JP2013096939A - Optical device and detector - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an optical device which enhances Raman scattering light in gaps among metal particles while securing a high density of hot sites from a relationship between the sizes of the metal particles and the gaps among the metal particles and enhances detection capability, and further to provide a detector.SOLUTION: An optical device 100 comprises: a substrate 110; a fine metal structure 120 constituted of a plurality of metal particles 120A which is formed on a surface of the substrate 110 and has sizes of 1 to 500 nm and intervals of 0.1 to 20 nm thereamong; and organic molecular films 130 on the fine metal structure 120. The organic molecular films 130 are absorbing films for capturing molecules and are arranged so as to cover minute gaps 121 on the surface of the substrate 110 individually formed by the metal particles 120A.

Description

  The present invention relates to an optical device, a detection apparatus, and the like.

  In recent years, the demand for sensor chips used for medical diagnosis, food and beverage inspection, etc. has increased, and the development of highly sensitive and small sensor chips has been demanded. In order to meet such demands, various types of sensor chips including an electrochemical method have been studied. Among these, spectroscopic analysis using surface plasmon resonance (SPR), especially surface-enhanced Raman scattering spectroscopy (especially for reasons such as integration, low cost, and choice of measurement environment) Interest in sensor chips using SERS (Surface Enhanced Raman Scattering) is increasing.

  Here, the surface plasmon is a vibration mode of an electron wave that causes coupling with light due to boundary conditions unique to the surface. As a method of exciting surface plasmons, there are a method of engraving a diffraction grating on a metal surface and combining light and plasmons and a method of using evanescent waves. For example, a sensor using SPR includes a total reflection prism and a metal film that contacts a target substance formed on the surface of the prism. With such a configuration, the presence or absence of target substance adsorption, such as the presence or absence of antigen adsorption in an antigen-antibody reaction, is detected.

  By the way, while propagation-type surface plasmons exist on the metal surface, localized surface plasmons exist on the metal fine particles. It is known that when a localized surface plasmon, that is, a surface plasmon localized on the surface metal microstructure is excited, a significantly enhanced electric field is induced.

  Furthermore, when the Raman scattered light is irradiated to the enhanced electric field formed by localized surface plasmon resonance (LSPR) using metal nanoparticles, the Raman scattered light is enhanced by the surface enhanced Raman scattering phenomenon. Is known, and a highly sensitive sensor (detection device) has been proposed. By using this principle, various trace amounts of substances can be detected.

  The enhanced electric field is large around the metal particles, particularly in the gap between adjacent metal particles, and it is necessary to stop the target molecule in the fluid sample in the gap between the metal particles. For example, in Patent Document 1 and Non-Patent Document 1, a self-assembled monolayer (SAM) is formed on a metal surface of a sensor chip.

JP 2009-222401 A

P. Freunscht et al., “Surface-enhanced Raman spectroscopy of trans-stilbene adsorbed on platinum or self-assembled monolayer-modified silver film over nanosphere surfaces”, Chemical Physics Letters, 281 (1997), 372-378

  10 and 12 of Patent Document 1, the metal pattern has a diameter of 800 nm. In Non-Patent Document 1, a silver film is formed on a spherical convex portion of polystyrene having a diameter of 542 nm. Patent Document 1 and Non-Patent Document 1 disclose forming a self-assembled monolayer on a metal pattern.

  According to such a structure, since the density of the metal particles serving as hot sites where an enhanced electric field is formed is small, there has been a limit to the improvement in detection capability of the sensor chip.

  According to some aspects of the present invention, while detecting the hot site density from the relationship between the size of the metal particles and the gap between the metal particles, the Raman scattered light is enhanced even in the gap between the metal particles, and the detection capability It is possible to provide an optical device and a detection apparatus with improved performance.

(1) One aspect of the present invention is
A substrate,
A metal microstructure comprising a plurality of metal particles formed on the surface of the substrate;
An organic molecular film formed on the metal microstructure,
The plurality of metal nanoparticles have a particle diameter in a plan view of 1 to 500 nm, and an interval between adjacent metal particles is 0.1 to 20 nm,
The organic molecular film is an adsorption film that traps molecules,
The organic molecular film is related to an optical device arranged to cover a gap between adjacent metal particles.

  According to one aspect of the present invention, the signal detection intensity in the optical device is determined by the density of the metal particles serving as hot sites (electric field enhancement field) and the target captured by the enhanced electric field formed around the metal particles. It is proportional to the number of molecules and inversely proportional to the size of the gap between metal particles. The density of the metal particles is determined by the size and interval (minute gap) of the metal nanoparticles. Here, when the metal particles are made smaller, the number of hot sites increases. However, when the processing accuracy cannot be ensured sufficiently and the variation in measurement sensitivity for each optical device increases, the metal particles are increased. However, when the diameter of the metal particles is increased, the number of hot sites is reduced. Therefore, in response to this sensitivity reduction, the sensitivity is improved by reducing the minute gap.

  Furthermore, the organic molecular film covering the minute gaps of the metal microstructure functions as an adsorption film that adsorbs molecules that are not adsorbed on the metal surface as it is, and also covers the minute gaps of the metal microstructure with a high strength of the enhanced electric field. For this reason, the signal detection intensity in the optical device can be increased.

  (2) In one embodiment of the present invention, the thickness of the organic molecular film can be 0.1 to 1 nm. The smaller the molecular film thickness is, the less sensitive to the attenuation of the enhanced electric field due to the distance from the surface of the metal nanoparticles, the signal can be detected with high sensitivity.

  (3) In one embodiment of the present invention, the thickness of the organic molecular film can be 0.1 to 0.4 nm. In particular, in metal microstructures with large metal particle diameters, it is necessary to improve the sensitivity by reducing the fine gaps between the metal particles, ensuring the density of the metal nanoparticles and the number of hot sites (the number of enhanced electric fields). . In this case, the thinner the organic molecular film, the easier it is to cover the entire gap between the metal particles.

  (4) In one embodiment of the present invention, the organic molecular film is an alkanethiol film, and the alkane may have 1 to 9 atoms of carbon in the main chain. The film thickness of the alkanethiol film has a correlation with the number of main chain carbon atoms, and the film thickness of the organic molecular film can be stably formed in the range of 0.1 to 1 nm by providing carbon of 9 atoms or less.

  (5) In one embodiment of the present invention, the organic molecular film is an alkanethiol film, and the alkane can have 1 to 3 atoms of carbon in the main chain. The film thickness of the alkanethiol film correlates with the number of main chain carbon atoms, and the film thickness of the organic molecular film can be stably formed in the range of 0.1 to 0.4 nm by providing carbon of 3 atoms or less.

  (6) In one embodiment of the present invention, the alkanethiol film may have 2 or more carbon atoms, and the two or more carbon atoms may have a linear arrangement. When the molecular chain of the organic molecular film is arranged in a linear form with an inclination of 60 ° or less with respect to the surface of the substrate, the film thickness of the organic molecular film 130 is 0.1 if the carbon number is 2-9. It can be stably formed in the range of ˜1 nm, and if the carbon number is 2 to 3, the film thickness of the organic molecular film 130 can be stably formed in the range of 0.1 to 0.4 nm.

  (7) In another aspect of the present invention, a light source, the above-described optical device that receives light from the light source, and a light detection unit that detects light reflecting a target material in a fluid sample emitted from the optical device. And a detection device having: This detection apparatus can perform highly sensitive detection by applying surface-enhanced Raman scattering.

FIG. 1A is an explanatory diagram of the principle of Raman scattering spectroscopy, and FIG. 1B is an example of a Raman spectrum acquired by Raman scattering spectroscopy. 2A is a partial cross-sectional view of the optical device, and FIG. 2B is a partial plan view of the optical device. It is a figure which shows the relationship between the organic molecular film from which film thickness (carbon number) differs, and Raman spectrum peak intensity. 4A shows the relationship between the film thickness (carbon number) of the organic molecular film and the SERS spectrum intensity, and FIGS. 4B and 4C show the relationship between the carbon number of the organic molecular film and the film thickness. It is. It is a top view of a metal microstructure with a large diameter of metal nanoparticles. 6A and 6B are diagrams showing the relationship between the diameter of the metal nanoparticles and the number of hot sites. It is the schematic of a detection apparatus. It is the figure which illustrated the organic molecular film on a metal surface. It is the figure which illustrated the molecular length of the organic molecular film. It is the figure which illustrated the relationship between the molecular length and film thickness of an organic molecular film. It is the figure which illustrated the relationship between CC bond distance and molecular length.

  Hereinafter, preferred embodiments of the present invention will be described in detail. The present embodiment described below does not unduly limit the contents of the present invention described in the claims, and all the configurations described in the present embodiment are indispensable as means for solving the present invention. Not necessarily. Moreover, in each figure, in order to make each component large enough to be recognized on the drawing, dimensions and ratios of each component are appropriately changed from actual ones.

1. Detection Principle FIG. 1A shows a principle explanatory diagram of Raman scattering spectroscopy. As shown in FIG. 1A, when the target molecule X (target object) is irradiated with light Lin having a single wavelength, Raman scattered light Ram having a wavelength λ2 different from the wavelength λin of the incident light Lin is included in the scattered light. Will occur. The energy difference between the Raman scattered light Ram and the incident light Lin corresponds to the vibration level, rotation level, and electron level energy of the target molecule X. Since the target molecule X has a specific vibration energy corresponding to its structure, the target molecule X can be specified by using light Lin having a single wavelength.

  For example, if the vibration energy of the incident light Lin is V1, the vibration energy of the target molecule X is V2, and the vibration energy of the Raman scattered light Ram is V3, then V3 = V1-V2. That is, since V3 becomes vibration energy corresponding to V2, the target molecule X can be specified by measuring the wavelength λ2 of the Raman scattered light Ram.

  Note that most of the incident light Lin has the same amount of energy after the collision with the target molecule X as before the collision. This elastic scattered light is called Rayleigh scattered light Ray. For example, when the vibration energy of Rayleigh scattered light Ray is V4, V4 = V1. That is, the wavelength λ1 of the Rayleigh scattered light Ray is λ1 = λin.

  FIG. 1B shows an example of a Raman spectrum (relation between Raman shift and Raman scattering intensity) acquired by Raman scattering spectroscopy. The horizontal axis of the graph shown in FIG. 1B indicates a Raman shift. The Raman shift is a difference between the wave number (frequency) of the Raman scattered light Ram and the wave number of the incident light Lin, and takes a value specific to the molecular binding state of the target molecule X.

  As shown in FIG. 1B, when the scattering intensity (spectrum peak) of the Raman scattered light Ram shown in B1 is compared with the scattering intensity of the Rayleigh scattered light Ray shown in B2, the Raman scattered light Ram is weaker. I understand that. As described above, the Raman scattering spectroscopy is a measurement technique that is excellent in the ability to discriminate the target molecule X, but has low sensitivity itself for sensing the target molecule X. For this reason, in the present embodiment, the sensitivity of the sensor is increased by using spectroscopy based on surface-enhanced Raman scattering.

2. Optical Device FIGS. 2A and 2B schematically show the structure of a surface plasmon resonance sensor chip (optical device) 100 according to an embodiment of the present invention. FIG. 2A is a cross-sectional view of the sensor chip 100, and FIG. 2B is a plan view of a metal microstructure, each showing a part of the sensor chip 100. FIG.

  In the sensor chip 100 shown in FIG. 2A, a plurality of metal particles 120A forming the metal microstructure 120 are periodically arranged, for example, vertically and horizontally as shown in FIG. Is formed. The plurality of metal particles 120A are formed of a metal such as Ag (silver) or Au (gold). The metal microstructure 120 may be manufactured by forming a concavo-convex pattern on the substrate 110 and forming a metal film on the concavo-convex pattern. The size (outer diameter) of the metal particles 120A in a plan view can be 1 to 500 nm, and the distance between two adjacent metal particles 120A (the size of the minute gap 121) can be 0.1 to 20 nm. More preferably, the size (outer diameter) of the metal particles 120A in plan view can be 10 to 300 nm, and the size of the gap 121 between the metal particles can be 0.1 to 10 nm.

  The metal particles 120A shown in the micrograph of FIG. 2B are formed of silver (Ag), the diameter of the metal particles 120A is 140 nm, and the minimum distance between two adjacent metal particles 120A is 10 nm.

  In the present embodiment, the organic molecular film 130 is provided on the metal microstructure 120. The organic molecular film 130 is an adsorption film that traps molecules, and forms a self-assembled monolayer SAM on the metal microstructure 120. The organic molecular film 130 is disposed so as to cover the minute gap 121 on the surface of the substrate 110 on which the plurality of metal particles 120A are formed, and also covers the outer surface of the plurality of metal nanoparticles 120A.

2.1. Example 1
In Example 1, three types of alkanethiol (Methanethiol CH ₃ SH: C1; Propanethiol C ₃ H ₇ SH: C3; ₁₆ H ₃₃ SH: C16) 1 mM ethanol solution is prepared, and the silver SERS chip 100 shown in FIG. 2 (B) is soaked overnight. As shown in FIG. A molecular film 130 was formed.

  FIG. 3 shows the SERS spectrum detected using the silver SERS chip 100 by exposing the surface of the silver SERS chip 100 to toluene gas as a target substance. FIG. 3 is a SERS spectrum obtained by exposing light having a wavelength of 632.8 nm from a 2 mW laser light source for 60 seconds.

In silver SERS chip 100 to form the C1 and C3 alkane thiol layer 130 in FIG. 3, characteristic of ^{785 cm} -1 in ^toluene, 1000 cm -1, a peak of 1030 cm ^-1 has been detected in high sensitivity, silver surface It became possible to detect molecules that couldn't be detected by itself.

When the above results are plotted with the carbon number of alkanethiol on the horizontal axis and the 1000 cm ⁻¹ peak of toluene on the vertical axis, FIG. 4A is obtained. As shown in FIG. 4 (A), the peak at 1000 cm ⁻¹ of toluene is represented by C 1 methanethiol CH ₃ SH expressed as C 1 and C ₃ propanethiol C ₃ H ₇ SH expressed as C _3. , C16 hexadecanethiol C ₁₆ H ₃₃ SH expressed as C16, in that order. The number of carbon atoms of the material forming the organic molecular film 130 is reflected in the film thickness of the organic molecular film 130 as shown in FIGS. The film thickness of the organic molecular film 130 made of C 1 methanethiol CH ₃ SH represented by C1 is 0.13 nm, whereas it is made of C ₁₆ hexadecanethiol C ₁₆ H ₃₃ SH represented by C16. The film thickness of the organic molecular film 130 is 1.76 nm. An example of calculating the film thickness will be described later.

From FIG. 4, the thinner organic molecular film 130 can be detected with high sensitivity without being affected by the attenuation of the enhanced electric field due to the distance from the metal surface. It can be seen that when the film thickness exceeds 1 nm (10 or more carbon atoms), the sensitivity is low and the toluene detection capability is low. This is because the range of the electric field enhancement E due to the localized surface plasmon resonance (LSPR) is larger as it is closer to the surface of the metal nanoparticle 120A, and is attenuated remarkably as it is farther away (SERS intensity ４E ⁴ ). From this, the film thickness of the organic molecular film 130 is preferably 0.1 to 1 nm, and more preferably 0.1 to 0.4 nm.

  In the case where the organic molecular film 130 is an alkanethiol film, if the alkane is provided with carbon of 1 atom or more and 9 atoms or less in the main chain, the film thickness of the organic molecular film 130 is reduced to 0. As shown in FIG. It can be set to 1-1 nm. Further, in the case where the organic molecular film 130 is an alkanethiol film, if the alkane has 1 to 3 atoms of carbon in the main chain, the thickness of the organic molecular film 130 is reduced as shown in FIG. The thickness can be 0.1 to 0.4 nm. In particular, in the structure in which the metal nanoparticles 120A have a large particle size and the number of hot sites is small, it is necessary to reduce the length of the minute gap 121 between the metal nanoparticles 120A to improve the sensitivity. The thickness is limited. This is because when the length of the minute gap 121 is small and the organic molecular film 130 is thick, it is difficult to cover the entire minute gap 121 with the organic molecule 130.

  When the number of carbon atoms is 2 to 9, it is preferable that two or more carbon atoms have a linear arrangement. When the molecular chain of the organic molecular film 130 is arranged in a straight line with an inclination of 60 ° or less with respect to the surface of the substrate 110, the film thickness of the organic molecular film 130 is reduced to 0 if the number of carbon atoms is 2-9. It can be stably formed in the range of 1 to 1 nm, and if the number of carbon atoms is 2 to 3, the thickness of the organic molecular film 130 can be stably formed in the range of 0.1 to 0.4 nm.

  Here, the relationship between the molecular structure of the organic molecular film (alkanethiol film) and the film thickness will be described. As shown in FIG. 8, the definition of the film thickness T is defined as the distance from the terminal S atom center on the metal side to the terminal C atom center on the opposite side when the alkanethiol is inclined, for example, 60 ° from the metal (eg, Ag) surface. did.

  The thickness T is calculated by first obtaining the alkanethiol molecular length (distance from the terminal S atom to the terminal C atom) as shown in FIG. 9 and FIG. I asked for it. For the calculation of film thickness T, the bond distance described in the Chemical Handbook (Basic Edition II, revised edition 2, edited by The Chemical Society of Japan, Maruzen) is CC bond distance = 1.54 mm, SC bond distance. = 1.82 mm and C—H bond distance = 1.10 mm, and all bond angles were 109.5 °.

Methanethiol (C1)
Molecular length = {CC bond distance x (C-1) + S-C bond distance x 1} x {sin (109.5 ° ÷ 2)}
= (1.54 x 0 + 1.82 x 1) x 0.8166
= 1.49 Å
Film thickness = molecular length × sin 60 °
= 1.49 × √3 / 2
= 1.29 Å
= 0.13 nm
Hexadecanethiol (C16)
Molecular length = {CC bond distance x (C-1) + S-C bond distance x 1} x {sin (109.5 ° ÷ 2)}
= (1.54 x 15 + 1.82 x 1) x 0.8166
= 20.35 Å
Film thickness = molecular length × sin 60 °
= 20.35 × √3 / 2
= 17.62 Å
= 1.76 nm
2.2. Example 2
FIG. 5 shows an example in which the particle diameter of the metal particles 120A is set to the upper limit of 500 nm instead of the metal microstructure shown in FIG. As the particle size of the metal particle 120A increases, as shown in FIGS. 6A and 6B, the number of localized surface plasmon resonance (LSPR) hot sites HS decreases accordingly. 6A and 6B show metal nanoparticles 120A having different particle diameters with respect to the laser beam diameter D. FIG. 6A in which the particle diameter is large is larger than that in FIG. The number of hot sites HS is decreasing.

  Here, when the number of hot sites is N and the size of the minute gap 121 is G, the SERS intensity is SERS intensity 微小 N / G.

  Thus, since the number N of hot sites is small in the structure in which the particle size of the metal particle 120A is large, it is necessary to improve the sensitivity by reducing the size G of the gap 121 between the metal particles. As described above, when the size G of the gap 121 between the metal particles is reduced, a molecule having a large molecular length cannot enter between the structures. Therefore, the size of the organic molecule film 130 depends on the size G of the gap 121 between the metal particles. The film thickness is limited. Therefore, when the metal particles 120A having a relatively large particle size are used as in the second embodiment, it is suitable that the thickness of the organic molecular film 130 is 0.1 to 0.4 nm.

3. FIG. 7 is a schematic diagram illustrating an example of a detection apparatus 200 including the sensor chip (optical device) 100 (reference numeral 260 in FIG. 7) described above. A target substance (not shown) is carried into the detection device 200 from the A direction and is carried out in the B direction. The laser emitted from the excitation light source 210 is collimated by a collimator lens, passes through the polarization control element 230, and is guided toward the sensor chip 260 by the dichroic mirror 240. The laser is condensed by the objective lens 250 and enters the sensor chip 260. At this time, a target substance (not shown) is arranged on the surface of the sensor chip 260 (for example, the surface on which the metal microstructure 120 is formed). By controlling the drive of a fan (not shown), the target substance is introduced from the carry-in port to the inside of the transfer unit and discharged from the discharge port to the outside of the transfer unit.

  When laser light is incident on the surface of the sensor chip 260, an extremely strong enhanced electric field is generated in the vicinity of the metal microstructure 120 via the surface plasmon resonance SPR. When one to several target substances enter the enhanced electric field and are adsorbed by the organic molecular film 130, Raman scattered light is generated therefrom. The Raman scattered light passes through the objective lens 250, is guided in the direction of the photodetector 280 by the dichroic mirror 240, is collected by the condenser lens 270, and enters the photodetector (for example, a diffraction grating type spectrometer) 280. To do. Then, the spectrum is decomposed by the photodetector 280, and the spectrum information as shown in FIG. 4B is obtained. According to this configuration, since the sensor chip 100 described above is provided, the sensor sensitivity is improved, and the target substance can be specified from the Raman scattering spectrum.

  Although the present embodiment has been described in detail as described above, it will be easily understood by those skilled in the art that many modifications can be made without departing from the novel matters and effects of the present invention. Accordingly, all such modifications are intended to be included in the scope of the present invention.

  For example, as a reagent for forming the organic molecular film 130, a reagent for forming a self-assembled monomolecular film (SAM) on the metal microstructure 120 can be used, and as this reagent, a thiol group, a disulfide group, a carbonyl group, etc. Can be used. Conventionally, as a SAM-forming reagent, a longer chain length (thick film thickness) is more stable and easier to arrange regularly because the intermolecular interaction between molecules is stronger. Long ones (thick film thickness) have been often used. However, as described above, it has been clarified through experiments that, when used for SERS, in order to efficiently use the range of LPSR electric field enhancement, a shorter chain length is more advantageous. The formation of the organic molecular film 130 is not limited to the liquid phase but may be a gas phase.

100, 260 optical device, 110 substrate, 120 metal microstructure,
120A metal particles, 121 gaps between metal particles, 130 organic molecular film,
200 detectors, 210 light sources, 280 photodetectors

Claims (7)

A substrate,
A metal microstructure comprising a plurality of metal particles formed on the surface of the substrate;
An organic molecular film formed on the metal microstructure,
The plurality of metal particles has a particle diameter in a plan view of 1 to 500 nm, and an interval between adjacent metal particles is 0.1 to 20 nm,
The organic molecular film is an adsorption film that traps molecules,
The organic molecular film is disposed so as to cover a gap between adjacent metal particles. The optical device according to claim 1.
An optical device, wherein the organic molecular film has a thickness of 0.1 to 1 nm. The optical device according to claim 1.
An optical device having a thickness of the organic molecular film of 0.1 to 0.4 nm. The optical device according to claim 2.
The organic molecular film is an alkanethiol film;
The alkane has carbon of 1 atom or more and 9 atoms or less in the main chain. The optical device according to claim 3.
The organic molecular film is an alkanethiol film;
The alkane has carbon of 1 atom or more and 3 atoms or less in the main chain. The optical device according to claim 4 or 5,
The number of carbon atoms is two or more, and the two or more carbon atoms have a linear arrangement. A light source;
The optical device according to any one of claims 1 to 6, wherein light from the light source is incident;
A light detection unit for detecting light reflecting a target material in a fluid sample emitted from the optical device;
A detection apparatus comprising: