JP2000356585A - Spr sensor cell and immune reaction-measuring device using it - Google Patents

Abstract

PROBLEM TO BE SOLVED: To easily fix an antibody and to retain a specimen and to improve measurement accuracy by setting the surface of a core other than a surface where a surface plasmon resonance(SPR) sensor part is formed and a surface that opposes it to a low light reflection factor surface. SOLUTION: A core 7 that is arranged on a plate-shaped clad 5 is pinched from both sides by a middle clad 6, and the surfaces are covered with a clad (upper-layer plate) 9 where a through hole (SPR sensor part) is formed at nearly the central part, thus forming an SPR sensor cell 3. Then, surface treatment such as slit glass and black painting is made to a side surface (junction surface with the middle clad 6) of the core 7 where no SPR sensor part is formed as a low reflection factor surface. As a result, only light being reflected mainly by the SPR sensor part and a surface that opposes it out of light that is applied to the core 7 is emitted from the SPR sensor cell 3, and light arriving at the low reflection factor surface is hardly ever reflected and is eliminated, thus determining only the wavelength distribution of light being used for an SPR phenomenon with improved sensitivity.

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)

[0005] The RIA method has recently been rarely used because it requires the use of isotopes. 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

[0007] 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.

[0008] Many reagent manufacturers provide various reagents as assay kits for the ELISA method. 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.

Incidentally, 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 the light, the wave number of the evanescent field and the wave number of the surface plasmon resonance can be matched, and the 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.
IACORE product 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 an immune reaction 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.

[0013]

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 an immunological reaction is actually measured, 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.

[0016]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an immunoreaction measuring apparatus using an SPR sensor cell in which the inconvenience of the prior art can be improved and an antibody can be fixed and a sample can be easily retained.
With that purpose. It is another object of the present invention to provide an SPR sensor cell with high measurement accuracy and an immunoreaction measurement device using the same.

[0017]

In order to achieve the above object, according to the present invention, there is provided a core having an SPR sensor portion formed on a surface thereof and transmitting light from a predetermined light source, and a core surrounding the core and having the SPR sensor portion. A cladding that covers a region other than the SPR sensor unit, and that a surface other than the surface on which the SPR sensor unit is formed and the surface facing the SPR sensor unit around the core is configured as a low-reflectance surface with low light reflectance. Is taking measures.

The function and function of the immunoreaction measuring apparatus thus constructed will be described. First, a light source emits light in a certain band. Then, this light is introduced into the core of the SPR sensor cell. In the core, light travels while repeating reflection, and causes surface plasmon resonance in the SPR sensor section in the SPR sensor cell. At this time, the wavelength at which surface plasmon resonance is generated differs depending on the presence or absence of an immune reaction.

Light that has caused surface plasmon resonance is emitted from the core. On the other hand, light that has reached the vicinity of the surface of the core other than the SPR sensor unit regardless of surface plasmon resonance is:
Does not reflect off low reflectance surfaces. Therefore, only the main light related to the surface plasmon resonance is emitted from the core. The optical analysis means analyzes the wavelength distribution of the light emitted from the core. In the actual measurement of the immune reaction, the wavelength distribution of the light from the light source is analyzed in advance, and the wavelength distribution after the immune reaction is compared to analyze which wavelength of the light has attenuated. An immunoreactivity measurement is performed by this analysis.

[0020]

DESCRIPTION OF THE PREFERRED EMBODIMENTS [First Embodiment] The first embodiment of the present invention
An embodiment will be described with reference to FIG.

[Overview of SPR Sensor Cell] FIG.
1 shows a perspective view of an SPR sensor cell according to the present embodiment. The SPR sensor cell 3 of the present embodiment uses an optical waveguide (core). More specifically, SPR sensor cell 3
A first clad (substrate) 5 in the form of a plate, a core 7 disposed on the first clad 5, two intermediate clads 6 sandwiching the core 7 from both sides, 6 and a second clad (upper plate) 9 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 first clad 5 is made of glass or the like and has a thin plate shape. The core 7 through which light is transmitted is mounted on the first clad 5. The core 7 extends over the entire length of the SPR sensor cell 3. The core 7 is made of glass, plastic, or the like.

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 attached to the core 7 and the intermediate clad 6. When attaching the core 7 to the first clad 5 using an adhesive, it is necessary to use an adhesive made of a material having a lower refractive index than the refractive index of the core 7 in consideration of attenuation of light by the adhesive. There is. Specifically, a UV adhesive may be used. In addition, a so-called matching oil or the like may be used for joining the core 7 and each clad. However, even when using matching oil, etc.,
It is necessary to select an appropriate refractive index.

As described above, the intermediate cladding 6 is mounted so as to sandwich the core from both sides. The intermediate cladding 6 has a thickness equivalent to that of the core 7. Therefore, when the core 7 and the intermediate clad 6 are joined, a plate-like member having a uniform thickness is obtained.

A predetermined through-hole 13 is formed substantially at the center of the second clad 9. More specifically, the through hole 1 extends from the upper surface of the second clad 9 to the upper surface of the core 7.
3 are formed. Therefore, a part of the surface of the core 7 is exposed toward the through hole 13. Then, a metal thin film is formed on a portion of the core 7 corresponding to the through-hole 13 as described later to form the SPR sensor unit 8.

Here, as a method of forming the through-hole 13 in the second clad 9, it is conceivable to make a hole in a single plate-shaped second clad 9. That is, the through-hole 13 is formed at a position corresponding to the core 7 using a predetermined drilling machine.

Since the second cladding 9 is configured as described above, a cubic space is formed in the SPR sensor cell 3 by the through hole 13 of the second cladding 9 and the surface of the core 7. This space serves as a sample storage unit 14 for storing a sample when performing an immune reaction measurement. As described above, in the present embodiment, the second clad 9 is formed from a single plate-like member. However, the present invention is not limited to this, and may be configured by combining a plurality of plate members. In this case, the processing step of the through-hole 13 of the second clad 9 becomes unnecessary. Also, the second
It is also desirable that the clad 9 and the intermediate clad 6 are integrally formed. This is because the assembly process of the SPR sensor cell 3 can be reduced.

The side surface of the core 7 is subjected to a predetermined surface treatment. This surface treatment is for removing light reflected on a surface other than the SPR sensor unit described later.
Specifically, in a core having a rectangular cross section, a side surface on which the SPR sensor section is not formed is ground glass, and Al coating or black coating is performed. These are surface treatments intended to prevent light from being reflected. The surface treatment is performed on the joint surface with the intermediate clad in the figure.

As described above, when the surface treatment is performed on the surface other than the surface on which the SPR sensor portion is formed and the surface opposite thereto,
Only light reflected mainly on the SPR sensor unit and the surface facing the SPR sensor unit is emitted from the SPR sensor cell. Therefore, if this light is analyzed by the optical analysis means, as described later,
Only the wavelength distribution of the light used for the surface plasmon resonance phenomenon can be known with high sensitivity. In the present embodiment, both sides of the core are subjected to surface treatment, but the present invention is not limited to this. For example, when the SPR sensor unit is formed on the upper surface of the core, the lower surface of the core may be subjected to a surface treatment.

There are various surface treatment techniques as described above (such as Al coating). However, if the surface is ground glass at the stage of manufacturing the core, even if the surface corresponding to the SPR sensor portion and only the surface facing this are polished without special surface treatment, It is possible to manufacture a core that can obtain the same function and effect. Therefore, if the core manufacturing process is devised and the surface of the core becomes ground glass, only the necessary surface needs to be polished, and the manufacturing process can be reduced.

[Structure of SPR Sensor Unit] Next, a detailed structure of a portion of the surface of the core 7 facing the specimen storage unit 14 will be described. Since this part is a part that actually functions as an SPR sensor (SPR sensor unit 8), its structure is important. FIG. 2 shows a sectional view of the SPR sensor cell 3. Specifically, a metal thin film 15 and a dielectric film 17 are sequentially formed on the surface of the core 7, and an antibody (or antigen) 19 is fixed on the surface of the dielectric film 17. This SPR sensor portion is a surface on which the above-described surface treatment has not been performed.

More specifically, in order to form the SPR sensor section 8, the core 7 is coated with Au (gold) as the metal thin film 15 by vapor deposition or the like. However, the SPR sensor section 8 can be configured even if the metal thin film 15 is not Au but Ag (silver). Here, when the core 7 is glass and the metal thin film 15 is Au, it is desirable to coat the surface of the core 7b with Cr (chromium) having a thickness of several nm. This is because the metal thin film 15 is stabilized by coating Au with Cr.

Next, an antibody (or antigen) 19 is immobilized on the surface of 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. This is because, by immobilizing an antibody that specifically reacts with an antigen contained in the specimen, the presence of the specific antigen in the specimen can be known by immunoreactivity measurement.

[Function of SPR Sensor Cell] Next, SPR
The function of the sensor cell 3 will be described. First, a sample containing a predetermined antigen is stored in the sample storage unit 14 of the SPR sensor cell 3. Accordingly, if an antigen specifically reacting with the antibody 19 fixed on the dielectric film 17 is contained in the specimen, an immune reaction occurs. Due to this immune reaction, surface plasmon resonance occurs in the SPR sensor unit 8. This attenuates the intensity of light of a specific wavelength that causes surface plasmon resonance.

At this time, of the light incident on the core, SP
Light that is reflected by the R sensor unit and does not reach the other surface passes through the core as it is and is emitted from the SPR sensor cell.
On the other hand, the light that reaches the surface subjected to the surface treatment described above is
Almost no reflection. Therefore, light not used for surface plasmon resonance is removed. As a result, when the light emitted from the SPR sensor cell is introduced into the optical analysis means and the wavelength distribution of the light L emitted from the core 7 after the immune reaction has occurred is analyzed, the wavelength distribution when no immune reaction occurs is obtained. Will be different.

The case where the low reflectance surface is formed on the core 7 in the SPR sensor cell 3 has been described above. However, the present invention is not limited to this.
That is, a surface treatment may be performed on the bonding surface on the clad side to be bonded to the core 7. As described above, by forming the low-reflectance surface on the clad side, the same effect as when the low-reflectance surface is formed on the core can be obtained.

[Immunological Reaction Measuring Apparatus] Next, the SP of the present invention
The immune reaction measuring device 1 using the R sensor cell 3 will be described. FIG. 3 is an overall schematic diagram of the immune reaction measuring device. As shown in this figure, a light source 11 is disposed in the vicinity of the SPR sensor cell 3, and a condensing lens 53 and an optical fiber 51 are sequentially disposed on the opposite side of the light source 11 with the SPR sensor cell 3 interposed therebetween.
And an optical analysis means 49 are provided. The light transmitted through the condenser lens 53 is incident on the optical fiber 51 via the receptacle 55 and the optical connector 57.

[Light Source] Next, the light source will be described. The light source 11 emits light L in a predetermined wavelength band, and specifically, a white LED lamp is used. The immune response measuring device 1 of the present invention analyzes the change in the wavelength distribution of the light L before and after the immune reaction in the light L transmitted through the SPR sensor cell 3, and thereby measures the immune response. Therefore, it is desirable that the light source 11 emits light L having a stable wavelength distribution. Commercially available white LED lamps have a wavelength band of light L to be irradiated from 450 [nm] to 750 [n].
m]. The light source 11 may be a light source 11 other than the above-mentioned white LED lamp as long as it can emit light in a certain wavelength band. In particular,
A halogen lamp may be used.

Directivity (irradiation angle) of white LED lamp
Is an irradiation angle of about 20 to 60 degrees as shown in FIG. In this point, it is different from a halogen lamp having an irradiation angle of 180 degrees or more. Here, the irradiation angle is, for convenience,
The angle is set at an intermediate point in the irradiation direction of the irradiation part having a predetermined luminance or higher. As described above, when the light source 11 having high directivity is used, a condenser lens, which will be described later, may not be necessary to make the light L incident on the SPR sensor cell 3. In addition, white L
Some ED lamps have an irradiation angle of about 140 degrees depending on the characteristics of the ED lamp. Therefore, the present invention can be applied to the case where the light L is applied to a plurality of cores in the SPR sensor cell 3.

When a white LED lamp is used as the light source 11, the cost is one tenth that of a halogen lamp.
And the power consumption is about 1/30.
For this reason, since the battery can be driven and the size can be reduced, portability is improved, and application to various uses is possible.

[Optical Analysis Means] The optical analysis means 49 shown in FIG.
Then, the wavelength distribution of the incident light L is analyzed. More specifically, the wavelength distribution before an immune reaction occurs is checked in advance. That is, the wavelength distribution is measured in a state where the sample is not put into the sample storage unit 14 (or a state where the sample is filled with no antigen). Then, the sample storage unit 1
A sample to be subjected to an immune reaction measurement is injected into 4 to generate an immune reaction. After that, 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. A spectroscope is used to measure the actual wavelength distribution.

For measuring the wavelength distribution, it is conceivable to use a photodiode in addition to using a spectroscope. In this case, a wavelength that is attenuated by the immune reaction is estimated in advance, a filter that can transmit only light of this wavelength is provided, and the immune reaction can be measured by knowing the attenuation of the light of the wavelength. Alternatively, with a plurality of photodiodes, to provide a filter that can transmit light of different wavelengths for each photodiode,
The immune response may be measured by analyzing the attenuation of light of each wavelength.

[Other Configurations] In this embodiment, as shown in FIG. 3, an optical fiber 5 is provided between an SPR sensor cell 3 and an optical analyzer (spectroscope or photodiode) 49.
1 is equipped. Further, the optical fiber 51 and the SPR
A condenser lens 53 is provided between the sensor cells 3. Therefore, the light L emitted from the SPR sensor cell 3
Is condensed by a condenser lens 53 and transmitted to an optical analyzer 49 via a receptacle 55 provided at the tip of the optical fiber 51. Here, the optical fiber 51 is connected to the optical analysis unit 49.
Is connected via the optical fiber connector 57, and can be detached as necessary. Therefore,
By connecting optical fibers of different lengths, it is also possible to measure an immune reaction at a location remote from the optical analysis means 49.

[Modification of SPR Sensor Cell] Next, FIG.
A modified example of the SPR sensor cell will be described based on FIG. The SPR sensor cell 3b differs from the SPR sensor cell described above in having two cores. More specifically, the SPR sensor cell 3b includes a plate-shaped first clad (substrate) 5, two cores 7a and 7b disposed on the first clad 5, and the core 7a and 7b. A center clad 6b, two end clads 6a sandwiching the two cores 7a and 7b from both outer sides, and a second covering the surfaces of the cores 7a and 7b, the center clad 6b and the both end clads 6a.
And a clad (upper plate) 9.

The center cladding 6b is divided into two, and a space is formed in the central region of the SPR sensor cell 3b. This space corresponds to a predetermined through hole 13 formed substantially at the center of the second clad 9.
More specifically, from the upper surface of the second clad 9, each core 7
The through hole 13 is formed up to the space between a and 7b. That is, the cores 7a and 7b are arranged parallel to each other at a predetermined interval. And each of these cores 7a,
A through-hole 13 having a width substantially equal to the interval of 7b is formed. Therefore, the cores 7a,
Part of the surface of 7b is exposed.

Since the second clad 9 is configured as described above, the through hole 13 of the second clad 9 and the two cores 7
Cube-shaped space is formed by a, 7b, the center clad 6b, the surface of the first clad 5, and the like. This space serves as a sample storage unit for storing a sample when performing an immune reaction measurement. The portion of the core of the SPR sensor cell that is exposed to the specimen storage unit is the SPR sensor unit. Specifically, two side surfaces of the surfaces of the two cores facing the sample storage unit are SPR sensor units.

On the other hand, both the upper and lower surfaces of each core are subjected to a surface treatment for obtaining a low reflectance surface, similarly to the above-described SPR sensor cell. Specifically, of the surfaces of the cores shown in FIG. 5C, both upper and lower surfaces are low-reflectance surfaces. Conversely, the surface (side surface of the core) facing the sample storage section is in a normal surface state. By setting the surface other than the surface on which the SPR sensor section is formed and the surface facing the SPR sensor portion as the low reflectance surface, the sensitivity at the time of measuring the immune reaction can be improved.

Further, by equipping two cores 7a and 7b for one specimen storage section as described above, it becomes possible to measure different immune reactions for one specimen. That is, different antibodies (or antigens) are provided on the surfaces of the cores 7a and 7b (positions exposed to the specimen storage section).
, And the immune response measurement can be performed separately for each item, so that the immune response measurement of multiple items can be performed in a short time.

[Another Modified Example of SPR Sensor Cell] FIG.
FIG. 9 is a perspective view showing another modification of the SPR sensor cell. The SPR sensor cells 3c and 3d are
The feature is that surface treatment is applied to portions other than the end surfaces of a and 7b. Specifically, the cores 7, 7a, 7b
The end faces of the first clad, the second clad, the intermediate clad, and the like except for the above are processed so as to be hard to transmit light.
As the processing, it is formed in the form of ground glass or aluminum (A
l) It is conceivable to apply a coating or a black paint. In the case of forming in a ground glass shape, a method such as sandblasting is conceivable.

The reason why light is hardly transmitted through the end face of each clad is to allow light to be incident only on the cores 7, 7a, and 7b. Because core 7,7
When light is incident from the cladding end faces other than a and 7b,
This is because the mixed light may enter the cores 7, 7a, and 7b, which may reduce the measurement accuracy of the immune reaction measurement.

[Second Embodiment] FIG. 7 shows a second embodiment of the present invention.
It is a schematic structure figure showing immune response measuring device 1B concerning an embodiment. This immunoreaction measurement device 1B is also provided with the S
The PR sensor cell 3 is used. Here, the same parts as those in the first embodiment will be described using the same reference numerals.
The immunoreaction measurement device 1B is different from the immunoreaction measurement device 1 according to the first embodiment in that the number of condenser lenses is further increased by one. More specifically, the light source (white L
A condenser lens 53b is provided between the ED lamp 11 and the SPR sensor cell 3. This condenser lens 53b
Is the light L emitted from the light source (white LED lamp) 11
In order to efficiently introduce the light L into the core.

The diameter and curvature of the condenser lens 53b are determined according to the irradiation angle (directivity) of the white LED lamp. In this embodiment, the white LED lamp and S
A condenser lens 53b between the PR sensor cells 3 and SP
The same condenser lens 53 is used between the R sensor cell 3 and the receptacle 55. This is because the production cost of the immune reaction measuring device can be reduced by suppressing the types of components. However, different condenser lenses 53 and 53b may be used depending on the characteristics of the white LED lamp and the SPR sensor cell 3.

[Third Embodiment] FIG. 8 is an overall schematic diagram of an immune reaction measuring device 1C according to a third embodiment.
The immunoreaction measurement device 1C is obtained by equipping the immunoreaction measurement device according to the second embodiment with another condensing lens 53c and an optical fiber 51b. More specifically, a condensing lens 53 is sequentially provided downstream of the white LED lamp.
c, a receptacle 55c, an optical fiber 51b, and a receptacle 55b. The condenser lens 53c used for them is the same as that used in the above-described embodiment. The same optical fiber 51b is used.

The receptacles 55b and 55c are for efficiently introducing the light transmitted through the condenser lens 53c and condensed into the optical fiber 51b. Here, the receptacle 5
Optical fiber connectors 57b and 57c are connected to 5b and 55c, respectively.
The optical fiber 51b is connected to the optical fiber 51b via c. As described above, by connecting the light source 11 and the SPR sensor cell 3 to each other by the optical fiber 51b, it is possible to arrange the light source 11 and the SPR sensor cell 3 apart from each other.

[Fourth Embodiment] FIGS. 9 and 10 are overall schematic diagrams showing an immune reaction measuring apparatus 1D according to a fourth embodiment of the present invention. The present embodiment is characterized in that the SPR sensor cell 3D includes a plurality of specimen storage units 14. Hereinafter, this will be described in detail.

First, the SPR sensor cell 3D has eight sample storage sections 14. And each sample storage unit 1
Eight cores 7 are provided corresponding to the four. In the present embodiment, the core 7 forms the bottom surface of the sample storage unit 14. Therefore, the bottom surface serves as the SPR sensor unit 8. In the SPR sensor section 8, a metal thin film, a dielectric film, and an antibody (or antigen) are fixed on the surface of the core 7 in the same manner as described above. In the immunoreaction measuring apparatus 1D of the present embodiment, eight cores 7 are arranged in parallel on the first clad 5d, and an intermediate clad 6d is provided between the cores 7 and on both outer ends. I do. The second cladding 9d is provided on the core 7 and the intermediate cladding 6d.

The side surface of each core, which is in contact with each intermediate clad 6d, has been subjected to the above-described surface treatment. In the present embodiment, eight cores 7 are used, and both side surfaces (a total of 16 surfaces) of each core 7 are low reflectance surfaces.
In addition, a surface treatment is performed on an end surface on the light incident surface side of the SPR sensor cell 3D. This is a ground glass like the surface treatment described above, and is an Al coating or a black coating. Note that all the cores 7 have the same characteristics.

The immunoreaction measuring apparatus 1D is provided with a light source (white LED lamp) 11, a condenser lens 53, a receptacle 55, and an optical fiber 51d corresponding to each core 7. That is, eight sets of these components are provided. Each optical fiber 51d is connected to an optical coupler 86. The optical coupler 86 has a function of transmitting the light transmitted from the eight optical fibers 51d to the optical analysis means.

As described above, the SPR provided with a plurality of cores 7
In the case where the sensor cell 3D is used, it is possible to easily perform the measurement of the immune reaction of multiple items (for other kinds of antigens or antibodies) in a short time. In the present embodiment, the case where eight cores 7 are used is described as an example, but the number of cores 7 may be 2 to 7 or 9 or more. Also in this case, it is necessary to equip the light source 11, the condenser lens 53 and the optical fiber 51d according to the number of the cores 7.

[Fifth Embodiment] FIG. 11 is an overall schematic diagram showing a fifth embodiment of the present invention. In this embodiment,
It has almost the same configuration as the fourth embodiment. The difference is that a condenser lens 53b is provided between the light source 11 and the SPR sensor cell 3E. That is, each light source 1
Condenser lens 53b between each core corresponding to 1
Are arranged. This is because, when the condenser lens 53b is provided as described above, the light emitted from the light source 11 is appropriately collected and can be efficiently introduced into the SPR sensor cell 3E.

Further, by providing a condenser lens 53b corresponding to each light source 11 and each core, each light source 1
Even when there is an individual difference between 1 and the core, the optimum condenser lens 53b can be selected and used according to the characteristics of each light source 11 and the core. Therefore, it is possible to reduce the measurement error between each core.

[Sixth Embodiment] FIG. 12 is an overall schematic diagram showing a sixth embodiment of the present invention. In this embodiment,
It has a configuration substantially similar to that of the fifth embodiment, except that an optical fiber 5 is provided between the light source 11 and the SPR sensor cell 3F.
1b. Thus, the optical fiber 5 is interposed between the light source 11 and the SPR sensor cell 3F.
1b, the light source 11 and the SPR sensor cell 3
F can be arranged apart from it. Further, even when the immune reaction measuring device 1E is configured to be small, the light source 1
1 and the SPR sensor cell 3F can be arranged more freely.

[Seventh Embodiment] FIG. 13 is an overall schematic diagram showing a seventh embodiment of the present invention. In the present embodiment, the SPR sensor cell 3 having the plurality of sample storages 14
G is an immunoreaction measurement device 1G which is simply equipped with a pair of light sources 11 and a condenser lens 53. In the actual measurement of the immune response, the SPR sensor cell 3G is moved to measure the immune response of a different specimen storage unit 14.
Hereinafter, this will be described in detail.

The SPR sensor cell 3G used in the present embodiment has eight cores and eight sample storage sections 14 corresponding to each core. The structure of the SPR sensor unit 8 is the same as that described above. The SPR sensor cell 3G is mounted on a predetermined cell moving mechanism 75.
The cell moving mechanism 75 moves the SPR sensor cells 3G along the arrangement direction of each core. Specifically, the SPR sensor cell 3G moves along the two rails 74.

The cell moving mechanism 75 has its stop position determined so that each core of the SPR sensor cell 3G stops at a position corresponding to the light source 11 and the condenser lens 53. Actually, in order to move the SPR sensor cell 3G, an external force for movement must be applied to the SPR sensor cell 3G from outside. For example, when the SPR sensor cell 3G is moved by a wire or a belt, or when the rail 74 is formed of a ball screw,
The SPR sensor cell 3G may be moved by rotating.

On the other hand, the light source 11 and the condenser lens 53 may be moved while the SPR sensor cell 3G is fixed. At this time, the receptacle 55 is also moved with the movement of the condenser lens 53. Since the receptacle 55 and the optical analysis means 49 are connected by the optical fiber 51, the receptacle 55 can be moved flexibly. However, when the light source 11 and the condenser lens 53 are moved, the setting of the optical system (for example, the distance between the light source 11 and the SPR sensor cell 3G, the distance between the condenser lens 53 and the SPR sensor cell 3G, etc.) does not change. You need to move it.

[Eighth Embodiment] FIG. 14 is an overall schematic diagram showing an eighth embodiment of the present invention. In this embodiment,
The difference from the seventh embodiment is that a condenser lens 53b is provided between the light source 11 and the SPR sensor cell 3H. Other configurations are the same. This condenser lens 5
3b is for condensing the light L emitted from the light source (white LED lamp) 11 and efficiently introducing the light L into the inside of the core.

The diameter and curvature of the condenser lens 53b are determined according to the irradiation angle (directivity) of the white LED lamp. In this embodiment, the white LED lamp and S
A condenser lens 53b between the PR sensor cells 3H and S
The same condenser lens 53 is used between the PR sensor cell 3H and the receptacle 55. This is because the production cost of the immune reaction measuring device can be reduced by suppressing the types of components. However, different condenser lenses 53 and 53b may be used depending on the characteristics of the white LED lamp and the SPR sensor cell 3.

[Ninth Embodiment] FIG. 15 is an overall schematic diagram showing a ninth embodiment of the present invention. In this embodiment,
It has a configuration substantially similar to that of the eighth embodiment, except that an optical fiber 5 is provided between the light source 11 and the SPR sensor cell 3I.
1b. Thus, the optical fiber 5 is interposed between the light source 11 and the SPR sensor cell 3I.
1b, the light source 11 and the SPR sensor cell 3
It is possible to dispose the I. Further, even when the immune reaction measuring device 1I is configured to be small, the light source 1
1 and the SPR sensor cell 3I can be arranged more freely.

[0070]

As described above, according to the present invention, S
A PR sensor part is formed and includes a core for transmitting light from a predetermined light source, and a clad surrounding the core and covering an area other than the SPR sensor part, and an SPR sensor part around the core is formed. The surfaces other than the surface and the surface facing the surface were configured as low reflectance surfaces having low light reflectance. For this reason, light that mainly causes surface plasmon resonance in the SPR sensor unit and that does not reach the other surface of the core is emitted from the core. On the other hand, light that has reached the vicinity of the surface of the core other than the SPR sensor unit irrespective of surface plasmon resonance is not reflected by the low reflectance surface. Therefore, only the main light related to the surface plasmon resonance is emitted from the core. As a result, it is possible to measure the wavelength of light that has caused surface plasmon resonance with high sensitivity.

[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, and FIG.
1B shows a first clad, FIG. 1C shows a core and a clad bonded to the core, and FIG. 1D shows a second clad.
Show cladding.

FIG. 2 shows a cross-sectional view of the SPR sensor cell disclosed in FIG.

FIG. 3 is an overall schematic diagram showing an immune reaction measuring device using the SPR sensor cell disclosed in FIG.

FIG. 4 is a diagram showing a light source (white LED lamp) used in the immune reaction measuring device disclosed in FIG.

FIG. 5 shows an SPR used in the immunological reaction measuring device of the present invention.
It is a perspective view which shows the modification of a sensor cell, FIG.5 (A) shows the whole view, FIG.5 (B) shows 1st clad, FIG.
FIG. 5C shows a core and a clad bonded to the core, and FIG. 5D shows a second clad.

FIG. 6 shows an SPR used in the immunological reaction measuring device of the present invention.
FIG. 6A is a perspective view showing a modified example of the sensor cell. FIG. 6A has one core, and FIG. 6B has two cores.

FIG. 7 is an overall schematic diagram showing a second embodiment of the present invention.

FIG. 8 is an overall schematic diagram showing a third embodiment of the present invention.

FIG. 9 is an overall schematic diagram showing a fourth embodiment of the present invention.

10 is a perspective view showing an SPR sensor cell used in the immunoreaction measurement device disclosed in FIG. 9, and FIG.
Shows an overall view, FIG. 10B shows a first clad,
FIG. 10C shows a core and an intermediate clad.
(D) shows the second clad.

FIG. 11 is an overall schematic diagram showing a fifth embodiment of the present invention.

FIG. 12 is an overall schematic diagram showing a sixth embodiment of the present invention.

FIG. 13 is an overall schematic diagram showing a seventh embodiment of the present invention.

FIG. 14 is an overall schematic diagram showing an eighth embodiment of the present invention.

FIG. 15 is an overall schematic diagram showing a ninth embodiment of the present invention.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Immune reaction measuring device 3 SPR sensor cell 5 First clad 7 Core 8 SPR sensor part 9 Second clad 11 Light source 13 Through hole 14 Sample storage part 49 Optical analysis means L Light

 ──────────────────────────────────────────────────続 き Continued on the front page F term (reference) 2G057 AA12 AA14 AB01 BA03 HA01 HB03 2G059 AA01 BB12 CC17 EE06 EE12 GG02 HH02 JJ11 JJ17 KK01

Claims (7)

[Claims] 1. A core having an SPR sensor portion formed on a surface thereof and transmitting light from a predetermined light source, and a clad surrounding the core and covering a region other than the SPR sensor portion, wherein a periphery of the core is provided. 2. The SPR sensor cell according to claim 1, wherein the surface other than the surface on which the SPR sensor portion is formed and the surface facing the SPR sensor portion are configured as low-reflectance surfaces having low light reflectance. 2. A core having an SPR sensor portion formed on a surface thereof and transmitting light from a predetermined light source, and a clad surrounding the core and covering a region other than the SPR sensor portion. An SPR sensor cell, characterized in that the surface facing the SPR sensor is a low reflectance surface having a low light reflectance. 3. The SPR sensor cell according to claim 1, wherein the low-reflectance surface has a ground glass shape. 4. The SPR according to claim 1, wherein the low reflectivity surface is formed by aluminum coating.
Sensor cell. 5. The SPR sensor cell according to claim 1, wherein the low reflectance surface is formed by coating with a black paint. 6. The light incident side end surface and the light exit side end surface of the SPR sensor cell, except for the core,
The SPR sensor cell according to claim 1, 2, 3, 4, or 5, wherein a surface treatment is performed so that light is hardly transmitted. 7. The SPR sensor cell according to claim 1, 2, 3, 4, 5, or 6, a light source for irradiating predetermined light to a core of the SPR sensor cell, and a wavelength distribution of light transmitted through the core. An immunological reaction measuring device comprising: an optical analysis means for analyzing.