WO2015002009A1

WO2015002009A1 - Spr sensor cell, and spr sensor

Info

Publication number: WO2015002009A1
Application number: PCT/JP2014/066597
Authority: WO
Inventors: 友広紺谷; 真由尾▲崎▼
Original assignee: 日東電工株式会社
Priority date: 2013-07-01
Filing date: 2014-06-24
Publication date: 2015-01-08
Also published as: JP2015010971A

Abstract

　A SPR sensor cell and SPR sensor having very excellent detection sensitivity are provided. The SPR sensor cell of the present invention is provided with an undercladding layer, a core layer provided so that at least a portion is adjacent to the undercladding layer, and a metal layer for covering the core layer. The undercladding layer contains an undercladding layer-forming resin and particles dispersed in the undercladding layer-forming resin.

Description

SPR sensor cell and SPR sensor

The present invention relates to an SPR sensor cell and an SPR sensor. More specifically, the present invention relates to an SPR sensor cell and an SPR sensor provided with an optical waveguide.

Conventionally, SPR (Surface Plasmon Resonance) sensors equipped with optical fibers have been used in fields such as chemical analysis and biochemical analysis. In an SPR sensor including an optical fiber, a metal thin film is formed on the outer peripheral surface of the tip portion of the optical fiber, an analysis sample is fixed, and light is introduced into the optical fiber. Among the introduced light, light of a specific wavelength generates surface plasmon resonance in the metal thin film, and the light intensity is attenuated. In such an SPR sensor, the wavelength for generating surface plasmon resonance usually varies depending on the refractive index of the analysis sample fixed to the optical fiber. Therefore, if the wavelength at which the light intensity is attenuated after the occurrence of surface plasmon resonance is measured, the wavelength at which the surface plasmon resonance is generated can be identified, and if it is detected that the attenuation wavelength has changed, the surface plasmon resonance is detected. Since it can be confirmed that the wavelength to be generated has changed, the change in the refractive index of the analysis sample can be confirmed. As a result, such an SPR sensor can be used for various chemical analysis and biochemical analysis such as measurement of sample concentration and detection of immune reaction.

In the SPR sensor including such an optical fiber, there is a problem that it is difficult to form a metal thin film and fix an analysis sample because the tip of the optical fiber has a fine cylindrical shape. In order to solve such a problem, for example, a core through which light passes and a clad covering the core are provided, and a through-hole that reaches the surface of the core is formed at a predetermined position of the clad, and this through-hole is supported. There has been proposed an SPR sensor cell in which a metal thin film is formed on the surface of the core at the position (for example, Patent Document 1). According to such an SPR sensor cell, it is easy to form a metal thin film for generating surface plasmon resonance on the core surface and to fix the analysis sample to the surface.

However, in recent years, in chemical analysis and biochemical analysis, there is an increasing demand for detection of minute changes and / or trace components, and further improvement in detection sensitivity of the SPR sensor cell is required.

JP 2000-19100 A

The present invention has been made to solve the above-described conventional problems, and an object thereof is to provide an SPR sensor cell and an SPR sensor having very excellent detection sensitivity.

According to the present invention, an SPR sensor cell is provided. The SPR sensor cell of the present invention comprises an under cladding layer, a core layer provided so that at least a part thereof is adjacent to the under cladding layer, and a metal layer covering the core layer, the under cladding layer comprising: An undercladding layer forming resin and particles dispersed in the undercladding layer forming resin.
In one embodiment, the filling rate of particles in the under cladding layer is 3% to 30%.
In one embodiment, the average particle diameter (φ) of the particles is 200 nm to 2.5 μm.
In one embodiment, the particle includes an inorganic oxide.
In one embodiment, the particles include a metal oxide.
In one embodiment, the particles include a metal.
According to another aspect of the present invention, an SPR sensor is provided. The SPR sensor of the present invention includes the SPR sensor cell.

According to the SPR sensor cell and the SPR sensor of the present invention, a sufficient S / N ratio can be obtained, so that highly accurate measurement is possible.

It is a schematic perspective view explaining the SPR sensor cell by preferable embodiment of this invention. FIG. 2 is a schematic sectional view taken along line Ia-Ia of the SPR sensor cell shown in FIG. 1. FIG. 3 is a schematic cross-sectional view of an SPR sensor cell according to another preferred embodiment of the present invention. It is a schematic sectional drawing explaining an example of the manufacturing method of the SPR sensor cell of this invention. It is a schematic sectional drawing explaining the SPR sensor by preferable embodiment of this invention. It is the transmittance | permeability spectrum obtained in the Example.

A. SPR Sensor Cell FIG. 1 is a schematic perspective view illustrating an SPR sensor cell according to a preferred embodiment of the present invention. FIG. 2 is a schematic sectional view taken along line Ia-Ia of the SPR sensor cell shown in FIG. In the following description of the SPR sensor cell, when referring to a direction, the upper side of the drawing is the upper side, and the lower side of the drawing is the lower side.

As shown in FIGS. 1 and 2, the SPR sensor cell 100 is formed in a bottomed frame shape having a substantially rectangular shape in plan view, and is embedded in the under cladding layer 11 so that the upper surface of the under cladding layer 11 is exposed. It has a core layer 12, an under cladding layer 11, and a metal layer 13 that covers the core layer 12. The under cladding layer 11, the core layer 12, and the metal layer 13 constitute an optical waveguide, and function as the detection unit 10 that detects the state of the sample and / or its change. In the illustrated form, the SPR sensor cell 100 includes a sample placement unit 20 provided so as to be adjacent to the detection unit 10. The sample placement portion 20 is defined by the over clad layer 14. The over clad layer 14 may be omitted as long as the sample placement portion 20 can be appropriately provided. In the sample placement unit 20, a sample to be analyzed (for example, a solution or a powder) is placed in contact with the detection unit (substantially a metal layer).

The under-cladding layer 11 is formed in a substantially rectangular flat plate shape in plan view having a predetermined thickness. The thickness of the under cladding layer (thickness from the upper surface of the core layer) is, for example, 5 μm to 400 μm.

The under clad layer 11 includes an under clad layer forming resin and particles dispersed in the under clad layer forming resin. By dispersing the particles in the undercladding layer, a sufficient S / N ratio can be obtained and measurement with high accuracy is possible. The reason why such an effect is obtained is not clear, but is presumed as follows. That is, by dispersing particles in the under cladding layer, the reflectance on the surface of the under cladding layer can be increased and light can be prevented from entering the under cladding layer. Further, even when light is incident on the under cladding layer, light scattering is induced by the particles, so that the intensity of light transmitted through the under cladding layer and emitted can be reduced. As a result, the difference between the light intensity transmitted through the core layer (that is, signal intensity) and the light intensity from the outside such as the under cladding layer (that is, noise intensity) can be increased. It is estimated that highly accurate measurement is possible by reducing the influence of factors.

As the particles, any appropriate particles that can increase the reflectivity of the underclad layer surface and / or reduce the light transmittance in the underclad layer can be used. For example, the particles are preferably formed from a material having a refractive index of 1.40 to 3.00, more preferably 1.43 to 2.60. When such a material is used, there is an advantage that the refractive index of the under cladding layer can be easily adjusted to a desired range. Also, for example, the particles are preferably formed from a material having an extinction coefficient of 0.1 or less, more preferably 0. In the present specification, the refractive index means a refractive index at a wavelength of 830 nm. The extinction coefficient means an extinction coefficient at a wavelength of 830 nm.

Specific examples of the particle forming material include metals and inorganic oxides. Preferred examples of the metal include titanium, tantalum, aluminum, zinc, chromium, iron and the like. Examples of the inorganic oxide include metal oxides (for example, titanium oxide (TiO ₂ ), tantalum oxide (Ta ₂ O ₅ ), aluminum oxide (Al ₂ O ₃ ), zinc oxide (ZnO), and chromium oxide (Cr ₂ O ₃ ), iron oxide (Fe ₂ O ₃ ), copper oxide (CuO)) and metalloid oxides (eg, boron oxide (B ₂ O ₃ ), silicon oxide (SiO ₂ ), germanium oxide (GeO ₂ )) Can be preferably exemplified. As said particle | grain, only 1 type may be used and it may be used in combination of 2 or more types.

The average particle diameter (φ) of the above particles is, for example, 10 nm to 5 μm. The lower limit of the average particle diameter is preferably 200 nm, more preferably 400 nm. Further, the upper limit of the average particle diameter is preferably 2.5 μm, more preferably 2.0 μm. With such an average particle diameter, it is possible to reduce the noise caused by the transmitted light of the under cladding layer and improve the S / N ratio. Further, light leakage from the core layer can be reduced and sufficient signal intensity can be maintained. In addition, in this specification, an average particle diameter means a median diameter. The average particle size of the particles in the under cladding layer is, for example, based on laser diffraction / scattering particle size distribution measurement or image processing of a SEM image of a cross section of the under cladding layer to obtain a particle size distribution, and a volume obtained therefrom. It can be obtained based on a reference particle size distribution.

As the undercladding layer forming resin, any appropriate resin capable of forming an undercladding layer having a refractive index lower than the refractive index of the core layer described later is used. Specific examples include fluororesins, epoxy resins, polyimide resins, polyamide resins, silicone resins, acrylic resins, and modified products thereof (for example, fluorene-modified products, deuterium-modified products, and fluorine-modified products other than fluororesins). Can be mentioned. These may be used alone or in combination of two or more. These can be used as a photosensitive material, preferably by blending a photosensitive agent.

The refractive index of the resin for forming the underclad layer is lower than the refractive index of the above particles. The difference between the refractive index of the undercladding layer forming resin and the refractive index of the particles is preferably 0.03 or more, more preferably 0.05 or more, still more preferably 0.07 or more, and even more preferably 0.00. 10 or more.

The refractive index of the resin for forming the underclad layer is preferably 1.42 or less, more preferably less than 1.40, and further preferably 1.38 or less.

The filling rate of the particles in the under cladding layer 11 is, for example, 1% to 50%. The lower limit of the filling rate is preferably 2%, more preferably 3%, still more preferably 5%. Further, the upper limit of the filling rate is preferably 30%, more preferably 25%. With such a filling rate, noise caused by the transmitted light of the under cladding layer can be reduced and the S / N ratio can be improved. Further, light leakage from the core layer can be reduced and sufficient signal intensity can be maintained.

The refractive index (N _CL ) of the under cladding layer 11 is lower than the refractive index (N _PA ) of the particles. The difference between the refractive index of the under cladding layer and the refractive index of the particles (N _PA −N _CL ) is preferably 0.03 or more, more preferably 0.05 or more, still more preferably 0.07 or more, and even more. Preferably, it is 0.10 or more. By setting it as such a range, the light-scattering characteristic in an under clad layer improves, sufficient S / N ratio is obtained, and a highly accurate measurement is attained.

The light transmittance of the under cladding layer 11 at a wavelength of 650 nm is, for example, 95% or less, and preferably 92% or less. With such a light transmittance, noise caused by the light transmitted through the under cladding layer can be reduced and the S / N ratio can be improved. The light transmittance of the under cladding layer is calculated as a transmittance (thickness: 100 μm) at a wavelength of 650 nm by a visible / ultraviolet absorption spectrum method using a spectrophotometer.

The core layer 12 is formed in a substantially prismatic shape extending in a direction orthogonal to both the width direction of the undercladding layer 11 (left and right direction in FIG. 2) and the thickness direction. Embedded in the upper end. The direction in which the core layer 12 extends is the direction in which light propagates in the optical waveguide.

The core layer 12 is arranged so that the upper surface thereof is flush with the upper surface of the under cladding layer 11. By arranging the upper surface of the core layer so as to be flush with the upper surface of the under cladding layer, the metal layer can be efficiently arranged only on the upper side of the core layer. Furthermore, the core layer is disposed so that both end surfaces in the extending direction thereof are flush with both end surfaces in the corresponding direction of the under cladding layer.

The refractive index (N _CO ) of the core layer 12 is preferably 1.43 or less, more preferably less than 1.40, and further preferably 1.38 or less. By setting the refractive index of the core layer to 1.43 or less, the detection sensitivity can be significantly improved. The lower limit of the refractive index of the core layer is preferably 1.34. If the refractive index of the core layer is 1.34 or more, SPR can be excited even with an aqueous sample (water refractive index: 1.33), and a general-purpose material can be used. it can.

The refractive index (N _CO ) of the core layer 12 is higher than the refractive index (N _CL ) of the under cladding layer 11. The difference (N _CO -N _CL ) between the refractive index of the core layer and the refractive index of the under cladding layer is preferably 0.010 or more, more preferably 0.020 or more, and further preferably 0.025 or more. . If the difference between the refractive index of the core layer and the refractive index of the under cladding layer is within such a range, the optical waveguide of the detection unit can be set to a so-called multimode. Therefore, the amount of light transmitted through the optical waveguide can be increased, and as a result, the S / N ratio can be improved. Further, the difference between the refractive index of the core layer and the refractive index of the under cladding layer is preferably 0.15 or less, more preferably 0.10 or less, and still more preferably 0.050 or less. If the difference between the refractive index of the core layer and the refractive index of the under cladding layer is within such a range, light having a reflection angle that causes SPR excitation can exist in the core layer.

The thickness of the core layer 12 is, for example, 5 μm to 200 μm, preferably 20 μm to 200 μm. The width of the core layer is, for example, 5 μm to 200 μm, preferably 20 μm to 200 μm. With such a thickness and / or width, the optical waveguide can be a so-called multimode. The length of the core layer 12 (waveguide length) is, for example, 2 mm to 50 mm, preferably 10 mm to 20 mm.

As the material for forming the core layer 12, any appropriate material can be used as long as the effects of the present invention can be obtained. For example, it can be formed from a resin similar to the undercladding layer-forming resin and adjusted to have a refractive index higher than that of the undercladding layer.

As shown in FIGS. 1 and 2, the metal layer 13 is formed so as to uniformly cover at least part of the upper surfaces of the under cladding layer 11 and the core layer 12. If necessary, an easy adhesion layer (not shown) may be provided between the under cladding layer and the core layer and the metal layer. By forming the easy adhesion layer, the under clad layer, the core layer, and the metal layer can be firmly fixed.

Examples of the material for forming the metal layer 13 include gold, silver, platinum, copper, aluminum, and alloys thereof. The metal layer may be a single layer or may have a laminated structure of two or more layers. The thickness of the metal layer (the total thickness of all layers in the case of a laminated structure) is preferably 20 nm to 70 nm, more preferably 30 nm to 60 nm.

As a material for forming the easy-adhesion layer, chrome or titanium is typically mentioned. The thickness of the easy adhesion layer is preferably 1 nm to 5 nm.

As shown in FIG. 1, the over clad layer 14 has a rectangular frame in plan view so that the outer periphery of the over clad layer 11 and the core layer 12 is substantially the same as the outer periphery of the under clad layer 11 in plan view. It is formed into a shape. A portion surrounded by the upper surfaces of the under-cladding layer 11 and the core layer 12 and the over-cladding layer 14 is defined as a sample placement portion 20. By arranging the sample in the section, the metal layer of the detection unit 10 and the sample come into contact with each other, and detection is possible. Furthermore, by forming such a partition, the sample can be easily placed on the surface of the metal layer, so that workability can be improved.

Examples of the material for forming the over clad layer 14 include a material for forming the core layer and the under clad layer, and silicone rubber. The thickness of the over cladding layer is preferably 5 μm to 2000 μm, more preferably 25 μm to 200 μm. The refractive index of the overcladding layer is preferably lower than the refractive index of the core layer. In one embodiment, the refractive index of the overclad layer is equivalent to the refractive index of the underclad layer.

Although the SPR sensor cell according to a preferred embodiment of the present invention has been described, the present invention is not limited thereto. For example, as illustrated in FIG. 3, a protective layer 15 may be provided between the under cladding layer 11 and the core layer 12 and the metal layer 13. In this case, the protective layer 15 can be formed as a thin film having the same shape as that of the under cladding layer in plan view so as to cover all the upper surfaces of the under cladding layer 11 and the core layer 12. By providing the protective layer, for example, when the sample is in a liquid state, the core layer and / or the clad layer can be prevented from swelling due to the sample. Examples of the material for forming the protective layer include silicon dioxide and aluminum oxide. These materials can preferably be adjusted to have a refractive index lower than that of the core layer. The thickness of the protective layer is preferably 1 nm to 100 nm, more preferably 5 nm to 20 nm.

Also, for example, in the relationship between the core layer and the under cladding layer, at least a part of the core layer may be provided adjacent to the under cladding layer. For example, in the above embodiment, the configuration in which the core layer is embedded in the under cladding layer has been described. However, the core layer may be provided so as to penetrate the under cladding layer. Moreover, it is good also as a structure which forms a core layer on an under clad layer and surrounds the predetermined part of the said core layer with an over clad layer.

Furthermore, the number of core layers in the SPR sensor may be changed according to the purpose. Specifically, a plurality of core layers may be formed at a predetermined interval in the width direction of the under cladding layer. With such a configuration, since a plurality of samples can be analyzed simultaneously, the analysis efficiency can be improved. As the shape of the core layer, any appropriate shape (for example, a semi-cylindrical shape or a convex column shape) can be adopted depending on the purpose.

Furthermore, a lid may be provided on the SPR sensor cell 100 (sample placement unit 20). With such a configuration, the sample can be prevented from coming into contact with the outside air. Further, when the sample is a solution, a change in concentration due to evaporation of the solvent can be prevented. When the lid is provided, an inlet for injecting the liquid sample into the sample placement portion and a discharge port for discharging from the sample placement portion may be provided. With such a configuration, the sample can be flowed and continuously supplied to the sample placement unit, so that the characteristics of the sample can be continuously measured.

The above embodiments may be appropriately combined with each other.

B. Method for Manufacturing SPR Sensor Cell The SPR sensor cell of the present invention can be manufactured by any suitable method. 4 (a) to 4 (i) are schematic cross-sectional views for explaining an example of the method for producing the SPR sensor cell of the present invention.

First, as shown in FIG. 4A, the material 12 'for forming the core layer is disposed on the surface of the mold 30 having the recess corresponding to the shape of the core layer. Next, as shown in FIG. 4B, the transfer film 40 is bonded to the surface of the mold 30 while being pressed by the pressing means 50 in a predetermined direction, and the recess is filled with the core layer forming material 12 ′. Excess core layer forming material 12 'is removed. Thereafter, as shown in FIG. 4C, the core layer forming material 12 ′ filled in the recesses is irradiated with ultraviolet rays, and the material is cured to form the core layer 12. Further, as shown in FIG. 4D, the transfer film 40 is peeled from the mold 30 and the core layer 12 is transferred onto the transfer film 40.

Next, as shown in FIG. 4E, an undercladding layer forming material 11 ′ including an undercladding layer forming resin and particles dispersed in the resin is applied so as to cover the core layer 12. Alternatively, unlike the illustrated example, the under-cladding layer forming material 11 ′ is previously coated on another support (for example, a corona-treated PET film), and the under-cladding layer forming material 11 ′ is used as the core layer 12. The support and the transfer film 40 may be bonded to cover the substrate. Thereafter, as shown in FIG. 4 (f), the under cladding layer forming material 11 ′ is irradiated with ultraviolet rays, and the material is cured to form the under cladding layer 11. Thereafter, as shown in FIG. 4G, the transfer film 40 is peeled and removed, and the top and bottom are reversed.

The irradiation condition of the ultraviolet rays can be appropriately set according to the type of material. If necessary, the material may be heated. Heating may be performed before ultraviolet irradiation, may be performed after ultraviolet irradiation, or may be performed in combination with ultraviolet irradiation. In addition, any appropriate method can be used as a method of dispersing particles in the undercladding layer forming resin.

Next, an easy-adhesion layer (not shown) is formed on the under cladding layer 11 and the core layer 14 as necessary. The easy adhesion layer is formed, for example, by sputtering chromium or titanium.

Next, as shown in FIG. 4 (h), the metal layer 13 is formed so as to cover the core layer 12 on the core layer and the undercladding layer (on the protective layer when the protective layer is formed). Form. Specifically, the metal layer 13 is formed, for example, by vacuum deposition, ion plating, or sputtering of a material for forming the metal layer through a mask having a predetermined pattern.

Finally, as shown in FIG. 4I, the over clad layer 14 having the predetermined frame shape is formed. The over clad layer 14 can be formed by any appropriate method. For example, the over clad layer 14 is formed by disposing a mold having the predetermined frame shape on the core layer and the under clad layer, filling the mold with a varnish of an over clad layer forming material, and drying, if necessary. It can be formed by curing and finally removing the mold. In the case of using a photosensitive material, the over clad layer 14 can be formed by applying varnish to the upper surfaces of the core layer and the under clad layer, and after drying and exposing and developing through a photomask having a predetermined pattern. .

As described above, the SPR sensor cell shown in FIG. 1 can be manufactured.

C. SPR Sensor FIG. 5 is a schematic cross-sectional view illustrating an SPR sensor according to a preferred embodiment of the present invention. The SPR sensor 200 includes an SPR sensor cell 100, a light source 110, and an optical measuring instrument 120. The SPR sensor cell 100 is the SPR sensor of the present invention described in the above items A and B.

Any appropriate light source may be employed as the light source 110. Specific examples of the light source include a white light source and a monochromatic light source. The optical measuring instrument 120 is connected to any appropriate arithmetic processing device, and can store, display and process data.

The light source 110 is connected to the light source side optical fiber 112 via the light source side optical connector 111. The light source side optical fiber 112 is connected to one end of the SPR sensor cell 100 in the propagation direction via the light source side fiber block 113. A measuring instrument side optical fiber 115 is connected to the other end portion in the propagation direction of the SPR sensor cell 100 via a measuring instrument side fiber block 114. The measuring instrument side optical fiber 115 is connected to the optical measuring instrument 120 via the measuring instrument side optical connector 116. The light source side optical fiber 112 and the measuring instrument side optical fiber 115 are preferably connected by a multimode optical fiber capable of propagating light having a reflection angle capable of SPR excitation into the optical waveguide.

In the SPR sensor of the present invention, an optical fiber having a diameter larger than that of the core layer 12 can be used as the light source side optical fiber 112 as shown in FIG. Since particles are dispersed in the underclad layer to reduce the incidence and transmission of light, when a large-diameter optical fiber is used, the optical fiber and the SPR sensor cell are maintained while maintaining a sufficient S / N ratio. There is an advantage that the alignment with the position becomes easy and the operability is improved. Similarly, the measuring instrument side optical fiber 115 may be an optical fiber having a diameter larger than that of the core layer 12. Needless to say, optical fibers having substantially the same diameter as the core layer 12 may be used as the light source side and measuring instrument side optical fibers.

The SPR sensor cell 100 is fixed by any appropriate sensor cell fixing device (not shown). The sensor cell fixing device is movable along a predetermined direction (for example, the width direction of the SPR sensor cell), and thereby, the SPR sensor cell can be arranged at a desired position.

The light source side optical fiber 112 is fixed by a light source side optical fiber fixing device 131, and the measuring instrument side optical fiber 115 is fixed by a measuring instrument side optical fiber fixing device 132. The light source side optical fiber fixing device 131 and the measuring instrument side optical fiber fixing device 132 are respectively fixed on any appropriate six-axis moving stage (not shown), and the propagation direction and width direction of the optical fiber ( It is movable in a propagation direction and a direction orthogonal to the horizontal direction) and a thickness direction (a direction orthogonal to the propagation direction in the vertical direction) and a rotation direction around each of these directions.

According to such an SPR sensor, the light source 110, the light source side optical fiber 112, the SPR sensor cell 100 (core layer 12), the measuring instrument side optical fiber 115, and the optical measuring instrument 120 can be arranged on one axis, Light can be introduced from the light source 110 to be transmitted.

Hereinafter, an example of usage of such an SPR sensor will be described.

First, the sample is placed in the sample placement portion 20 of the SPR sensor cell 100, and the sample and the metal layer 13 are brought into contact with each other. Next, predetermined light from the light source 110 is introduced into the SPR sensor cell 100 (core layer 12) via the light source side optical fiber 112 (see arrow L1 in FIG. 5). The light introduced into the SPR sensor cell 100 (core layer 12) is transmitted through the SPR sensor cell 100 (core layer 12) while repeating total reflection in the core layer 12, and part of the light is on the upper surface of the core layer 12. Is incident on the metal layer 13 and attenuated by surface plasmon resonance. The light transmitted through the SPR sensor cell 100 (core layer 12) is introduced into the optical measuring instrument 120 through the measuring instrument side optical fiber 115 (see arrow L2 in FIG. 5). That is, in the SPR sensor 200, the light intensity of the light introduced into the optical measuring instrument 120 is attenuated at the wavelength that caused the surface plasmon resonance in the core layer 12. Since the wavelength for generating surface plasmon resonance depends on the refractive index of the sample in contact with the metal layer 13, the attenuation of the light intensity of the light introduced into the optical measuring instrument 120 is detected to detect the refractive index of the sample. Changes can be detected.

For example, when a white light source is used as the light source 110, the optical measuring instrument 120 measures the wavelength at which the light intensity attenuates after transmission through the SPR sensor cell 100 (the wavelength that generates surface plasmon resonance), and the attenuation wavelength changes. If this is detected, a change in the refractive index of the sample can be confirmed. For example, when a monochromatic light source is used as the light source 110, the optical measuring instrument 120 measures the change (degree of attenuation) of the monochromatic light after passing through the SPR sensor cell 100, and the degree of attenuation changes. If it is detected, it can be confirmed that the wavelength for generating surface plasmon resonance has changed, and the change in the refractive index of the sample can be confirmed.

As described above, such an SPR sensor cell can be used for various chemical analysis and biochemical analysis such as measurement of sample concentration and detection of immune reaction based on the change in the refractive index of the sample. More specifically, for example, when the sample is a solution, the refractive index of the sample (solution) depends on the concentration of the solution. Therefore, if the refractive index of the sample is detected, the concentration of the sample is measured. Can do. Furthermore, if it is detected that the refractive index of the sample has changed, it can be confirmed that the concentration of the sample has changed. For example, in detecting an immune reaction, an antibody is immobilized on the metal layer 13 of the SPR sensor cell 100 via a dielectric film, and a specimen is brought into contact with the antibody. Since the refractive index of the sample changes when the antibody and the specimen are immunoreacted, it is possible to determine that the antibody and the specimen have immunoreacted by detecting the change in the refractive index of the sample before and after contact between the antibody and the specimen. it can.

Hereinafter, the present invention will be specifically described by way of examples, but the present invention is not limited to these examples. In Examples and Comparative Examples, the measurement wavelength of the refractive index is 830 nm unless otherwise specified.

<Refractive index>
The refractive index was measured at a wavelength of 830 nm using a prism coupler type refractive index measuring device after forming a 10 μm thick film on a silicon wafer.

<Filling rate>
The filling rate of the particles was calculated by the following formula.
Filling rate (%) = ((particle mixing rate (wt%) / bulk specific gravity (g / mL)) / (100 + particle mixing rate (wt%))) × 100

<Bulk specific gravity>
The bulk specific gravity of the particles was calculated by putting the particles in a cup having a known volume (mL), measuring the weight (g) of the particles, and dividing the particle weight by the cup volume.

<Average particle size>
The median diameter was calculated by laser diffraction / scattering particle size distribution measurement to obtain an average particle diameter.

<Example 1>
An SPR sensor cell was fabricated by the method shown in FIG. Specifically, the core layer forming material was dropped on the surface of a mold (length: 200 mm, width: 200 mm) in which a concave portion for forming a core layer having a width of 50 μm and a thickness (depth) of 50 μm was formed on the surface. One end of the corona-treated surface of a PP film (thickness: 40 μm) having a corona-treated one surface was brought into contact with the surface of the mold, and the other end was warped. In this state, the roller was rotated toward the other end side while pressing the roller from the PP film side against the contact portion between the mold and the PP film, and the two were bonded together. Thereby, the core layer forming material was filled in the concave portion of the mold, and the excess core layer forming material was extruded. Next, the obtained laminate was irradiated with ultraviolet rays from the PP film side, and the core layer forming material was completely cured to form a core layer (refractive index: 1.384). The core layer forming material is composed of 60 parts by weight of fluorine-based UV curable resin (DIC, trade name “OP38Z”) and 40 parts by weight of fluorine-based UV curable resin (DIC, trade name “OP40Z”). Was prepared by stirring and dissolving. Next, the PP film was peeled from the mold, and a substantially prismatic core layer having a thickness of 50 μm and a width of 50 μm was transferred onto the film.

The under cladding layer forming material was applied on the PP film so as to cover the core layer. The under clad layer forming material is 99.4 parts by weight of fluorine-based UV curable resin (manufactured by Solvay Specialty Polymer Japan, trade name “Fluorolink MD700”, refractive index: 1.348) and silica particles (manufactured by Admatech Co., Ltd.). The product name “Admafine SC2500-SMJ” and refractive index 1.45) were prepared by mixing 0.6 parts by weight. At this time, the coating was applied so that the thickness from the core layer surface (upper surface) was 100 μm. Next, the undercladding layer forming material was cured by irradiating with ultraviolet rays to form an undercladding layer (light transmittance: 95% or less), and then the PP film was peeled off to remove the undercladding layer and the core layer. As described above, the optical waveguide fill having the core layer embedded in the underclad layer. It was produced.

Next, the optical waveguide film is diced and cut to a length of 22.25 mm × width of 20 mm, and then chromium and gold are sequentially sputtered through a mask having an opening of length 6 mm × width 1 mm so as to cover the core layer. An easy adhesion layer (thickness: 1 nm) and a metal layer (thickness: 50 nm) were sequentially formed. Finally, a frame-shaped overcladding layer was formed using a fluorine-based UV curable resin (trade name “Fluorolink MD700” manufactured by Solvay Specialty Polymer Japan Co., Ltd.) in the same manner as the undercladding layer was formed. In this manner, an SPR sensor cell similar to the SPR sensor cell shown in FIGS. 1 and 2 was produced.

A halogen light source (manufactured by Ocean Optics, trade name “HL-2000-HP”, white light) was connected to the incident side end face including the core layer of the SPR sensor cell obtained above through a multimode optical fiber (φ1000 μm). . White light from the halogen light source is incident on the incident side end surface including the core layer of the SPR sensor cell via a multimode optical fiber (φ1000 μm), and the light emitted from the emission side end surface of the core layer and the end surface of the core layer are horizontal. The light emitted from the emission side end face of the under cladding layer shifted by 100 μm in the direction was measured with a power meter through a multimode optical fiber (φ50 μm).

The S / N ratio was calculated with the light intensity (μW) at the output side end face of the core layer as signal (S) and the light intensity (μW) at the output side end face of the under cladding layer as noise (N). The results are shown in Table 1.

<Example 2>
An SPR sensor cell was fabricated in the same manner as in Example 1 except that the mixing ratio of the silica particles in the undercladding layer forming material was 2.5% by weight. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 3>
An SPR sensor cell was produced in the same manner as in Example 1 except that the mixing ratio of the silica particles in the under cladding layer forming material was changed to 5% by weight. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 4>
An SPR sensor cell was produced in the same manner as in Example 1 except that the mixing ratio of the silica particles in the under cladding layer forming material was 10% by weight. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 5>
Example 1 except that different silica particles (manufactured by Admatech Co., Ltd., trade name “Admafine SC5500-SMJ”) were used, and the mixing ratio of the silica particles in the undercladding layer forming material was 0.8% by weight. Similarly, an SPR sensor cell was produced. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 6>
The same as in Example 1 except that different silica particles (manufactured by Admatech Co., Ltd., trade name “Admafine SC5500-SMJ”) were used and the mixing ratio of the silica particles in the undercladding layer forming material was 2 wt%. Thus, an SPR sensor cell was produced. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 7>
The same as in Example 1 except that different silica particles (manufactured by Admatech Co., Ltd., trade name “Admafine SC5500-SMJ”) were used and the mixing ratio of the silica particles in the undercladding layer forming material was 5% by weight. Thus, an SPR sensor cell was produced. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 8>
The same as in Example 1 except that different silica particles (manufactured by Admatech Co., Ltd., trade name “Admafine SC5500-SMJ”) were used and the mixing ratio of the silica particles in the undercladding layer forming material was 10 wt%. Thus, an SPR sensor cell was produced. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 9>
Except for using different silica particles (made by Nippon Aerosil Co., Ltd., trade name “AEROSIL R974”, refractive index 1.45) and that the mixing ratio of the silica particles in the under cladding layer forming material was 2.6% by weight. An SPR sensor cell was produced in the same manner as in Example 1. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 10>
Example except that different silica particles (manufactured by Nippon Aerosil Co., Ltd., trade name “AEROSIL R974”, refractive index 1.45) were used and the mixing ratio of the silica particles in the undercladding layer forming material was 5 wt%. In the same manner as in Example 1, an SPR sensor cell was produced. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 11>
Other than using different silica particles (manufactured by Fuji Silysia Chemical Co., Ltd., trade name “SYLOPHOBIC507”, refractive index 1.45) and mixing the silica particles in the under cladding layer forming material to 3.2 wt% An SPR sensor cell was produced in the same manner as in Example 1. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 12>
Example except that different silica particles (manufactured by Fuji Silysia Chemical Co., Ltd., trade name “SYLOPHOBIC702”, refractive index 1.45) were used, and the mixing ratio of the silica particles in the under cladding layer forming material was 4% by weight. In the same manner as in Example 1, an SPR sensor cell was produced. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 13>
Other than using different silica particles (manufactured by Fuji Silysia Chemical Co., Ltd., trade name “SYLOPHOBIC702”, refractive index 1.45) and that the mixing ratio of the silica particles in the under cladding layer forming material is 7.2% by weight. An SPR sensor cell was produced in the same manner as in Example 1. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Example 14>
Use of titania particles (manufactured by Sakai Chemical Industry Co., Ltd., trade name “SRD 02-W”, crystal phase: rutile type, refractive index 2.72) and the mixing ratio of silica particles in the undercladding layer forming material is 2 wt. A SPR sensor cell was produced in the same manner as in Example 1 except that the percentage was changed to%. The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

<Comparative Example 1>
An SPR sensor cell was produced in the same manner as in Example 1 except that the mixing ratio of the silica particles in the undercladding layer forming material was 0% by weight (that is, no silica particles were used). The obtained SPR sensor cell was used for the same evaluation as in Example 1. The results are shown in Table 1.

The detection sensitivity and detection accuracy of the SPR sensor cells produced in Example 3 and Comparative Example 1 were evaluated. Specifically, white light from a halogen light source (trade name “HL-2000-HP” manufactured by Ocean Optics, Inc.) is incident on an incident side end face including the core layer of the SPR sensor cell via an optical fiber (φ1000 μm). The light emitted from the end surface on the emission side of the core layer was introduced into the spectroscope through an optical fiber (φ200 μm), and the transmittance spectrum was measured. When ethylene glycol aqueous solutions of different concentrations are used as samples, the ethylene glycol concentration in the aqueous solution is the X axis, the wavelength corresponding to the minimum value of the transmittance is the Y axis, and the relationship is plotted on the XY coordinates to obtain a calibration curve. The slope and the correlation coefficient were obtained. The greater the slope, the greater the sensitivity, and the closer the correlation coefficient to 1, the higher the detection accuracy. The results are shown in Table 2. Further, FIG. 6 shows the transmittance spectrum when an aqueous solution having ethylene glycol concentrations of 0% and 10% is used as a sample.

<Evaluation>
As is apparent from Tables 1 and 2 and FIG. 6, the SPR sensor cell of the example has a larger S / N ratio than the SPR sensor cell of the comparative example, and is excellent in detection sensitivity and detection accuracy. This is because, in the SPR sensor of the example, light is guided only in the core layer and the SPR spectrum absorption caused by the light is measured, whereas in the SPR sensor cell of the comparative example, the light guided in the cladding layer is Since the SPR spectrum absorption caused by the light guided in the core layer is measured with respect to the total amount of light guided in the core layer, unnecessary light guided in the cladding layer increases, and as a result This is probably because the signal is small. Furthermore, it is considered that the detection accuracy is lowered due to variations in light guided in the cladding layer. From the above, it can be seen that the SPR sensor cell of the present invention and the SPR sensor using the same are less susceptible to external factors and can be measured with excellent accuracy.

The SPR sensor cell and SPR sensor of the present invention can be suitably used for various chemical analysis and biochemical analysis such as measurement of sample concentration and detection of immune reaction.

DESCRIPTION OF SYMBOLS 10 Detection part 11 Under clad layer 12 Core layer 13 Metal layer 14 Over clad layer 20 Sample arrangement | positioning part 100 SPR sensor cell 110 Light source 120 Optical measuring device 200 SPR sensor

Claims

An under clad layer, a core layer provided so that at least a part thereof is adjacent to the under clad layer, and a metal layer covering the core layer,
The SPR sensor cell, wherein the under cladding layer includes an under cladding layer forming resin and particles dispersed in the under cladding layer forming resin.
The SPR sensor cell according to claim 1, wherein the under-cladding layer has a particle filling rate of 3% to 30%.
2. The SPR sensor cell according to claim 1, wherein an average particle diameter (φ) of the particles is 200 nm to 2.5 μm.
The SPR sensor cell according to claim 1, wherein the particles contain an inorganic oxide.
The SPR sensor cell according to claim 4, wherein the particles include a metal oxide.
The SPR sensor cell according to claim 1, wherein the particles include a metal.
An SPR sensor comprising the SPR sensor cell according to claim 1.