WO2012066829A1

WO2012066829A1 - Colorimetric sensor cell, colorimetric sensor, method for producing colorimetric sensor cell, spr sensor cell, spr sensor, and method for producing spr sensor cell

Info

Publication number: WO2012066829A1
Application number: PCT/JP2011/067883
Authority: WO
Inventors: 友広紺谷; 潤一藤澤
Original assignee: 日東電工株式会社
Priority date: 2010-11-15
Filing date: 2011-08-04
Publication date: 2012-05-24

Abstract

[Problem] To provide: a colorimetric sensor cell which has excellent sensing accuracy; a colorimetric sensor; a method for producing a colorimetric sensor cell; an SPR sensor cell; an SPR sensor; and a method for producing an SPR sensor cell. [Solution] A colorimetric sensor cell (1) which is provided with a sensing part (30) and a sample disposition part (31) that is adjacent to the sensing part (30). The sensing part (30) is provided with an optical waveguide which has an under cladding layer (3) that is formed of a first resin and a core layer (4) that is formed of a second resin and covered with the under cladding layer (3). A resin mixture layer (23), in which the first resin permeates into the second resin, is formed in the surface layer of the core layer (4), said surface layer being in contact with the under cladding layer (3). An SPR sensor cell (41) wherein: a sensing part (30) is provided with an optical waveguide which has an under cladding layer (3) that is formed of a first resin and a core layer (4) that is formed of a second resin and covered with the under cladding layer (3); and a resin mixture layer (23), in which the first resin permeates into the second resin, is formed in the surface layer of the core layer (4), said surface layer being in contact with the under cladding layer (3).

Description

Colorimetric sensor cell, colorimetric sensor, method for producing colorimetric sensor cell, SPR sensor cell, SPR sensor, and method for producing SPR sensor cell

The present invention relates to a colorimetric sensor cell, a colorimetric sensor, a method for producing a colorimetric sensor cell, an SPR sensor cell, an SPR sensor and a method for producing an SPR sensor cell, and more specifically, a colorimetric sensor cell comprising an optical waveguide, and a colorimetric comprising the colorimetric sensor cell. The present invention relates to a sensor, a colorimetric sensor cell manufacturing method, an SPR sensor cell including an optical waveguide, an SPR sensor including the SPR sensor cell, and a method of manufacturing the SPR sensor cell.

Conventionally, in the fields of chemical analysis and biochemical analysis, a colorimetric sensor has been used as a sensor for detecting the concentration of a sample and its change.

As such a colorimetric sensor, for example, an optical waveguide layer formed on a glass substrate, a reaction film formed on the optical waveguide layer, the absorption spectrum of which changes in response to a gas to be detected, A sensor chip including a right-angle prism for light extraction has been proposed (for example, see Patent Document 1 below).

In the sensor chip described in Patent Document 1 below, the reaction film reacts with the gas to be detected, and changes color depending on the concentration of the gas to be detected.

When light is introduced into the optical waveguide layer of such a sensor chip, the guided light travels while repeating total reflection in the optical waveguide layer, and evanescent waves are oozed out on the surface of the optical waveguide layer. At this time, since a part of the evanescent wave is absorbed by the reaction film, the intensity of the light output from the optical waveguide layer using the right-angle prism is reduced.

Absorption of light (evanescent wave) by the reaction film depends on the degree of discoloration of the reaction film, that is, the concentration of the gas to be detected. Therefore, the concentration of the gas to be detected is detected by measuring the output intensity of the guided light. be able to.

Further, the colorimetric sensor as described above can be used not only for gas detection using a reaction film but also for concentration detection of a solution that causes a color change depending on the concentration.

In the fields of chemical analysis and biochemical analysis, for example, an SPR (Surface Plasmon Resonance) sensor including an optical fiber is used in addition to the above-described colorimetric sensor.

In an SPR sensor equipped with an optical fiber, a metal thin film is formed on the outer peripheral surface of the tip of the optical fiber, an analysis sample is fixed, and light is introduced into the optical fiber. Then, light of a specific wavelength in the introduced light generates surface plasmon resonance in the metal thin film, and attenuates the light intensity.

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 attenuates 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, a 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.

For example, when the sample is a solution, the refractive index of the sample (solution) depends on the concentration of the solution. Therefore, in the SPR sensor in which the sample (solution) is in contact with the metal thin film, the concentration of the sample can be detected by measuring the refractive index of the sample (solution), and the refractive index has changed. By confirming, it can be confirmed that the concentration of the sample (solution) has changed.

In the analysis of immune reaction, for example, an antibody is immobilized on a metal thin film of an optical fiber in an SPR sensor via a dielectric film, a specimen is brought into contact with the antibody, and surface plasmon resonance is generated. At this time, if the antibody and the specimen undergo an immunoreaction, the refractive index of the sample changes. Therefore, by confirming that the refractive index of the sample has changed before and after contact between the antibody and the specimen, the antibody and specimen Can be judged to have immunoreacted.

However, the SPR sensor equipped with such an optical fiber has a problem that it is difficult to form a metal thin film or 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 is formed at a predetermined position of the clad up to the surface of the core. An SPR sensor cell in which a metal thin film is formed on the surface of a core at a corresponding position has been proposed (for example, see Patent Document 2 below).

According to this 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.

JP 2009-250858 A JP 2000-19100 A

However, in recent years, in various chemical analyses, further improvement in detection accuracy of colorimetric sensor cells and SPR sensor cells is required.

An object of the present invention is to provide a colorimetric sensor cell having excellent detection accuracy, a colorimetric sensor, a method for producing a colorimetric sensor cell, an SPR sensor cell, an SPR sensor, and a method for producing an SPR sensor cell.

In order to achieve the above object, a colorimetric sensor cell of the present invention includes a detection unit and a sample placement unit adjacent to the detection unit, and the detection unit includes an under cladding layer made of a first resin, and a second The first resin is infiltrated into the second resin in a surface layer that is made of resin and includes a core layer that is covered with the under cladding layer, and that is in contact with the under cladding layer of the core layer. A resin mixed layer is formed.

According to such a colorimetric sensor cell, since the resin mixed layer made of the second resin infiltrated with the first resin is formed in the core layer, it is possible to accurately detect the concentration or change of the sample. .

Further, the colorimetric sensor of the present invention is characterized by comprising the above colorimetric sensor cell.

Since this colorimetric sensor uses a colorimetric sensor cell in which a resin mixed layer made of a second resin infiltrated with a first resin is formed in the core layer, it can accurately detect the concentration and change of the sample. Can do.

The method for producing a colorimetric sensor cell of the present invention includes a step of forming a core layer made of a second resin in a predetermined pattern on a substrate, and covering the core layer with the first resin on the substrate. And applying and heating the surface layer of the core layer so as to penetrate the first resin, and curing the first resin to form an undercladding layer made of the first resin, Forming a resin mixed layer in which the first resin is infiltrated into the second resin on a surface layer of the core layer that is in contact with the under cladding layer.

According to such a colorimetric sensor cell manufacturing method, a resin mixed layer made of the second resin infiltrated with the first resin can be formed in the core layer, so that the concentration and change of the sample can be accurately detected. A possible colorimetric sensor cell can be manufactured.

The SPR sensor cell of the present invention includes a detection unit and a sample placement unit adjacent to the detection unit, and the detection unit includes an under cladding layer made of a first resin and a second resin, and the under cladding. A resin mixed layer in which the first resin is infiltrated into the second resin is formed on a surface layer of the core layer that is in contact with the under cladding layer. It is characterized by having.

According to such an SPR sensor cell, since the resin mixed layer made of the second resin infiltrated with the first resin is formed in the core layer, the concentration and change of the sample can be accurately detected.

Further, the SPR sensor of the present invention is characterized by including the above SPR sensor cell.

Since this SPR sensor uses an SPR sensor cell in which a resin mixed layer made of a second resin infiltrated with the first resin is formed in the core layer, it is possible to accurately detect the concentration and change of the sample. .

The method for manufacturing an SPR sensor cell according to the present invention includes a step of forming a core layer made of a second resin in a predetermined pattern on a substrate, and covering the core layer with the first resin on the substrate. And applying and heating the first resin so as to penetrate the surface layer of the core layer, and curing the first resin to form an undercladding layer made of the first resin, and Forming a resin mixed layer in which the first resin is infiltrated into the second resin on a surface layer of the core layer that is in contact with the under cladding layer.

According to such a method for manufacturing an SPR sensor cell, since the resin mixed layer made of the second resin infiltrated with the first resin can be formed in the core layer, the concentration or change of the sample can be accurately detected. An SPR sensor cell can be manufactured.

According to the colorimetric sensor cell, the colorimetric sensor, the colorimetric sensor cell manufacturing method, the SPR sensor cell, the SPR sensor and the SPR sensor cell manufacturing method of the present invention, the detection accuracy can be improved with a simple configuration.

It is a perspective view which shows one Embodiment of the colorimetric sensor cell of this invention. It is sectional drawing of the colorimetric sensor cell shown in FIG. It is process drawing which shows the manufacturing method of the colorimetric sensor cell shown in FIG. 1, Comprising: (a) The process of forming the core layer which consists of 2nd resin on a board | substrate, (b) A step of coating and heating the first resin so as to allow the first resin to permeate into the surface layer of the core layer while covering the core layer; and (c), curing the first resin and forming an undercladding made of the first resin. Forming a layer and forming a resin mixed layer on the surface layer in contact with the undercladding layer of the core layer, (d) separating the substrate from the core layer and the undercladding layer, and (e) (F) shows the process of forming an over clad layer on the surface of a protective layer, and the process of forming a protective layer in the surface of a core layer and an under clad layer exposed by peeling. FIG. 4 is a schematic sectional side view showing one embodiment of the colorimetric sensor of the present invention. It is a perspective view which shows one Embodiment of the SPR sensor cell of this invention. It is sectional drawing of the SPR sensor cell shown in FIG. FIGS. 6A and 6B are process diagrams illustrating a method of manufacturing the SPR sensor cell illustrated in FIG. 5, in which FIG. 5A is a process of forming a core layer made of a second resin on a substrate, and FIG. A step of coating and heating one resin so that the core layer is coated and allowing the first resin to penetrate into the surface layer of the core layer; and (c) is a step of curing the first resin and forming an undercladding layer made of the first resin. And (d) is a step of peeling the substrate from the core layer and the under-cladding layer, and (e) is a step of peeling the substrate. A step of forming a protective layer on the surfaces of the core layer and the undercladding layer exposed by the step, (f) a step of forming an overcladding layer on the surface of the protective layer, and (g) a step of forming the overcladding layer. From dew The surface of the protective layer being, a process of forming a metal thin film so as to cover the core layer. It is sectional drawing which shows other embodiment of the SPR sensor cell of this invention. It is a schematic sectional side view which shows one Embodiment of the SPR sensor of this invention. The evaluation result of the colorimetric sensor in an Example and a comparative example is shown.

FIG. 1 is a perspective view showing an embodiment of a colorimetric sensor cell of the present invention. FIG. 2 is a cross-sectional view of the colorimetric sensor cell shown in FIG.

As shown in FIGS. 1 and 2, the colorimetric sensor cell 1 is formed in a bottomed frame shape having a substantially rectangular shape in plan view, and includes a detection unit 30 and a sample placement unit 31 adjacent to the detection unit 30. Yes.

The detecting unit 30 is provided to detect the state of the sample arranged in the sample arranging unit 31 and the change thereof, and includes the optical waveguide 2.

In the following description of the colorimetric sensor cell 1, when referring to the direction, the state when the sample is arranged in the colorimetric sensor cell 1 is the upper and lower reference. That is, in FIG. 1, the upper side of the page is the upper side, and the lower side of the page is the lower side.

In the present embodiment, the optical waveguide 2 is the colorimetric sensor cell 1 itself, and includes an under cladding layer 3, a core layer 4, a protective layer 5, and an over cladding layer 6.

The under-cladding layer 3 is made of a first resin (described later) and is formed in a substantially rectangular flat plate shape in plan view having a predetermined thickness in the vertical direction.

The core layer 4 is made of a second resin (described later) different from the first resin (described later), and is orthogonal to both the width direction (the direction orthogonal to the thickness direction, hereinafter the same) and the thickness direction of the under cladding layer 3. The under-cladding layer 3 is covered (embedded) at the upper end of the substantially center portion of the under-cladding layer 3 in the width direction. In the following description of the colorimetric sensor cell 1, a direction in which the core layer 4 extends is a propagation direction in which light propagates in the optical waveguide 2.

Further, the core layer 4 is disposed such that both propagation directions thereof are flush with both propagation directions of the under cladding layer 3, and the upper surface thereof is flush with the upper surface of the under cladding layer 3. In other words, the upper surface of the core layer 4 is exposed from the under cladding layer 3.

The core layer 4 is formed of a single resin layer 22 and a resin mixed layer 23.

The single resin layer 22 is formed in a substantially prismatic shape (specifically, a rectangular cross section flattened in the width direction), and is arranged so that the upper surface thereof is flush with the upper surface of the under cladding layer 3.

More specifically, the single resin layer 22 is formed in a substantially prismatic shape in which the length in the thickness direction and the length in the width direction are short with respect to the entire core layer 4 and the length in the propagation direction is equal. The resin mixed layer 23 is covered (embedded) at the upper end portion of the core layer 4 in the substantially central portion in the width direction.

The resin mixed layer 23 is formed as a surface layer in contact with the under cladding layer 3 of the core layer 4, and more specifically, in the lower part of the core layer 4 and both sides in the width direction, the cross-sectional view surrounding the single resin layer 22 is omitted. It is formed in a concave shape (U shape). The resin mixed layer 23 is disposed so that the upper surface thereof is flush with the upper surfaces of the under cladding layer 3 and the single resin layer 22.

That is, the upper surface of the core layer 4 is formed from the single resin layer 22 and the resin mixed layer 23 so as to be flush with the under cladding layer 3, and both the width direction both surfaces and the lower surface are formed from the resin mixed layer 23. ing.

Also, a light source 12 (described later) and an optical measuring instrument 13 (described later) are optically connected to both ends in the propagation direction of the core layer 4.

The protective layer 5 is formed as a thin layer having the same shape as the under-cladding layer 3 in plan view so as to cover the upper surfaces of the under-cladding layer 3 and the core layer 4 as necessary.

When the protective layer 5 is formed, for example, when the sample is in a liquid state, the core layer 4 can be prevented from swelling due to the sample.

The over clad layer 6 is formed in a rectangular frame shape in plan view on the protective layer 5 so that the outer periphery thereof is substantially the same as the outer periphery of the under clad layer 3 in plan view.

Thus, the optical waveguide 2 is formed in a bottomed frame shape having the protective layer 5 formed on the under cladding layer 3 and the core layer 4 as a bottom wall and the over cladding layer 6 as a side wall.

The sample placement unit 31 is provided to accommodate a sample to be analyzed by the colorimetric sensor 11 (described later), and is placed adjacent to the detection unit 30.

More specifically, the sample placement portion 31 is partitioned as a portion surrounded by the protective layer 5 and the over clad layer 6 on the upper side of the core layer 4.

Although not described in detail, the colorimetric sensor cell 1 can be provided with a support member (not shown) for supporting the optical waveguide 2 as necessary.

FIG. 3 is a process diagram showing a method for manufacturing the colorimetric sensor cell shown in FIG.

Next, a method for manufacturing the colorimetric sensor cell 1 will be described with reference to FIG.

In this method, first, as shown in FIG. 3A, a flat substrate 9 is prepared, and then the core layer 4 is formed on the substrate 9.

The substrate 9 is formed of a ceramic material such as silicon or glass, a metal material such as copper, aluminum, stainless steel, or an iron alloy, for example, a resin material such as polyimide, glass-epoxy, or polyethylene terephthalate (PET). ing. Preferably, it is formed from a ceramic material. The thickness of the substrate 9 is, for example, 10 to 5000 μm, preferably 10 to 1500 μm.

The core layer 4 is formed of a second resin. Examples of such a second resin include a polyimide resin, a polyamide resin, a silicone resin, an epoxy resin, an acrylic resin, and their fluorinated modified products and deuterium. Examples thereof include resin materials such as chemical-modified products and fluorene-modified products. These resin materials are preferably used as a photosensitive resin by blending a photosensitive agent.

In order to form the core layer 4, for example, the above-described resin varnish (resin solution) is prepared, the varnish is applied to the surface of the substrate 9 in the above-described predetermined pattern, dried, and heated as necessary. Harden. When a photosensitive resin is used, varnish is applied to the entire surface of the substrate 9 and dried, irradiated with ultraviolet rays through a photomask, developed into a pattern, and then heat-cured as necessary.

As heating conditions, the heating temperature is, for example, 70 to 250 ° C., preferably 70 to 150 ° C., and the heating time is, for example, 10 seconds to 2 hours, preferably 5 minutes to 1 hour.

The thickness of the core layer 4 thus formed is, for example, 5 to 100 μm, and the width is, for example, 5 to 200 μm.

Next, in this method, as shown in FIG. 3B, the core layer 4 is coated on the substrate 9 and the first resin is infiltrated into the surface layer of the core layer 4 in contact with the first resin. The first resin is applied and heated in the above pattern.

As the first resin, for example, a resin material adjusted to have a refractive index lower than that of the single resin layer 22 of the core layer 4 from the same resin material as described above.

In order to apply the first resin onto the substrate 9, for example, the above-described resin varnish (resin solution) is prepared, and the varnish is applied onto the substrate 9 by, for example, casting, spin coater or the like. After coating, the coating is dried if necessary. Next, heating is performed so that the first resin penetrates the core layer 4 (second resin).

As heating conditions, the heating temperature is, for example, 60 to 150 ° C., preferably 100 to 150 ° C., and the heating time is, for example, 1 to 30 minutes.

If a photosensitive resin is used, it is then irradiated with ultraviolet rays. At this time, if necessary, UV irradiation is performed through a photomask, and development is performed if necessary.

Next, in this method, as shown in FIG. 3C, the first resin is cured by, for example, heating to form the under cladding layer 3 made of the first resin. At this time, as the core layer 4, a resin mixed layer 23 in which the first resin is infiltrated into the second resin is formed on the surface layer of the core layer 4 that is in contact with the under cladding layer 3, and is embedded in the resin mixed layer 23. A single resin layer 22 is formed.

The thickness of the under cladding layer 3 formed in this way from the surface of the core layer 4 is, for example, 2 to 500 μm.

The thickness of each side of the resin mixed layer 23 surrounding the single resin layer 22 and the thickness of the single resin layer 22 are not particularly limited, and the degree of penetration of the first resin into the second resin, etc. Is appropriately determined.

Thereby, the under cladding layer 3 and the core layer 4 are formed flush with each other on the lower surface in contact with the substrate 9.

Note that the refractive index of the under-cladding layer 3 formed in this way is set lower than the refractive index of the single resin layer 22 of the core layer 4, and is, for example, 1.42 or more and less than 1.55. .

Further, the refractive index of the single resin layer 22 of the core layer 4 is set to be higher than the refractive index of the under cladding layer 3 and is, for example, 1.44 or more and 1.65 or less.

Further, the refractive index of the resin mixed layer 23 usually exceeds the refractive index of the undercladding layer 3 and is lower than the refractive index of the single resin layer 22. Specifically, the undercladding layer 3 in the stacking direction thereof. From the side to the single resin layer 22 side, the refractive index of the under cladding layer 3 continuously changes from the refractive index of the single resin layer 22.

Next, in this method, as shown in FIG. 3D, the substrate 9 is peeled from the under cladding layer 3 and the core layer 4, and the under cladding layer 3 and the core layer 4 are turned upside down.

Then, the surfaces of the under cladding layer 3 and the core layer 4 that are in contact with the substrate 9 are exposed as the upper surface.

Next, in this method, as shown in FIG. 3 (e), the protective layer 5 is formed on the under cladding layer 3 and the core layer 4.

Examples of the material for forming the protective layer 5 include silicon dioxide, aluminum oxide, and the like. Preferably, materials adjusted so as to have a refractive index lower than that of the core layer 4 are included.

Examples of a method for forming the protective layer 5 include a sputtering method and a vapor deposition method, and a sputtering method is preferable.

The thickness of the protective layer 5 thus formed is, for example, 1 to 100 nm, preferably 5 to 20 nm. Moreover, the refractive index of the protective layer 5 is set lower than the refractive index of the core layer 4, for example, is 1.25 or more and less than 1.55.

Next, in this method, as shown in FIG. 3 (f), the over clad layer 6 is formed on the protective layer 5 in the pattern described above.

Examples of the material for forming the over clad layer 6 include silicone rubber and the same resin material (first resin) as the above under clad layer 3.

In order to form the over clad layer 6, for example, a sheet having a rectangular frame shape in plan view is separately formed from the above-described material, and the sheet is laminated on the protective layer 5 as the over clad layer 6.

In order to form the over clad layer 6, for example, the above-described resin varnish (resin solution) is prepared, and the varnish is applied to the surface of the protective layer 5 in the above-described pattern, and then dried. Can also be cured. When a photosensitive resin is used, a varnish is applied to the entire surface of the protective layer 5, and after drying, exposed through a photomask. If necessary, after exposure, heated, and then developed into a pattern. It can also be heated.

The thickness of the over clad layer 6 thus formed is, for example, 5 to 200 μm, preferably 25 to 100 μm. Further, the refractive index of the over clad layer 6 is set lower than the refractive index of the core layer 4, for example, the same as the refractive index of the under clad layer 3. Note that when the refractive index of the protective layer 5 is lower than the refractive index of the core layer 4, the refractive index of the over clad layer 6 is not necessarily lower than the refractive index of the core layer 4.

Further, in such an overcladding layer 6, the size and shape of the sample placement portion 31 are not particularly limited, and are appropriately determined according to the type and use of the sample. When the colorimetric sensor cell 1 is to be miniaturized, the sample placement portion 31 is preferably formed small.

In this way, the colorimetric sensor cell 1 can be manufactured.

According to such a method for manufacturing the colorimetric sensor cell 1, the resin mixed layer 23 made of the second resin in which the first resin is infiltrated can be formed in the core layer 4. The colorimetric sensor cell 1 that can be detected with high accuracy can be manufactured.

In the colorimetric sensor cell 1, the sample is accommodated (arranged) in the sample arrangement part 31, so that the sample is surrounded by the over clad layer 6 in the sample arrangement part 31, and the core layer 4 (single resin layer) 22 and the resin mixed layer 23) are brought into contact with the sample.

According to such a colorimetric sensor cell 1, it is possible to accurately detect the concentration and change of the sample.

That is, according to such a colorimetric sensor cell 1, since the resin mixed layer 23 made of the second resin infiltrated with the first resin is formed in the core layer 4, the concentration and change of the sample can be accurately measured. Can be detected.

FIG. 4 is a schematic sectional side view showing an embodiment of the colorimetric sensor of the present invention.

Next, the colorimetric sensor 11 including the colorimetric sensor cell 1 will be described with reference to FIG.

As shown in FIG. 4, the colorimetric sensor 11 includes a light source 12, an optical measuring instrument 13, and the colorimetric sensor cell 1 described above.

The light source 12 is a known light source such as a white light source or a monochromatic light source, and is connected to a light source side optical fiber 15 via a light source side optical connector 14, and the light source side optical fiber 15 is connected to the light source side optical fiber. The colorimetric sensor cell 1 (core layer 4) is connected to one end portion in the propagation direction via the block 16.

A measuring instrument side optical fiber 18 is connected to the other end portion in the propagation direction of the colorimetric sensor cell 1 (core layer 4) via a measuring instrument side optical fiber block 17, and the measuring instrument side optical fiber 18. Are connected to the optical measuring instrument 13 via the measuring instrument side optical connector 19.

Although not shown, the optical measuring instrument 13 is connected to a known arithmetic processing unit, and can display, store and process data.

In such a colorimetric sensor 11, the colorimetric sensor cell 1 is fixed by a known sensor cell fixing device (not shown). The sensor cell fixing device (not shown) is movable along a predetermined direction (for example, the width direction of the colorimetric sensor cell 1), whereby the colorimetric sensor cell 1 is arranged at an arbitrary position.

Further, the light source side optical fiber 15 is fixed to the light source side optical fiber fixing device 20, and the measuring instrument side optical fiber 18 is fixed to the measuring instrument side optical fiber fixing device 21.

The light source side optical fiber fixing device 20 and the measuring instrument side optical fiber fixing device 21 are fixed on a known six-axis moving stage (not shown), and the propagation direction and width direction of the optical fiber (the propagation direction and the horizontal direction). It is movable in a direction perpendicular to the direction) and a thickness direction (a direction perpendicular to the propagation direction perpendicular to the propagation direction) and a rotation direction (three directions) with these directions (three directions) as axes.

According to such a colorimetric sensor 11, the light source 12, the light source side optical fiber 15, the colorimetric sensor cell 1 (core layer 4), the measuring instrument side optical fiber 18, and the optical measuring instrument 13 can be arranged on one axis. Light can be introduced from the light source 12 so as to transmit these.

In the colorimetric sensor 11, the colorimetric sensor cell 1 described above, that is, the colorimetric sensor cell 1 in which the core layer 4 is formed with the resin mixed layer 23 made of the second resin infiltrated with the first resin is used. Therefore, it is possible to accurately detect the concentration and change of the sample.

Hereinafter, one usage mode of the colorimetric sensor 11 will be described.

In this embodiment, for example, first, a sample is accommodated (arranged) in the sample arrangement portion 31 of the colorimetric sensor cell 1 shown in FIG. 4, and the sample and the core layer 4 (the single resin layer 22 and the resin mixed layer 23) are arranged. Make contact. Next, predetermined light from the light source 12 is introduced into the colorimetric sensor cell 1 (core layer 4) via the light source side optical fiber 15 (see the broken line arrow L1 shown in FIG. 4).

The light introduced into the colorimetric sensor cell 1 (core layer 4) passes through the colorimetric sensor cell 1 (core layer 4) while repeating total reflection in the core layer 4, and a part of the light is cored as an evanescent wave. It exudes from the layer 4 and is incident on the sample via the protective layer 5 on the upper surface of the core layer 4 and attenuated.

Thereafter, the light transmitted through the colorimetric sensor cell 1 (core layer 4) is introduced into the optical measuring instrument 13 through the measuring instrument side optical fiber 18 (see the broken line arrow L2 shown in FIG. 4).

That is, in the colorimetric sensor 11, the light intensity introduced into the optical measuring instrument 13 is attenuated in the light intensity of the wavelength absorbed by the sample in the core layer 4.

Since the wavelength absorbed by the sample depends on the color of the sample accommodated (arranged) in the colorimetric sensor cell 1, the attenuation of the light intensity of the light introduced into the optical measuring instrument 13 is detected. The color and its change can be detected.

More specifically, for example, when a white light source is used as the light source 12, the optical measuring instrument 13 measures the wavelength at which the light intensity attenuates after transmission through the colorimetric sensor cell 1, and the attenuation wavelength has changed. Once detected, the color of the sample and its change can be confirmed.

Further, for example, when a monochromatic light source is used as the light source 12, a change (attenuation degree) of the light intensity of the monochromatic light after transmission through the colorimetric sensor cell 1 is measured by the optical measuring device 13, and the degree of the attenuation. If the change is detected, the color of the sample and its change can be confirmed in the same manner as described above.

Therefore, such a colorimetric sensor 11 can be used for various chemical analyses, such as measurement of the concentration of the sample, based on the change in the color of the sample.

More specifically, for example, when the sample is a solution, the color of the sample (solution) depends on the concentration of the solution. Therefore, in the colorimetric sensor 11 in which the sample (solution) is arranged, the sample (solution) ), The concentration of the sample can be measured. Further, if it is detected that the color of the sample (solution) has changed, it can be confirmed that the concentration of the sample (solution) has changed.

For example, when using a sample (gas to be detected) and a reaction film whose absorption spectrum changes (that is, changes in color) in response to the gas, the core layer 4 in the sample placement unit 31 is used. The reaction film is fixed so as to be in contact with (single resin layer 22 and resin mixed layer 23), and gas is introduced into sample placement portion 31.

At this time, the reaction film reacts with the gas to be detected and causes a color change depending on its concentration. That is, the color of the reaction film depends on the concentration of the gas to be detected. Therefore, if the color of the reaction film is detected by the colorimetric sensor 11 in which the reaction film is arranged, the concentration of the gas to be detected can be measured. Further, if it is detected that the color of the reaction film has changed, it can be confirmed that the concentration of the gas to be detected has changed.

Further, according to the colorimetric sensor cell 1, the colorimetric sensor 11, and the method for manufacturing the colorimetric sensor cell 1, the detection sensitivity can be improved with a simple configuration.

In the above-described embodiment, one core layer 4 is formed in the colorimetric sensor cell 1, but the number of core layers 4 is not particularly limited, and a plurality of core layers 4 are formed at intervals in the width direction. You can also.

When the optical waveguide 2 includes a plurality of core layers 4, the colorimetric sensor 11 including the colorimetric sensor cell 1 can simultaneously analyze a sample a plurality of times, thereby improving the analysis efficiency.

In the above-described embodiment, the core layer 4 is formed in a substantially prismatic shape. However, the shape of the core layer 4 is not particularly limited, and the core layer 4 is, for example, a substantially semicircular shape (semi-cylinder in a cross-sectional view). Shape) and a substantially convex shape (convex column shape) in cross-sectional view.

In the above-described embodiment, the upper end portion of the colorimetric sensor cell 1 is open, but a lid that covers the sample placement portion 31 can be provided on the upper end portion of the colorimetric sensor cell 1. According to this, it can prevent that a sample contacts external air during a measurement.

In addition, the lid that covers the sample placement unit 31 is provided with an injection port for injecting the sample (liquid) into the sample placement unit 31 and a discharge port for discharging the sample from the sample placement unit 31. It is also possible to inject from the injection port, pass through the inside of the sample placement portion 31, and discharge from the discharge port. According to this, it is possible to continuously measure the physical properties of the sample while flowing the sample through the sample placement unit 31.

FIG. 5 is a perspective view showing an embodiment of the SPR sensor cell of the present invention. 6 is a cross-sectional view of the SPR sensor cell shown in FIG. In addition, about the member corresponding to an above-described member, the same referential mark is attached | subjected in each following figure, and the detailed description is abbreviate | omitted.

The SPR sensor cell 41 includes a detection unit 30 and a sample placement unit 31 adjacent to the detection unit 30 in the same manner as the colorimetric sensor cell 1 (see FIGS. 1 and 2) described above.

Further, in the SPR sensor cell 41, the sample placement unit 31 is provided with the metal thin film 7.

As shown in FIG. 6, the metal thin film 7 is formed so as to uniformly cover the protective layer 5 in the sample placement portion 31. That is, the metal thin film 7 is formed so as to uniformly cover the upper surface of the core layer 4.

In the SPR sensor cell 41, as described above, if the core layer 4 is covered (embedded) in the under cladding layer 3 so that the upper surface thereof is flush with the upper surface of the under cladding layer 3, the metal thin film 7 or When the metal particle layer 8 (described later) is formed, the metal material (described later) and the metal particles 10 (described later) can be efficiently arranged only on the upper side of the core layer 4.

FIG. 7 is a process diagram showing a method of manufacturing the SPR sensor cell shown in FIG.

Next, a method for manufacturing the SPR sensor cell 41 will be described with reference to FIG.

In this method, first, as shown in FIG. 7A, the plate-like substrate 9 described above is prepared in the same manner as in the method for manufacturing the colorimetric sensor cell 1 (see FIG. 3A). A core layer 4 is formed on the substrate 9.

The thickness of the substrate 9 is, for example, 10 to 5000 μm, preferably 10 to 1500 μm. The core layer 4 has a thickness of 2 to 150 μm, for example, and a width of 2 to 150 μm, for example.

Next, in this method, as shown in FIG. 7B, the core layer 4 is coated on the substrate 9 in the same manner as in the method for manufacturing the colorimetric sensor cell 1 (see FIG. 3B). The first resin is applied and heated in the above pattern so that the first resin penetrates into the surface layer of the core layer 4 in contact with the first resin.

Next, in this method, as shown in FIG. 7C, the first resin is cured by heating, for example, in the same manner as in the method for manufacturing the colorimetric sensor cell 1 (see FIG. 3C). An undercladding layer 3 made of one resin is formed. At this time, as the core layer 4, a resin mixed layer 23 in which the first resin is infiltrated into the second resin is formed on the surface layer of the core layer 4 that is in contact with the under cladding layer 3, and is embedded in the resin mixed layer 23. A single resin layer 22 is formed.

Next, in this method, as shown in FIG. 7D, the substrate 9 is peeled from the under-cladding layer 3 and the core layer 4 in the same manner as the method for manufacturing the colorimetric sensor cell 1 (see FIG. 3D). The under cladding layer 3 and the core layer 4 are turned upside down.

Next, in this method, as shown in FIG. 7E, a protective layer is formed on the under-cladding layer 3 and the core layer 4 in the same manner as in the method for manufacturing the colorimetric sensor cell 1 (see FIG. 3E). 5 is formed.

Next, in this method, as shown in FIG. 7 (f), the over-cladding layer 6 is formed on the protective layer 5 in the same manner as the method for manufacturing the colorimetric sensor cell 1 (see FIG. 3 (f)). The pattern is formed as described above.

As a material for forming the over clad layer 6, the same resin material (first resin) as that of the above under clad layer 3 is used.

In addition, when laminating | stacking the over clad layer 6 on the protective layer 5, it can also laminate | stack, after processing well-known primers, such as a silane coupling agent, on the surface of the protective layer 5 previously. If the surface of the protective layer 5 is treated with the above-described primer, when the metal thin film 7 and the metal particle layer 8 (described later) are formed, the metal material (described later) and the metal particles 10 (described later) are applied to the protective layer 5. It can be firmly fixed to.

Examples of the silane coupling agent include amino group-containing silane coupling agents such as γ-aminopropyltriethoxysilane.

When the silane coupling agent is treated as a primer, for example, an alcohol solution of the silane coupling agent is applied to the protective layer 5 and then heat-treated.

Next, in this method, as shown in FIG. 7G, the metal thin film 7 is formed so as to cover the core layer 4 in the sample placement portion 31.

Examples of the metal material for forming the metal thin film 7 include gold, silver, platinum, copper, aluminum, and alloys thereof.

These metal materials can be used alone or in combination of two or more.

In order to form the metal thin film 7, for example, if necessary, first, a resist having a pattern opposite to the pattern of the metal thin film 7 is formed, and the periphery of the portion where the metal thin film 7 is formed is masked. Thereafter, the metal thin film 7 is formed on the upper surface of the core layer 4 (the core layer 4 exposed from the resist formed if necessary) by, for example, a vapor deposition method such as a vacuum vapor deposition method, an ion plating method, or a sputtering method. Thereafter, if a resist is formed, the resist is removed by etching or peeling.

In addition, the metal thin film 7 can be laminated | stacked if necessary.

The thickness of the metal thin film 7 thus formed (when a plurality of metal thin films 7 are stacked, the total thickness) is, for example, 40 to 70 nm, preferably 50 to 60 nm.

In this way, the SPR sensor cell 41 can be manufactured.

According to such a method for manufacturing the SPR sensor cell 41, the resin mixed layer 23 made of the second resin infiltrated with the first resin can be formed in the core layer 4, so that the concentration and change of the sample can be accurately measured. An SPR sensor cell 41 that can be detected well can be manufactured.

And in this SPR sensor cell 41, when the sample is accommodated (arranged) in the sample arrangement part 31, the metal thin film 7 and the sample are brought into contact with each other. That is, the sample is surrounded by the over clad layer 6 in the sample placement portion 31.

Such an SPR sensor cell 41 can accurately detect the concentration and change of the sample.

That is, according to such an SPR sensor cell 41, since the resin mixed layer 23 made of the second resin infiltrated with the first resin is formed in the core layer 4, the concentration or change of the sample can be accurately detected. can do.

FIG. 8 is a cross-sectional view showing another embodiment of the SPR sensor cell of the present invention. In addition, about the member corresponding to an above-described member, the same referential mark is attached | subjected in each following figure, and the detailed description is abbreviate | omitted.

In the above description, the metal thin film 7 is provided in the sample placement portion 31, but for example, the metal placement layer 31 can be provided with the metal particle layer 8 instead of the metal thin film 7.

As shown in FIG. 8, the metal particle layer 8 is formed so as to uniformly cover the protective layer 5 in the sample placement portion 31. That is, the metal particle layer 8 is formed so as to uniformly cover the upper surface of the core layer 4.

As the metal particles 10 forming the metal particle layer 8, for example, the surface of particles made of metal such as gold, silver, copper, aluminum, chromium and platinum, for example, inorganic particles such as silica and carbon black is made of the metal described above. Examples of the coated particles include particles in which the surface of an organic particle such as a resin is coated with the metal described above. Preferably, the particle | grains which consist of metals are mentioned, More preferably, a chromium particle and a gold particle are mentioned.

The average particle diameter of the metal particles 10 is calculated, for example, as an average value of arbitrary 100 particles observed by electron microscope observation, and is, for example, 5 to 300 nm, preferably 10 to 150 nm.

For forming the metal particle layer 8, although not shown in detail, for example, the above-described metal particles 10 are dispersed in a known solvent to prepare a particle dispersion, and the particle dispersion is applied to the protective layer 5. ,dry.

In addition, the gold particle dispersion liquid in which gold particles are dispersed as the metal particles 10 is commercially available, and examples thereof include EMGC series (manufactured by British BioCell International Ltd.).

In the metal particle layer 8 formed in this way, the metal particles 10 are preferably formed as a single particle layer without being stacked on each other in the thickness direction. Further, the respective metal particles 10 are arranged independently at a slight interval so as not to contact each other.

The metal particle layer 8 is, for example, 15 to 60%, preferably 20 to 50% of the surface area of the core layer 4 exposed from the under cladding layer 3, that is, the area of the sample placement portion 31, in plan view. % Coating. When the metal particle layer 8 covers the core layer 4 exposed from the under-cladding layer 3 at the above-described ratio (coverage), as a single particle layer in which almost all the metal particles 10 are independently arranged. Since the metal particle layer 8 is formed, the concentration and change of the sample can be detected with higher accuracy.

And in this SPR sensor cell 41, the sample is accommodated (arranged) in the sample arrangement part 31, whereby the metal particle layer 8 and the sample are brought into contact with each other. That is, the sample is surrounded by the over clad layer 6 in the sample placement portion 31.

That is, according to the SPR sensor cell 41 as described above, since the over clad layer 6 is formed so as to surround the sample in contact with the metal particle layer 8, the sample can be easily disposed on the surface of the metal particle layer 8. Therefore, workability can be improved.

FIG. 9 is a schematic sectional side view showing an embodiment of the SPR sensor of the present invention.

Next, the SPR sensor 42 including the SPR sensor cell 41 will be described with reference to FIG.

As shown in FIG. 9, the SPR sensor 42 includes the light source 12, the optical measuring instrument 13, and the SPR sensor cell 41, similar to the colorimetric sensor 11 (see FIG. 4). Yes.

The light source 12 is connected to the light source side optical fiber 15 via the light source side optical connector 14 in the same manner as the colorimetric sensor 11 (see FIG. 4), and the light source side optical fiber 15 is connected to the light source side optical fiber block 16. Is connected to one end of the SPR sensor cell 41 (core layer 4) in the propagation direction.

A measuring instrument side optical fiber 18 is connected to the other end of the SPR sensor cell 41 (core layer 4) in the propagation direction via a measuring instrument side optical fiber block 17, and the measuring instrument side optical fiber 18 is The optical measuring instrument 13 is connected to the measuring instrument side optical connector 19.

In such an SPR sensor 11, the SPR sensor cell 1 is fixed by a known sensor cell fixing device (not shown). The sensor cell fixing device (not shown) is movable along a predetermined direction (for example, the width direction of the SPR sensor cell 1), whereby the SPR sensor cell 1 is disposed at an arbitrary position.

According to such an SPR sensor 11, the light source 12, the light source side optical fiber 15, the SPR sensor cell 1 (core layer 4), the measuring instrument side optical fiber 18 and the optical measuring instrument 13 can be arranged on one axis, and these The light can be introduced from the light source 12 so as to transmit the light.

The SPR sensor 11 uses the SPR sensor cell 1 described above, that is, the SPR sensor cell 1 in which the resin layer 23 made of the second resin in which the first resin is infiltrated is formed in the core layer 4. It is possible to accurately detect the concentration and change of the sample.

Hereinafter, one usage mode of the SPR sensor 11 will be described.

In this aspect, for example, first, a sample is accommodated (arranged) in the sample arrangement portion 31 of the SPR sensor cell 41 shown in FIG. 9, and the sample and the metal thin film 7 (or the metal particle layer 8) are brought into contact with each other. Next, predetermined light from the light source 12 is introduced into the SPR sensor cell 41 (core layer 4) through the light source side optical fiber 15 (see the broken line arrow L1 shown in FIG. 9).

The light introduced into the SPR sensor cell 41 (core layer 4) passes through the SPR sensor cell 41 (core layer 4) while repeating total reflection in the core layer 4, and part of the light is on the upper surface of the core layer 4. , The light is incident on the metal thin film 7 (or the metal particle layer 8) through the protective layer 5 and is attenuated by surface plasmon resonance.

Thereafter, the light transmitted through the SPR sensor cell 41 (core layer 4) is introduced into the optical measuring instrument 13 through the measuring instrument side optical fiber 18 (see the broken line arrow L2 shown in FIG. 9).

That is, in the SPR sensor 42, the light intensity of the light introduced into the optical measuring instrument 13 is attenuated at the wavelength at which the surface plasmon resonance is generated in the core layer 4.

Since the wavelength for generating the surface plasmon resonance depends on the refractive index of the sample accommodated (arranged) in the SPR sensor cell 41, by detecting the attenuation of the light intensity of the light introduced into the optical measuring instrument 13, A change in the refractive index of the sample can be detected.

More specifically, for example, when a white light source is used as the light source 12, the optical measuring instrument 13 measures a wavelength at which the light intensity attenuates after transmission through the SPR sensor cell 41 (a wavelength that generates surface plasmon resonance), If it is detected that the attenuation wavelength has changed, the change in the refractive index of the sample can be confirmed.

Further, for example, when a monochromatic light source is used as the light source 12, the optical measuring instrument 13 measures the change (degree of attenuation) of the monochromatic light after passing through the SPR sensor cell 41, and the degree of attenuation is measured. If the change is detected, it can be confirmed that the wavelength for generating the surface plasmon resonance has changed, and the change in the refractive index of the sample can be confirmed as described above.

Therefore, such an SPR sensor 42 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, since the refractive index of the sample (solution) depends on the concentration of the solution, the sample (solution) is removed from the metal thin film 7 (or the metal particle layer 8). If the refractive index of the sample (solution) is detected in the SPR sensor 42 brought into contact with (), the concentration of the sample can be measured. Moreover, if it detects that the refractive index of the sample (solution) has changed, it can be confirmed that the concentration of the sample (solution) has changed.

In the detection of an immune reaction, for example, an antibody is immobilized on the metal thin film 7 (or metal particle layer 8) of the SPR sensor cell 41 via a dielectric film, and a specimen is brought into contact with the antibody. At this time, since the refractive index of the sample changes if the antibody and the specimen undergo an immunoreaction, by detecting that the refractive index of the sample changes before and after contact between the antibody and the specimen, the antibody and the specimen are immune. It can be judged that it reacted.

And according to the manufacturing method of such SPR sensor cell 41, SPR sensor 42, and SPR sensor cell 41, improvement in detection sensitivity can be aimed at by simple composition.

In the above-described embodiment, one core layer 4 is formed in the SPR sensor cell 41, but the number of core layers 4 is not particularly limited, and a plurality of core layers 4 may be formed at intervals in the width direction. it can.

When the optical waveguide 2 includes a plurality of core layers 4, the SPR sensor 42 including the SPR sensor cell 41 can simultaneously analyze the sample a plurality of times, so that the analysis efficiency can be improved.

In the embodiment described above, the metal thin film 7 (or the metal particle layer 8) is formed so as to cover the entire protective layer 5 in the sample placement portion 31, but the metal thin film 7 (or the metal particle layer) is formed. 8) may be formed only on the upper side of the core layer 4 so as to cover at least the core layer 4.

In the above-described embodiment, the upper end portion of the SPR sensor cell 41 is open, but a lid that covers the sample placement portion 31 can be provided on the upper end portion of the SPR sensor cell 41. According to this, it can prevent that a sample contacts external air during a measurement.

Hereinafter, the present invention will be described more specifically with reference to examples and comparative examples. However, the present invention is not limited to the examples and comparative examples.

Production Example 1 (Production of first resin)
35 parts by mass of bisphenoxyethanol fluorene glycidyl ether, 40 parts by mass of 3 ′, 4′-epoxycyclohexylmethyl-3,4-epoxycyclohexanecarboxylate which is an alicyclic epoxy resin, (3 ′, 4′-epoxycyclohexane) methyl- 25 parts by weight of 3 ′, 4′-epoxycyclohexylcarboxylate and 50% by weight propionate carbonate solution of 4,4′-bis [di (β-hydroxyethoxy) phenylsulfinio] phenyl sulfide-bis-hexafluoroantimonate 2 The first resin (non-solvent photosensitive epoxy resin composition) was prepared by mixing parts by mass.

Production Example 2 (Production of second resin)
70 parts by mass of bisphenoxyecnol fluorene glycidyl ether, 30 parts by mass of 1,3,3-tris {4- [2- (3-oxecenyl)] butoxyphenyl} butane and 4,4′-bis [di (β-hydroxy A second resin (photosensitive epoxy resin composition) was prepared by dissolving 1 part by mass of a 50 mass% propion carbonate solution of (ethoxy) phenylsulfinio] phenyl sulfide-bis-hexafluoroantimonate in ethyl lactate.
<Colorimetric sensor cell>
Example 1
On the silicon substrate (substrate), the second resin obtained in Production Example 2 was applied to form a substantially prismatic shape having a thickness of 50 μm and a width of 50 μm, and then the solvent was volatilized by heating at 70 ° C. for 10 minutes. It was. Next, the reaction was completed by irradiation with ultraviolet rays through a photomask and further heating at 70 ° C. for 10 minutes. Next, development was performed with a developer of γ-butyrolactone to form a substantially prismatic core layer having a thickness of 50 μm and a width of 110 μm (see FIG. 3A).

Next, the first resin obtained in Production Example 1 was applied on the substrate so as to show the core layer so that the thickness from the surface (upper surface) of the core layer was 100 μm, and the coating was performed at 140 ° C. for 20 minutes. Heated. By this heat treatment, the first resin penetrated into the second resin on the surface layer of the core layer (see FIG. 3B).

Then, the reaction was completed by irradiation with ultraviolet rays and further heating at 120 ° C. for 10 minutes. As a result, an undercladding layer is formed, and a resin mixed layer in which the first resin is infiltrated into the second resin is formed on the surface layer that is in contact with the undercladding layer of the core layer, and is embedded in the resin mixed layer. A single resin layer was formed (see FIG. 3C).

Next, the silicon substrate was peeled from the under cladding layer and the core layer (see FIG. 3D), and the under cladding layer and the core layer were turned upside down.

Next, a 10 nm thick silicon dioxide thin film was formed as a protective layer on the undercladding layer and the core layer by sputtering (see FIG. 3E).

Separately, a silicone rubber sheet having substantially the same shape as the silicon substrate in plan view and having an opening having a width direction length of 1 mm and a propagation direction length of 12 mm was prepared and laminated on the protective layer. Thereby, the sample arrangement | positioning part of width direction length 1mm and propagation direction length 12mm was divided (refer FIG.3 (f)).

Thus, a colorimetric sensor cell was obtained. The refractive index of the under cladding layer is 1.531, the refractive index of the resin mixed layer is 1.584, and the refractive index of the mixed resin layer is a single resin layer from the under cladding layer side in the stacking direction. Towards the side, it continuously changed from 1.531 to 1.584.

Comparative Example 1
The resin mixing layer is not provided in the same manner as in Example 1 except that the step of heating at 140 ° C. for 20 minutes is omitted so that the first resin does not penetrate into the second resin (surface layer of the core layer). A colorimetric sensor cell was obtained.

Evaluation The colorimetric sensor cell obtained in each example and each comparative example was fixed to a colorimetric sensor (see FIG. 4).

Thereafter, in the sample container of the colorimetric sensor cell, as a sample, four types of rhodamine B (also known as Basic Violet 10) aqueous solutions (concentration: 1 ng / mL (light red), 10 ng) having different color concentrations depending on the solute concentration. / ML (slightly red), 100 ng / mL (slightly red), 1000 ng / mL (dark red)), and 50 μL of water (rhodamine B concentration 0 ng / mL) are added, and a wavelength of 555 nm is applied from one end of the core layer. Light was incident and the intensity of the light emitted from the other end was measured.

And the transmittance | permeability (%) when the intensity | strength of light in the state which does not have rhodamine B aqueous solution or water was set to 100% was calculated | required. The results are shown in Table 1.

Then, the concentration of the rhodamine B aqueous solution was plotted on the XY coordinates with the X axis as the concentration and the transmittance as the Y axis. The result is shown in FIG.

Results In the example in which the resin mixed layer was formed, the concentration of the rhodamine B aqueous solution could be detected with higher accuracy than in the comparative example in which the resin mixed layer was not formed.
<SPR sensor cell>
Example 2
On the silicon substrate (substrate), the second resin obtained in Production Example 2 was applied to form a substantially prismatic shape having a thickness of 50 μm and a width of 50 μm, and then the solvent was volatilized by heating at 70 ° C. for 10 minutes. It was. Next, the reaction was completed by irradiation with ultraviolet rays through a photomask and further heating at 70 ° C. for 10 minutes. Next, development was performed with a developer of γ-butyrolactone to form a substantially prismatic core layer having a thickness of 50 μm and a width of 50 μm (see FIG. 7A).

Next, the first resin obtained in Production Example 1 was applied on the substrate so as to show the core layer so that the thickness from the surface (upper surface) of the core layer was 100 μm, and the coating was performed at 140 ° C. for 5 minutes. Heated. By this heat treatment, the first resin penetrated into the second resin on the surface layer of the core layer (see FIG. 7B).

Then, the reaction was completed by irradiation with ultraviolet rays and further heating at 120 ° C. for 10 minutes. As a result, an undercladding layer is formed, and a resin mixed layer in which the first resin is infiltrated into the second resin is formed on the surface layer that is in contact with the undercladding layer of the core layer, and is embedded in the resin mixed layer. A single resin layer was formed (see FIG. 7C).

Next, the silicon substrate was peeled from the under cladding layer and the core layer (see FIG. 7D), and the under cladding layer and the core layer were turned upside down.

Next, a 10 nm-thick silicon dioxide thin film was formed as a protective layer on the undercladding layer and the core layer by sputtering (see FIG. 7 (e)).

Next, an over clad layer is formed on the under clad layer and the core layer in a shape having an opening using the first resin, thereby partitioning the sample placement portion (see FIG. 7F). .

Next, a 1 nm chromium thin film and a 50 nm gold thin film were sequentially laminated on the sample arrangement part (opening of the over clad layer) by sputtering to form a metal thin film (see FIG. 7G).

Thus, an SPR sensor cell was obtained. The refractive index of the under cladding layer is 1.584, the refractive index of the single resin layer is 1.531, and the refractive index of the mixed resin layer is a single resin from the under cladding layer side in the stacking direction. It changed continuously from 1.531 to 1.584 toward the layer side.

Example 3
A gold particle dispersion liquid (EMGC50, manufactured by British BioCell International Ltd.) was applied to the protective layer in the sample storage portion instead of the chromium thin film and the gold thin film, dried, and then the gold particles not attached to the protective layer. The SPR sensor cell was obtained in the same manner as in Example 2 except that the protective layer in the sample container was washed with ethanol and a metal particle layer was formed on the protective layer (see FIG. 8). . The coverage with metal particles (gold particles) was 30%.

Comparative Example 2
The resin mixing layer is not provided in the same manner as in Example 2 except that the step of heating at 140 ° C. for 5 minutes is omitted so that the first resin does not penetrate into the second resin (surface layer of the core layer). An SPR sensor cell was obtained.

Comparative Example 3
The resin mixing layer is not provided in the same manner as in Example 3 except that the step of heating at 140 ° C. for 5 minutes is omitted so that the first resin does not penetrate into the second resin (surface layer of the core layer). An SPR sensor cell was obtained.

Evaluation The SPR sensor cell obtained by each Example and each comparative example was fixed to the SPR sensor (see FIG. 9).

Thereafter, five types of ethylene glycol aqueous solutions having different concentrations as samples (concentration: 1 mass% (refractive index: 1.33389), 5 mass% (refractive index: 1.33764), 10 mass in the sample storage portion of the SPR sensor cell. % (Refractive index: 1.34245), 20% by mass (refractive index: 1.325231), 30% by mass (refractive index: 1.36249)) were added in an amount of 50 μL. In Example 2, light having a wavelength of 555 nm was used. In Example 3 and Comparative Example 3, light having a wavelength of 633 nm was incident, and the intensity of the light emitted from the other end was measured.

Then, the transmittance (%) was determined when the light intensity in the absence of the aqueous ethylene glycol solution was 100%.

Then, with the refractive index of the ethylene glycol aqueous solution as the X axis and the transmittance as the Y axis, the relationship was plotted on the XY coordinates, a calibration curve was created, and the slope was determined. The values are shown in Table 2. In addition, it shows that a detection sensitivity is so high that inclination (absolute value) is large.

Results Each example in which the resin mixed layer was formed had a larger slope (absolute value) than the comparative example in which the resin mixed layer was not formed.

The colorimetric sensor of the present invention comprising the colorimetric sensor cell of the present invention obtained by the method of producing a colorimetric sensor cell of the present invention, and the SPR sensor cell of the present invention obtained by the method of producing the SPR sensor cell of the present invention. The SPR sensor is suitably used as a sensor for detecting the concentration of a sample and its change in fields such as chemical analysis and biochemical analysis.

Claims

A detection unit, and a sample placement unit adjacent to the detection unit,
The detection unit includes an optical waveguide including an under cladding layer made of a first resin and a core layer made of a second resin and covered with the under cladding layer,
A colorimetric sensor cell, wherein a resin mixed layer in which the first resin is infiltrated into the second resin is formed on a surface layer of the core layer that is in contact with the under cladding layer.
A colorimetric sensor comprising the colorimetric sensor cell according to claim 1.
Forming a core layer made of the second resin in a predetermined pattern on the substrate;
Applying and heating the first resin on the substrate so as to cover the core layer and to allow the first resin to penetrate into the surface layer of the core layer;
By curing the first resin, an undercladding layer made of the first resin is formed, and the first resin is infiltrated into the second resin in a surface layer of the core layer that contacts the undercladding layer. And a step of forming a resin mixed layer. A method for producing a colorimetric sensor cell.
A detection unit, and a sample placement unit adjacent to the detection unit,
The detection unit includes an optical waveguide including an under cladding layer made of a first resin and a core layer made of a second resin and covered with the under cladding layer,
An SPR sensor cell, wherein a resin mixed layer in which the first resin is infiltrated into the second resin is formed on a surface layer of the core layer that is in contact with the under cladding layer.
An SPR sensor comprising the SPR sensor cell according to claim 4.
Forming a core layer made of the second resin in a predetermined pattern on the substrate;
Applying and heating the first resin on the substrate so as to cover the core layer and to allow the first resin to penetrate into the surface layer of the core layer;
By curing the first resin, an undercladding layer made of the first resin is formed, and the first resin is infiltrated into the second resin in a surface layer of the core layer that contacts the undercladding layer. Forming a resin mixed layer. A method for manufacturing an SPR sensor cell.