JP2000019100A - Spr sensor cell and immunoreaction-measuring device using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily immobilize an antibody and retain a specimen by forming a through hole communicating with a core at the specific position of a clad and forming a specific metal film on a core surface at a position corresponding to the through hole. SOLUTION: A core 7 made of glass, plastic, or the like where light is transferred is placed on a first clad (substrate) 5 that is formed in a thin-plate shape of glass or the like. Then, a second clad 9 is provided on the surface of the clad 5 so that it straddles the core 7. In this case, the core 7 is fitted to a recessed part 11 being formed on the bottom surface of the clad 9 and at the same time the bottom surface of the clad 9 is glued to the surface of the clad with an adhesive or the like. A through hole 13 reaching the surface of the core 7 from the upper surface is formed in the clad 9, and a metal thin film such as Au is formed on the surface of the core 7 corresponding to the through hole 13, thus easily retaining an antigen (antibody) in a space formed by the through hole 13 and the core 7.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an immunological reaction measuring device, and more particularly to a so-called surface plasmon resonance (Surface) device.
The present invention relates to an SPR sensor cell utilizing the phenomenon of Plasmon Resonance (hereinafter abbreviated as "SPR") and an immunoreaction measuring device using the same.

[0002]

2. Description of the Related Art Conventionally, in the field of biochemical analysis, immunoassay has been widely used as a method for detecting an extremely small amount of protein in a specimen. In this immunization method, a predetermined antigen concentration in a specimen is quantified by a specific immune reaction between an antigen (a protein to be detected) and an antibody (an antibody produced using the antigen). This immunization method can measure even a specimen in which a plurality of types of antigens are mixed without isolating the antigen to be detected. This is different from the chemical measurement method or the physical measurement method.

[0003] Among the immunization methods, there are various methods as described below. radio immunoassay: RIA (radioimmunoassay) enzyme immunoassay: EIA (enzyme immunoassay) fluoroimmunassay: FIA (fluorescence immunoassay)

[0004] Since the RIA method requires the use of an isotope, it has not been widely used recently. Also, EI
The method A is widely used at present because the immune reaction can be easily measured. Furthermore, the FIA method is positioned as a highly sensitive and highly accurate measurement method. Among the EIA methods, a method using a solid phase for antibody measurement, particularly ELISA (enzymelinke)
d immunosorbent assay), and the ELISA has the following two methods.

A. Indirect method: a method using an antigen as a solid phase b. Antibody capture method: a method using an anti-IgM antibody as a solid phase

[0006] The above-mentioned ELISA method is used for quantification of an antibody against a specific pathogen, quantification of an antibody against an allergen, and screening of a monoclonal antibody. The measurement kit used for the ELISA method includes:
Generally, a microplate in which 96 concave portions are formed is used, and an immunoreaction measurement is performed on this microplate. Therefore, a large number of samples can be measured at the same time, and in recent years, many automated immune reaction measuring devices have been on the market.

As reagent kits for ELISA, various reagent manufacturers provide various reagents. For example, there is tPA, an enzyme that acts indirectly in the direction of dissolving fibrin involved in blood coagulation and thrombus in blood. PAI-1 is an enzyme that suppresses tPA and acts in the direction of blood coagulation and thrombus formation.

By the way, a so-called SPR sensor is known as a sensor used in an immune reaction measuring device.
This SPR sensor is a sensor using the surface plasmon resonance phenomenon, and is measured based on the following principle. That is, 50
A thin metal film (such as gold or silver) having a thickness of about nm is deposited on the bottom surface of the prism having a high refractive index. Then, predetermined light is incident from the prism side toward the metal thin film at an angle equal to or greater than the critical angle. Since the metal thin film is translucent at about 50 nm, the light incident from the prism side passes through the metal thin film, reaches the surface of the metal thin film on the side opposite to the prism, and reaches the surface of the metal thin film on the side opposite to the prism. Generate an evanescent field.

By adjusting the incident angle of light, the wave number of the evanescent field and the wave number of surface plasmon resonance can be matched, and surface plasmon resonance can be excited on the surface of the metal thin film. In this case, the wave number of the surface plasmon resonance depends on the dielectric constant of the metal thin film and the refractive index of the specimen fixed to the surface opposite to the prism when viewed from the metal thin film. Therefore, the refractive index and the dielectric constant of the specimen can be checked. As described above, since the optical system and the sample are located on opposite sides of the metal thin film as a boundary, it is easy to construct a sensor.

By applying the above principle, an SPR sensor for an immune reaction measuring device using an optical fiber has been developed (B
Manufactured by IACORE-trade name: BIACORE Probe). In the SPR sensor using this optical fiber, first, the clad on the outer peripheral surface of the distal end portion of the optical fiber is removed, and the end surface of the distal end of the optical fiber is cut or polished. Coated. In addition, a metal thin film (such as gold or silver) is coated on the outer peripheral surface of the tip of the optical fiber. Further, the metal thin film on the outer peripheral surface of the distal end of the optical fiber is covered with a dielectric film, and the antibody used for the immunological reaction measurement is fixed on the dielectric film. A predetermined light source is provided on the other end side of the optical fiber so that light can be introduced into the optical fiber.

A method for measuring the immune response of the SPR sensor having the above-described configuration will be described. First, as for light introduced into the optical fiber, light of a specific wavelength excites surface plasmon resonance at the tip of the optical fiber. The wavelength of the light that excites the surface plasmon resonance changes depending on the refractive indices of the dielectric film and the antibody. The intensity of light having a wavelength that causes surface plasmon resonance is attenuated. Therefore, the immune response can be measured by comparing the wavelength of the light that attenuates the most before the immune reaction with the wavelength of the light that attenuates the most after the immune reaction. In addition, SPR sensors using prisms have been developed in addition to those using optical fibers.

[0012]

However, each of the above-mentioned prior arts has the following disadvantages. That is, when an SPR sensor is configured by an optical fiber, it is necessary to form a metal thin film (for example, Au is vapor-deposited) on the outer peripheral surface of the tip of the optical fiber core. However, since the optical fiber itself is fine, there has been an inconvenience that a metal thin film cannot be appropriately formed.

When actually performing an immunoreaction measurement, it is necessary to immobilize the antibody on the surface of the metal thin film. However, as described above, the tip of the core of the optical fiber is fine and cylindrical. As a result, it is difficult to immobilize the antibody.

Further, the conventional immunological reaction measuring device using the SPR sensor has only one SPR sensor composed of one optical fiber, and thus has the following disadvantages. That is, in the enzyme immunoassay, many steps are required for measurement, and a long time is required for an immune reaction. For this reason, it may take several hours to several tens of hours to measure one sample, and the measurement efficiency cannot be improved.

Also, in an immunoreaction measuring device using an SPR sensor composed of an optical fiber, a specific antibody to be used for the immunoreaction measurement is fixed in advance to the tip of the optical fiber, and the antigen in the specimen to be measured is detected by this SPR sensor. It reacts with the antibody of the sensor. For this reason, there has been a disadvantage that the immune reactions to a large number of antigens in the sample must be measured one by one. In addition, in the conventional immunoreaction measurement device, since the optical fiber is of an integral type, there is a disadvantage that when the measurement item is changed, the entire optical fiber needs to be replaced.

[0016]

SUMMARY OF THE INVENTION An object of the present invention is to provide an SPR sensor cell and an immunoreaction measuring device which can solve the disadvantages of the conventional example and can easily fix an antibody and hold a sample. It is another object of the present invention to provide an immune response measurement device capable of quickly performing an immune response measurement.

[0017]

In order to achieve the above-mentioned object, the invention according to claim 1 includes a core through which light is transmitted, and a clad that covers the core. Is formed, and a predetermined metal thin film is formed on the surface of the core at a position corresponding to the through hole.

With the above configuration, when performing an immunoreaction measurement, first, an antibody is immobilized on a metal thin film of an SPR sensor cell via a dielectric film, and then SP
Light is incident on the R sensor cell, and the wavelength at which the light intensity is attenuated is analyzed. Thereafter, the through-hole is filled with a specimen to be subjected to an immune reaction measurement, and an immune reaction is caused. And again, SP
Light is incident on the R sensor cell, and the wavelength of the light whose light intensity is attenuated is analyzed. At this time, if the wavelength at which the light intensity is attenuated changes, it can be determined that an immune reaction has occurred.
The sample is easily held in the space formed by the through hole and the core.

According to the second aspect of the present invention, a plate-shaped first clad, a core disposed on the first clad,
An optical waveguide comprising a second clad that covers the core; a through hole communicating with the core at a predetermined position of the second clad; and a predetermined metal on a surface of the core at a position corresponding to the through hole. It is configured to form a thin film.

According to the third aspect of the present invention, at least two cores are provided, and at least two or more through holes are formed in the clad corresponding to these cores.
Other configurations are the same as those of the first or second aspect.

According to a fourth aspect of the present invention, a configuration is adopted in which a light reflecting surface is formed on one of the two end faces in the longitudinal direction of the core, and the other configuration is the first, second or third aspect. This is the same as the described invention.

According to a fifth aspect of the present invention, at least one of the two end faces in the longitudinal direction of the core is inclined with respect to the longitudinal direction of the core. This is the same as the invention described in 2, 3 or 4.

According to the sixth aspect of the present invention, a gap is formed in the clad along the core, and a through-hole is communicated with the gap. Or, it is the same as the invention described in 5.

According to a seventh aspect of the present invention, a configuration is adopted in which the area of one end and the other end in the longitudinal direction of the core is different from each other. This is the same as the invention described in Item 6.

According to the present invention, a light source for irradiating a predetermined light, an SPR sensor cell for emitting the light to generate surface plasmon resonance, and a spectroscopic element for analyzing a wavelength distribution of the light emitted from the SPR sensor cell are provided. And S
The PR sensor cell is constituted by a core through which light is transmitted and a clad that covers the core, a through hole communicating with the core is formed at a predetermined position of the clad, and a surface of the core at a position corresponding to the through hole is formed on the surface of the core. The configuration is such that a predetermined metal thin film is formed.

[0026]

DESCRIPTION OF THE PREFERRED EMBODIMENTS [First Embodiment] The first embodiment of the present invention
Will be described with reference to the drawings. First, the SPR sensor cell 3, which is a characteristic part of the immune response measurement device according to the present embodiment, will be described with reference to FIGS. The SPR sensor cell 3 of the present invention uses an optical waveguide. More specifically, the SPR sensor cell 3 includes a plate-shaped first clad (substrate) 5, a core 7 disposed on the first clad 5, the core 7 and the first clad 5.
And a second clad (upper plate) covering the surface of the second clad. There are various types of optical waveguides, such as a planar type, a strip type, an embedded type, and a lens type. The details will be described below.

The first clad 5 is made of glass or the like, and has a thin plate shape. And this first clad 5
A core 7 to which light is transmitted is placed on the top. The core 7 extends over the entire length of the optical waveguide. The core 7 is made of glass, plastic, or the like. Further, a second clad 9 is provided on the surface of the first clad so as to straddle the core 7 described above. More specifically, a concave portion 11 corresponding to the core 7 is formed on the bottom surface of the second clad 9. When the second clad 9 is disposed on the first clad 5, the core 7 is fitted into the recess 11, and the bottom surface of the second clad 9 is in close contact with the first clad 5.

When the core 7 is mounted on the first clad 5, a method of using an adhesive or heating to melt the boundary surface between the core 7 and the first clad 5 can be considered. The same applies to the case where the second clad 9 is mounted on the first clad 5. When attaching the core 7 to the first clad 5 using an adhesive, it is necessary to use an adhesive having a lower refractive index than the refractive index of the core 7 in consideration of light attenuation.

The second clad 9 has a predetermined through hole 1.
3 are formed. More specifically, a through hole 13 is formed from the upper surface of the second clad 9 to the surface of the core 7. Therefore, the surface of the core 7 is exposed through the through hole 13. However, the through hole 13
In the portion of the core 7 corresponding to the above, a metal thin film is formed as described later. In addition, as a method of forming the through-hole 13 in the second clad 9, a case where a hole is formed in one plate-shaped clad may be considered. Further, the through hole 13 may be provided in the center of the second clad 9 by bonding a plurality of block-shaped members instead of drilling.

Here, in order for the core 7 to function as an optical waveguide, the first clad 5, the core 7, and the second clad 9
It is necessary that a certain relationship be established with respect to the refractive index. Specifically, the refractive index of the core 7 needs to be the largest, and then the refractive index of the second clad 9 needs to be the largest. Further, the refractive index of the first cladding 5 may be equal to or smaller than the refractive index of the second cladding 9.

FIG. 3 is a diagram for explaining a state in which light L passes through the SPR sensor cell 3. Thus, SP
The light L incident on one end of the R sensor cell 3 travels in the core 7 by repeating total internal reflection, and is emitted from the other end.

FIG. 4 is a cross-sectional view in which a metal thin film 15 made of Au is formed on the surface of the core 7. In order to form the SPR sensor, the core 7 is coated with Au by vapor deposition or the like. However, the SPR sensor can be configured even with Ag. As shown in FIG. 4B, when broadband light L is incident on a core coated with Ag or the like, a surface plasmon resonance phenomenon occurs in this region. Specifically, light of a predetermined wavelength causes surface plasmon resonance, and the light intensity of the light of this wavelength is attenuated. Accordingly, when the wavelength distribution of the light L emitted from the SPR sensor cell 3 is analyzed, the light intensity in a predetermined wavelength range decreases as shown in FIG.

Next, as shown in FIG. 5, an antibody (or antigen) 19 is immobilized on the Au metal thin film 15 via a predetermined dielectric film 17. As the antibody (or antigen) 19 or the like, an appropriate one is selected according to the antigen (or antibody) contained in the sample to be measured. When the light L is incident on the core 7 as shown in FIG. 6A after the antibody 19 and the like are immobilized in this way, surface plasmon resonance occurs as described above. However, the wavelength of light that causes surface plasmon resonance changes due to the immobilization of the antigen. Therefore, as shown in FIG. 6B, the curve indicating the wavelength distribution slightly moves as compared with before the antibody 19 is immobilized.

FIG. 7 shows a state in which the specimen 21 is filled in the through-hole 13 formed in the second clad 9. The specimen 21 contains a predetermined antigen 23. Therefore, if the specimen 21 contains the antigen 23 that specifically reacts with the antibody 19 immobilized on the Au film, an antigen-antibody reaction occurs. The wavelength of light that causes surface plasmon resonance also changes due to the antigen-antibody reaction. Therefore, FIG.
As shown in (A), the immune response can be measured by irradiating light L to the core 7 and analyzing the wavelength distribution after the antigen-antibody reaction has occurred, and knowing the wavelength of the attenuated light. . FIG. 8B is a diagram illustrating a state in which the wavelength of the attenuated light changes in the wavelength distribution.

FIG. 9 is an overall schematic diagram of the immune reaction measuring device 1. The light source 25 for irradiating the test light for measuring the immune reaction will be described. The light source 25 irradiates the light L with a broadband wavelength, and for example, a halogen lamp or the like can be used. Light L emitted from the light source 25 is condensed by the condenser lens 27 and is incident on the receptacle 29. Since the receptacle 29 is connected to the optical fiber connector 31, the light enters the optical fiber 33 via the optical fiber connector 31. The light L passing through the optical fiber 33 is
Further, the light passes through the optical fiber connector 35 and the receptacle 37 and passes through the condenser lens 39. The light L transmitted through the condenser lens 39 enters the SPR sensor cell 3.

The light L incident on the SPR sensor cell 3 is
It passes through the core 7. At this time, surface plasmon resonance occurs in the Au metal thin film as described above. Then, due to surface plasmon resonance, the light intensity of light of a specific wavelength decreases, and light L is emitted from the SPR sensor cell 3. Then, the light L emitted from the SPR sensor cell 3
Is transmitted through the condenser lens 41 and is incident on the receptacle 43. The light L incident on the receptacle 43 is incident on a predetermined spectroscope 49 via an optical fiber connector 45 and an optical fiber 47 connected to the receptacle 43.

In the spectroscope 49, the wavelength distribution of the incident light L is analyzed. More specifically, the wavelength distribution before an immune reaction occurs is checked in advance. Then, the wavelength distribution of the light L after the immune reaction actually occurs is examined. The presence or absence of an immune reaction and the state of the immune reaction can be determined from the difference in the obtained wavelength distribution.

[Second Embodiment] FIG. 10 is a perspective view showing an SPR sensor cell 3b used in an immune reaction measuring device according to a second embodiment. This SPR sensor cell 3b
Is basically the same as the first embodiment, except that a plurality of cores 7b are provided in one SPR sensor cell 3b. A plurality of through holes 13b are provided corresponding to each core 7b.

As a method of manufacturing the SPR sensor cell 3b, a plurality of cores 7b are arranged in parallel with each other on a first clad 5b made of a predetermined glass, and
The second clad 9b is fixed to the fixed first clad so as to cover b. At this time, an adhesive (not shown) or the like is used for fixing the first clad 5b and the core 7b and fixing the first clad 5b and the second clad 9b.

When actually performing an immunoreaction measurement, a specimen is filled in each through-hole 13b, and light L is incident on the core 7b. At this time, it is desirable that different types of antibodies be immobilized on each core 7b according to the type of antigen to be measured. This is because multiple items of the immune reaction measurement can be performed quickly. Alternatively, it is also possible to fix the same type of antibody, fill each through-hole with a different sample, and perform an immunoreaction measurement on each different sample.

FIG. 11 shows the SP of the second embodiment.
FIG. 2 is an overall schematic diagram of an immune reaction measurement device 1b having an R sensor cell 3b. In the present embodiment, the light source 25 and the spectroscope 4
9 is equipped with only one each. Therefore,
It is necessary to measure the immune reaction of each core 7b by switching the optical path. For this reason, the SPR sensor cell 3b is formed to be movable. Specifically, the SPR sensor cell moves perpendicular to the optical path direction from the light source 25 to the spectroscope 49. And it stops at the position corresponding to each core 7b of SPR sensor cell 3b, respectively.

In this embodiment, the case where the optical fiber 33, the optical fiber connector 31, and the receptacle 29 are provided between the light source 25 and the spectroscope 49 has been described. However, the present invention is not limited to this, and the light L from the light source 25 is directly incident on the SPR sensor cell 3b, and the emitted light L from the SPR sensor cell 3b.
May be directly incident on the spectroscope 49.

As described above, the SP of this embodiment
The R sensor cell 3b has a plurality of through holes 13b formed in the second clad 9b. This through-hole 13b may be formed by extruding each through-hole 13b in a single member later, or by combining and bonding a plurality of block-shaped members, as shown in FIG. Mouth 13b
May be formed.

Third Embodiment FIG. 12 is a perspective view showing a sensor cell fixing base 51 for fixing the SPR sensor cell 3 described in the first embodiment. This sensor cell fixing base 51 fixes each SPR sensor cell 3 at a constant interval. In this figure, three SPR sensor cells 3 can be fixed, but this is an example, and the number can be freely increased or decreased as needed.

On the sensor cell fixing base 51, a partition plate 53 for partitioning each SPR sensor cell 3 is formed.
The movement of the R sensor cell 3 in the arrangement direction (the left-right direction in the figure) is restricted. The partition plate 53 is provided with a locking portion 55 for restricting the movement of the SPR sensor cell 3 in the longitudinal direction of the core 7. Therefore, the SPR sensor cell 3 can be taken out from the sensor cell fixing base 51 in the vertical direction, but the movement in the horizontal direction is completely restricted.

Further, the sensor cell fixing table 51 is configured to be movable by a moving mechanism (not shown). Then, by moving the sensor cell fixing base 51, a different core 7 can be moved to the optical path from the light source. Therefore, it is possible to continuously and quickly measure an immune reaction for a plurality of samples. When the measurement of the immune reaction is completed, the SPR sensor cell 3 can be easily replaced.

FIG. 13 shows the SP described in the second embodiment.
This is a sensor cell fixing base 51c for fixing the R sensor cell 3b. This sensor cell fixing base 51c is provided with a plurality of cores 7b.
This is for the SPR sensor cell 3b having the following structure, and can restrict the movement in the horizontal direction with respect to the sensor cell fixing base 51c. Note that the sensor cell fixing base 51c is also configured to be movable by a predetermined moving mechanism. In particular, in the case of an SPR sensor cell 3b having a plurality of cores 7b, it is necessary to position each core 7b in the optical path.

[Fourth Embodiment] FIG. 14 is a view showing an SPR sensor cell 3d used in an immune reaction measuring device according to a fourth embodiment. This SPR sensor cell 3d
Has the same basic configuration as the first embodiment. However, in the SPR sensor cell 3d according to the present embodiment, the length of the core 7d is
Is slightly shorter than the overall length of As described above, even when the length of the core 7d is reduced, if the light L is incident from one end of the core 7d, as shown in FIG. The light L is emitted from.

However, in this embodiment, as shown in FIG. 16, a metal thin film 61 of Ag is deposited on the other end of the core 7d. This is because the other end of the core 7d is used as a light reflecting surface. Further, in a portion corresponding to the through-hole 13d on the surface of the core 7d, similarly to the first embodiment,
A metal thin film 15 of Au is formed. FIG. 17 shows a case where the light L is actually incident on the core 7d of the SPR sensor cell 3d. Light L incident from one end of the core 7d
Causes surface plasmon resonance in the Au metal thin film 15. The metal thin film 61 at the other end of the core 7d
Reflected by

The metal thin film 61 on the other end of the core 7d
When the light L reflected by the light source is analyzed, as shown in FIG. 17B, the light intensity of the light having the specific wavelength decreases. As shown in this figure, comparing the case where the Ag metal thin film 61 is present and the case where the Ag metal thin film 61 is not present, the light intensity of light of a specific wavelength is
The intensity of light of a specific wavelength is lower when the light is reflected by. On the other hand, the light intensity of other wavelengths hardly decreases. This is presumably because light causes surface plasmon resonance before reaching the other end of the core 7d, and also causes surface plasmon resonance when reflected and returned. Therefore, the sensitivity of the SPR sensor cell 3d is substantially improved.

Next, as shown in FIG. 18, an antibody (or antigen) 19 is immobilized on the Au thin metal film 15 via a predetermined dielectric film 17. As the antibody (or antigen) 19 or the like, an appropriate one is selected according to the antigen (or antibody) contained in the sample to be measured. When the light L is incident on the core 7d as shown in FIG. 19A after the antibody 19 and the like are fixed in this way, surface plasmon resonance occurs. However,
The immobilization of the antibody 19 changes the wavelength of light that causes surface plasmon resonance. Therefore, FIG.
As shown in (B), the curve showing the wavelength distribution slightly moves as compared with before the antibody 19 is immobilized.

FIG. 20 shows a through hole 1 formed in the second clad 9d in the SPR sensor cell 3d of the present embodiment.
The state where the sample 21 is filled in 3d is shown. The specimen 21 contains a predetermined antigen 23. Therefore, if an antigen specifically reacting with the antibody 19 fixed on the Au dielectric film 17 is contained in the specimen 21, an antigen-antibody reaction occurs. The wavelength of light that causes surface plasmon resonance also changes due to the antigen-antibody reaction. Therefore,
As shown in FIG. 21 (A), light L is incident on the core 7d, the wavelength distribution after the antigen-antibody reaction occurs is analyzed, and the immune response is measured by knowing the wavelength of the attenuated light. Can be. FIG. 21B is a diagram illustrating a state in which the wavelength of the attenuated light changes in the wavelength distribution.

FIG. 22 is a sectional view showing a state in which an Ag metal thin film 63 is formed on the entire end face of the SPR sensor cell 3d1. The reason why the metal thin film 63 is formed on the entire end face of the SPR sensor cell 3d1 in this manner is as described above.
This is because it is easier than forming a metal thin film only on the end face of d. That is, in order to form a metal thin film only on the end face of the core 7d, it is necessary to selectively perform vapor deposition on the core 7d. SP configured in this way
Even if the R sensor cell 3d1 is used, the wavelength attenuated by the immune reaction changes as shown in FIG.
An immune response measurement can be performed.

FIG. 23 is an overall schematic diagram of the immune reaction measuring device 1d. The light source 25 that emits the test light L for measuring an immune reaction will be described. The light source 25 irradiates the light L with a broadband wavelength, and for example, a halogen lamp or the like can be used. Light L emitted from the light source 25 is condensed by the condenser lens 27 and is incident on the receptacle 29. Since the receptacle 29 is connected to the optical fiber connector 31, the light L from the light source 25 is incident on the optical fiber 33 via the optical fiber connector 31.
The light L that has passed through the optical fiber 33 further passes through the optical fiber connector 35 and the receptacle 37, and passes through the condenser lens 39. Part of the light L transmitted through the condenser lens 39 is transmitted through the beam splitter 65, and is further incident on one end of the SPR sensor cell 3d through the condenser lens 67.

Light L incident on SPR sensor cell 3d
Penetrates the core. At this time, surface plasmon resonance occurs in the Au metal thin film as described above. Then, due to the surface plasmon resonance, the light intensity of the light of the specific wavelength decreases, and the light is reflected at the end face of the core in the SPR sensor cell 3d. Then, the light L reflected on the end face of the core returns inside the SPR sensor cell 3d and is emitted from one end of the SPR sensor cell 3d. The emitted light L passes through the condenser lens 67 described above and further enters the beam splitter 65. A part of the light L incident on the beam splitter 65 is reflected at right angles by the reflection surface of the beam splitter 65.

The light L reflected at right angles passes through a predetermined condenser lens 69. The light L transmitted through the condenser lens 69 is incident on the spectroscope 49 through the receptacle 71, the optical connector 73, the optical fiber 75, and the optical fiber connector 77.

FIG. 24 shows an SPR sensor cell 3d1 having a plurality of cores. As described above, when the SPR sensor cell 3d1 has a plurality of cores, there are the following advantages. That is, by immobilizing the same antibody on each of the cores, it is possible to quickly measure the immune reaction of a plurality of different samples. In addition, by immobilizing different antibodies on each core, it is possible to quickly measure the immune reaction of different antigens for the same specimen. For this reason, the SPR sensor cell 3d1 can move with respect to the optical path from the light source 25.

Next, FIG. 25 shows a modification of the immune reaction measuring device shown in FIG. FIG. 7 is a diagram illustrating a case where an incident angle of light L from a light source 25 is not parallel to a longitudinal direction of a core of the SPR sensor cell 3. FIG. 25 (A) is an overall schematic diagram of the immune reaction measuring device 1 already described, and FIG.
(B) shows a case where the light L is incident on the SPR sensor cell 3 at a predetermined angle. Even with this configuration,
If the light L is incident on the core, the light L is totally reflected and transmitted through the core 7, so that the function as the SPR sensor is not lost. In particular, it is known that when light is incident on the end face of the core at a predetermined angle, the light incidence efficiency is improved under certain conditions.

[Fifth Embodiment] Next, a fifth embodiment will be described with reference to FIG. In this embodiment, the end face of the SPR sensor cell 3e is provided with an inclination. In the present embodiment, the end face of the core 7e is inclined, and the end face of the second clad 9e is also inclined. However, the inclination of the second cladding 9e may or may not be present. As described above, when the end face of the core 7e is inclined, the light L incident from the normal direction of the inclination is used.
Can be efficiently introduced into the core 7e. Therefore,
The angle of the inclination formed on the core 7e is equal to the light L from the light source 25.
Is appropriately set according to the direction in which the light is incident. In this drawing, as an example, an inclined surface of about 45 degrees is formed with respect to the bottom surface of the SPR sensor cell 3e.

FIG. 27 shows an SPR having an inclination in the core 7e.
1 shows an overall schematic diagram of an immune reaction measuring device 1e using a sensor cell 3e. FIG. 28 is an overall schematic diagram of the immune reaction measuring device 1e in which the SPR sensor cell 3e is a side sectional view. As shown in FIG. 28B, when the light L is incident at a certain angle with respect to the longitudinal direction of the core 7e,
The light L can be efficiently introduced by the inclination formed on the end face of the core 7e. Further, in this figure, between the light source 25 and the spectroscope 49, a plurality of condenser lenses 27, 39, 41,
Optical fibers 33, 47, optical fiber connectors 31, 3
5, 45, and receptacles 29, 37, 43 are provided. However, the present invention is not limited to this. Light L from the light source 25 is directly condensed by the condensing lens, and S
The light L is made incident on the PR sensor cell 3e and the SPR
The light L emitted from the sensor cell 3e may be condensed by a condenser lens and directly enter the spectroscope 49. Further, an angle adjusting mechanism (not shown) capable of changing the emission angle of the light L is provided in the condenser lens on the upstream side of the SPR sensor cell 3e, and as shown in FIG.
Light may be incident on the core 7e at a predetermined angle.

[Sixth Embodiment] FIGS. 29 to 31
FIG. 14 is a diagram showing a sixth embodiment. S of the embodiment
The PR sensor cell has a first clad 5f and a second clad 9
f, a third cladding 8f, a core 7f, and a substrate 6f. The core 7f is sandwiched between two third claddings 8f, and is a plate-like member as a whole. The plate-like member and the first clad 5f are bonded together. in this way,
After the third clad 8f, the core 7f, and the first clad 5f are bonded, these members are fixed to the substrate 6f, and the second clad 9f is fixed on the core 7f. A through hole 13f is formed in the second clad 9f, and the through hole 13f reaches the core 7f. However, even if there is no first clad 5f, the SPR
It has a function as a sensor cell.

In this embodiment, the core 7f, the first clad 5f, the second clad 9f, the third clad 8f and the substrate 6
f is made of glass or plastic. In addition, comparing the refractive indices of the respective constituent elements,
The refractive index of f is the largest, the refractive index of the third cladding 8f is next largest, and the refractive index of the first cladding 5f is equal to or less than the refractive index of the third cladding 8f. Also,
The refractive index of the substrate 6f is equal to or less than the refractive index of the first clad 5f.

FIG. 31 shows the core 7 of the SPR sensor cell 3f.
FIG. 6 is a diagram in which light L is incident on f. The light L incident from the end of the core 7f travels inside the core 7f while repeating total reflection, and is emitted from the other end of the core 7f.

FIG. 32 shows a modification of the second clad.
The second clad 9f1 has a rectangular through hole 13f1 and a cylindrical chip fixing hole 14f at one end thereof.
Are formed. The tip fixing hole 14f is for inserting a tip 81 (see FIG. 33B) for injecting and aspirating a sample. The tip 81 is attached to the tip of a micropipette (not shown), and a sample is injected and aspirated. The tip 81 is detachable from the micropipette.

The reason for forming the chip fixing hole 14f1 is as follows. That is, when the sample is injected or aspirated into the SPR sensor cell 3f, the tip of the chip 81 is prevented from contacting the antibody on the core 7f. Therefore, the shapes of the chip 81 and the chip fixing hole 14f1 correspond to each other.

FIG. 33 shows a case where the tip fixing hole 14f2 and the tip 81 are tapered. Second
The chip fixing hole 14f2 formed in the clad 9f is tapered at a predetermined angle as shown in FIG. As shown in FIG. 33B, the tip of the tip 81 also has a conical shape with the same angle. The thickness T of the second clad 9 f is larger than the length L of the tip of the chip 81. The tip 81 has a step formed between the tip and the main body. Therefore, this step comes into contact with the surface of the second clad 9f. Therefore, as described above, it is possible to prevent the tip of the tip 81 from contacting the core 7f.

[Seventh Embodiment] Next, FIG. 34 and FIG.
The seventh embodiment will be described based on FIG. In the SPR sensor cell 3g according to the present embodiment, two through holes 13g are formed in the second clad 9g, and a gap 83 communicating with these through holes 13g is formed. Specifically, the gap 83 is formed on the bottom side of the second clad 9g and at a position corresponding to the core 7g of the SPR sensor cell 3g. That is, the second clad 9 and the core 7
Thus, a predetermined space is formed between g. This void serves as a reservoir for the specimen during the measurement of the immune reaction,
It has a rectangular shape along the core 7g. However, if the gap 83 is formed at a position corresponding to the core 7g,
Its shape may be any.

One of the two through-holes 13g is used for injecting a sample into the space 83 or sucking the sample. That is, the tip 81 of the micropipette (see FIG. 33B) is inserted. The other through-hole 13g is an air hole through which air passes when a sample is injected or aspirated. This means that the gap is 2
This is because the space is a closed space except for the 13 g of the through holes. In this way, when the void is formed inside the second clad 9g, the leakage of the specimen can be prevented when the specimen is injected into the SPR sensor cell 3g. Further, even when the SPR sensor cell 3g itself is attached to or detached from the immunoreaction measurement device, leakage of the sample can be prevented.

In the above-described embodiment, the through-hole 13g for injecting the specimen is cylindrical. However, the present invention is not limited to this, and one or both of the through-holes may be formed in a tapered shape as shown in FIG. The tapered shape at this time corresponds to the shape of the tip 83 of the micropipette.

[Eighth Embodiment] FIG. 37 is an overall schematic diagram of an immune reaction measuring apparatus 1h according to an eighth embodiment. In this embodiment, the light path from the light source 25 to the SPR sensor cell 3h, and the light path from the SPR sensor cell 3h to the spectroscope 4
The branching of the optical path to 9 is performed using an optical coupler 85. That is, the light L of the light source 25 is incident on the optical coupler 85 through the condenser lens 27. In the optical coupler 85, the incident light L passes to the SPR sensor cell 3h side. The light L that has passed further passes through the condenser lens 41 and enters the SPR sensor cell 3h.

The light L incident on one end of the SPR sensor cell 3h travels inside the core while repeating total reflection, and reaches the other end of the core. At the other end of the core, a metal thin film of Ag is formed to serve as a reflection surface of light L. Therefore,
The light L transmitted through the core causes surface plasmon resonance and is reflected by the reflecting surface of the core. And light L
Returns inside the core and exits from one end of the SPR sensor cell. At this time, since the returning light L also causes surface plasmon resonance, the intensity of light of a specific wavelength is attenuated, and the SPR
The sensitivity as a sensor is improved.

The light L emitted from one end of the SPR sensor cell 3h passes through the condenser lens 41 and enters the optical coupler 85. In the branching section 86 of the optical coupler 85, the SPR
Light L from the sensor cell 3h is branched to the spectroscope 86 side. Then, the wavelength distribution of the light L is analyzed by the spectroscope 49 connected to the optical coupler 85.

FIG. 38 shows an immune reaction measuring device 1h1 having a plurality of cores in the SPR sensor cell 3h1. As shown in this figure, eight cores are formed in the SPR sensor cell 3h. Then, when actually performing the immune reaction measurement, the SPR sensor cell 3h1 is positioned such that the optical axis of the light L from the light source coincides with any one of the cores. Then, when measuring the immune response in the next core, the SPR sensor cell 3h moves. Thus, S
By moving the PR sensor cell 3h, an immune reaction measurement can be rapidly performed on a large number of samples. If different antibodies are immobilized on each core, it is possible to rapidly measure the immune reaction of the same sample with respect to many types of antigens. The number of cores is not particularly limited.

There are various types of the optical coupler 85 described above. For example, a melting type, an electro-optic effect type, a temperature adjusting type, a stress adjusting type and the like can be used. The fusion mold is one in which two light paths are bundled by fusion. In addition to a normal optical coupler, an electro-optical effect type optical coupler changes a wavelength characteristic by applying a voltage to an electro-optical crystal. This makes it possible to control the division ratio of the light L passing through the optical path and the path selection. Further, the temperature control type optical coupler changes the wavelength characteristic by enclosing silicon around a coupling portion of an optical path in the optical coupler and adjusting the temperature with a Peltier element. Further, the stress-adjusting type optical coupler changes the wavelength characteristic by applying a twist or a bending to an optical path in the optical coupler.

[Ninth Embodiment] FIG. 39 is a view showing an SPR sensor cell 3i used in an immune reaction measuring device according to a ninth embodiment. This SPR sensor cell 3i is characterized by the shape of the core 7i. That is, FIG.
As shown in the figure, the cross-sectional area of the core 7i is different at both ends. As an example, in the present embodiment, the cross-sectional area of the light L on the incident side of the core 7i is larger than the cross-sectional area of the light L on the outgoing side. The cross-sectional shape is rectangular. in this way,
By reducing the cross-sectional area on the emission side of the core 7i, the emitted light L is condensed and efficiently enters the spectroscope 49 and the like. The shape of the cross section of the core 7i is not particularly limited. That is, the shape may be a circle, a triangle, or another polygon.

FIG. 39A is a perspective view showing the SPR sensor cell 3i. This SPR sensor cell 3i is shown in FIG.
It consists of the parts shown in FIGS. That is,
First clad 5i made of glass or plastic
A core 7i provided on the first clad 5i,
The second clad 9i is fixed on the first clad 5i so as to cover the core 7i. Therefore, a concave portion 11i corresponding to the core 7i is formed on the bottom surface of the second clad 9i. The first clad 5i,
The core 7i and the second clad 9i are fixed to each other with a predetermined adhesive.

The refractive index of each component is as follows.
That is, the core 7i is made of a material having the largest refractive index, the second clad 9i is made of a material having the next largest refractive index, and the first clad 5i has the same refractive index as that of the second clad 9i. It is formed of a material having a lower refractive index.

[Tenth Embodiment] FIG. 40 shows a tenth embodiment. FIG. 40A is a perspective view showing the sensor cell fixing base 87, and FIG. 40B is a perspective view showing a state where the SPR sensor cell 3j is fixed to the sensor cell fixing base 87. The SPR sensor cell 3j according to the present embodiment has a plurality of cores 7j and all the cores 7
A through-hole 13j crossing j is formed. Therefore,
By immobilizing different types of antibodies on the surface of each core 7j via a metal thin film and a dielectric film and injecting a sample into the through-hole 13j, an immune reaction of the same sample with various antigens is rapidly performed. be able to.

[0079]

As described above, according to the first aspect of the present invention, a through hole communicating with the core is formed at a predetermined position of the clad, and a predetermined surface is formed on the surface of the core at a position corresponding to the through hole. A metal thin film was formed. Therefore, a metal thin film for generating surface plasmon resonance can be easily formed on the surface of the core, and the antibody (or antigen) can be easily fixed on the surface of the metal thin film.

According to the second aspect of the present invention, the SPR sensor cell is constituted by using a plate-shaped optical waveguide. Then, a through hole is formed in the clad that covers the upper surface of the core. For this reason, since the sample is held in the region surrounded by the core and the through-hole, a special container or the like for holding the sample is unnecessary. Further, by using a plate-shaped optical waveguide, a sufficient contact area between the antibody fixed to the metal thin film and the specimen can be ensured, so that the sensitivity as an SPR sensor can be improved.

According to the third aspect of the present invention, a plurality of cores are provided, and a plurality of through holes are formed in the clad corresponding to these cores. For this reason, by immobilizing a plurality of antibodies on each core, it is possible to quickly measure an immune response to different types of antigens. In addition, by immobilizing the same type of antibody on each core, an excellent effect is obtained in that an immune reaction measurement for the same antigen can be performed quickly for different samples.

According to the fourth aspect of the present invention, a light reflecting surface is formed on one of the two end faces in the longitudinal direction of the core. Therefore, the light incident on the SPR sensor cell is
Since the surface plasmon resonance is generated, the surface plasmon resonance is generated when the light is reflected at the end face of the core and further returned, an excellent effect that the sensitivity as the SPR sensor is improved is obtained.

In the fifth aspect of the present invention, at least one of the two end faces in the longitudinal direction of the core is inclined with respect to the longitudinal direction of the core. As described above, in the case where the slope is formed on the end face of the core, an excellent effect that light from a light source can be efficiently introduced into the core is obtained.

According to the sixth aspect of the present invention, a void is formed in the clad along the core, and the through hole communicates with the void. For this reason, the sample can be injected and aspirated from the through-hole, and at the same time, since the space is a closed space except for the through-hole, when the SPR sensor cell is moved or removed from the immune reaction measurement device. But
An excellent effect that leakage of the sample can be prevented is produced.

According to the seventh aspect of the present invention, one end and the other end in the longitudinal direction of the core have different areas. As described above, when the cores have different cross-sectional areas, when light enters from the side having the larger cross-sectional area and exits from the side having the smaller cross-sectional area, the light is condensed and the light is efficiently transmitted to the spectroscope. And an excellent effect that light can be incident.

According to the eighth aspect of the present invention, a light source for irradiating predetermined light, an SPR sensor cell for generating surface plasmon resonance by receiving the light, and a spectrometer for analyzing a wavelength distribution of light emitted from the SPR sensor cell And a container.
The SPR sensor cell is constituted by a light-transmitting core and a clad that covers the core, a through hole communicating with the core is formed at a predetermined position of the clad, and the core at a position corresponding to the through hole is formed. A predetermined metal thin film was formed on the surface. As described above, the use of the SPR sensor cell in which the through-hole communicating with the core is formed in the clad has an excellent effect that the specimen can be easily held in the SPR sensor cell.

[Brief description of the drawings]

FIG. 1 is a perspective view showing an SPR sensor cell according to a first embodiment of the present invention. FIG. 1 (A) is a completed view, FIG.
(B) is the first clad, FIG. 1 (C) is the core, FIG. 1 (D)
Indicates the second cladding, respectively.

2 is a view showing the SPR sensor cell disclosed in FIG. 1, FIG. 2 (A) is an overall perspective view, and FIG. 2 (B) is a side sectional view.

FIG. 3 shows a view in which light is incident on the SPR sensor cell disclosed in FIG. 1, FIG. 3 (A) shows an overall perspective view, and FIG.
(B) is a side sectional view.

4A and 4B are diagrams illustrating a case where a metal thin film is formed on the SPR sensor cell disclosed in FIG. 1; FIG. 4A is a side cross-sectional view, and FIG. 4B is a diagram in which surface plasmon resonance occurs. FIG. 4C is a graph showing a wavelength distribution of light emitted from the SPR sensor cell.

FIG. 5 is a diagram illustrating a case where an antibody is immobilized on the SPR sensor cell disclosed in FIG.

6 is a diagram in which light is incident on the SPR sensor cell disclosed in FIG. 5, FIG. 6 (A) is a side sectional view when surface plasmon resonance occurs, and FIG. 6 (B) is an SPR sensor cell; 6 is a graph showing a wavelength distribution of outgoing light of FIG.

FIG. 7 is a side sectional view showing a case where a sample is injected into the SPR sensor cell disclosed in FIG. 6;

8 is a diagram in which light is incident on the SPR sensor cell disclosed in FIG. 7, FIG. 8 (A) is a side sectional view when surface plasmon resonance is generated, and FIG. 8 (B) is an SPR sensor cell; 6 is a graph showing a wavelength distribution of outgoing light of FIG.

FIG. 9 is a plan view showing an immunoreaction measurement device including the SPR sensor cell disclosed in FIG. 7;

FIG. 10 is a perspective view showing an SPR sensor cell according to a second embodiment of the present invention.

FIG. 11 is a plan view showing an immune reaction measuring device provided with the SPR sensor cell disclosed in FIG.

FIG. 12 is a perspective view showing a third embodiment of the present invention, and FIG. 12 (A) shows a sensor cell fixing base;
(B) is a diagram in which SPR sensor cells are arranged on a sensor cell fixing base.

FIG. 13 is a perspective view showing a modification of the third embodiment, and FIG. 13 (A) shows a sensor cell fixing base;
(B) is a diagram in which SPR sensor cells are arranged on a sensor cell fixing base.

FIG. 14 is a view showing a fourth embodiment, and FIG.
14A shows an overall perspective view, FIG. 14B shows a side sectional view, and FIG. 14C shows a plan view.

15 is a diagram in which light is incident on the SPR sensor cell disclosed in FIG. 14, FIG. 15 (A) is an overall perspective view, and FIG. 15 (B) is a side sectional view.

FIG. 16 is a side sectional view showing a case where a metal thin film is formed on the SPR sensor cell disclosed in FIG. 14;

17A and 17B are diagrams illustrating a case where light is incident on the SPR sensor cell disclosed in FIG. 16; FIG. 17A is a side sectional view when surface plasmon resonance occurs, and FIG. () Is a graph showing the wavelength distribution of light emitted from the SPR sensor cell.

FIG. 18 is a diagram illustrating a case where an antibody is immobilized on the SPR sensor cell disclosed in FIG.

19 is a diagram in which light is incident on the SPR sensor cell disclosed in FIG. 18, FIG. 19A is a side cross-sectional view when surface plasmon resonance occurs, and FIG.
4 is a graph showing a wavelength distribution of light emitted from a PR sensor cell.

FIG. 20 is a side sectional view showing a case where a sample is injected into the SPR sensor cell disclosed in FIG. 18;

21 is a diagram in which light is incident on the SPR sensor cell disclosed in FIG. 20, FIG. 20 (A) is a side sectional view when surface plasmon resonance occurs, and FIG.
4 is a graph showing a wavelength distribution of light emitted from a PR sensor cell.

FIG. 22 is a view for explaining a modification of the fourth embodiment. FIG. 22 (A) is a side perspective view, and FIG. 22 (B) is a graph showing a wavelength distribution of light emitted from an SPR sensor cell. is there.

FIG. 23 is a plan view showing an immunoreaction measurement device including the SPR sensor cell disclosed in FIG.

FIG. 24 is a plan view showing an immune reaction measurement device provided with a plurality of SPR sensor cells.

FIG. 25 is a diagram showing an immunoreaction measurement device provided with the SPR sensor cell of the present invention. FIG. 25 (A) shows the already-described immunoreaction measurement device, and FIG. FIG. 3 is a diagram showing a state where light is incident at an angle of.

FIG. 26 is a view showing an SPR sensor cell according to a fifth embodiment of the present invention. FIG. 26 (A) shows an overall perspective view, and FIG. 26 (B) shows a side sectional view.

FIG. 27 is a plan view showing an immune reaction measuring device having the SPR sensor cell disclosed in FIG. 26.

28 is a diagram showing the immune reaction measurement device disclosed in FIG. 27, and FIG. 28 (A) shows a case where a central axis of light from a light source and a longitudinal direction of a core are parallel, and FIG. 28 (B). Is SPR
FIG. 4 is a diagram illustrating a case where light is incident on a core of a sensor cell at a predetermined angle.

FIG. 29 is a perspective view showing an SPR sensor cell according to a sixth embodiment of the present invention. FIG. 29A shows an optical waveguide, and FIG. 29B shows a first example of the SPR sensor cell.
FIG. 29C shows a state in which the core and the third clad are joined.

30 is a perspective view showing an SPR sensor cell provided with the optical waveguide disclosed in FIG. 29, FIG. 30 (A) shows an overall perspective view, FIG. 30 (B) shows a substrate, and FIG. 30 (C) Indicates a second clad.

31 shows a diagram in which light is incident on the SPR sensor cell disclosed in FIG. 30, FIG. 31 (A) shows an overall perspective view, and FIG. 31 (B) shows a side sectional view.

FIG. 32 is a view showing a modified example of the second clad used in the SPR sensor cell of the present invention. FIG. 32 (A) shows a perspective view of the second clad, and FIG. 32 (B) shows a plan view. 32 (C) shows a side sectional view.

FIG. 33 (A) is a side sectional view showing another modified example of the second clad used in the SPR sensor cell of the present invention, and FIG. 33 (B) is a specimen injection sample corresponding to the second clad. It is a front view which shows the chip of FIG.

34 is a perspective view showing an SPR sensor cell according to a seventh embodiment of the present invention, FIG. 34 (A) shows an overall perspective view, FIG. 34 (B) shows a substrate, and FIG. 34 (C). Indicates a second clad.

35 shows the second cladding disclosed in FIG. 34, and FIG.
5A shows a plan view, and FIG. 35B shows a cross-sectional view.

FIG. 36 is a sectional view showing a modification of the second clad disclosed in FIG. 35;

FIG. 37 is a plan view showing an immune reaction measuring device according to an eighth embodiment of the present invention.

FIG. 38 is a plan view showing a modified example of the immune reaction measurement device disclosed in FIG. 37.

39 is a perspective view showing a ninth embodiment of the present invention, FIG. 39 (A) is an overall view, FIG. 39 (B) shows a substrate, FIG. 39 (C) shows a core, FIG. 39D shows the second clad.

FIG. 40 is a perspective view showing a tenth embodiment of the present invention, and FIG. 40 (A) shows a sensor cell fixing base;
(B) shows a state where the ER sensor cell on the sensor cell fixing base is fixed.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Immune reaction measuring device 3 SPR sensor cell 5 1st clad 7 Core 9 2nd clad 11 Depression 13 Through hole 15 Metal thin film 17 Dielectric film 19 Antibody (antigen) 21 Sample 23 Antigen (antibody) 25 Light source 49 Spectroscope L Light

 ────────────────────────────────────────────────── ─── Continuing on the front page (72) Inventor Kazuho Suzuki 2-1, Sakuranamiki, Tsuzuki-ku, Yokohama-shi, Kanagawa Prefecture F-term in the Suzuki R & D Co., Ltd. DA20 DB10 2G059 AA01 BB13 EE02 FF20 JJ17 KK01

Claims (8)

[Claims] 1. A core, through which light is transmitted, and a clad that covers the core, a through hole communicating with the core is formed at a predetermined position of the clad, and a surface of the core at a position corresponding to the through hole is provided. An SPR sensor cell, wherein a predetermined metal thin film is formed thereon. 2. An optical waveguide comprising: a plate-shaped first clad; a core provided on the first clad; and a second clad covering the core. An SPR sensor cell, wherein a through hole communicating with the core is formed at a predetermined position, and a predetermined metal thin film is formed on a surface of the core at a position corresponding to the through hole. 3. The SPR sensor cell according to claim 1, wherein at least two cores are provided, and at least two through holes are formed in the clad corresponding to the cores. 4. The SPR sensor cell according to claim 1, wherein a light reflecting surface is formed on one of the two end surfaces in the longitudinal direction of the core. 5. The SPR according to claim 1, wherein at least one of the end faces in the longitudinal direction of the core is inclined with respect to the longitudinal direction of the core. Sensor cell. 6. The S according to claim 1, wherein a void is formed in the clad along the core, and the through hole is communicated with the void.
PR sensor cell. 7. The core according to claim 1, wherein the one end and the other end of the core in the longitudinal direction have different areas.
7. The SPR sensor cell according to 2, 3, 4, 5 or 6. 8. The SPR comprising: a light source for irradiating a predetermined light; an SPR sensor cell for emitting the light to generate surface plasmon resonance; and a spectroscope for analyzing a wavelength distribution of light emitted from the SPR sensor cell. The sensor cell includes a core through which the light passes and a clad that covers the core, a through hole communicating with the core at a predetermined position of the clad, and a surface of the core at a position corresponding to the through hole. An immunological reaction measuring device characterized in that a predetermined metal thin film is formed on the device.