Substrate for spectroscopy including polycrystal

Abstract

The present invention relates to a substrate for spectroscopic analysis comprising a polycrystalline structure and a method for manufacturing the same. More specifically, the present invention relates to a substrate for spectral analysis based on a general-purpose material including a polycrystalline structure having improved signal strength and signal uniformity, and a method for manufacturing a substrate for spectral analysis including a polycrystalline structure having a shape controlled by a simple process on the surfaces of various materials.

Description

Technical Field

[0001] The present invention relates to a substrate for spectral analysis including a polycrystalline structure and a method for manufacturing the same. More specifically, the present invention relates to a substrate for spectral analysis based on a universal material including a polycrystalline structure with improved signal intensity and signal uniformity, and a method for manufacturing a substrate for spectral analysis including a polycrystalline structure whose shape is controlled by a simple process on the surface of various materials. Background Art

[0002] Raman scattering is an inelastic scattering in which the incident light energy changes. When light is irradiated onto a specific molecular sieve, the inherent vibration transition of the molecular sieve generates light with a wavelength slightly different from that of the irradiated light.

[0003] In fact, almost all organic molecules have an inherent Raman shift, so Raman spectroscopy using Raman scattering can obtain signals even in the case of non-polar molecules that induce changes in molecular polarizability. In addition, Raman spectroscopy is not interfered by water molecules, so it is more suitable for detecting biomolecules such as proteins and genes.

[0004] Since the wavelength of the Raman emission spectrum has the chemical composition and structural characteristics of the molecules that absorb light in the sample, the target material can be directly analyzed by analyzing these Raman signals.

[0005] As the background technology of the present invention, Korean Patent No. 10-1867670 discloses a method for manufacturing a paper-based surface enhanced Raman scattering substrate using a continuous chemical reaction method. However, in the above patent, since metal nanoparticles with a diameter of 1 to 100 nm are manufactured and a first metal precursor solution, a second metal precursor solution, a first reducing agent solution and a second reducing agent solution are used, the process is complicated, and since the precursor adsorption step, the precursor washing step, the loading step in the reducing agent solution and the reducing agent solution washing step are repeatedly performed many times, there is a problem of being difficult to control. Summary of the invention

[0006] An object of the present invention is to provide a substrate for spectral analysis, wherein nanoparticles containing a noble metal are directly grown on a base member and which has excellent sensitivity and signal uniformity when used for spectral analysis.

[0007] Another object of the present invention is to provide a substrate for spectroscopic analysis that has excellent flexibility and can be easily applied to various three-dimensional surfaces.

[0008] Another object of the present invention is to provide a composition for manufacturing a substrate for spectral analysis, which can easily adjust the shape of the formed precious metal nanocrystal particles regardless of the material of the base component, and can easily form polycrystalline particles, thereby improving the sensitivity and signal uniformity of the surface enhanced Raman spectroscopy (SERS) signal.

[0009] Another object of the present invention is to provide a Raman spectroscopic device capable of performing on-site diagnosis of cancer and the like.

[0010] Another object of the present invention is to provide a method for manufacturing a substrate for spectral analysis, which can effectively manufacture a substrate for spectral analysis having excellent SERS signal sensitivity and signal uniformity through a simple process regardless of the material of the base member.

[0011] The objects of the present invention are not limited to the above-mentioned objects, and other objects not mentioned can be clearly understood from the description of the detailed description.

[0012] According to one aspect, the present invention provides a substrate for spectral analysis, comprising: a base member; and a polycrystalline structure composed of a plurality of clusters of nanoparticles formed on the base member, having a plurality of grain boundaries, and formed by a solution process.

[0013] According to an embodiment, the base member may be composed of one or more of paper, polymer, well plate, wafer and protein.

[0014] According to one embodiment, the nanoparticles may be connected by a branching structure, and the average particle size of the polycrystalline structure may be 1 μm to 100 μm.

[0015] According to one embodiment, the electrochemically active surface area (EASA) of the substrate for spectral analysis of the present invention may be 0.1 cm 2 Up to 10.0cm 2 .

[0016] According to an embodiment, the nanoparticles may be composed of one or more of Au, Ag and Pt.

[0017] According to one embodiment, the spectral analysis substrate may be applicable to a Raman spectroscopy system using a wavelength of 500 nm or more or a Fourier transform near-infrared (near-IR FT) Raman spectroscopy system using a wavelength of 1064 nm.

[0018] According to one embodiment, the substrate for spectral analysis may be composed of a three-dimensional swab strip, a wearable substrate, or a plasma aperture plate.

[0019] According to another aspect, the present invention provides a composition for manufacturing a substrate for spectral analysis, wherein the composition contains a noble metal precursor and a reducing agent, and the ratio of the reducing agent to the noble metal precursor is 1:0.5 to 1:15.

[0020] According to one embodiment, in the composition for manufacturing a substrate for spectral analysis of the present invention, as the ratio of the reducing agent to the noble metal precursor increases, the size of the polycrystalline structure formed on the substrate for spectral analysis decreases and the density of the polycrystalline structure increases.

[0021] According to one embodiment, the noble metal precursor may be one or more of HAuCl 4 and NaAuCl 4 .

[0022] According to an embodiment, the reducing agent may be one or more of hydroxylamine, ascorbic acid, FeSO 4 and hydroxyquinone.

[0023] According to another aspect, the present invention provides a Raman spectroscopic device, comprising: a light source; the spectral analysis substrate described in the present invention; and a detector for detecting the Raman spectrum.

[0024] According to one embodiment, the Raman spectroscopic device of the present invention may further include: an adapter, which is cylindrical with an open first end, the first end having a coupling portion coupled to the Raman spectroscopic device, and the second end having a coupling portion formed with a through hole for inducing light from a light source; and a measuring member, which is spoon-shaped, consisting of a head and a straight-line main body extending from the head, the head having: a hemispherical mounting portion for mounting the coupling portion of the second end of the adapter; and a mounting groove, extending in the length direction from the center of the main body to the hemispherical mounting portion, for mounting a straight-line strip substrate for spectroscopic analysis.

[0025] According to an embodiment, the mounting groove may be formed in a T-shape to prevent a tip of the strip substrate for spectral analysis from being separated from the hemispherical mounting portion.

[0026] According to one embodiment, the target material of the detector may be selected from one or more of cells, metabolites, proteins, nucleic acids, DNA, RNA, enzymes, organic molecules, viruses, extracellular vesicles, microvesicles, exosomes and fat in urine, saliva, sweat and tears.

[0027] According to one embodiment, the Raman spectroscopy device is capable of on-site diagnosis of cancer.

[0028] According to another aspect, the present invention provides a method for manufacturing a substrate for spectral analysis, which is the method for manufacturing a substrate for spectral analysis described in the present invention, comprising: a) a substrate member preparation step of preparing a substrate member; and b) a step of loading the substrate member in a composition for manufacturing a substrate for spectral analysis containing a noble metal precursor and a reducing agent solution, and forming a polycrystalline structure composed of clusters of multiple nanoparticles on the substrate member to have multiple grain boundaries, including a step of adjusting the shape of the polycrystalline structure by setting the ratio of the reducing agent to the noble metal precursor solution to 1:0.5 to 1:15 in the step b).

[0029] According to one embodiment, the step a) of the method for manufacturing a substrate for spectroscopic analysis of the present invention may further include a surface modification step of modifying the surface of the base member before the step of forming the polycrystalline structure.

[0030] According to one embodiment, in the method for manufacturing a substrate for spectral analysis of the present invention, the surface modification step may include: containing at least one selected from 1% to 3% of a base and 1% to 3% of an acid, and using a 1-5 A step of treating the surface of the base member with a surface modifying composition of alcohol or water as a solvent.

[0031] Effects of the Invention

[0032] According to one embodiment, in the substrate for spectral analysis of the present invention, the nanoparticles containing noble metals are directly grown and connected into a branched structure, and may include a polycrystalline structure of particle size, so that when used for spectral analysis, the sensitivity and signal uniformity are excellent.

[0033] According to one embodiment, the base member of the substrate for spectroscopic analysis of the present invention is composed of a plurality of materials, and thus has excellent flexibility and can be easily applied to various three-dimensional surfaces.

[0034] According to one embodiment, the composition of the present invention for manufacturing a substrate for spectral analysis can easily adjust the shape of the formed precious metal nanocrystal particles by adjusting the ratio of the precursor and the reducing agent, regardless of the material of the substrate component, and can easily form polycrystalline particles, thereby improving the sensitivity and signal uniformity of the SERS signal.

[0035] According to one embodiment, the Raman spectroscopic device of the present invention can confirm the type of unlabeled analytes on site and perform quantitative analysis.

[0036] According to one embodiment, the Raman spectroscopic device of the present invention can perform on-site diagnosis of cancer and the like using a small amount of biological samples (eg, urine).

[0037] According to one embodiment, the method for manufacturing a substrate for spectral analysis of the present invention directly grows a polycrystalline structure containing precious metals on a substrate component through a simple process, so-called a single solution process, regardless of the material of the substrate component. Thus, a substrate for spectral analysis having excellent SERS signal intensity and signal uniformity can be effectively manufactured.

[0038] According to one embodiment, the method for manufacturing a substrate for spectral analysis of the present invention can effectively manufacture a substrate for spectral analysis having excellent particle density and improved signal uniformity through surface modification. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] The objects, specific advantages and novel features of the present invention will be clearly understood from the following detailed description taken in conjunction with the accompanying drawings.

[0040] The terms or words used in this specification and claims shall not be construed as limited to their ordinary or dictionary meanings, but shall be construed as meanings and concepts consistent with the technical ideas of the present invention based on the principle that the inventor can appropriately define the concepts of the terms or words in order to explain his invention in the best way.

[0041] In this specification, when it is mentioned that a component such as a layer, a part or a substrate is "connected" or "bonded" to another component "on", it should be understood that it can be directly "connected" or "bonded" to another component "on", or other components can exist between the two components. Conversely, when it is mentioned that a component is "directly connected" or "directly bonded" to another component "on", no other components can exist between the two components.

[0042] The terms used in this specification are only used to describe specific embodiments and are not intended to limit the present disclosure. Unless the context clearly indicates otherwise, a singular expression includes a plural expression.

[0043] In this specification, it should be understood that terms such as "including" or "having" are intended to indicate the existence of the features, numbers, steps, operations, components, parts or their combinations described in the specification, and are not intended to exclude in advance the existence or additional possibilities of one or more other features, numbers, steps, operations, components, parts or their combinations.

[0044] In this specification, when a part "includes" a certain component, it does not exclude other components, but may also include other components. In addition, throughout the specification, "upper" means located above or below a part of an object, and does not necessarily mean located above the direction of gravity.

[0045] The present invention may be subjected to various modifications and may have various forms, and therefore specific embodiments are illustrated in the drawings and described in detail in this specification. However, it should be understood that this does not limit the present invention to specific embodiments, but includes all modifications, equivalent technical solutions and alternative solutions included in the concept and technical scope of the present invention. When describing the present invention, if it is judged that the specific description of the relevant known technology will make the gist of the present disclosure unclear, the detailed description thereof will be omitted.

[0046] Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. In the description with reference to the accompanying drawings, the same or corresponding components are denoted by the same reference numerals and their repeated description will be omitted.

[0047] Figure 1 (a) shows a paper-based substrate for spectroscopic analysis manufactured using cellulose acetate as a base member according to an embodiment of the present invention. Figure 1 (b) to Figure 1 (e) shows Figure 1 (a) SEM photograph of the substrate for spectral analysis ( Figure 1 (b)), polycrystalline verification results ( Figure 1 (c)), particle formation mechanism ( Figure 1 (d)) and particle distribution curve ( Figure 1 (e)).

[0048] Figure 2 : is a SEM photograph showing the shape of particles grown using nano cellulose (Nano Cellulose, NC), mixed cellulose ester (Mixed Cellulose Ester, MCE), chromatography paper and printing paper as base members according to an embodiment of the present invention.

[0049] Figure 3 (a) to Figure 3 (c) is a graph showing the results of measuring the electrochemical surface area according to the ratio of the reducing agent contained in the composition for producing a substrate for spectroscopic analysis according to an example of the present invention.

[0050] Figure 4 (a) to Figure 4 (d) is a photograph showing various forms of substrates for spectral analysis according to examples of the present invention.

[0051] Figure 5(a) to (c) of 5 show curves of SERS signal intensity at wavelengths of 633nm and 785nm after methylene blue (MB) is treated according to concentration when the reducing agent applied to the substrate for spectral analysis according to one embodiment of the present invention is hydroxylamine (the ratio of the reducing agent to the metal precursor is 1:2). Figure 5 (d) and Figure 5 (e) is a graph showing the signal uniformity of the substrate for spectral analysis according to one embodiment of the present invention, Figure 5 (f) is a diagram showing the flexibility of the substrate for spectroscopic analysis according to an embodiment of the present invention.

[0052] Figure 6 (a) is a SEM photograph showing changes in particle shape according to the ratio of the metal precursor and the reducing agent in the composition for manufacturing a substrate for spectroscopic analysis according to one embodiment of the present invention. Figure 6 (b) shows the variation of the absorption surface plasmon resonance (SPR) of the substrate for spectral analysis with wavelength according to the ratio of the metal precursor and the reducing agent in the composition for manufacturing the substrate for spectral analysis in one embodiment of the present invention, Figure 6 (c) is a graph showing the change in the SERS signal intensity of the substrate for spectral analysis with the wavelength according to the ratio of the metal ion precursor to the reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention.

[0053] Figure 7 (a) and Figure 7 (b) is a SEM photograph showing the change in particle shape according to the reaction time after the base member is supported in the composition for producing a substrate for spectral analysis according to the present invention ( Figure 7 (a)) and a graph showing the change in absorption SPR ( Figure 7 (b)).

[0054] Figure 8 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the hydroxylamine reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Figure 8 (b) shows Figure 8 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Figure 8 (c) shows the Figure 8 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Figure 8 (d) shows the Figure 8 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Figure 8 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the hydroxylamine reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0055] Fig. 9 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the ascorbic acid reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Fig. 9 (b) shows Fig. 9 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Fig. 9 (c) shows the Fig. 9 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Fig. 9 (d) shows the Fig. 9 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Fig. 9 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the ascorbic acid reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0056] Fig.10 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the FeSO4 reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Fig.10 (b) shows Fig.10 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Fig.10 (c) shows the Fig.10 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Fig.10 (d) shows the Fig.10 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Fig.10 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the FeSO4 reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0057] Fig.11 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the hydroxyquinone reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Fig.11 (b) shows Fig.11 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Fig.11 (c) shows the Fig.11 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Fig.11 (d) shows the Fig.11 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Fig.11 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the hydroxyquinone reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0058] Fig.12 (a) and Fig.12 (b) shows the substrate for spectral analysis according to an embodiment of the present invention at a wavelength of 633 nm ( Fig.12 (a)) and 785nm( Fig.12 (b) is a graph comparing SERS intensities of a substrate for spectral analysis produced by a composition for producing a substrate for spectral analysis containing a metal ion precursor and each reducing agent at an optimal ratio.

[0059] Fig.13 (a) to Fig.13 (d) schematically shows a portable Raman spectroscopic device ( Fig.13 (a) Method for on-site diagnosis of cancer.

[0060] Fig.14 FIG. 1 is a diagram showing a Raman spectroscopic apparatus according to an embodiment of the present invention.

[0061] Fig.15 (a) is a stereoscopic photograph of an adapter for a Raman spectroscopy device according to an embodiment of the present invention, Fig.15 (b) is Fig.15 (a) a front view of the adapter, Fig.15 (c) is Fig.15 (a) The front view of the adapter, Fig.15 (d) is Fig.15 (a) Bottom view of the adapter. Fig.15 (e) is Fig.15(a) A stereoscopic view of the adapter.

[0062] Fig.16 (a) is a plan view of an analysis component for a Raman spectroscopic device according to an embodiment of the present invention, Fig.16 (b) is Fig.16 (a) Plan view of the analysis component, Fig.16 (c) is Fig.16 (a) is the main view of the analysis component in the A direction, Fig.16 (d) is Fig.16 (a) is a side view of the analysis component in the B direction, Fig.16 (e) is Fig.16 (a) A stereogram of the analysis components.

[0063] Fig.17 is a photograph schematically showing a method of performing analysis by combining an adapter and an analysis component with a Raman spectroscopic apparatus according to an embodiment of the present invention.

[0064] Fig.18 A Raman spectroscopic device ( Fig.18 (a) Raman spectra of prostate cancer and pancreatic cancer measured Fig.18 (b) and Fig.18 (c)) and multivariate analysis data of prostate cancer and pancreatic cancer based on this ( Fig.18 (d) and Fig.18 (e)).

[0065] Fig.19 (a) is a SEM photograph showing the result of increasing the particle density as a result of surface modification using the surface modification composition according to one embodiment of the present invention, Fig.19 (b) is a graph showing the result of correspondingly improving signal uniformity. DETAILED DESCRIPTION

[0066] Figure 1 (a) shows a paper-based substrate for spectroscopic analysis manufactured using cellulose acetate as a base member according to an embodiment of the present invention. Figure 1 (b) to Figure 1 (e) shows Figure 1 (a) SEM photograph of the substrate for spectral analysis ( Figure 1 (b)), polycrystalline verification results ( Figure 1 (c)), particle formation mechanism ( Figure 1 (d)) and particle distribution curve ( Figure 1 (e)). Figure 2: is a SEM photograph showing the shape of particles grown using nano cellulose (Nano Cellulose, NC), mixed cellulose ester (Mixed Cellulose Ester, MCE), chromatography paper and printing paper as base members according to an embodiment of the present invention.

[0067] Figure 3 (a) to Figure 3 (c) is a graph showing the results of measuring the electrochemical surface area according to the ratio of the reducing agent contained in the composition for producing a substrate for spectroscopic analysis according to an example of the present invention.

[0068] The substrate for spectroscopic analysis of the present invention comprises: a base member; and a polycrystalline structure consisting of a plurality of nanoparticle clusters formed on the base member and having a plurality of grain boundaries, the substrate being formed by a solution process.

[0069] Reference Figure 1 (a) to Figure 1 (e) and Figure 2 , it can be confirmed that the formation of cellulose acetate (refer to Figure 1 (a) to Figure 1 (e)), and multiple nanoparticles on various other substrate members form clusters of polycrystalline (refer to Figure 2 ). Reference Figure 1 (d) shows that the Au precursor in the precious metal forms nanoparticles and forms clusters, especially, these are grown directly on the substrate member by solution process, but not limited to this. Specifically, the clustered nanoparticles form small-sized polygonal structure particles (grains) through coalescence, after which the particles gradually grow larger through oriented attachment growth. Thus, a polycrystalline structure with multiple grain boundaries is formed. Although not limited to this, the polycrystalline structure, that is, the particles in the form of precious metal corals, can grow to micrometer sizes on average (refer to Figure 1 As described above, when a polycrystalline structure having multiple grain boundaries is used as a substrate for spectral analysis because scattering at the multiple grain boundaries is increased, signal intensity and signal uniformity can be greatly improved.

[0070] There is no particular limitation on the base member applicable to the present invention, and various materials can be used. Although not limited to this, the base member can be composed of one or more of paper, polymer, orifice plate, chip and protein. Although not limited to this, the paper can be cellulose acetate, nanocellulose (Nano Cellulose, NC), mixed cellulose ester (Mixed Cellulose Ester, MCE), chromatography paper and commonly used printing paper. In addition, the substrate for spectral analysis can be a porous polymer, a plasma orifice plate, a chip and a protein membrane composed of one or more proteins such as silk, collagen, chitin, elastin, keratin, etc. Reference Figure 2 , it can be confirmed that the growth on nanocellulose (Nano Cellulose, NC) ( Figure 2 (a)), mixed cellulose ester (Mixed Cellulose Ester, MCE) ( Figure 2 (b)), chromatography paper ( Figure 2 (c)) and commonly used printing paper ( Figure 2 (d)) The polycrystalline structure of the similar structure on the base member. Although not limited to this, the base member can be a porous and / or flexible base member according to the field of application, and can also be a paper, polymer or protein film. In addition, the plasma aperture plate can be suitable for detecting multiple samples at the same time.

[0071] Although not limited thereto, the nanoparticles are connected in a branch structure, and the average particle size of the polycrystalline structure can be 1 μm to 100 μm. The substrate for spectral analysis of the present invention is grown into a polycrystalline structure by a solution process and connected in a branch structure, and the average particle size can be 1 μm to 100 μm. Although not limited thereto, the average particle size of the polycrystalline structure can be suitable for improving signal intensity and signal uniformity within the above range.

[0072] Although not limited thereto, the electrochemically active surface area (EASA) of the substrate for spectral analysis of the present invention may be 0.1 cm 2 Up to 10.0cm 2 The substrate for spectral analysis of the present invention is grown into a polycrystalline structure by a solution process, and the surface area can be increased. Figure 3 (a) to Figure 3 (c) It can be confirmed that the electrochemical surface area (EASA, cm 2) increases with the increase of the ratio of the reducing agent to the metal ion precursor contained in the composition for manufacturing a substrate for spectral analysis according to the present invention. In addition, when the ratio of the reducing agent to the metal ion precursor is less than 1:0.5, the density of the noble metal polycrystalline structure is low, resulting in the possibility of failure to conduct electricity.

[0073] Although not limited thereto, the nanoparticles may be composed of one or more of Au, Ag and Pt, and Au may be most suitable in terms of improving signal intensity and signal uniformity.

[0074] Although not limited thereto, the substrate for spectral analysis of the present invention may be applied to a Raman spectroscopy system having a wavelength of 500 nm or more or a Fourier transform infrared (near-IR FT) Raman spectroscopy system having a wavelength of 1064 nm.

[0075] Reference Figure 6 (b) It can be confirmed that when the substrate for spectral analysis according to the present invention is used, since a wide absorption region with a wavelength of 500 nm or more is displayed, a Raman spectroscopy system currently using various wavelengths can be utilized. Although not limited thereto, a wavelength of 633 nm or 785 nm may be more suitable.

[0076] Figure 4 (a) to Figure 4 (d) is a photograph showing various types of substrates for spectroscopic analysis according to an embodiment of the present invention.

[0077] Although not limited thereto, the spectral analysis substrate may be composed of a three-dimensional swab strip, a wearable substrate, or a plasma aperture plate. The spectral analysis substrate of the present invention may include various base members, may be made of flexible materials, and may have various shapes. Figure 4 In addition to the planar substrate, various forms can also be applied, such as a three-dimensional swab strip using a three-dimensional porous material, a wearable substrate form, a well plate form, and a protein membrane form.

[0078] The three-dimensional swab strip-shaped substrate for spectral analysis can easily collect samples, and the wearable substrate is composed of a patch or lens form, which can collect samples for a long time and can collect samples through the eyes. In addition, the plasma aperture plate can analyze a large number of samples at the same time, thereby shortening the analysis time.

[0079] According to another aspect of the present invention, the composition for manufacturing a substrate for spectral analysis of the present invention comprises a noble metal precursor and a reducing agent.

[0080] Figure 5 (a) to Figure 5(c) shows a curve graph of the SERS signal intensity at wavelengths of 633 nm and 785 nm after methylene blue (MB) is treated according to concentration when the reducing agent applied to the substrate for spectral analysis according to one embodiment of the present invention is hydroxylamine (the ratio of the reducing agent to the metal precursor is 1:2). Figure 5 (d) and Figure 5 (e) is a graph showing the signal uniformity of the substrate for spectral analysis according to one embodiment of the present invention, Figure 5 (f) is a diagram showing the flexibility of the substrate for spectroscopic analysis according to an embodiment of the present invention.

[0081] Reference Figure 5 (a) to Figure 5 (f) , using the spectral analysis substrate of the present invention made of cellulose acetate as the base member, after measuring the intensity of the SERS signal according to the concentration of methylene blue (MB), the SERS signal intensity was verified at wavelengths of 633nm and 785nm according to the concentration of methylene blue. When the spectral analysis substrate of the present invention is used, it can be confirmed that the signal uniformity is high and constant. In addition, the spectral analysis substrate of the present invention is small in size and flexible, and therefore, it is easy to carry and can be applied to various surfaces.

[0082] Although not limited thereto, if the ratio of the reducing agent to the noble metal precursor is less than 1:0.5, Raman spectroscopy systems of various wavelengths cannot be used, and if it exceeds 1:15, a film is formed and it is difficult to obtain a substrate for spectral analysis with excellent signal intensity and signal uniformity.

[0083] Therefore, in the composition for manufacturing a substrate for spectral analysis of the present invention, when the ratio of the reducing agent to the noble metal precursor is 1:0.5 to 1:15, it is suitable for manufacturing a substrate for spectral analysis with excellent signal intensity and signal uniformity, and can be 1:0.5 to 1:12, 1:0.5 to 1:10, 1:1 to 1:10, 1:1 to 1:9, 1:1 to 1:8, 1:1 to 1:7, 1:1 to 1:6, 1:1 to 1:5, 1:1 to 1:4, or 1:1 to 1:3. In addition, this range may be slightly different depending on the type of reducing agent.

[0084] Although not limited thereto, in the composition for manufacturing a substrate for spectroscopic analysis of the present invention, as the ratio of the reducing agent to the noble metal precursor increases, the size of the polycrystalline structure formed on the substrate for spectroscopic analysis decreases, and the density of the polycrystalline structure increases.

[0085] Figure 6(a) is a SEM photograph showing changes in particle shape according to the ratio of the metal precursor and the reducing agent in the composition for manufacturing a substrate for spectroscopic analysis according to one embodiment of the present invention. Figure 6 (b) shows the variation of the absorption surface plasmon resonance (SPR) of the substrate for spectral analysis with wavelength according to the ratio of the metal precursor and the reducing agent in the composition for manufacturing the substrate for spectral analysis in one embodiment of the present invention, Figure 6 (c) is a graph showing the change in the SERS signal intensity of the substrate for spectral analysis with the wavelength according to the ratio of the metal ion precursor to the reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention.

[0086] Reference Figure 6 It can be confirmed that when the ratio of the reducing agent to the metal precursor is low, the size of the polycrystalline structure is larger and the branch structure is less connected, but as the ratio of the reducing agent to the metal precursor increases, the size of the polycrystalline structure decreases and more branch structures are connected. In addition, according to the optimal ratio range of the reducing agent to the metal precursor in the composition for manufacturing the substrate for spectral analysis, the density of the polycrystalline structure increases, the transmittance decreases, and the absorbance increases, so that a Raman spectroscopic device with higher sensitivity can be manufactured.

[0087] Figure 7 (a) and Figure 7 (b) is a SEM photograph showing the change in particle shape according to the reaction time after the base member is supported in the composition for producing a substrate for spectral analysis according to the present invention ( Figure 7 (a)) and a graph showing the change in absorption SPR ( Figure 7 (b)).

[0088] In addition, refer to Figure 7 , showing the shape of particles over time when the substrate is supported in the composition for producing a substrate for spectral analysis according to the present invention. In particular, it can be confirmed that the absorbance increases as the load time increases.

[0089] Although not limited thereto, the noble metal precursor may be selected from the group consisting of HAuCl4, AuCl, AuCl2, AuCl3, Na2Au2Cl8 and NaAuCl2, but one or more of HAuCl4 and NaAuCl4 may be more suitable.

[0090] Although not limited thereto, the reducing agent may be one or more of hydroxylamine, ascorbic acid, FeSO 4 , and hydroxyquinone.

[0091] Figure 8 (a) to Fig.12 The optimal ratio of reducing agent to noble metal precursor is shown by comparing the SERS signal intensity when using hydroxylamine, ascorbic acid, FeSO4 and hydroxyquinone reducing agents.

[0092] Figure 8 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the hydroxylamine reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Figure 8 (b) shows Figure 8 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Figure 8 (c) shows the Figure 8 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Figure 8 (d) shows the Figure 8 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Figure 8 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the hydroxylamine reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0093] Reference Figure 8 In the case of hydroxylamine reducing agent, the particle density increases from a ratio of 1:1, and as the ratio of reducing agent to noble metal precursor increases, the SERS intensity also increases. The ratio of 1:2, where the strongest SERS signal is observed, can be set as the optimal ratio, and a ratio of more than 1:1 and less than 1:5 can be set as the optimal ratio range.

[0094] Fig. 9 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the ascorbic acid reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Fig. 9 (b) shows Fig. 9 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Fig. 9 (c) shows the Fig. 9 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Fig. 9 (d) shows the Fig. 9 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Fig. 9 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the ascorbic acid reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0095] Reference Fig. 9 In the case of ascorbic acid reducing agent, at a wavelength of 785 nm, as the ratio of reducing agent to noble metal precursor increases, the intensity of SERS signal also increases. The ratio of 1:10 at which the strongest SERS signal is observed can be set as the optimal ratio, and the ratio of 1:0.5 to 1:15 can be set as the optimal ratio range. However, at a wavelength of 633 nm, the ratio of 1:1 at which the strongest SERS signal is observed can be set as the optimal ratio, and 1:0.5 to 1:15 can be set as the optimal ratio range.

[0096] Fig.10 (a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the FeSO4 reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Fig.10 (b) shows Fig.10 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Fig.10 (c) shows the Fig.10 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Fig.10 (d) shows the Fig.10 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Fig.10 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the FeSO4 reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0097] Reference Fig.10 In the case of FeSO4 reducing agent, as the ratio of reducing agent to noble metal precursor increases, the SERS intensity also increases. The ratio of 1:5, where the strongest SERS signal is observed, can be set as the optimal ratio, and the ratio exceeding 1:1 and below 1:15 can be set as the optimal ratio range.

[0098] Fig.11(a) is a photograph showing the color change of the substrate for spectral analysis according to the ratio of the metal ion precursor and the hydroxyquinone reducing agent in the composition for manufacturing the substrate for spectral analysis according to one embodiment of the present invention, Fig.11 (b) shows Fig.11 (a) is a graph showing the change in the absorption SPR of the substrate for spectral analysis, Fig.11 (c) shows the Fig.11 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 633 nm for the spectral analysis substrate. Fig.11 (d) shows the Fig.11 (a) is a graph showing the change in SERS signal intensity measured at a wavelength of 785 nm for a spectral analysis substrate. Fig.11 (e) is a SEM photograph showing the particle shape of the substrate for spectral analysis according to an embodiment of the present invention, showing the ratio of the metal ion precursor and the hydroxyquinone reducing agent in the composition for manufacturing the substrate for spectral analysis.

[0099] Reference Fig.11 In the case of a hydroxyquinone reducing agent, a ratio of 1:2 at which the observed SERS signal is the strongest can be set as an optimal ratio, and a ratio of 1:0.5 to less than 1:15 can be set as an optimal ratio range.

[0100] Fig.12 (a) and Fig.12 (b) shows the substrate for spectral analysis according to an embodiment of the present invention at a wavelength of 633 nm ( Fig.12 (a)) and 785nm( Fig.12 (b) is a graph comparing SERS intensities of a substrate for spectral analysis produced by a composition for producing a substrate for spectral analysis containing a metal ion precursor and each reducing agent at an optimal ratio.

[0101] Reference Fig.12 , the optimal ratio for each reducing agent was derived, and the optimized conditions for all reducing agents were confirmed at wavelengths of 633 nm and 785 nm.

[0102] According to another aspect of the present invention, there is provided a Raman spectroscopic device, comprising: a light source; the spectral analysis substrate described in the present invention; and a detector for detecting the Raman spectrum.

[0103] Fig.13 (a) to Fig.13 (d) schematically shows a portable Raman spectroscopic device ( Fig.13 (a) Method for on-site diagnosis of cancer.

[0104] Reference Fig.13 (a) to Fig.13 (d) shows, as an example, a Raman spectroscopic device and an analysis method, wherein a spectral analysis substrate (sensor) and a portable Raman spectroscopic device according to the present invention are used to analyze urine excretion containing cancer cell metabolites, and Raman spectra are derived to diagnose prostate cancer and pancreatic cancer through multivariate analysis and on-site analysis.

[0105] Fig.14 FIG. 1 is a diagram showing a Raman spectroscopic apparatus according to an embodiment of the present invention. Fig.15 (a) is a stereoscopic photograph of an adapter for a Raman spectroscopy device according to an embodiment of the present invention, Fig.15 (b) is Fig.15 (a) a front view of the adapter, Fig.15 (c) is Fig.15 (a) The front view of the adapter, Fig.15 (d) is Fig.15 (a) Bottom view of the adapter. Fig.15 (e) is Fig.15 (a) A stereoscopic view of the adapter.

[0106] Fig.16 (a) is a plan view of an analysis component for a Raman spectroscopic device according to an embodiment of the present invention, Fig.16 (b) is Fig.16 (a) Plan view of the analysis component, Fig.16 (c) is Fig.16 (a) is the main view of the analysis component in the A direction, Fig.16 (d) is Fig.16 (a) is a side view of the analysis component in the B direction, Fig.16 (e) is Fig.16 (a) A stereogram of the analysis components.

[0107] Reference Figures 14 to 16 The Raman spectroscopic device 200 of the present invention may further include: an adapter 100 coupled to the Raman spectroscopic device 200; and an analysis component 10 installed on the adapter 100 and the strip substrate for spectroscopic analysis for analysis.

[0108] Reference Figures 14 to 16The adapter 100 has a cylindrical main body 110, a first end of which is open and has a hollow portion 112, and the first end is provided with a coupling portion 112a coupled to the Raman spectroscopic device 200. The coupling portion 112a may be a thread formed on the inner side of the cylindrical main body 110. In addition, the second end of the adapter 100 is provided with a coupling portion 114 formed with a through hole 116 for guiding light from a light source. The coupling portion 114 may be configured to be stably coupled to the analysis component 10.

[0109] Reference Fig.15 and Fig.16 The analysis component 10 is formed in a spoon shape, including a head 20 and a straight-line main body 22 extending from the head 20. The head 20 includes: a hemispherical mounting portion 30 for mounting the coupling portion 114 of the second end of the adapter 100; and a mounting groove 40 extending from the center of the main body 22 along the length direction to the hemispherical mounting portion 30 for mounting the straight-line strip substrate for spectral analysis.

[0110] Although not limited thereto, the mounting groove 40 has a terminal portion 42 extending to the mounting portion 30 to form a T-shape so that the terminal of the spectral analysis strip substrate does not separate from the hemispherical mounting portion 30 , thereby improving analysis accuracy.

[0111] Fig.17 is a photograph schematically showing a method of performing analysis by combining an adapter and an analysis component with a Raman spectroscopic apparatus according to an embodiment of the present invention.

[0112] Reference Fig.17 First, screw the adapter onto the Raman spectroscopy device ( Fig.17 (a) and Fig.17 Then, the adapter coupled to the Raman spectroscopy device is connected to the analysis component ( Fig.17 (c)). The strip substrate for spectral analysis is pushed into the mounting groove of the analysis component and then the analysis is performed.

[0113] Although not limited thereto, the target material of the detector may be selected from one or more of cells, metabolites, proteins, nucleic acids, DNA, RNA, enzymes, organic molecules, viruses, extracellular vesicles, microvesicles, exosomes and fat in urine, saliva, sweat and tears.

[0114] Although not limited thereto, the target material is a liquid sample, and since conventional substrates for spectral analysis have low hygroscopicity, the sensitivity is low when measuring liquid samples. However, the substrate for spectral analysis according to the present invention has hygroscopicity, so even liquid samples can be quickly diagnosed on site.

[0115] Although not limited to this, the Raman spectroscopy device can realize on-site diagnosis of cancer. Although not limited to this, the information required for cancer diagnosis can be provided by analyzing the metabolites of the above-mentioned target material, cancer can be diagnosed at an early stage through non-invasive examination, and multiple analyses with extremely high sensitivity can be performed.

[0116] The cancer can be one or more selected from the group consisting of lung cancer, bronchial cancer, colorectal cancer, prostate cancer, breast cancer, gastric cancer, ovarian cancer, bladder cancer, brain cancer, thyroid cancer, esophageal cancer, uterine cancer, liver cancer, kidney cancer, biliary tract cancer, prostate cancer and pancreatic cancer, but is not limited to these. Prostate cancer or pancreatic cancer may be more suitable.

[0117] Fig.18 A Raman spectroscopic device ( Fig.18 (a) Raman spectra of prostate cancer and pancreatic cancer measured Fig.18 (b) and Fig.18 (c)) and multivariate analysis data of prostate cancer and pancreatic cancer based on this ( Fig.18 (d) and Fig.18 (e)).

[0118] According to another aspect, the cancer diagnosis method using the Raman spectroscopic device according to the present invention can be performed according to known multivariate analysis methods. For the multivariate analysis method of the entire spectrum, it can be analyzed by known analysis methods, such as the commonly used partial least squares discriminant analysis (PLS-DA), discriminant analysis (GDA) and principal component analysis (PCA), parallel factor analysis (PARAFAC), neural network analysis (NNA) and / or support vector machine (SVM), etc., but not limited to this.

[0119] Although not limited thereto, a method for diagnosing cancer according to an embodiment may include: a step of removing a background signal from an acquired spectrum; a step of performing a partial least squares discriminant analysis (PLS-DA) on the entire spectrum to obtain a latent variable; a step of distinguishing between two input groups based on the variable; and a step of confirming its reliability.

[0120] As described above, according to the present invention, cancer can be accurately and quickly diagnosed on site, especially prostate cancer and pancreatic cancer with a diagnostic accuracy rate exceeding 90%.

[0121] According to another aspect, a method for manufacturing a substrate for spectral analysis is a method for manufacturing a substrate for spectral analysis described in the present invention, comprising: a) preparing a substrate member; b) forming a polycrystalline structure by supporting the substrate member in a composition for manufacturing a substrate for spectral analysis. A detailed description of the parts that overlap with the description of the substrate for spectral analysis described above will be omitted.

[0122] Step a) is a step of preparing a base member. As described above, various base members can be used in the present invention. Although not limited thereto, a base member composed of one or more of paper, polymer, well plate, wafer and protein can be prepared.

[0123] Step b) is a step of forming a polycrystalline structure by loading a substrate member in a composition for manufacturing a substrate for spectral analysis. The composition for manufacturing a substrate for spectral analysis comprises a noble metal precursor and a reducing agent solution, and is composed of a plurality of clusters of nanoparticles formed directly on the substrate member by a solution process to form a polycrystalline structure with a plurality of grain boundaries.

[0124] Step b) may include a shape adjustment step for adjusting the shape of the polycrystalline structure by setting the ratio of the reducing agent to the precious metal precursor solution to 1:0.5 to 1:15. By adjusting the optimal ratio of the reducing agent according to the type of the reducing agent, the shape of the polycrystalline structure formed on the substrate for spectral analysis can be easily adjusted. In addition, by adjusting the time for loading the base member in the composition for manufacturing the substrate for spectral analysis, the shape of the polycrystalline structure formed on the substrate for spectral analysis can be easily adjusted. The method for manufacturing a substrate for spectral analysis of the present invention can improve signal intensity and signal uniformity at the same time through a single process so-called one-time loading.

[0125] Although not limited thereto, the step a) in the method for manufacturing a substrate for spectral analysis of the present invention may further include a surface modification step of modifying the surface of the base member before forming a polycrystalline structure. The surface modification step is not limited thereto, and particle formation may be adjusted by chemical surface treatment, and particle density may be increased when particles are formed after surface modification.

[0126] Although not limited thereto, in the method for manufacturing a substrate for spectral analysis of the present invention, the surface modification step includes at least one selected from 1% to 3% of a base and 1% to 3% of an acid, and a solvent containing C 1-5 The surface of the base member is treated with a surface modification composition of alcohol or water. Although not limited thereto, using 1% of the base and acid and using ethanol as a solvent may be suitable for improving signal intensity and signal uniformity.

[0127] Fig.19 (a) and Fig.19 (b) shows the result of surface modification using the surface modification composition according to one embodiment of the present invention. Fig.19 (a) is a SEM photograph showing the result of increasing the particle density as a result of surface modification using the surface modification composition according to one embodiment of the present invention, Fig.19 (b) is a graph showing the result of correspondingly improving the signal uniformity. It can be confirmed that the particle density is increased by using the surface modification composition according to one embodiment of the present invention, and the signal uniformity is improved by the increase in the particle density.

[0128] Example

[0129] 1. Manufacturing of substrates for spectral analysis

[0130] A three-dimensional swab stick, a wearable patch and a film-like substrate member composed of paper and a porous polymer are manufactured. A composition for manufacturing a substrate for spectral analysis is prepared by mixing a reducing agent solution to a noble metal precursor solution at a ratio of 5:1, 2:1, 1:1 to 1:15. The substrate member must be loaded within 1 minute after the composition is prepared. In the case of an orifice plate, the composition is loaded in each hole of the orifice plate for preparation. The prepared substrate member is loaded in a mixed composition for manufacturing the substrate for spectral analysis for 30 seconds to 24 hours to form a polycrystalline structure formed by a cluster of multiple nanoparticles on the substrate member. The composition for manufacturing the substrate uses HAuCl4 as a noble metal precursor solution, and uses hydroxylamine, ascorbic acid, FeSO4 and hydroxyquinone as a reducing agent. After forming a polycrystalline structure, wash at least twice with water or ethanol to remove the remaining precursor and reducing agent. Then, dry at room temperature for more than 1 hour to complete the manufacture of the substrate for spectral analysis.

[0131] result

[0132] Regardless of the composition and form of the base member, such as a three-dimensional swab stick made of paper, a porous sponge, a patch, and a membrane, the greater the ratio of the reducing agent solution to the precious metal precursor solution contained in the composition used to manufacture the substrate for spectral analysis, the smaller the size of the aggregated polycrystalline structure on the manufactured substrate for spectral analysis, and the higher the density of the polycrystalline structure.

[0133] Thus, the transmittance decreases and the absorbance increases. In addition, most of the polycrystalline structures are distributed between an average particle size of 1 μm and 100 μm, and the optimal ratio of the reducing agent to the noble metal precursor is derived according to the type of reducing agent, taking into account the SERS sensitivity and the SERS signal intensity.

[0134] Table 1 below shows the optimal ratio range of the reducing agent to the noble metal precursor according to the kind of the reducing agent.

[0135]

Table 1

[0136] Reducing agent type Optimal ratio range of reducing agent Hydroxylamine (HA) 1:1 or more and less than 1:5 Ascorbic acid (AA) 1:0.5 to 1:15 <![CDATA[FeSO4]]> More than 1:1 and less than 1:15 Hydroxyquinone (HQ) 1:0.5 to less than 1:15

[0137] Above, the specific parts of the content of the present invention are described in detail. It should be clear to those skilled in the art that these specific descriptions are only preferred embodiments and are not intended to limit the scope of the present invention. Therefore, the actual scope of the present invention will be defined by the appended claims and their equivalents.

Claims

1. A substrate for spectral analysis, wherein: include: Base member; as well as A polycrystalline structure consisting of a plurality of nanoparticle clusters formed on the base member composition, has multiple grain boundaries, and is formed by solution processing.

2. The substrate for spectral analysis according to claim 1, wherein The base member is composed of one or more of paper, polymer, well plate, chip and protein.

3. The substrate for spectral analysis according to claim 1, wherein The nanoparticles are connected by a branch structure, and the average particle size of the polycrystalline structure is 1 μm to 100 μm.

4. The substrate for spectral analysis according to claim 1, wherein The electrochemically active surface area is 0.1 cm 2 Up to 10.0cm 2 .

5. The substrate for spectral analysis according to claim 1, wherein The nanoparticles are composed of one or more of Au, Ag and Pt.

6. The substrate for spectral analysis according to claim 1, wherein The substrate for spectral analysis can be applied to a Raman spectroscopy system using a wavelength of 500 nm or more or a Fourier transform near-infrared Raman spectroscopy system using a wavelength of 1064 nm.

7. The substrate for spectral analysis according to claim 1, wherein The substrate for spectral analysis is composed of a three-dimensional swab strip, a wearable substrate or a plasma aperture plate.

8. A composition for manufacturing a substrate for spectral analysis, wherein: Contains a noble metal precursor and a reducing agent, wherein the ratio of the reducing agent to the noble metal precursor is 1:0.5 to 1:

15.

9. The composition for producing a substrate for spectral analysis according to claim 8, wherein As the ratio of the reducing agent to the noble metal precursor increases, the size of the polycrystalline structure formed on the substrate for spectral analysis decreases, and the density of the polycrystalline structure increases.

10. The composition for producing a substrate for spectral analysis according to claim 8, wherein The noble metal precursor is one or more of HAuCl4 and NaAuCl4.

11. The composition for producing a substrate for spectral analysis according to claim 8, wherein The reducing agent is one or more of hydroxylamine, ascorbic acid, FeSO4 and hydroxyquinone.

12. A Raman spectroscopy device, wherein: include: light source; The substrate for spectral analysis according to claim 1; as well as A detector is used to detect Raman spectra.

13. The Raman spectroscopy device according to claim 12, wherein: Also includes: an adapter, which is cylindrical with an open first end, the first end having a coupling portion coupled to the Raman spectroscopic device, and a second end having a coupling portion formed with a through hole for inducing light from a light source; and The measuring member is spoon-shaped and consists of a head and a straight-line main body extending from the head. The head has: a hemispherical mounting portion for mounting a coupling portion of the second end of the adapter; and a mounting groove extending along the length direction at the center of the main body to the hemispherical mounting portion for mounting a straight-line strip substrate for spectral analysis.

14. The Raman spectroscopic device according to claim 13, wherein: The mounting groove is formed in a T-shape to prevent a distal end of the bar substrate for spectral analysis from being separated from the hemispherical mounting portion.

15. The Raman spectroscopic device according to claim 12, wherein: The target material of the detector is selected from one or more of cells, metabolites, proteins, nucleic acids, DNA, RNA, enzymes, organic molecules, viruses, extracellular vesicles, microvesicles, exosomes and fats in urine, saliva, sweat and tears.

16. The Raman spectroscopy device according to claim 12, wherein: The Raman spectroscopy device can perform on-site diagnosis of cancer.

17. A method for producing a substrate for spectral analysis, which is the method for producing a substrate for spectral analysis according to claim 1, wherein: include: a) a base member preparation step of preparing a base member; as well as b) The step of loading the base member in a composition for manufacturing a substrate for spectral analysis containing a noble metal precursor and a reducing agent solution, and forming a polycrystalline structure composed of a plurality of clusters of nanoparticles on the base member to have a plurality of grain boundaries, including the step of adjusting the shape of the polycrystalline structure by setting the ratio of the reducing agent to the noble metal precursor solution to 1:0.5 to 1:15 in the step b).

18. The method for producing a substrate for spectral analysis according to claim 17, wherein: The step a) further comprises a surface modification step of modifying the surface of the base member before the step of forming the polycrystalline structure.

19. The method for producing a substrate for spectral analysis according to claim 18, wherein: The surface modification step includes at least one selected from 1% to 3% of a base and 1% to 3% of an acid, and using a 1-5 A step of treating the surface of the base member with a surface modifying composition of alcohol or water as a solvent.

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