JP2000321280A - Immunoreaction measuring apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an immunoreaction measuring apparatus using an SPR sensor cell by which an antibody is immobilized easily and by which a specimen is held easily and to provide a small immunoreaction measuring apparatus. SOLUTION: An SPR sensor cell 3 in which an SPR sensor part 8 is formed is provided. A light source 11 by which the SPR sensor cell 3 is irradiated with light at a prescribed wavelength band is provided. A light analytical means 49 which analyzes the wavelength distribution of light which is transmitted through the SPR sensor cell 3 is provided. The light source 11 is constituted of a white LED lamp.

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

A method for measuring 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.

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

In addition, although a predetermined light source is required for the immunoreaction measurement device, a halogen lamp or the like may be used as a device capable of emitting light of a broadband wavelength. However, halogen lamps are often expensive and the size of the main body of the halogen lamp is large, so that the size of the immunoreaction measurement device itself has been disadvantageously increased.

[0018]

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 a small-sized immune reaction measuring device.

[0019]

In order to achieve the above object, the present invention provides an SP having an SPR sensor section.
An R sensor cell, a light source that irradiates the SPR sensor cell with light in a predetermined wavelength band, and an optical analysis unit that analyzes a wavelength distribution of light transmitted through the SPR sensor cell, wherein the light source is configured by a white LED lamp. Has been adopted.

The function and operation of the immunoreaction measuring device having the above-described configuration will be described. First, a white LED as a light source is used.
A certain band of light is emitted from the lamp. 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.

The light that has caused the surface plasmon resonance is emitted from the core and introduced into the optical analysis means. The light analyzing means analyzes the wavelength distribution of light. 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. When a white LED lamp is used as the light source, the size of the immune reaction measuring device itself can be reduced, and the degree of freedom in the layout of the SPR sensor cell and the optical analysis means is improved.

[0022]

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 Immune Reaction Measuring Apparatus] FIG.
1 shows an overall schematic diagram of an immune reaction measuring device 1. FIG. The immune reaction measurement device 1 analyzes a white LED lamp as a light source 11 that irradiates light, an SPR sensor cell 3 that transmits light to generate surface plasmon resonance, and a wavelength distribution of light emitted from the SPR sensor cell 3. An optical analyzer 49 is provided. Hereinafter, each component will be described in detail.

[Light Source] First, the light source 11 for irradiating the light L for measuring the immune reaction will be described. The light source 11 emits light L in a predetermined wavelength band, and specifically, a white LE
A D 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, light source 1
It is desirable that 1 irradiates light L having a stable wavelength distribution. Commercially available white LED lamps have a wavelength band of light L to be applied of about 450 [nm] to 750 [nm].
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.

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.

[SPR Sensor Cell] Next, the SPR sensor cell 3 will be described with reference to FIG. The SPR sensor cell 3 of the present embodiment uses an optical waveguide (core). More specifically, the SPR sensor cell 3 includes a plate-shaped first clad (substrate) 5, a core 7 disposed on the first clad 5, and two intermediate clads 6 sandwiching the core 7 from both sides. And a second clad (upper plate) 9 covering the surfaces of the core 7 and the intermediate clad 6. Hereinafter, the SPR sensor cell of the present invention will be described in detail. The optical waveguide has a flat type, a strip type,
There are various types such as 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.

Further, 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 inner surface of the through hole 13. However, a metal thin film is formed on the portion of the core 7 corresponding to the through-hole 13 to form the SPR sensor unit 8 as described later.

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 by the through-hole 13 of the second cladding 9, the surface of the core 7, and the like. 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. It is also desirable that the second 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.

Here, in order for the core 7 to function as an optical waveguide, a certain relationship must be established between the refractive indices of the first clad 5, the core 7, the intermediate clad 6, and the second clad 9. Specifically, the core 7 needs to have the largest refractive index. Further, the first clad 5, the intermediate clad 6, and the second clad 9 may have the same refractive index. When this is expressed by a relational expression, for example, the refractive index of the first clad 5 is set to N
1, assuming that the refractive index of the core 7 is N2, the refractive index of the intermediate cladding 6 is N3, and the refractive index of the second cladding 9 is N4, N2> N1 and N2> N3 and N2> N4 or N2> N1 = N3 = N4.

[Structure of Core Surface] Next, a detailed structure of a portion of the surface of the core 7 facing the specimen storage section 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. 4 shows a sectional view of the SPR sensor cell 3. Specifically, the metal thin film 1 is sequentially placed on the surface of the core 7.
5, the dielectric film 17 is formed and the dielectric film 17 is formed.
An antibody (or antigen) 19 is immobilized on the surface of.

More specifically, in order to form the SPR sensor section 8, the core 7 is coated with Au (gold) as a 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, the 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.

For this reason, when the light L is introduced into the core 7 and the wavelength distribution of the light L emitted from the core 7 after the occurrence of the immune reaction is analyzed, it is different from the wavelength distribution when the immune reaction does not occur. Becomes

[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, a spectroscope or a photodiode may be used (FIG. 7).
50). 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, a plurality of photodiodes may be provided, and a filter capable of transmitting light of different wavelengths may be provided for each photodiode, and an immune response may be measured by analyzing the attenuation of light of each wavelength. Good.

[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] 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 sandwiched between the cores 7a and 7b. A center clad 6b, two end clads 6a sandwiching the two cores 7a, 7b from both outer sides, and a second covering the surfaces of the cores 7a, 7b, the center clad 6b and the both end clads 6a.
And a clad (upper plate) 9.

The center clad 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.

As described above, two samples are stored in one sample storage unit.
By equipping the cores 7a and 7b, it is possible to measure different immune responses to one sample.
That is, different antibodies (or antigens) are immobilized on the surfaces of the cores 7a and 7b (positions exposed to the specimen storage sections), and the immunoreaction measurement can be performed separately for each. 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 enter only 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. Here, the same parts as those in the first embodiment will be described using the same reference numerals. The immune response measurement device 1B according to the first embodiment
On the other hand, the difference is that the number of condenser lenses is further increased by one. More specifically, a condenser lens 53b is provided between the light source (white LED lamp) 11 and the SPR sensor cell 3. This condenser lens 53b is provided with a light source (white LE
The light L emitted from the D lamp 11 is condensed 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 condensed through the condenser lens 53c 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 immunoreaction measuring device 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 light from the eight optical fibers 51d to the optical analysis means. Here, since the white LED lamps are turned on one by one in order, the light passing through each core 7 is sequentially transmitted to the light analyzing 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 has been described as an example. However, the number of cores 7 may be two to seven or nine or more. Also in this case, the light source 11 and the condensing lens 53 according to the number of cores 7
And the optical fiber 51d.

[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.

By providing the 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 this embodiment,
This is an immunoreaction measurement device 1G using a SPR sensor cell 3G having a plurality of specimen storage sections 14 and only having a set of a light source 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 this 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 stop position of the cell moving mechanism 75 is 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.

[0067]

As described above, the present invention relates to an SPR sensor cell having an SPR sensor section, a light source for irradiating the SPR sensor cell with light in a wide wavelength band, and a wavelength distribution of light transmitted through the SPR sensor cell. The light source was constituted by a white LED lamp. For this reason, it becomes possible to manufacture the immune reaction measuring device at low cost, and it is possible to reduce the size of the entire immune reaction measuring device. In addition, since the power consumption of the white LED lamp is very small, the immune reaction measuring device can be configured using a small battery or the like as a power source, and can be made portable.

Further, by configuring the light analyzing means with a predetermined photodiode, the immune reaction measuring device itself can be further reduced in cost and size.

Further, at least two SPR sensor cells are used.
A plurality of cores and a clad covering these cores, an optical fiber for transmitting light passing through each core to the optical analysis means is provided, and light passing through each core is transmitted to the optical fiber by the optical analysis means. Equipped with an optical coupler to transmit to.
For this reason, it is possible to quickly perform an immune reaction measurement on a plurality of samples.

Further, in the end face on the light incident side in the SPR sensor cell, a region other than the core is subjected to a surface treatment for suppressing light incidence. With this configuration, unnecessary light does not enter the core, and the accuracy of the immune reaction measurement can be improved.

Further, a plurality of light sources are provided in the vicinity of each of the cores so as to correspond to the cores, and each light source is sequentially turned on corresponding to any one of the cores. Alternatively, the SPR sensor cell is constituted by at least two or more cores and a clad covering these cores, and the light source is disposed near the SPR sensor cell, and the optical analysis means is arranged in correspondence with the light source. And the SPR sensor cell is configured to be movable along the arrangement direction of the cores. For this reason, it is possible to quickly perform a multi-item immune reaction measurement.

[Brief description of the drawings]

FIG. 1 is an overall schematic diagram showing an immune reaction measurement device according to a first embodiment of the present invention.

FIG. 2 is a diagram showing a light source (white LED lamp) used in the immunoreaction measurement device disclosed in FIG.

3 is a perspective view showing an SPR sensor cell used in the immunoreaction measurement device disclosed in FIG. 1; FIG. 3 (A) shows an overall view; FIG. 3 (B) shows a first clad; 3
FIG. 3C shows a core and a clad bonded to the core, and FIG. 3D shows a second clad.

FIG. 4 shows a cross-sectional view of the SPR sensor cell 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.

FIG. 10 is a perspective view showing an SPR sensor cell used in the immunoreaction measurement device disclosed in FIG.

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

Continued on the front page F term (reference) 2G059 AA01 BB12 CC17 DD13 EE01 EE04 GG02 HH02 JJ12 JJ17 KK01 LL03 2G065 AB04 AB27 AB28 BA09 BA33 BB02 BB05 BB10 BB26 BB28 BB29 BB44 DA08 DA10

Claims (7)

[Claims] 1. An SPR sensor cell in which an SPR sensor unit is formed, a light source for irradiating the SPR sensor cell with light in a predetermined wavelength band, and an optical analyzer for analyzing a wavelength distribution of light transmitted through the SPR sensor cell. An immunoreaction measurement device, wherein the light source is constituted by a white LED lamp. 2. The immunoreaction measuring apparatus according to claim 1, wherein said optical analysis means is constituted by a spectroscope. 3. The apparatus according to claim 1, wherein said light analyzing means is constituted by a predetermined photodiode. 4. The method according to claim 1, wherein the SPR sensor cell comprises at least two cells.
An optical fiber for transmitting light transmitted through each core to the optical analysis means, and one of the cores in the optical fiber. 4. The immunoreaction measurement device according to claim 1, further comprising an optical coupler that transmits only light from the core. 5. The apparatus according to claim 4, wherein a plurality of light sources are provided in the vicinity of each of said cores so as to correspond to said cores, and each of said light sources is sequentially turned on corresponding to any one of said cores. Immune reaction measurement device. 6. The method according to claim 1, wherein the SPR sensor cell is at least 2
Comprising at least one core and a clad covering these cores, arranging the light source in the vicinity of the SPR sensor cell, arranging the light analyzing means in correspondence with the light source, The immunoreaction measurement device according to claim 1, 2 or 3, wherein the device is configured to be movable along the arrangement direction of the cores. 7. A surface treatment for suppressing light incidence on a region other than the core in an end surface on the light incidence side of the SPR sensor cell.
7. The immune reaction measuring device according to 3, 4, 5, or 6.