JP2009115546A - Analyzer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To effectively generate enhanced electric field in an analyzer for placing a material to be analyzed on the surface of an optical resonator for generating the enhanced electric field on the surface, into which a light of a particular wavelength is incident on, utilizing the enhanced electric field generated on the surface of the optical resonator, and analyzing the characteristics of the material. <P>SOLUTION: The analyzer includes: the optical resonator for internally resonating the light beam, having a predetermined wavelength and making the light beam enter from the surface into the interior, and for generating the enhanced electric field on the surface; a wavelength-variable laser light source for irradiating the light beam incident on the surface of the optical resonator, and continuously making the wavelength of the irradiated light beam change; and a wavelength setting means for making the wavelength of the light beam change, determining the resonance wavelength of the optical resonator having the maximum strength for the enhanced electric field, and setting the wavelength of the light beam irradiated from the wavelength-variable laser light source, to the determined resonance wavelength. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention arranges an analyte on the surface of an optical resonator that generates an enhanced electric field when a light beam having a predetermined wavelength is incident, and uses the enhanced electric field generated on the surface of the optical resonator to The present invention relates to an analyzer for analyzing physical characteristics.

  Raman spectroscopy is a method of obtaining a spectrum of Raman scattered light (Raman spectrum) by dispersing scattered light obtained by irradiating a substance with single wavelength light, and is used for identification of substances. Since this Raman scattered light is weak light, this Raman scattered light is enhanced by utilizing localized plasmon resonance (plasmon effect) caused by the fine structure of metal in the nano order (hereinafter referred to as metal nanostructure). A method for expressing the surface enhanced Raman scattering (SERS) effect is known, and in order to obtain the SERS effect, a method using the cavity effect has been proposed.

  Patent Document 1 discloses an apparatus and a detection method for detecting a Raman signal from a medium by disposing a medium including a plurality of agglomerated nanoparticles including fractals near a microcavity and allowing light from the light source to enter the medium. Is described. In addition, Patent Document 1 is known that a device having fractal aggregates and microcavities causes a large enhancement of light emission, and puts nanoparticles and / or fractal aggregates into high-Q microcavities. Thus, it is described that combining the properties of these light enhancement processes.

Japanese translation of PCT publication No. 2004-530867

By the way, a microcavity / microresonator as described in Patent Document 1 is designed and manufactured in accordance with the wavelength of measurement light so that the wavelength is a resonance wavelength. For example, the outer diameter and length of a columnar microresonator are designed according to the wavelength of measurement light, and the inner diameter of a device (optical resonator) having a cylindrical microcavity is designed.
However, the microcavity / microresonator is a very fine structure, and it is very difficult to fabricate as designed. Therefore, even if the measurement light is designed to have a resonance wavelength, the actually produced microcavity / microresonator has a problem that it is difficult to make the resonance wavelength coincide with the design value.

  The object of the present invention is to solve the above-mentioned problems of the prior art, and to place an analyte on the surface of an optical resonator, such as a microcavity / microresonator, where a specific wavelength of light is incident to generate an enhanced electric field. In the analyzer that analyzes the characteristics of the analyte by using the enhanced electric field generated on the surface of the optical resonator, an analyzer that can generate the enhanced electric field more effectively and enable high-precision analysis. It is to provide.

  In order to achieve the object of the present invention, the present invention includes an optical resonator that resonates a light beam of a predetermined wavelength incident from the surface to the inside to generate an enhanced electric field on the surface, and the optical resonance. Irradiating the light beam to be incident on the surface of the body and irradiating the light beam by changing the wavelength of the light beam, and a tunable laser light source that continuously changes the wavelength of the irradiated light beam To determine the resonance wavelength of the optical resonator that maximizes the intensity of the enhanced electric field generated on the surface of the optical resonator, and the light emitted from the wavelength tunable laser light source to the determined resonance wavelength. Analyte disposed on the surface of the optical resonator using wavelength setting means for setting the wavelength of the beam and the enhanced electric field generated on the surface by irradiation of the light beam having the resonance wavelength There is provided an analysis apparatus characterized by having an analysis means for analyzing the properties.

Here, the optical resonator includes a first reflector having transflective properties, a translucent material, and a second reflector having complete reflectivity or transflective properties as the surface side. It is preferable that they are sequentially provided.
Moreover, it is preferable that the first reflector has a metal fine structure capable of generating localized plasmons. The analyzer according to claim 1 or 2.

The analyzer of the present invention may further include a spectroscopic unit that splits scattered light generated on the surface of the optical resonator to obtain a spectrum of Raman scattered light, and the wavelength setting unit includes a signal of the Raman scattered light. It is preferable that the wavelength of the light beam obtained strongly is set to the resonance wavelength at which the intensity of the enhanced electric field is maximized.
Alternatively, it further comprises spectroscopic means for dispersing scattered light generated on the surface of the optical resonator to obtain a spectrum of the scattered light, and the wavelength setting means is configured to change the wavelength of the absorption spectrum of the scattered light to the enhanced electric field. It is preferable that the resonance wavelength is set to the resonance wavelength that maximizes the intensity.
Alternatively, the wavelength setting means sets the wavelength at which the intensity of the reflected light or transmitted light of the optical resonator is maximized to the resonance wavelength at which the intensity of the enhanced electric field is maximized. It is preferable.

  Here, the cut wavelength is further changed according to the wavelength of the light beam that is disposed downstream of the optical resonator in the traveling direction of the light beam and is irradiated from the wavelength tunable laser light source. It is preferable to provide a variable filter that cuts the light beam.

  It is preferable that the analyzing unit is a spectroscopic unit that spectrally scatters scattered light generated on the surface of the optical resonator to obtain a spectrum of Raman scattered light.

  The analyzing means is a mass analyzing means for analyzing the mass of the analyte, and has the resonance wavelength from the wavelength tunable laser light source on the surface of the optical resonator on which the analyte is disposed. Using the enhanced electric field generated on the surface by irradiating the light beam, the analyte is desorbed from the surface, and the mass of the desorbed analyte is analyzed by the mass analyzing means. It is preferable.

In this specification, the arrangement of the analyte on the surface of the optical resonator means that the analyte is placed in direct contact with the surface of the optical resonator, or the analyte is placed on the optical resonator. This includes the case where it is arranged (closed) near the surface.
Moreover, in this specification, a sample means what contains various members used for arrange | positioning a to-be-analyzed substance and this to-be-analyzed substance on the surface of an optical resonator. Here, the various types of members other than the analyte include a holding member such as a solvent that holds the analyte and holds the analyte on the surface of the optical resonator, and specifically binds to the analyte. For example, a capturing member that captures the analyte on the surface of the optical resonator. Here, for example, when the analyte is an antigen, the capture member is an antibody that can specifically bind to the antigen.

  According to the analyzer of the present invention, the wavelength of the light beam is changed, and the resonance wavelength of the optical resonator that maximizes the intensity of the enhanced electric field generated on the surface of the optical resonator by irradiation with the light beam is determined. A wavelength setting means for setting the wavelength of the light beam emitted from the wavelength tunable laser light source to the set resonance wavelength, and setting the wavelength of the light beam emitted from the wavelength tunable laser light source as the resonance wavelength of the optical resonator. Therefore, even if the resonant wavelength of the optical resonator is deviated from its design value, the resonant wavelength of the optical resonator and the wavelength of the light beam can be accurately matched, so that an enhanced electric field is effectively applied to the surface. Can be generated.

Hereinafter, an analysis apparatus according to the present invention will be described in detail based on a preferred embodiment shown in the accompanying drawings.
Hereinafter, a Raman spectroscopic device, which is an embodiment of an analyzer according to the present invention, will be described. FIG. 1 is a configuration diagram schematically showing one embodiment of a Raman spectroscopic device according to the present invention. FIG. 2 is a block diagram showing a drive control system that controls the operation of each part of the Raman spectroscopic device. FIG. 3 is a configuration diagram showing an embodiment of a Raman spectroscopic device used in the Raman spectroscopic apparatus according to the present invention, FIG. 3A is a perspective view, and FIG. It is sectional drawing.

A Raman spectroscopic device 100 shown in FIG. 1 includes a Raman spectroscopic device 1, a wavelength tunable laser 50, a tunable filter 60, a wavelength cut detector 70, a spectroscopic means 80, a mirror 72, and various optical members not shown. And a light guiding optical system. In addition, the Raman spectroscopic device 100 includes a control unit 90 that controls the operation of each unit of the Raman spectroscopic device 100, as shown in FIG.
The Raman spectroscopic device 100 causes the measurement light L1 from the wavelength tunable laser 50 to enter the measurement target material arranged on the surface of the Raman spectroscopic device 1, and scatters the scattered light from the measurement target material to obtain a Raman scattering spectrum. To get.

  The Raman spectroscopic device 1 shown in FIGS. 1 and 3 includes a first reflector 10 having transflective properties from the incident side (the upper side in the drawing) of the measurement light L1 emitted from the wavelength tunable laser 50; A translucent body 20 and a second reflector 30 having complete reflectivity are sequentially provided. Here, transflective means that it has both translucency and reflectivity, and the transmissivity and reflectivity are arbitrary.

  The Raman spectroscopic device 1 enhances an electric field on the surface 1 s by resonating a light beam having a predetermined wavelength incident on the inside from the surface (light scattering surface) 1 s of the first reflector 10 (enhanced electric field). This is an optical resonator. That is, in the Raman spectroscopic device 1 of the present embodiment, the electric field is enhanced on the surface (light scattering surface) 1s of the first reflector 10, and a surface enhanced Raman effect can be obtained. It can be placed to analyze the analyte.

Here, the arrangement of the analyte on the surface 1s of the Raman spectroscopic device 1 means that the analyte is placed in direct contact with the surface 1s or the electric field in the vicinity of the surface 1s is enhanced. It is not particularly limited, including the case where it is arranged (adjacent) in a region to be processed.
For example, a surface modification (capturing member) that specifically binds to the analyte and captures the analyte is applied to the surface 1s, and the analyte is disposed on the surface 1s via the surface modification, The analysis substance may be brought close to the surface 1s.

  In this embodiment, the analyte is combined with the analyte combined with the surface modification and the surface modification, or a holding member such as a solvent that holds the analyte and holds it on the surface 1s. This is also called a sample. In addition, the state in which the analyte is disposed on the surface 1s through the surface modification or the holding member is referred to as the state in which the sample is disposed on the surface 1s.

  Further, for example, when the analyte is an antigen, an antibody that can specifically bind to the antigen is modified on the surface 1s, and the analyte that is the antigen by the antigen-antibody reaction, the antibody (surface modification), And the analyte may be disposed on the surface 1s via the antibody, that is, the analyte may be disposed in the vicinity of the surface 1s. By using the antigen-antibody reaction to capture and arrange the analyte on the surface 1s, the amount of the analyte to be arranged on the surface 1s can be increased, and the sensitivity of the Raman spectroscopic measurement is improved. Can do.

The translucent body 20 is composed of a translucent flat substrate, and the first reflector 10 is composed of a metal pattern layer in which fine metal wires 11 are formed in a regular lattice pattern on one surface of the translucent body 20. The second reflector 30 is composed of a solid metal layer formed on the other surface of the translucent body 20.
The material of the translucent body 20 is not particularly limited, and examples thereof include translucent ceramics such as glass and alumina, translucent resins such as acrylic resins and carbonate resins, and the like.

  As a material of the first reflector 10 and the second reflector 30, any reflective metal can be used, and examples thereof include Au, Ag, Cu, Al, Pt, Ni, Ti, and alloys thereof. The first reflector 10 and the second reflector 30 may include two or more of these reflective metals.

  The second reflector 30 that is a solid metal layer can be formed by, for example, metal vapor deposition. The first reflector 10 can be formed, for example, by performing a known photolithography process after forming a solid metal layer by metal deposition or the like.

  Although the first reflector 10 is made of a reflective metal, it has a plurality of pattern gaps 12 which are gaps through which the measurement light irradiated on the surface of the device is transmitted. Have sex. The line width and pitch of the fine metal wires 11 of the first reflector 10 are designed to be smaller than the wavelength of the measurement light L1, and the first reflector 10 has an uneven structure smaller than the wavelength of the measurement light L1. It has become. Therefore, the first reflector 10 has a metal microstructure that can generate localized plasmons. The first reflector 10 having a concavo-convex structure smaller than the wavelength of the measurement light L1 acts as a semi-transmissive and semi-reflective thin film with respect to light due to a so-called electromagnetic mesh shielding effect.

  The pitch of the thin metal wires 11 is not particularly limited as long as the condition smaller than the wavelength of the measurement light L1 is satisfied. For example, when visible light is used as the measurement light L1, it is preferably 200 nm or less. The line width of the fine metal wire 11 is preferably equal to or less than the mean free path of electrons that vibrate in the metal by light, specifically 50 nm or less, and particularly preferably 30 nm or less.

  As shown in FIG. 3B, when the measurement light L1 is incident on the Raman spectroscopic device 1, a part of the surface 1s of the first reflector 10 depends on the transmittance and the reflectance of the first reflector 10. (Not shown), and part of the light passes through the first reflector 10 and enters the light transmitting body 20. The light incident on the translucent body 20 is repeatedly reflected between the first reflector 10 and the second reflector 30. That is, the Raman spectroscopic device 1 has a resonance structure in which multiple reflection occurs between the first reflector 10 and the second reflector 30. Accordingly, multiple interference due to multiple reflected light occurs inside the translucent body 20, resonates at a specific wavelength that satisfies the multiple interference condition (hereinafter, this specific wavelength is referred to as a resonance wavelength), and light at the resonance wavelength is selectively absorbed. Absorption characteristics are shown. In the Raman spectroscopic device 1, the electric field is enhanced according to the absorption characteristics, and a surface enhanced Raman scattering effect can be obtained on the surface 1 s.

  In the Raman spectroscopic device 1, the multiple interference condition is that the average complex refractive index of the first reflector 10, the average complex refractive index of the second reflector 30, the average complex refractive index and the thickness of the translucent body 20 are set. Since it changes according to these factors, the absorption characteristic of absorbing light of a specific wavelength (resonance wavelength) according to these factors is shown. Then, emitted light L2 having physical characteristics different from the measurement light L1 corresponding to the absorption characteristics is emitted. The Raman spectroscopic device 1 of the present embodiment is a reflective device in which the emitted light L2 is emitted only from the first reflector 10 because the second reflector 30 has complete reflectivity.

Here, in the Raman spectroscopic device 1, the average complex refractive index of the first reflector 10 is n ₁ −ik ₁ , the average complex refractive index of the light transmitting body 20 is n ₂ , and the average complex refractive index of the second reflector 30 is. The refractive index is n ₃ −ik ₃ , and the thickness of the translucent body 20 is d (k ₁ and k ₃ are extinction coefficients, and −ik ₁ and −ik ₃ are imaginary parts. The imaginary part of the average complex refractive index of the light body 20 is 0.), the phase shift φ1 when reflected by the first reflector 10 and the phase shift φ2 when reflected by the second reflector 30 are Are each represented by the following formula.
φ1 = tan ⁻¹ [2n ₂ k ₁ / (n ₂ ² −n ₁ ² −k ₁ ² )]
φ2 = tan ⁻¹ [2n ₂ k ₃ / (n ₂ ² −n ₃ ² −k ₃ ² )]
The resonance wavelength λ, which is the peak wavelength of light absorbed by multiple interference, is expressed by the following equation.
λ = 4πn ₂ d / (2π−φ1−φ2)

  In particular, when at least one of the first reflector 10, the translucent body 20, and the second reflector 30 is configured by a light absorber whose imaginary part of the complex dielectric constant is not 0, the absorption peak becomes sharp and specific. It shows strong absorption with respect to light of a wavelength. In the present embodiment, the first reflector 10 and the second reflector 30 that are metal layers are light absorbers whose imaginary part is not zero.

  The thickness d of the translucent body 20 is not limited, and is preferably 300 nm or less because the absorption peak wavelength in the visible light wavelength region due to multiple interference is one and is easy to detect, and multiple reflection occurs effectively and the absorption peak due to multiple interference. The wavelength is preferably 100 nm or more because detection is easy in the visible light region.

  The Raman spectroscopic device 1 preferably has a device structure with optical impedance matching so that the number of multiple reflections (finesse) in the translucent body 20 is maximized. Such a configuration is preferable because the absorption peak becomes sharper and more accurate analysis can be performed.

  The Raman spectroscopic device 1 according to the present embodiment configured as described above is configured such that light transmitted through the first reflector 10 and incident on the transparent body 20 is the first reflector 10 and the second reflector. Thus, multiple reflections (resonance) occur effectively by repeating reflections with 30, and multiple interference due to multiple reflected light occurs effectively. In the Raman spectroscopic device 1 of the present embodiment, the multiple interference condition is that the average complex refractive index of the first reflector 10, the average complex refractive index of the second reflector 30, the average complex refractive index and thickness of the translucent body 20. Therefore, the first reflecting body 10 emits outgoing light L2 having physical characteristics different from that of the measuring light L1 corresponding to the absorption characteristics. The

  Further, in the Raman spectroscopic device 1 of the present embodiment, localized plasmon resonance can be effectively caused on the surface 1 s of the first reflector 10 made of a metal pattern layer. Local plasmon resonance is a phenomenon in which a metal free electron resonates with an electric field of light and vibrates to generate an electric field. In particular, in a metal layer having a concavo-convex structure, it is said that a free electric field in a convex portion oscillates in resonance with an electric field of light, thereby generating a strong electric field around the convex portion and effectively causing localized plasmon resonance. In the present embodiment, since the first reflector 10 has a concavo-convex structure smaller than the wavelength of the measurement light L1, localized plasmon resonance occurs effectively.

  For the wavelength at which the local plasmon resonance occurs, the scattering and absorption of the measurement light L1 are remarkably increased, and the intensity of the reflected light is remarkably reduced for this specific wavelength. The light wavelength (resonance peak wavelength) at which this localized plasmon resonance occurs and the degree of scattering and absorption of the measurement light L1 depend on the refractive index of the sample on the surface 1s of the Raman spectroscopic device 1 and the like.

  Usually, since the absorption peak due to multiple interference and the absorption peak due to localized plasmon resonance appear at different wavelengths, the Raman spectroscopic device 1 of the present embodiment detects physical changes due to multiple interference phenomenon and localized plasmon resonance phenomenon, respectively. Thus, it is possible to perform a more accurate analysis. Note that the absorption peak due to multiple interference and the absorption peak due to localized plasmon resonance may overlap.

  The material of the first reflector 10 and the second reflector 30 is preferably a metal because an electric field enhancement effect by local plasmon resonance can be obtained as described above, but a reflective material other than a metal is used. Also good.

In the present embodiment, the case where the first reflector 10 has a regular lattice pattern has been described. However, the pattern shape of the first reflector 10 is arbitrary and may be a random pattern. However, higher structural regularity is preferable in terms of sensitivity and the like because the in-plane uniformity of the resonance structure is higher and the characteristics are concentrated.
In addition, the second reflector 30 is a reflector having complete reflectivity, but is not limited to this, and the metal thin wires 31 are formed in a regular lattice pattern like the first reflector 10. It may be made of a metal pattern layer and have transflective properties.

The Raman spectroscopic device 1 configured as described above is designed according to the wavelength of the measurement light L1, for example, so that the design value of the resonance wavelength matches the measurement light L1. Note that the resonance wavelength can be adjusted by adjusting the thickness d of the transparent body 20 according to the wavelength of the measurement light L1 using a material having a predetermined refractive index. Here, it is not easy to set the thickness of the actual translucent body 20 as designed, and the resonance wavelength of the actually produced Raman spectroscopy device 1 deviates from the designed value, and the measurement light L1 The value may be different from the wavelength, and the surface-enhanced Raman effect may not be sufficiently obtained.
As will be described in detail below, the Raman spectroscopic device of the present invention adjusts the wavelength of the measurement light L1 to the resonance wavelength of the Raman spectroscopic device even when the actual resonant wavelength of the Raman spectroscopic device deviates from its design value. And by setting, the surface enhancement Raman effect can be effectively obtained.

A wavelength tunable laser 50 shown in FIG. 1 is a light source that irradiates laser light having a single wavelength as measurement light L1 and enters the Raman spectroscopic device 1. The wavelength tunable laser 50 is a light source that can change the wavelength of the emitted light, and therefore can change the wavelength of the measurement light L1, and is, for example, a Ti—Al ₂ O ₃ laser or an OPO (optical parametric oscillation). ) Various wavelength tunable laser light sources such as a light source can be preferably used.

The wavelength tunable laser 50 may be configured to change the wavelength in the range of all wavelengths normally used as the wavelength of the measurement light L1, for example, in a Raman spectroscope, and is measured according to the characteristics of the analyte. The wavelength of the light L1 may be determined.
The wavelength tunable laser 50 determines the wavelength of the measurement light L1 in advance according to the characteristics of the analyte, for example, and continuously sets the wavelength of the measurement light L1 within a predetermined range from this wavelength, for example, several tens of nm It may be configured to be changeable.

  The wavelength tunable laser 50 is designed so that the determined wavelength of the measurement light L1 is a resonance wavelength. Even if the resonance wavelength of the manufactured Raman spectroscopy device 1 deviates from the design value, the wavelength is continuously increased. The wavelength of the measurement light L1 and the resonance wavelength of the Raman spectroscopic device 1 can be exactly matched.

  The variable filter 60 includes a multilayer filter 62 and a filter driving unit 64 that changes the angle of the multilayer filter 62, and is disposed on the downstream side of the Raman spectroscopic device 1. The variable filter 60 adjusts the angle of the multilayer filter 62 according to the adjustment or change of the wavelength of the measurement light L1 emitted from the wavelength tunable laser light source 50, and changes the cut wavelength to the wavelength of the measurement light L1. Then, the light beam having the wavelength of the changed measurement light L1 is cut. In the present embodiment, the variable filter 60 is, in particular, the measurement light L1 among the scattered light by the measurement light L1 generated on the surface 1s of the Raman spectroscopic device 1 by the irradiation of the measurement light L1 and the reflected light of the measurement light L1. The light of the component of the wavelength is removed. The cut wavelength is not limited to the wavelength of the measurement light L1, and may be set so as to cut light having a desired wavelength such as stray light inside the apparatus.

The multilayer filter 62 selectively removes light having a predetermined wavelength according to the angle of incident light. In the present embodiment, a diffraction grating, an absorption filter, or the like can be used instead of the multilayer filter 62.
The filter driving unit 64 changes and adjusts the angle of the multilayer filter 62 in accordance with the cut wavelength. In the present embodiment, the filter driving unit 64 adjusts the angle of the multilayer filter 62 so as to cut the light of the wavelength component of the measurement light L1 emitted from the wavelength tunable laser 50, that is, the measurement light L1.

The wavelength cut detection unit 70 is for detecting that the multilayer filter 62 of the variable filter 60 has cut light having a predetermined wavelength, for example, the wavelength of the measurement light L1, and the multilayer filter of the variable filter 60 When the angle of 62 is adjusted, it is arranged at a detection position on the optical path of the transmitted light of the multilayer filter 62 and detects the amount of the transmitted light. In the present embodiment, scattered light or the like from the Raman spectroscopic device 1 is incident on the variable filter 60, but a large amount of the measurement light L1 is also incident. Therefore, when the variable filter 60 cuts light having the wavelength of the measurement light L1. The amount of transmitted light is significantly reduced.
The control unit 90 described later receives the measurement signal from the wavelength cut detection unit 70, determines that the light of the wavelength of the measurement light L1 has been cut by the variable filter 60 at the timing when the amount of transmitted light is minimized. Then, the drive of the filter driving unit 64 is stopped, and the adjustment of the cut wavelength is finished.

The mirror 72 is arranged downstream of the wavelength cut detection unit 70, reflects the scattered light generated on the surface 1s of the Raman spectroscopic device 1 and transmitted through the multilayer filter 62 of the variable filter 60, and will be described later. It is the light guide member made to enter.
The spectroscopic means 80 is composed of a spectroscopic detector or the like, and spectrally scatters the scattered light generated on the surface 1s of the Raman spectroscopic device 1, obtains the spectrum of the Raman scattered light (Raman spectrum), and analyzes the characteristics of the analyte. Is.

As shown in FIG. 2, the control unit 90 is connected to the wavelength tunable laser 50, the tunable filter 60, the wavelength cut detection unit 70, and the spectroscopic unit 80, and controls the operation of the Raman spectroscopic device 100. .
The controller 90 is a wavelength setting unit that sets the excitation wavelength of the wavelength tunable laser 50 in accordance with the Raman signal obtained by the spectroscopic unit 80.
In addition, the control unit 90 controls the operation of the variable filter 60 so as to cut the light of the excitation wavelength of the set wavelength variable laser 50, that is, the measurement light L1. At that time, the operation of the wavelength cut detection unit 70 is controlled, and the cut wavelength is adjusted by the variable filter 60 according to the signal transmitted from the wavelength cut detection unit 70, and the wavelength of the measurement light L1 becomes the cut wavelength. Do as follows.

  Hereinafter, the operation of the Raman spectroscopic device 100 configured as described above will be described, and the measurement of the Raman spectroscopic spectrum using the Raman spectroscopic device 100 will be described.

  An analyte is placed on the surface 1 s of the Raman spectroscopic device 1. The measurement light L1 is made incident from the wavelength tunable laser 50 on the surface 1s of the Raman spectroscopic device 1 on which the analyte is arranged, and the generated scattered light is dispersed by the spectroscopic means 80 to obtain a Raman spectrum.

Here, the wavelength tunable laser 50 measures the spectrum of the scattered light while continuously changing the wavelength of the measurement light L 1, and transmits a measurement signal to the control unit 90.
The controller 90 detects the wavelength of the light beam from which a strong signal is obtained from the measured Raman spectrum. This wavelength is a resonance wavelength that satisfies the multiple interference condition of the Raman spectroscopic device 1, and is a wavelength at which the intensity of the enhanced electric field generated on the surface 1s of the Raman spectroscopic device 1 is maximized. The controller 90 sets this resonance wavelength to the excitation wavelength of the wavelength tunable laser light source 50 (the wavelength of the measurement light L1), and transmits a setting signal to the wavelength tunable laser light source 50.
The wavelength tunable laser light source 50 that has received the setting signal from the control unit 90 changes the wavelength of the measurement light L1 to the set resonance wavelength.

The control unit 90 also adjusts the angle of the multilayer filter 62 by controlling the filter driving unit 64 so that the variable filter 60 removes the wavelength component of the measurement light L1 set to the resonance wavelength.
In adjusting the cut wavelength of the variable filter 60, the control unit 90 moves the wavelength cut detection unit 70 to the detection position. The wavelength cut detector 70 detects the amount of light transmitted through the multilayer filter 62 and transmits a detection signal to the controller 90.

The control unit 90 measures the amount of light transmitted through the multilayer filter 62 by the wavelength cut detection unit 70 while adjusting the angle of the multilayer filter 62, and measures light with the variable filter 60 at the timing when the light amount becomes minimum. It is determined that the light having the wavelength of L1 has been cut, and the driving of the filter driving unit 64 is stopped.
The control unit 90 drives a moving unit (not shown) to move the wavelength cut detection unit 70 from the detection position to a retracted position (indicated by a broken line in FIG. 1) that is out of the optical path of the transmitted light of the multilayer filter 62.

In this manner, in the Raman spectroscopic device of the present embodiment, the wavelength of the measurement light L1 emitted from the wavelength tunable laser light source 50 can be matched with the resonance wavelength of the Raman spectroscopic device. An effect can be acquired more suitably and highly accurate Raman spectroscopy measurement is attained.
Here, since the wavelength component of the measurement light L1 is cut, scattered light from the device can be detected with high accuracy, and highly accurate Raman spectroscopic measurement can be performed.

  As described above, in the Raman spectroscopic device 1, the resonance wavelength is usually determined according to the characteristics of the substance to be measured, and the thickness d and the average refractive index are designed so as to be the determined resonance wavelength. Although it is fabricated, it is difficult to make the actual resonance wavelength completely match the design value. Even for such a problem, the resonance wavelength of the Raman spectroscopic device can be detected and the wavelength of the measurement light L1 can be matched with the detected resonance wavelength, so that the Raman spectroscopic device need not be manufactured with high accuracy. Highly accurate Raman spectroscopic measurement becomes possible.

  Moreover, since the cut wavelength can be changed by the variable filter according to the change of the wavelength of the measurement light L1 from the wavelength tunable laser light source, the light of the wavelength of the measurement light L1 can be suitably cut. Accurate Raman spectroscopic measurement is possible.

Here, in the above embodiment, the wavelength of the measurement light L1 from which a strong Raman scattered light signal is obtained is set to the resonance wavelength, but the present invention is not limited to this.
For example, the measurement light L1 is incident on the surface of the Raman spectroscopic device without placing the analyte, and the generated scattered light is dispersed to obtain the scattered light spectrum. From the peak wavelength of the absorption spectrum of the scattered light, Alternatively, the resonance wavelength that maximizes the intensity of the enhanced electric field may be determined, and the wavelength of the measurement light L1 may be set to the determined resonance wavelength.
Alternatively, the reflection intensity of the reflected light of the Raman spectroscopic device may be measured in advance for a plurality of wavelengths, and the wavelength at which the reflection intensity is maximized may be set to the resonance wavelength at which the intensity of the enhanced electric field is maximized. . Further, when the second reflector of the Raman spectroscopic device has transflective properties, the transmitted intensity of the transmitted light of the Raman spectroscopic device is measured, and the wavelength at which the transmitted intensity is maximized is determined as an enhanced electric field. You may set to the resonant wavelength from which intensity | strength of this becomes the maximum.

In the Raman spectroscopic device of this embodiment, since the first reflector has a metal fine structure capable of generating localized plasmons, an enhanced electric field is generated on the surface of the device due to localized plasmon resonance in the first reflector. The surface enhanced Raman effect can be obtained.
By the way, “T. Itoh et.al, Applied Physics Letters, 83, 2274-2276 (2003)” describes that a correlation exists between the surface enhanced Raman intensity and the localized plasmon resonance. As described in the above document, there is a correlation between the surface-enhanced Raman intensity and the localized plasmon resonance. Therefore, the first reflected light is measured by measuring the absorption spectrum, reflected light, or transmitted light of the scattered light of the Raman spectroscopic device. By determining the wavelength at which localized plasmon resonance is generated in the body, the optimum wavelength (excitation wavelength) of the measurement light L1 for effectively obtaining the surface-enhanced Raman effect due to this localized plasmon resonance is determined. Can do.

  Here, in the above-described embodiment, as the analyzing means for analyzing the characteristics of the analyte, the spectroscopic means 80 that obtains a Raman spectrum by dispersing the scattered light from the surface of the Raman spectroscopy device in which the analyte is arranged on the surface. Although the Raman spectroscopic device 100 having the above has been described, the analysis device of the present invention is not limited to this.

  In the Raman spectroscopic device 1, when an analyte or a sample containing an analyte is disposed on the first reflector 10 and / or the second reflector 30 (preferably the first reflector 10), reflection occurs. It has been found that the average complex refractive index (effective complex refractive index) of the reflector on which the sample is arranged changes due to the interaction between the body and the sample, and the multiple interference conditions change. That is, the absorption characteristics due to multiple interference vary depending on the sample. The sample can be analyzed by using the Raman spectroscopic device 1 as the sensor device 1 utilizing the above characteristics and detecting the physical characteristics of the emitted light L2 that varies depending on the absorption characteristics. Examples of the physical characteristics of the emitted light L2 that change depending on the absorption characteristics include the light intensity of the emitted light L2 or the amount of change in the light intensity, the absorption wavelength of light absorbed by the sensor device 1, or the shift of the absorption wavelength. In this case, as the analysis apparatus, an analysis unit that analyzes the characteristics of the sample includes a light amount detection unit that detects the amount of reflected light and / or transmitted light of the sensor device 1, and a spectrum of reflected light or transmitted light. One having a spectroscopic means for measuring is mentioned.

In this manner, the sensor device 1 can analyze the refractive index and / or concentration of the sample, and can also identify the sample by analyzing the refractive index of the sample. Further, after fixing a binding substance (surface modification) that specifically binds to the analyte (specific substance) to the reflector (first reflector 10 and / or second reflector 30) on which the sample is placed. The sample containing the analyte is brought into contact, the measurement light L1 is irradiated to the Raman spectroscopic device 1, and the emission light L2 is detected, whereby the presence of the analyte and / or the amount of the analyte contained in the sample is detected. Can also be analyzed. Examples of the specific substance / binding substance combination include antigen / antibody (which may be any binding substance) and the like, and in the present embodiment, analysis over time such as antigen-antibody reaction is also possible.
Even in this case, even if the wavelength of the measurement light L1 is changed, the changed measurement light L1 component can be efficiently cut and the emitted light L2 can be detected with high accuracy. Analysis is possible, and the amount of antigen / antibody can be analyzed with high accuracy.

Hereinafter, a second embodiment of a Raman spectroscopic device will be described with reference to FIG. 4A is a perspective view corresponding to FIG. 1A of the first embodiment, and FIG. 4B is a top view of the Raman spectroscopic device. In the present embodiment, the same components as those in the first embodiment are denoted by the same reference numerals, and description thereof is omitted. The Raman spectroscopic device 2 of this embodiment has the same basic configuration as that of the first embodiment except that the first reflector 10 is made of a metal particle layer. The same effect is produced.
Also in the present embodiment, as in the first embodiment, multiple reflection (resonance) occurs effectively by repeating reflection between the first reflector 10 and the second reflector 30, and multiple reflected light The multiple interference due to is effectively generated, and an enhanced electric field is generated on the surface.

  As shown in FIG. 4, the Raman spectroscopic device 2 of the present embodiment is similar to the first embodiment in that the first reflector 10 having transflective properties and the translucent property are transmitted from the incident side of the measurement light L1. The device structure includes a body 20 and a second reflector 30 having complete reflectivity.

  The difference between the present embodiment and the first embodiment is that the first reflector 10 is a patterned metal layer in the first embodiment, whereas the first reflector 10 is translucent. This is a point composed of a metal particle layer in which a plurality of metal particles 13 having substantially the same diameter are regularly arranged and fixed in a matrix on the surface of the body 20. The material of the metal particles 13 is not limited, and the same metal as that of the first reflector 10 of the first embodiment can be exemplified.

  The first reflector 10 can be formed, for example, by applying a dispersion solution of the metal particles 13 to the surface of the translucent body 20 by a spin coat method or the like and drying. It is preferable that the dispersion solution contains a binder such as resin or protein, and the metal particles 13 are fixed to the surface of the light transmitting body 20 through the binder. When a protein is used as the binder, the metal particles 13 can be fixed to the surface of the light-transmitting body 20 by utilizing a binding reaction between the proteins.

  Although the first reflector 10 is made of a reflective metal, it has a plurality of particle gaps 14 that are voids, so that it has light transmissivity and transflective properties. The diameter and pitch of the metal particles 13 are designed to be smaller than the wavelength of the measurement light L1, and the first reflector 10 has an uneven structure smaller than the wavelength of the measurement light L1. Accordingly, the first reflector 10 (metal fine particle layer) has a metal microstructure that can generate localized plasmons. Also in this embodiment, the 1st reflector 10 acts as a semi-transmissive semi-reflective thin film with respect to light by what is called an electromagnetic mesh shielding effect.

  Also in the Raman spectroscopic device 2 of the present embodiment, the electric field is enhanced on the surface 2s of the first reflector 10 by irradiation with the measurement light L1 having the resonance wavelength, and the surface enhanced Raman effect can be suitably obtained. Yes, the analyte can be analyzed by disposing the analyte on the surface 2s.

  The pitch of the metal particles 13 is not particularly limited as long as the condition smaller than the wavelength of the measurement light L1 is satisfied. For example, when visible light is used as the measurement light L1, it is preferably 200 nm or less. The diameter of the metal particles 13 is preferably equal to or less than the mean free path of electrons that vibrate in the metal by light, specifically 50 nm or less, and particularly preferably 30 nm or less.

  In the present embodiment, the case where the first reflector 10 is composed of a metal layer in which a plurality of metal particles 13 having substantially the same diameter are arranged and fixed in a matrix is described. However, the metal particles 13 are distributed in diameter. The arrangement pattern may be arbitrary and may be a random arrangement. Moreover, although the case where the 2nd reflector 30 consists of a solid metal layer was demonstrated, the 2nd reflector 30 can also be comprised with a metal particle layer similarly to the 1st reflector 10. FIG. In this case, the second reflector 30 has transflective properties.

  Hereinafter, a third embodiment of the Raman spectroscopic device will be described with reference to FIGS. 5 and 6. FIG. 5 is a perspective view of a Raman spectroscopic device, and FIG. 6 is a manufacturing process diagram thereof. In the present embodiment, the same components as those in the first embodiment are denoted by the same reference numerals, and description thereof is omitted.

  As shown in FIG. 5, the Raman spectroscopic device 3 of the present embodiment is similar to the first embodiment in that the first reflector 10 and the translucent body having transflective properties from the incident side of the measurement light L <b> 1. 20 and a second reflector 30 having complete reflectivity are sequentially provided.

In the present embodiment, unlike the first embodiment, the light transmitting body 20 is a metal oxide body (Al ₂ O ₃ ) obtained by anodizing a part of the anodized metal body (Al) 40 shown in FIG. 41, and the second reflector 30 is made of a non-anodized portion (Al) 42 of the anodized metal body 40 shown in FIG. The second reflector 30 has complete reflectivity.

  The translucent body 20 is a translucent microporous body in which a plurality of substantially straight micropores 21 extending from the first reflector 10 side to the second reflector 30 side are opened. The plurality of micro holes 21 are opened on the surface on the first reflector 10 side, and the second reflector 30 side is closed. In the light transmitting body 20, the plurality of micro holes 21 are substantially regularly arranged with a diameter and a pitch smaller than the wavelength of the measuring light L <b> 1.

  Anodization can be carried out by using the metal body to be anodized 40 as an anode, immersing it in an electrolyte together with a cathode, and applying a voltage between the anode and the cathode. The shape of the anodized metal body 40 is not limited, and a plate shape or the like is preferable. Further, it may be used in a form with a support such as a layer in which the anodized metal body 40 is formed on a support. Carbon, aluminum, or the like is used as the cathode. The electrolytic solution is not limited, and an acidic electrolytic solution containing one or more acids such as sulfuric acid, phosphoric acid, chromic acid, oxalic acid, sulfamic acid, benzenesulfonic acid, and amidosulfonic acid is preferably used.

As shown in FIG. 6, when the anodized metal body 40 is anodized, an oxidation reaction proceeds from the surface 40s of the anodized metal body in a direction substantially perpendicular to the surface, and the metal oxide body (Al ₂ O _3). ) 41 is generated. The metal oxide body 41 generated by anodization has a structure in which a large number of fine columnar bodies 41a having a substantially regular hexagonal shape in plan view are arranged without gaps. A minute hole 21 extending substantially straight from the surface 40s in the depth direction is opened at a substantially central portion of each minute columnar body 41a, and the bottom surface of each minute columnar body 41a has a rounded shape. The structure of the metal oxide body produced by anodization is Hideki Masuda, “Preparation of mesoporous alumina by anodization and application as a functional material”, Material Technology Vol.15, No.10, 1997, p.34, etc. It is described in.

  As an example of suitable anodizing conditions for producing the metal oxide body 41 having an ordered arrangement structure, when oxalic acid is used as the electrolytic solution, the electrolytic solution concentration is 0.5 M, the liquid temperature is 14 to 16 ° C., and the applied voltage is 40 to 40. ± 0.5V or the like can be mentioned. The fine holes 21 generated under these conditions have, for example, a diameter of about 30 nm and a pitch of about 100 nm.

  In the present embodiment, the first reflector 10 is formed of a metal layer formed along the surface shape of the light transmitting body 20 by being deposited on the light transmitting body 20 by metal vapor deposition or the like. Since no metal film is formed at the opening portions of the micro holes 21 of the light transmitting body 20, the first reflector 10 has a substantially regular hexagonal metal body 15 in plan view having the micro holes 16 in the substantially central portion without any gaps. It exhibits the shape. Since the micro holes 16 of the first reflector 10 are opened in the same pattern as the micro holes 21 of the translucent body 20, the micro holes 16 are substantially regularly arranged with a diameter and pitch smaller than the wavelength of the measurement light L1. It will be.

  The first reflector 10 is made of a reflective metal, but has a plurality of fine holes 16 that are voids, so that it has optical transparency and transflective properties. Since the first reflector 10 is a substantially regular hexagonal metal body 15 in a plan view having a size smaller than the wavelength of the measurement light L1 having the fine hole 16 in the substantially central portion, the first reflector 10 is substantially regularly arranged. It has an uneven structure smaller than the wavelength of the measuring light L1. Also in this embodiment, the 1st reflector 10 acts as a semi-transmissive semi-reflective thin film with respect to light by what is called an electromagnetic mesh shielding effect.

  The pitch of the metal bodies 15 (the pitch of the fine holes 16) is not particularly limited as long as the condition smaller than the wavelength of the measurement light L1 is satisfied. For example, when visible light is used as the measurement light L1, it is preferably 200 nm or less.

  The separation distance between the adjacent fine holes 16 (the width W of the metal body 15 between the adjacent fine holes 16) is not particularly limited and may be set as appropriate. The width W corresponds to the width of the fine metal wires 11 and the diameter of the metal particles 13 in the first and third embodiments. The width W is preferably equal to or less than the mean free path of electrons that vibrate in the metal by light.

  Also in the present embodiment, similarly to the first embodiment, the light transmitted through the first reflector 10 and incident on the light transmitting body 20 is between the first reflector 10 and the second reflector 30. In this case, reflection is repeated and multiple reflection occurs, and multiple interference due to multiple reflected light occurs effectively, and resonance occurs at a specific wavelength that satisfies the resonance condition. Resonance absorbs light at the resonance wavelength, enhances the electric field in the device, and generates an enhanced electric field on its surface 3s.

  The Raman spectroscopic device 3 according to the present embodiment includes a translucent microporous body having a plurality of microscopic holes 21 in which the translucent body 20 is opened on the surface on the first reflecting body 10 side. The basic configuration is the same as that of the first embodiment except that the first layer is composed of a metal layer formed with a plurality of fine holes 16 along the surface shape of the translucent body 20. The same effects as those of the embodiment are obtained.

  Since the Raman spectroscopic device 3 of the present embodiment is manufactured using anodization, the fine holes 21 of the light transmitting body 20 and the fine holes 16 of the first reflector 10 are substantially regularly arranged. The Raman spectroscopic device 4 can be easily produced, which is preferable. However, the arrangement of these fine holes may be a random arrangement.

  In the present embodiment, only Al is cited as the main component of the anodized metal body 40 used in the manufacture of the translucent body 20, but any metal oxide that can be anodized and has translucency can be used. Any metal can be used. Other than Al, Ti, Ta, Hf, Zr, Si, In, Zn, etc. can be used. The anodized metal body 40 may include two or more types of metals that can be anodized.

  In the present embodiment, the case where the second reflector 30 has complete reflectivity has been described. However, the entire anodized metal body 40 is anodized or a part of the anodized metal body 40 is anodized. Further, the non-anodized portion 42 of the anodized metal body 40 and the vicinity thereof are removed to obtain the light transmitting body 20 through which the fine hole 21 penetrates the light transmitting body 20, and the fine hole 21 is further transmitted. A second reflector 30 is formed along the surface shape of the translucent body 20 in the translucent body 20 penetrating the optical body 20, and has a fine hole as in the first reflector 10 and is semitransparent reflective. You may form the 2nd reflector 30 which has these.

  Hereinafter, a fourth embodiment of the Raman spectroscopic device will be described with reference to FIGS. 7 and 8. FIG. 7 is a cross-sectional view of a Raman spectroscopic device, and FIG. 8 is a manufacturing process diagram. In the present embodiment, the same components as those in the first embodiment and the third embodiment are denoted by the same reference numerals, and description thereof is omitted.

As shown in FIG. 7, the Raman spectroscopic device 4 of the present embodiment is similar to the third embodiment in that the first reflector 10 having transflective properties and the translucent property are transmitted from the incident side of the measurement light L1. The light transmitting body 20 has a device structure including a body 20 and a second reflecting body 30 having complete reflectivity, and the light transmitting body 20 anodizes a part of the anodized metal body (Al) 40 shown in FIG. a metal oxide body _{(Al 2} O 3) 41 obtained Te, the second reflector 30 is formed of a non anodized portion (Al) 42 of the anodized metal body 40 shown in FIG. The second reflector 30 has complete reflectivity. The Raman spectroscopic device 4 has the same configuration except that the configurations of the Raman spectroscopic device 3 of the third embodiment and the first reflector 10 are different, and obtains the same effect.

  The Raman spectroscopic device 4 includes a filling portion 45 filled in the micropores 21 and an outer diameter larger than the outer diameter of the filling portion 45 formed on the micropores 21 so as to protrude from the surface 20 s of the light transmitting body 20. The surface of the metal portion 44 on the side of the protrusion 46 is a surface on which the analyte is disposed, and the surface 4s of the first reflector 10 is provided on the surface 4s of the first reflector 10. It is. That is, in the present embodiment, the first reflector 10 is configured by the protruding portions 46 of the plurality of metal portions 44.

The metal part 44 composed of the filling part 45 and the protruding part 46 is formed by subjecting the fine hole 21 of the translucent body 20 to electroplating.
When electroplating is performed, the second reflector 30 functions as an electrode, and the metal is preferentially deposited from the bottom of the fine hole 21 where the electric field is strong. By continuously performing this electroplating process, the fine holes 12 are filled with metal, and the filling portion 45 of the metal portion 44 is formed. If the electroplating process is further continued after the filling portion 45 is formed, the filling metal overflows from the fine holes 21, but the metal is continuously deposited around the fine holes 21 due to the strong electric field near the fine holes 21. Then, a protruding portion 46 that protrudes from the translucent surface 20s and has a diameter larger than the diameter of the filling portion 45 is formed on the filling portion 45 (see FIG. 8C).

  When the metal part 44 is grown by electroplating, a thin layer between the bottom surface of the fine hole 21 and the conductor 13 composed of the non-anodized part of the metal body 10 to be anodized is broken depending on conditions, 44 filling portions 45 may reach the rear surface 20r of the transparent body 20.

  In the present embodiment, the plurality of metal portions 44 are close to each other, and the first reflector 10 has an air gap, so that it has light transmissivity and transflective properties. The pitch between adjacent micropores 21 is, for example, 10 to 400 nm, and the pore diameter of the micropores 21 is 5 to 200 nm. Since the first reflector 10 is composed of a plurality of metal portions 44 each having a filling portion 45 filled in the fine holes 21 and a protruding portion 46 having an outer diameter larger than the outer diameter of the filling portion 45, measurement is performed. It becomes a transflective thin film having an uneven structure smaller than the wavelength of the light L1 and having an electromagnetic mesh shielding function.

  Also in the present embodiment, similarly to the first embodiment, the light transmitted through the first reflector 10 and incident on the light transmitting body 20 is between the first reflector 10 and the second reflector 30. And multiple interference due to multiple reflected light occurs effectively, and resonates at a specific wavelength that satisfies the resonance condition. By resonance, an electric field enhancing effect can be obtained at the surface 4s. Similar to the first embodiment, the resonance wavelength changes according to the average refractive index and thickness of the transparent body 20, and therefore, a high electric field enhancement effect (for example, an enhancement of 100 times or more) at a wavelength according to these factors. Effect).

  In the present embodiment, the protruding portion 46 of the metal portion 44 is in the form of particles, and when viewed from the surface 20 s side, a metal fine particle layer is formed on the surface 20 s of the translucent body 20. In such a configuration, since the protruding portion 46 is a convex portion of the metal portion 44, it is preferable that the average outer diameter and pitch are designed to be smaller than the wavelength of the measuring light L1. The metal portion 44 is preferable if the size of the protruding portion 46 is such that the localized plasmon can be excited because an electric field enhancing effect by localized plasmon resonance can be obtained. In this case, the metal fine particle layer composed of the protrusions 46 has a metal fine structure capable of generating localized plasmons.

  Hereinafter, a fifth embodiment of the Raman spectroscopic device will be described with reference to FIG. FIG. 9 is a top view schematically showing the Raman spectroscopic device of the present embodiment. The Raman spectroscopic device 5 of this embodiment is a metal formed by arranging a plurality of metal nanorods in place of the first reflector 10 made of the metal particle layer in the Raman spectroscopic device 2 of the second embodiment. It has the 1st reflector 10 which consists of a layer of a nanorod, and since it has the same composition as device 2 for Raman spectroscopy of a 2nd embodiment other than that, it is the same component. Are denoted by the same reference numerals, and description thereof is omitted.

  As shown in FIG. 9, the Raman spectroscopic device 5 of the present embodiment is similar to the second embodiment in that the first reflector 10 having a transflective property, a translucent material 20, and a completely reflective property are used. The second reflector 30 having the above structure is sequentially provided. In the present embodiment, the first reflector 10 is composed of a plurality of metal nanorods 48 disposed on the translucent body 20.

  The metal nanorod 48 is a rod-shaped metal nanoparticle having a short axis length and a long axis length different from each other. The metal nanorods 48 have a minor axis length of about 3 nm to 50 nm and a major axis length of about 25 nm to 1000 nm, and the major axis length is smaller than the wavelength of the measurement light L1. It is preferable that the metal nanorod 48 is mainly composed of at least one metal selected from the group consisting of Au, Ag, Cu, Al, Pt, Ni, Ti, and alloys thereof. The metal nanorod is described in, for example, Japanese Patent Application Laid-Open No. 2007-139612.

  Although the 1st reflector 10 consists of a reflective metal, since it has the gap | interval 49 formed between the metal nanorods 48, it has a light transmittance, and has a transflective property. As described above, the diameter and pitch of the metal nanorods 48 are designed to be smaller than the wavelength of the measurement light L1, and the first reflector 10 has an uneven structure that is smaller than the wavelength of the measurement light L1. Accordingly, the first reflector 10 has a metal microstructure composed of a plurality of metal nanorods that can generate localized plasmons. Also in this embodiment, the 1st reflector 10 acts as a semi-transmissive semi-reflective thin film with respect to light by what is called an electromagnetic mesh shielding effect.

  Further, the first reflector 10 is composed of a plurality of metal nanorods 48 having a size smaller than the wavelength of the measurement light L1, and has a concavo-convex structure smaller than the wavelength of the measurement light L1, so that the first reflector 10 is irradiated with the measurement light L1. Local plasmon resonance can be effectively generated, and an electric field enhancement effect by local plasmon resonance can be suitably obtained on the surface.

Also in the Raman spectroscopic device 2 of the present embodiment, multiple reflection (resonance) is effective by repeating reflection between the first reflector 10 and the second reflector 30 by irradiation of the measurement light L1 having the resonance wavelength. Multiple interference due to multiple reflected light occurs effectively, and an enhanced electric field is generated on the surface. Moreover, the surface-enhanced Raman effect can be suitably obtained by enhancing the electric field on the surface of the first reflector 10.
Further, an enhanced electric field due to localized plasmon resonance can be generated on the surface of the first reflector 10, and a surface enhanced Raman effect can be suitably obtained.

  Hereinafter, an optical modulation device that can be used as a variable filter of the Raman spectroscopic apparatus 100 will be described. The light modulation device of this embodiment is described in detail in Japanese Patent Application Laid-Open No. 2007-17953.

  The light modulation device 5 shown in FIG. 10 has a diameter sufficiently smaller than the wavelength of the incident light L3 filled with the first reflector 110 having transflective properties and the translucent material 122 from the light incident side. A translucent microporous body 120 having a plurality of micropores 121 and a second reflector 130 having semi-transmissive and semi-reflective properties, and an average complex refractive index of the first reflector 110, Depending on the average complex refractive index of the second reflector 130 and the average complex refractive index and thickness of the translucent microporous body 120, the absorption characteristic of absorbing light of a specific wavelength is shown. L3 is modulated, and modulated light L4 is emitted from the first reflector 10 and / or the second reflector 30.

  In addition, the light transmitting material 122 is filled in the plurality of fine holes 121. The translucent substance 122 is not particularly limited. However, since the light-transmitting substance 122 can enter and exit, a fluid substance, that is, a liquid, a liquid crystal, or the like is preferable. Examples of the liquid include inorganic solvents such as water, organic solvents such as alcohol (methanol, ethanol, etc.), mixed solutions thereof, various solutions in which solutes such as glycerol and sucrose are dissolved in inorganic solvents and / or organic solvents, and the like. It is done. Although it is difficult to enter and exit the translucent substance 122, a solid such as powder may be used as the translucent substance 122. A gas may be used as the translucent substance 122.

  As shown in FIG. 10A, when the incident light L3 is incident on the light modulation device 1, a part of the light is reflected on the surface of the first reflector 110 according to the transmittance and the reflectance of the first reflector 110. A part of the light is reflected (not shown), and part of the light passes through the first reflector 110 and enters the light-transmitting microporous body 120. The light incident on the translucent fine hole body 120 is repeatedly reflected between the first reflector 110 and the second reflector 130. That is, the light modulation device 5 has a resonance structure in which multiple reflection occurs between the first reflector 110 and the second reflector 130.

  In such a device, multiple interference due to multiple reflected light occurs, and an absorption characteristic in which light of a specific wavelength is selectively absorbed is exhibited. The multiple interference conditions vary depending on the average complex refractive index of the first reflector 110, the average complex refractive index of the second reflector 130, and the average complex refractive index and thickness of the translucent microporous body 120. Absorption characteristics that absorb light of a specific wavelength according to a factor are shown.

  In the light modulation device 5, an example of a change in the reflected light spectrum (the spectrum of light emitted from the first reflector 10) when the average complex refractive index of the translucent microporous body 120 is changed is shown in FIG. Shown in FIG. 10B shows how the absorption peak wavelength changes from λ1 to λ2. The light modulation device 5 is capable of adjusting the absorption peak wavelength of the light modulation device 5 by adjusting the average complex refractive index of the light-transmitting fine pores 120, and used as a filter that absorbs a desired wavelength. Can do.

  In the present embodiment, (1) switching between an empty state in which the micropores 121 of the translucent microporous body 120 are not filled with the translucent substance 122 and a filled state in which the translucent substance 122 is filled, or (2 ) The average complex refractive index of the translucent microporous body 120 can be changed by changing the type and / or amount of the translucent substance 122 filled in the micropores 121 of the translucent microporous body 120. . “Changing the type of translucent substance 122” includes changing the concentration of the translucent substance 122 and changing the concentration of the same component. Further, when the translucent material 122 is a liquid crystal or the like, (3) the complex refractive index of the translucent material 122 filled in the translucent microporous body 120 is electrically changed, so that the translucent micro The average complex refractive index of the hole 120 can also be changed. The average complex refractive index can be changed by combining the above (1) to (3).

  In the Raman spectroscopic device 100 shown in FIG. 1, the light modulation device 5 is disposed in place of the variable filter, and the translucent fine pore body is changed according to the change or adjustment of the wavelength of the measurement light L1 from the variable wavelength laser 50. The average complex refractive index of 120 may be changed and adjusted to selectively remove the wavelength component of the measurement light L1.

Hereinafter, a mass spectrometer will be described as another embodiment of the analyzer of the present invention.
The mass spectrometer uses the Raman spectroscopic device as a mass spectrometric device, and the resonance of the device from the wavelength tunable laser light source to the analyte (sample containing the analyte) placed on the surface of the device. Mass spectrometry means for irradiating a light beam having a wavelength and desorbing an analyte from the device surface using an enhanced electric field generated on the surface of the device and analyzing the mass of the desorbed analyte Is.
As the device for mass spectrometry used in the mass spectrometer, the same devices as those described in the first to fifth embodiments of the Raman spectroscopic device can be used. Hereinafter, in the mass spectrometer of the present embodiment, the Raman spectroscopic device 1 is used as the mass spectrometric device 1.

  In the device 1 for mass spectrometry, the sample containing the analyte to be disposed on the surface 1s is irradiated with the measurement light, and the surface of the first reflector 10 (sample placement surface) 1s is irradiated with the measurement light L1. Since the electric field is enhanced, the electric field is enhanced on the sample arrangement surface and the energy of the measurement light is increased on the sample arrangement surface, and the analyte contained in the arranged sample is increased by the increased energy. It can be detached from the sample placement surface 1s. Also in this embodiment, by adjusting the wavelength of the measurement light to the resonance wavelength of the mass spectrometric device 1, the electric field enhancement effect on the sample arrangement surface can be more suitably obtained, and the desorption of the analyte is ensured. In addition, it can be performed efficiently.

Here, the mass spectrometric device 1 has a surface modification (capturing member) on its surface 1s capable of capturing the analyte and capable of desorbing the analyte by irradiation with the measuring light L1. It is. For example, when the analyte is an antigen, the amount of the analyte disposed on the surface 1s is modified by modifying the surface 1s of the first reflector 10 with an antibody that can specifically bind to the antigen. Can be increased, and the sensitivity of mass spectrometry can be improved.
In the present embodiment, the sample refers to a combination of the surface modification and the analyte captured (bound) by the surface modification.

  Fig.11 (a) is a figure which shows the preferable 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. The surface modification R includes, on the surface 1s of the first reflector 10, a first linker function unit A that binds to the analyte S, a second linker function unit C that binds to the analyte S, and a first And a decomposition function part B that is decomposed by an electric field generated by irradiation of the measurement light L1. The decomposition function part B is interposed between the linker function part A and the second linker function part C. In the illustrated example, the analyte S is disposed in the vicinity of the surface 1 s of the mass spectrometry device 1 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. 11B shows a state in which the analyte S is desorbed by irradiation with the measurement light L1 when the device 1 for mass spectrometry has the surface modification R as shown in FIG. It is. When the measurement light L <b> 1 is irradiated onto the mass spectrometry device 1, resonance inside the device and localized plasmon resonance in the first reflector 10 occur, and the electric field is enhanced on the surface 1 s of the mass spectrometry device 1. The optical energy of the measurement light L1 is increased in the vicinity of the surface 1s by the electric field enhanced on the surface 1s, and the decomposition function part B of the surface modification R is decomposed by the increased energy. The one to which the linker function part C is bonded is detached from the surface 1s.

  As shown in FIG. 11A, when the surface modification R is provided, the analyte S is present away from the surface 1 s of the mass spectrometry device 1. In the device 1 for mass spectrometry, the optical energy of the measurement light L1 is increased on the surface 1s by using the electric field enhancement effect generated on the surface 1s, and is used for desorption of the analyte S. Here, the electric field enhancement effect obtained on the surface 1 s of the device 1 for mass spectrometry is an electric field enhancement effect due to light absorption caused by resonance inside the device and / or an electric field enhancement effect due to near-field light generated by localized plasmon resonance. Therefore, it decreases exponentially with respect to the distance from the surface 1s. Therefore, as shown in FIG. 11 (a), the analyte S is present relatively far from the surface 1s, so that the optical energy of the measurement light L1 irradiated to the analyte S is affected by the electric field enhancement. It can be less. That is, the analyte S can be prevented from being damaged by the increased light energy, and high-accuracy mass analysis can be performed.

  An embodiment of a mass spectrometer using the mass spectrometry device 1 will be described. The mass spectrometer of this embodiment is a time-of-flight mass spectrometer (TOF-MS). FIG. 12 is a configuration diagram showing the configuration of the mass spectrometer.

  The mass spectrometer 150 includes a mass analysis device 1 according to the above-described embodiment, a device holding unit 160 that holds the mass analysis device 1, and a first reflection of the mass spectrometry device in a box 168 that is kept in a vacuum. The sample placed on the surface 1s of the body 10 is irradiated with the measuring light L1, and the light irradiation means 161 for detaching the analyte S in the sample from the surface 1s of the first reflector 10; A mass analyzing means 164 for detecting the analyte S and analyzing the mass of the analyte S, and facing the surface 1s of the first reflector 10 between the mass analyzing device 1 and the mass analyzing means 164; A lead grid 162 arranged at a position where the lead grid 162 is located, an end plate 163 arranged opposite to the surface of the lead grid 162 opposite to the surface on the mass spectrometry device 1 side, and the spectroscopic means 80 shown in FIG. Is the example was constructed.

The light irradiation means 161 is a laser light source configured to be variable in wavelength, and is configured to be able to adjust the wavelength of the light beam to be irradiated to the resonance wavelength of the mass spectrometry device 1. Further, the spectroscopic means 80 obtains a Raman spectrum by spectroscopically dispersing the scattered light from the light irradiation means 161.
Also in the mass spectrometer 150 of the present embodiment, the Raman spectrum is obtained by the spectroscopic means 80 while the light irradiating means 161 changes the wavelength of the measurement light L1 (light beam), and the Raman signal is obtained. The wavelength of the measurement light L1 is adjusted and changed with the wavelength of the measurement light L1 that can be strongly obtained as the resonance wavelength of the mass spectrometry device 1. Thereby, the measurement light L1 can be incident on the surface 1s of the device 1 for mass spectrometry to cause resonance due to multiple reflection of the measurement light L1, and an enhanced electric field can be suitably generated on the surface 1s. Further, since the optical energy of the measurement light L1 can be suitably increased in the vicinity of the surface 1s by the enhanced electric field, the light energy of the measurement light L1 necessary for desorption of the analyte can be reduced.

  Here, also in this embodiment, it is not limited to setting the wavelength of the measurement light L1 from which the signal of Raman scattered light is strongly obtained to the resonance wavelength, and the analyte is not disposed on the surface of the device for mass spectrometry. The measurement light L1 is incident, the generated scattered light is dispersed by a spectroscopic means, and the spectrum of the scattered light is obtained. From the peak wavelength of the absorption spectrum of the scattered light, the resonance wavelength at which the intensity of the enhanced electric field is maximized is determined. The wavelength of the measurement light L1 may be set to the determined resonance wavelength.

  Alternatively, the reflection intensity of the reflected light of the device for mass spectrometry may be measured in advance for a plurality of wavelengths, and the wavelength at which the reflection intensity is maximized may be set to the resonance wavelength at which the intensity of the enhanced electric field is maximized. . In addition, when the second reflector of the device for mass spectrometry has semi-transmission / semi-reflectivity, the transmission intensity of the transmitted light of the Raman spectroscopic device is measured, and the wavelength at which the transmission intensity is maximized is determined as an enhanced electric field. You may set to the resonant wavelength from which intensity | strength of this becomes the maximum. Even in such a case, since the enhanced electric field can be suitably generated and the light energy of the measurement light L1 can be suitably increased in the vicinity of the surface 1s, the light energy of the measurement light L1 necessary for desorption of the analyte is detected. Can be reduced.

  The mass spectrometric means 164 detects the analyte S that has been desorbed from the surface 1 s of the mass spectrometric device 1 by irradiation with the measurement light L 1 and has flown through the central holes of the extraction grid 162 and the end plate 163. The detector 165, an amplifier 166 that amplifies the output of the detector 165, and a data processor 167 that processes an output signal from the amplifier 166 are roughly configured.

Mass spectrometry using the mass spectrometer 150 configured as described above will be described.
First, the voltage Vs is applied to the mass spectrometric device 1 on which the sample is arranged, and the measurement light L1 adjusted to the resonance wavelength of the mass spectrometric device 1 from the light irradiation means 161 by a predetermined start signal is used for mass spectrometry. The surface 1 s of the device 1 is irradiated. By irradiation with the measurement light L1, the electric field is enhanced on the surface 1s of the mass spectrometry device 1, and the analyte S in the sample is desorbed from the surface 1s by the optical energy of the measurement light L1 enhanced by the electric field. . In addition, since the wavelength of the measurement light L1 is adjusted to the resonance wavelength of the device for mass spectrometry, the electric field can be effectively enhanced on the surface 1s of the device for analysis 1, thereby reliably and efficiently The analyte S can be desorbed well.

  The desorbed analyte S is extracted and accelerated in the direction of the extraction grid 162 due to the potential difference Vs between the mass spectrometry device 1 and the extraction grid 162, and travels substantially straight in the direction of the end plate 163 through the central hole. Then, it passes through the hole of the end plate 163 and reaches the detector 165 to be detected.

Since the flying speed of the analyte S after desorption depends on the mass of the substance, and the smaller the mass, the faster the detection speed is detected by the detector 165 in ascending order.
The output signal from the detector 165 is amplified to a predetermined level by the amplifier 166 and then input to the data processing unit 167. In the data processing unit 167, 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 166. A mass spectrum can be obtained by deriving mass from time.

  The case where the mass spectrometer 1 uses the time of flight mass spectrometry (TOF-MS) as described above has been described as an example, but the present invention is not limited to this. There is no particular limitation as long as it uses an enhanced electric field generated on the surface of the analytical device 1 to desorb the analyte placed on the surface, and it is also applicable to analyzers using other mass spectrometry methods. Is possible.

  The analyzer according to the present invention has been described in detail above. However, the present invention is not limited to the above-described embodiment, and various modifications and changes may be made without departing from the spirit of the present invention. It is.

Hereinafter, the results of electric field intensity simulation by FDTD in the Raman spectroscopic device 3 will be described. In this simulation, when the wavelength of incident light incident on the surface of the Raman spectroscopic device 3 is changed in the Raman spectroscopic device 3 having a predetermined translucent thickness (resonator length) d, The intensity of the generated enhanced electric field E was calculated by FDTD. The calculation results are shown in the graph of FIG. Graph of Figure 13, the horizontal axis represents the wavelength of the incident light and the vertical axis | took ⁴ volume integral | E.

  Further, in the graph of FIG. 13, the result when d = 180 nm is shown as a graph of result 1, the result when d = 210 nm is shown as the graph of result 2, and the result when d = 240 nm is shown as the graph of result 3. The result when d = 270 nm is shown as a graph of Result 4.

  From the graph of FIG. 13, in the result 1 (d = 180 nm), the enhancement electric field is maximum near the wavelength of 700 nm, and in the result 2 (d = 210 nm), the enhancement electric field is maximum near the wavelength of 760 nm, and the result 3 (d = 240 nm). ), The enhancement electric field is maximized in the vicinity of the wavelength of 820 nm, and as a result 4 (d = 270 nm), the enhancement electric field is maximized in the vicinity of the wavelength of 910 nm. That is, it was shown that the wavelength of incident light that maximizes the enhanced electric field varies depending on the thickness d (resonator length) of the light transmitting body.

It is a block diagram which shows typically the Raman spectrometer which is one Embodiment of the analyzer which concerns on this invention. It is a block diagram which shows the drive control system containing the control part of a Raman spectroscopy apparatus. It is a block diagram which shows 1st Embodiment of the device for Raman spectroscopy, (a) is a perspective view, (b) is sectional drawing. It is a block diagram which shows 2nd Embodiment of the device for Raman spectroscopy, (a) is a perspective view, (b) is a top view. It is a block diagram which shows typically 3rd Embodiment of the device for Raman spectroscopy. FIG. 6 is a process diagram schematically showing a manufacturing process of the spectroscopic device shown in FIG. 5. It is sectional drawing which shows typically 4th Embodiment of the device for Raman spectroscopy. FIG. 8 is a process diagram schematically showing a manufacturing process of the spectroscopic device shown in FIG. 7. It is a top view which shows typically 5th Embodiment of the device for Raman spectroscopy. (A) is a block diagram which shows typically the light modulation device which is other embodiment of a variable filter, (b) is an example of the reflected light spectrum of a light modulation device. (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. 1 is a mass spectrometer that is an embodiment of an analyzer according to the present invention. It is a graph which shows the simulation result of the intensity | strength of an enhanced electric field with respect to the wavelength of the incident light in the device for Raman spectroscopy.

Explanation of symbols

1, 2, 3, 4, 5 Raman spectroscopy device 1s, 2s, 3s, 4s Surface 6 Light modulation device 10, 110 First reflector 11 Metal fine wire 12 Pattern gap 13 Metal particle 14 Particle gap 15 Metal body 16 Fine Hole 20 Translucent body 20s Translucent surface 21, 121 Micro hole 30, 130 Second reflector 40 Anodized metal body 40s Surface of anodized metal body 41 Metal oxide body 41a Fine columnar body 42 Non-anodized body Part 44 Metal part 45 Filling part 46 Projection part 48 Metal nanorod 49 (Between metal nanorods) 50 Wavelength variable laser 60 Variable filter 62 Multi-layer filter 64 Filter drive part 70 Wavelength cut detection part 72 Mirror 80 Spectroscopic means 90 Control part 100 Raman spectroscopic device 120 Translucent fine pores 122 Translucent material 150 Mass spectrometer 1 0 device holding means 161 illumination means 162 extraction grid 163 end plate 164 mass analysis means 165 detector 166 amplifier 167 the data processing unit 168 box

Claims (9)

An optical resonator for generating an enhanced electric field on the surface by resonating a light beam of a predetermined wavelength incident on the inside from the surface;
A tunable laser light source that irradiates the light beam incident on the surface of the optical resonator and continuously changes the wavelength of the irradiated light beam;
The wavelength of the light beam is changed, and the resonance wavelength of the optical resonator that maximizes the intensity of the enhanced electric field generated on the surface of the optical resonator by irradiation of the light beam is determined. Wavelength setting means for setting the wavelength of the light beam emitted from the wavelength tunable laser light source to a resonant wavelength;
Analysis means for analyzing the characteristics of the analyte disposed on the surface of the optical resonator using the enhanced electric field generated on the surface by irradiation of the light beam having the resonance wavelength. Characteristic analyzer.   The optical resonator includes a first reflector having transflective properties, a translucent material, and a second reflector having complete reflectivity or transflective properties from the surface side. The analyzer according to claim 1, wherein the analyzer is one.   The analyzer according to claim 2, wherein the first reflector has a metal fine structure capable of generating localized plasmons. In addition, the light scattering device is provided with spectroscopic means for spectrally scattering the scattered light generated on the surface of the optical resonator to obtain a spectrum of Raman scattered light,
The said wavelength setting means sets the wavelength of the said light beam from which the signal of a Raman scattered light is obtained strongly to the said resonant wavelength from which the intensity | strength of the said enhancement electric field becomes the maximum. Analysis equipment. In addition, the apparatus further comprises a spectroscopic means for dispersing scattered light generated on the surface of the optical resonator and obtaining a spectrum of the scattered light,
The analyzer according to any one of claims 1 to 3, wherein the wavelength setting means sets the wavelength of the absorption spectrum of the scattered light to the resonance wavelength that maximizes the intensity of the enhanced electric field.   The wavelength setting means sets a wavelength at which the intensity of reflected light or transmitted light of the optical resonator is maximized, which is measured in advance, as the resonance wavelength at which the intensity of the enhanced electric field is maximized. The analyzer in any one of 1-3.   Further, the optical resonator is arranged downstream of the light beam in the traveling direction of the optical resonator, and the cut wavelength is changed in accordance with the wavelength of the light beam emitted from the wavelength tunable laser light source so that a light beam having a desired wavelength is obtained. The analyzer according to claim 1, further comprising a variable filter to be cut.   The analyzer according to claim 1, wherein the analyzing means is a spectroscopic means that obtains a spectrum of Raman scattered light by dispersing scattered light generated on the surface of the optical resonator. The analyzing means is a mass analyzing means for analyzing the mass of the analyte;
The surface of the optical resonator on which the analyte is disposed is irradiated with the light beam having the resonance wavelength from the wavelength tunable laser light source, and the enhanced electric field generated on the surface is used to irradiate the surface. The analyzer according to any one of claims 1 to 6, wherein an analyte is desorbed from the surface, and the mass of the desorbed analyte is analyzed by the mass analyzer.

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