WO2019147056A1 - Method for manufacturing metal nanocube with controlled edge sharpness index - Google Patents

Abstract

The present invention relates to a method for manufacturing a metal nanocube with a controlled edge sharpness index, comprising a step of reacting with a first surfactant and a predetermined surface protective agent; a method for preparing a metal nanocube aggregate having a purity of 95% or more, comprising a step of centrifuging in the presence of a second surfactant; a probe composition comprising the metal nanocube or metal nanocube aggregate prepared by the method; and a gold (Au) nanocube having an average edge length of 20 nm or less.

Description

Manufacturing method of metal nanocubes with controlled edge sharpness index

The present invention relates to a method for preparing a metal nanocube having an edge sharpness index controlled, comprising the step of reacting with a first surfactant and a predetermined surface protecting agent; A step of centrifuging in the presence of a second surfactant; a method for producing a metal nanocube aggregate having a purity of 95% or more; A probe composition comprising a metal nanocube or a metal nanocube aggregate prepared by the above method; And gold (Au) nanocubes having an average edge length of 20 nm or less.

Localized surface plasmon resonance (LSPR) is a unique feature of plasmonic nanostructures that makes it applicable to a variety of applications including sensing, bioimaging, therapeutics, nonlinear optics and catalysis. Since the LSPR is mainly influenced by the size and shape of the plasmonic nanostructure, various studies on precise structure control have been performed. Fundamental nanostructures such as gold nanospheres and gold nanorods have been extensively studied over decades. For example, a cyclic process of growth and oxidative etching has been developed to produce a gold spheres that are highly-smooth and highly spherical. In addition, attempts have been made to adjust the aspect ratio and facet morphology of gold nano rods to obtain an LSPR suitable for the application field. Concave AuNC and tetrahexahedron structures have been fabricated in gold nanocubes (AuNCs), which are known to exhibit increased plasmon properties due to the edges and planes perpendicular to the edges, but with variable size and sharpness control Was not implemented. Methods for synthesizing AuNCs based on seed-mediated growth reactions have been proposed, but low reproducibility limits the use of effective and feasible AuNCs. Low reproducibility could be partially solved by universal gold nanoparticle seeds obtained through iterative oxidative dissolution and re-growth reaction. However, complex and time-consuming seed-preparation procedures make it difficult to synthesize AuNCs with ease.

The inventors of the present invention have made intensive researches to find an easy and feasible method for manufacturing metal nanocubes with high precision in size and shape, especially with sharpness of corner sharpness, and as a result, they have found that fine adjustment of surface- the nanocubes can be precisely controlled by controlling the growth rate by fine-tuning, and can be purified in a form-selective manner by a simple coagulation step to obtain metal nano-cubes with a yield of 95% or higher. The present inventors have confirmed that the metal nano-cube structures having precisely controlled shapes can be used in various fields by controlling their optical properties and completed the present invention.

According to one aspect of the present invention, there is provided a method for manufacturing a metal nanocube having a corner sharpness index (CSI) adjusted, wherein the surface area of the metal nanocube to be finally produced and the CSI index Determining the amount of surface-protecting agents to be added as a base in the following mixed aqueous solution production step; Preparing a mixed aqueous solution by mixing a first surfactant, an amount of a surface protective agent determined according to the surface protective agent amount crystallization step, and metal nanoparticles having an average diameter of 3 to 30 nm to prepare a mixed aqueous solution; And a metal ion precursor adding step of adding a reducing agent and a precursor solution containing a metal ion to the mixed aqueous solution to cause the metal ions to react with the precursor solution, wherein the metal is selected from the group consisting of gold (Au), silver (Ag), palladium (Pd) (Cu), aluminum (Al), lead (Pb), or a combination thereof.

In another aspect, the present invention provides a method for preparing a metal nanocube, comprising centrifuging a solution containing a metal nanocube, recovering the precipitate and redispersing the solution in a solution, centrifuging and redispersing; And a second surfactant addition and centrifugation step in which the second surfactant is added to the redispersed solution and centrifuged, thereby producing a metal nanocube aggregate having a purity of 95% to 99.9% .

In another aspect, the present invention relates to metal nanocubes prepared by the above methods; Or a metal nanocube aggregate.

In another aspect, the present invention provides a gold (Au) nanocube having an average of edge lengths of 20 nm or less.

Hereinafter, the present invention will be described in detail.

The present invention relates to a method of growing nanocubes having a diameter of from about 10 nm to about 10 nm and a diameter of from several tens nm to several hundreds of nm from a metal nanoparticle having a diameter of about 10 nm, based on the discovery that the addition of a small amount of NaBr to provide bromide ions as a noble metal-protecting agent can control the edge shape, e.g., sharpness or roundness, of the nanocubes being formed. Specifically, the amount of bromide ions required is proportional to the surface area of the final formed nanocube. When the bromide ion is added in a multiple of a specific range, sharp corners are formed. In the case of addition in a range other than the range, nanocubes having rounded corners are formed Further, when excess bromide ion was added at a specific level or higher, it was not possible to grow into a certain type of particles, but various types of particle mixture were produced.

Further, in the case of particles prepared in such a predetermined size and shape, when the particles are dispersed and centrifuged in a surfactant solution, it is found that the space is compressed between the particles of the same size and shape by the osmotic pressure, . Therefore, by using this phenomenon, particles having the same size and shape, for example, particles having a deviation of 10% or less in terms of size and edge sharpness can be purified to a high purity of 95% or more.

In the present invention, a corner sharpness index (CSI) is defined by an edge length (EL) and a corner radius (CR) of a manufactured nanocube, as shown in Equation 1 below Value is a measure of the shape of the edge of the nanocube, specifically, the degree of sharpness or roundness of the edge, and has a value close to 1 as the edge is sharp.

[Formula 1]

In this case, EL and CR can be defined as the radius of a circle perfectly matching the corner curvature and the shortest distance from one point on the flat surface of the nanocube to the other surface parallel thereto.

The metal used in the metal nanocubes of the present invention may be, for example, a noble metal. The metal may be a material exhibiting localized surface plasmon resonance. The metal may be, but is not limited to, gold (Au), silver (Ag), palladium (Pd), platinum (Pt), copper (Cu), aluminum Do not. Specifically, the metal may be gold, silver, palladium, platinum, copper, or a combination thereof. In the embodiment of the present invention, a metal nano-cube, that is, AuNC was produced using gold, which is a representative noble metal.

In the production method of the present invention, metal nanoparticles having an average diameter of 3 to 30 nm can be used as seed particles. Specifically, the average diameter of the metal nanoparticles may be 5 to 30 nm, or 6 to 30 nm, more specifically 5 to 15 nm, or 6 to 15 nm. As the metal nanoparticles, for example, gold nanospheres capped with CTAC may be used, but the present invention is not limited thereto. Furthermore, the metal nanoparticles may be prepared by using commercially available nanoparticles as they are or by surface modification, or by using particles of smaller size, for example, 1 to 2 nm, using nanoparticle synthesis methods known in the art But is not limited thereto.

The term "surface-protecting agent" in the present invention means a substance capable of controlling the morphology of the final product by selectively binding to a specific surface of the metal nanocube to control crystal growth on the surface . For example, the surface-protective agent may be a metal nanocube that specifically binds to the (100) surface of the metal nanocube to control the growth from the surface to control the shape and edge sharpness of the finally formed particle, Organic or inorganic salts of bromine ions. Is not limited to the chemical species so long as it can quantitatively provide bromine ions in the reaction solution. Specifically, it may be an organic salt of bromine such as CTAB (hexadecyltrimethylammonium bromide) or a metal salt of bromine such as NaBr, KBr, MgBr ₂ , CaBr ₂ , but is not limited thereto.

The term "first surfactant " in the present invention may mean a molecule capable of preventing aggregation of metal nanoparticles used as seeds in a reaction solution. For example, the first surfactant may be hexadecyltrimethylammonium chloride (CTAC), but is not limited thereto. As long as it can serve as the first surfactant defined above, surfactants known in the art can be used without limitation have. However, in the present invention, when bromine ions are used as the surface protecting agent, it is preferable that the reactants other than the surface protective agent do not contain bromine ions in order to precisely control the concentration of bromine ions in the reaction system. Therefore, in the present invention, as the first surfactant, a surfactant containing no bromine ion can be used.

The term "reducing agent" in the present invention may mean a reagent capable of reducing the metal ion to grow crystals. For example, the reducing agent may be ascorbic acid, but is not limited thereto.

Precursor solutions containing the metal ion may be an aqueous solution of HAuCl _4, but is not limited thereto.

The nanocube manufacturing method of the present invention comprises: centrifuging a reaction solution according to the metal ion precursor adding step, centrifuging and redispersing the precipitate to recover and redispersing the solution; And a second surfactant addition and centrifugation step in which a second surfactant is added to the redispersed reaction solution and centrifuged. By purifying through this additional step, metal nanocubes with CSI values adjusted to within +/- 10% deviation can be provided with a purity of 95% or greater.

The metal nanocubes produced by the method of the present invention have not only the edge sharpness but also the size, that is, the edge length, are uniform. Therefore, through the additional purification process, the metal nanocubes having an edge length adjusted within a deviation of 10% or less can be provided with a purity of 95% or more.

For example, the metal nanocubes prepared by the method of the present invention are uniformly controlled in both the CSI value and the edge length, and the metal nanocubes having the CSI value and the edge length all adjusted to within a deviation of 10% The cube can be obtained with a purity of 95% or more.

In the centrifugal separation and redispersion step, a third surfactant may be further added to prevent aggregation of particles, but the present invention is not limited thereto. The third surfactant may be hexadecyltrimethylammonium bromide (CTAB), but is not limited thereto.

In the second surfactant addition and centrifugation step, centrifugation is carried out using a second surfactant existence To carry out Feature. The second surfactant may be a substance capable of forming osmotic pressure by forming a micelle in a solution and causing a concentration difference between a narrow space between particles and a bulk solution phase due to its size. As the second surfactant, any known surfactant can be used as long as it can perform the above-mentioned role. The second surfactant may be the same as or different from the first surfactant and / or the third surfactant. On the other hand, unlike the first surfactant which does not contain bromine ions, the second surfactant and / or the third surfactant are not limited to the types of ions contained therein. For example, when BDAC (benzyldimethyldodecylammonium chloride) is used as the second surfactant, since BDAC can form micelles with a small number of molecules due to high cohesive potential as compared with CTAC exemplified as the first surfactant, Can provide a greater number of micelles. This indicates that the amount of the second surfactant can be adjusted in consideration of the physical properties of the selected surfactant species.

For example, when the CR value of the metal nano-cube to be finally produced by using the nanocube manufacturing method of the present invention is less than 5 nm or the CSI value is 0.7 or more, the amount of NaBr added in the first step, of NaBr be added in step 2. the amount of the surface area values of the nano-metal cubes to be the final production (in nm ²⁾ may be 200 to 700 times the number of molecules of.

Alternatively, when the CR value of the metal nanocube to be finally prepared by using the nanocube production method of the present invention is 5 nm or more, or the CSI value is less than 0.7, the amount of NaBr to be added, determined in the first step, The amount of NaBr to be added in the second step may be less than 200 times the surface area value (unit nm ² ) of the metal nano-cube to be finally produced or 700 times to 10,000 times the molecular number.

In a specific embodiment of the present invention, irrespective of the absolute size of the metal nano-cube to be finally produced, when the bromide ion is added per unit surface area, i.e., 100 nm or less per 1 nm ² or 1000 or more, relatively rounded corners That is, a low CSI value is formed. When the bromide ion is added to about 390 per 1 nm ² , a CSI having a relatively sharp edge, that is, a nearer to 1, of about 0.7 to 0.8, Of the nanocubes were formed. However, in the case of small nanocubes with edge lengths of 17-18 nm, rounded corners can be observed when the bromide ion is added in an amount of 100 or less or 1,000 or more per 1 nm ^{2 of the} surface area, When the bromide ion was added to form 390 cations, it was confirmed that the cube had a sharp corner shape. However, the CSI value was as low as 0.3 to 0.5 due to the small EL value.

The metal nanocubes prepared by the method of the present invention may have an average length of 15 to 300 nm. Conventionally, nanocubes having a small size of 20 nm or less have been difficult to fabricate. In particular, it is impossible to finely adjust the corner shapes of the nanocubes.

For example, in the production method of the present invention, the first surfactant is used at a concentration of 30 to 70 mM based on the volume of the whole solution used But it is not limited thereto. For example, CTAC (hexadecyltrimethylammonium chloride) may be used as the first surfactant, but the present invention is not limited thereto.

For example, in the production method of the present invention, the reducing agent is preferably used at a concentration of 0.1 to 0.5 mM based on the volume of the total solution used, but is not limited thereto. For example, ascorbic acid may be used as the reducing agent, but is not limited thereto.

For example, in the production method of the present invention, the precursor solution containing the gold ions is preferably used at a concentration of 0.1 to 0.4 mM based on the volume of the whole solution, but is not limited thereto.

When the concentrations of the reactants are significantly lower or higher than the range, polyhedral particles other than the desired cube-shaped particles may be formed.

In each step of the present invention, the materials to be mixed or added may be mixed, or added simultaneously, sequentially, or at the same time. For example, the mixed aqueous solution preparation step may be carried out by adding metal nanoparticles having an average diameter of 3 to 30 nm to a mixed aqueous solution containing an amount of a surface protecting agent determined according to the first surfactant and the surface protective agent amount crystallization step, Or by adding a first surfactant and a surface protecting agent to an aqueous solution containing nanoparticles. For example, the metal ion precursor adding step may be a step of simultaneously or sequentially adding a reducing agent and a precursor solution containing a metal ion to the mixed aqueous solution, and then reacting.

The present invention also provides a method for preparing a metal nanocube, comprising centrifuging a solution containing a metal nanocube, recovering the precipitate and redispersing the solution in a solution; And a step of adding a second surfactant and centrifuging to obtain a metal nanocube aggregate having a purity of 95% or more.

As described above, the solution in the redispersing step may further include, but is not limited to, a third surfactant to prevent aggregation.

Also, the second surfactant is as defined above.

When the metal nanoparticles having a size equal to or larger than a certain size are centrifuged in the presence of the second surfactant, for example, BDAC, the outward osmotic pressure is generated between the particles contacting with the surface-to-surface, and agglomeration occurs between the particles. Accordingly, it is possible to purify particles of the same size and shape with high purity by centrifuging for a short time of 5 to 10 minutes at a temperature of several hundreds to 1000 rpm. The principle of such agglomeration is as shown in Fig.

Therefore, it is possible to provide a metal nanocube aggregate having a purity of 95% or more by using the purification method of the present invention. In this case, the deviation of the CSI value of the individual nanocubes constituting the metal nanocube aggregate may be within +/- 10% , But is not limited thereto.

In addition, by using the purification method of the present invention, the edge length of the individual nanocubes having a purity of 95% or more can be within ± 10%, but the present invention is not limited thereto.

In particular, the metal nanocube aggregate having a purity of 95% or more by using the purification method of the present invention may have a deviation of the CSI value and the edge length of the individual nanocubes from each other within ± 10%, but the present invention is not limited thereto.

Furthermore, the metal nanocubes prepared by the method of the present invention and having a controlled angle of sharpness; Or a high purity metal nanocube aggregate of a certain size and shape prepared by the method of the present invention can be used in a probe composition.

Preferably, the metal nanocubes have been prepared by the method of the present invention and have an edge sharpness controlled; Or a high purity metal nanocube aggregate of a certain size and shape produced by the method of the present invention has a CSI value and a corner length both controlled to within a deviation of 10% so that the individual particles constituting the aggregate have uniform physical and / or chemical properties .

As described above, the manufacturing method of the present invention can provide a metal nanocube having precisely controlled size and shape, for example, a corner sharpness. Further, the metal nanocube having a predetermined size and shape can be uniformly modified by 95% Or more of a nanocube aggregate having a high purity can be provided. Furthermore, nanocubes having controlled size and shape can exhibit constant optical properties that vary depending on the size and shape of the corners, and thus can be used in an optically detectable probe composition.

In a specific embodiment of the present invention, a series of metal nanocubes with sharp or rounded corners with edge lengths in the range of 17 nm to 68 or 78 nm are prepared while controlling the size and shape of the particles, Each of the nanocubes has a unique optical characteristic depending on the size or edge shape. As shown in FIG. 6, as the edge length increases, that is, as the particle size increases, the maximum extinction wavelength appears at a longer wavelength. Also, in the nanocube having the same or similar size, That is, it was confirmed that the absorption spectrum was shifted by a longer wavelength with a higher CSI index.

In addition, the metal nanocubes and complexes thereof produced by the method of the present invention can exhibit various spectroscopic signals such as absorption, fluorescence, or scattering signals based on excellent local surface plasmon resonance characteristics, and thus can be used as probes in various assay methods. have.

In a specific example of the present invention, it was confirmed that these particles had an absorption spectrum at various wavelengths (Fig. 6E). On the surface of metal nanocubes prepared by the method according to the present invention, 1,4-dibenzenethiol (BDT) (SERS) in the case of forming a metal nanocube dimer as a linking molecule after forming the self-assembled monolayer of the Raman scattering signal (SERS).

The probe composition comprising the metal nano-cube or the aggregate thereof according to the present invention can be used for sensors, bio-imaging, or therapy, but the application is not limited thereto.

In particular, the metal nanocubes or aggregates thereof according to the present invention exhibit specific and distinct optical characteristics depending on their size and / or edge shape, and the signals therefrom have high reproducibility in each particle and / or in repeated experiments , It can be used for qualitative analysis as well as for multiple analysis simultaneously analyzing two or more samples and also for quantitative analysis.

Further, in order to be applied to various fields, the metal nanocubes may be surface-modified with appropriate functional groups, polymers, proteins and the like according to need, but the present invention is not limited thereto.

In addition, since the metal nanocubes according to the present invention are particles whose size and shape are finely adjusted, they can be used as a building block, metamaterials or optical nanoantenna for forming a three-dimensional nanostructure. .

Further, the present invention provides a gold (Au) nanocube having an average of edge lengths of 20 nm or less.

According to the manufacturing method of the present invention, it is possible to obtain an extremely small-sized gold nanocube having a corner length of 17 nm to 18 nm which has not been obtained by a conventional method. Such small size nanocube particles have a very large ratio of volume to surface area and have an advantage in application to the fields of catalyst, biology, and medicine.

The gold nanocubes may be substantially cubic in shape, but there may be some differences in edge length. The average length of each edge of one of the gold nanocubes may be 20 nm or less, specifically, 10 nm to 20 nm. In addition, the CSI value of the edge of the gold nanocube may be adjusted to a deviation within ± 10%, or the edge length may be adjusted to a deviation within ± 10%.

The manufacturing method of the present invention can finely control the size and / or shape of the finally prepared metal nanocubes and further the sharpness of the edges by a simple method of controlling the amount of reactant without troublesome additional steps, It is possible to purify only by an additional process of short centrifuging in a solution containing an activator, thereby providing an aggregate of metal nanocubes having a uniform size and shape at a purity of 95% or more, It is possible to mass-produce metal nanocubes having controlled optical characteristics.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is a schematic representation of a method for the synthesis and purification of form-regulated AuNCs according to the present invention. (a) shows selective surface-protection-directed anisotropic growth of sharp-regulated AuNCs at various bromide densities. The proposed mechanism to modulate reaction kinetics is based on the preferential adsorption of bromide ions on the (100) face of AuNC. (b) shows the purification of synthesized AuNC by centrifugation-driven depletion-induced flocculation in a surfactant micelle solution and subsequent redispersion in DIW. The lower image shows the attractive osmotic pressure between the AuNCs during the flocculation process.

FIG. 2 is a TEM image showing the morphology of nanoparticles according to AuNC and Comparative Examples 1 and 2 according to an embodiment of the present invention. FIG. The scale bar represents 100 nm.

FIG. 3 is a view illustrating an image of a nanocube manufactured by adjusting shape and / or edge sharpness according to an embodiment of the present invention. (a) is a representative TEM image of AuNC obtained by adjusting the bromide concentration from 0 mM to 200 mM using a fixed seed gold precursor. From the left to right, 0 mM, 1 mM, 40 mM, and 200 mM < / RTI > concentration of bromide. The scale bar represents 20 nm. (b) is the CSI value of AuNC in (a).

Figure 4 is a diagram showing bromide-concentration-dependent growth kinetics obtained using a UV-vis spectrophotometer.

Figure 5 is a diagram illustrating the characteristics of form-regulated AuNCs. (a) is a TEM image of purified AuNCs prepared using different amounts of seeds and bromide, and the degree of insertion shows a representative single-particle image for clearly visualizing sharpness differences. In the notation, the numbers correspond to edge lengths, and R and S represent rounded-cornered AuNCs and sharp-cornered AuNCs, respectively. From the left to the right, each column is a particle prepared by using 300 μl, 30 μl, 9 μl, 6 μl, and 2 μl each of the same concentration of seed solution. We also used a fixed amount of seed, adjusted the angle of sharpness by varying the bromide concentration, and obtained R AuNCs and S AuNCs. (b) is a low magnification SEM image showing AuNCs obtained at high yield after purification. The scale bar represents 1 mu m.

Figure 6 is a diagram illustrating the characteristics of form-regulated AuNCs. (a) shows the definitions of edge length (EL), corner radius (CR), and corner sharpness index (CSI). (b) shows the edge length and corner radius of a series of AuNCs according to an embodiment of the present invention, and (c) shows the CSI of a series of AuNCs according to an embodiment of the present invention. (d) shows the number of bromide ions added per AuNC calculated for a series of AuNCs according to an embodiment of the present invention. (e) shows the normalized UV-vis spectrum for a series of AuNC solutions according to an embodiment of the present invention. Solid lines and dashed lines correspond to R AuNCs and S AuNCs, respectively.

Figure 7a shows a low magnification SEM image of 37R and 32S AuNCs. The scale bar represents 1 mu m.

Figure 7b shows a low magnification SEM image of 41R and 41S AuNCs. The scale bar represents 1 mu m.

Figure 7c shows a low magnification SEM image of 54R and 53S AuNCs. The scale bar represents 1 mu m.

Figure 7d shows a low magnification SEM image of 78R and 72S AuNCs. The scale bar represents 1 mu m.

Figure 8 is a representative excitation spectrum for 50R AuNCs before and after purification.

FIG. 9 is a diagram showing far-field scattering analysis results for AuNCs at a single particle level. FIG. (a) shows a dark-field microscope image of individual AuNCs, (b) shows Rayleigh scattering spectra obtained continuously from 25 different AuNCs, and (c) Represents the Rayleigh scattering spectrum of AuNCs, corresponding to the data. (a), the scale bar indicates 0.2 mu m. (d) to (f) show the maximum peak position, the scattering intensity at the maximum peak, and the line width of the scattering spectrum, respectively, depending on the size and shape of AuNCs, and (g) shows a series of Rayleigh scattering Figure 3 shows the reproducibility of the synthesis by three-dimensionally arranging the spectra.

10 is a graph showing the results of single particle SERS analysis for the plasmonic nanogaps between nanocubes in 78R and 72S AuNCs duplexes. (a) is a schematic diagram of 78R and 72S duplexes using 1,4-dibenzenethiol, (b) is a Raman enhancer by dimerization derived by simulation, and (c) (f) and (g) are graphs showing Raman amplification factors measured from 22 individual dimers, and FIG. 8 (d) is a graph showing the signal according to the polarization direction of the laser in the dimer, The distribution is represented by a logarithmic scale and a linear scale, respectively.

11 is a TEM image of (a) a TEM image of nanoparticles synthesized in large quantities in Example 3, and (b) a result of purification of a nanoparticle solution having a total volume of 10 mL at one time.

Hereinafter, the present invention will be described in more detail with reference to Examples. These embodiments are only for describing the present invention more specifically, and the scope of the present invention is not limited by these examples.

<Material>

Hexadecyltrimethylammonium bromide (CTAB), ascorbic acid (AA), and gold chloride trihydrate (HAuCl ₄ .3H ₂ O) were purchased from Sigma-Aldrich. Sodium borohydride was purchased from DaeJung Chemicals & Metals. Hexadecyltrimethylammonium chloride (CTAC) was purchased from Tokyo Chemical Industry (TCI). Deionized water (DIW, Milli-Q,> 18.0 MΩ) was used for all experiments and all compounds were used without further purification.

Manufacturing example 1: 10 nm Diameter Nano spheres  Synthesis of Seeds

Capped 10 nm gold nanospheres were synthesized according to the protocol disclosed by Zheng, Y. et al. (Part. Part. Syst. Charact., 2014, 31: 266-273). All solutions were prepared based on deionized water (DIW). First, a CTAB-capped seed having a size of 1 to 2 nm was prepared. To synthesize the seeds, 9.75 ml of 100 mM CTAB solution in a 50 ml round bottom flask was mixed with 250 l of 10 mM HAuCl ₄ solution. Then 600 μl of freshly prepared ice-cold 10 mM NaBH ₄ solution was added rapidly. The solution was stirred and mixed for 3 minutes and stored at 27 [deg.] C for 3 hours before proceeding to the next step. Then, 10 nm gold nanospheres were synthesized from the seed thus prepared. To a 10 ml vial, 2 ml of 200 mM CTAC, 1.5 ml of 100 mM ascorbic acid, and 50 占 퐇 of the previously prepared CTAB-capped seed solution were sequentially mixed. While mixing the solution at a constant rate, 2 ml of 5 mM HAuCl ₄ solution was injected at one time. The solution was incubated at room temperature for 15 minutes with constant mixing at 300 rpm. The solution was centrifuged twice (20600 g, 30 min.), Redispersed first in 1 ml of DIW and then redispersed in 1 ml of 20 mM CTAC solution for further use.

Example  1: Adjusted size and / or shape Nanocube  synthesis

Synthesis of nanocubes (NC) was carried out in 20 ml glass vials. Prior to use, the vial was washed with acetone and DIW. 6 ml of 100 mM CTAC were mixed with 30 [mu] l of sodium bromide at the concentrations shown in Table 1 below. The 10 nm seed solution prepared according to Preparation Example 1 was diluted at 520 nm to an absorbance of 5.6 OD and added by the volume as shown in Table 1 below. 390 [mu] l of 10 mM ascorbic acid solution was added and mixed thoroughly. Finally, while mixing and stirring the solution at 500 rpm, 6 ml of 0.5 mM HAuCl ₄ solution was added in one go. The solution was incubated with mixing for 19 minutes, redispersed in DIW by centrifugation twice.

Example  2: Nanocube  refine

The nanocubes synthesized according to Example 1 were centrifuged and precipitated. The precipitate was redispersed in a 10 mM CTAB solution to a concentration two times that of the original nanocube solution. The calculated amounts of BDAC (benzyldimethyldodecylammonium chloride, Sigma-Aldrich) stock solution and DIW were added to obtain the appropriate BDAC concentration and the same nanocube concentration shown in Table 1 for each sample. DIW was added to prevent unwanted flocculation. The solution was mixed and centrifuged according to the titration conditions. 18R and 17S were too small to agglomerate, so they were excluded from the purification process. 37R and 32S were centrifuged at 1000 rpm for 10 minutes. Other samples were centrifuged at 500 rpm for 5 minutes. The supernatant was removed with a microwave pet, and the remaining precipitate was redispersed in DIW.

sample	Seed volume (μl)	Bromide concentration (mM)	BDAC concentration (mM)
18R	300	20	-
17S	300	120	-
37R	30	2	100
32S	30	40	60
41R	9	5	60
41S	9	20	50
54R	6	6	40
53S	6	20	33
78R	2	2	40
72S	2	20	18

Comparative Example  One: CTAC  Instead of CTAB  Methods for the synthesis of nanoparticles that use but do not use additional bromide sources

Gold nanoparticles were prepared in the same manner as in Example 1, except that CTAB was used in place of CTAC and CTAB was used and the same volume of DIW was used instead of sodium bromide.

Comparative Example  2: as a source of bromide CTAB  Use, CTAC  Synthesis of unused nanoparticles

In the same manner as in Example 1 except that the same volume of DIW was used instead of CTAC to contain CTA ⁺ in an insufficient amount and a volume of 20 mM CTAB was used in place of the same sodium bromide as the bromide source, Particles were prepared.

Example  3: Nanocube  Bulk synthesis and purification

On the basis of Example 1, the scale of the reaction solution was increased to synthesize a large amount of gold nanoparticles. Experimental method sikidoe increase the volume of all solutions used in Example 1 to the same magnification, HAuCl ₄ The HAuCl ₄ solution concentrated in a 10 mM DIW after the first, which was added as much as the amount required for diluting with 0.5 mM HAuCl ₄ in the volume in order to facilitate the addition at a time when the solution.

As a result, it was confirmed that gold nanocube was synthesized even in a 248 mL volume reaction solution of 20 times scale of Example 1, and gold nanocubes of about 10 mg or more could be obtained. 11A is a TEM image of nanoparticles synthesized in large quantities.

Since nanocubes are nanoparticles formed by kinetic control, the control of the reaction rate is a very important factor. In conventional gold nanocube synthesis methods, there is a difference in the synthesis yield and particle shape depending on the stirring conditions of the solution, that is, the stirring speed or stirring method, and there is a lack of reproducibility and difficulty in increasing the synthesis scale.

According to our understanding, conventional gold nano-cube synthesis synthesis has not shown an example of mass synthesis by synthesizing within about 50 mL of reaction solution, and the amount of compound and the volume of reaction solution are limited. However, according to the manufacturing method of the present invention, it is possible to obtain nanocubes with high reproducibility even when thorough stirring is performed using a stirring bar, and even if the scale is increased 20 times or more, uniform nanocubes can be successfully .

Also, the nanoparticles of Example 2 can be purified in a large amount. In Example 2, the total volume of the mixed solution before centrifugation was adjusted to be 0.2 mL. However, it was confirmed that the tablets were well formed even when the total volume was increased to 10 mL. FIG. 11B is a TEM image of the resultant product obtained by purifying a nanoparticle solution having a total volume of 10 mL at one time, and it can be confirmed that purification is performed with high purity even when the scale is increased.

Experimental Example  1: Darkfield image and spectrum measurement

A dark-field (DF) image was obtained using a 40X objective. The exposure time was set to 80 ms for 78R and 72S and to 120 ms for 41R. DF spectra were measured with an inverted microscopy system (Ntegra, NT-MDT). For DF measurement, an oil condenser with a numerical aperture (NA) of 1.3 was used. For the scattering spectrum measurement, UNPLAN (60X, NA 0.90, air objective) was used. The washed glass was prepared by sonication in acetone and DIW for 5 minutes each. A sample was prepared by drop casting gold nanocubes (AuNC) on the cleaned glass and spin-coated with a microcentrifuge. Spectra were obtained with an exposure time of 3 seconds from randomly selected particles observed in DF.

Experimental Example  2: Raman measurement

An AuNC solution mixed with 1,4-benzenedithiol (BDT) was drop-cast on a TEM grid to prepare a sample for Raman measurement. Raman measurements were performed using an inverted microscope system (Ntegra, NT-MDT) equipped with UNPLAN (100X, NA 1.3, oil). The particles were identified as a single particle by correlation between Rayleigh scattering image and TEM image. Each Raman signal was acquired by exposure to a linearly polarized 785 nm laser (230 μW) for 30 seconds. The signal was detected with a charge-coupled device (CCD) cooled down to -70 ° C (Andor Newton DU920P BEX2-DD). Enhancement factors were calculated by comparing signals from a 2.5 mM 1,4-benzenedithiol bulk solution. Spectra were obtained by exposure to linearly polarized 785 nm laser (17.6 μW) for 180 seconds using a low magnification lens (PLAN N, 10X, NA 0.25, air). The difference between the two lenses was measured using 1 mM rhodamine 6G (rhodamine 6G) Respectively. The signal was estimated to be proportional to the power and acquisition time of the laser. The excitation volume was assumed to be cylindrical, and the excitation volume was calculated to be 28 fL. Assuming that one molecule of BDT on the gold thin film has a molecular footprint of 5.4 x 10 ^-19 m ² and a height of 7.6 x 10 ^-19 m, the molecules in the gap using the volume of the molecule and the volume of the hot spot The number of enhancement factors (EF) was calculated by the following equation:

Experimental Example  3: Simulation

Finite element method (FEM) simulations were performed using commercial software (COMSOL) in scattered-field mode. Linearly polarized plane-wave excitation was used. The nanocube model was based on TEM image analysis. In order to create a model similar to the system of the present invention, two modeled nanocubes were arranged in parallel and the spacing between the structures was 1.1 nm. All of the nanocubes were modeled as gold. The interval length was calculated based on TEM image analysis. The surrounding medium containing the gaps was modeled in air.

Experimental Example  4: Device

TEM and SEM images were obtained from JEM-2100 (JEOL) and Helios NanoLab 650 (FEI) systems at the National Center for Inter-University Research Facilities (NCIRF, Seoul National University, Korea).

<Result>

First, selective surface-protection-directed anisotropic growth of AuNCs was performed. Starting from CTAC-capped 10 nm gold nanospheres, seed-mediated growth reaction with CTAC, NaBr, and ascorbic acid proceeded at room temperature and the process is schematically illustrated in FIG. 1A. In this process, the bromide concentration dependent growth rate determined the corner sharpness of the resulting AuNCs. The growth characteristics of nanocrystals were determined by the ratio between growth rates on different crystal planes. In order to induce anisotropic growth and to form cubic nanostructures, the growth rate along [100] decreased as the growth rate relative to [110] / [111] increased, The surface could be exposed preferentially. The relative growth rate difference between the (100) plane and the other plane changed when the amount of bromide was adjusted so as to favorably adhere to the (100) plane, thus resulting in a round-cornered or pointed-edge sharp-cornered AuNCs were formed. When the bromide density was less than 100 ions / nm ² , the number of bromide ions was insufficient to completely block the (100) plane. Thus, the relative growth rate difference between [100] and [111] / [110] did not change significantly, thus forming AuNCs with rounded edges. When an adequate amount of facet-directing agents (~ 350 ions / nm ² ) is provided, effective and preferential binding to the (100) plane reduces the rate of growth and (111) / (110) The surface was less influenced by the bromide ion and AuNCs with sharp-edges were formed. If the bromide concentration is excessive, it can be adsorbed on the (111) / (110) and (100) surfaces, thereby reducing the overall growth rate and the difference in growth rate between the surfaces. The shape of the synthesized AuNCs-shape-selective sedimentation was used to maximize the yield (Fig. 1B). This method is based on centrifugation-driven depletion-induced flocculation, which consists of reversible redispersion of aggregated and precipitated nanoparticles only with surfactant micelles Based. When the particles were dispersed in a surfactant solution above the critical micelle concentration, exclusion of the micelle molecules from the space between the AuNCs caused osmotic pressure, resulting in intergranular aggregation. Agglomeration was applied to select nanorods or nanobipyramids in the nanoparticle mixture and it took more than 10 hours for the agglomeration to settle the nanoparticles. In the present invention, the time was remarkably shortened by short centrifugation. After centrifugation of the nanoparticle solution in the surfactant micellar solution, the inter-particle distance between AuNCs decreased, and it was possible to perform effective coagulation in a very short time. Since the attractive force between two particles is proportional to the surface area facing each other, NCs with a flat surface have an advantage over particles with a curved surface like a rod, or with a small surface such as a cornice. In the present invention, AuNC yield of 95% or more can be achieved by controlling the micelle concentration in order to selectively induce AuNC aggregation.

Further, the role of each component used in the method for manufacturing AuNC with controlled shape and / or edge sharpness according to the present invention was confirmed. For this purpose, AuNC was prepared by the method of Example 1 using 6 ml of 100 mM CTAC as an experimental group and 30 20 of 20 mM sodium bromide as a bromide ion source. Further, a sufficient amount of surfactant was used as the comparative group, but CTAB containing bromide was used in the same amount instead of chloride, and the additional bromide ion source was prepared by using the same volume of DIW instead of using the sodium bromide solution The morphology of one nanoparticle (Comparative Example 1) and AuNC and nanoparticles prepared under the above three conditions was observed with SEM, and the results are shown in FIG. As shown in FIG. 2A, AuNC according to the present invention prepared by using a sufficient amount of surfactant CTAC and adding a small amount of sodium bromide was uniformly prepared in the form of a cube. However, in the case of Comparative Example 1 in which CTAB was used instead of CTAC to provide a sufficient amount of surfactant and bromide ion to prepare nanoparticles, although individual particles showed a specific crystal form as shown in FIG. 2B, It was difficult to refine high-purity nanocubes from a mixture of nanoparticles, nanoparticles, nanoparticles, nanoparticles, and nanoparticles. Further, when CTAB was added at the same level as the concentration of bromide provided by sodium bromide in Example 1, that is, in Comparative Example 2 where the surfactant was used at a significantly low concentration, as shown in Fig. 2C, Irregular nucleation occurs in the solution as well as on the surface of the amorphous particle mixture in which neither the size nor the shape are defined.

Furthermore, it has been confirmed that the present invention can fine-tune the corner sharpness. AuNCs with different edge sharpness were obtained, varying the bromide concentration from 0 mM to 200 mM (Figure 3). As the bromide concentration increased, the corner sharpness initially increased and then decreased. At the highest bromide concentration, the size of AuNCs decreased somewhat due to the increase in the number of byproducts. In order to investigate the mechanism of edge sharpness control, the growth rate during morphological development was studied by UV-vis spectroscopy. The CTAC, seed and AA were kept in the same amounts and the bromide concentration was varied. The maximum localized surface plasmon resonance (LSPR) wavelength (544 nm for 1 mM NaBr, 560 nm for 40 mM NaBr and 556 nm for 200 mM NaBr) of fully grown structures after addition of the gold precursor Changes in extinction intensity were monitored at 10 second intervals (Figure 4). A slow increase of the absorbance to 200 mM indicates that the increased bromide concentration inhibits the reduction, which supports the synthetic mechanism proposed in Fig. In the present invention, it was confirmed that the introduction of seeds uniquely initiates the growth event. Thus, seedless additional nucleation was not detected in the UV-vis measurement.

To demonstrate the above principle, simultaneous adjustment of size and edge sharpness was performed by varying the amount of seed and bromide. The amount of seed was adjusted to the volume of the seed solution (300, 30, 9, 6, and 2 μl). In order to adjust the edge sharpness, the amount of seed was fixed and the concentration of bromide was changed. The bromide was applied at a lower density to produce AuNCs with rounded corners. As the overall size decreased, the concentration of bromide added to obtain AuNCs decreased. This is the result of a reduction in the number of particles, despite a significant increase in surface area in larger AuNCs. After preparation, AuNCs were dispersed in the BDAC solution and centrifuged for 5-10 minutes. Cohesion was positively correlated with the overlaid surface area between nanoparticles and micelle concentration, so the concentration required for coagulation decreased with increasing AuNCs size. The TEM images represent refined AuNCs of different sizes and representative images are shown for the insertions to clearly visualize the structural variations (Fig. 5A). Each column represents the result of adjusting the amount of seeds, with the upper and lower rows corresponding to AuNCs with rounded corners and AuNCs with sharp corners, respectively. In order to analyze the structural characteristics of each AuNC based on the TEM image, the edge length was defined as the distance between the two ends of the AuNCs, the corner radius as the corner curvature, Defined as the radius of a perfectly matched circle (Fig. 6A). In the notation of the sample, the numbers represent the edge lengths, and R and S correspond to NCs with rounded edges and NCs with sharp edges, respectively. After purification, the yield of all AuNCs except the smallest was improved to over 95% (enlarged SEM image of Fig. 5b and Fig. 7). The 32S AuNCs showed cohesive potential similar to gold nanorods, a byproduct, and were provided at a yield of about 95%. The yield for other AuNCs was achieved in excess of 97% (n &gt; 400). It has been difficult to find a suitable surfactant capable of minimizing aggregation due to its small surface area. As the seed volume decreased, the edge length increased from 17 nm to 78 nm. To illustrate sharpness intuitively, the corner radius was plotted in Figure 7b. AuNCs of less than 25 nm have higher self-diffusion coefficients (3 to 12 nm) of gold atoms than values (0.3 to 1 nm) for other metals such as platinum, It was not expected to be possible to synthesize using a solution method, since it promotes migration of gold atoms to (100) low energy and inhibits effective exposure of the (100) plane. Nevertheless, AuNCs with a corner length of 17 nm were successfully synthesized by the method of the present invention. This is the smallest known AuNCs to date.

The present inventors have proposed the term corner sharpness index (CSI) to characterize the sharpness irrespective of the edge length. A scheme for defining CSI is schematically shown in FIG. 6A. The NCs at the pointed edge have a CSI value closer to one. The CSI values of the four large, pointed-edge AuNCs were similar, while the value of 17S was lower than that for others (FIG. 6C). It is considered that this is due to the relatively high surface tension due to the small size. In order to provide stoichiometry information for AuNCs with sharp-edges, the number of bromide ions required per AuNC was calculated (Fig. 6d). This is not the number of ions adsorbed on the surface, but rather the number of ions added. The linear correlation between the surface area and the number of added bromide ions indicates a uniform density of bromide of ~ 390 ions / nm ² regardless of size. This provided an approximate number of bromide ions required to form AuNCs with pointed-edges of a certain size. The normalized UV-vis spectra for a series of AuNC solutions show progressive red-shifts due to the sharpness of the corners and by the retardation effect as the edge length increases. (Fig. 6E). The narrower spectral bandwidths after purification show a high degree of monodispersibility of AuNCs (Figure 8).

It has been noted in the present invention that its optical properties can be controlled by controlling the AuNC structure. A Rayleigh scattering signal was measured at a single-particle level using a dark-field microscope, and the results are shown in FIG. 9A. As shown in FIG. 9, a dark field microscope (DF micrograph, FIG. 9a) and a scattering spectrum (FIG. 9b) measured from 25 AuNCs showed uniform scattering characteristics. Due to the narrow distribution of AuNCs and high yields, the spectra obtained for the 25 individual particles are in good agreement, and representative spectra averaged to these are shown in Figure 9c. Also, the maximum peak positions obtained from the scattering spectra measured for a series of AuNCs of different sizes, i.e., corner lengths and / or shapes, and the scattering intensities at the peak positions are shown in Figures 9d and 9e, respectively. As shown in FIGS. 9D and 9E, the position and intensity of the maximum scattering wavelength varied depending on the size and / or shape of the AuNC, and the scattering signal increased as the sharpness of the edge was higher in AuNCs of similar size, The average peak position was found to be shifted by a long wavelength. This is mainly due to the delay effect due to the large size. In this case, the 72S had a somewhat reduced scattering intensity despite the high sharpness of the edge compared to the 78R. This is because the Rayleigh scattering generally increases in proportion to the square of the volume, It is thought that this is due to the fact that it appears complex. On the other hand, the spectrum of each AuNCs is shown in Fig. As shown in FIG. 9F, it was confirmed that these AuNCs had scattering spectra of a constant line width regardless of their sizes and shapes. Further, 53S AuNCs having the same size and edge shape were synthesized in various batches, and the Rayleigh scattering spectrum of AuNCs obtained from each batch was measured, and a comprehensive spectrum profile was shown three-dimensionally in FIG. 9G. As shown in FIG. 9g, the Rayleigh Raman spectra measured from AuNCs produced in several different batches were all consistent, indicating that using the synthesis method of the present invention, uniform AuNCs could be produced regardless of batch.

Finally, we have studied the structural effects of near-field enhancement by surface-enhanced Raman scattering (SERS) with 78R and 72S in the present invention. Specifically, a self-assembled monolayer of BDT was formed on the surface of AuNC and assembled into an AuNC dimer. The form of the AuNC dimer formed is schematically shown in Fig. 10a. FIG. 10C shows TEM images of the dimers of 78R and 72S, respectively. Each of the 22 individual dimers was analyzed to have an average gap size of 1.1 nm (within a deviation of 10%). The maximum Raman signal enhancement from the polar plot of the Raman signal generated by varying the polarization angle of the irradiating laser was found to be large in the long axis resonance mode of the dimer and / or at 78R. In the present invention, the Raman enhancer of the dimer prepared by using BDT was calculated to be 8.0x10 ⁷ at 72R and 1.6x10 ⁷ at 72S (FIGS. 10f and 10g). This tendency agrees with the simulation result shown in Fig. 10B. This indicates that the control of edge sharpness is an adjustable factor not only in the single particle but also in the optical properties of the dimer. On the other hand, the 72S dimer exhibited a narrower spectrum spectrum than the 78R dimer, which is thought to be due to the higher homogeneity of the 72S compared to the 78R, because the edge radius deviation is smaller, and the corner radius Was 1.9 times larger than that of 72S. This pattern also appeared in AuNC of different sizes.

In conclusion, the present invention proposes a method of producing metal nanocubes at a high yield while accurately controlling the size and edge sharpness of the metal nanocubes. The method of the present invention provides a simple method of adjusting the size by adjusting the ratio of seed to precursor amount as well as adjusting the edge sharpness by changing the amount of bromide ion added. From the stoichiometric information, when the metal nanocube size is selected, the concentration of bromide required for metal nanocubes with round-edged or sharp edges can be readily determined. Centrifugation-induced coagulation of synthesized metal nanocubes is a simple and feasible method for morphological-selective nanoparticle purification, and is a scalable method to any type of nanoparticle mixture without complex preparation. Accurate morphological control of metal nanocubes enables efficient fine-tuning of far-field and near-field reactions, thereby making it possible to convert structural differences into modulation of optical properties. Therefore, based on this, it is possible to develop a feasible and mass-produced synthesis method of metal nanocubes that can be used as basic nanostructures for synthesis or self-assembly into 2D or 3D materials. Furthermore, application of highly improved plasmon properties achieved through precisely controlled design of novel nanostructures can be expected.

Claims (24)

1. 1. A method of manufacturing a metal nanocube having a corner sharpness index (CSI) controlled by the following formula 1,

   Determining the amount of a surface-protecting agent to be added in the following step of preparing a mixed aqueous solution based on the surface area of the metal nanocube to be finally produced and the CSI index;

   Preparing a mixed aqueous solution by mixing a first surfactant, an amount of a surface protective agent determined according to the surface protective agent amount crystallization step, and metal nanoparticles having an average diameter of 3 to 30 nm to prepare a mixed aqueous solution; And

   And adding a metal ion precursor by adding a reducing agent and a precursor solution containing metal ions to the mixed aqueous solution,

   Wherein the metal is one of gold (Au), silver (Ag), palladium (Pd), platinum (Pt), copper (Cu), aluminum (Al), lead (Pb) Manufacturing method:

   [Formula 1]

   

   In Equation (1)

   EL denotes an edge length defined as the shortest distance from one point on a flat surface of a metal nanocube to another surface parallel thereto,

   CR denotes the corner radius, defined as the radius of the circle that perfectly matches the corner curvature.
2. The method according to claim 1,

   Centrifuging the reaction solution according to the metal ion precursor adding step, centrifuging and redispersing the precipitate to recover and redispersing the precipitate; And a second surfactant addition and centrifugation step of adding a second surfactant to the redispersed reaction solution and centrifuging the second surfactant.
3. 3. The method of claim 2,

   Wherein the metal nanocubes whose CSI values are adjusted to within a deviation of 10% are provided with a purity of 95% or more.
4. 3. The method of claim 2,

   Wherein the metal nano-cubes are adjusted to have a deviation within a range of 10% or less in corner purity at a purity of 95% or more.
5. The method according to claim 1,

   Or CR value of the metal nano-cubes to be the final production is less than 5 nm, not less than the CSI value of 0.7, a specific surface area value of the metal nano-cubes to be the final production amount of the surface protective agent to be added is determined in step 1 (in nm ²⁾ Of the metal nanocubes is 200 to 700 times the molecular number of the metal nanocubes.
6. The method according to claim 1,

   Or end-CR value of the metal nano-cubes to be manufactured is more than 5 nm, less than the CSI value of 0.7, a specific surface area value of the metal nano-cubes to be the final production amount of the surface protective agent to be added is determined in step 1 (in nm ²⁾ Or more than 700 times to 10000 times the molecular weight of the metal nanocube.
7. The method according to claim 1,

   Wherein the metal nanocubes have an average edge length of 15 to 300 nm.
8. The method according to claim 1,

   Wherein the first surfactant is used in a concentration of 30 to 70 mM based on the volume of the whole solution used.
9. The method according to claim 1,

   Wherein the reducing agent is used in a concentration of 0.1 to 0.5 mM based on the volume of the total solution used.
10. The method according to claim 1,

    Wherein the precursor solution containing the metal ions is used at a concentration of 0.1 to 0.4 mM based on the volume of the whole solution used.
11. The method according to claim 1,

    Wherein the surface protecting agent is NaBr, and the reducing agent is ascorbic acid.
12. The method according to claim 1,

    Wherein the metal ion precursor adding step comprises reacting the mixed aqueous solution with a reducing agent and a precursor solution containing metal ions at the same time, sequentially or at the same time, to react them.
13. Preparing metal nanocubes by the method of claim 1; Centrifuging the solution containing the metal nanocubes, collecting the precipitate and redispersing the solution in the solution; And a step of adding a second surfactant and centrifuging the mixture to obtain a metal nano-cube aggregate having a purity of 95% to 99.9%.
14. 14. The method of claim 13,

    Wherein the metal nanocube aggregate having a purity of 95% to 99.9% has a deviation of CSI value of individual nanocubes within +/- 10%.
15. 14. The method of claim 13,

    Wherein the metal nanocube aggregate having a purity of 95% to 99.9% has a variation in the edge length of the individual nanocubes within 占 10%.
16. A metal nanocube produced by the method of any one of claims 1 to 12; Or a metal nanocube aggregate produced by the method according to any one of claims 13 to 15.
17. 17. The method of claim 16,

    Wherein the probe is optically detectable.
18. 17. The method of claim 16,

    Exhibit an absorption, fluorescence, or scattering signal.
19. 17. The method of claim 16,

    Sensor, bioimaging, or therapeutic.
20. 17. The method of claim 16,

    Qualitative, multimeric, quantitative, or two or more of these.
21. 17. The method of claim 16,

    Wherein the metal nanocube or metal nanocube aggregate is surface-modified.
22. A gold (Au) nanocube having an average edge length of 20 nm or less.
23. 23. The gold nanocube of claim 22, wherein the CSI value of the edge is adjusted to a deviation within +/- 10%, or the edge length is adjusted to a deviation within +/- 10%.
24. 23. The gold nanocube of claim 22, wherein the average of edge lengths is 10 nm to 20 nm.

Images