Raman spectroscopic device, capillary tube, and method for manufacturing capillary tube

Abstract

To provide a Raman spectroscopic device that accurately detects a target molecule from a minute amount of sample without requiring a large-sized laser scanning microscope.SOLUTION: A Raman spectroscopic device comprises: a capillary tube that has an inner wall modified by a metal nano structure; an optical system that makes excitation light incident from one end of the capillary tube to be coupled to a guided mode of the capillary tube, and takes out Raman scattered light from one end or the other end of the capillary tube; and a spectroscope that detects the Raman scattered light.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to a Raman spectroscopic device, a capillary tube used in Raman scattering spectroscopy, and a method for producing a capillary tube. [Background technology]

[0002] In modern society, environmental pollution and destruction of nature are progressing on a global scale, and a wide variety of diseases are spreading. Preservation of the living environment and food safety are urgent issues, and highly sensitive and easy-to-use molecular detection technology is required to detect harmful substances such as microplastics, dioxins, and food additives, as well as viruses and cancer cells. Surface-enhanced Raman scattering (SERS) has a higher detection sensitivity than conventional Raman spectroscopy. Raman spectroscopy measures the characteristic spectrum that appears in the Raman scattered light generated by the interaction between molecular vibrations and the electric field on the surface of a material, but the signal strength is generally weak and it is not suitable for detecting trace amounts of molecules. In contrast, SERS increases the detection sensitivity of Raman spectroscopy by adsorbing target molecules onto a surface modified with metal nanoparticles and utilizing the electric field enhancement effect on the surface of the metal nanoparticles.

[0003] A method for producing a substrate for SERS measurement in which dendrites are formed on the surface of the substrate has been proposed (see, for example, Patent Document 1 and Non-Patent Document 1). A SERS tube is known in which the inner wall of a cylindrical container with an inner diameter of 0.1 mm to 10 mm is coated with metal nanoparticles by a laser ablation method (see, for example, Patent Document 2). [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Patent No. 6813894 [Patent Document 2] Special table 2014-509744 [Non-patent literature]

[0005] [Non-Patent Document 1] K. Nogami, K. Kishimoto, Y. Hashimoto, H. Watanabe, Y. Hishii, Q. Ma, T. Niki, T. Kotani, T. Kiwa, S. Shoji, T. Ohkubo, J. Kano, N. Takeyasu, "Self-growth of silver tree-like fractal structures with different geometries", Appl. Phys. A 128(10), 860 (2022) Summary of the Invention [Problem to be solved by the invention]

[0006] Current SERS measurements, which use Raman spectroscopy as a core technology, require a large laser scanning microspectrometer (sometimes called a "Raman microscope"). In addition, the intensity of Raman scattered light varies greatly depending on the variation in metal nanoparticles and the degree of adsorption between target molecules and metal nanoparticles, making reproducibility low and quantitative evaluation difficult. A large volume of sample is required for SERS measurements, and there is a limit to the detectable concentration. The present invention aims to provide a Raman spectrometer that detects target molecules with high sensitivity from a small amount of sample without requiring a large laser scanning microscope, and a capillary tube used for Raman spectroscopy. [Means for solving the problem]

[0007] A capillary tube whose inner wall is modified with a metal nanostructure is used as a sample container and at the same time functions as an optical waveguide to measure Raman scattered light. a capillary tube whose inner wall is modified with a metal nanostructure; an optical system for inputting excitation light into one end of the capillary tube and coupling it with a waveguide mode of the capillary tube, and extracting Raman scattered light from the light emitted from the one end or the other end of the capillary tube; a spectrometer for detecting the Raman scattered light; Equipped with.

[0008] In another aspect, the capillary tube comprises: A hollow tube having an inner diameter of 1 μm or more and less than 100 μm; A metal nanostructure formed on the inner wall of the hollow tube; has. Effect of the Invention

[0009] A Raman spectroscopic device is realized that can detect target molecules from a minute amount of sample with high sensitivity without requiring a large laser scanning microspectroscopic device. [Brief description of the drawings]

[0010] [Figure 1] FIG. 1 is a system block diagram of a Raman spectroscopic apparatus according to an embodiment. [Diagram 2] FIG. 2 is a schematic diagram of a capillary tube according to an embodiment. [Diagram 3] These are an optical image and a scanning electron microscope (SEM) image of a hollow glass tube used in a capillary tube. [Figure 4] SEM images of silver nanoparticles formed on the inner wall of a hollow glass tube using silver nitrate solutions of different concentrations. [Diagram 5] FIG. 1 is a schematic diagram of the silver mirror reaction. [Figure 6] This is an SEM image of silver nanostructures deposited on the inner wall of a hollow glass tube by the silver mirror reaction. [Figure 7] FIG. 1 is a diagram showing the relationship between the size of silver nanoparticles and the resonance wavelength. [Figure 8] FIG. 1 is a diagram showing the setup for SERS measurements. [Figure 9] FIG. 1 shows a comparison of a SERS spectrum obtained using a capillary tube according to an embodiment with a spectrum obtained using a flat SERS substrate. [Figure 10]1 shows Raman spectra of Rhodamine 6G measured in capillary tubes made with different silver ion concentrations. [Figure 11] These are Raman spectra of Rhodamine 6G measured using capillary tubes of the same inner diameter but different lengths. [Figure 12] FIG. 1 shows the relationship between the length of a capillary tube and SERS intensity. [Figure 13] 1 shows Raman spectra of samples with different concentrations. [Figure 14] FIG. 10 is a diagram showing a comparison of a Raman spectrum measured using a capillary tube according to an embodiment with a Raman spectrum measured using a hollow glass tube whose inner wall is not modified. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Hereinafter, the embodiments of the present invention will be described in detail with reference to the drawings. In the drawings, components having the same functions are given the same reference numerals, and duplicated descriptions may be omitted. The size, positional relationship, etc. of each member shown in each drawing may be exaggerated to facilitate understanding of the invention.

[0012] <Configuration of Raman spectrometer and capillary tube> FIG. 1 is a system block diagram of a Raman spectroscopic device 10 according to an embodiment. The Raman spectroscopic device 10 includes a capillary tube 15 whose inner wall is modified with a metal nanostructure, an excitation light source 11, an objective lens 13, an optical filter 18, and a spectrometer 17. The excitation light source 11, the objective lens 13, and the optical filter 18 are part of an optical system 130 that couples the excitation light to the waveguide mode of the capillary tube 15 and guides the excitation light and Raman scattered light that have been guided through the capillary tube 15 to the spectrometer 17. The objective lens 13 focuses the excitation light emitted from the excitation light source 11 on one end of the capillary tube 15 and couples it to the waveguide mode of the capillary tube 15. The optical filter 18 removes unnecessary wavelength components from the light emitted from one end or the other end of the capillary tube 15, and extracts the Raman scattered light. The spectrometer 17 disperses the Raman scattered light that has passed through the optical filter 18 and detects its intensity.

[0013] The capillary tube 15 functions as a sample container and also as an optical waveguide, enabling detection of dilute molecules contained in a very small amount of sample. By the capillary tube 15 functioning as a waveguide, the entire sample inside the capillary tube 15 can be irradiated with the excitation light incident on the capillary tube 15, and the generated Raman scattered light can be guided to the end of the capillary tube 15 without leaking to the outside.

[0014] 2 is a schematic diagram of the capillary tube 15 of the embodiment. Fig. 2(A) shows the coupling of the pump light Lpump to the waveguide mode of the capillary tube 15, and Fig. 2(B) shows the waveguide state in the capillary tube 15 and the generation of Raman scattered light.

[0015] The capillary tube 15 has a hollow tube 151 and a metal nanostructure 153 formed on the inner wall of the hollow tube 151. The hollow tube 151 is, for example, a glass hollow tube with an inner diameter of 1 μm or more and less than 100 μm, and the length of the hollow tube 151 is 500 times or more, preferably 1000 times or more, more preferably more than 1000 times longer than the inner diameter. During SERS measurement, a sample solution containing target molecules 155 is introduced into the capillary tube 15. Excitation light Lpump is incident from one end of the capillary tube 15 and coupled to the waveguide mode of the capillary tube 15. The excitation light Lpump is guided inside the capillary tube 15 along the optical axis of the capillary tube 15.

[0016] As described later, the longer the length of the capillary tube 15 capable of guiding the light, the higher the detection sensitivity and the more efficient the SERS measurement becomes. This is because the surface area of ​​the inner wall of the capillary tube 15 can be increased, and the opportunities for interaction between the target molecules and the excitation light Lpump near the inner wall can be increased.

[0017] As shown in FIG. 2B, when the metallic nanostructure 153 formed on the inner wall of the capillary tube 15 is irradiated with the excitation light Lpump, an optical electric field 154 is formed which is enhanced by local plasmon resonance. When exposed to the strong optical electric field 154, substances (including target molecules 155) adsorbed or bound to the surface of the metallic nanostructure 153 generate Raman scattering light (indicated as "SERS" in the figure) which is tens of thousands of times stronger than normal Raman scattering. Raman scattering is inelastic scattering, and information on the target molecule can be obtained from the frequency shift.

[0018] The generated Raman scattered light and excitation light Lpump are guided to the end of the capillary tube 15. This guided mode uniformly excites the metal nanostructure 153 formed on the inner wall of the capillary tube 15. The Raman scattered light from the target molecules is enhanced by an optical electric field 154 caused by local plasmon resonance. The enhanced Raman scattered light is guided through the capillary tube 15 together with the excitation light, and thus its intensity is cumulatively increased, thereby increasing the detection sensitivity.

[0019] The Raman spectroscopic device 10 using the capillary tube 15 is not only capable of detecting chemical information of organic or inorganic materials through label-free observation, but also has high detection sensitivity and can be widely used in biomedical and medical diagnosis.

[0020] FIG. 3 shows an optical image and an SEM image of a hollow tube 151 used for a capillary tube. The hollow tube 151 is formed by working a glass tube. The hollow tube 151 has an inner diameter of 20 μm, an outer diameter of 25 μm, and a length of 20 mm, but the inner diameter, outer shape, and length of the hollow tube 151 can be appropriately set depending on the purpose of use. From the viewpoint of attaching a metal nanostructure 153 having a size of 5 nm to several hundreds of nm to the inner wall and securing a guided mode of excitation light and SERS light, it is desirable that the inner diameter of the hollow tube 151 is 1 μm or more and less than 100 μm. From the viewpoint of securing the surface area of ​​the inner wall and sufficiently increasing the detection sensitivity, the length of the hollow tube 151 is 500 times or more, preferably 1000 times or more, and more preferably longer than 1000 times the inner diameter.

[0021] FIG. 4 shows SEM images of silver nanoparticles formed on the inner wall of the hollow tube 151 using silver nitrate solutions of different concentrations. The silver ion concentration of the ammoniacal silver nitrate aqueous solution is changed to (a) 0.8 mol / L, (b) 1.0 mol / L, (c) 1.2 mol / L, (d) 1.4 mol / L, (e) 1.6 mol / L, and (f) 1.8 mol / L. The silver nitrate aqueous solution is introduced into the inside of the hollow glass tube in FIG. 3 together with a reducing agent by capillary action, and silver nanoparticles are generated on the inner wall of the hollow glass tube by the silver mirror reaction. The density of silver nanoparticles attached to the inner wall of the hollow tube 151 can be controlled by adjusting the silver ion concentration of the silver nitrate aqueous solution used.

[0022] When the silver ion concentration is 0.8 mol / L (a), the silver particles grow as thin, sharp, plate-like crystals with diameters of 100 nm to 200 nm. Increasing the silver ion concentration to 1.0 mol / L (b) and 1.2 mol / L (c) does not significantly change the length of the silver particles produced, but the crystals begin to swell into the shape of rice grains. When the silver ion concentration is increased to 1.4 mol / L (d), the surfaces of the silver particles grow into a more irregular, random shape. Careful observation of the particle surfaces reveals that each particle is formed as an aggregate of many small nanoparticles. When the silver ion concentration is further increased to 1.6 mol / L (e) and 1.8 mol / L (f), the particles grow into round, three-dimensional shapes and the particle density increases.

[0023] Figure 5 is a schematic diagram of the silver mirror reaction. Ammoniacal silver nitrate solution contains diamine silver ions [Ag(NH3)2] + and hydroxide ion OH - When this ammoniacal silver nitrate solution is introduced into the glass hollow tube, 1.0 mL of a glucose solution with a concentration of 1.0 mol / L is added. This glucose (CH 12 O6) forms a chain structure in aqueous solution and functions as a reducing agent with an aldehyde group (R-CHO).

[0024] When a mixture of an aqueous solution of ammoniacal silver nitrate and an aqueous solution of glucose is introduced into the inside of a hollow glass tube by capillary action, silver ions (Ag+) are reduced by the aldehyde group to produce silver (Ag), which is then oxidized to a carboxylic acid (R-COOH).

[0025] FIG. 6 is an SEM image of silver nanoparticles formed on the inner wall of a hollow glass tube. Various particles with diameters of 10 nm to several hundred nm are formed. As described with reference to FIG. 4, the shape and density of the generated silver nanoparticles can be adjusted by controlling the silver ion concentration of the silver nitrate aqueous solution. To use a hollow tube with silver nanoparticles formed on its inner wall as the capillary tube 15 of the embodiment, first, deionized water is introduced into the hollow tube with the silver nanoparticles formed thereon to remove excess silver ions and glucose residues, and then the tube is dried.

[0026] Figure 7 shows the relationship between the size of silver nanoparticles and the resonance wavelength. The horizontal axis is the wavelength of the excitation light, and the vertical axis is the absorbance. The resonance wavelength is measured for silver nanoparticles of sizes 50 nm, 75 nm, and 110 nm. Silver nanoparticles with a diameter of 50 nm have an absorption peak near a wavelength of 420 nm (spectrum A). Silver nanoparticles with a diameter of 75 nm have a high absorption peak near a wavelength of 450 nm (spectrum B). Silver nanoparticles with a diameter of 110 nm show absorption in a wide range from 410 nm to 700 nm (spectrum C). When the spectra in Figure 7 are interpolated to the long wavelength side, it is predicted that absorption will occur even on the wavelength side longer than 700 nm with silver nanoparticles with a diameter of several hundred nanometers.

[0027] It can be seen that by forming silver nanostructures with diameters of 10 nm to several hundred nm on the inner wall of capillary tube 15, an optical electric field can be generated by local plasmon resonance using an excitation light source with a wavelength of 400 nm to 800 nm.

[0028] <Measurement and evaluation using Raman spectroscopy> 8 is a diagram showing a setup for SERS measurement. In this setup, a Raman spectroscopic device 10A includes a capillary tube 15 whose inner wall is modified with a metal nanostructure 153, an optical system for inputting excitation light into one end of the capillary tube 15 and coupling it to the waveguide mode of the capillary tube 15, and extracting Raman scattered light from the light emitted from the one end or the other end of the capillary tube, and a spectrometer 17 for detecting the Raman scattered light. The optical system includes at least an objective lens 13 for coupling the excitation light to the waveguide mode of the capillary tube 15, and an optical filter 18 for extracting the SERS light generated inside the capillary tube 15.

[0029] When using the capillary tube 15 for SERS measurement, silver nanoparticles are formed as metal nanostructures on the inner wall, and deionized water is introduced into the hollow tube 151 in which the silver nanoparticles are formed to remove silver ions and glucose residues, followed by drying. Then, a sample solution is introduced into the capillary tube 15.

[0030] A He-Ne laser with a wavelength of 633 nm is used as the excitation light source 11 that outputs excitation light. In the setup shown in Fig. 8, the excitation light is incident on one end of the capillary tube 15, and the excitation light and scattered light (including SERS light and Rayleigh scattered light) are extracted from the same incident end, but the excitation light and scattered light that have been guided inside the capillary tube 15 may be extracted from the other end of the capillary tube 15.

[0031] In the optical system, the excitation light output from the excitation light source 11 is expanded by the beam expander 12. The beam expander 12 is composed of a first lens 121 and a second lens 122. As an example, the focal length of the first lens is 25.4 mm, and expands the diameter of the incident excitation light. The focal length of the second lens is 100.0 mm, and outputs the excitation light whose diameter has been expanded by the first lens 121 as collimated light.

[0032] The collimated light passes through the dichroic filter 131, mirrors M1 and M2, and the objective lens 13 and enters one end of the capillary tube 15. The dichroic filter 131 reflects the excitation light with a wavelength of 633 nm and transmits light with other wavelengths. In this example, the numerical aperture of the objective lens 13 is 0.35, and the excitation light is focused at one end of the capillary tube 15 and coupled to the waveguide mode of the capillary tube 15.

[0033] The excitation light guided inside the capillary tube 15 interacts with target molecules in the sample solution to generate inelastic Raman scattered light. The Raman scattered light is amplified by the optical electric field of the excited metal nanoparticles. The amplified light is guided inside the capillary tube 15 together with the excitation light as SERS light including backward Raman scattered light. The excitation light and scattered light, which are guided through the capillary tube 15 and emitted from the end, are collected by the objective lens 13 and enter the dichroic filter 131 via mirrors M2 and M1.

[0034] The SERS light passes through the dichroic filter 131, and the excitation light and the Rayleigh scattered light are reflected. The actual reflectance of the dichroic filter 131 is not 100%, and some of the excitation light and the Rayleigh scattered light may pass through the dichroic filter 131. The measurement light that passes through the dichroic filter 131 passes through mirrors M4 and M5, and the beam diameter is expanded by the beam expander 16. The beam expander 16 is, for example, composed of a third lens 161 with a focal length of 35.0 mm and a fourth lens 162 with a focal length of 200.0 mm. The measurement light expanded by the beam expander 16 is guided to the optical filter 18 by the mirror M6. The optical filter is a notch filter that cuts off the 633 nm excitation light, removes the excitation light and the Rayleigh scattered light mixed in the measurement light, and transmits the SERS light. The SERS light is detected by the spectrometer 17. The spectrometer 17 includes, for example, a CCD array cooled by liquid nitrogen.

[0035] FIG. 9 is a diagram showing a SERS spectrum (D) obtained using the capillary tube 15 of the embodiment in comparison with a spectrum (E) obtained using a flat SERS substrate. 28 H 31 ClN2O3) 5.0×10 -3 A mol / L solution is used. The output power of a He-Ne laser with a wavelength of 632.8 nm is 30 mW, and the exposure time is 10 seconds. In the SERS measurement using a capillary tube 15, the wave number is 615 cm -1 , 775cm -1 , 1300cm -1 , 1360cm -1 , 1500cm -1 , 1645cm -1 A sharp peak of rhodamine 6G is observed at wavenumber 615 cm. -1 The peak at 775m is the in-plane bending vibration mode of the C-C bond. -1 The peak at 1300 cm is the out-of-plane bending vibration mode of the C-H bond. -1 , 1360cm -1 , 1500cm -1 , and 1645 cm -1 The peak indicates an aromatic stretching vibration mode.

[0036] For comparison, the measurement results using a known flat SERS substrate are shown. The peak intensity is very small compared to the SERS measurement using the capillary tube 15 of the embodiment. Conversely, the peak intensity of the SERS measurement using the capillary tube 15 of the embodiment is high, and the detection efficiency is greatly improved. In particular, at 650 cm -1 , 900cm -1 , 1250cm -1 , 1550cm -1 A small peak observed nearby is not detected at all with conventional SERS substrates, but is well visualized using the capillary tube 15 .

[0037] A notable feature of the SERS measurement of the embodiment is that even with a very small amount of sample solution, accurate measurement results as shown in FIG. 9 can be obtained. The amount of sample solution used is determined by the inner diameter and length of the capillary tube 15. The capillary tube 15 used in the setup of FIG. 8 and the measurement of FIG. 9 has an inner diameter of 20 μm and a length of 10 mm, which corresponds to a volume of about 3.0 nL. This volume is only one ten-thousandth of the volume of a typical water droplet.

[0038] <Metal ion concentration> In order to investigate the optimal concentration for forming silver nanoparticles on the inner wall of the capillary tube 15, a 5.0×10 silver ion concentration was measured using capillary tubes 15 prepared with different silver ion concentrations. -3 Obtain SERS spectra using mol / L rhodamine 6G solution.

[0039] FIG. 10 shows the results of the measurement of the concentration of rhodamine 6G (5.0×10 -36 shows the Raman spectrum of a silver nitrate solution containing 0.8 mol / L silver ions. The silver ion concentration of the silver nitrate solution is changed to 0.8 mol / L, 1.0 mol / L, 1.2 mol / L, 1.4 mol / L, and 1.8 mol / L. The maximum SERS intensity is obtained when the silver ion concentration is 1.4 mol / L. This indicates that the local surface plasmon resonance is most efficiently generated in the capillary tube 15 by the 632.8 nm excitation light.

[0040] As shown in the SEM image of FIG. 4, the shape of the silver nanoparticles is irregular, with numerous protrusions due to aggregation of tiny nanoparticles. In general, it is known that symmetric silver nanoparticles, such as spherical ones, exhibit strong localized surface plasmon resonance at 450 nm, but the excitation light used in the embodiment is outside the resonant wavelength of the localized surface plasmon resonance of typical silver nanoparticles. It is believed that the random nanoscale shape of the metal particle surface enhances the efficiency of localized surface plasmon resonance by 632.8 nm excitation light, forming SERS "hot spots."

[0041] <Capillary tube length> FIG. 11 shows the concentration of rhodamine 6G (5.0×10 -3 The Raman spectra of 1.4 mol / L silver nitrate solution are shown in Fig. 11. The inner diameter of all capillary tubes is 20 μm, and silver nanoparticles formed by silver mirror reaction of 1.4 mol / L silver nitrate solution are formed on the inner wall. The length of the capillary tube is changed to 10 mm, 15 mm, 20 mm, and 25 mm, and SERS measurements are performed on each capillary tube. The output power of the excitation light is 30 mW, and the irradiation time is 10 seconds. From the results in Fig. 11, it can be seen that all SERS peaks increase as the length of the capillary tube increases.

[0042] When the length of the capillary tube is 10 mm, it is 500 times longer than the inner diameter of 20 μm. By making the length of the capillary tube 500 times longer than the inner diameter, the Raman shift peaks at each wavenumber are clearly observed. When the length of the capillary tube is 20 mm, it is 1000 times longer than the inner diameter of 20 μm, and each peak appears more prominently compared to when the length is 10 mm or 15 mm. When the length of the capillary tube is 25 mm, the peaks become sharper and stronger.

[0043] Figure 12 shows the relationship between the length of the capillary tube and the SERS intensity. -1 FIG. 12 shows the Raman peaks re-plotted at 100 nm. The Raman intensity is linearly proportional to the length of the capillary tube. In other words, the detection sensitivity of the SERS measurement is improved simply by increasing the length of the capillary tube 15. This result is derived rationally from the measurement principle of the embodiment that utilizes the waveguide mode of the capillary tube 15.

[0044] <Concentration of sample solution> Figure 13 shows Raman spectra of sample solutions with different concentrations. To investigate the detection limit of the SERS measurement using the capillary tube 15, the concentration of the rhodamine 6G aqueous solution was (a) 1.0 × 10 -5 mol / L, (b) 1.0×10 -6 mol / L, (c) 1.0×10 -8 mol / L, (d) 1.0×10 -9 mol / L. The output power of the excitation light with a wavelength of 632.8 nm is 30 mW, and the irradiation time is 10 seconds. As the concentration of the sample solution decreases, the peak intensity of the SERS measurement decreases. In Figure 13, the peak intensity of the lowest sample concentration (d) is 10 times that of the other measurements (a), (b), and (c). From Figure 13, it can be seen that when the sample concentration is 1.0 × 10 -9 This shows that molecular detection is possible even from extremely dilute solutions of mol / L.

[0045] The detection sensitivity of the Raman spectrometer 10A using the capillary tube 15 of the embodiment is such that about 200,000 molecules can be detected from a sample solution of only 3 nL. The detection limit can be further improved by extending the irradiation time of the excitation light, increasing the output power of the excitation light, or reducing the inner diameter of the capillary tube 15.

[0046] <SERS effect of capillary tube> To confirm that the high-sensitivity Raman spectroscopy described above can be achieved by the SERS effect, -9 Using a mol / L rhodamine 6G aqueous solution (FIG. 13(d)), SERS measurements are performed in a capillary tube whose inner wall is not modified with silver nanoparticles.

[0047] 14 shows a Raman spectrum (a) measured using the capillary tube of the embodiment, together with a spectrum (b) measured using a capillary tube whose inner wall is not modified with silver nanoparticles. No Raman peaks are observed in the measurement results using a capillary tube without surface modification with silver nanoparticles. High-sensitivity Raman spectroscopy using the capillary tube 15 of the embodiment is largely due to the effect of the optical electric field caused by the local surface plasmon formed by the metal nanostructure on the inner wall of the tube, as well as the waveguiding characteristics of the capillary tube 15.

[0048] In this way, by using the capillary tube 15 of the embodiment, stronger Raman scattering light can be obtained compared to the conventional SERS substrate, and target molecules can be detected even with a very small amount of sample solution or a very dilute sample solution. By making the capillary tube 15 thinner and longer, the detection sensitivity is improved. This is because the ratio of target molecules that enter the optical electric field of the local surface plasmon formed along the inner wall of the capillary tube 15 increases, and the interaction between the excitation light and the target molecule is accumulated by the guided mode. The capillary tube 15 does not need to be linear. This is because the excitation light and Raman scattered light are guided in the internal space of the tube even in a hollow tube that is slightly curved. The detection sensitivity can be maximized by optimizing the length of the capillary tube 15.

[0049] By using the capillary tube 15 of the embodiment, it is possible to detect a target molecule with high sensitivity even from a very small amount of sample solution on the order of a few nanoliters. -5 ~1.0×10 -9 It is possible to detect target molecules in a dilute sample solution of mol / L. When a silver nanostructure with a diameter of 10 nm to several hundred nm is formed on the inner wall of the capillary tube 15, it is possible to use excitation light in the wavelength range of 400 nm to 800 nm. The Raman spectroscopy device of the embodiment can be constructed without using the optical system of a laser scanning microscope normally used in Raman spectroscopy, as long as there is an excitation light source of an appropriate wavelength, a coupler with the capillary tube 15, and a small spectroscope.

[0050] The capillary tube 15 and the Raman spectrometer 10 or 10A of the embodiment can detect microplastics, various dioxins, drugs such as cocaine, cancer cells, and the like. When forming metal dendrites as the metal nanostructure, the dendrites can be adsorbed on the inner wall of the capillary tube 15 by a rapid reduction reaction of a high-concentration metal ion solution inside the hollow tube. Alternatively, the metal dendrites may be modified with a molecule that is compatible with the metal (for example, silver dendrites and a silane coupling agent), dispersed in a low-viscosity solvent, and introduced into the inside of the hollow tube. Unlike highly symmetrical spherical nanoparticles, dendrites can excite local surface plasmons over a wide range of wavelengths from visible light to near-infrared light. Therefore, it is possible to freely select the wavelength of the excitation laser according to the optical properties (absorption spectrum, etc.) of the molecules to be detected. In addition, dendrites have a hierarchical fractal structure on the nanoscale, and have a very high surface area compared to their volume. This increases the number of molecules that reside within the electric field of the localized surface plasmon, increasing the probability of enhancing Raman scattered light, dramatically improving detection sensitivity. These effects mean that the use of dendrites can further enhance the effectiveness of this technology.

[0051] As the material of the metal nanostructure, in addition to silver (Ag), gold (Au), copper (Cu), platinum (Pt), etc. may be used. The outer surface of the capillary tube 15 may be coated with a material having a lower refractive index than the hollow tube 151. In this case, too, the inner space of the hollow tube 151 can be used as a waveguide core to guide the excitation light and Raman scattered light to the end of the hollow tube while keeping them confined inside the hollow tube. The capillary tube and Raman spectrometer of the embodiment enable highly sensitive molecular detection even in a very small amount or a very dilute sample liquid.

[0052] The above disclosure includes the following features. (Section 1) a capillary tube whose inner wall is modified with a metal nanostructure; an optical system for inputting excitation light into one end of the capillary tube and coupling it with a waveguide mode of the capillary tube, and extracting Raman scattered light from the light emitted from the one end or the other end of the capillary tube; a spectrometer for detecting the Raman scattered light; A Raman spectroscopic apparatus comprising: (Section 2) The inner diameter of the capillary tube is less than 100 μm, and the internal space of the capillary tube is a waveguide core that guides the excitation light and the Raman scattered light. Item 1. The Raman spectroscopic device according to item 1. (Section 3) The length of the capillary tube is at least 500 times the inner diameter. Item 3. The Raman spectroscopic device according to item 2. (Section 4) The capillary tube guides the excitation light and the Raman scattered light in a direction along an optical axis of the capillary tube. Item 4. The Raman spectroscopic device according to any one of items 1 to 3. (Section 5) The optical system includes a lens that focuses the excitation light on the one end of the capillary tube, and an optical filter that extracts the Raman scattered light from the guided light that is guided through the capillary tube and emitted from the one end or the other end. Item 5. The Raman spectroscopic device according to any one of items 1 to 4. (Section 6) A hollow tube having an inner diameter of 1 μm or more and less than 100 μm; A metal nanostructure formed on the inner wall of the hollow tube; A capillary tube having (Section 7) The length of the hollow tube is 500 times or more the inner diameter. Item 7. The capillary tube according to item 6. (Section 8) The outer surface of the hollow tube is coated with a material having a lower refractive index than the hollow tube. Item 6. The capillary tube according to item 6 or 7. (Section 9) The metal nanostructure is a metal nanoparticle or a metal dendrite. Item 9. The capillary tube according to any one of items 6 to 8. (Section 10) Providing an aqueous solution of an ammoniacal metal nitrate; A reducing agent is added to the aqueous solution, and the aqueous solution containing the reducing agent is introduced into a capillary tube by capillary action; reducing metal ions contained in the aqueous solution to form metal nanostructures on the inner wall of the capillary tube; How to make a capillary tube. [Explanation of symbols]

[0053] 10, 10A Raman spectrometer 11 Excitation light source 12, 16 Beam expander 13 Objective Lens 15 Capillary Tube 17 Spectrometer 18 Optical Filters 130 Optical system 151 Hollow tube 153 Metal Nanostructures 154 Optical electric field 155 Target Molecules Lpump Excitation light

Claims

1. a capillary tube whose inner wall is modified with a metal nanostructure; an optical system for inputting excitation light into one end of the capillary tube and coupling it with a waveguide mode of the capillary tube, and extracting Raman scattered light from the light emitted from the one end or the other end of the capillary tube; a spectrometer for detecting the Raman scattered light; A Raman spectroscopic apparatus comprising:

2. The inner diameter of the capillary tube is less than 100 μm, and the internal space of the capillary tube is a waveguide core that guides the excitation light and the Raman scattered light.

2. The Raman spectroscopy apparatus of claim 1.

3. The length of the capillary tube is at least 500 times the inner diameter.

3. The Raman spectroscopy apparatus of claim 2.

4. The capillary tube guides the excitation light and the Raman scattered light in a direction along an optical axis of the capillary tube.

2. The Raman spectroscopy apparatus of claim 1.

5. The optical system includes a lens that focuses the excitation light on the one end of the capillary tube, and an optical filter that extracts the Raman scattered light from the guided light that is guided through the capillary tube and emitted from the one end or the other end.

2. The Raman spectroscopy apparatus of claim 1.

6. A hollow tube having an inner diameter of 1 μm or more and less than 100 μm; A metal nanostructure formed on the inner wall of the hollow tube; A capillary tube having

7. The length of the hollow tube is 500 times or more the inner diameter. The capillary tube according to claim 6.

8. The outer surface of the hollow tube is coated with a material having a lower refractive index than the hollow tube. The capillary tube according to claim 6.

9. The metal nanostructure is a metal nanoparticle or a metal dendrite. The capillary tube according to claim 6.

10. Providing an aqueous solution of an ammoniacal metal nitrate; A reducing agent is added to the aqueous solution, and the aqueous solution containing the reducing agent is introduced into a capillary tube by capillary action; reducing metal ions contained in the aqueous solution to form metal nanostructures on the inner wall of the capillary tube; How to make a capillary tube.

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