JPH1164338A - Immunoreaction measuring apparatus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To measure many items with a small amount of test bodies in real time, by setting a plurality of optical fibers each having a surface plasmon resonance(SPR) sensor part at one end part. SOLUTION: An optical fiber 5a has an SPR sensor part 3 at one end part. A light source 9 projects a specific white light 7 from the side of the other end part of the optical fiber 5a. A spectroscope 13 analyzes a wavelength distribution of a light 11 reflected from the SPR sensor part 3. A main control part 15 controls operations of the light source 9 and spectroscope 13. An apparatus main body 17 stores these parts therein. At least two optical fibers 5a are provided. Since an immunoreaction is measured by the SPR sensor part 3 utilizing the optical fibers 5a, measurements in real time can be achieved, and the immunoreaction can be measured with a small amount of test bodies. In addition, since the plurality of optical fibers 5a are used for the measurement, many items can be measured in a short time.

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.
Plasmon Resonance (hereinafter abbreviated as "SPR").

[0002]

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

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

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

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

The above-mentioned ELISA method is used for quantification of an antibody against a specific pathogen, quantification of an antibody against allergen, and screening of a monoclonal antibody. E
The measurement kit used for the LISA method is generally 96
Using a microplate in which the inner part is formed, the process is performed on this microplate. Therefore, a large number of samples can be measured at the same time, and in recent years, many automated immune reaction measuring devices have been on the market.

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

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

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

By applying the above principle, an SPR sensor for an immune reaction measuring device using an optical fiber has been developed (B
IACORE-BIAcoreProbe). In the SPR sensor using the optical fiber, first, the end face of the tip of the optical fiber is polished, and then the end face is coated with silver. Also, the clad (Clad) on the outer peripheral surface of the tip of the optical fiber is removed, and this portion is coated with a metal thin film (such as gold or silver). Further, a metal thin film on the outer peripheral surface of the distal end portion of the optical fiber is covered with a dielectric film, and an antibody used for an 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 white light can be introduced into the optical fiber.

A method for measuring the immune response of the SPR sensor having the above-described configuration will be described. First, as for the white light introduced into the optical fiber, a wave of a specific wavelength in the white light excites surface plasmon resonance at the tip of the optical fiber. The wavelength for exciting the surface plasmon resonance changes depending on the refractive index between the dielectric film and the antibody. Therefore, the immune response can be measured by comparing the wavelength that attenuates the most before the immune reaction with the wavelength that attenuates the most after the immune reaction. FIG. 21 is an explanatory diagram showing a principle experiment of an immune reaction measuring device using an SPR sensor. As shown in FIG. 21, attenuated between a case where a sample was a reference test solution (for example, phosphate buffer) containing no antigen and a case where a predetermined test solution (containing an antigen) was used as a sample. Wavelengths are different.

The optical fiber itself is thin,
Further, loss of light transmitted in the optical fiber is small. Therefore, an advantage is that the size of the immune reaction measuring device can be reduced and remote measurement can be performed. These lead to improvement in the operability of the immune reaction measuring device.

[0013]

However, each of the above-mentioned prior arts has the following disadvantages. That is, ELI
In an enzyme immunoassay such as SA, a large number of measurement steps are required, and the reaction requires a long time. Therefore, 1
It may take several hours to several tens of hours to measure one sample, and the measurement efficiency cannot be improved. In the enzyme immunoassay, an immune reaction is measured for a large number of samples for each item. For this reason, there has been an inconvenience that the method is not suitable for an application in which a plurality of items are measured at a time for one specific sample.

In an immunoreaction measurement device using an SPR sensor composed of an optical fiber, a specific antibody used for the immunoreactivity measurement is fixed to the tip of the optical fiber in advance, and the antigen in the specimen to be measured is determined. The SPR sensor reacts with the antibody. For this reason, there has been an inconvenience that multiple items cannot be measured at once.
In addition, since the optical fiber is of an integral type, there is a problem that the entire optical fiber must be replaced when the measurement item is changed.

Further, in the SPR sensor using an optical fiber, consideration for so-called biohazard is lacking. That is, since an infectious sample such as blood is used in the measurement of the immune reaction, all areas that come into direct contact with the sample should be used fresh, and those that have been used should be discarded. However, in reality, there is an inconvenience that some of the antigens and antibodies used for measurement may remain on the SPR sensor because they are repeatedly used by washing or the like.

[0016]

SUMMARY OF THE INVENTION The object of the present invention is to provide an immunological reaction measuring apparatus which can solve the disadvantages of the prior art and, in particular, can perform a multi-item measurement with a small amount of sample in real time. With that purpose.

[0017]

In order to achieve the above-mentioned object, according to the first aspect of the present invention, an optical fiber having an SPR sensor at one end and a predetermined optical fiber from the other end of the optical fiber are provided. A light source that emits white light, a spectroscope that analyzes the wavelength distribution of the reflected light reflected from the SPR sensor unit, a main control unit that controls the operation of the light source and the spectrometer, and a device main body that accommodates these units , At least two optical fibers
Equipped with this. With the above configuration, a plurality of reactions can be measured at one time.

According to the second aspect of the present invention, a predetermined optical path selecting means is provided between the light source and the other end of the optical fiber, and the other configuration is the same as that of the first aspect. is there. With the configuration described above, the optical path to another optical fiber can be cut off when the immunoreactivity measurement is performed on one optical fiber.

According to a third aspect of the present invention, the optical path selecting means is constituted by a predetermined liquid crystal mask, and the liquid crystal mask has a selective transmission function of transmitting white light to only one of the optical fibers. The other configuration is the same as that of the second aspect. With the above configuration, by electrically controlling the liquid crystal mask, it is possible to irradiate only one of the plurality of optical fibers with white light.

According to a fourth aspect of the present invention, a multi-fiber connector capable of simultaneously connecting a plurality of optical fibers is provided in the vicinity of the SPR sensor portion, and the other configurations are the same as those of the first aspect. . With the above configuration, the necessary SPR sensor unit can be quickly replaced.

According to a fifth aspect of the present invention, an optical switch for switching transmission and cutoff of white light is provided in the other end side region of each optical fiber. Same as the invention. With the configuration described above, white light is incident on only one of the plurality of optical fibers by the action of the optical switch.

The invention according to claim 6 employs a configuration in which a branching means for branching white light to the SPR sensor side and the spectroscope side is provided between the light source and each optical switch. Is the same as the fifth aspect of the invention. With the above configuration, the white light incident on each optical fiber is incident on the spectroscope by the branching unit,
It is also irradiated on the SPR sensor side.

According to the seventh aspect of the present invention, a cap member for covering the SPR sensor portion is provided around the SPR sensor portion, and a suction port for sucking a sample is formed in a part of the cap member, so that the inside of the main body of the apparatus is formed. Is provided with a suction pump for sucking the sample into the cap member at a predetermined position, and the other structure is the same as that of the first aspect. With the above-described configuration, it is possible to hold a fixed amount of the sample in the cap member and measure in this state during the measurement of the immune reaction.

The invention according to claim 8 employs a configuration in which a storage buffer is filled in advance in the cap member.
Other configurations are the same as those of the fifth aspect of the invention. With the above configuration, denaturation of the antibody in the SPR sensor portion is suppressed. In addition, by performing an immune reaction measurement while the storage buffer is being filled, the immune reaction measurement device can be checked.

According to the ninth aspect of the present invention, a predetermined transmitter is provided in the apparatus main body, the output of the spectroscope is transmitted to the transmitter, and the transmitter is transmitted from the transmitter to a receiver connected to a predetermined higher-level device. The configuration of transmitting the output of the spectroscope is adopted, and the other configuration is the same as that of the first aspect. With the configuration described above, the measured result is sent to the host device by the transmitter, and is used for various data processing.

The invention according to claim 10 employs a configuration in which an antibody serving as a positive sensor and an antibody serving as a negative sensor are fixed to the SPR sensor portion, respectively.
Other configurations are the same as those of the first aspect. With the above configuration, if the positive control responds properly, the measurement system is determined to be normal, and if the negative control does not respond,
It can be determined that a non-specific reaction has not occurred.

[0027]

BEST MODE FOR CARRYING OUT THE INVENTION

[First Embodiment] An embodiment of the present invention will be described with reference to the drawings. In the immunoreaction measurement device according to the present embodiment, as shown in FIG. 1, an optical fiber 5a having an SPR sensor unit 3 at one end and a predetermined white light 7 is irradiated from the other end of the optical fiber 5a. Light source 9, a spectroscope 13 for analyzing the wavelength distribution of the reflected light 11 reflected from the SPR sensor unit 3, a main control unit 15 for controlling the operation of the light source 9 and the spectroscope 13, and an apparatus main body containing these units And at least two optical fibers 5a. This will be described in detail below.

[SPR Sensor Unit] First, a plurality of optical fibers 5a made of quartz are put together to form a multi-optical fiber 5, and the tip of the multi-optical fiber 5 is an SP.
The R sensor unit 3 is provided. The SPR sensor unit 3 can connect all the optical fibers 5a at a time by the multi-fiber connector 19. The tip of each optical fiber 5a in the SPR sensor unit 3 is shown in FIGS.
As shown in (1), the distal end surface of the core 3a of the optical fiber 5a is coated with silver, and this portion plays the role of the reflection mirror 3b. An optical fiber 5 is provided on the outer peripheral surface of the tip.
The surface of the core 3a is coated with a silver or gold metal thin film 3c, a dielectric film 3d is formed on the metal thin film 3c, and an antibody 3e is further fixed thereon. There are various types of optical fiber structures. That is, the core is made of quartz or plastic (polymer), and the clad is made of quartz or plastic. The SPR sensor section uses quartz or plastic. In practice, these materials are used in an appropriate combination.

The dielectric film 3d has a role as an adhesive for binding the antibody 3e fixed to the metal thin film 3c. Many proposals have been made for the specific configuration of the dielectric film 3d. In the present embodiment, as shown in FIG. 3, a multi-membered ring 3d containing a sulfur atom is provided immediately above a metal thin film 3c.
1 (sulfide, disulfide, thiol, isonitrile, etc.). This multi-membered ring 3d1 is covered with a saturated hydrocarbon chain 3d2 (12 to 30 atoms that are not branched and interrupted by hetero atoms). Further, an active group 3d3 (amino group, aldehyde group, epoxy group, carboxyl group, etc.) is coated on the saturated hydrocarbon chain 3d2. The antibody 3e is fixed to the active group 3d3.

Various combinations of the type of the antibody 3e immobilized on the dielectric film 3d are considered depending on the antigen 3f in the specimen to be measured. That is, when the antigen 3f in the sample to be measured is determined, the SPR sensor unit 3 on which the plurality of antibodies 3e such as a protein, a positive control, and a negative control corresponding thereto are individually fixed is selected. The SPR sensor unit 3 is connected by the multi-fiber connector 19 as described above. Therefore, only the SPR sensor unit 3 can be removed at once and replaced with another SPR sensor unit. Actually, in the immune reaction measuring device 1 using the SPR sensor unit 3,
Cancer, diabetes, bacteria (O-157), thrombus / head injury, water quality test (toxin test), and various endocrine tests can be performed.

As described above, a plurality of antibodies 3e (in FIG. 2, antibody A, antibody B, antibody C,
Immobilizing antibody P and antibody N)
Multiple items can be measured simultaneously with one operation. This is S
Various antibodies 3e immobilized on the dielectric film 3d at the tips of the plurality of optical fibers 5a of the PR sensor unit 3 are made possible by specifically binding to the proteins to be the respective antigens 3f contained in the sample. . For example, in a cancer test, a tumor marker is generally used as a test reagent. When gastric cancer is considered, three to four types of tumor markers are often used in combination as a prognostic diagnosis. In such a case, if these tumor markers are fixed to each of the SPR sensor units 3, a large number of items can be measured by one measurement, so that the effect of improving the measurement efficiency is large.

Even in the case of diabetes, it is not sufficient to simply examine the concentration of insulin in a sample to determine what is abnormal in endocrine and is causing symptoms of diabetes. In such a case as well, by measuring (quantifying) the secretion concentration of the protein showing a causal relationship, it becomes easier to determine the subsequent treatment and administration of the drug. Other bacteria, thrombosis,
The benefits of multiple measurements, such as toxin testing, are endless.

Further, in the immunoreaction measuring apparatus 1 according to the present embodiment, as shown in FIG. 2, a positive control (antibody P) is provided on a part of the antibody in order to improve the accuracy of the measurement.
And a negative control (antibody N). Here, the positive control refers to an antibody that specifically reacts with a protein existing as an antigen in a specimen. Depending on the sample, blood, urine, saliva, and the like may contain a protein whose concentration does not change much even when the physical condition of the human changes. An antibody P that specifically reacts with this protein is
a, which is used as a positive control.

Conversely, an antibody N corresponding to an antigen that cannot be present in the specimen at all is used as a negative control. When the antibody N used as a negative control reacts, it can be estimated that a non-specific reaction has occurred, so that various measures can be taken. In addition, the negative control is an antigen (protein) of another species.
The selection range is abundant because antibodies that react with

If the sample does not contain an appropriate protein, a method of adding it to the sample later may be considered. That is, an antigen and an antibody which react specifically with each other are used. Then, a predetermined amount of the antigen is added to the sample before measurement. And S
An antibody corresponding to this antigen is immobilized on the PR sensor as a positive control. At this time, it is preferable that the antigen has affinity with the specimen (blood, saliva, urine, etc.). This method increases the work itself, but improves the accuracy of quantification. In addition, the positive control and the negative control are used when both are used simultaneously,
Only one of them may be used.

[Cap member] The SPR sensor unit 3
Around a predetermined cap member 2 as shown in FIG.
1 is provided to cover the entire SPR sensor unit 3. The cap member 21 is used to temporarily hold a fixed amount of a sample when measuring an immune reaction. Therefore, a suction port 2323 for sucking a sample is formed at the tip of the cap member 21. Further, a suction pump 25 provided in the apparatus main body 17 is connected to the internal space of the cap member 21.

Before the measurement of the immune reaction, a predetermined storage buffer 27 is filled in the cap member 21. This storage buffer 27 is for suppressing the denaturation of the antibody 3e before the measurement of the immune reaction. Specifically, a phosphate buffer or an acetate buffer is used. The storage buffer 27
Is filled, the tip of the cap member 21 is sealed. Then, this seal is peeled off at the time of measuring the immune reaction and used. Here, since the diameter of the suction port 23 of the cap member 21 is small, even if the seal is removed, the storage buffer 27 does not easily spill. In addition, by performing an immune reaction measurement in a state where the storage buffer 27 is filled in the cap member 21, it is possible to check and correct the characteristics and variations of each SPR sensor unit 3.

[Suction Pump] The suction pump 25 connected to the internal space of the cap member 21 is for sucking a sample into the cap member 21 through the above-described suction port 23. The immune reaction measurement device 1 of the present embodiment is configured to automatically aspirate a sample. This is because a certain amount of the sample to be aspirated is necessary to guarantee the accuracy of the measurement. Therefore, a small-sized suction pump having a small suction capacity and high accuracy is used. A secondary battery 29 is used as a power supply for the suction pump 25.
The secondary battery 29 includes a nickel hydride battery, a lithium ion battery, a lithium manganese dioxide battery, a nickel cadmium battery, and the like. In order to reduce the size of the device main body 17, it is constituted by a battery having a high energy density.

[Light Source] As the light source 9 for irradiating the optical fiber 5a with white light, a halogen lamp is used (see FIG. 1). The halogen lamp of this light source contains light of various wavelengths, and the optical fiber 5a is constantly used during the immunoreaction measurement.
Is irradiated with white light 7. The light source 9 is not limited to a halogen lamp. That is, any light containing a light in a predetermined wavelength band may be used. When the wavelength of the light attenuated by the immune reaction can be estimated to some extent in advance, a light source including only the light of the estimated wavelength may be used. The operation of the light source 9 depends on the device main body 17.
Is controlled by the main control unit 15.

On the downstream side of the light source 9, as shown in FIG.
Predetermined lenses 31 and 33 for condensing light are provided. The lens 31 has a role of temporarily converging the white light 7 radiated from the light source 9 radially. Then, the converged white light 7 enters the lens 33. The lens 33 has a role of converting the converged white light 7 into parallel light. Then, the parallel white light 7 is irradiated on the optical fiber 5a side. When a light source capable of irradiating parallel light is used in advance, these lenses 31 and 33 are unnecessary. A polarizing plate 35 is provided downstream of the lens 33. The polarizing plate 35 converts the white light 7 into P (parallel).
It is polarized.

[Optical Path Selection Means] As shown in FIGS. 1 and 5, an optical path selection means 37 is disposed downstream of the light source 9 and further downstream of the lenses 31 and 33. ing. The optical path selection means 37 has a selective transmission function for selectively transmitting the white light 7 to the plurality of optical fibers 5a. This is because a plurality of antibodies 3e are preliminarily fixed to the SPR sensor unit 3 when measuring the immune reaction, and the immune reaction of each of the antibodies 3e is individually measured.

The optical path selection means 37 is specifically composed of a liquid crystal mask. The liquid crystal mask is controlled so that the white light 7 is transmitted in a spot manner and is sequentially incident on the individual optical fibers 5a. That is, one optical fiber 5
While a is selected and the white light 7 is incident and its wavelength distribution (spectral pattern) is measured, the white light 7 to the other optical fiber is blocked by the liquid crystal. The optical fibers 5a shown in FIG. 5 are arranged in a circle,
The light path selecting means 37 also changes the transmission position in a circular shape correspondingly. The operation of the optical path selection means 37 is controlled by the main control unit 15 in the apparatus main body 17. Since the optical path selecting unit 37 using the liquid crystal mask does not have a mechanical driving unit, the optical path selecting unit 37 itself can be reduced in size and failure can be reduced. Further, the optical path can be freely set with high accuracy.

[Splitter] As shown in FIGS. 1 and 5, a splitter 39 composed of a half mirror is disposed between the optical path selecting means 37 and the optical fiber 5a.
The splitter 39 splits the white light 7 from the light source 9 in two directions. A part of the light is directly incident on the optical fiber 5a by the splitter 39, and the other part is split by the splitter 39 into the optical fiber 5a.
The light is reflected in a direction different from a. In the present embodiment, the white light 7 reflected by the splitter 39 is directly incident on a spectroscope 13 described later.

[Spectroscope] As shown in FIGS. 1 and 4, a predetermined spectroscope 13 is provided in the immunological reaction measuring device 1 of this embodiment.
Is equipped. The spectroscope 13 analyzes the wavelength distribution (spectral pattern) of the white light 7 used for measuring the immune reaction. Here, one of the lights incident on the spectroscope 13 is output from the light source 9 and
1, lens 33, polarizing plate 35, and optical path selecting means 37
White light 7 transmitted through and reflected by the splitter 39
It is. In addition, the spectroscope 13 includes an optical fiber 5a.
And the reflected light 11 reflected from the SPR sensor unit 3 is also incident. The spectroscope 39 can know which wavelength in the reflected light 11 is attenuated by comparing the wavelength distribution of the incident white light 7 and the reflected light 11. In addition, from the splitter 39 to the spectroscope 13,
The white light 7 and the reflected light 1 are passed through predetermined light collecting lenses 40a and 40b and light guide tubes (optical fibers) 41a and 41b.
1 is transmitted.

[Main Control Unit] The main control unit 15 provided in the apparatus main body 17 includes a light source 9 and a light source 9 as shown in FIGS.
The operation of the optical path selection means 37, the spectroscope 13, and the like is controlled. Further, the main control unit 15 has a function of acquiring information on the wavelength distribution of the reflected light 11 obtained by the spectroscope 13 and transmitting the information to the display unit 43 and the transmitter 45 provided in the apparatus main body 17. doing. Further, the main control unit 15
Also controls the operation of the suction pump 25 and the like. Further, the information of the analysis result by the spectroscope is transmitted from the transmitter 45 to a receiver to which a higher-level device (medical device, computer, or the like) is connected (see FIG. 10).

Next, the operation of the immune reaction measuring device 1 configured as described above will be described.

[Overview of Overall Operation] First, the white light 7 emitted from the light source 9 is converted into parallel light by the lenses 31 and 33 as shown in FIG. After being P-polarized, the optical path selection means 37 transmits white light in a spot only at a position corresponding to one optical fiber 5a.
Thereafter, a part of the white light 7 is reflected by the splitter 39 and is incident on the spectroscope 13, and the remaining part is branched to the SPR sensor unit 3 as it is.

The white light 7 directed to the SPR sensor 3 is
While traveling while reflecting on the outer peripheral surface of the tip of the SPR sensor section 3,
Further, the light is reflected by the reflection mirror 3b (mirror coated with gold or silver) on the end face of the SPR sensor unit 3, and returns as reflected light 11 in the optical fiber 5a. At this time, S
In the PR sensor section 3, white light 7 excites surface plasmon resonance. Excitation of the surface plasmon resonance is light of a specific wavelength in the white light 7. Accordingly, the intensity of the light of the specific wavelength is attenuated, and the light of a part of the wavelength is returned as the reflected light 11 in an attenuated state.

The returned reflected light 11 is again transmitted to the splitter 39.
And is incident on the spectroscope 13 via the light guide tube (optical fiber) 41b. The spectroscope 13 analyzes the white light 7 before traveling to the SPR sensor unit 3 and the reflected light 11 reflected by the reflection mirror 3b of the SPR sensor unit 3, and measures a wavelength distribution (spectral pattern). The white light 7 before reflection is measured as a wavelength distribution of the halogen lamp itself having a broadband wavelength. However, the reflected light 11
Is, as described above, the metal thin film 3c of the SPR sensor unit 3.
Attenuation is observed in a certain wavelength range due to surface plasmon resonance generated between the substrate and the dielectric film 3d.

[Calibration] It is necessary to calibrate the SPR sensor unit 3 before measuring the immune reaction. That is, the above-described dielectric film 3d (see FIG. 3) is formed on the surface of the SPR sensor unit 3. The reflected light 11 from the SPR sensor unit 3 enters the spectroscope 13 by the splitter 39. In the spectroscope 13, the reflected light 11
Is analyzed. Thus, a diagram of the wavelength distribution as shown in FIG. 6 can be obtained. As shown in FIG. 6, the intensity of a specific wavelength band becomes low.

When the wavelength having the minimum intensity is obtained from the obtained wavelength distribution, this wavelength is the wavelength at which surface plasmon resonance is excited. Thereby, the wavelength of light that excites surface plasmon resonance in a state where the antibody 3e is not fixed to the dielectric film 3d becomes clear, and the SPR sensor unit 3 can be calibrated.

[Preparation of Data Table] Next, a data table of the immune reaction measuring device 1 using the SPR sensor unit 3 is prepared. This data table refers to various antibodies 3 in the immunoreaction measurement device 1 using the SPR sensor unit 3.
Fig. 9 shows the relationship between the concentration dependence of antigen 3f and e. That is, when the concentration of the antigen in the specimen is high, the wavelength of light that excites surface plasmon resonance changes according to the concentration. Therefore, if the relationship between the concentration of the antigen corresponding to the specific antibody and the decaying wavelength is checked in advance, the concentration of the antigen in the sample can be estimated when actually measuring the immune reaction.

[Actual Immune Response Measurement] When actually performing an immune response measurement, the antibody 3 immobilized on the SPR sensor unit 3
It is necessary to consider e. This is because it is necessary to use an antibody corresponding to an antigen considered to be contained in the sample to be used for measurement and specifically reacting with this antigen. Further, in the immune reaction measurement device 1 of the present embodiment,
An antibody P and an antibody N functioning as a positive control and a negative control are used for the SPR sensor unit 3. In general, a specimen such as serum sometimes contains a protein that does not change much. If an appropriate protein is not contained, an inexpensive protein (such as albumin) is selected, and a monoclonal antibody of this protein is used as a positive control.

On the other hand, the protein serving as the negative control may be an antibody corresponding to an antigen not contained in the specimen, and thus, an antibody from a different animal or the like may be used. The antibody P and the antibody N are separately fixed to the SPR sensor unit 3, and various antibodies A, B and C are fixed to the SPR sensor unit 3 corresponding to the other optical fiber 5a. (See FIG. 2). For each of the antibodies A, B, and C, an optimal antibody corresponding to each test item is selected. As described above, an actual immune reaction measurement is performed using the SPR sensor unit 3 on which various antibodies A, B, C, P, and N are immobilized.

As shown in FIG. 7, the SPR sensor unit 3 corresponding to the test item is connected to the optical fiber 5a for measuring the immune reaction of a predetermined sample. The connection of the SPR sensor unit 3 is as follows.
The multi-fiber connector 19 can perform this at one time. Then, the storage buffer 2 in the cap member 21
7 is discharged outside. Thereafter, a sample tube 49 filled with the sample 47 is prepared. The sample 47 is aspirated from the sample tube 49 into the cap member 21. The suction pump 25 described above is used for aspirating the sample 47. The sample tube 49 contains a sample 47 of about 500 [μl] in advance. However, only about 100 μl is sucked into the cap member 21 in practice (see FIG. 8).

When the sample 47 is filled in the cap member 21, an immune reaction measurement is performed. Specifically, one optical fiber 5a is irradiated with the white light 7 via the optical path selecting means 39. Then, the wavelength distribution of the reflected light 11 reflected from the SPR sensor unit 3 at this time is analyzed by the spectroscope 13. Next, the optical path selecting means 3 is connected to another optical fiber 5a.
Irradiate white light 7 through 9. And S at this time
The spectroscope 13 also analyzes the wavelength distribution of the reflected light 11 reflected from the PR sensor unit 3. Thus, the measurement is performed on the SPR sensor units 3 corresponding to all the optical fibers 5a. When the measurement is completed, the SPR sensor unit 3 is removed, and a new SPR sensor unit 3 is connected for the next measurement.

[Data Processing] Next, a case where data processing is performed based on information obtained from the spectroscope 13 will be described. Here, as an example, an immunoreaction measurement using the SPR sensor unit 3 on which the antibodies P and N and different types of antibodies A, B, and C are immobilized as positive and negative controls will be described. FIG. 9 is a diagram showing a result of measuring an immune reaction of a certain specimen. FIGS. 9A and 9B show the relationship between the attenuation wavelength of the reflected light corresponding to the antibody P and the antibody N and the time t. 9 (C), 9 (D) and 9 (E) show the relationship between the attenuation wavelength of the reflected light corresponding to each of the antibodies A, B and C and the time t. Note that t1 in FIG. 9 is the time when the immune reaction ends.

The obtained information is converted into an A / D signal in the main controller 15.
It is converted and stored in a predetermined memory. Then, when one type of measurement is completed, the information is transmitted via the transmitter 45 to the device 5.
3 (computer: see FIG. 10). These operations are performed on the operation panel 51 (FIG. 4) of the immune reaction measurement device 1.
(See key). The state during operation and measurement is displayed on the display unit 43 each time. As this display method, LCD or LED is used. Presentation by a buzzer is also possible.

The host device 53 analyzes the received information (corrects, corrects, and compensates for the data), displays the wavelength distribution, and calculates the concentration of the light source contained in the sample 47 from the plurality of obtained wavelength distributions. Is quantified and displayed. Host machine 5
No. 3 is installed in a nurse center (see FIG. 10) to check the measurement contents on the spot and to use it as a means for deciding treatment and drug administration. Further, at a house call or at a treatment site, as shown in FIG. 11, the portable computer 55 and the portable telephone 57 are used in combination to transmit the measurement result to the hospital (see FIG. 11).

FIG. 12 is a block diagram showing the flow of control information when the main control unit 15 of the immune reaction measuring device 1 controls the operation of each unit. As shown in this figure, the main control unit 15 acts on the optical path selection unit control unit of the optical path selection unit and the spectroscope control unit of the spectroscope to select the optical path and measure the wavelength distribution of the reflected light by the spectroscope. Control. Further, the main control unit 15 works on the measurement data processing unit to perform data processing based on the information obtained from the spectroscope 13. Then, the processed data is stored in the database.
In addition, the main control unit 15 causes the display control unit to display the measurement result of the immune reaction on the display unit 43 and also causes the transmission control unit of the transmitter 45 to transmit information.

FIG. 13 is a block diagram showing a flow of information on the host device 53 (computer) side displaying the result of the immune reaction measurement. The measurement result received by the receiver is
3 (Computer) is stored in the database, and sent to the data calculation unit and the diagnosis unit, where a specific measurement result is determined. The result of the determination is displayed on the display unit.

The specific determination of the measurement of the immune reaction will be described with reference to FIG. FIG. 9 shows the results when normal immune reaction measurement was performed. The vertical axis in each of these figures shows the change with time of the wavelength at which the attenuation due to surface plasmon resonance is the largest. As shown in FIG. 9A, when the wavelength of attenuation of the antibody P as a positive control changes, if this change is the same as a change in the previously measured data table of the antibody N,
It can be determined that appropriate measurements have been made. Conversely, if there is a significant difference from the values in the data table, it can be assumed that there is some defect in the measurement system.

As shown in FIG. 9B, when the attenuation wavelength of the antibody N hardly changes,
It is determined that appropriate measurements have been made. This is because an antibody that specifically reacts with an antigen that should not be included in the sample is used as a negative control. Therefore, conversely, when the wavelength of attenuation of the antibody N changes significantly, it is estimated that a non-specific reaction has occurred, and the measurement accuracy is determined to be unreliable.

When the attenuation wavelength of each of the antibodies A, B, and C is as shown in FIGS. 9C, 9D, and 9E, the attenuation of the antibody B is reduced. The wavelength changes most, and the wavelength of attenuation for antibody C hardly changes. Therefore, from this result, it can be determined that the sample has a high concentration of the antigen specifically reacting with the antibody B, and the concentration of the antigen reacting with the antibody A is next to the second. In addition, it can be assumed that the antigen which reacts with the antibody C is not included.
In the above series of measurements, one sample can be measured at a time. Also, the measurement time is about 3 minutes.

As various antibodies used for measurement, many tumor markers are used for diagnosis of cancer. When you have cancer,
This is because abnormalities occur in specific proteins secreted into the blood. The protein is quantified using a tumor marker made from a monoclonal antibody of this protein as an antibody. When a plurality of tumor markers are used in combination, measurement reliability is improved. In the case of diabetes, the concentrations of a plurality of endocrine proteins related to diabetes change. By quantifying the endocrine proteins, treatment of a patient and dosage of a drug are determined. This is because if the concentration of a plurality of antigens can be known using a plurality of antibodies, the cause of the appearance of the symptoms of diabetes can be quickly and accurately determined. Furthermore, the same can be said for various infectious diseases and blood disorders.

[Second Embodiment] Next, another embodiment of the present invention will be described. In the immunoreaction measurement apparatus according to the present embodiment, as shown in FIG.
Optical switches 101, 102, 103... 109 for switching the transmission and blocking of the white light 7 are arranged in the other end side area of “a”. Then, each of the optical switches 101, 102,
On the downstream side of 103... 109, a splitter 11 that splits the white light 7 into the SPR sensor unit 3 side and the spectroscope 13 side
1, 112, 113... 118 are provided. still,
The present embodiment shares the basic configuration with the first embodiment, and therefore, the same configuration will not be described repeatedly.

As shown in FIG. 14, unlike the first embodiment, the immunoreaction measuring device does not have an optical path selecting means. That is, the optical switches 101, 102, 103 ...
Reference numeral 109 changes to an optical path selection unit. The optical switches 101, 102, 103...
a is disposed on the other end side. This optical switch 10
1, 102, 103... 109 are the main control unit 15 (FIG. 1).
5) controls its operation. In the present embodiment, a total of nine optical switches 101, 102, 103... 1
09 is provided for each optical fiber 5a. Also, splitters 111, 112, 113,... Disposed downstream of the optical switches 101, 102, 103,.
.. 118 are constituted by half mirrors.

The light density of the white light 7 emitted from the halogen lamp as the light source 9 is improved by the condensing lenses 31 and 33. However, since the luminous intensity tends to vary, the integrating sphere 32 is arranged in front of the optical fiber 5a to suppress the variation in the density. The white light 7 exiting the integrating sphere 32 further passes through the polarizing plate 35 and enters the optical fiber 5a. As described above, the optical switches 101, 102, 103,... 109 are provided in each optical fiber 5a, and only one of the optical switches (for example, 101) is turned on under the control of the main control unit 15. It is supposed to be.

The white light 7 that has passed through the optical switch 101 that has been turned on reaches the SPR sensor unit 3 via the splitter 111. In the SPR sensor unit 3, the white light 7 is attenuated by surface plasmon resonance. Then, the light is reflected by the end face of the SPR sensor unit 3 and is split by the splitter 1.
Reflects to the 11 side. In the splitter 111, the reflected light 11
Is incident on the spectroscope 13 via another splitter 39a. As shown in FIG. 14, among the plurality of optical fibers, the one provided with the optical switch 109 is directly introduced into the splitter 39a on the spectroscope 15 side.
Therefore, the white light 7 of the light source 9 and the reflected light 11 from the SPR sensor unit 3 can be compared.

In FIG. 14, each optical fiber 5a is separately illustrated. However, in practice, as shown in FIG. 15, all the optical fibers 5a are bundled to form a multi-optical fiber. Has become. In addition, the immunoreaction measurement device
As in the first embodiment, a predetermined display unit 43 is provided.

[Third Embodiment] Next, a third embodiment will be described. In the immunoreaction measurement apparatus according to the present embodiment, as shown in FIG. 16, an optical switch 121 for switching transmission and cutoff of the white light 7 is provided in the other end side region of each optical fiber 5a. Between the light source 9 and each of the optical switches 121, there is provided a branching unit 37a for branching the white light 7 to the SPR sensor unit 3 side and the spectroscope 13 side.

The branching means 37a has a second optical switch 37b on the side closest to the light source 9, and the second optical switch 37b transmits the white light 7 to the SPR sensor unit 3 and the spectroscope 15 side. The irradiation is switched. In addition, a splitter 37d is disposed downstream of the second optical switch 37b and on the SPR sensor unit 3 side via an isolator 37e. On the other hand, a splitter 37c is provided downstream of the second optical switch 37b on the spectroscope 13 side. in addition,
A predetermined optical fiber is provided between the splitter 37d on the SPR sensor unit 3 side and the splitter 37c on the spectroscope 13 side.

In this embodiment, since the SPR sensor is selected using the optical switch 121, the optical switch 121 is used.
The path on the upstream side may be a single-core optical fiber. That is, the white light 7 emitted from the light source 9 is collected by the focusing lens 31 and the lens 3.
3, the branching means 37 passing through the integrating sphere 32 and the polarizing plate 35
The light enters the single-core optical fiber 5b in FIG. Here, one of the paths on the SPR sensor unit 3 side and the spectroscope 13 side is selected by the second optical switch 37b. The white light 7 directed to the SPR sensor unit 3 enters the optical switch 121 via the isolator 37e and the splitter 37d. In this optical switch 121, only one optical fiber is selected, and the white light 7 enters the SPR sensor unit 3 side.

In the SPR sensor section 3, the reflected light 11 whose wavelength is partially attenuated by the surface plasmon resonance returns to the optical switch 121 side. Then, the reflected light 11 returned to the optical switch 121 is split by the splitter 37d. At this time, the reflected light 11 is transmitted to the spectroscope 13 side,
It does not return to the second optical switch 37b due to the action of the isolator 37e. Then, the reflected light 11 incident on the spectroscope 13 is subjected to wavelength analysis. In addition, the white light 7 incident from the second optical switch 37b also enters the spectroscope 13, whereby the white light 7 and the reflected light 11 are compared. Note that, as shown in FIG. 17, the immune reaction measuring device of the present embodiment is also provided with a predetermined control unit 15 and a display unit 43.

Next, a modification of the branching means will be described. First, FIG. 18A shows an example in which a third optical switch 38c is provided immediately upstream of the spectroscope 13. By using the optical switch 38c in this way, unlike the case of a splitter, since only light from one side is completely selected,
There is no need to consider the state of the other light.

FIG. 18B shows an example in which a circulator 40d for switching the light path is used. When the path of the second optical switch 40b is selected by the circulator 40d, the white light 7 enters the terminal T1 of the circulator 40d and exits from the terminal T2 of the circulator 40d. This white light 11 is transmitted to the SPR sensor unit 3
(Not shown in FIG. 18B), and returns to the terminal T2 of the circulator 40d. Reflected light 11 returning to terminal T2
Comes out of the terminal T3 of the circulator 40d this time.
Then, the light enters the spectroscope 13 via the third optical switch 40c. Further, the white light 7 is directly incident on the spectroscope 13 by switching the second optical switch 40b. The second
The optical switch 40b and the third optical switch 40c operate synchronously. Thereby, the white light 7 and the reflected light 11 can be compared.

The immunoreaction measuring device of the present invention can be used for measuring bacterial species such as bacteria, for examining river and sea water quality,
The present invention can also be applied to inspection of poisons, quality inspection of food such as meat and vegetables, and the like.

[Fourth Embodiment] Next, a fourth embodiment will be described. In the immunoreaction measurement device according to the present embodiment, as shown in FIG. 19, a circulator 51 is provided in the middle of an optical fiber extending from a light source. The circulator 51 has a role of branching the white light 7 from the light source in two directions, one of which is on the side of the SPR sensor unit 3 and the other is on the side of the spectroscope. These optical paths are switched at a predetermined timing.

An optical switch 52 is provided on the downstream side of the circulator 51 where the SPR sensor unit 3 is provided. The optical switch 52 is connected to one optical fiber for incidence, and is connected to a large number of optical fibers on the SPR sensor unit 3 side. This many SP
Except for one of the optical fibers on the R-sensor side, the rest of the optical fiber has an SPR sensor section 3 at its tip. S
One other than the PR sensor unit 3 has a role of transmitting the white light 7 of the light source to the spectroscope side.

On the other hand, the reflected light 11 reflected from the SPR sensor unit 3 is returned to the circulator 51 by the action of the optical switch 52. That is, only the light reflected from one optical fiber of the SPR sensor unit 3 is
The reflected light 11 is transmitted to the spectroscope by the action of the circulator 51.

The white light 7 directly incident from the optical switch 52
Then, the reflected light 11 incident from the circulator 51 is once incident on the splitter 53. This splitter 53
Is located immediately upstream of the spectrometer.
Then, the wavelength distribution of the white light 7 and the reflected light 11 is analyzed by the spectroscope provided on the downstream side of the splitter 53. Note that the splitter 53 on the upstream side of the spectroscope can be replaced with an optical switch.

Next, a modification of the embodiment will be described. In this modification, as shown in FIG. 20, a splitter 62 is provided instead of the above-described circulator 51, and an isolator 61 is provided upstream of the splitter 62. The functions of the splitter 62 and the isolator 61 alone are the same as those described above.

The white light 7 passing through the isolator 61 and the splitter 62 is transmitted to the SPR sensor 3 side. Then, the reflected light 11 reflected by the SPR sensor unit 3 returns to the splitter 62 side. At this time, since the isolator 61 is provided upstream of the splitter 64, the reflected light 11 is not transmitted to the light source side. The reflected light 11 returned to the splitter 62 is incident on a splitter 64 disposed immediately upstream of the spectroscope.

On the other hand, of the white light emitted from the optical switch 63, that is not transmitted to the SPR sensor section 3 side, is directly incident on the splitter 64. That is, white light 7 and reflected light 1
1 enter the spectroscope via the splitter 64. Thereby, the spectroscope downstream of the splitter 64
The wavelength distribution of the white light 7 and the reflected light 11 is analyzed.

[0085]

As described above, in the immunoreaction measuring apparatus of the present invention, since the immunoreaction is measured by the SPR sensor using the optical fiber, real-time measurement is possible, and the immunoreaction is performed with a small amount of the sample. This produces an excellent effect that the reaction can be measured. In addition, since measurement is performed using a plurality of optical fibers, there is an excellent effect that multiple items can be measured in a short time.

Further, since the optical path selecting means is provided between the light source and the optical fiber, the optical path can be switched corresponding to each optical fiber, so that a single spectrometer can measure a large number of items of the immune reaction. The effect is excellent. In addition, since the optical path selecting means is constituted by a liquid crystal mask, the optical path selecting means itself can be configured in a small size, and the optical path selecting means does not have a mechanical driving portion, so that the optical path selecting means becomes a highly reliable optical path selecting means. Is generated.

Further, since the SPR sensor section is connected to the optical fiber by the multi-fiber connector, the SPR sensor section can be easily removed and replaced.
This is convenient when measuring the immune reaction of another sample. In addition, since all of the touching portions of the sample can be exchanged, it is excellent from the viewpoint of biohazard.

Further, since the optical switch for switching the transmission and blocking of the white light is provided in the other end region of each optical fiber, the optical path of the white light can be easily and reliably switched. In particular, an optical path switching unit using liquid crystal leaks some light, but an optical switch has an excellent effect that light can be completely blocked.

Further, between the light source and each optical switch, a branching means for branching the white light into the SPR sensor unit side and the spectroscope side is provided. For this reason, an advantageous effect is obtained in that the upstream side of the optical switch can have a simple configuration and the configuration can be simplified as compared with a case where a splitter is provided in each optical fiber. .

Further, since a cap member is provided in the SPR sensor unit, a suction pump for sucking a sample into the internal space of the cap member is provided in the apparatus main body, and the operation of the suction pump is controlled by the main control unit. This produces an excellent effect that the amount of sample required for measurement can be accurately aspirated.

Further, since the storage buffer is previously filled in the cap member, the antibody fixed to the SPR sensor can be stably held. In addition, by performing the immunoreaction measurement while the storage buffer of the sensor head is being filled, an excellent effect that the storage buffer can be used for verifying the measurement accuracy of the immunoreaction measurement device is obtained.

Further, a transmitter is provided in the main body of the apparatus, and the output of the spectroscope is transmitted from the transmitter to the host apparatus. Therefore, it is possible to avoid the restriction by a cable or the like, and to improve the operability of the immunoreaction measurement apparatus itself. An excellent effect of being able to be performed.

Further, since antibodies as a positive control and a negative control are fixed to the SPR sensor portion, it is possible to easily determine a defect of the measurement system itself and a possibility of non-specific reaction with the antigen, There is an excellent effect that the accuracy can be improved.

[Brief description of the drawings]

FIG. 1 is a block diagram showing a first embodiment of the present invention.

FIG. 2 is a partially cutaway side view showing the SPR sensor unit disclosed in FIG. 1;

FIG. 3 is a sectional view showing a surface structure of an SPR sensor unit disclosed in FIG. 2;

FIG. 4 is a cross-sectional view showing the overall configuration of the immune reaction measurement device disclosed in FIG.

FIG. 5 is a perspective view showing the vicinity of the other end of the multi-optical fiber of the immune reaction measuring device disclosed in FIG. 1;

FIG. 6 is a diagram illustrating that a specific wavelength is attenuated by surface plasmon resonance.

FIG. 7 is an explanatory diagram showing a process of measuring an immune reaction.

FIG. 8 is an explanatory diagram showing a case where a specimen is aspirated into a cap member in the immunoreaction measurement process disclosed in FIG. 7;

FIG. 9 is a diagram showing a change in attenuated wavelength with respect to time when an immunoreaction measurement is performed. FIG. 9 (A) shows the case of antibody P, FIG. 9 (B) shows the case of antibody N, FIG.
(C) shows the case of antibody A, FIG. 9 (D) shows the case of antibody B, and FIG. 9 (E) shows the case of antibody C.

FIG. 10 is an explanatory diagram illustrating a communication state between the immune reaction measurement device and a host machine.

FIG. 11 is an explanatory diagram illustrating another communication state between the immune reaction measurement device and the host machine.

FIG. 12 is a block diagram showing a flow of information in the immune reaction measuring device.

FIG. 13 is a block diagram showing a flow of information in a host machine.

FIG. 14 is a block diagram showing a second embodiment of the present invention, particularly an enlarged view of an optical fiber and an SPR sensor unit.

FIG. 15 is a block diagram showing the overall configuration of the immune reaction measurement device disclosed in FIG.

FIG. 16 is a block diagram showing a third embodiment of the present invention, particularly an enlarged view of an optical fiber and an SPR sensor unit.

FIG. 17 is a block diagram showing the overall configuration of the immune reaction measurement device disclosed in FIG.

FIG. 18 is a block diagram showing a modification of the branching means disclosed in FIG. 16; FIG. 18A shows an example using an optical switch, a splitter and an isolator, and FIG.
Indicates an optical switch, an optical switch, a splitter and a circulator.

FIG. 19 is a block diagram illustrating another example of the branching unit according to the fourth embodiment of this invention.

FIG. 20 is a block diagram showing a modification of the branching means disclosed in FIG.

FIG. 21 is a diagram illustrating the principle of surface plasmon resonance.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Immune reaction measuring device 3 SPR sensor part 5 Multi optical fiber 7 White light 9 Light source 11 Reflected light 13 Spectroscope 15 Main control part 17 Device body 19 Multi-fiber connector 21 Cap member 23 Suction port 25 Suction pump 27 Storage buffer 37 Optical path selection Means 45 Transmitter 53 Host machine P Positive control N Negative control

Claims (10)

[Claims] 1. An optical fiber having an SPR sensor at one end, a light source for irradiating predetermined white light from the other end of the optical fiber, and a wavelength distribution of light reflected from the SPR sensor. An immunoreaction measurement device comprising: a spectroscope to be analyzed; a main control unit that controls the operation of the light source and the spectroscope; and a device main body that houses these components; and at least two optical fibers are provided. . 2. The immunoreaction measuring apparatus according to claim 1, wherein a predetermined optical path selecting means is provided between the light source and the other end of the optical fiber. 3. The optical path selecting means is constituted by a predetermined liquid crystal mask, wherein the liquid crystal mask has a selective transmission function of transmitting white light to only one of the optical fibers. Item 3. The immunological reaction measuring device according to Item 2. 4. The immunoreaction measurement device according to claim 1, wherein a multi-fiber connector is provided near the SPR sensor unit so that a plurality of the optical fibers can be simultaneously connected. 5. The immunoreactivity measurement device according to claim 1, wherein an optical switch for switching transmission and cutoff of the white light is provided in a region on the other end side of each of the optical fibers. 6. The immunity according to claim 5, wherein a branching unit for branching the white light into the SPR sensor unit side and the spectroscope side is arranged between the light source and each optical switch. Reaction measurement device. 7. The SP around the SPR sensor section
In addition to providing a cap member for covering the R sensor unit, a suction port for sucking a sample is formed in a part of the cap member, and a suction pump for sucking the sample into the cap member at a predetermined position in the apparatus body. The immune reaction measuring device according to claim 1, wherein the device is provided. 8. The immunological reaction measuring device according to claim 5, wherein a storage buffer is previously filled in the cap member. 9. A predetermined transmitter is provided in the apparatus main body, an output of the spectroscope is transmitted to the transmitter, and the spectroscope is transmitted from the transmitter to a receiver connected to a predetermined host device. The immunoreaction measurement device according to claim 1, wherein the output of (1) is transmitted. 10. The immunoreactivity measurement device according to claim 1, wherein an antibody serving as a positive sensor and an antibody serving as a negative sensor are fixed to the SPR sensor unit.