JP2000230929A - Spr sensor cell and immunoreaction measuring device using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an SPR(surface plasmon resonance) sensor cell easily fixing an antibody and holding a specimen and an immunoreaction measuring device using the same and to provide the SPR sensor cell capable of rapidly measuring immunoreaction of every kind. SOLUTION: The SPR sensor cell 3 is equipped with cores 7a, 7b having SPR sensor portions 8 formed to a part of the surfaces thereof, clads 5, 9 covering the cores 7a, 7b and the through-holes 13 formed to the clads 5, 9 to communicate with the SRP portions 8. At least two cores 7a, 7b are provided and the through-holes 13 are formed so as to simultaneously communicate with the SPR portions 8 formed to at least two cores 7a, 7b.

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 a sample 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, by comparing the wavelength of light that attenuates the most before the immune reaction and the wavelength of light that attenuates the most after the immune reaction, the immune reaction can be measured. 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.

[0017]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an SPR sensor cell in which the inconvenience of the prior art can be improved, and in which an antibody can be fixed and a sample can be easily retained, and an immunoreaction measuring device using the same. . It is another object of the present invention to provide an SPR sensor cell capable of performing various immune reaction measurements quickly.

[0018]

In order to achieve the above object, according to the present invention, there is provided a core having an SPR sensor portion formed on a part of its surface, a clad covering the core, and a clad formed on the clad. A through hole communicating with the SPR sensor unit, at least two cores, and at least two SPRs formed with the through holes in at least two cores.
The configuration is such that it is formed so as to communicate with the sensor unit at the same time.

With the above configuration, first, a sample to be subjected to an immune reaction measurement is injected into the through hole.
As a result, one sample can be used for each S of at least two cores.
Contact with PR sensor. Then, an immune reaction occurs in the SPR sensor section. Analyzing the wavelength distribution of the light incident on each core and emitted from the SPR sensor cell,
The immune response in each core can be measured.

[0020]

DESCRIPTION OF THE PREFERRED EMBODIMENTS [First Embodiment] [Overall Overview of SPR Sensor Cell] A first embodiment of the present invention will be described with reference to the drawings.

First, an SPR sensor cell 3 according to the present embodiment will be described with reference to FIGS. Here, FIG. 2A is a cross-sectional view taken along line XX of FIG. 1A. The SPR sensor cell 3 of the present invention uses an optical waveguide. More specifically, SPR sensor cell 3
Is a plate-shaped first clad (substrate) 5, two cores 7 a and 7 b disposed on the first clad 5, and a second covering the surfaces of the cores 7 a and 7 b and the first clad 5. And a clad (upper plate) 9. There are various types of optical waveguides, such as a planar type, a strip type, an embedded type, and a lens type. The details will be described below.

The first clad 5 is made of glass or the like and has a thin plate shape. And this first clad 5
On top, two cores 7a and 7b to which light is transmitted are mounted. The cores 7a and 7b extend over the entire length of the SPR sensor cell. These cores 7a, 7b
It is made of glass or plastic. Also,
A second clad 9 is provided on the surface of the first clad 5 so as to straddle the cores 7a and 7b. More specifically, two concave grooves 11a and 11b corresponding to the cores 7a and 7b are formed on the bottom surface of the second clad 9.
When the second clad 9 is disposed on the first clad 5, the cores 7a and 7b are fitted into the concave grooves 11a and 11b, and the bottom surface of the second clad 9 is
It comes to adhere to.

When the cores 7a and 7b are mounted on the first clad 5, an adhesive may be used or the cores 7a and 7b may be heated and heated.
A method of melting the boundary surface between the first clad 7b and the first clad 5 is considered. The same applies to the case where the second clad 9 is mounted on the first clad 5. In addition, the core 7 is formed using an adhesive.
When a and 7b are mounted on the first clad 5, it is necessary to use an adhesive having a lower refractive index than the cores 7a and 7b in consideration of the attenuation of light by the adhesive.

A predetermined through-hole 13 is formed substantially at the center of the second clad 9. More specifically, a through hole 13 is formed from the upper surface of the second clad 9 to between the cores 7a and 7b. That is, each core 7
a and 7b are arranged in parallel with each other at a predetermined interval. A through-hole 13 having a width substantially equal to the interval between the cores 7a and 7b is formed. Therefore, a part of the surface of the cores 7a and 7b is exposed toward the inner surface of the through hole 13. However, the through hole 13
In the portions of the cores 7a and 7b corresponding to the above, a metal thin film is formed as described later to form the SPR sensor section 8.

As a method of forming the through-hole 13 in the second clad 9, it is conceivable that a single plate-shaped second clad is punched. That is, the two concave grooves 11a,
A through-hole 13 is formed in the second clad 9 on which the 11b is formed, at a position corresponding to between the concave grooves 11a and 11b. The through-hole 13 is formed from the front surface of the second clad 9 to the back surface (the side corresponding to the first clad 5).

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 surface of the first clad 5, and the like. This space serves as a sample storage unit 14 for storing a sample when performing an immune reaction measurement.

Here, in order for each of the cores 7a and 7b to function as an optical waveguide, the first clad 5 and each of the cores 7a and 7b are required.
It is necessary that a certain relationship be established between b and the refractive index of the second cladding 9. Specifically, it is necessary that the cores 7a and 7b have the largest refractive index, and then the second clad 9 has the largest refractive index. Further, the refractive index of the first cladding 5 may be equal to or smaller than the refractive index of the second cladding 9. If this is expressed by a relational expression, for example, the first
Assuming that the refractive index of the cladding 5 is N1, the refractive index of each of the cores 7a and 7b is N2, and the refractive index of the second cladding 9 is N4, N2> N1 = N4 or N2>N4> N1.

[Structure of core surface] Next, the cores 7a, 7
The detailed structure of the part b facing the sample storage unit 14 will be described. Since this part is a part that actually functions as an SPR sensor (SPR sensor unit 8), its structure is important. FIG. 2B is an enlarged view of the surface of the core 7b in FIG. Specifically, FIG.
As shown in (B), a metal thin film 15 and a dielectric film 17 are sequentially formed on the surface of the core 7b, and an antibody (or antigen) is fixed on the surface of the dielectric film 17.

More specifically, in order to form the SPR sensor portion, the core 7b is coated with Au as the metal thin film 15 by vapor deposition or the like. However, the metal thin film 15 may be made of Ag instead of Au. An SPR sensor unit can be configured. Here, the core 7b is glass,
When the metal thin film 15 is made of Au, the surface of the core 7b may be coated with chromium (Cr) having a thickness of several nm. This is because the metal thin film 15 is stabilized by coating Au with chromium.

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]
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. This immune reaction also changes the wavelength of light that causes surface plasmon resonance.

For this reason, when light is introduced into each of the cores 7a and 7b and the wavelength distribution of the light emitted from the cores 7a and 7b after the immune reaction is generated is analyzed, the wavelength distribution when no immune reaction is generated is obtained. Will be different. Specifically, since light of a specific wavelength that causes surface plasmon resonance is attenuated, an immune reaction can be measured by knowing the wavelength of the attenuated light.

[Immune Reaction Measuring Apparatus] FIG.
1 is an overall schematic diagram of an immune reaction measurement device 1 using a PR sensor cell 3. FIG. Light source 2 for irradiating test light for measuring immune reaction
Explanation will be made starting from 5. The light source 25 irradiates the light L with a broadband wavelength, and for example, a halogen lamp or the like can be used. As the light source 25, a white LED lamp other than a halogen lamp can be used. If a white LED lamp is used, the cost is
It is about 1/30, 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. The light L emitted from the light source 25 is condensed by the condenser lens 27 and is incident on the receptacle 29. Since the receptacle 29 is connected to the optical fiber connector 31, the light enters the optical fiber 33 via the optical fiber connector 31. The light L passing through the optical fiber 33 is further transmitted to the optical fiber connector 35 and the receptacle 3.
7, the light passes through the condenser lens 39. Condensing lens 3
The light L transmitted through 9 enters the SPR sensor cell 3.

The light L incident on the SPR sensor cell 3 is
The light passes through the cores 7a and 7b. At this time, surface plasmon resonance occurs in the metal thin film 15 made of Au as described above. And by surface plasmon resonance,
The light intensity of the light of the specific wavelength is attenuated, and then the light L is emitted from the SPR sensor cell 3. Then, the light L emitted from the SPR sensor cell 3 passes through the condenser lens 41 and enters the receptacle 43. The light L incident on the receptacle 43 is incident on a predetermined spectroscope 49 via an optical fiber connector 45 and an optical fiber 47 connected to the receptacle 43.

The spectroscope 49 analyzes the wavelength distribution of the incident light L. More specifically, the wavelength distribution before an immune reaction occurs is checked in advance. Specifically, the sample storage unit 1
The wavelength distribution is measured in a state where no sample is put in 4 (or a state where the sample is filled with no antigen). Next, a sample to be subjected to an immune reaction measurement is injected into the sample storage unit 14, and the light L after the immune reaction actually occurs
Examine the wavelength distribution of. Due to the difference in the obtained wavelength distribution,
The presence or absence of an immune reaction and the state of the immune reaction can be determined. In addition to using the spectroscope 49 to measure the wavelength distribution,
It is also conceivable to use a photodiode. In this case, it is conceivable that a wavelength that is attenuated by the immune reaction is estimated in advance, and a filter that can transmit only light of this wavelength is provided. Alternatively, a plurality of photodiodes may be provided, and a filter capable of transmitting light of a different wavelength may be provided for each photodiode.

[Second Embodiment] FIG. 4 shows a second embodiment of the present invention.
It is a perspective view showing SPR sensor cell 3b concerning an embodiment. Here, the same parts as those in the first embodiment will be described using the same reference numerals. This SPR sensor cell 3
b is the SPR whose basic shape is described in the first embodiment.
It is the same as the sensor cell 3. However, in the present embodiment, members constituting the SPR sensor cell 3b are different. That is, the SPR sensor cell 3b has a three-layer structure. Details will be described below.

First, as shown in FIG. 4B, the first clad 5 is made of a plate-like member as in the first embodiment.
The cores 7a. The second layer including 7b is configured by combining a plurality of claddings. That is, two cores 7a and 7b are arranged in parallel with each other at a predetermined interval, and two short claddings 10b are arranged between these cores 7a and 7b. This short clad 10b
The length of the cores 7a, 7b is shorter than the entire length of the cores 7a, 7b.
b are disposed on both ends. Therefore, the cores 7a. 7
The short cladding 10b does not exist at the center of b. The region where the short clad 10b does not exist becomes the specimen storage unit and the SPR sensor unit at the same time. Therefore, short clad 10
The difference between the length of two consecutive b's and the length of each of the cores 7a and 7b is the total length of the sample storage section. The thickness of the short clad 10b described here is equal to the thickness of the cores 7a and 7b.

A long clad 10a is provided on both outer sides of each of the cores 7a and 7b. This long clad 10
“a” has the same length as each of the cores 7a and 7b. The thickness of each long clad 10a is equal to that of each core 7a, 7b. Therefore, the second layer in which the cores 7a and 7b, the short clad 10b, and the long clad 10a are combined becomes a plate member having a constant thickness. In addition, these short claddings 10b,
The width of the combination of the cores 7a, 7b and the long clad 10a is equal to the width of the first clad 5 described above.
The short clad 10b and the long clad 10a have the same refractive index as the second clad 9b.

Further, the third layer is the second clad 9b. The second clad 9b is a plate having a constant thickness,
A through-hole 13b is formed in the central region. The length of the through-hole 13b corresponds to the specimen storage section, and is substantially equal to the distance between the short clads 10b described above. The width of the second cladding 9b is equal to the width of the first cladding 5. In addition, the position of the through-hole 13b is not limited to the central portion, but may be any position corresponding to the sample storage unit.

In the SPR sensor cell 3b of the present embodiment, the first layer 5 and the second layer in which the cores 7a and 7b are combined with the clads 10a and 10b, and the third layer composed of the second clad are sequentially arranged. It is laminated. Each member may be joined with an adhesive or joined with oil. Thus, in the present embodiment, the second layer and the third layer are formed separately. For this reason, as described in the first embodiment, the concave grooves 11a and 11b are formed in the second clad 9.
(See FIG. 1) may not be formed. Therefore, it is easy to configure the SPR sensor cell 3b.

Third Embodiment Next, a third embodiment will be described with reference to FIG. This embodiment shows a case where the second cladding 9b in the second embodiment is configured by a different method. The second claddings 9c1 and 9c2 shown in FIG. 5 are formed by bonding four members. First, the second clad 9c1 in FIG. 5A includes a short clad 9c11 sandwiching the through hole 13c1 in the longitudinal direction and a long clad 9c12 sandwiching the through hole 13c1 in the width direction.

Each of the two short claddings 9c11 has a length equal to or less than half the length of the above-mentioned core, and is disposed at a predetermined interval from each other. The space between the short clads 9c11 is a through hole 13c1. The two long claddings 9c12 have the same length as the entire length of the core.
1 is sandwiched from both sides. That is, the through hole 13c is formed by each short clad 9c11 and long clad 9c12.
1 is formed. And since each clad has the same thickness, it becomes a plate-shaped clad after being mutually bonded.

Further, the second cladding 9 shown in FIG.
c2 is a short clad 9 sandwiching the through hole 13c2 from the width direction.
c21 and a long clad 9c22 sandwiching the through hole 13c2 and the short clad 9c21 from the longitudinal direction of the core.

The two short claddings 9c21 each have a length equal to the length of the through hole 13c2, and are arranged at a predetermined interval from each other. The space between the short clads 9c11 is a through hole 13c1.

The two long claddings 9c22 are formed by SP
It has a length equal to the width of the R sensor cell, and sandwiches each short clad 9c21 described above from both sides. That is, each short clad 9c21 and long clad 9c22
Thereby, a through hole 13c2 is formed. And since each clad has the same thickness, it becomes a plate-shaped clad after being mutually bonded.

As described above, by combining a plurality of members having the same thickness, the second claddings 9c1 and 9c2 having the through holes 13c1 and 13c2 can be easily formed. Therefore, unlike the first and second embodiments, there is no need to perform a complicated and difficult operation of forming a through hole in a plate-shaped clad.

[Fourth Embodiment] Next, a fourth embodiment will be described with reference to FIG. In this embodiment, the second clad 9 in the first embodiment is configured by a different method. It is characterized in that the second clad 9d is configured by combining six members having different thicknesses. 2
The cores 7a and 7b and the first clad 5 are the same as in the first embodiment.

The second cladding 9d of the present embodiment firstly
Two short claddings 9d1 are arranged in series, and an interval corresponding to the through-hole 13d is provided between the short claddings 9d1. Each of these short claddings 9d1 is composed of two intermediate claddings 9d2 from both sides in the width direction.
Is held by The intermediate cladding 9d2 has substantially the same length as the cores 7a and 7b. Thereby, the through hole 13d is formed by the short clad 9d1 and the intermediate clad 9d2.

Here, the short cladding 9d1 and the intermediate cladding 9d2 have different thicknesses. That is, the thickness of the intermediate cladding 9d2 is smaller than the thickness of the short cladding 9d1 by the thickness of the cores 7a and 7b. This is the second cladding 9
This is to make the thickness of the short cladding 9d1 equal to the thickness of the short cladding 9d in a state where the cores 7a and 7b are incorporated in the portion of the intermediate cladding 9d2.

A long clad 9d3 is provided on both sides of each intermediate clad 9d2 in the width direction. The length of the long clad 9d3 is substantially equal to the length of the cores 7a and 7b. However, the thickness of the long clad 9d3 is equal to that of the short clad 9d1. Accordingly, when the core, the short clad 9d1, the intermediate clad 9d2, and the long clad 9d3 are all bonded, a member having a constant thickness is obtained. By bonding the first clad 5 to this, the same SP as in the first embodiment is obtained.
An R sensor cell can be configured.

As described above, the bonding process is increased by combining a plurality of members, but it is necessary to machine the concave grooves 11a and 11b and the through-hole 13 as shown in the first embodiment. Therefore, the SPR sensor cell can be easily manufactured. In particular, when the material of the clad is glass, there is an inconvenience that chipping or the like occurs at the time of processing and the yield is reduced. However, such a problem does not occur in the SPR sensor cell according to the present embodiment.

[Fifth Embodiment] Next, a fifth embodiment will be described with reference to FIG. In the present embodiment, the second
This embodiment has the same basic configuration as the first embodiment. However, in this embodiment, the end face of each clad is different from that of the second embodiment. That is, the first clad 5d, the short clad 10e1, the long clad 10e2, and the second clad 9
e, each end face is formed in a ground glass shape or is made of aluminum (A
l) Coating or black paint is applied.

The reason why light does not easily pass through the end face of each clad is to allow light to enter only the cores 7a and 7b. This is because, if light enters from a clad other than the cores 7a and 7b, the mixed light may enter the cores 7a and 7b, which may reduce the measurement accuracy of the immunoreaction measurement.

The means described above is merely an example, and is not particularly limited as long as it makes it difficult for light to enter from the end face of each clad. For example, a plate-like member (for example, made of rubber or plastic) that does not transmit light may be attached to the end surface of the clad.

FIG. 8 is a view showing a state in which light for measuring an immune reaction is incident on the SPR sensor cell 3e according to the present embodiment. SPR sensor cell 3e of the present embodiment
Has two cores 7a and 7b. For this reason,
The light for the measurement of the immune reaction is simultaneously emitted from the two cores 7a and 7
b (the elliptical part in the figure).

As described above, by allowing light to be incident on the two cores 7a and 7b at the same time, one optical system such as a light source and a condenser lens may be provided. And
By fixing the same antibody to each of the cores 7a and 7b, the measurement accuracy of the immune reaction can be improved. If different antibodies are immobilized on the cores 7a and 7b, immune reactions of different antigens on the same specimen can be simultaneously measured. In addition, by sequentially irradiating light to each of the cores 7a and 7b, two items of immune reaction measurement can be performed for one sample. Alternatively, one of the cores can be used for reference.

As described above, the result of the immune reaction measurement can be measured as a change in the wavelength distribution of light emitted from the SPR sensor cell. Therefore, for example, when the same antibody is immobilized on each of the cores 7a and 7b, the light emitted from each of the cores 7a and 7b is collected into one, and the wavelength distribution is measured by one spectroscope. can do. On the other hand, when a different antibody is immobilized on each of the cores 7a and 7b, the respective immune reactions must be measured. Therefore, in this case, the optical path of each core 7a, 7b is sequentially switched, and the wavelength distribution is measured by one spectroscope. If it is possible to equip a plurality of spectroscopes, each core 7
What is necessary is just to arrange a spectroscope corresponding to a and 7b. As a result, it is possible to simultaneously measure different items of the immune response for each of the cores 7a and 7b.

[Sixth Embodiment] FIG. 9 shows a sixth embodiment of the present invention.
It is a perspective view which shows embodiment. The feature of this embodiment is that it has five cores 7a to 7e and four through holes 13f3 to 13f4 communicating with these cores. That is, the through hole 13 is provided between the adjacent cores 7a and 7b.
f1 is formed, and the through hole 1 is also provided between the cores 7b and 7c.
3f2 is formed. The same applies to the following.

As described above, when a plurality of cores 7a... 7e and a plurality of through holes 13f1... 13f4 corresponding thereto are provided, the following advantageous effects are obtained. That is, a part of the surface of the core 7a facing the through hole 13f1 functions as an SPR sensor unit. Further, a part of the surface of the core 7b facing the through hole 13f1 also functions as an SPR sensor unit. In addition, the surface which is a part of the surface of the core 7b and faces the through hole 13f2 is also SP
Functions as an R sensor unit. The same applies to the following.

In this embodiment, five cores 7a... 7
13f4 and eight through holes 13f1 to 13f4, eight apparent SPR sensor units can be obtained. However, even if SPR sensor sections are provided on both sides of the core, the light emitted from each core has a wavelength distribution measured by a single spectrometer, so that it is not possible to actually measure eight types of immune reactions. Can not. Therefore, for example, as an example of how to use the SPR sensor cell 3f of the present embodiment, the SP of one core
Immobilize the same antibody on the portion that functions as the R sensor,
It is conceivable to improve the sensitivity of the immune response measurement.

In this embodiment, the case where the number of through holes is smaller by one than the number of cores has been described. However, the present invention is not limited to this. That is, one more through hole may be provided for the number of cores.
By doing so, the surface of the core becomes more SP
It can be used as an R sensor unit. For example, by providing five cores and six through-holes, a total of ten locations on both surfaces of each core can be formed as SPR sensor sections.

The number of cores described above is merely an example, and 5
It is not limited to books. The number may be three or four, or six or more. In the present embodiment, each core is provided on both sides of the through hole, but the present invention is not limited to this. That is, a core may be further provided directly below the through hole. In this way, by making the three cores face each through-hole at the same time, it is possible to perform more various items of immune reaction measurement.

In each of the above embodiments, the light incident on the SPR sensor cell for measuring the immune reaction is emitted from the opposite side of the SPR sensor cell as it is. However, the present invention is not limited to this. That is, a metal thin film made of Ag or the like is deposited on the other end surface of the core. This is because the other end of the core is used as a light reflecting surface. As described above, when the reflection surface is formed on the other end surface of the core,
Light incident from one end surface of the core causes surface plasmon resonance in a central region of the core. Then, the light is reflected by the metal thin film 61 on the other end surface of the core.

When the light reflected by the metal thin film on the other end face of the core is analyzed, the light intensity of light of a specific wavelength decreases.
Thus, when comparing the case where the metal thin film is present and the case where the metal thin film is not present, the light intensity of the specific wavelength is reduced when the light intensity of the specific wavelength is reflected by the metal thin film. On the other hand, the light intensity of other wavelengths hardly decreases. This is considered to be because surface plasmon resonance is generated before the light of the specific wavelength reaches the other end surface of the core, and surface plasmon resonance is generated when the light is reflected back. Therefore, the S
PR sensor cells have substantially improved sensitivity.

[0065]

As described above, according to the first aspect of the present invention, the core having the SPR sensor portion formed on a part of the surface thereof, the clad covering the core, and the SPR sensor formed on the clad. And a through hole communicating with the at least two cores, and the through hole is formed so as to simultaneously communicate with each of the SPR sensor portions formed on the at least two cores. For this reason, it is possible to perform an immune reaction measurement with at least two SPR sensor units simply by forming one through hole. Therefore, the amount of the sample injected into the SPR sensor cell can be reduced. Further, the size of the SPR sensor cell itself can be reduced. In addition, when two cores are used for measuring the immunoreactivity of the same antigen, an excellent effect that the sensitivity of the measurement can be improved is produced.

Further, in the invention according to claim 2, the SP
An R sensor unit is formed on at least two cores of one core, a plurality of the through holes are provided, and the mutually adjacent ones of the plurality of the through holes are simultaneously connected to the respective SPR sensor units. Formed. Therefore, if the same antibody is immobilized on the two SPR sensor portions of the core, the measurement sensitivity can be improved. Other effects similar to those of the first aspect are obtained.

[Brief description of the drawings]

FIG. 1 is a perspective view showing an SPR sensor cell according to a first embodiment of the present invention, and FIG.
FIG. 1B shows a core.

2 shows a cross-sectional view of the SPR sensor cell disclosed in FIG. 1, FIG. 2 (A) shows a cross-sectional view of a through-hole region, and FIG.
FIG. 2B is an enlarged cross-sectional view of the SPR sensor unit in FIG.

FIG. 3 is a schematic explanatory view showing an immune reaction measuring device provided with the SPR sensor cell disclosed in FIG.

FIG. 4 is a perspective view showing a second embodiment of the present invention,
4A shows an overall view, FIG. 4B shows a first clad, FIG. 4C shows a core and a clad joined to the core, and FIG. 4D shows a second clad. Show.

FIG. 5 is a perspective view showing a third embodiment of the present invention,
FIG. 5 (A) shows a diagram in which the second clad used in the second embodiment is constituted by four clad members, and FIG. 5 (B) also shows an example in which the second clad is similarly constituted by four clad members.

FIG. 6 is a perspective view showing a fourth embodiment of the present invention,
FIG. 3 shows an exploded view of a first clad, a second clad, and a core.

FIG. 7 is a perspective view showing a fifth embodiment of the present invention,
7A shows an overall view, FIG. 7B shows a first clad, FIG. 7C shows a core and each clad, FIG.
(D) shows the second clad.

FIG. 8 shows a state in which light is incident on the SPR sensor cell disclosed in FIG. 7;

FIG. 9 is a perspective view showing a sixth embodiment of the present invention;
3 shows an SPR sensor cell having a plurality of cores and through holes.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Immune reaction measuring apparatus 3 SPR sensor cell 5 First clad 7a, 7b Core 8 SPR sensor part 9 Second clad 13 Through hole 14 Sample storage part 25 Light source 49 Spectroscope L Light

Continued on the front page F term (reference) 2G057 AA01 AA12 AB06 AC01 BA03 BB01 BB06 BD03 BD04 CB03 2G059 AA06 AA10 BB13 CC17 DD03 EE04 JJ17

Claims (9)

[Claims] A core having an SPR sensor portion formed on a part of a surface thereof, a clad covering the core, and a through hole formed in the clad and communicating with the SPR sensor portion; An SPR, wherein two SPRs are provided and the through holes are formed so as to simultaneously communicate with each of the SPR sensor portions formed on at least two cores.
Sensor cell. 2. The SPR sensor section is formed in at least two places of one core, and a plurality of the through-holes are provided, and the mutually adjacent ones of the plurality of through-holes are
The SPR sensor cell according to claim 1, wherein the SPR sensor cell is formed so as to communicate with each of the SPR sensor units at the same time. 3. An end face of each of the claddings is formed so that light does not enter from the outside.
Or the SPR sensor cell according to 2. 4. A core having an SPR sensor part formed on a part of its surface, a clad covering the core, and a through-hole formed in the clad and communicating with the SPR sensor part, wherein the core is at least provided. An SPR sensor cell formed so as to simultaneously communicate with each of the SPR sensor units formed in at least two cores, a light source for entering light into the core, and light emitted from the SPR sensor cell. A spectroscope or a photodiode for receiving the light and analyzing the wavelength distribution. 5. The SPR sensor section is formed in at least two places of one core, and a plurality of the through-holes are provided, and the mutually adjacent ones of the plurality of through-holes are
The immunoreaction measurement device according to claim 4, wherein the device is formed so as to communicate with each of the SPR sensor units simultaneously. 6. The immunoreactivity measurement device according to claim 4, wherein the light source is capable of simultaneously entering light into at least two of the cores. 7. The immunoreactivity measurement device according to claim 4, wherein the light source is capable of sequentially inputting light to one of the cores. 8. The immunoreactivity measurement device according to claim 4, wherein the light source is a white LED lamp or a halogen lamp that can emit light of different wavelengths. 9. The immunoreaction measuring apparatus according to claim 4, wherein an end face of each clad of the SPR sensor cell is formed so that light does not enter from the outside.