WO2008075578A1 - Détecteur de plasmon de surface - Google Patents

Détecteur de plasmon de surface Download PDF

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Publication number
WO2008075578A1
WO2008075578A1 PCT/JP2007/073763 JP2007073763W WO2008075578A1 WO 2008075578 A1 WO2008075578 A1 WO 2008075578A1 JP 2007073763 W JP2007073763 W JP 2007073763W WO 2008075578 A1 WO2008075578 A1 WO 2008075578A1
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WIPO (PCT)
Prior art keywords
core
dielectric layer
light
surface plasmon
measurement
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PCT/JP2007/073763
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English (en)
Japanese (ja)
Inventor
Tomohiko Matsushita
Takeo Nishikawa
Jun Kishimoto
Hideyuki Yamashita
Ryosuke Hasui
Shigeru Aoyama
Original Assignee
Omron Corporation
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Publication of WO2008075578A1 publication Critical patent/WO2008075578A1/fr

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
    • G01N21/251—Colorimeters; Construction thereof
    • G01N21/253—Colorimeters; Construction thereof for batch operation, i.e. multisample apparatus
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55—Specular reflectivity
    • G01N21/552—Attenuated total reflection
    • G01N21/553—Attenuated total reflection and using surface plasmons
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
    • G01N33/553—Metal or metal coated

Definitions

  • the present invention relates to a surface plasmon sensor. More specifically, a surface plasmon sensor that detects the surface state of each measurement region by dispersing signals from a plurality of measurement regions having dielectric layers having different refractive indexes, and the surface plasmon sensor are used.
  • the present invention relates to medical testing equipment and chemical testing equipment.
  • Patent Document 1 proposes a fluorescence detection type inspection apparatus. This is a device that observes fluorescence emitted from biomolecules that are specifically bound to cDNA immobilized on a slide glass by modifying biomolecules with fluorescent dyes. In such a fluorescence detection system, it is possible to analyze many types of genes and proteins simultaneously by applying different cDNAs on the slide glass in the form of dots. ing.
  • Patent Document 2 proposes a Balta type surface plasmon sensor. This is on the bottom surface of the substrate with a metal thin film formed on the top surface. A triangular prism is arranged, and light is incident on the interface between the metal thin film and the prism at various angles by the light projection optical system, and the intensity of the light reflected at the interface between the metal thin film and the prism is measured. The measurement is made with a photodetector. According to such an apparatus, a reaction of an antigen that specifically binds to an antibody or the like immobilized on a metal thin film can be detected as a change in received light intensity in the photodetector.
  • Balta-type surface plasmon sensor In such a Balta-type surface plasmon sensor, errors due to fluorescent molecules do not occur, but it is difficult to make an array due to the structure, and one surface plasmon sensor only performs one inspection at a time. I could not.
  • the conventional Balta-type surface plasmon sensor requires image processing in order to perform analysis, and the surface plasmon sensor becomes larger and takes longer to analyze! /.
  • an optical waveguide type surface plasmon sensor As means for downsizing the surface plasmon sensor, various optical waveguide type surface plasmon sensors using waveguide type surface plasmon resonance have been proposed.
  • a metal thin film is provided on the upper surface of a core embedded in a cladding layer, light is incident from one end of the core, and light emitted from the other end of the core is received by a photodetector. To do.
  • Patent Document 3 Japanese Patent Laid-Open No. 2002-162346
  • a core is provided with a switching portion and branched to form a plurality of cores in parallel.
  • a single core only one metal thin film can be provided, and multiple inspections cannot be performed at one time.
  • Patent Document 2 JP-A-6-167443
  • Patent Document 3 JP 2002-162346 A
  • the present invention has been made in view of the technical problems as described above, and an object of the present invention is to obtain signals from a plurality of measurement regions having dielectric layers having different refractive indexes from each other (hereinafter, referred to as the following).
  • the object is to provide a small surface plasmon sensor with high measurement accuracy that can detect the surface state of each measurement region at the same time by spectroscopically analyzing the light reflected from the measurement region.
  • a first waveguide chip of the present invention includes a core formed on a substrate for guiding light for measurement, and the core disposed on at least a part of the core.
  • a dielectric layer having a different refractive index, and a measurement region is formed in a region where the core and the dielectric layer overlap each other. According to such a waveguide chip, measurement of biomolecules and the like can be performed in the measurement region on the dielectric layer, and the dielectric layer is provided on the core.
  • the refractive index it is possible to change the characteristic wavelength of the signal light in the measurement region relatively freely.
  • An embodiment of the first waveguide chip of the present invention includes a plurality of the dielectric layers having different refractive indexes from each other. According to the embodiment, since the inspection can be performed in the regions of the plurality of dielectric layers, the plurality of inspections can be performed at a time. In addition, since the dielectric constants of the dielectric layers are different from each other, the characteristic wavelengths of the signal light in each measurement region can be separated from each other, and the measurement accuracy can be improved.
  • Another embodiment of the first waveguide chip of the present invention includes a plurality of the cores. Therefore, according to the embodiment, more inspections can be performed at one time.
  • a core for guiding measurement light is formed on the clad, and a plurality of dielectric layers having different refractive indexes are arranged in the length direction of the core. An intersection between the core and the dielectric is formed on the top surface of the core so as to intersect. A metal layer is formed on the top surface of the dielectric layer.
  • An embodiment of the second waveguide chip of the present invention includes a plurality of the cores, and each of the dielectric layers intersects with the length direction of all the cores. It is laminated on the top. According to this embodiment, since the measurement regions provided with the metal layer are arranged in a matrix, more inspections can be performed at one time.
  • Another embodiment of the second waveguide chip of the present invention is such that when the refractive index of the core is n2 and the refractive index of the dielectric layer is n3,
  • the light guided through the core can enter the dielectric layer and interact with the measurement region (metal layer).
  • the refractive index of the core is n2
  • the dielectric layer When the skewer is n3
  • the light guided through the core can enter each dielectric layer and interact with the measurement region (metal layer).
  • the core and the dielectric layer are substantially orthogonal to each other at the intersecting portion when viewed from a direction perpendicular to the top surface of the core.
  • the upper surface of the dielectric layer in a cross section perpendicular to the length direction of the dielectric layer at the intersecting portion forms an inverted V shape.
  • Still another embodiment of the second waveguide chip of the present invention is the longitudinal direction of the dielectric layer.
  • the upper surface of the dielectric layer has two inclined surfaces having different inclination directions, the inclined surfaces have the same length in the inclination direction, the inclination angle of the inclined surface is ⁇ , and
  • the angle formed by the light incident on the dielectric layer with respect to the normal formed at the interface between the core and the dielectric layer is ⁇ 4
  • the light reflected by one slope of the top surface of the dielectric layer travels parallel to the top surface of the core, so that the propagation angle of the light guided through the core before and after passing through the dielectric layer Does not change.
  • Yet another embodiment of the second waveguide chip according to the present invention is such that the core is incident on the dielectric layer from the core, is totally reflected on one inclined surface of the dielectric layer, and is directed on the other inclined surface.
  • the propagation angle of the light guided in the core is made different depending on the wavelength of the light so that the light travels in parallel with the upper surface of the core regardless of the wavelength.
  • the light propagating through the core does not change the propagation angle in the core before and after passing through the dielectric layer, regardless of its wavelength.
  • the core and the dielectric layer are substantially orthogonal to each other at the intersecting portion when viewed from a direction perpendicular to the top surface of the core. And when the width of the dielectric layer in the length direction of the core at the intersecting portion is W,
  • ⁇ 2 is the incident angle at which the light guided in the core enters the core interface
  • the core and the dielectric layer are substantially orthogonal to each other at the intersecting portion when viewed from a direction perpendicular to the top surface of the core.
  • the width of the dielectric layer in the length direction of the core at the intersection is W,
  • a is the inclination angle of the upper surface of the dielectric layer
  • ⁇ 2 is the incident angle at which the light guided in the core enters the core interface
  • ⁇ 4 is the angle formed by the light incident on the dielectric layer from the core with respect to the normal line standing at the interface
  • a flow path for allowing a sample to pass is formed along the length direction of the dielectric layer. According to this embodiment, it is possible to perform the inspection by flowing the sample along the flow path, and the inspection work is facilitated.
  • a molecule that specifically binds to a specific biomolecule is immobilized on the surface of the metal layer.
  • the characteristic wavelength changes, so that the presence or absence of the molecule and the amount thereof can be measured.
  • the surface plasmon sensor of the present invention includes the waveguide chip of the present invention, a light source that emits measurement light and enters the core of the waveguide chip, and light emitted from the waveguide chip.
  • a spectroscopic means for performing spectroscopic analysis and a light receiving element for receiving light split by the spectroscopic means are provided.
  • An embodiment of the surface plasmon sensor according to the present invention includes an optical path changing means for aligning the light emitted from the light source at a predetermined angle, and therefore irradiates the measurement region with light from the predetermined angle. Measurement accuracy is improved.
  • the regions where the metal layer is formed in the waveguide chip each form a measurement region, and the characteristic wavelengths of light reflected by the measurement region are different from each other. Are more than 50nm apart from each other. According to the embodiment, it is possible to maintain the independence of each measurement region force and other signals, and to perform measurement or inspection with high accuracy.
  • Still another embodiment of the surface plasmon sensor according to the present invention is such that a region where the metal layer is formed on the waveguide chip is a measurement region, and the dielectric layers are mutually connected. The refractive index difference is 0.02 or more. According to such an embodiment, the independence of signals from each measurement region can be maintained, and measurement or inspection can be performed with high accuracy.
  • the light source has a white light source or a multi-wavelength light source, it is possible to irradiate the measurement region with light having different wavelengths at a time. , Inspection efficiency is improved.
  • the metal layer is made of Au Ag or Cu and has a film thickness of lOOnm or less. According to such an embodiment, surface plasmon resonance can be effectively performed in the measurement region.
  • the surface plasmon sensor of the present invention has applications as various medical inspection apparatuses and chemical substance inspection apparatuses.
  • a method for manufacturing a waveguide chip according to the present invention is a method for manufacturing a waveguide chip according to the present invention, wherein a shape of a dielectric layer is transferred to a resin by a stamper on the upper surface of the core or the cladding.
  • the method includes a step of forming a dielectric layer and a step of forming the metal layer on at least a part of the dielectric layer. According to this manufacturing method, the waveguide chip can be mass-produced at a low cost by the stamper method.
  • FIG. 1 is a perspective view showing a surface plasmon sensor according to Embodiment 1 of the present invention.
  • FIG. 2 is a partially omitted plan view showing the surface plasmon sensor of the first embodiment.
  • FIG. 3 is a cross-sectional view for explaining the operation of the surface plasmon sensor according to the first embodiment.
  • FIG. 4 is a cross-sectional view illustrating another method for preventing light reflection at the interface of the spectroscopic means.
  • FIG. 5 shows how the light guided in the core is totally reflected at the interface between the dielectric layer and the metal layer.
  • FIG. 6 Fig. 6 (a) is a diagram showing a surface plasmon sensor in which an antibody is immobilized on the upper surface of the metal layer to form a measurement region
  • Fig. 6 (b) is a diagram showing characteristics detected by the light receiving section. It is. 7]
  • FIG. 7 (a) is a view showing a surface plasmon sensor in which a dielectric layer is provided on a metal layer
  • FIG. 7 (b) is a view showing characteristics detected by the light receiving portion.
  • FIG. 8 is a diagram showing spectral characteristics obtained by a surface plasmon sensor having a plurality of dielectric layers having different thicknesses.
  • Fig. 9 shows the characteristics R0 (E), R1 (E), R2 ( ⁇ ) of the light totally reflected in each measurement region and the reflectance characteristics Rt ( ⁇ ) detected by the light receiving element. It is a figure showing the relationship.
  • Figure 10 shows the relationship between the characteristics R0 (E), R1 (E) and R2 ( ⁇ ) of the light totally reflected in each measurement area and the reflectance characteristics Rt ( ⁇ ) detected by the light receiving element. This is a diagram showing the case of poor independence.
  • FIG. 11 is a diagram for explaining an independence condition.
  • FIG. 12 is a side view showing a modification of the first embodiment.
  • FIG. 13 is a perspective view showing another modified example of the first embodiment.
  • FIG. 14 is a perspective view showing a surface plasmon sensor 31 according to Embodiment 2 of the present invention.
  • FIG. 15 is a cross-sectional view for explaining the operation of the surface plasmon sensor according to the second embodiment.
  • FIG. 16 is a schematic diagram for explaining conditions for guiding light.
  • FIG. 17 is a schematic diagram for explaining conditions for guiding light.
  • FIGS. 18 (a) and 18 (b) are schematic views for explaining the effects of the second embodiment in comparison with the first embodiment.
  • FIGS. 19 (a) and 19 (b) are schematic diagrams showing optical paths of light having different wavelengths.
  • FIG. 20 is a diagram showing a simulation result of the first embodiment.
  • FIG. 21 shows the simulation conditions of FIG.
  • FIG. 22 is a diagram showing a simulation result of the second embodiment.
  • FIG. 23 shows the simulation conditions of FIG.
  • FIG. 24 is a diagram showing another simulation result of the second embodiment.
  • FIG. 25 shows the simulation conditions of FIG.
  • FIG. 26 is a diagram showing still another simulation result of the second embodiment.
  • FIG. 27 is a diagram showing still another simulation result of the second embodiment.
  • FIG. 28 shows the simulation conditions of FIG. 27.
  • FIG. 29 is a sectional view showing the structure of the surface plasmon sensor according to the third embodiment of the present invention.
  • FIG. 30 is a cross-sectional view showing a modification of the third embodiment.
  • FIGS. 31 (a) to 31 (e) are schematic views showing the method of manufacturing the surface according to the present invention.
  • FIGS. 32 (a)-(e) are schematic views showing a method of manufacturing a surface substrate according to the present invention and are continued from FIG.
  • FIGS. 33 (a) to 33 (d) are schematic views showing the method of manufacturing the surface according to the present invention and are continued from FIG.
  • FIG. 34 is a block diagram showing a configuration of an inspection apparatus using the surface sensor of the present invention.
  • FIG. 1 is a perspective view showing a surface plasmon sensor 11 according to Embodiment 1 of the present invention
  • FIG. 2 is a plan view in which the light receiving element is omitted.
  • FIG. 3 is a cross-sectional view for explaining the operation of the surface plasmon sensor 11.
  • the surface plasmon sensor 11 is an optical waveguide type surface plasmon sensor using a multimode optical waveguide, and has a structure as described below!
  • the surface plasmon sensor 11 includes a waveguide chip 12, a plurality of light projecting units 13, and a plurality of light receiving elements 14.
  • the waveguide chip 12 is provided with a plurality of measurement regions 16 a, 16 b, 16 c and a spectroscopic means 17 on a substrate 15.
  • the substrate 15 of the waveguide chip 12 is formed by forming a plurality of grooves to the end in a clad 18 made of transparent plastic or glass such as PMMA, polycarbonate (PC), polystyrene (PS), etc.
  • a core 19 having a rectangular cross section made of transparent plastic or glass having a refractive index higher than that of the clad 18 is formed, and a multimode type optical waveguide is formed.
  • the thickness of the core 19 is preferably set to several tens of inches to several hundreds of meters, which is the core thickness of a normal multimode waveguide. However, when the thickness of the core 19 is increased, an area for forming a measurement region to be described later is increased. Therefore, in order to reduce the size of the waveguide chip 12, it is desirable that the core thickness is several tens of meters.
  • a plurality of dielectric layers 2 Oa, 20b, and 20c made of dielectric materials having different refractive indexes are arranged on the upper surface of the substrate 15 with a gap therebetween.
  • Each dielectric layer 20a, 20b, 20c extends from one side edge to the other side edge on the upper surface of the substrate 15, and the length direction of the dielectric layers 20a, 20b, 20c is the core in plan view. It is orthogonal to the 19 length direction.
  • These dielectric layers 20a, 20b and 20c are made of high dielectric constant materials such as Ta 2 O and TiO, or P
  • It is made of a dielectric resin material with a high refractive index, such as MMA or polycarbonate, and has a higher refractive index than the core 19.
  • each dielectric layer 20a, 20b, 20c in the area where each core 19 and each dielectric layer 20a, 20b, 20c intersect in plan view, a rectangular metal layer 21 is provided. (Metal thin film) is formed.
  • the metal layer 21 is formed by depositing a thin film of Au, Ag, Cu or the like on the upper surface of the dielectric layers 20a, 20b, 20c by vacuum evaporation or sputtering, and the film thickness is preferably 100 ⁇ m or less. If the metal layer 21 is formed of Au, Ag, Cu or the like, a surface plasmon resonance signal can be obtained efficiently.
  • the individual measurement regions 16a, 16b, and 16c are formed by forming the metal layer 21 on the dielectric layers 20a, 20b, and 20c.
  • each core 19 is exposed at the end of the substrate 15, and one end face thereof is a white light source that emits white light or a multi-wavelength light source that emits light in a predetermined multiple wavelength region.
  • the light projecting unit 1 3 is arranged.
  • the light projecting unit 13 converts a light source 22 such as a light emitting diode (LED), a semiconductor laser element (LD), or a halogen lamp, and linearly polarized light in a direction parallel or perpendicular to the metal layer 21. It has a polarizer 23 and a collimating optical system 24 for collimating the light emitted from the light source 22 and emitting it at a predetermined angle.
  • the light emitted from the light projecting unit 13 has a divergence angle, a measurement error corresponding to the divergence angle will occur, so the light emitted from the light projecting unit 13 is collimated. Light is incident on the core 19 from a certain direction to reduce the measurement error.
  • the spectroscopic means 17 is disposed so as to be in close contact with the upper surface of the other end of each core 19, and the light receiving element 14 is disposed above the spectroscopic means 17.
  • the upper surface of the core 19 on which the spectroscopic means 17 is installed may be inclined as shown in FIG.
  • the upper surface of the core 19 may be inclined so that the incident angle of the light L incident on the interface of the spectroscopic means 17 becomes smaller. By doing so, the light L guided through the core 19 is totally reflected at the interface with the spectroscopic means 17.
  • Such a method is not limited to the first embodiment and will be described below.
  • the present invention can also be applied to an optical waveguide surface plasmon sensor according to another embodiment.
  • the spectroscopic means 17 is for diffracting the light L that has been guided through the core 19 after being totally reflected at the interface between the dielectric layers 20a, 20b, 20c and the metal layer 21, and is a diffraction grating. Consists of.
  • the light receiving element 14 has a plurality of light receiving regions 25 (light receiving cells) that receive light of each wavelength dispersed by the spectroscopic means 17, and a one-dimensional photodiode array or the like is used. Since a plurality of light receiving elements 14 having light receiving regions 25 arranged in a row are arranged, the light receiving regions 25 are two-dimensionally arranged as a whole.
  • the collimated white light or the light L having a plurality of wavelengths is emitted from the light projecting unit 13, and the light L emitted from the light projecting unit 13 is shown in FIG.
  • the light enters the core 19 from one end face of the facing core 19. Since the waveguide chip 12 is a multimode type optical waveguide, the white light or the light L in a plurality of wavelengths is guided in the core 19 without being attenuated while repeating total reflection.
  • the emission direction of the light L emitted from the light projecting unit 13 is determined so that the light L follows the following path. That is, the light L guided in the core 19 is incident obliquely on the dielectric layer 20a in the measurement region 16a and totally reflected at the interface between the metal layer 21 and the dielectric layer 20a, and the totally reflected light L is again the core. 19 is guided into the dielectric layer 20b in the measurement region 16b, is totally reflected at the interface between the metal layer 21 and the dielectric layer 20b, and the totally reflected light L is guided through the core 19. Then, it is obliquely incident on the dielectric layer 20c in the measurement region 16c and totally reflected at the interface between the metal layer 21 and the dielectric layer 20c.
  • the light L guided in the core 19 reaches the upper surface of the end of the core 19 and exits from the spectroscopic means 17 to the outside.
  • the light L that has passed through the spectroscopic means 17 is split into light of each wavelength by the spectroscopic means 17.
  • the light of each wavelength split by the spectroscopic means 17 is emitted in different directions for each wavelength and received by the light receiving element 14.
  • the light receiving regions 25 of the light receiving element 14 are arranged along the spectral direction of the spectroscopic device 17, and each light receiving region 25 receives light of different wavelengths. Therefore, the power S is obtained from the amount of light received by each light receiving region 25 to obtain the spectral allowance of the light reflected by the measurement region 16.
  • FIG. 5 shows core 1.
  • 9 is a schematic diagram showing how light guided in 9 is totally reflected at the interface between dielectric layer 20 and metal layer 21.
  • FIG. The refractive index of the cladding 18 is nl
  • the refractive index of the core 19 is n2
  • the refractive index of the dielectric layer 20 is n3
  • the refractive index of the medium (antigen, antibody) on the measurement region 16 is n4
  • the sample solution on the upper surface of the core 19 Is the refractive index of n5, and the incident angle of light incident on the interface of the core 19 (hereinafter referred to as the propagation angle of the light guided in the core) is 62.
  • the conditions for the light in the core 19 to be guided by repeated total reflection at the interface with the clad 18 and the interface with the sample solution are:
  • the incident angle of light incident on the measurement region 16 from the dielectric layer 20 side is ⁇ 3
  • the condition for total reflection of this light in the measurement region 16 is
  • the conditions for the light guided in the core 19 to be totally reflected and interacted with each measurement region 16 are as shown in FIG.
  • the light totally reflected at the end A of the layer 20 without entering the dielectric layer 20 may be totally reflected by the measurement region 16 and returned to the core 19.
  • the horizontal distance between AB is 2 X Dtan ⁇ 2 + 2 X dtan ⁇ 3 as shown in Fig. 5.
  • D is the thickness of the core 19
  • d is the thickness of the dielectric layer 20. Therefore, the light power propagating in the core 19 is a condition for total reflection in all the measurement regions 16a, 16b, 16c.
  • the width W along the core length direction of any measurement region is
  • FIG. 6A shows a surface plasmon sensor 28 (comparative example) in which one measurement region is formed by immobilizing an antibody 26 on a metal layer 21 formed on the upper surface of the core 19.
  • Fig. 6 (b) shows the total reflection at the interface between the core 19 and the metal layer 21 in the measurement region when light L is irradiated at an incident angle that causes total reflection in the measurement region of the surface plasmon sensor 28. This shows the spectral characteristics of the light L. In the measurement region where total reflection of the light L occurs, an evanescent wave having an electric field distribution is generated on the surface of the metal layer 21.
  • a dielectric layer 20 having a predetermined refractive index is provided on the core 19, and a metal layer 21 is provided on the dielectric layer 20.
  • the characteristic when the antigen 27 is not bound to the antibody 26 is the characteristic Rl () shown in FIG. 7 (b). That is, even in the case where the antigen 27 is not bound to the antibody 26, the spectral characteristic of the reflected light does not have the dielectric layer 20! /, The characteristic R0 ( ⁇ ) force of the case, FIG. It changes to the characteristic R1 ( ⁇ ) of b), and the characteristic wavelength (absorption wavelength) is shifted by ⁇ to become ⁇ 1.
  • the characteristic wavelength becomes as shown by the characteristic Rls () in FIG. 7 (b), and the characteristic wavelength is changed from ⁇ .
  • the shift amount ⁇ varies depending on the refractive index value of the dielectric layer 20.
  • the metal layer 21 is formed on the dielectric layers 20a 20b 20c having different refractive indexes in the respective measurement regions 16a 16 b 16c. Therefore, as shown in Fig. 8, each measurement region 16a 16b, 16c force, where the antibody 26a 26b 26c is immobilized, and their special signals R1 (E), R2 (E), R3 () The regions 16a 16 b 16c are shifted by different wavelength shift amounts and separated from each other. Therefore, the signals from the measurement regions 16a, 16b, and 16c are not mixed, and the characteristic wavelengths 1 ⁇ 2 ⁇ 3 of each signal can be accurately separated.
  • the signal from the measurement region 16a has a characteristic wavelength of ⁇ 1 as shown by the characteristic R1 ( ⁇ ) in FIG. 8 when no antigen is bound to the antibody 26a.
  • the characteristic wavelength becomes the characteristic of ⁇ Is as shown by the characteristic Rls ( ⁇ ) in FIG.
  • the signal from the measurement region 16b has a characteristic wavelength of ⁇ 2 as shown by the characteristic R2 ( ⁇ ) in FIG. 8 when the antigen is not bound, and specifically binds to the antibody 26b.
  • the characteristic wavelength becomes a characteristic of ⁇ 2s as shown in the characteristic R2s ( ⁇ ) of FIG.
  • the signal from the measurement region 16c has a characteristic wavelength of ⁇ 3 as shown by the characteristic R3 () in Fig. 8 when the antigen is not bound, and the antigen that specifically binds to the antibody 26c is bound.
  • the characteristic wavelength is ⁇ 3s as shown in the characteristic R3s ( ⁇ ) in Fig. 8. Therefore, each characteristic wavelength ⁇ 1 ⁇ 2 ⁇ can be obtained by differentiating the refractive indexes of the dielectric layers 20 a 20b 20 c so that the characteristic wavelengths 1 ⁇ 2 ⁇ 3 are sufficiently separated and separated.
  • each characteristic wavelength after change ⁇ ls ⁇ 2s ⁇ 3 s can be detected accurately without mixing, and the presence or absence of antigen and the amount of antigen binding in each measurement region 16a 16b, 16c can be detected.
  • the light receiving element 14 needs to cover all characteristic wavelengths. That is, in this case, a light receiving element 14 having a size and the number of cells capable of receiving at least light with wavelengths ⁇ 1 to ⁇ 3s with a necessary resolution is required.
  • the refractive index of each dielectric layer is designed in advance to an appropriate refractive index in accordance with the type of antibody or antigen, as shown in FIG.
  • different antibodies 26a, 26b, and 26c are immobilized on each measurement region 16a, 16b, and 16c on each core 19, different antigen-antibody reactions can be detected at a time, and multiple tests can be performed. You can do it at once. Therefore, the measurement area can be made into a two-dimensional array, and multiple inspections can be performed efficiently at the same time (high measurement throughput), making it possible to produce a small but inexpensive Balta-type surface plasmon sensor 11. it can.
  • each dielectric layer is not necessarily equal, if the thickness of each dielectric layer is equal as in the surface plasmon sensor 11 of the first embodiment, the waveguide chip 12 and the surface plasmon Manufacture of the sensor 11 is facilitated.
  • each measurement region 16a, 16b, 16c the spectral characteristics of the light L reflected by each measurement region 16a, 16b, 16c are not detected separately as shown in FIG. 8, but are detected by one light receiving element 14. Considering this point, the interval between the characteristic wavelengths must be set. For this purpose, the refractive index of each dielectric layer must be determined so as to satisfy the condition called independence. The concept of independence necessary to separate the characteristic wavelengths of each signal is described below.
  • FIG. 9 shows the characteristics R1 (E), R2 (E), R3 ( ⁇ ) of the light totally reflected in the measurement regions 16a, 16b, and 16c and the reflectance characteristic Rt ( ⁇ ) detected by the light receiving element 14.
  • the reflectance characteristic Rt ( ⁇ ) detected by the light receiving element 14 is obtained by multiplying the reflectances of the characteristics R1 (e), R2 (e), and R3 ( ⁇ ).
  • the characteristic detected by the light receiving element 14 is as shown by Rt ( ⁇ ) in FIG.
  • the characteristic wavelengths are expressed as 1, 2, 3, 3, ... in order from the shortest side.
  • the characteristic wavelengths when antigens are bound to these measurement regions are ms and ns, the respective wavelength shifts are
  • the characteristic wavelength is an arbitrary set of adjacent spectral characteristics
  • the number of measurement regions in measurement region 16 is k + l
  • the wavelength of light is ⁇
  • the reflectance in each measurement region is R1 (E), R2 (E), ..., Rk ( ⁇ )
  • each measurement is performed.
  • the reflectance when the antigen specifically binds to the region is Rls (E), R2s (E), R3s ( ⁇ ), -—, 13 ⁇ 43 ⁇ 4 (é)
  • nRj (e) is the characteristic of the signal measured by the light receiving element 14 when no antigen is bound to any measurement region
  • nRjs () This is a characteristic of a signal measured by the light receiving element 14 when an antigen is bound to the region.
  • the independence condition 2 is that when an arbitrary adjacent spectral characteristic Rm ( ⁇ ), Rn ( ⁇ ) as shown in FIG.
  • Equation 6 is the force that can be used when the waveform is symmetrical and the center wavelength of the minimum inter-wavelength distance is the inflection point. Otherwise (when the waveform is not symmetrical) (Equation 6) ) Is not available! If the waveform is left-right symmetric, the second derivative must be zero! /.
  • the independence condition 2 is that a minimum value Ris ( ⁇ is) force S of an arbitrary spectral characteristic after the antigen is attached, Fk ( ⁇ at an arbitrary ⁇ mn defined in the above (formula 6) ) / Ri ( ⁇ ) less than the value
  • Ris ( ⁇ ) is an antigen attached.
  • the spectral characteristic Ris ( ⁇ ) is a value at the characteristic wavelength ⁇ is
  • Ri ( ⁇ ) is the spectral characteristic before the antigen of Ris ( ⁇ ) is bound.
  • the value on the right side of (Equation 8) is more than 10% larger than the value on the left side! Desire! /.
  • the independence condition of (Equation 5) and the independence condition of at least one of (Equation 7) and (Equation 8) are used. Care must be taken to satisfy [0069] Usually, glass or PMMA is used for the core 19, Au is used for the metal layer 21, and TaO or PMMA is used for the dielectric layers 20a, 20b, and 20c.
  • the characteristic wavelength of the signal shifts by about 50 nm. Therefore, if the characteristic wavelength interval AG of each signal is set to be lOOnm or more, the characteristic wavelength of the signal can be detected with high accuracy.
  • the light receiving element 14 needs to cover all the characteristic wavelengths. That is, a light-receiving element having a size and the number of cells that can receive at least light having a wavelength of ⁇ 1 to ⁇ ks with a necessary resolution.
  • the surface plasmon sensor of the first embodiment can be variously modified in addition to the above structure.
  • a single core may be used, and a plurality of measurement regions composed of dielectric layers and metal layers having different refractive indexes may be arranged in a line.
  • FIG. 12 is a side view showing a modification of the first embodiment.
  • the light L guided through the core 19 is emitted from the end surface opposite to the light projecting portion 13 of the core 19, and the light splitting means 17 is provided on the end surface to split the light L.
  • the light receiving element 14 arranged vertically on the spectroscopic means 19 side receives the signal.
  • FIG. 13 shows another modification of the first embodiment, in which the dielectric layers 20a, 20b, and 20c are provided only under the metal layer 21, and the dielectric layers 20a, 20b, 20c is separated independently.
  • each core 19 has the same refractive index using the same core material, the manufacture of the waveguide chip 12 can be facilitated.
  • the measurement conditions can be changed for each core 19 and the characteristic wavelength range of the signal can be made different, so that more samples can be measured. it can.
  • the characteristic wavelength range of the signal can be changed by changing the measurement conditions for each core 19 so that more samples can be measured. can do.
  • FIG. 14 is a perspective view showing a surface plasmon sensor 31 according to Embodiment 2 of the present invention
  • FIG. 15 is a cross-sectional view for explaining its operation.
  • Surface Plasmon Sensor 31 according to Embodiment 2 31 the upper surface of each dielectric layer 20a, 20b, 20c formed of dielectric materials having different refractive indexes has a roof shape, and the metal layer 21 is formed along the upper surface.
  • the top surfaces of the dielectric layers 20a, 20b, and 20c are isosceles triangles having the same inclination angle and the same length in the inclination direction.
  • the inclination angles (base angles) of the top surfaces of the dielectric layers 20a, 20b, and 20c are larger as the dielectric layers 20a, 20b, and 20c have a higher refractive index.
  • the light L emitted from the light projecting unit 13 is guided in the core 19 and is respectively dielectric layers 20a, 20b, 20c. Then, the light is totally reflected on one slope of the upper surface of each dielectric layer 20a, 20b, 20c and travels parallel to the top surface of the core 19, and then totally reflected on the other slope and returns into the core 19. Therefore, dielectric layer 20a, 20b, 20c force, etc.
  • Propagation angle in 19 Guides in the core 19 with a propagation angle equal to ⁇ 2. Then, the light is received by the light receiving element 14 through the spectroscopic means 17 at the end of the core 19.
  • the top surfaces of the dielectric layers 20a, 20b, and 20c are formed in a roof shape in this way, the light L is reflected twice in the measurement regions 16a, 16b, and 16c, so that the measurement sensitivity of the surface plasmon sensor 31 is improved.
  • the interval between the characteristic wavelength ranges is widened, and the measurement accuracy of the surface plasmon sensor 31 is improved.
  • the X axis is defined along the interface between the core 19 and the dielectric layer 20
  • the Y axis is defined along one side end face of the dielectric layer 20.
  • the thickness of the core 19 is D
  • the height of the end of the dielectric layer 20 is h
  • the propagation angle of light in the core 19 is ⁇ 2
  • the interface between the core 19 and the dielectric layer 20 from the interface to the dielectric layer 20 is Let the incident angle be ⁇ 4.
  • the cross section of one slope K1 shown in Figure 16 is
  • the condition that the light guided in the core 19 is always incident on the inclined surface Kl of the dielectric layer 20 is that if the width of the dielectric layer 20 is W,
  • the inclination angle of the slope K1 on the upper surface of the dielectric layer 20 is ⁇
  • the incident angle of light incident on the dielectric layer 20 from the interface between the core 19 and the dielectric layer 20 is ⁇ 4
  • the dielectric layer If the incident angle of light incident on the slope K1 of the dielectric layer 20 from the 20 side is ⁇ 3
  • the condition for total reflection of light on the slope K1 of the dielectric layer 20 is that the critical angle of total reflection on the slope K1 is / 3.
  • the refractive index of the core 19 is n2
  • the propagation angle of the light guided in the core 19 is ⁇ 2
  • n2-sin ⁇ 2 n3-sin ⁇ 4
  • the conditions for the light to be totally reflected by the inclined surface K1 are as follows. Must be satisfied. To that end, it is sufficient if V, Eq. 11 or Eq. 12 is satisfied for the dielectric layer with the smallest inclination angle a! /.
  • the tilt angle a must be increased so that the dielectric layer having a higher refractive index ⁇ 3 satisfies Equation 15.
  • Embodiment 1 Comparing Embodiment 1 and Embodiment 2, in the case of Embodiment 1, as shown in FIG. 18 (a), the incident angle ⁇ 3 of light on the upper surface of the dielectric layer 20 becomes small. The shift of the reflectance intensity curve (characteristic wavelength range) due to the difference in refractive index is not so large.
  • Embodiment 2 as shown in FIG. 18 (b), since the upper surface of the dielectric layer 20 is inclined, the incident angle ⁇ 3 of light on the upper surface of the dielectric layer 20 is The dielectric layer can be large Since it is totally reflected twice on the upper surface of 20 and returns to the core 19 at the propagation angle before entering the dielectric layer 20, the characteristic wavelength region can be shifted more greatly to obtain good signal strength and measurement accuracy.
  • FIG. 19 (a) when light of each wavelength is guided through the core 19 at the same propagation angle ⁇ 2, the light when entering the dielectric layer 20 from the core 19 is shown. Due to the difference in the refractive index depending on the wavelength, the propagation angle ⁇ 2 of the light guided through the core 19 changes as it passes through the dielectric layer 20. When such a change in the propagation angle ⁇ 2 becomes a problem, as shown in Fig. 19 (b), the direction force from the slope K1 to the slope K2 in the dielectric layer 20 is not affected by the wavelength. If the propagation angle ⁇ in the core 19 is different depending on the wavelength so that it is parallel to the top surface of the core 19, it is possible to eliminate the change in the propagation angle ⁇ 2 due to light of any wavelength passing through the dielectric layer 20. S can.
  • FIG. 20 shows the simulation result of the first embodiment.
  • a surface plasmon sensor in which measurement regions S 11 -S15 and S17-S21 were formed on the substrate was simulated.
  • Figure 21 shows the simulation conditions.
  • the substrate is obtained by forming a core having a refractive index n2 of 1.425 in a clad having a refractive index nl of 1.4.
  • the critical angle of total reflection at the interface between the core and the cladding is 79.25176 °, and light is propagated at a propagation angle ⁇ 2 of 80 ° to the core interface while repeating total reflection. The inside of the core was guided.
  • Measurement region S11 is obtained by forming a metal layer made of an Au film having a thickness of 50 nm on a dielectric layer having a refractive index n3 of 1.425.
  • the critical angle of total reflection at the interface between the dielectric layer and the metal layer was 0.
  • Measurement region S13 is obtained by forming a metal layer made of an Au film having a thickness of 50 nm on a dielectric layer having a refractive index n3 of 1.475.
  • Measurement region S14 is obtained by forming a metal layer made of an Au film having a thickness of 50 nm on a dielectric layer having a refractive index n3 of 1.5.
  • Measurement region S15 is obtained by forming a metal layer made of an Au film having a thickness of 50 nm on a dielectric layer having a refractive index ⁇ 3 of 1.55.
  • Measurement regions S17 to S21 are obtained by immobilizing biomolecules having a refractive index of 1.57 and a thickness of 10 nm on the upper surfaces of measurement regions S11 to S15, respectively.
  • FIG. 22 shows the simulation result of the second embodiment.
  • a surface plasmon sensor in which measurement regions S31-S34 and S37-S40 were formed on a substrate was simulated.
  • Figure 23 shows the simulation conditions.
  • the substrates used in the measurement regions S31-S34, S37-S40 are obtained by forming a core having a refractive index n2 of 1.4 in a clad having a refractive index nl of 1.39.
  • the critical angle 0 of total reflection at the interface with the cladding of the core is 83.14776 °, and light is guided to the core interface at a propagation angle ⁇ 2 of 85 ° with respect to the core interface while repeating total reflection. The inside was guided.
  • Measurement region S31 is obtained by forming a metal layer made of an Au film having a thickness of 50 nm on a dielectric layer having a refractive index ⁇ 3 of 1.4. Total reflection at the interface between the dielectric layer and the metal layer The critical angle ⁇ is 71.80513 °, and the inclination angle ⁇ of the slope of the dielectric layer is 0 °. Measurement In the region S31, light is incident on the dielectric layer at an incident angle ⁇ 4 of 85 °, and light is incident on the interface with the metal layer at an incident angle ⁇ 3 of 85 ° and totally reflected.
  • the measurement region S32 is obtained by forming a metal layer made of an Au film having a thickness of 50 nm on a dielectric layer having a refractive index n3 of 1.427, and having a total reflection at the interface between the dielectric layer and the metal layer.
  • the critical angle / 3 force is 68.75274 °
  • the slope angle ⁇ of the slope of the dielectric layer is 7.218967 °.
  • light is incident on the dielectric layer at an incident angle ⁇ 4 of 77.78103 °, and light is incident on the interface with the metal layer at an incident angle ⁇ 3 of 85 ° and is totally reflected.
  • the measurement region S33 is obtained by forming a metal layer made of an Au film with a thickness of 50 nm on a dielectric layer with a refractive index ⁇ 3 of 1.415.
  • the total reflection at the interface between the dielectric layer and the metal layer is as follows.
  • the critical angle / 3 force is 70.03969 °
  • the slope angle ⁇ of the slope of the dielectric layer is 4.723483 °.
  • light is incident on the dielectric layer at an incident angle ⁇ 4 of 80.27652 °, and light is incident on the interface with the metal layer at an incident angle ⁇ 3 of 85 ° and is totally reflected.
  • a metal layer made of an Au film having a thickness of 50 nm is formed on a dielectric layer having a refractive index ⁇ 3 of 1.42, and the total reflection at the interface between the dielectric layer and the metal layer is measured.
  • the critical angle / 3 force is 69.49142 °
  • the slope angle ⁇ of the slope of the dielectric layer is 5.837687 °.
  • light is incident on the dielectric layer at an incident angle ⁇ 4 of 79.16231 °, and light is incident on the interface with the metal layer at an incident angle ⁇ 3 of 85 ° and is totally reflected.
  • Measurement regions S37 to S40 are obtained by immobilizing biomolecules having a refractive index of 1.57 and a thickness of 10 nm on the upper surfaces of the measurement regions S31 to S34, respectively.
  • Fig. 20 shows the results of measurement using the embodiment 1 as described above.
  • the difference between the characteristic wavelength ranges is small in the measurement region S11-S15, and also in the measurement region S17-S21.
  • the difference in the characteristic wavelength range should be small!
  • Fig. 22 shows the results of measurement using the embodiment 2 as described above.
  • the difference in the characteristic wavelength range is that of the embodiment 1. Compared to that, it is wide enough.
  • the refractive index difference of the dielectric layer is 0.015
  • the measurement region S31 (before the biomolecule reaction) and the measurement region S39 (after the biomolecule reaction) overlap each other and the signal
  • the refractive index difference of the dielectric layer is 0.02 or more
  • the signal is not as shown in measurement area S31 (before biomolecule reaction) and measurement area S40 (after biomolecule reaction). Does not overlap. Therefore, it is desirable that the refractive index difference between the dielectric layers be 0.02 or more.
  • FIG. 24 shows another simulation result of the second embodiment.
  • a surface plasmon sensor in which measurement regions S41-S45 and S47-S51 were formed on a substrate was simulated.
  • Figure 25 shows the simulation conditions.
  • the measurement region S41 is the same as the measurement region S11.
  • the measurement regions S47 to S51 are obtained by immobilizing biomolecules having a refractive index of 1.57 and a thickness of 10 nm on the upper surfaces of the measurement regions S41 to S45, respectively.
  • FIG. 26 shows a signal St obtained by superimposing the respective signals from the measurement regions S41, S42, S44, S45, S47, S48, S50, and S51 and the absorptions in these measurement regions except for the measurement region S43 (S49).
  • the measurement regions S43 and S45 need not be provided, and the surface plus and the mon sensor 31 having the three measurement regions S41, S42 and S44 can be obtained.
  • FIG. 27 shows still another simulation result of the second embodiment.
  • a surface plasmon sensor in which measurement regions S31, S32, S35, S37, S38, and S42 were formed on a substrate was simulated.
  • Figure 28 shows the simulation conditions.
  • the measurement area S31 (S37) and the measurement area S32 (S38) are those described above.
  • Measurement area S35 (S42) is a new measurement area.
  • the signal Su in FIG. 27 is obtained by superimposing the absorption of each signal by the measurement regions S31, S32, S35, S37, S38, and S42.
  • Figure 27 also shows that the signal independence is maintained if there are three measurement areas.
  • FIG. 29 is a cross-sectional view showing the structure of the surface plasmon sensor 41 according to the third embodiment of the present invention.
  • the flow path cover 42 is overlaid on the upper surface of the surface plasmon sensor of Embodiment 1, and along the dielectric layers 20a, 20b, and 20c between the flow path cover 42 and the upper surface of the substrate 15.
  • a plurality of flow paths 43 are formed.
  • the force and surface plasmon sensor 41 since different sample solutions can flow through the respective channels 43, a plurality of inspections of a plurality of sample solutions can be performed at a time. Moreover, according to the surface plasmon sensor 41, since the dielectric layers 20a, 20b, and 20c have the same film thickness, the channel cross-sectional areas of the channels 43 are equal, and the inspection of each sample solution is the same. Can be done.
  • Such a flow path cover 42 may be provided in the surface plasmon sensor of Embodiment 2 like the surface plasmon sensor 44 shown in FIG.
  • a method of manufacturing the surface plasmon sensor 44 shown in FIG. 30 by the stamper method will be described with reference to FIGS.
  • a master 52 having the same shape as the clad is fabricated on the substrate 51 by an electroplating method or the like (FIG. 31 (a)).
  • the stamper 53 is prepared by using the master 52 mold (FIG. 31 (b)).
  • FIG. 31 (c) shows a state in which the substrate 15 on which the core 19 is formed is rotated by 90 °.
  • a master 56 for producing a dielectric layer is fabricated on the substrate 55 (Fig. 32 (a)), and a stamper 57 is fabricated using the master 56 (Fig. 32 (b) )).
  • the stamper 57 is turned upside down to fill the concave portion with the transparent resin 58 (FIG. 32 (c)).
  • the stamper 57 filled with the transparent resin 58 is returned to the original position and overlaid on the substrate 15, and the transparent resin 58 is cured so that the dielectric layers 20a, 20b, and 20c are formed on the substrate 15. ( Figure 32 (d)). Further, a metal layer 21 is formed on the top surface of each dielectric layer 20a, 20b, 20c to obtain a waveguide chip (FIG. 32 (e)).
  • FIG. 33 (a) a prototype 59 of the flow path cover is produced (FIG. 33 (a)), and a stamper 60 is produced using the prototype 59 (FIG. 33 (b)).
  • the resin dropped on the substrate 61 is pressed by the stamper 60, and the resin is cured to produce the flow path cover 42 on the substrate 61 (FIG. 33 (c)).
  • the dielectric layers 20a, 20b, and 20c are placed in the flow path 43 so that the dielectric layers 20a, 20b, and 20c are placed in the thread, and the flow path canopy 42 is superimposed on the substrate 15 to produce a surface plasmon sensor (FIG. 33 (d)).
  • examples of the present invention are not limited to antigens and antibodies, but include DNA, RNA, proteins, sugar chains, and the like. It can be used for measurement and observation of various biomolecules.
  • FIG. 34 is a block diagram showing the configuration of the inspection apparatus 121 using the surface plasmon sensor 122 of the present invention.
  • This inspection device 121 is used as a medical inspection device or a chemical substance inspection device depending on the inspection object.
  • a biomolecule recognition functional substance that specifically binds to a biomolecule is immobilized on the dielectric layer, and when used as a chemical inspection device, the dielectric layer A chemical substance recognition function substance that binds to a specific chemical substance may be immobilized on the top.
  • the inspection apparatus 121 has a structure for sending a sample to the surface plasmon sensor 122.
  • the sample solution dropped on the sample dropping unit 123 is pumped.
  • the sample solution that has been supplied to the surface plasmon sensor 122 by the sample flow control unit 124 at a constant flow rate and passed through each measurement region of the surface plasmon sensor 122 is sent to the waste liquid processing unit 125 and collected.
  • the surface plasmon sensor 122 outputs the spectral characteristics of the sample solution as inspection data to the data processing unit 126, and the data is stored in the storage device 127 through the determination processing unit 128 and the determination result by the determination processing unit 128. Is output to an external output device. Note that the storage device 127 and the determination processing unit 128 may be omitted.
  • test apparatus 121 in addition to antigen-antibody reaction, analysis of SNP (single nucleotide polymorphism), metabolism, absorption, excretion route or state of substances administered to experimental mice. Confirmation, intracellular ion concentration measurement, protein identification or functional analysis can be performed. Furthermore, it can also be used for health checkups that determine the health status of individuals and for inspections for personal security.
  • SNP single nucleotide polymorphism

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Abstract

Un détecteur de plasmon de surface comprend un substrat (15), des noyaux (19) formés sur le substrat (15), des couches diélectriques (20a, 20b, 20c) faites de matières diélectriques ayant différents indices de réfraction et disposées sur et le long des noyaux (19), des couches métalliques (21) formées sur les couches diélectriques, faites d'un métal tel que l'or, et ayant des régions de mesure (16a, 16b, 16c). Sur les parties supérieures des régions de mesure (16a, 16b, 16c), différents types d'anticorps sont immobilisés. A l'aide du détecteur de plasmon de surface ayant une telle structure, des signaux provenant des régions de mesure (16a, 16b, 16c) ayant les couches diélectriques (20a, 20b, 20c) de différents indices de réfraction sont dispersés, les états de surface des régions de mesure (16a, 16b, 16c) sont détectés à un certain temps et des antigènes peuvent être inspectés à un certain temps.
PCT/JP2007/073763 2006-12-19 2007-12-10 Détecteur de plasmon de surface WO2008075578A1 (fr)

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