 4.34 nm). This is because reaction conditions, which play an important role in the growth of metal structures, have been slowed down. During the temperature increase from 4 ° C. to 65 ° C., the size of the nanoparticles decreased and there was a shift in the weak blue light absorption peak at 500-800 nm.

Experimental Example 5. Confirmation of interaction between nanoparticles and CD

In order to investigate the CD interaction of the nanoparticles, the FT-IR spectra of CD and CD capped silver nanoparticles were confirmed, respectively.

The silver nanoparticles alone are not characteristic in the spectrum, and the CD FT-IR spectrum of the CD itself and the FT-IR spectrum of the silver-capped CD nanoparticles are shown in FIG. 5. Both spectra showed almost similar shapes except for new peaks of CD-capped-AgNPs appearing at 1384 cm ⁻¹ . In other words, it can be seen that CD is an indispensable element in nanoparticles.

The peaks seen at 1384 cm ⁻¹ and 1644 cm ⁻¹ are due to symmetric and asymmetric carboxylate ions. This is because in the absence of other reducing agents, the CD acts as a reducing agent, oxidizes itself to form carboxylic acids, and is effectively capped on the surface of the silver nanoparticles.

CD's own 946 cm ^-1 (skeletal vibration involving a-1,4 linkag), 759 cm ^-1 (ring-breathing-vibration), 708 cm ^-1 (pyranose ring vibration), 574 cm ^-1 (pyranose ring vibration) spectrum peak Was decreased in CD-capped AgNPs because the CD was fixed and the pyranose ring vibration and skeletal vibration were inhibited. In the CD-capped AgNPs spectrum, -OH shift was observed from 3391 cm ⁻¹ to 3416 cm ⁻¹ , which is due to the interaction between CD and silver nanoparticles.

Cavities of CD without polarity (inner diameter 780 pm) are known to form host-guest complexes of various hydrophobic molecules. Silver atoms (288 pm) or silver nanoparticles of 1 nm or less may form a complex in the cavity of the CD. However, the silver nanoparticles according to the present invention have a size larger than 780 pm to form a complex in the internal cavity of the CD.

Experimental Example 6. Surface-Enhanced Raman Scattering (SERS) Activity

PATP was used as a probe to measure SERS activity of silver nanoparticles. 6 is a result of measuring the wavelength and intensity of the relative shifted by the thiol group of PATP bonded to the surface of the silver nanoparticles and the Raman spectrum of PATP itself on the SERS substrate. As shown in FIG. 6A, the Raman spectrum measured from the silver nanoparticles prepared according to Synthesis Example 5 has a ₁ oscillation mode such as v (CC) and v (CS) at 1597 cm ⁻¹ and 1078 cm ⁻¹ . in-plane, in-phase modes) dominated. In addition, the peak disappeared at 467 cm ⁻¹ , and a peak was observed at 388 cm ⁻¹ as a vibration mode enhanced by CS coupling. In addition, b ₂ oscillation mode (in-plane, in-phase mode) was observed at 1489, 1179, and 1003 cm ^-1 , due to the transfer of the charge of the metal to the adsorbed molecules, whereby the silver nanoparticle surface It can be seen that a strong Ag-S bond was formed by the interaction of PTAP molecules at. The charge transfer couples the metal orbital and the orbital of the molecular sieve, resulting in Raman resonance at lower energy. Aggregation of nanoparticles plays an important role in the SERS effect. Aggregation of silver nanoparticles occurs by coupling of silver nanoparticles rather than separate individual silver nanoparticles, resulting in a stronger SERS effect.

As such, the shape and size of the nanoparticles vary according to the reaction conditions for preparing the silver nanoparticles, and as a result, the intensity of the SERS signal for each silver nanoparticle is changed.

6A to 6D are results for silver nanoparticles produced under different conditions with NaOH concentrations of 5, 10, 20, and 40 mM, respectively. As the NaOH concentration decreases, the nanoparticles agglomerate and increase in size, and the agglomeration and size change of the silver nanoparticles are confirmed by the difference in the CD concentration. In other words, as the NaOH concentration decreases and as the CD concentration decreases, the particle size increases and thus the intensity of the SERS signal increases. Similarly, the SERS signal is weaker in silver nanoparticles produced at 65 ° C than silver nanoparticles produced at 4 ° C. This is also because the size of the silver nanoparticles is reduced.

Therefore, according to the present invention, silver nanoparticles protected by CD, which can be manufactured in various sizes and shapes, can be utilized as a biosensor for efficiently detecting a label using SERS substrate.

Claims (10)

1. Metal salt aqueous solution; Cyclodextrin aqueous solution; And a base; mixing the metal nanoparticles.
2. The method of claim 1,

   The cyclodextrin is any one selected from α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin, the base is prepared of metal nanoparticles, characterized in that any one selected from sodium hydroxide, calcium hydroxide and magnesium hydroxide Way.
3. The method of claim 1,

   The metal salt is a method for producing metal nanoparticles, characterized in that the metal salt containing any one metal selected from Au, Ag, Pt, Pd, Ru, Rh, Fe, Co, Ni, Cu, Zn and Ti.
4. The method of claim 3, wherein

   The metal salt is selected from AgNO ₃ , AgCl, AgBr, AgI, CH ₃ COOAg, AgBF ₄ , KAuCl ₄ , NaAuCl ₄ · xH ₂ O, NaAuBr ₄ · xH ₂ O, AuCl ₃ , AuBr ₃ , AuCl and mixtures thereof Method for producing a metal nanoparticles, characterized in that any one.
5. The method of claim 1,

   The metal nanoparticles are capped with cyclodextrin manufacturing method of metal nanoparticles, characterized in that.
6. The method of claim 1,

   Method for producing a metal nanoparticles, characterized in that the size and shape of the metal nanoparticles can be adjusted by adjusting one or more of the concentration of the cyclodextrin, the concentration of the base and the reaction temperature of the mixing step.
7. The method of claim 6,

   The metal salt concentration of 2-10 mM, the cyclodextrin concentration of 2-10 mM, the base concentration of 2-60 mM, the reaction temperature is independently adjusted to 4-80 ℃ of the metal nanoparticles Method for producing metal nanoparticles, characterized in that the size and shape can be adjusted respectively.
8. The method of claim 1,

   The diameter of the metal nanoparticles is a manufacturing method of metal nanoparticles, characterized in that 1 nm-1 ㎛.
9. Surface-enhanced Raman scattering (SERS) substrate comprising metal nanoparticles capped with cyclodextrin prepared according to claim 1; Raman probes; laser; And a Raman detector.
10. The method of claim 9,

    The Raman probe is a biosensor, characterized in that the P-aminothiophenol.

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