JP2009109395A - Fine structure manufacturing method, fine structure, Raman spectroscopic device, Raman spectroscopic apparatus, analyzer, detector, and mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method of manufacturing a fine structure which enables easy production of a fine structure capable of forming a hot spot near metal fine particles without a step of densely disposing the metal fine particles with several-ten-nm or smaller gap therebetween. <P>SOLUTION: The method of manufacturing a fine structure is characterized by a step of dispersing and fixing the plurality of metal fine particles having a size capable of inducing localized plasmon on a surface of a substrate, a step of forming a metal film in a gap between the plurality of metal fine particles, wherein the metal fine particles have a portion in which an area of a cross-section of a cut face parallel to a surface of the substrate gets maximum, and have a shape such that the cross-sectional area reduces toward the surface of the substrate from the portion in which the cross-sectional area gets maximum, and wherein the metal fine particles get spaced apart from the metal film. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a manufacturing method of a fine structure having a localized plasmon enhancement function, a fine structure, and a Raman spectroscopic device, a Raman spectroscopic apparatus, an analysis apparatus, a detection apparatus, and a mass spectrometry apparatus including the fine structure. It is about.

  There are known electric field enhancement devices such as a sensor device and a Raman spectroscopic device using an electric field enhancement effect by a localized plasmon resonance phenomenon on a metal surface. For example, Raman spectroscopy is a method of obtaining a spectrum (Raman spectrum) of Raman scattered light by dispersing scattered light generated by irradiating a substance with single wavelength light. Raman spectroscopy is known as Raman spectroscopy that uses an electric field enhanced by localized plasmon resonance, called surface enhanced Raman (SERS), in order to enhance weak Raman scattered light.

  It is also known that the electric field is greatly enhanced in the gap between the metal fine particles when the metal fine particles are close to several tens of nm or less. The region where the highly enhanced electric field is generated is called a hot spot, and a high enhancement effect can be obtained in the surface-enhanced Raman scattering measurement by arranging a measurement substance in the hot spot.

  In Patent Document 1, the dielectric or semiconductor fine particles densely arranged on the substrate are reduced by anisotropic dry etching, and the metal or semiconductor is deposited in a hemispherical shape on the fine particles by vapor deposition or sputtering. In addition, a two-dimensional array structure substrate formed by controlling the gap between fine metal particles to an arbitrary distance and a method for manufacturing the same are described.

Further, in Non-Patent Document 1, using angle-resolved nanosphere lithography technology (AR-NSL), a single layer film of polystyrene (PS) particles formed on a glass substrate is used to form Ag at different angles. It is described that a layer of Ag nanodot dimer is formed by performing vapor deposition and then removing the polystyrene particles.
JP-A-2005-144568 “J.AM.CHEM.SOC.” 2007,129,1658-1662

By the way, in the method described in Patent Document 1, it is necessary to densely fix and arrange fine particles on the substrate. However, if the fine particles are arranged in a very close state, the fine particles are aggregated. It is very difficult to densely arrange the fine particles while preventing the fine particles from aggregating. Therefore, with the method described in Patent Document 1, it is difficult to bring the gap between adjacent fine metal particles close to several tens of nm or less.
Further, in the method described in Non-Patent Document 1, a polystyrene monomolecular layer formed on a substrate is used as a mask. However, even in the method described in Non-Patent Document 1, the gap between fine metal particles is several tens of nm. It is difficult to closely approach the following.

  As described above, in the conventional technique, it is very difficult to bring the metal fine particles close to several tens of nm or less, and it is not easy to form hot spots densely. Therefore, there is a problem that the SERS effect cannot be sufficiently obtained even when a structure manufactured by a conventional method is used as a Raman spectroscopic device.

The object of the present invention is to solve the above-mentioned problems of the prior art and easily produce a microstructure capable of forming a hot spot in the vicinity of the metal fine particles without performing a step of densely arranging the metal fine particles to several tens of nm or less. It is an object of the present invention to provide a method for manufacturing a fine structure. Another object of the present invention is to provide a microstructure manufactured by this method for manufacturing a microstructure.
Another object of the present invention is to provide a Raman spectroscopic device, a Raman spectroscopic device, an analysis device, a detection device, and a mass spectroscope provided with this fine structure.

  In order to achieve the above object, a first aspect of the present invention includes a step of arranging and fixing a plurality of metal fine particles having a size capable of inducing localized plasmons in a dispersed state on a substrate surface, Forming a metal film in the gap between the metal fine particles, and the metal fine particles have a portion where the cross-sectional area of the cut surface parallel to the substrate surface is maximum, and the cross-sectional area is maximum. In another aspect of the present invention, there is provided a method for manufacturing a microstructure having a shape in which the cross-sectional area decreases from the portion to the surface of the base material and is separated from the metal film.

  In the first aspect of the present invention, when the effective particle diameter of the metal fine particles is Re and the effective height of the metal film from the substrate surface is he, the step of forming the metal film includes the metal It is preferable to form the metal film which is separated from the fine particles and satisfies the relationship of he <Re / 2.

  Further, after the step of forming the metal film, the constituent metals of the metal film are aggregated into particles by heat treatment, thereby separating the metal fine particles into the gaps between the plurality of metal fine particles, It is preferable to have a heat treatment step of forming at least one film-like metal and / or a plurality of massive metals having a size capable of inducing localized plasmons, and in the heat treatment step, the temperature of the heat treatment is set to More preferably, the melting point is equal to or higher than the melting point and lower than the melting point of the base material.

  Further, the second aspect of the present invention includes a base material, a plurality of metal fine particles having a size capable of inducing localized plasmons arranged and fixed in a dispersed state on the surface of the base material, and a gap between the metal fine particles. And at least one film-like metal and / or a plurality of massive metals arranged on the surface of the base material in a state of being separated from and close to the metal fine particles and capable of inducing localized plasmons. It is intended to provide a fine structure.

In the second aspect of the present invention, the metal fine particles have a portion where the cross-sectional area of the cut surface parallel to the substrate surface is maximum, and from the portion where the cross-sectional area is maximum toward the substrate surface. When the effective height of the metal fine particles is He and the effective height of the film metal and / or the bulk metal is he, the relationship of He / 2> he is obtained. It is preferable to satisfy.
The effective height He of the metal fine particles and the effective height he of the film-like metal and / or the bulk metal are high in frequency among the results of measuring the height from the surface of the substrate at a plurality of points. It is preferably measured as a value of thickness.
Further, the main component of the metal fine particles and the film metal and / or the bulk metal is at least one selected from the group consisting of Au, Ag, Cu, Al, Pt, Ni, Ti and alloys thereof. It is preferable that it is a metal.
Moreover, it is preferable that the distance between the metal fine particles and the film metal and / or the bulk metal adjacent to the metal fine particles is equal to or less than an average particle diameter of the metal fine particles.

  The third aspect of the present invention is a Raman spectroscopic device having a light scattering surface that is used for Raman spectroscopy to obtain a spectrum of Raman scattered light by dispersing scattered light and is irradiated with measurement light and scattered. The microstructure of the second aspect of the present invention is provided, and the surface of the microstructure including the surface of the metal fine particles and the film metal and / or the bulk metal is used as the light scattering surface. A device for Raman spectroscopy is provided.

  According to a fourth aspect of the present invention, there is provided the Raman spectroscopic device according to the third aspect of the present invention, a light irradiation means for irradiating the light scattering surface of the Raman spectroscopic device with measurement light, and the light scattering surface. And a spectroscopic means for obtaining a spectrum of the Raman scattered light.

  Further, a fifth aspect of the present invention is the measurement on the surface of the fine structure including the fine structure of the third aspect of the present invention and the surface of the metal fine particles and the film metal and / or the bulk metal. It is an object of the present invention to provide an analyzing apparatus comprising a light irradiating means for irradiating light and a signal detecting means for detecting a signal irradiated from the surface of the fine structure.

  Further, a sixth aspect of the present invention is the measurement on the surface of the fine structure including the fine structure of the third aspect of the present invention and the surface of the metal fine particles and the film metal and / or the bulk metal. The present invention provides a detection apparatus including light irradiation means for irradiating light and detection means for detecting physical characteristics of light generated on the surface of the fine structure.

  Further, a seventh aspect of the present invention is the measurement on the surface of the fine structure including the fine structure of the third aspect of the present invention and the surface of the metal fine particles and the film metal and / or the bulk metal. Irradiating light to ionize the measurement sample placed on the surface of the microstructure, and light irradiation means for desorption from the surface of the microstructure, and desorption from the surface of the microstructure, ionization And a detection device for detecting the mass of the measured sample.

  According to the manufacturing method of the microstructure of the first aspect of the present invention, the cross-sectional area of the cut surface parallel to the surface of the base material increases as the distance from the base material surface increases, and the cross-sectional area has a maximum portion. After arranging and fixing a plurality of metal fine particles dispersed in a base material, a metal film is formed in the gap between the metal fine particles, so that the metal fine particles and the metal film can be arranged close to each other. A microstructure capable of forming a hot spot in an adjacent region can be easily manufactured.

Further, according to the microstructure of the second aspect of the present invention, the surface of the base material in the state of being separated from and close to the metal fine particles is disposed in the gap between the plurality of metal fine particles arranged in a dispersed state on the surface of the base material. By having the arranged film-like metal and / or massive metal, a hot spot can be formed between the metal fine particles and the film-like metal and / or massive metal adjacent to each other.
In particular, when the effective height of the metal fine particles satisfies He and the effective height of the film-like metal and / or bulk metal satisfies the relationship He / 2> he, the metal fine particles, the film-like metal, and / or Or it arrange | positions in the state which adjoined the lump metal, and a hot spot can be formed in this adjacent area | region.

According to the Raman spectroscopic device of the third aspect of the present invention, the microstructure includes the fine structure of the second aspect of the present invention and includes the surface of metal fine particles and film-like metal and / or bulk metal. The surface-enhanced Raman scattering effect can be suitably obtained by using the surface of the light scattering surface.
According to the Raman spectroscopic apparatus of the fourth aspect of the present invention, the surface-enhanced Raman scattering effect can be suitably obtained by providing the Raman spectroscopic device of the third aspect of the present invention. Raman spectroscopic measurement is possible.

Moreover, according to the analyzer of the 5th aspect of this invention, by providing the microstructure of the 3rd aspect of this invention, a measurement object substance can be analyzed with high precision.
In addition, according to the detection device of the sixth aspect of the present invention, the fine structure including the surface of the metal fine particles and the film-like metal and / or the bulk metal by including the fine structure of the third aspect of the present invention. The physical characteristics of light generated on the surface of the film can be suitably detected.
Further, according to the mass spectrometer of the seventh aspect of the present invention, by providing the fine structure according to the third aspect of the present invention, ionization and desorption of the measurement sample arranged on the surface of the fine structure can be performed. This can be suitably performed, and the mass of the measurement sample can be suitably detected.

Hereinafter, a fine structure manufacturing method and a fine structure according to the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings.
FIG. 1 is a perspective view schematically showing one embodiment of a microstructure according to the present invention. FIG. 2 is a process diagram showing a manufacturing process of the microstructure shown in FIG. 1 as an embodiment of the manufacturing method of the microstructure according to the present invention.

A microstructure 10 shown in FIG. 1 includes a base metal 12, a plurality of metal fine particles 14 dispersed and fixed on the surface 12s of the base 12, and a metal fine particle composite formed on the metal fine particles 14. 18 and a metal film 20 that is separated (separated) from the metal fine particles 14 and formed in a close proximity in the gap between the metal fine particles 14 on the surface 12s.
In the microstructure 10, the metal fine particle composite 18 (metal fine particle 14) and the metal film 20 are arranged close to each other, and a hot spot can be formed in this gap.
In the present specification, the metal fine particle composite 18 is a metal fine particle in a state in which the metal film 16 is formed on the metal fine particle 14, and is simply a metal unless otherwise distinguished from the metal fine particle 14. Also referred to as fine particles 18.

Hereinafter, a manufacturing method of the fine structure 10 will be described, and the fine structure 10 will be described in more detail.
In the manufacturing method of the microstructure 10 of the present embodiment, first, the base material 12 is prepared as shown in FIG. The base material 12 is an insulating plate-like member that supports the plurality of metal fine particle composites 18 and the metal film 20 disposed on the surface 12s thereof.
The substrate 12 is not particularly limited as long as it can electrically insulate and support the metal film 20 and the metal fine particle composite 18, and silicon, glass, yttrium stabilized zirconia (YSZ), sapphire, and silicon. Carbide etc. are mentioned.

Next, it fixes in the state which disperse | distributed the metal microparticle 14 to the surface 12s of the base material 12 shown to FIG. 2 (B). In the present embodiment, the metal fine particles 14 are dispersed and fixed on the surface 12 s of the substrate 12 by silane coupling.
Here, the filling rate of the metal fine particles 14 with respect to the area of the surface 12s is not particularly limited, and the size and material of the metal fine particles 14 and the material and surface state of the base material 12 so that the metal fine particles 14 do not aggregate. The conditions for silane coupling may be appropriately set according to the above.
In addition, it is preferable that the metal fine particles 14 are densely arranged within a range of the filling rate in which the metal fine particles 14 do not aggregate. This can increase the number of the metal fine particles 14 per unit area and increase the number of hot spots. Can be made.

The metal fine particles 14 need only have a size (particle diameter) that can induce localized plasmons, and may be less than or equal to half the wavelength of excitation light that excites localized plasmons. Specifically, considering that the microstructure 10 is used as a sensor device such as a Raman spectroscopic device, the metal fine particles 14 may be half or less of the wavelength of the measurement light.
The metal fine particles 14 include, as a main component, at least one metal selected from the group consisting of Au, Ag, Cu, Al, Pt, Ni, Ti, and alloys thereof, and has a high electric field enhancing effect. Au, Ag and the like are particularly preferable.

  Here, the metal fine particle 14 is schematically shown as a perfect sphere, but the present invention is not limited to this, and is in a granular form and cut parallel to the surface 12s in a state of being arranged on the surface 12s. What is necessary is just to have the shape which has the part where the cross-sectional area of a surface becomes the largest, and a cross-sectional area decreases as it goes to the surface 12s from the part where a cross-sectional area becomes the largest. Note that the shape in which the cross-sectional area decreases means that the cross-sectional area decreases toward the base material 12 when the shape of the metal fine particles 14 is approximated to be spherical. The metal fine particle 14 has a smaller cross-sectional area at the contact point with the surface 12 s of the base material 12 than a portion where the cross-sectional area is maximum.

Further, each of the plurality of metal fine particles 14 is not limited to having the completely same shape.
Here, the effective particle diameter is defined as the particle diameter of the metal fine particles 14. The effective particle diameter is an average value of the particle diameters measured for a plurality of metal fine particles actually used.
Alternatively, the effective particle diameter may be the sphere diameter when the volume of the metal fine particles is converted to a sphere, and the average particle diameter may be a value obtained by averaging the effective particle diameters with respect to the plurality of metal fine particles 14.

  Next, as shown in FIG. 2C, a metal film 20 is formed in the gaps between the plurality of fine metal particles 14 dispersed and fixed on the base material 12. The metal film 20 is formed by vapor deposition from the surface 12s side of the substrate 12, that is, from above in the drawing. A metal film 16 is formed on the metal fine particles 14 to form a metal fine particle composite 18.

The metal film 20 is a film-like metal and / or a massive metal arranged in a region where the metal fine particles 14 are not arranged on the substrate 12s. The massive metal includes island-like structures and particles. The metal film 20 may have a plurality of film-like metals and / or bulk metals dispersed and arranged on the surface 12s in a state of being separated from each other. It may be a metal. In addition, it is preferable that each of the film-like metal and the massive metal of the metal film 20 has a size capable of inducing localized plasmons.
The metal film 20 includes, as its main component, at least one metal selected from the group consisting of Au, Ag, Cu, Al, Pt, Ni, Ti and alloys thereof, Au having a high electric field enhancing effect, Ag and the like are particularly preferable.

Here, the conditions for forming the metal film 20 will be described with reference to FIG. As shown in FIG. 3, as the effective particle diameter Re of the metal fine particles 14 already dispersed and fixed on the base material 12 and the effective height he from the surface 12s of the metal film 20, the metal is perpendicular to the surface 12s. When deposited, the film forming condition of the metal film 20 is Re / 2> he.
The effective height he of the metal film 20 is an average value of the film thickness of the formed metal film 20, and is an average value of the height from the surface 12s.

Thus, the metal film 20 can be formed between the dispersed and fixed metal fine particles 14 in a state of being separated from and close to the metal fine particles 14. By adjusting the film thickness (height) of the metal film 20, the metal fine particles 14 and the metal film 20 can be brought close to each other, and a hot spot can be formed in the gap (a region indicated by a broken line in FIG. 3). ).
Here, by setting the distance between the metal fine particles 14 and the metal film 20 to be equal to or smaller than the particle size (effective particle size) of the metal fine particles 14, the near-field light of the metal fine particles 14 and the near-field light of the metal film 20 are reduced. Overlapping regions can be provided and hot spots can be formed.

  The metal film 20 is formed, for example, by knowing in advance the film formation speed through experiments, etc., and in accordance with the effective particle diameter (average particle diameter) of the metal fine particles to be used, the film formation time is within a range that satisfies the above conditions. This can be done by setting.

  2, specifically, using a glass substrate as the base material 12 and gold (Au) metal fine particles having a particle diameter of 30 nm (made by Tanaka Kikinzoku, sample name: Au 30 nm A06080819-2E, The average particle size: 30.29 nm) is dispersed on a glass substrate by silane coupling, and then gold is deposited to a thickness of 5 nm to form the metal film 20 to produce the microstructure 10.

In the microstructure 10 thus manufactured, the height from the surface 12s was measured at a plurality of points, and as shown in FIG. 4, the horizontal axis was measured for the height value, and the vertical axis was measured. When a graph is created as the frequency, two peaks can be obtained as illustrated.
Here, the effective height He of the metal fine particle composite 18 is defined (see FIG. 3). The effective height He is the average value of the height from the surface 12 s of the metal fine particle composite 18. Alternatively, the effective height He may be the diameter of a sphere when the volume of the metal fine particle composite 18 is converted to a sphere.

  The effective height He of the metal fine particle composite 18 and the effective height he of the metal film 20 are measured as values having a high measurement frequency, and the effective heights He and he have a relationship of He / 2> he. That is, the fine structure 10 specifies the effective height He of the metal fine particle composite 18 and the effective height he of the metal film 20 by measuring the height from the surface 12 s of the substrate 12 at a plurality of locations. The microstructure 10 can be specified as those relationships satisfying the relationship of He / 2> he.

  According to the microstructure manufacturing method of the present embodiment, after the plurality of metal fine particles 14 are dispersed and fixed on the surface 12 s of the substrate 12, the metal film 20 is formed in the gaps between the plurality of metal fine particles 14. Thus, it is easy to bring the metal fine particles 14 and the metal film 20 close to a distance at which a hot spot can be formed.

  In addition, when the metal fine particle has an effective particle size Re, the metal film 20 is formed so that the effective height he from the surface 12s of the base material 12 of the metal film 20 satisfies he <Re / 2. In a state where the metal fine particles 14 and the metal film 20 are separated, they can be brought close to a distance where a hot spot can be formed.

  As described above, the microstructure manufactured by such a manufacturing method has a portion where the cross-sectional area of the cut surface parallel to the surface of the substrate is maximum, and the portion where the cross-sectional area is maximum is directed to the surface. And the metal fine particles (metal fine particle composite) have an effective height He and the metal film effective height he satisfy the relationship He / 2> he. It can be specified as a thing.

In addition, according to the method for manufacturing a microstructure of the present invention, the metal fine particles 14 may be dispersed on the surface 12s of the substrate 12 with a filling rate that does not agglomerate, and the metal fine particles 14 need to be densely packed. Therefore, the fine metal particles 14 can be easily dispersed and the fine structure 10 can be easily manufactured.
In addition, since the fine metal body 14 can be formed by vapor deposition after the metal fine particles 14 are dispersed by silane coupling, the fine structure 10 can be manufactured. Can be made.

Here, in this embodiment, the silane coupling is used to disperse the plurality of metal fine particles 14 on the surface 12s of the substrate 12, but the present invention is not limited to this, and the silane coupling is not limited thereto. The treatment liquid in which the citric acid in CTAB is replaced with CTAB (surfactant) may be naturally evaporated after being applied to the surface 12s.
Alternatively, the solution containing the metal fine particles 14 may be naturally evaporated after being applied to the surface 12s. In this case, the concentration of the metal fine particles 14 in the solution is set such that the metal fine particles 14 do not aggregate when applied to the surface 12s.
Alternatively, after forming a metal film on the surface 12s by vapor deposition or sputtering, the metal film 14 may be formed on the surface 12s by scraping the metal film using electron beam (EB) lithography or various etching techniques.

In this embodiment, the metal film 20 is formed in the gap between the plurality of metal fine particles 14 by vapor deposition from above the surface 12s. However, the angle at the time of vapor deposition is perpendicular to the surface 12s. It is not limited, You may perform diagonal vapor deposition which has an angle with respect to an orthogonal direction.
When performing oblique vapor deposition, the angle of oblique vapor deposition is set so that the metal film 20 can be formed between the metal fine particles 14 with high efficiency in accordance with the effective particle size of the metal fine particles 14, the filling rate of the metal fine particles 14, and the like. That's fine. In the case of performing oblique vapor deposition, if the vapor deposition angle θ during oblique vapor deposition is an angle from the orthogonal direction of the surface 12s, the effective particle diameter Re of the metal fine particles 14 and the effective height he of the metal film 20 are Re (1− By forming the film so as to satisfy sin θ) / 2> he, the metal fine particles 14 and the metal film 20 can be brought close to each other to the extent that a hot spot can be formed.
In the present embodiment, the metal film 20 is formed by vapor deposition. However, the present invention is not limited to this, and the metal film 20 may be formed by sputtering.

As another method, a metal-containing solution in which a metal as a material of the metal film 20 is dispersed in a solution at a very thin concentration is flowed on the surface 12s in a state where a plurality of metal fine particles 14 are dispersed and fixed. There is a method of drying the solvent after it has been sunk. As a result, a metal film 20 in which film-like metal or bulk metal is dispersed and formed between the plurality of metal fine particles 14 is formed, and the film-like metal or bulk metal and the metal fine particles 14 are brought close to each other. And hot spots can be formed.
Alternatively, the metal film 20 may be formed by lithography using a mask for depositing metal in the gaps between the metal fine particles 14.

Here, after the method for manufacturing the microstructure 10 shown in FIG. 2, an annealing treatment (heat treatment) may be further performed.
The constituent elements of the metal film 20 are agglomerated and formed into particles by annealing treatment, and as shown in FIG. 5, a film-like metal having a size capable of inducing localized plasmons in the gaps between the plurality of metal fine particles 22 and A metal body 24 including / or a bulk metal can be formed. The annealing temperature is not lower than the melting point of the metal film 20 and lower than the melting point of the substrate 12.

  The metal fine particles 22 are the metal fine particle composites 18 that have been annealed, and are metal fine particles that are finally formed on the surface 12 s of the substrate 12. In the illustrated example, the metal fine particles 14 and the metal film 16 are schematically illustrated as an integrated sphere, but the present invention is not limited to the integrated sphere.

  Here, although the metal body 24 is shown in FIG. 5 as the end of the bottom surface contacting the surface 12s, the shape of the metal body of the present invention is not limited to this, and the end floats. A shaped metal body 26 is also included. Depending on the material of the metal film 20, the wettability depending on the properties of the substrate 12 such as the material of the substrate 12 and the surface state of the surface 12 s, any one of the metal body 24 and the metal body 26 Take shape.

  By performing the annealing treatment, the metal particles 24 capable of inducing localized plasmons and the metal body 24 or 26 can be brought close to each other regardless of the shape of the metal body 24 shown in FIGS. Since hot spots (indicated by broken lines in FIGS. 5 and 6) can be formed, a greater Raman enhancement effect can be obtained.

Next, an embodiment of the Raman spectroscopic apparatus of the present invention using the above-described fine structure 10 as a Raman spectroscopic device will be described with reference to FIG.
The Raman spectroscopic device 50 according to the present embodiment includes the fine structure 10 as a Raman spectroscopic device, a light irradiation unit 52 that irradiates light of a specific wavelength, and a spectroscopic unit 54 that splits scattered light.

  The fine structure 10 (hereinafter also referred to as a Raman spectroscopic device 10) uses a surface of the fine structure, which is a surface on the surface 12s side of the substrate 12, as a light scattering surface, and a measurement sample (not shown) is placed on the light scattering surface. In the arranged state, it is held by holding means (not shown).

  In this specification, the surface of the fine structure 10 includes the surface 12s of the base material 12, and the metal fine particle composite 18 and the metal film 20 (or metal metal) disposed on the surface 12s side of the base material 12. The surfaces of the fine particles 22 and the metal bodies 24, 26) are collectively referred to. When the fine structure is used as a Raman spectroscopic device, the surface of the fine structure 10 is also referred to as a light scattering surface.

The light irradiation means 52 includes a light source such as a laser and a light guide system that guides light emitted from the light source, and is configured to irradiate the light scattering surface of the Raman spectroscopic device 10 with light having a specific wavelength. .
The spectroscopic means 54 comprises a spectroscopic detector or the like, and spectrally scatters scattered light generated on the light scattering surface of the Raman spectroscopic device 10 to obtain a spectrum of Raman scattered light (Raman spectrum). The spectroscopic means 54 is configured such that scattered light generated on the light scattering surface of the Raman spectroscopic device 10 is incident thereon.

  Although not shown, the Raman spectroscopic device 50 includes various devices such as a case that covers the Raman spectroscopic device 10, the light irradiation unit 52, and the spectroscopic unit 54, and a filter that removes stray light generated inside the Raman spectroscopic device 50. And various members necessary for the Raman spectroscopic device 50, such as an optical member and a control unit that controls the operation of the Raman spectroscopic device 50.

  In the Raman spectroscopic device 50 of the present embodiment having the above-described configuration, the light having a specific wavelength irradiated from the light irradiation means 52 is scattered by the light scattering surface of the Raman spectroscopic device 10 facing the measurement sample and generated scattered light. Is incident on the spectroscopic means 54, and the scattered light is split by the spectroscopic means 54 to generate a Raman spectrum. Since the Raman spectrum changes depending on the type of sample to be measured, identification of substances can be performed.

In the present embodiment, the method for disposing the measurement sample on the light scattering surface (surface) of the Raman spectroscopic device 10 is not particularly limited, and the measurement sample may be directly disposed on the light scattering surface.
In addition, a surface modification that specifically binds to the measurement sample is applied to the light scattering surface, and the measurement sample is attached to the surface modification (that is, via the surface modification) to the light scattering surface of the Raman spectroscopic device. You may arrange in.
Here, for example, when the measurement sample contains an antigen, an antibody that can specifically bind to the antigen is modified on the light scattering surface, and the measurement sample that is the antigen by the antigen-antibody reaction and the antibody (surface modification) And measurement data may be arranged on the light scattering surface via an antibody. By using the antigen-antibody reaction to capture the measurement sample and place it on the light scattering surface, the amount of analyte to be placed on the light scattering surface can be increased, improving the sensitivity of Raman spectroscopic measurement. be able to.

In this way, when a known antibody is immobilized on the light scattering surface of the Raman spectroscopic device 10 and measurement is performed, if an antigen is contained in the measurement sample, the binding between the two occurs and the resulting Raman spectrum changes. The antigen can be identified. If a known antigen is immobilized on the light scattering surface, the antibody can be identified in the same manner.
The Raman spectroscopic device (fine structure) 10 is housed in a container, the container is filled with a solution containing a measurement sample, the Raman spectroscopic device is immersed, and Raman spectroscopic measurement is performed in the solution. You may do it.

Since the Raman spectroscopic apparatus 50 according to the present embodiment is configured using the Raman spectroscopic device 10, it can obtain a large Raman enhancement effect, has higher data reliability, and high data reproducibility. Accurate Raman spectroscopy can be performed.
In the Raman spectroscopic apparatus 50, hot spots are formed in substantially the entire area of the Raman spectroscopic device 10, and the reproducibility is good even if the same sample is measured by changing the light irradiation location. Data is obtained. Therefore, it is possible to take a plurality of data by changing the light irradiation location for the same sample, and to improve the reliability of the data.

  Although the Raman spectroscopic device 50 including the spectroscopic means that obtains the spectrum of the Raman scattered light by dispersing the scattered light from the light scattering surface (surface) of the fine structure 10 has been described, the present invention is not limited to this, and the fine structure The microstructure of the present invention can also be suitably applied to various detection devices having detection means for detecting the physical characteristics of light generated on the surface of the body 10. Here, the physical characteristics of light generated on the surface of the fine structure 10 are physical characteristics of scattered light, reflected light, emitted light, and absorbed light from the measurement material. In addition to the above-described Raman scattered light, Rayleigh scattered light is exemplified as the scattered light. Examples of light emission include fluorescence, phosphorescence and spontaneous light emission.

More specifically, a detection device that detects reflected light generated on the light scattering surface of the microstructure 10 and measures a reflected light intensity change from the measurement sample, and a detection unit that measures light emission from the measurement sample are provided. The microstructure of the present invention can also be suitably applied to a detection device that measures luminescence from a measurement sample. Moreover, the microstructure of the present invention can be suitably applied to a detection device that detects an absorption spectrum (absorbed light) of reflected light. A local plasmon device is exemplified as a detection device that measures a change in reflected light intensity from a measurement sample.
In any case, the intensity of the scattered light generated on the light scattering surface, the reflected light, and the light emission from the measurement sample is increased by the enhanced electric field effect of the hot spot formed on the light scattering surface of the microstructure 10. Therefore, detection of scattered light, reflected light, and light emission can be suitably performed.

  Further, although the Raman spectroscopic device 50 has been described as an example of an analysis device that analyzes the characteristics of a sample using the fine structure 10 described above, the invention is not limited thereto, and an enhanced electric field generated by the fine structure 10 is used. Then, the measurement sample arranged on the surface of the fine structure 10 is ionized, and m / z, which is a value obtained by dividing the mass m of the ionized measurement sample by the charge valence z, is detected. The microstructure of the present invention can also be suitably applied to a specified mass spectrometer.

Also in such a mass spectrometer, the method for arranging the measurement sample on the surface of the fine structure 10 is not particularly limited, and the measurement sample may be arranged directly on the surface of the fine structure 10.
Moreover, the surface of the fine structure 10 is subjected to surface modification that can capture measurement data and can be detached by irradiation of the measurement light, and the measurement sample is bonded to the surface modification. You may arrange | position to 10 surfaces. When the measurement sample contains an antigen, an antibody that can specifically bind to the antigen may be modified on the surface of the fine structure 10. Thereby, the quantity of the measurement sample arrange | positioned on the surface of a fine structure can be increased, and the sensitivity of a mass spectrometry measurement can be improved.
In any case, the measurement sample can be efficiently ionized by the enhanced electric field of the hot spot formed on the surface of the microstructure 10, and the measurement sample can be efficiently desorbed from the surface of the microstructure 10. it can.

Here, FIG. 8A is a diagram showing a preferred form of surface modification. In the figure, the surface modification R and the components of the surface modification R are shown enlarged for easy visual recognition. In the drawing, the surface of the fine structure 10 is simply shown as a plane for simplicity.
On the surface of the microstructure 10, a first linker function part A that binds to the measurement sample S, a second linker function part C that binds to the analyte S, the first linker function part A, and the second linker function part A It has a decomposition function part B that is interposed between the linker function part C and decomposes by an electric field generated by irradiation of the measurement light L1. In the illustrated example, the measurement sample S is arranged on the surface (near the surface) of the microstructure 10 via the surface modification R.

  The surface modification R may be one substance that includes all of the first linker function part A, the decomposition function part B, and the second linker function part C, and each of them is made of a different substance. It may be. Further, the first linker function part A and the decomposition function part B, or the decomposition function part B and the second linker function part C may be one substance.

  FIG. 8B is a view showing a state in which the analyte S is desorbed by irradiation with the measurement light L1 when the microstructure 10 has the surface modification R as shown in FIG. 8A. is there. When the microstructure 10 is irradiated with the measurement light L1, the electric field is enhanced on the surface thereof. The optical energy of the measurement light L1 is increased in the vicinity of the surface by the electric field enhanced on the surface, and the decomposition function part B of the surface modification R is decomposed by the increased energy, and the second linker function part is added to the measurement sample S. Those to which C is bonded are detached from the surface. Further, the measurement sample S is ionized by the increased energy near the surface.

  Hereinafter, the mass spectrometer of the present invention will be described based on an embodiment shown in FIG. The mass spectrometer of the present embodiment is a time-of-flight mass spectrometer that uses time-of-flight mass spectrometry (TOF-MS). FIG. 9 is a configuration diagram showing the configuration of the mass spectrometer.

  The mass spectrometer 100 includes a fine structure 10 according to the above-described embodiment (hereinafter also referred to as a mass analysis device 10), a device holding unit 60 that holds the mass analysis device 10, and a box 68 kept in a vacuum. The measurement sample S arranged on the surface of the mass spectrometric device 10 is irradiated with the measurement light L1 to desorb the measurement sample S, and the desorbed measurement sample S is detected and the measurement sample S is detected. And a drawer grid 62 disposed between the mass analyzing device 10 and the mass analyzing means 64 at a position facing the surface of the mass analyzing device 10, and a drawer grid. 62 is configured to include an end plate 63 disposed to face a surface opposite to the surface on the mass spectrometry device 10 side.

  The light irradiation means 61 includes a single wavelength light source such as a laser, and may include a light guide system such as a mirror that guides light emitted from the light source. Examples of the single wavelength light source include a pulse laser having a wavelength of 337 nm and a pulse width of about 50 ps to 50 ns.

  The mass spectrometric means 64 detects a measurement sample S that is detached from the surface of the mass spectrometric device 10 by irradiation with the measurement light L1 and flies through the central hole of the extraction grid 62 and the end plate 63. 65, an amplifier 66 that amplifies the output of the detection unit 65, and a data processing unit 67 that processes an output signal from the amplifier 66.

Mass spectrometry using the mass spectrometer 100 configured as described above will be described.
First, the voltage Vs is applied to the mass spectrometry device 10 on which the measurement sample S is arranged, and the surface of the mass spectrometry device 10 is irradiated with the measurement light L1 having a specific wavelength from the light irradiation means 61 by a predetermined start signal. The By irradiation with the measurement light L1, the electric field is enhanced on the surface of the mass spectrometry device 10, and the measurement sample S is ionized and desorbed from the surface by the optical energy of the measurement light L1 enhanced by the electric field.

  The desorbed measurement sample S is extracted in the direction of the extraction grid 62 due to the potential difference Vs between the mass spectrometry device 10 and the extraction grid 62, accelerates, and travels substantially straight in the direction of the end plate 63 through the central hole. And then passes through the hole of the end plate 63 and reaches the detector 65 to be detected.

  The flight speed of the measurement sample S after desorption depends on the value of m / z obtained by dividing the mass m of the measurement sample S by the charge valence z of the ionized measurement sample S, and the value of m / z is Larger is slower, smaller is faster. In the mass spectrometer 100 of the present embodiment, after the measurement sample S is desorbed from the surface of the mass spectrometry device 10 and ionized, the measurement sample S flies a predetermined distance from the mass spectrometry device 10 to the detector 65 to detect the detector 65. The value of m / z can be obtained by obtaining the time until it is detected.

  An output signal from the detector 65 is amplified to a predetermined level by the amplifier 66 and then input to the data processing unit 67. In the data processing unit 67, a synchronization signal synchronized with the start signal is input, and the flight time of the analyte S can be obtained based on the synchronization signal and the output signal from the amplifier 66. From time, the value of m / z can be obtained. Further, since the value of the charge valence z can be determined according to the measurement sample, the value of the mass m of the measurement sample can be obtained.

  As described above, the case where the mass spectrometer 100 uses time-of-flight mass spectrometry (TOF-MS) as described above has been described as an example. However, the present invention is not limited to this, and the surface of the mass spectrometry device 10 is not limited thereto. The method is not particularly limited as long as the measurement sample placed on the surface is ionized and desorbed by using the generated enhanced electric field, and the present invention can also be applied to analyzers using other mass spectrometry methods.

Hereinafter, the simulation regarding the electric field enhancement effect in the fine structure 10 will be described with reference to FIGS.
As shown in FIG. 10 and FIG. 11, the metal spheres were arranged in a grid pattern on the substrate. The diameter (particle diameter) R of the metal spheres was 30 nm, and the intersphere distance X was 30 nm. A metal ellipsoidal sphere was placed between the metal spheres. The elliptic sphere has a length D of 30 nm, a width L of 10, 20, or 30 nm, and a height h of 8, 15 nm. That is, in this simulation, simulation was performed for each of six types of elliptic spheres. In addition, a simulation was performed using a state in which the metal ellipsoidal sphere illustrated in FIG. 10 is not disposed as a comparative example.

  In this simulation, the average value of the fourth power of the intensity of the electric field E generated in a solid with a height of 30 nm, a width of 30 nm and a length of 30 nm sandwiched between two metal spheres when incident light of a certain wavelength enters. Calculated. Moreover, it calculated about the incident light of the some wavelength of the range of 500-1000 nm.

Here, the reason why the average value of the fourth power of the intensity of the electric field E in the solid is calculated will be described.
“Hongxing Xu et.al, Phys. Rev. E vol. 62, p4318-4324, (2000)” describes the surface enhanced Raman scattering intensity. In the above document, the following mathematical formulas (1) to (3) are described. By substituting the mathematical formula (2) or the mathematical formula (3) into the mathematical formula (1), the surface-enhanced Raman scattering intensity is reduced to a metal. Is proportional to the fourth power of the local electric field. Therefore, in this simulation, the value of the fourth power of the enhanced electric field E is calculated so that the relationship between the enhanced electric field E and the surface enhanced Raman scattering intensity can be easily understood with respect to the wavelength of the incident light.

  Hereinafter, the simulation results are set as a result 1 when [D = 30 nm, L = 10 nm, h = 8 nm], as a result 2 when [D = 30 nm, L = 10 nm, h = 15 nm], and [D = 30 nm, L = 20 nm, h = 8 nm] as a result 3, and [D = 30 nm, L = 20 nm, h = 15 nm] as a result 4, [D = 30 nm, L = 30 nm, h = 8 nm] The result of 5 is the result 5, the result 6 is [D = 30 nm, L = 30 nm, h = 15 nm], the result is 7 when there is no elliptic sphere, and the simulation result is shown in FIG. In the graph of FIG. 12, the horizontal axis is the wavelength, and the vertical axis is the average value of the fourth power of the intensity of the electric field E generated in the solid.

  From the graph of FIG. 12, it was found that the results 1 to 6 in the case where the elliptic sphere was arranged had higher electric field enhancement strength than the result 7 in the case where only the metal sphere was arranged. That is, a result showing that the electric field enhancement is improved by arranging the ellipsoidal spheres close to each other between the metal spheres was obtained. Further, when the results 1, 3 and 5 in the case of the height h = 8 are compared with the results 2, 4 and 6 in the case of the height h = 15, the case of the height h = 15, that is, the metal sphere The results showed that the electric field enhancement was improved when the distance from the ellipsoid was closer.

In addition, the electric field strength generated around the metal sphere and the elliptic sphere was calculated by simulation. In this simulation, the intensity of the electric field was calculated at intervals of 30 nm in the range where the wavelength of incident light was 610 to 1000 nm.
Further, in this simulation, the result when there is no ellipsoidal sphere and only a metal sphere is shown as a result 8 in FIG. 13A, and an ellipsoidal sphere of [D = 30 nm, L = 20 nm, h = 8 nm] is arranged. FIG. 13B shows the result when the elliptical sphere of [D = 30 nm, L = 20 nm, h = 15 nm] is arranged, and the result 10 is shown in FIG. 13C. It was.

Here, FIG. 13 is a diagram expressing the intensity of the electric field with shading. Originally, a diagram in which a region where the electric field is strong and a region where the electric field is strong with a white color as a center is represented by different colors. It attached to this specification as a figure expressed with these. In order to help understanding of FIG. 13, regions shown as regions where the electric field is strong in FIG. 13 are shown in FIG. 14.
As shown in FIGS. 13 and 14, it can be seen that there are more regions with a strong electric field in the results 9 and 10 when the ellipsoidal sphere is arranged than the result 8 when only the metal sphere is used. Further, as shown in FIG. 14, it can be seen that a region having a strong electric field is formed in a region where the metal sphere and the elliptical sphere are close to each other, that is, a hot spot is formed.

  From the above simulation, it has been found that when a metal ellipsoid is placed in the vicinity of the metal sphere, a hot spot that enhances the electric field is formed around the close position. It was also found that the higher the height of the ellipsoid, the smaller the distance between the metal sphere and the ellipsoid and the electric field enhancement effect is improved.

It is sectional drawing which shows typically one Embodiment of the microstructure based on this invention. It is process drawing which shows typically one Embodiment of the manufacturing method of the microstructure based on this invention. In the microstructure according to the present invention, it is an explanatory view for explaining the positional relationship between metal fine particles and a metal film. It is a graph which shows the relationship between the measured value at the time of measuring the height from the base-material surface of the microstructure based on this invention, and a measurement frequency. It is sectional drawing which shows the principal part of other embodiment of the microstructure based on this invention. It is sectional drawing which shows the principal part of other embodiment of the microstructure based on this invention. It is sectional drawing which shows one Embodiment of the Raman spectroscopy apparatus which concerns on this invention. (A) is a block diagram which shows typically an example of the surface modification of the device for mass spectrometry, (B) is explanatory drawing which shows a mode that a to-be-analyzed substance is desorbed by measurement light irradiation. It is a block diagram which shows typically the mass spectrometer which is one Embodiment of the analyzer which concerns on this invention. It is zx plane sectional drawing which shows the position of the metal sphere in simulation. (A) is zx plane sectional drawing at the time of arrange | positioning an ellipsoid between the metal spheres shown in FIG. 10, (B) is the top view which looked at (A) from the z direction. It is a graph which shows the result of a simulation by making a horizontal axis into a wavelength and a vertical axis | shaft to the 4th power of the electric field E. It is a side view which shows the result of the simulation regarding the intensity | strength of the electric field around a metal sphere. It is explanatory drawing which shows the area | region where the electric field is reinforced in FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Fine structure 12 Base material 12s Surface 14, 22 Metal microparticle 16 Metal film 18 Metal microparticle composite 20, 24, 26 Metal film (formed on base material surface) 50 Raman spectroscopic device 52 Light irradiation means 54 Spectroscopic means 60 Device holding means 61 Light irradiation means 62 Drawer grid 63 End plate 64 Mass analysis means 65 Detector 66 Amplifier 67 Data processing unit 68 Box 100 Mass spectrometer

Claims (14)

Arranging and fixing a plurality of fine metal particles having a size capable of inducing localized plasmons in a dispersed state on the substrate surface;
Forming a metal film in the gap between the plurality of metal fine particles,
The metal fine particles have a portion where the cross-sectional area of the cut surface parallel to the substrate surface is maximum, and the cross-sectional area decreases from the portion where the cross-sectional area is maximum toward the substrate surface. A method for manufacturing a fine structure, which is separated from the metal film.   When the effective particle diameter of the metal fine particle is Re and the effective height of the metal film from the substrate surface is he, the step of forming the metal film is separated from the metal fine particle, and he <Re / The method for manufacturing a microstructure according to claim 1, wherein the metal film satisfying the relationship 2 is formed.   Further, after the step of forming the metal film, the constituent metals of the metal film are aggregated into particles by heat treatment to be separated from the metal fine particles in the gaps between the metal fine particles and localized. The method for producing a microstructure according to claim 1, further comprising a heat treatment step of forming at least one film-like metal and / or a plurality of massive metals having a size capable of inducing plasmons.   4. The method for manufacturing a microstructure according to claim 3, wherein in the heat treatment step, the temperature of the heat treatment is set to be equal to or higher than a melting point of the metal and lower than a melting point of the base material. A substrate;
A plurality of fine metal particles having a size capable of inducing localized plasmons arranged and fixed in a dispersed state on the substrate surface;
At least one film-like metal and / or a plurality of massive metals arranged on the surface of the base material in a state of being spaced apart from and close to the metal fine particles and capable of inducing localized plasmons A fine structure characterized by comprising: The metal fine particles have a portion where the cross-sectional area of the cut surface parallel to the substrate surface is maximum, and the cross-sectional area decreases from the portion where the cross-sectional area is maximum toward the substrate surface. And
The microstructure according to claim 5, wherein the effective height of the metal fine particles is He and the effective height of the film metal and / or the bulk metal is he, and satisfies the relationship of He / 2> he.   The effective height He of the metal fine particles and the effective height he of the film-like metal and / or the massive metal are high in frequency among the results of measuring the height from the substrate surface at a plurality of points. The microstructure according to claim 6, which is measured as a value.   At least one metal selected from the group consisting of Au, Ag, Cu, Al, Pt, Ni, Ti, and alloys thereof is used as the main component of the metal fine particles and the film metal and / or the bulk metal, respectively. The microstructure according to any one of claims 5 to 7.   The microstructure according to any one of claims 5 to 8, wherein a distance between the metal fine particles and the film metal and / or the bulk metal adjacent to the metal fine particles is equal to or less than an average particle diameter of the metal fine particles. body. A Raman spectroscopic device having a light scattering surface that is used in Raman spectroscopy to obtain a spectrum of Raman scattered light by dispersing scattered light and is irradiated with measurement light and scattered.
A surface of the microstructure including the surface of the metal fine particles and the film metal and / or the bulk metal is provided as the light scattering surface. A device for Raman spectroscopy. The Raman spectroscopic device according to claim 10;
A light irradiation means for irradiating the light scattering surface of the Raman spectroscopic device with measurement light;
A Raman spectroscopic apparatus comprising: a spectroscopic unit that spectrally scatters scattered light generated on the light scattering surface to obtain a spectrum of the Raman scattered light. The fine structure according to any one of claims 5 to 9,
A light irradiating means for irradiating the surface of the microstructure including the surface of the metal fine particles and the film metal and / or the bulk metal with measurement light;
An analyzer comprising: signal detection means for detecting a signal generated from the surface of the fine structure. The fine structure according to any one of claims 5 to 9,
A light irradiating means for irradiating the surface of the microstructure including the surface of the metal fine particles and the film metal and / or the bulk metal with measurement light;
And a detection unit that detects a physical property of light generated on the surface of the fine structure. The fine structure according to any one of claims 5 to 9,
Irradiating measurement light onto the surface of the fine structure including the surfaces of the metal fine particles and the film-like metal and / or the bulk metal to ionize the measurement sample disposed on the surface of the fine structure, and Light irradiation means for desorption from the surface of the microstructure,
A mass spectrometer comprising: detection means for detecting the mass of the measurement sample desorbed and ionized from the surface of the microstructure.