JP2000346845A - SPR sensor cell and immunoreaction measuring device using the same - Google Patents

Abstract

(57) [Problem] To provide an inexpensive SPR sensor cell and an immune reaction measuring device using the same. SOLUTION: An SPR sensor unit 8 is formed in a predetermined area, and a plate-shaped core 7 transmitting light from a light source 11 is provided.
A first clad 5 covering the plate-shaped core 7 from one surface; and a second clad 8 covering a region other than the SPR sensor portion of the plate-shaped core 7 from the other surface.

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 SPR sensor cell in which the inconvenience of the prior art can be improved, and in which an antibody can be fixed and a sample can be easily retained, and an immunoreaction measuring device using the same. .

[0017]

In order to achieve the above object, in the SPR sensor cell of the present invention, an SPR sensor portion is formed in a predetermined area and a plate-shaped core for transmitting light from a light source is provided. The first clad covers the plate-shaped core from one surface, and the second clad covers a region other than the SPR sensor portion of the plate-shaped core from the other surface.

The function and function of the immunoreaction measuring apparatus thus constructed will be described. First, light of a certain wavelength band is emitted from the light source. 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. 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.

Further, in the immunoreaction measuring apparatus of the present invention, a light source for emitting light in a predetermined wavelength band, an SPR sensor cell which receives the light from the light source to generate surface plasmon resonance, and emits the light from the SPR sensor cell. Light analyzing means for analyzing the wavelength distribution of the reflected light, wherein the SPR sensor cell includes a plate-shaped core having an SPR sensor portion formed in a predetermined region and transmitting light from a light source, and The first cladding covers one surface and the second cladding covers the plate-like core from the other surface.

[0021]

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
Is a plate-shaped first clad (substrate) 5, a plate-shaped core 7 disposed on the first clad 5, and a second clad (upper plate) 9 disposed on the core 7. It consists of. 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. Since the core 7 is placed on the upper surface of the first clad, the surface is polished smoothly. Other surfaces need not be polished or the like. This is because it is better that light does not enter from the end face of the first clad, and it is sometimes better that the end face is not smooth.

The core 7 is a member through which light for measuring an immune reaction is transmitted, and is made of glass, plastic, or the like. The core 7 is made of a plate-like member like the first clad 5, and has a width and a length substantially equal to those of the first clad 5. Therefore, the core 7 covers almost the entire upper surface of the first clad 5. The lower surface of the core is the first clad 5
And is polished smoothly. Similarly, the light incident surface and the light exit surface of the core 7 are also polished smoothly. Here, 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.

When the core 7 is attached to the first clad 5 using an adhesive, an adhesive made of a material having a lower refractive index than the core 7 is used in consideration of attenuation of light by the adhesive. Must be used. As an example, 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 a matching oil or the like is used, it is necessary to select an appropriate refractive index. The upper surface of the core 7 is also polished smoothly, and a second clad 9 described later is joined to the upper surface of the core 7.

The second clad 9 is also made of glass or plastic, and has a length and a width substantially equal to those of the first clad 5 and the core 7. The lower surface of the second clad 9 is also polished smoothly, and is joined to the upper surface of the core 7. Further, a predetermined through hole 13 is formed at a substantially central portion of the second clad 9. More specifically, a through hole 13 is formed from the upper surface of the second clad 9 to the upper surface of the core 7. 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 the surface 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 that a single plate-shaped second clad 9 is punched. That is, the through-hole 13 is formed at a position corresponding to the core 7 using a predetermined drilling machine. 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 drilling of the through-hole 13 of the second clad 9 becomes unnecessary.

Since the second clad 9 is configured as described above, a cubic space is formed on the upper surface of the SPR sensor cell 3 by the through-hole 13 of the second clad 9 and the surface of the core 7. This space serves as a sample storage unit 14 for storing a sample to be measured for an immune reaction.

Next, the relationship between the refractive indices of the first clad 5, the second clad 9, and the core 7 will be described.
In the SPR sensor cell 3, the following relationship is established between the refractive indices of the respective members so that the light introduced into the core 7 is appropriately transmitted through the core 7. For example, assuming that the refractive index of the first cladding is n1, the refractive index of the core is n2, and the refractive index of the second cladding 9 is n3, the relationship of n2> n3 = n1 or n2> n3 and n2> n1 holds. . This is a requirement for the light introduced into the core 7 to travel by repeating total reflection.

As described above, when the core is formed of one plate-shaped member, there are the following advantages as compared with the case where a plurality of members are combined. That is, when the surface of the core needs to be polished smoothly, a large area can be polished in one polishing step, and the working efficiency is high. Further, the number of joining steps can be reduced as compared with a case where a plurality of members are combined, and precision processing of the joining surface for joining is unnecessary. Therefore, it is possible to reduce the manufacturing cost of the PR sensor cell. In addition, individual differences (variations in performance) in characteristics of each SPR sensor cell can be suppressed.

[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. When forming the SPR sensor section 8, the metal thin film 15 may be formed before the second clad 9 is mounted on the core 7, or the metal thin film may be formed after mounting.

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 related to surface plasmon resonance in the R sensor unit 8 passes through the core and is emitted from the SPR sensor cell 3. 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.

[Immune 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 provided near the SPR sensor cell 3, and a condenser lens 53b is provided between the SPR sensor cell 3 and the light source. Also, on the opposite side of the light source 11 across the SPR sensor cell 3,
The condensing lens 53, the optical fiber 51, and the light analyzing means 4 in this order.
9 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.

Further, in this embodiment, a pinhole plate 52 is provided between the SPR sensor cell 3 and the condenser lens 53b.
b is provided. The pinhole plate 52 b is for increasing the degree of parallelism of the light condensed by the condenser lens 52 b and introducing substantially parallel light toward the core 7. FIG.
It is a perspective view showing pinhole board 52b in which one pinhole was formed, and pinhole board 52c in which a plurality of pinholes were formed. The pinhole plate 52c in which a plurality of pinholes are formed is used in an immune reaction measuring device equipped with a plurality of light sources, as described later.

FIG. 5 is a perspective view showing a state in which light from the light source 11 is condensed by the condenser lens 53b, passes through the pinhole plate 52b, and is introduced into the core 7. In particular, FIG. 5 shows a case where the diameter of the light from the light source is equal to or slightly smaller than the diameter of the pinhole near the pinhole plate 52b. When the light is condensed and transmitted through the pinhole in this manner, a highly sensitive immunoreaction measurement can be performed without a decrease in light intensity.

FIG. 6 is a perspective view showing a state in which light from the light source 11 is condensed near the pinhole plate 52b, but is condensed to a diameter larger than the diameter of the pinhole. By setting the diameter to be larger than the diameter of the pinhole, it is easy to set the direction of the optical axis with respect to the pinhole. This is because even if the optical axis is slightly shifted, the entire pinhole is irradiated with light, and the light necessary for measuring the immune reaction reaches the core 7.

[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. 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, an angle at an irradiation direction intermediate point of an irradiation part having a predetermined luminance or more. As described above, when the light source 11 with high directivity is used, SP
In some cases, a condenser lens, which will be described later, is not required to make the light L incident on the R sensor cell 3. It should be noted that some of the white LED lamps have an irradiation angle of about 140 degrees depending on the characteristics of the white LED lamp.

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.

[Light analysis means] Light 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, a spectroscope or a photodiode may be used. 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. 1, 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] FIG.
It is a perspective view which shows the modification of a PR sensor cell. This SP
The R sensor cell 3B is characterized in that it has eight sample storage units 14. Specifically, the core 7B is joined to the upper surface of the first clad 5B, and the second clad 9B is joined to the upper surface of the core 7. Eight through-holes 13 are formed in the second clad, and the upper surface of the core 7 </ b> B 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 7B, as described above.

As described above, when the SPR sensor cell 3B having the plate-shaped core 7B and the plurality of specimen storage sections is used, it is possible to easily measure a variety of items (for other kinds of antigens or antibodies) in a short time. Can be done. In the present embodiment, the core 7B having eight sample storage units has been described as an example, but the number of the sample storage unit cores 7B is two.
There may be seven or nine or more locations from the location.

[Another Modified Example of SPR Sensor Cell] FIG.
FIG. 9 is a perspective view showing a modification of the SPR sensor cell. The SPR sensor cell 3C is a light incident side end face 7 of the core 7C.
It is characterized in that surface treatment is applied to C1 and a part of the light emitting side end face 7C2. Specifically, the through hole 13 of the second clad 9C is located substantially at the center of the light incident side end face.
Except for the position corresponding to, a surface treatment is made such that light is hardly transmitted. As a method of the surface treatment, AL coating, black coating, or the like is used in addition to the formation of a ground glass. The surface treatment is performed in such a manner
The SPR sensor unit 8 is formed at a position corresponding to
This is to prevent unnecessary light from entering from the end face of the core 7C. The same applies to the light emitting side end face 7C2.

The first clad 5C and the second clad 9C used in the SPR sensor cell 3C are also partially surface-treated. More specifically, the same surface treatment as described above is applied to the end surfaces of the core 7C with respect to the light incident side end surface 7C1 and the light emission side end surface. The surface treatment is performed in this way to prevent unnecessary light from being incident on the first clad 5C and the second clad 9C. If unnecessary light enters and enters the core 7C, the accuracy of the immune reaction measurement is affected.

FIG. 9 is a perspective view of an SPR sensor cell 3D in which eight through-holes 13 are formed in the second clad 9D and eight SPR sensor portions are formed. The core 7D of the SPR sensor cell 3D is also subjected to surface treatment except for the position corresponding to each through hole 13.

FIG. 10 is a perspective view showing an SPR sensor cell in which the core is constituted by a plurality of light transmitting members. The materials used for each light transmitting member are all the same. FIG.
As shown in FIG. 0 (D), the core 7E includes a light propagation core 7a that transmits light from the light source, and cores 7b at both ends sandwiching the light propagation core 7a from both sides. FIG.
As shown in (F), the light transmission core 7a is subjected to a surface treatment on both side surfaces. This is for suppressing only the reflection on the side surface of the light incident on the light propagation core 7a, and making the light hardly reflected on these surfaces. Then, both end cores 7b are joined to both side surfaces of the light propagation core 7a subjected to the surface treatment. Light propagation core 7a and both ends core 7b
Various methods are conceivable for the bonding with the metal. For example, bonding using an adhesive, fusion bonding by heating, and the like are also conceivable.

FIG. 11 is a perspective view showing an SPR sensor cell 3F provided with two cores into which light is introduced.
The SPR sensor cell 3F is the first SPR sensor cell shown in FIG.
A core 7F1 and a light propagation core 7F2 shown in FIG.
And a third core 7F3 shown in FIG. 11 (G). Specifically, two short third cores 7F
2 are arranged in the longitudinal direction at predetermined intervals. The two light propagation cores 7F2 sandwich the third core 7F3 from both sides. Further, the first cores 7F1 are respectively joined from outside the light propagation cores 7F2 on both sides. FIG.
1 (D) shows the core 7F after the respective cores are joined. In the SPR sensor cell 3F, one side surface of the two light propagation cores 7F2 is configured as an SPR sensor unit. Specifically, it is a surface facing the gap of the third core 7F3. Therefore, both side surfaces of the light propagation core 7F2 are smoothly polished. On the other hand, the upper and lower surfaces of the light propagation core 7F2 are subjected to a surface treatment so that light is hardly reflected.

In the SPR sensor cells 3E and 3F shown in FIG. 10 and FIG.
cores 7b and 7F as light transmitting members other than a and 7F2
1,7F3 is subjected to a surface treatment on its end face.
Surface treatment is a process that makes it difficult for light to enter,
It is processed into ground glass, AL coating and black paint.

FIG. 12 is a perspective view of an SPR sensor cell provided with eight cores to which light is incident. The SPR sensor cell 3G includes eight light propagation cores 7G2 shown in FIG. 12 (E), and seven third cores 7G3 alternately joined to each of the light propagation cores 7G2. Further, two first cores 7G1 are provided, one at each end.
Are joined. The same surface treatment as described above is applied to both side surfaces of each light propagation core 7G2. Furthermore, the end surfaces (the light incident side end surface and the light emission side end surface) of the first core 7G1 and the third core 7G3 are also subjected to surface treatment.

As described above, a plurality of cores are joined to form a plate-shaped core 7G. Then, the plate-shaped core 7 </ b> G is joined to the upper surface of the first clad 5. Further, the second clad 9G is joined to the upper surface of the core 7G. Second clad 9G
, A through hole 13 is formed at a position corresponding to the light propagation core 7G2, and the through hole 13 and the upper surface of the light propagation core 7G2 form a specimen storage section. Then, a metal thin film, a dielectric film, and the like (not shown) are formed as SPR sensor portions at positions corresponding to the through holes 13 on the surface of the light propagation core 7G2. By adopting the above configuration, SP capable of performing eight kinds of immune reaction measurements
An R sensor cell can be manufactured. Note that the number of the light propagation cores 7G2 is an example, and is not limited to eight.

As described above, when the core is made of the same material, the following advantages are obtained. That is,
When the same material is used, the cost of the members is naturally lower than when different materials are used. Also,
Even when each light transmitting member (core) is processed, the characteristics (hardness, brittleness, surface smoothness) and the like of the material are the same. It has an excellent effect that the same processing can be performed.

[Second Embodiment] FIG. 13 is a schematic configuration diagram showing an immune reaction measuring apparatus 1B according to another embodiment of the present invention. This immune response measurement device 1B has a configuration substantially similar to that of the immune response measurement device 1 shown in FIG.
The difference is that an optical fiber 51b is provided between the light source 11 and the condenser lens 53b. More specifically, the light emitted from the light source 11 is
The light is condensed by c and is introduced into the optical fiber 51b through the receptacle 55c.

The light transmitted through the optical fiber enters the condenser lens 53 through the receptacle 55b. SPR passing through the pinhole plate 52b through the condenser lens 53b
Light is introduced into the sensor cell 3, and thereafter, an immunoreaction measurement is performed in the same steps as described above. Thus, the optical fiber 5 is connected between the light source 11 and the SPR sensor cell 3.
When the connection is made by 1b, the degree of freedom in the layout of the light source 11 and the SPR sensor cell 3 is improved. Also, since the optical fibers 51b are connected using the optical connectors 57b and 57c, the light source 11 and the SPR sensor cell 3 can be easily removed.

[Third Embodiment] FIG. 14 is a plan view showing an immune reaction measuring apparatus 1C provided with an SPR sensor cell 3C comprising two light propagation cores 7. As shown in the figure, a specimen storage section 14 is formed between the two cores 7. The SPR sensor cell 3 itself is mounted on a predetermined rail, and is movable in a direction perpendicular to the optical axis direction from the light source 11 to the SPR sensor cell. Pinhole plates 52a and 52b are provided on both sides of the SPR sensor cell, respectively. The pinhole plates 52a and 52b are
The light source 11 is fixed so as not to move. For this reason, the SPR sensor cell 3 is
a and 52b.

In this figure, the SPR sensor cell 3 is 2
The figure shows a state in which one of the cores 7 of the book is positioned so as to coincide with the optical axis of the light source 11. In this state, the immune reaction can be measured by analyzing the wavelength distribution of the light passing through the SPR sensor cell 3 by the optical analysis means. Next, the SPR sensor cell 3 is moved (upward in the figure). Then, the other core 7 is stopped at a position corresponding to the optical axis of the light source 11. Then, the light source 11 is turned on to measure the immune reaction.

[Fourth Embodiment] FIG. 15 is a plan view showing an immune reaction measuring apparatus 1D including two light propagation cores 7, two sets of light sources, two sets of condensing lenses and an optical coupler. It is. This immunoreaction measurement device 1D is for performing an immunoreaction measurement with one of the light transmission cores 7 by switching the lighting of the light source 11. The pinhole plates 52c and 52d have two pinholes corresponding to the respective light transmission cores 7. On the optical analysis means 49 side, two relay optical fibers 5 for guiding light from each condenser lens 53 are provided.
1c is provided. The two optical fibers 51 c are connected to an optical coupler 86, and light is transmitted to the optical analyzer 49 through the optical coupler 86. Thus, the optical system is 2
In the case of mounting as a set, it is not necessary to move the SPR sensor cell 3c, so that the immune response measuring device 1D itself is simply configured, and a rapid immune response measurement can be performed.

[Fifth Embodiment] FIG. 16 is a modification of the immunoreaction measuring apparatus shown in FIG. 14, and specifically, an optical fiber 51b is provided between the light source 11 and the SPR sensor cell 3E. Is different.

[Sixth Embodiment] FIG. 17 is a view similar to FIG.
5 is a modification of the immunoreaction measurement apparatus shown in FIG. 5, and specifically differs in that an optical fiber 51b is provided between the light source 11 and the SPR sensor cell 3F.

[Seventh Embodiment] Also, FIG.
Is characterized in that the SPR sensor cell of the immunoreaction measurement device shown in (1) is replaced with an SPR sensor cell 3G having eight light transmission cores 7. The SPR sensor cell 3G is also mounted on a predetermined rail, and can move along the rail. Then, the light source 11 and the condenser lens 5
3b is provided as one set. Further, one set of the condenser lens 53 and the optical fiber 51 on the side of the light analyzing means 49 is also provided. The light emitted from the SPR sensor cell 3G is collected by the condenser lens 5
The light is transmitted to the optical analyzing means 49 by the optical fiber 3 and the optical fiber 51.

[Eighth Embodiment] FIG. 19 shows a configuration in which the light source 11, the condenser lens 53b,
The difference is that eight sets 53 and optical fibers 51c are provided. Further, pinhole plates 52a and 53b are provided on both sides of the SPR sensor cell 3H. The pinhole plates 52a and 52b are fixed to the SPR sensor cell 3H, and have eight pinholes corresponding to each light source 11 and the condenser lens 53. The eight light sources 11 are configured so that one of them is turned on. For this reason, any one of the cores 7 performs an immune reaction measurement.

[Ninth Embodiment] FIG. 20 is an overall schematic diagram showing an immune response measuring device 1I obtained by modifying the immune response measuring device of FIG. The feature of the immune response measuring device 1I is that the SPR sensor cell 3I includes eight cores 7, and the other configuration is the same as that of the immune response measuring device of FIG.

[Tenth Embodiment] Further, the immunoreaction measuring apparatus 1J shown in FIG. 21 is different from the immunoreaction measuring apparatus shown in FIG. 17 in that the distance between each light source 11 and the SPR sensor cell 3J is eight. The difference is that they are connected by an optical fiber 51b. The rest is the same as the immunoreaction measurement device shown in FIG.

As described above, when the optical fiber 51b is provided between the light source 11 and the SPR sensor cell 3J, the light source 11 and the SPR sensor cell 3J can be arranged apart from each other. In addition, the immune reaction measuring device 1J
In this case, the degree of freedom in the arrangement of the light source 11 and the SPR sensor cell 3J is improved.

[Eleventh Embodiment] FIGS. 22 and 23
FIG. 21 is a diagram showing an eleventh embodiment of the present invention. Here, FIG. 22 shows an overall schematic view of the SPR sensor cell 1K, and FIG. 23 shows an optical fiber fixing section 67, respectively. As shown in FIG. 22, in the present embodiment, the light sources 11K to S
An optical fiber 61b for transmitting light to the PR sensor cell 3K is fixed to the block member 65. In the block member 65, a through hole as a predetermined optical fiber fixing portion 67 is formed in parallel with the optical axis of the core 7K.

Further, a ferrule 63 larger than the diameter of the optical fiber 61b is attached to the end (the SPR sensor cell side) of the optical fiber 61b. This ferrule 63
Has a diameter slightly smaller than the inner diameter of the optical fiber fixing portion 67.
7 can be fixed.
In FIG. 22, a cylindrical member is attached to the optical fiber fixing portion 67, and the condensing lens 53b is provided inside the cylindrical member 68.
And the ferrule 67 are fixed. Therefore, when such a structure is adopted, the condensing lens 5
3b and the optical fiber 61b can be integrally removed. FIG. 23A is an enlarged view of the optical fiber fixing section 67 when the cylindrical member 68 is used.

Next, FIG. 23B shows a case where the ferrule 63 and the condenser lens 53b are mounted directly on the optical fiber fixing portion 67b. The optical fiber fixing portion 67b
In the figure, a V-groove is formed vertically at a predetermined interval, and a circular condenser lens 53b is fixed to the V-groove.

As described above, when an optical fiber is connected by using the block member 65, the distance between the optical fibers adjacent to each other is larger than when a conventional optical connector having a large diameter is used. Can be narrowed. Further, the block member 65 may be provided not only on the light source 11K side but also on the optical analysis means 49k side.

[Twelfth Embodiment] FIG. 24 is a diagram showing an immune reaction measuring device according to a twelfth embodiment. This immunoreaction measurement device is similar to the immunoreaction measurement device shown in FIG. 22 except that the light source 11 (white LED or halogen lamp, etc.) is directly fixed to the block member 65. Thus, the plurality of light sources 11
By fixing to the vicinity of the PR sensor cell 3L via a block member, a plurality of optical fibers become unnecessary.

[0074]

The SPR sensor cell according to the present invention has a plate-shaped core having an SPR sensor portion formed in a predetermined region and transmitting light from a light source, and a plate-shaped core which covers the plate-shaped core from one surface. There is provided one clad and a second clad that covers a region other than the SPR sensor portion of the plate-shaped core from the other surface. Therefore, there are the following advantages as compared with a case where a core is manufactured by combining a plurality of members. That is,
If the surface of the core needs to be polished smoothly,
A large area can be polished in one polishing step, and the working efficiency is high.
Further, the number of joining steps can be reduced as compared with a case where a plurality of members are combined, and precision processing of the joining surface for joining is unnecessary. Therefore, it is possible to reduce the manufacturing cost of the SPR sensor cell. In addition, individual differences (variations in performance) in the characteristics of each SPR sensor cell can be suppressed.

In the present invention, the core is formed of a light transmitting member made of the same material. Therefore, the cost of the members is lower than when different materials are used. Also, when the respective light transmitting members (cores) are processed, since the properties (hardness, brittleness, surface smoothness) and the like of the materials are the same, by setting the same processing conditions, It has an excellent effect that the same processing can be performed on the members.

[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.
FIG. 1B shows a first clad, FIG. 1C shows a core, and FIG. 1D shows a second clad.

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

3 is a cross-sectional view showing an immunoreaction measuring device using the SPR sensor cell disclosed in FIG. 1, wherein FIG. 1 (A) shows a side cross-sectional view and FIG. 3 (B) shows an upper cross-sectional view.

FIG. 4 is a perspective view showing a pinhole plate used in the immunoreaction measurement device of the present invention, wherein FIG. 4 (A) shows one having one pinhole, and FIG. 4 (B) shows eight pins. Shows those with holes.

FIG. 5 is a schematic perspective view illustrating an optical path from a light source to an SPR sensor cell.

FIG. 6 is a schematic perspective view illustrating an optical path from a light source to an SPR sensor cell.

FIG. 7 is a perspective view showing a modification of the SPR sensor cell. FIG. 7 (A) shows an overall view, FIG. 7 (B) shows a first clad, and FIG. 7 (C) shows a plate-shaped core. FIG. 7
(D) shows the second clad.

8 is a perspective view showing another example of the SPR sensor cell, FIG. 8 (A) shows an overall view, FIG. 8 (B) shows a first clad, and FIG. 8 (C) shows a plate-shaped core. FIG.
(D) shows the second clad.

9 is a perspective view showing another example of the SPR sensor cell, FIG. 9 (A) shows an overall view, FIG. 9 (B) shows a first clad, and FIG. 9 (C) shows a plate-shaped core. FIG. 9
(D) shows the second clad.

FIG. 10 is a perspective view showing another example of the SPR sensor cell, FIG. 10 (A) showing an overall view, and FIG. 10 (B) showing a second example.
FIG. 10C shows a first clad,
FIG. 10D shows a plate-shaped core, FIG. 10E shows a light transmitting member constituting the core, and FIG. 10F shows a light propagation core constituting the core.

11 is a perspective view showing another example of the SPR sensor cell, FIG. 11 (A) shows an overall view, and FIG. 11 (B) shows a second example.
11C shows a clad, FIG. 11C shows a first clad,
FIG. 11D shows a plate-shaped core, FIG. 11E shows a light transmitting member constituting the core, FIG. 10F shows a light propagation core constituting the core, and FIG. Denotes a light propagation core constituting the core.

12 is a perspective view showing another example of the SPR sensor cell, FIG. 12 (A) shows an overall view, and FIG. 12 (B) shows a first example.
FIG. 12C shows a clad, and FIG.
(D) shows a light transmitting member constituting the core, and FIG.
(E) shows a light propagation core, FIG. 12 (F) shows a light transmitting member constituting the core, and FIG. 12 (G) shows a second clad.

FIG. 13 is an overall schematic diagram showing a second embodiment of the immune reaction measuring device of the present invention.

FIG. 14 is an overall schematic diagram showing a third embodiment of the immune reaction measuring device of the present invention.

FIG. 15 is an overall schematic diagram showing a fourth embodiment of the immune reaction measuring device of the present invention.

FIG. 16 is an overall schematic diagram showing a fifth embodiment of the immune reaction measurement device of the present invention.

FIG. 17 is an overall schematic diagram showing a sixth embodiment of the immune reaction measuring device of the present invention.

FIG. 18 is an overall schematic diagram showing a seventh embodiment of the immune reaction measuring device of the present invention.

FIG. 19 is an overall schematic diagram showing an eighth embodiment of the immune reaction measuring device of the present invention.

FIG. 20 is an overall schematic diagram showing a ninth embodiment of the immune reaction measuring device of the present invention.

FIG. 21 is an overall schematic diagram showing a tenth embodiment of the immune reaction measuring device of the present invention.

FIG. 22 is an overall schematic view showing an eleventh embodiment of the immune reaction measuring device of the present invention, FIG. 22 (A) is a plan view, and FIG. 22 (B) is a side view.

23 shows an enlarged view of an optical fiber fixing section of the immunoreaction measurement device disclosed in FIG. 22, FIG. 23 (A) shows a side view of the optical fiber fixing section, and FIG. 23 (A) shows an optical fiber fixing section. 23 (C) shows a side view of another example of the optical fiber fixing section, and FIG. 23 (D) shows a front view of the optical fiber fixing section of FIG. 23 (C).

FIG. 24 is an overall schematic diagram showing a twelfth embodiment of the immune reaction measuring device of the present invention, FIG. 24 (A) is a plan view, and FIG. 24 (B) is a side view.

[Explanation of symbols]

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

Claims (9)

[Claims] 1. A plate-shaped core having an SPR sensor portion formed in a predetermined area and transmitting light from a light source, a first clad covering the plate-shaped core from one surface, A second clad for covering a region other than the SPR sensor portion of the core from the other surface.
Sensor cell. 2. A low light transmitting surface on which light is hardly transmitted, except for a light incident surface and a light emitting surface of the core other than a region corresponding to the SPR sensor unit. The SPR sensor cell as described. 3. An SPR according to claim 1, wherein said SPR sensor section is formed at a plurality of positions on said core.
PR sensor cell. 4. The light transmission member, wherein the core is constituted by a plurality of light transmission members having a rectangular cross section made of the same material, and the light transmission member having the low light transmission surface and the light having no low light transmission surface are formed. 4. The SPR sensor cell according to claim 2, wherein the transmitting members are joined alternately. 5. A side surface of the light transmitting member on which the low light transmitting surface is formed, wherein a joining surface between the light transmitting member and an adjacent light transmitting member is a low light reflecting surface that hardly reflects light. The SPR sensor cell according to claim 4. 6. A side surface of the light transmitting member on which the low light transmitting surface is not formed, wherein a joining surface between the light transmitting member and an adjacent light transmitting member is a low light reflecting surface that hardly reflects light. The SPR sensor cell according to claim 4, wherein 7. The SPR sensor cell according to claim 1, 2, 3, 4, 5 or 6, a light source for entering light into a core of the SPR sensor cell, and a wavelength distribution of light emitted from the SPR sensor cell. An immunoreaction measuring device comprising: an optical analysis means for analyzing. 8. In the vicinity of at least one of the light incident side end surface and the light exit side end surface of the SPR sensor cell,
The immunoreaction measurement device according to claim 7, further comprising a pinhole plate that allows light to pass therethrough corresponding to the core. 9. An SPR sensor cell, comprising: a predetermined block member near an end surface on the light incident side or an end surface on the light output side of the SPR sensor cell; and an optical fiber connecting the block member to the light source or the light analyzing means. 8. An optical fiber fixing portion corresponding to the core of the SPR sensor cell is formed, and the optical fiber is fixed to the optical fiber fixing portion via a ferrule attached to the optical fiber. 9. The immunological reaction measuring device according to 8.