Multi-purpose meta-material analysis device and analysis method

Abstract

To provide a multi-purpose meta-material analysis device and method capable of identifying the chemical species of an unknown substance and performing state analysis and quantitative analysis of the unknown substance.SOLUTION: A multi-purpose meta-material analysis device comprises: a meta-material substrate 1 on which a metal nanostructure array 62 is formed; a light source 11 capable of selectively irradiating the meta-material substrate 1 with white light and laser light; a spectrometer 12 that acquires a spectrum of a desired wavelength from reflected light and transmitted light reflected and transmitted by the meta-material substrate 1; and a detector 13 that detects the reflected light and transmitted light output from the spectrometer 12. The device further includes a data analysis unit 53 configured to: measure the Raman spectrum of a sample adsorbed on the meta-material substrate 1 on the basis of the spectrum of the wavelength included in the reflected light when laser light is irradiated from the light source 11; measure the refractive index of the sample on the basis of the spectrum of the wavelength included in the reflected light and transmitted light when white light is irradiated from the light source 11; and perform state analysis and quantitative analysis of the sample on the basis of the Raman spectrum and the refractive index.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a multipurpose metamaterial analysis device and method. [Background technology]

[0002] Spectroscopic sensing using surface plasmons does not require complex sample pretreatment and can perform quantitative analysis with simple operations when the chemical species of the sample to be analyzed is known, so it is used as a practical analytical technique, particularly for biosensing purposes.

[0003] Furthermore, in fields such as biosensing, environmental analysis, food analysis, and component / impurity analysis, there is a demand for the development of devices that can rapidly identify the chemical species of unknown substances, perform quantitative analysis, directly identify the molecules of unknown substances, and perform state analysis of the molecular structure, oxidation state, proton dissociation, etc. in a series of operations.

[0004] In biosensing, it is useful for medical diagnosis such as gene diagnosis, enzyme reaction analysis, ion channel analysis, virus analysis, etc. In environmental analysis, it is useful for analysis of air pollutants such as PM2.5 and volatile organic molecules, residual pesticides in natural water, industrial wastewater, and drinking water in developing countries, heavy metal ions such as mercury and chromium, inorganic ions such as cyanide and arsenic ions, benzene, PCB, dioxin, and other harmful molecules.

[0005] In addition, in food analysis, it is useful for analyzing residual pesticides, harmful colorants, and toxic substances, and in component and impurity analysis, it is useful for analyzing various components and impurities in the manufacturing processes of pharmaceuticals, semiconductors, steel, etc.

[0006] Patent Document 1 discloses an invention regarding a refractive index sensor that uses a metamaterial substrate having a microstructure smaller than the wavelength of incident light, and is capable of precisely measuring the refractive index of a sample to quantitatively analyze the sample. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2019 / 039551 Summary of the Invention [Problem to be solved by the invention]

[0008] However, although the technique disclosed in Patent Document 1 can precisely measure the refractive index of a sample, it has a problem in that it is difficult to quantitatively analyze an unknown substance whose chemical species is not specified.

[0009] The present invention has been made to solve the above-mentioned problems in the conventional art, and an object of the present invention is to provide an analytical apparatus and an analytical method capable of identifying the chemical species of an unknown substance and performing state analysis and quantitative analysis of the unknown substance. [Means for solving the problem]

[0010] In order to achieve the above-mentioned object, the multipurpose metamaterial analysis device of the present invention comprises a substrate on which an array of metal nanostructures is formed, a light source capable of switching between irradiating the substrate with white light and laser light, a spectrometer for acquiring a spectrum of a desired wavelength from the reflected light, transmitted light and Raman scattered light reflected and transmitted by the substrate, a detector for detecting the reflected light, transmitted light and Raman scattered light output from the spectrometer, and a data analysis unit for measuring the Raman spectrum of a sample adsorbed on the substrate based on the spectrum of wavelengths contained in the Raman scattered light when irradiated with laser light from the light source, measuring the refractive index of the sample based on the spectrum of wavelengths contained in the reflected light and transmitted light when irradiated with white light from the light source, and performing state analysis and quantitative analysis of the sample based on the Raman spectrum and the refractive index.

[0011] The multipurpose metamaterial analysis method of the present invention comprises the steps of adsorbing a sample to be measured onto a substrate on which an array of metal nanostructures is formed; irradiating the substrate with laser light and identifying the sample from the spectrum of Raman scattered light reflected and transmitted by the substrate; irradiating the substrate with white light and detecting the refractive index of the sample from the spectrum of the reflected light and transmitted light reflected and transmitted by the substrate; and performing state analysis and quantitative analysis of the sample based on the identification results and the refractive index of the sample. Effect of the Invention

[0012] According to the present invention, it is possible to identify the chemical species of an unknown substance and to perform state analysis and quantitative analysis of the unknown substance. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a block diagram showing the configuration of an analysis device according to an embodiment. [Diagram 2] FIG. 2 is a block diagram showing a detailed configuration of the control unit shown in FIG. [Figure 3A] FIG. 3A is an example of a plan view showing the configuration of a metallic nanostructure array. [Figure 3B] FIG. 3B is an example of a side view showing the configuration of a metallic nanostructure array. [Figure 4] FIG. 4 is a flowchart showing a processing procedure of the analysis device according to the embodiment of the present invention. [Diagram 5] FIG. 5 is an explanatory diagram showing a state in which a sample solution is adsorbed onto a multipurpose metamaterial substrate. [Figure 6] FIG. 6 is a characteristic diagram showing a Raman spectrum. [Figure 7] FIG. 7 is a characteristic diagram showing a reflectance spectrum. [Figure 8A] FIG. 8A is a side view SEM image of a substrate coated with a monolayer of nanoparticles and a metal deposition film thereon. [Figure 8B]FIG. 8B is a top view of an SEM image of a substrate coated with a monolayer of nanoparticles and a metal deposition film thereon. [Figure 9A] FIG. 9A is an explanatory diagram showing an SEM image of an AuPS-NP system in which 40 nm-thick Au was evaporated onto PS nanoparticles. [Figure 9B] FIG. 9B is a magnified SEM image of the AuPS-NP system in which 40 nm-thick Au was deposited on the PS nanoparticles. [Figure 10A] FIG. 10A shows an SEM image of a SiO2-NP system in which 40 nm thick Au was deposited on silica nanoparticles. [Figure 10B] FIG. 10B is a close-up SEM image of the SiO2-NP system in which 40 nm thick Au was deposited on the silica nanoparticles. [Figure 11A] FIG. 11A is an experimental characteristic curve showing the relationship between the wavelength of laser light and the absorbance when a substrate with 40 nm of silver (Ag) deposited on SiO2-NP nanoparticles is used. [Figure 11B] FIG. 11B is an experimental characteristic curve showing the relationship between the wavelength of the laser light and the absorbance when a substrate with 40 nm of gold (Au) deposited on SiO2-NP nanoparticles is used. [Figure 12A] FIG. 12A is a theoretically calculated characteristic curve showing the relationship between wavelength and reflectance for various medium refractive indices when a substrate with gold evaporated onto the surface of nanoparticles is used. [Figure 12B] FIG. 12B is a theoretically calculated characteristic curve showing the relationship between wavelength and reflectance for various medium refractive indices when a substrate with silver evaporated onto the surface of nanoparticles is used. [Figure 13A] FIG. 13A is a plan view showing a configuration in which cylindrical silica nanoparticles are formed on the surface of a substrate. [Figure 13B] FIG. 13B is a side view showing a configuration in which cylindrical silica nanoparticles are formed on the surface of a substrate. [Figure 14] FIG. 14 is a characteristic curve showing the relationship between the medium refractive index n and the wavelength shift. [Figure 15A]FIG. 15A is a characteristic curve showing the relationship between the wave number of the incident light and the intensity of the Raman scattered light when a substrate was used in which TP was adsorbed onto the surface of nanoparticles and silver (Ag) was evaporated onto silica nanoparticles. [Figure 15B] FIG. 15B is a characteristic curve showing the relationship between the wave number of the incident light and the intensity of the Raman scattered light when a substrate was used in which TP was adsorbed onto the surface of nanoparticles and gold (Au) was deposited onto silica nanoparticles. [Figure 16A] FIG. 16A is a characteristic curve showing the relationship between the wave number of the incident light and the intensity of the Raman scattered light when a substrate in which silver is deposited on silica nanoparticles is used, and shows the case in which a NaCl solvent of catechol is used. [Figure 16B] FIG. 16B is a characteristic curve showing the relationship between the wave number of the incident light and the intensity of the Raman scattered light when a substrate in which silver is deposited on silica nanoparticles is used, and shows the case in which a NaOH solvent of catechol is used. [Figure 17] FIG. 17 is a characteristic curve showing the relationship between the Raman spectrum of incident light and measurement time when a substrate in which silver is deposited on silica nanoparticles is used. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] [Configuration of the embodiment] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. Fig. 1 is a block diagram showing the configuration of a multipurpose metamaterial analysis device according to an embodiment of the present invention. As shown in Fig. 1, a multipurpose metamaterial analysis device 100 (hereinafter abbreviated as "analysis device 100") includes a multipurpose metamaterial substrate 1 (hereinafter abbreviated as "metamaterial substrate 1"), a spectrometer 2, a driving unit 3, and a control unit 4.

[0015] 3A and 3B are examples of explanatory diagrams, with Fig. 3A being a plan view and Fig. 3B being a side view, that typically show the configuration of the first embodiment of the metamaterial substrate 1. As shown in Fig. 3A and 3B, the metamaterial substrate 1 includes a transparent substrate 61 such as a glass substrate or a silicon substrate, and a metal nanostructure array 62 (also referred to as a "metamaterial") is formed on the surface of the transparent substrate 61.

[0016] The shape and size of the metallic nanostructure array 62 are set so that the wavelength of surface plasmon resonance (SPR) falls within the visible to near infrared range (500 to 1000 nm).

[0017] Furthermore, the shape and size of the metallic nanostructure array 62 are optimized so that the refractive index sensitivity is maximized and the electric field strength in the vicinity of the metallic nanostructure array 62 during light irradiation is maximized. As an example, the metallic nanostructure array 62 can be formed by arranging eight metallic nanostructures so that w=90 nm, g=150 nm, d=150 nm, l=330 nm, and Λ=1000 nm as shown in Fig. 3A. Also, t=40 [nm] as shown in Fig. 3B can be used.

[0018] As described above, by controlling the size w, axial ratio (w:l), and spacing (g) of each metal nanostructure in the metal nanostructure array 62 (see FIG. 3A), it is possible to change the white light to a short wavelength in the near-infrared region (<1000 nm) that is the plasmon resonance wavelength. Note that the metamaterial substrate 1 can also be configured as in the second embodiment, as described later.

[0019] When the metamaterial substrate 1 is irradiated with laser light having a wavelength close to that of surface plasmon resonance, the metal nanostructure array 62 is irradiated with 10 times more light than the incident light near the surface of the metal nanostructure array 62. 2 ~10 5 By utilizing this enhanced electric field, the Raman scattering of the adsorbed species on the substrate surface can be increased by 10 4 ~10 10 fold increase from a single molecule to a monolayer (approximately 10 6 It is now possible to measure Raman spectra of up to 100 molecules.

[0020] In other words, by using the metamaterial substrate 1 having the metal nanostructure array 62, the refractive index of a sample (unknown substance) can be measured in the visible to near-infrared wavelength range (500 to 1000 nm) by surface plasmon resonance. Furthermore, it becomes possible to measure the Raman spectrum of a sample solution with a wide range of concentrations.

[0021] As shown in FIGS. 3A and 3B, metallic nanostructure array 62 has a structure that is approximately the same as the wavelength of incident light or is equal to or smaller than the wavelength of incident light, and is made up of unit structures that are two-dimensionally and periodically arranged with rotational symmetry.

[0022] The metamaterial substrate 1 is configured to exhibit wavelength-selective optical response by increasing the optical coupling between the incident light and a surface plasmon mode dependent on the metallic nanostructure array 62 under a resonance condition. The metallic nanostructure array 62 has unit structures formed in rotational symmetry and is polarization independent.

[0023] As an example, the metallic nanostructure array 62 can be made of gold (Au), which has a high reflectance in the near-infrared region. The metallic nanostructure array 62 may be made of silver, copper, or transition metal nitrides and oxides having a high carrier concentration and exhibiting plasmonic properties, in addition to gold. In a specific example shown in Figures 3A and 3B, the metallic nanostructure array 62 is formed by electron beam lithography technology, and has a structure in which two parallel-arranged rectangular parallelepipeds are arranged in four-fold symmetry.

[0024] Returning to FIG. 1, the spectrometer 2 includes a light source 11, a spectrometer 12, and a detector 13.

[0025] The light source 11 includes a white light source 31 that emits white light and a laser light source 32 that emits laser light. The light source 11 can select either the white light source 31 or the laser light source 32 under the control of the drive unit 3.

[0026] The white light source 31 is a light source for reflection and transmission spectroscopy, and emits light in the visible to near infrared range (500 to 1000 nm), for example. The white light source 31 is, for example, a xenon lamp or a halogen lamp.

[0027] Laser light source 32 irradiates narrowband laser light for Raman spectroscopy having an oscillation line near the resonance wavelength of metallic nanostructure array 62. Laser light source 32 is a solid-state laser or a semiconductor laser, and irradiates laser light of a single wavelength (for example, 671 nm, 785 nm).

[0028] The light source 11 irradiates the metamaterial substrate 1 on which a sample is adsorbed with white light or laser light via the incident light probe 41. The reflected light, transmitted light, and Raman scattered light scattered by the metamaterial substrate 1 on which a sample is adsorbed (hereinafter, the reflected light, transmitted light, and Raman scattered light are collectively referred to as "signal light") are collected on the entrance slit 38 of the spectrometer 12 via the signal light probe 42. The incident light probe 41 and the signal light probe 42 can be a microscope probe or an optical fiber probe. The use of an optical fiber probe allows flexibility between the metamaterial substrate 1 and the spectrometer 12, which is useful, for example, when the analysis device 100 is made portable.

[0029] The spectrometer 12 is capable of performing Raman spectroscopy simultaneously with reflection and transmission spectroscopy. The spectrometer 12 has a housing structure that is entirely light-shielded. The spectrometer 12 includes a diffraction grating unit 33, a collimator mirror 34, and a camera mirror 35. The spectrometer 12 has an entrance slit 38. The signal light emitted from the metamaterial substrate 1 on which the sample chemical species are adsorbed passes through a signal light probe 42 and enters the inside of the spectrometer 12 from the entrance slit 38.

[0030] The collimator mirror 34 converts the light incident on the spectrometer 12 through the entrance slit 38 into parallel light and introduces it to the diffraction grating section 33 .

[0031] Diffraction grating unit 33 separates the light reflected by collimator mirror 34. Diffraction grating unit 33 is rotationally controlled by drive unit 3 so that light of a desired wavelength among the separated wavelengths (frequencies) is irradiated onto camera mirror 35, and multiple diffraction gratings having different ruling numbers can be selected for use.

[0032] The camera mirror 35 reflects the light of the desired wavelength diffracted by the diffraction grating unit 33 in the direction of the detector 13. That is, by controlling the rotation of the diffraction grating unit 33, it is possible to select light of the desired wavelength contained in the light introduced into the spectrometer 12 and introduce it into the camera mirror 35 and then into the detector 13.

[0033] The detector 13 includes a single channel detector 36 for reflection / transmission spectroscopy and a CCD type multichannel detector 37 for Raman spectroscopy. The single channel detector 36 is, for example, a silicon-based photodiode. In addition to the single channel detector 36, a semiconductor detector such as a photomultiplier tube or an InGaAs (indium gallium arsenide) detector may be used as a detector for reflection / transmission spectroscopy. By providing an exit slit immediately before the single channel detector for reflection / transmission spectroscopy, high-resolution measurement is realized. In this embodiment, an example in which both the single channel detector 36 for reflection / transmission spectroscopy and the CCD type multichannel detector 37 for Raman spectroscopy are installed will be described. However, if sufficient wavelength resolution and sensitivity for a wide range of wavelengths and reflection / transmission and Raman spectrum measurement can be realized, one multichannel detector may be used.

[0034] As a detector for Raman spectroscopy, in addition to the CCD type multichannel detector 37, a multichannel detector equipped with a photodiode array (PDA) may be used.

[0035] The single channel detector 36 detects light over a wide range of wavelengths. In this embodiment, the single channel detector 36 is used to detect signal light when the metamaterial substrate 1 is irradiated with white light from the white light source 31 before and after the sample chemical species are adsorbed. In other words, the single channel detector 36 is used to detect a change in the resonance wavelength from the reflection and transmission spectra of the adsorbed sample to measure the refractive index of the sample.

[0036] The CCD type multichannel detector 37 detects the Raman scattering spectrum of light scattered from the sample adsorbed on the metamaterial substrate 1 and separated by the spectrometer 12 into intensities for each wave number.

[0037] That is, the detector 13 includes a single channel detector 36 that detects the reflection and transmission spectrum from the metamaterial substrate 1 on which the sample is adsorbed and is output from the spectrometer 12, and a CCD type multichannel detector 37 that detects Raman scattered light from the sample due to laser light, and the single channel detector 36 and the CCD type multichannel detector 37 can be selectively switched under the control of the control unit 4.

[0038] The control unit 4 controls the switching of the light source 11, the rotation of the diffraction grating unit 33, and the switching of the detector 13. The control unit 4 identifies the chemical species of the sample (unknown substance) to be measured based on the measurement data detected by the detector 13, and performs state analysis and quantitative analysis of the sample. Fig. 2 is a block diagram showing the detailed configuration of the control unit 4.

[0039] As shown in FIG. 2, the control unit 4 includes an input unit 51, a drive control unit 52, a data analysis unit 53, a database 54, and an output unit 55.

[0040] The control unit 4 can be configured as an integrated computer including, for example, a central processing unit (CPU) and storage means such as RAM, ROM, and a hard disk.

[0041] The input unit 51 accepts an input operation by a user. When a Raman analysis of a sample is to be performed by a user operation, an input operation to the effect of Raman analysis is performed. When a refractive index measurement of a sample is to be performed by a user operation, an input operation to the effect of refractive index measurement is performed.

[0042] The drive control unit 52 outputs control signals for the light source 11, the diffraction grating unit 33, and the detector 13 based on the operation input input to the input unit 51. Specifically, when the measurement of the reflection / transmission spectrum is set by the input unit 51, the drive control unit 52 outputs a control signal for setting the light source 11 shown in FIG. 1 to the white light source 31 and for setting the detector 13 to the single channel detector 36. When the measurement of the Raman spectrum is set by the input unit 51, the drive control unit 52 outputs a control signal for setting the light source 11 to the laser light source 32 and for setting the detector 13 to the CCD type multichannel detector 37.

[0043] Furthermore, when measurement of the reflection / transmission spectrum is set, the drive control unit 52 sets and controls a diffraction grating with an appropriate number of rulings and an angle in the diffraction grating unit 33 so that a desired wavelength band contained in the reflected light / transmitted light is irradiated onto the camera mirror 35. When measurement of the Raman spectrum is set, the drive control unit 52 sets the diffraction grating unit 33 so that a desired wavelength band is irradiated onto the camera mirror 35.

[0044] The data analysis unit 53 acquires and analyzes the measurement data detected by the detector 13. Specifically, the data analysis unit 53 identifies the chemical species of the sample based on the Raman spectrum detected by the CCD type multichannel detector 37. Furthermore, the data analysis unit 53 performs a state analysis of the sample.

[0045] The data analysis unit 53 also acquires the reflection and transmission spectra detected by the single channel detector 36, and performs quantitative analysis of the chemical species of the sample. When performing state analysis and quantitative analysis, the data analysis unit 53 refers to data stored in a database 54, which will be described later. The database 54 has a calibration curve for performing state analysis and quantitative analysis of the sample based on the sample identification result and the refractive index of the sample. The user can also create and use a new calibration curve (concentration and reflection and transmission peak shifts) for the sample identified in the data analysis unit 53.

[0046] Based on a drive command output from the drive control unit 52, the drive unit 3 controls the settings of the light source 11, the settings of the detector 13, the settings of the diffraction grating in the diffraction grating unit 33, and the rotation angle of the diffraction grating. Specifically, the drive unit 3 switches the output of the light source 11 to either the white light source 31 or the laser light source 32. The drive unit 3 switches the detector 13 to either the single channel detector 36 or the CCD type multichannel detector 37. The drive unit 3 controls the diffraction grating and rotation angle in the diffraction grating unit 33.

[0047] The database 54 classifies and stores data of each sample analyzed by the data analysis unit 53 into a plurality of fields. Specifically, a plurality of fields such as biosensing, environmental analysis, food analysis, and component / impurity analysis are set, and data of Raman spectra and reflection / transmission spectra of many chemical species are stored for each field. The spectral data of each chemical species stored in the database 54 is used by the data analysis unit 53 for identification, state analysis, and quantitative analysis of the chemical species.

[0048] The database 54 is constructed by performing reflection and transmission spectrum and high-sensitivity Raman spectroscopy measurements in advance on the metamaterial substrate 1 for candidate substances to be analyzed for each application field, collecting the results obtained, and constructing a database of Raman spectra and reflection and transmission spectra. By referring to the various data stored in the database 54, it becomes possible to easily identify the chemical species of unknown substances, and perform state analysis and quantitative analysis.

[0049] The database 54 can be created, for example, by the following procedures (a) to (c).

[0050] (a) The sample solution in which the metamaterial substrate 1 shown in Figure 1 is immersed is replaced with a solution of a candidate substance for analysis in each field, and the reflection and transmission spectra and high-sensitivity Raman spectrum are measured for each type.

[0051] (b) For each candidate chemical species, its state of existence, such as its proton dissociation state, oxidation state, orientation, and interaction with the substrate, is analyzed by quantum chemical calculations based on the high-sensitivity Raman spectrum measured using the metamaterial substrate 1. Conversely, this analysis allows the identification of the unknown chemical species as well as the acquisition of high-sensitivity Raman spectra for each of its different states of existence. These will be accumulated for multiple types of candidate substances in multiple fields, and a database will be constructed for the state analysis of candidate substances in each field.

[0052] (c) For each candidate substance, the relationship between the concentration in the sample solution and the reflection / transmission spectra (resonance peak shift) is plotted to create a calibration curve for state analysis and quantitative analysis. This data is also added to the database. In other words, the database stores multiple substances and the reflection / transmission spectra and Raman spectra for each substance, as well as data for the calibration curve and state analysis.

[0053] The data shown in (b) and (c) above are then loaded onto a personal computer or other device for spectrum measurement together with software for database analysis.

[0054] [Operation of the embodiment] Next, the processing procedure of the analyzer according to this embodiment will be described with reference to the flowchart shown in FIG.

[0055] First, in step S11 of Fig. 4, an operator immerses the metamaterial substrate 1 in a sample solution 71 containing an unknown substance. Alternatively, the sample solution may be dropped onto the surface of the metamaterial substrate 1. That is, as shown in Fig. 5, the sample solution 71 adheres to the surface of the metamaterial substrate 1, and chemical species in the sample solution 71 are adsorbed to the metallic nanostructure array 62 formed on the surface of the metamaterial substrate 1. Alternatively, the sample solution may be supplied to a flow cell using a pump and adsorbed onto the metamaterial substrate 1.

[0056] In step S12, the operator performs an input operation to the input unit 51 (see FIG. 2) to indicate that a Raman spectrum measurement is to be performed. The drive control unit 52 outputs a drive command to the drive unit 3 for the light source 11, the detector 13, and the diffraction grating unit 33.

[0057] The driving unit 3 sets the light source 11 to a laser light source 32. The driving unit 3 sets the detector 13 to a CCD type multichannel detector 37. The driving unit 3 sets the ruling number of the diffraction grating unit 33 to that for measuring the Raman spectrum.

[0058] In response to a drive command from the drive unit 3, the laser light source 32 irradiates laser light. The laser light is irradiated onto the metamaterial substrate 1 via the incident light probe 41. The Raman scattered light reflected by and transmitted through the metamaterial substrate 1 is introduced into the spectrometer 12 from the entrance slit 38 via the signal light probe 42.

[0059] The Raman scattered light introduced into the spectrometer 12 passes through a collimator mirror 34, a diffraction grating unit 33, and a camera mirror 35, undergoes wavelength dispersion, and is then detected by a CCD multichannel detector 37. The CCD multichannel detector 37 measures the Raman spectrum. For example, as shown in FIG. 6, -1 ) and an aggregate of Raman bands having intensities, that is, a Raman spectrum, is obtained. The Raman spectrum data is sent to the data analysis unit 53 (see FIG. 2).

[0060] In step S13, the data analysis unit 53 identifies and analyzes the chemical species of the unknown substance by comparing the measured Raman spectrum with the Raman spectra of each chemical species stored in the database 54. At this time, before comparing the measured spectrum with the database 54, analysis software can be used to perform baseline correction of the Raman spectrum and correction of the wavelength dependency of the sensitivity of the detector 13 and the wavelength dependency of the diffraction efficiency of the diffraction grating.

[0061] In step S14, the operator performs an input operation to the effect that measurement of the reflection / transmission spectrum is to be performed at the input unit 51. The drive control unit 52 outputs a drive command for the light source 11, the detector 13, and the diffraction grating unit 33 to the drive unit 3.

[0062] The driving unit 3 sets the light source 11 to a white light source 31, and sets the detector 13 to a single channel detector 36. The driving unit 3 also sets and controls the number of rulings and the rotation angle of the diffraction grating unit 33 to those for measuring the reflection and transmission spectra.

[0063] In response to a drive command from the drive unit 3, the white light source 31 irradiates white light. The white light is irradiated onto the metamaterial substrate 1 via the incident light probe 41. The reflected, transmitted and Raman scattered light from the metamaterial substrate 1 is introduced into the spectrometer 12 from the entrance slit 38 via the signal light probe 42.

[0064] The reflected and transmitted light introduced into the spectrometer 12 is dispersed according to wavelength via a collimator mirror 34, a diffraction grating unit 33, and a camera mirror 35, and then detected by a single channel detector 36. The single channel detector 36 measures the reflection and transmission spectra (the intensity of the reflected and transmitted light for each wavelength). The reflection and transmission spectrum data detected by the single channel detector 36 is sent to a data analysis unit 53 (see FIG. 2).

[0065] In step S15, the data analysis unit 53 creates a calibration curve for the unknown substance based on the resonance wavelength peak shift after the adsorption of the target chemical species (sample) on the metamaterial substrate 1, which is measured in the reflection and transmission spectrum before the sample is adsorbed. FIG. 7 is a graph showing the relationship between the wavelength [nm] of light and the reflectance [%], and shows data for a substance with a refractive index of n=1.0 to 1.5. For example, when white light is irradiated onto a substance with a refractive index of n=1.0, the reflectance peaks (about 70%) for light with a wavelength of 1250 [nm]. Therefore, by measuring the reflection spectrum of the unknown substance, the refractive index of the unknown substance can be obtained, which in turn makes it possible to quantitatively analyze the sample.

[0066] In step S16, the data analysis unit 53 quantitatively analyzes the unknown substance contained in the sample solution based on the refractive index of the unknown substance identified in step S13. In this way, by using the analysis device 100 according to this embodiment, it becomes possible to identify the chemical species of the unknown substance, and further to perform state analysis and quantitative analysis of the unknown substance.

[0067] [Effects of the embodiment] Thus, the analytical apparatus 100 of this embodiment comprises a metamaterial substrate 1 (substrate) on which an array of metal nanostructures is formed, a light source 11 capable of switching between irradiating the metamaterial substrate 1 with white light and laser light, a spectrometer 12 that acquires a spectrum of a desired wavelength from the reflected light and transmitted light reflected and transmitted by the metamaterial substrate 1, a detector 13 that detects the reflected light and transmitted light output from the spectrometer 12, and a data analysis unit 53 that measures the Raman spectrum of a sample adsorbed on the metamaterial substrate 1 based on the spectrum of wavelengths contained in the reflected light and transmitted light when irradiated with laser light from the light source 11, measures the refractive index of the sample based on the spectrum of wavelengths contained in the reflected light and transmitted light when irradiated with white light from the light source 11, and performs quantitative state analysis of the sample based on the Raman spectrum and refractive index.

[0068] The analytical device 100 according to this embodiment is capable of identifying an unknown substance in a sample, the chemical species of which has not been identified, and performing state analysis and quantitative analysis of this unknown substance.

[0069] In addition, in this embodiment, the detector 13 includes a single channel detector 36 that irradiates white light onto the sample 71 and the metamaterial substrate 1 and detects the reflection and transmission spectra output from the spectrometer 12, and a CCD type multichannel detector 37 that detects the high-sensitivity Raman scattering spectrum of the sample by laser light, and since the single channel detector 36 and the CCD type multichannel detector 37 are switched alternatively, it is possible to easily switch between measuring the Raman spectrum and measuring the reflection and transmission spectrum.

[0070] In this embodiment, a metamaterial substrate 1 in which a metal nanostructure array is formed on a glass substrate or a silicon substrate is used as a substrate for adsorbing a sample, so that Raman spectra and reflection / transmission spectra can be measured efficiently.

[0071] In this embodiment, the wavelength of the surface plasmon resonance of the metallic nanostructure array 62 formed on the metamaterial substrate 1 is set to be less than 1000 [nm], and the resonance wavelength can be changed to the visible to near infrared region. Therefore, the Raman scattering spectrum and the refractive index can be measured with high sensitivity.

[0072] In this embodiment, as the white light source 31, a highly versatile lamp such as a halogen lamp or a xenon lamp can be used.

[0073] In this embodiment, reflection and transmission spectra and Raman spectra for a plurality of substances are collected in advance, classified according to the substances used in a plurality of fields, and stored in the database 54. Therefore, when the reflection and transmission spectra and Raman spectra for an unknown substance are measured, the unknown substance can be easily identified, and further, state analysis and quantitative analysis can be performed. In addition, by having the AI ​​learn, even an operator with little experience can easily identify, state analysis, and quantitative analysis of the unknown substance.

[0074] Next, a second embodiment of the metamaterial substrate 1 will be described. In this embodiment, nanoparticles are formed on a substrate such as a silicon substrate or a glass substrate, and a metal overlayer is further formed to generate a metamaterial substrate. At this time, the nanoparticle size and the thickness of the metal overlayer are adjusted to set a desired resonance wavelength. Furthermore, by coating the substrate with APTES (aminopropyltrimethoxysilane), a positive charge is imparted to the substrate, and the substrate is strongly fixed by utilizing the electrostatic attraction with the negative charges on the surface of the silica particles, thereby forming a silica monoparticle layer and a metal overlayer layer that can be stably held in the sample aqueous solution.

[0075] [Explanation of the formation method of nanoparticle metal overlayer] (1) Substrate cleaning For example, a 25 mm square substrate (such as a glass slide substrate or a silicon wafer substrate) is cleaned (removed from the surface organic contaminants) in a solvent such as IPA (isopropyl alcohol) using an ultrasonic cleaner (40 kHz, 30 to 50 W, room temperature for about 15 minutes).

[0076] (2) APTES Coat The substrate is immersed in a 1-2% by volume ethanol solution of APTES (aminopropyltriethoxysilane) at room temperature for about 30 minutes. As a result, the ethoxy group of APTES is decomposed. APTES is fixed to the slide glass substrate or silicon wafer substrate by a covalent bond of "-Si-O-Si-".

[0077] Next, the substrate is taken out and washed with ethanol to remove excess APTES. It is then heated on a hot plate maintained at about 110°C for about 15 minutes to strengthen the covalent bonds of APTES and further promote polymerization between silane molecules.

[0078] Through this series of operations, a monolayer of APTES is firmly fixed onto the substrate by covalent bonds. The amino group at the solution side of APTES has a pKa (equilibrium constant) of approximately 10, and exists as a protonated cation in a neutral pH aqueous solution. The APTES coating is essential for fixing silica nanoparticles and for use in aqueous solutions.

[0079] (3) Fixation of silica nanoparticles 0.1 mL of an aqueous dispersion (0.01-0.1 wt%) of spherical silica nanoparticles (diameter 500 nm) is dropped onto an APTES-coated substrate (a glass slide substrate or a silicon wafer substrate, 25 mm square). A substrate that is not APTES-coated (a glass slide substrate or a silicon wafer substrate, 25 mm square) is placed on top of the substrate. This operation results in a dispersion of silica nanoparticles sandwiched between the two substrates. This is stored in a plastic case for several days, and the solvent water is allowed to dry slowly and naturally.

[0080] The surface of silica nanoparticles is hydrated and has an isoelectric point of about 3. In a neutral pH aqueous solution, the water molecules on the silica surface are proton-dissociated, so the silica nanoparticles have a negative charge. As a result, the silica nanoparticles are fixed to the APTES-coated substrate surface by electrostatic attraction. On the other hand, they are not fixed to the upper substrate, which is not APTES-coated. In addition, electrostatic repulsion acts between the silica nanoparticles. This operation results in the silica nanoparticles being fixed in a monolayer only on the lower APTES-coated substrate.

[0081] (4) Formation of thin metal film On the substrate on which the monolayer of silica nanoparticles is formed, a metal film such as gold (Au), silver (Ag) or copper (Cu) is vacuum-deposited to a thickness of about 20 to 50 nm by resistance heating or sputtering. In order to strengthen the adhesion of the metal deposition film to the silica surface, it is effective to deposit a thin film of chromium (thickness 1 to 2 nm) on the silica particle surface, and then deposit a thin film of gold or silver.

[0082] It was confirmed by measuring the transmission spectrum or reflection spectrum of this substrate that this nanoparticle metal overlayer (NSMOL) has surface plasmon resonance in the wavelength region of 400 to 700 nm depending on the film thickness and the type of metal. At the same time, by irradiating a narrow band laser light near the resonance wavelength, the Raman spectrum of the chemical species adsorbed on the substrate surface can be detected with high sensitivity. In other words, by using a substrate on which the above-mentioned nanoparticle metal overlayer is formed, it becomes possible to have surface plasmon resonance and detect Raman spectrum with high sensitivity.

[0083] (5) Nanoparticle material Instead of silica nanoparticles, polystyrene (PS) nanoparticles can also be used by fixing them to a substrate (glass slide substrate, silicon wafer substrate) that is not APTES-coated. Polystyrene that is not surface-modified with polar groups, etc. is an organic molecule and does not have a free substituent on the surface, so there is no repulsion between particles and no electrostatic interaction with the substrate.

[0084] For this reason, PS nanoparticles can be used without problems in organic solvent systems, but in polar solvents with high surface tension such as water, they do not adhere well to the substrate and tend to peel off easily. In contrast, by modifying the polystyrene surface with proton dissociating substituents such as carboxyl groups, PS nanoparticles can be firmly fixed to the substrate using electrostatic interactions, just like silica nanoparticles.

[0085] Next, a specific configuration of the substrate will be described.

[0086] (1) SEM image (scanning electron microscope image) of nanoparticles 8A and 8B are schematic diagrams of a substrate 81 (a slide glass substrate or a silicon wafer substrate) on which nanoparticles are formed by the metal nano-overlayer method, with 8A being a side view and 8B being a plan view. As shown in 8A and 8B, the substrate 81 is coated with APTES 84 (aminopropyltrimethoxysilane). Next, a monoparticle layer 82 of silica nanoparticles is formed, and further, Au layers (or Ag layers, Cu layers) 83 and 85 having a thickness of about 20 to 50 nm are formed by vacuum deposition.

[0087] Figures 9A and 9B are SEM images of a substrate in which a 40 nm thick Au layer was deposited on a single particle layer of PS-NP (polystyrene nanoparticles). As shown in Figures 9A and 9B, a close-packed structure was formed very easily in the PS-NP system.

[0088] Figures 10A and 10B are SEM images of a substrate in which 40 nm-thick Au was deposited onto a monolayer of silica nanoparticles (SiO2-NP). As shown in Figures 10A and 10B, the SiO2-NP system had a slightly larger gap than the PS-NP system, but still had a closely packed structure.

[0089] (2) Function as a refractive index sensor 11A and 11B are graphs showing the relationship between the wavelength and absorbance of the laser light irradiated to the substrate, and Fig. 11A is a characteristic graph showing the experimental relationship between the wavelength and absorbance when a substrate with 40 nm of silver (Ag) deposited on a SiO2-NP monolayer is used. Fig. 11B is a characteristic curve showing the experimental relationship between the wavelength and absorbance when a substrate with 40 nm of gold (Au) deposited on SiO2-NP nanoparticles is used.

[0090] Curve s1 in Fig. 11A shows the experimental characteristics when the substrate is measured in air, curve s2 shows the characteristics when thiophenol (TP) is adsorbed on the substrate and measured in air, and curve s3 shows the characteristics when TP is adsorbed on the substrate and measured in water. Curve s4 in Fig. 11B shows the characteristics when the substrate is measured in air, curve s5 shows the characteristics when thiophenol (TP) is adsorbed on the substrate and measured in air, curve s6 shows the characteristics when TP is adsorbed on the substrate and measured in water, and curve s7 shows the characteristics when TP is adsorbed on the substrate and measured in an ethylene glycol solvent.

[0091] Thus, as shown in Figures 11A and 11B, in the SiO2-NP system (silica nanoparticles), a surface plasmon resonance peak that depended on the type of metal, film thickness, etc. was detected in the wavelength range of 550 to 650 nm.

[0092] When the sample was adsorbed with thiophenol (TP) as a chemical species to be analyzed, the wavelength of this peak shifted by about 2 to 5 nm. Furthermore, when the sample was immersed in a solvent such as water or ethylene glycol, the wavelength shifted by more than 100 nm. In this case, the refractive index sensitivity was 250 to 300 nm / RIU (refractive index unit), which was a sufficiently large value.

[0093] Figures 12A and 12B are characteristic curves showing the dependence of the medium refractive index n calculated by the RCWA method using a two-dimensional model, with the horizontal axis showing the wavelength and the vertical axis showing the reflectance. Figure 12A shows the results when gold (Au) was used as the metal evaporated onto the nanoparticle surface, and Figure 12B shows the results when silver (Ag) was used. In order to make effective use of computational resources without losing the essence, the calculation was performed assuming a configuration in which cylindrical silica nanoparticles 92 are formed on the surface of a substrate 91, as shown in Figures 13A and 13B.

[0094] Curve s11 in Fig. 12A shows the results when the medium refractive index n = 1.00, curve s12 shows the results when n = 1.15, curve s13 shows the results when n = 1.25, and curve s14 shows the results when n = 1.35. As can be seen from Fig. 12A, when gold (Au) is used as the metal evaporated onto the nanoparticle surface, the wavelength at which the reflectance becomes the minimum value shifts significantly when the refractive index changes.

[0095] Curve s15 in Fig. 12B shows the results when the medium refractive index n = 1.00, curve s16 shows the results when n = 1.15, curve s17 shows the results when n = 1.25, and curve s18 shows the results when n = 1.35. As can be seen from Fig. 12B, when silver (Ag) is used as the metal evaporated onto the nanoparticle surface, as in the case of gold, the wavelength at which the reflectance is at its minimum value shifts significantly when the refractive index changes.

[0096] 14 is a graph showing the relationship between the refractive index n of the medium and the wavelength shift, where curve s21 shows the case where gold is used and curve s22 shows the case where silver is used. It can be seen that in each of curves s21 and s22, the wavelength shifts linearly (linearly) with respect to the refractive index n of the medium.

[0097] It was also confirmed that the refractive index sensitivity shown in FIGS. 11A and 11B corresponds well to the prediction by theoretical calculation shown in FIGS. 12A and 12B.

[0098] For example, at the resonant wavelength of a metal nanoparticle, large polarization occurs when the dielectric constant of the medium and the real part (negative value) of the metal's dielectric constant are equal. For example, when the real part of the medium's dielectric constant changes from 1.00 for air to 1.77 for water, which is a larger value (positive value), this is realized by the real part of the metal's dielectric constant becoming a larger negative value at longer wavelengths. The resonant wavelength of a nanoparticle metal overlayer also changes due to a similar effect of the dielectric constant of the medium. Furthermore, the metal nanoparticle overlayer remained extremely stable even after repeated immersion in these aqueous solutions and rinsing with alcohol.

[0099] The above results show that by adopting the metamaterial substrate of the second embodiment, the shift range of the refractive index between air and a solvent can be made large, making it possible to detect the refractive index with high accuracy.

[0100] (3) Function as a Raman sensor Figures 15A and 15B are characteristic curves showing the relationship between the wave number of the incident light and the Raman scattered light intensity (ISERS). Figure 15A shows the characteristics when thiophenol (TP) is adsorbed on the nanoparticle surface and a substrate with silver (Ag) evaporated onto silica nanoparticles is used. Figure 15B shows the characteristics when thiophenol (TP) is adsorbed on the nanoparticle surface and a substrate with gold (Au) evaporated onto silica nanoparticles is used.

[0101] As shown in Figures 15A and 15B, the SiO2-NP-based metal nanoparticle overlayers exhibited a stable 10% thermal expansion over the TP monolayer regardless of the location on the substrate, on different substrates, and over several days. 4 ~10 5 For gold and silver, the Raman signal obtained was several times stronger for silver than for gold, as expected from the dielectric constant.

[0102] Figures 16A and 16B are characteristic curves showing the relationship between the wave number of the incident light and the Raman scattered light intensity (ISERS) when a substrate with silver evaporated onto silica nanoparticles is used. Figure 16A shows the characteristics when an aqueous solution of catechol in sodium chloride (NaCl) (concentration 2 mM) is used, and Figure 16B shows the characteristics when an aqueous solution of catechol in sodium hydroxide (NaOH) (concentration 2 mM) is used. When an aqueous solution of catechol (1,2-dihydroxybenzene), a more common adsorbate species other than thiols, was brought into contact with the metal nanoparticle overlayer substrate in a simple solution cell consisting of a rubber spacer and a cover glass, a clear Raman spectrum of the catechol molecule was measured. In this case too, it was found that the metal nanoparticle overlayer was extremely stable against changes in the aqueous solution composition (NaCl, NaOH).

[0103] Fig. 17 is an experimental characteristic curve showing the relationship between the Raman spectrum of incident light (relationship between wavenumber and Raman scattered light intensity (ISERS)) and measurement time when a substrate with silver vapor-deposited on silica nanoparticles is used, where curve s31 shows the case where the measurement time is 2 seconds, curve s32 shows the case where the measurement time is 0.2 seconds, and curve s33 shows the case where the measurement time is 0.05 seconds. In Fig. 17, curve s31 corresponds to the right scale, and curves s32 and s33 correspond to the left scale.

[0104] As can be seen from the curves s31, s32, and s33 in FIG. 17, the ISERS peak value is obtained at almost the same wave number at each measurement time. Therefore, it can be said that one Raman spectrum can be measured even in a short measurement time of about 0.05 seconds. In other words, by using the substrate according to this embodiment, it becomes possible to measure the Raman spectrum with high accuracy in a very short time.

[0105] In this way, by adopting the metamaterial substrate of the second embodiment, it has high functionality as a Raman sensor and a refractive index sensor, so that it is possible to measure Raman spectra and reflection / transmission spectra with high accuracy and efficiency using a single substrate.

[0106] Although the embodiment of the present invention has been described above, the description and drawings forming a part of this disclosure should not be understood as limiting the present invention. Various alternative embodiments, examples and operating techniques will become apparent to those skilled in the art from this disclosure. [Explanation of symbols]

[0107] 1 Metamaterial substrate (substrate) 2 spectrometer 3 Drive unit 4. Control section 11 Light source 12 Spectrometer 13 Detector 31 White light source 32 Laser light source 33 Diffraction grating section 34 Collimator mirror 35 Camera Mirror 36 Single Channel Detectors 37 CCD type multi-channel detector 38 Entrance slit 41 Incident light probe 42 Signal Light Probe 51 Input section 52 Drive control unit 53 Data Analysis Department 54 Database 55 Output section 61 Transparent Substrate 62 Metal Nanostructure Array 71 Sample Solution 100 Analyzer

Claims

1. A substrate on which a metal nanostructure array is formed; a light source capable of switching between irradiating the substrate with white light and laser light; a spectroscope for acquiring a spectrum of a desired wavelength from the reflected light and transmitted light reflected by and transmitted through the substrate and the Raman scattered light; a detector for detecting reflected light, transmitted light and Raman scattered light output from the spectrometer; a data analysis unit that measures a Raman spectrum of a sample adsorbed on the substrate based on a spectrum of wavelengths contained in Raman scattered light when irradiated with laser light from the light source, measures a refractive index of the sample based on a spectrum of wavelengths contained in reflected light and transmitted light when irradiated with white light from the light source, and performs a state analysis and a quantitative analysis of the sample based on the Raman spectrum and the refractive index; A multipurpose metamaterial analysis instrument equipped with

2. The detector includes a single channel detector that detects a desired frequency band of reflected light and transmitted light by the white light among the signal light output from the spectrometer, and a CCD type multichannel detector that detects a frequency band of Raman scattered light output from the spectrometer, and is capable of switching between the single channel detector and the CCD type multichannel detector. A multipurpose metamaterial analysis device as claimed in claim 1.

3. The multipurpose metamaterial analysis device according to claim 1 or 2, wherein the metal nanostructure array has a surface plasmon resonance wavelength of 500 to 1000 nm.

4. The substrate is a metamaterial substrate in which a metal nanostructure array is formed on a glass substrate or a silicon substrate. A multipurpose metamaterial analysis device according to claim 1 or 2.

5. The metamaterial substrate is formed by coating the glass substrate or silicon substrate with APTES, fixing nanoparticles thereon, and further evaporating a thin metal film thereon. A multipurpose metamaterial analysis device as claimed in claim 4.

6. The nanoparticles are silica nanoparticles or polystyrene nanoparticles. A multipurpose metamaterial analysis device as claimed in claim 5.

7. The metal thin film is gold or silver. A multipurpose metamaterial analysis device as claimed in claim 5.

8. A database that stores data showing the relationship between a plurality of substances and the reflection / transmission spectrum and Raman spectrum for each substance. A multipurpose metamaterial analysis device as described in claim 1, comprising:

9. A step of adsorbing a sample to be measured onto a substrate on which a metallic nanostructure array is formed; irradiating the substrate with laser light and identifying the sample from the spectrum of Raman scattered light reflected and transmitted by the substrate; a step of irradiating the substrate with white light and detecting a refractive index of the sample from a spectrum of the reflected light and the transmitted light reflected by the substrate; performing a state analysis and a quantitative analysis of the sample based on the identification result of the sample and the refractive index of the sample; A versatile metamaterial analysis method with

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