JP2009092405A - Target material detection element, target material detection device using it, kit, and detection method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a local surface plasmon resonance (LSPR) sensor element having high responsiveness to a target material. <P>SOLUTION: This target material detection element includes a support, and an open ring-shaped metal structure having a part or a plurality of parts of gaps existing on the support surface, and is formed by fixing a capturing body of the target material on the surface of the metal structure, and by arranging it on the substrate surface. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an element, a detection device, a detection kit, and a detection method for detecting a target substance in a specimen with high sensitivity using metal plasmon resonance.

  First, the background art in the present invention will be described.

<Target substance sensor>
There are multiple markers in blood for specific diseases such as cancer, hepatitis, diabetes, and osteoporosis. When affected, the concentration of a specific protein increases during normal times. It is expected as a next-generation medical technology because it is possible to detect a serious illness early by monitoring these from normal times. In addition, it is considered that metastasis can be detected at an early stage by monitoring the prognosis after tumor removal, and it is expected to contribute greatly to the improvement of medical quality.

  In recent years, the Food Sanitation Act has been amended to require businesses to display eggs, peanuts, buckwheat, wheat, and milk. However, few people know quantitatively how much they are allergic to what food. It is important to know these data scientifically as numerical values from the viewpoints of health promotion and preventive medicine for each person, and great expectations are placed on the technical field disclosed in the present invention.

  One method for analyzing raw and unpurified proteins is based on sensors that use biological ligand-analyte interactions to identify specific compounds.

  Development of an accurate target substance sensor for detecting the above-described disease markers, food allergens, and the like as detection targets, that is, target substances for detection, is required.

  As a typical target substance sensor system, a fluorescence immunization method, a plasmon resonance method, an optical interference method and the like can be mentioned. In both cases, ligands or analytes are immobilized on the sensor surface, and the ligands or analytes in the sample are selected and bound with high selectivity to eliminate impurities and capture only the target substance of interest with high efficiency. It is a common step.

<Localized Surface Plasmon Resonance (LSPR)>
In the sensor using the plasmon resonance method, a ligand is immobilized on a metal thin film or a metal fine particle by utilizing the high sensitivity of the metal plasmon to the change in the refractive index of the interface substance, and the ligand specifically The concentration of analyte bound is measured. The ligand is immobilized on the sensor surface using chemical or physical means. By using this technique, it is possible to obtain information on the kinetics of the reaction between ligand analytes, and it is considered to be an advantage of LSPR together with the feature that labeling is unnecessary.

  In addition, since the LSPR sensor senses by utilizing the fact that the resonance condition of the metal plasmon changes when the refractive index around the metal fine particles changes, the sensor having a large change in the optical characteristics with respect to the change in the refractive index has high sensitivity. It can be said. In other words, the greater the peak shift amount of the transmission or absorption spectrum when the refractive index changes, and the more the same peak shift amount, the narrower the peak width and the higher the peak height or depth, the higher the sensitivity. It can be said.

  Patent Document 1 discloses a method for manufacturing a localized surface plasmon (LSPR) sensor by self-organizing and immobilizing metal fine particles on a glass substrate surface-modified with an amino group. Has been. Patent Document 1 also describes the basic characteristics of this sensor. Patent Document 1 further describes a technique for measuring the concentration and kinetics of the target substance by detecting the intensity change of the absorption spectrum.

  The technique disclosed in Non-Patent Document 1 relates to an LSPR sensor in which metal fine particles are immobilized on a chemically modified glass substrate, as in Patent Document 1. Non-Patent Document 1 further discloses that a streptavidin-biotin reaction can be observed from a change in the intensity of an absorption spectrum. In Non-Patent Document 1, it is reported that the refractive index response when the surrounding medium is changed is 76.4 nm / index.

Non-Patent Document 2 discloses a technique for producing an LSPR sensor by arranging Ag dots by using nanosphere lithography (lithography technique using polystyrene nanobeads). The refractive index response when the surrounding medium is changed is reported to be 200 nm / index.
Japanese Patent No. 3452837 Anal. Chem. 2002, 74, 504-509, A Colorimetric Gold Nanoparticle Sensor To Interrogate Biomolecular Interactions in Real Time on a Surface J. Phys. Chem. B 1999, 103, 9846-9853, Nanosphere Lithography: Effect of External Dielectric Medium on the Surface Plasmon Resonance Spectrum of a Periodic Array of Silver Nanoparticle

  However, in the technique disclosed above, the amount of shift of the spectrum when the target substance is captured on the surface of the target substance detection element by the capturing body may not be sufficient. In addition, there is room for improvement in spectral width and peak height or depth. Therefore, the technique disclosed above has a problem that the detection limit of the target substance concentration cannot be lowered. When the technology is applied to clinical examination, further improvement in performance is desired as a chemical substance sensor for detecting a target substance.

  In view of the above problems, the present invention has been invented for the purpose of further improving the performance of a chemical sensor for capturing a target substance.

That is, the target substance detection element of the present invention is a target substance detection element in a specimen,
The target substance detection element is
A support and a metal structure present on the surface of the support;
A target substance capturing body present on the surface of the metal structure,
The element for detecting a target substance is characterized in that the metal structure has a ring structure partially opened.

A target substance detection apparatus according to the present invention is a target substance detection apparatus,
Holding means for holding the target substance detection element having the above-described configuration;
Light irradiation means for irradiating the target substance detection element with incident light for detection;
A light receiving means for receiving outgoing light composed of transmitted light or reflected light obtained by irradiating the target substance detection element with the incident light;
A reading means for reading a change in the emitted light caused by the presence of the target substance in the specimen;
It is a target substance detection apparatus characterized by having.

  A target substance detection kit according to the present invention is a kit for detecting the presence or amount of a target substance in a sample, the target substance detection element having the above configuration, the detection device having the above structure, and a target substance And a reagent for detecting the target substance.

The target substance detection method of the present invention is a method for detecting a target substance in a sample using the target substance detection element having the above-described configuration,
Contacting the specimen with the target substance detection element;
And a step of detecting an optical change that occurs when the target substance is captured by the target substance detection element.

  The open annular metal structure having a gap (gap) of a part or a plurality of parts disclosed in the present invention can provide an LSPR sensor having a large change in optical characteristics with respect to the presence or absence of a target substance.

The target substance detection element of the present invention comprises:
It has a support, a metal structure existing on the surface of the support, and a target substance capturing body existing on the surface of the metal structure, and the metal structure has a ring structure in which a part of the ring is opened. The target substance detection element characterized by the above. Moreover, one unit (unit) can be formed from two or more of the open ring metal structure.

A device for detecting a target substance can be constructed by incorporating an element in which a metal structure on which a target substance capturing body is fixed is arranged on a substrate together with the following means.
(1) Holding means for holding the target substance detection element.
(2) Light irradiation means for irradiating the target substance detection element held by the holding means with incident light for detection.
(3) Light receiving means for receiving outgoing light composed of transmitted light or reflected light obtained by irradiating the target substance detection element with incident light.
(4) Reading means for reading a change in emitted light caused by the presence of the target substance in the specimen.

Further, the target substance detection element of the present invention can be used together with the following elements to form a target substance detection kit for detecting the presence or absence or amount of the target substance in a sample.
(A) The detection device having the above configuration.
(B) A reagent necessary for capturing the target substance in the device.

A target substance in a sample can be detected by a method having the following steps using the target substance detection element of the present invention.
(I) A step of bringing the specimen into contact with the target substance detection element.
(Ii) A step of detecting an optical change that occurs when the target substance is captured by the target substance detection element.

  An optical change regarding the case where the target substance is captured by the metal structure and the case where the target substance is not captured is obtained in advance, and is stored as known sample data. By comparing this known sample data with the optical change obtained in the above step (ii) with the known sample data, the presence or absence of the target substance in the specimen or its concentration can be determined.

  Embodiments relating to the present invention will be described below with reference to the drawings. Although specific embodiments will be described in detail herein in order to provide a thorough understanding of the present invention, the present invention is not limited to what is described herein.

<Target substance detection element>
This will be described with reference to FIG. In this target substance detection element, a large number of metal structures 101 as metal structures are regularly arranged on the surface of the substrate 102. The shape of each metal structure 101 in the surface direction of the substrate 102, that is, its planar shape, is an open ring (divided ring shape) with one gap. Further, a target substance capturing body 103 is fixed on the surface of each metal structure 101, whereby the target substance 104 can be captured.

  The shape of the metal structure 101 is particularly limited as long as it has a part or a plurality of parts, has a divided ring shape (ring-opening shape), and a pattern in which plasmon is generated at the interface with the specimen or buffer solution. There is no.

  As the divided ring, there is no problem even if a quadrangular or triangular ring as shown in FIG. 2 is divided. Further, as shown in (a) and (b), there may be two gaps, and one unit such as a double ring structure divided as shown in FIGS. 3 (c) and 3 (d). May consist of a plurality of metal structures. In the structures of FIGS. 3C and 3D, the rings having the same planar shape are doubled in one unit, but the rings having different planar shapes may be doubled. Furthermore, as shown in FIGS. 4A, 4B, 4C, and 4D, a split ring having a plurality of gaps may be used.

  The in-plane size (longest part) of the ring-shaped structure is preferably in the range of 10 to 1450 nm, and more preferably in the range of 50 to 1000 nm. The size of the gap (distance between the ends facing the ring-opened portion) is preferably in the range of 1 to 100 nm, and more preferably in the range of 1 to 50 nm. The distance between each metal structure is preferably in the range of 50 to 2000 nm.

  When a large number of metal structures are arranged on the substrate, in addition to the tetragonal lattice arrangement as shown in FIGS. 1 to 3, a triangular lattice arrangement, a hexagonal lattice arrangement, a rotation target arrangement, and a quasi-periodic arrangement There are no particular restrictions on any arrangement.

  As a constituent material of the metal structure, a noble metal such as Au, Ag, Cu, or Pt is preferably used. The film thickness is in the range of 10 to 200 nm, and is appropriately selected and used in the wavelength band of the irradiation light.

<Production process of metal structure>
As a method for producing the metal structure of the target substance detection element, any method can be used as long as a desired pattern can be formed. There is no problem even if it is a technique using electron beam (EB) lithography, a technique using nanoimprint technology, or a technique using photolithography or X-ray lithography. As a method for transferring the pattern to Au, etching may be used, and there is no problem even if the pattern is formed by lift-off.

<Capturer and target substance>
The target substance capturing body 103 is not particularly limited as long as it forms a specific binding pair with the target substance 104. Here, it is preferable to use an antibody or a nucleic acid.

  The target substance is not particularly limited as long as it forms a specific binding pair with the target substance capturing body. Specifically, target substances contained in a specimen are roughly classified into non-biological substances and biological substances. Industrially useful non-biological substances include PCBs with different chlorine substitution numbers / positions as environmental pollutants, dioxins with different chlorine substitution numbers / positions, endocrine disrupting substances called so-called environmental hormones, etc. Can be mentioned.

  The biological material is selected from nucleic acids, proteins, sugar chains, lipids, and complexes thereof.

  Biological substances are included, and more specifically, biomolecules selected from nucleic acids, proteins, sugar chains, and lipids. Specifically, DNA, RNA, aptamers, genes, chromosomes, cell membranes, viruses The present invention can be applied to any substance as long as it contains a substance selected from any of antigens, antibodies, lectins, haptens, hormones, receptors, enzymes, peptides, sphingosaccharides, and sphingolipids. Furthermore, bacteria and cells themselves that produce the above-mentioned “biological substances” can also be target substances as “biological substances” targeted by the present invention.

  Note that the specimen in the present invention can be contacted with the target substance detection element, and when the target substance is present in the specimen, the target substance and the capturing body fixed on the metal structure react. Any material that can capture the target substance by the capturing body may be used. If the collected sample such as a liquid containing the target substance as the detection target can be directly reacted with the target substance detection element, it becomes a specimen. Alternatively, a sample obtained by appropriately diluting a collected sample with a buffer solution or a liquid in which a portion assumed to contain a target substance is transferred from the collected sample can be handled as a specimen.

<Operation principle of sensor>
Next, the operation principle of the target substance detection element (chemical sensor) according to the present invention will be described with reference to FIG. In FIG. 5B, incident light 501 is incident from the upper direction to the lower direction (+ z direction) in the drawing. Incident light is coupled with free electrons in the metal structure, and when the target substance is bound to the trapping body immobilized on the metal structure, the refractive index around the structure changes. Therefore, the resonance frequency of plasmon resonance changes, and the peak of the absorption spectrum shifts. This principle can be used to detect biochemical reactions such as antigen antibodies.

  FIG. 5C shows the state. First, the spectrum is measured in a state where the capture molecules are immobilized. Next, after the antigen-antibody reaction, when the spectrum is measured, the absorption spectrum of the gold nanostructure shifts. Since this shift amount is proportional to the concentration of the antigen, the concentration of the antigen can be measured.

The sensitivity of the measurement depends on how much the change in refractive index around the structure changes the absorption spectrum. Specifically, it can be said that the sensitivity is higher as the peak shift amount is larger, the peak width is narrower, and the peak depth is larger. Au colloid and Au rod structure are known as conventional LSPR sensors, but Au colloid has a small peak shift amount as described above. In addition, since a structure such as an Au rod responds to only one polarized light, about half of the light passes through when the non-polarized light is incident, and the peak depth is reduced. By adopting the open ring structure of the present invention, optical characteristics having a peak shift amount larger than that of the Au colloid and a larger peak depth can be obtained, and a highly sensitive target substance can be detected.

  In the example shown in FIG. 5, transmitted light is used as outgoing light, but reflected light from the element surface may be used as outgoing light.

<Target substance measuring device>
(Measurement device using reaction well)
This will be described with reference to FIG. The light source 602 that is a light irradiation unit is not particularly limited as long as it is a stable light source. In the present invention, it is preferable to use a halogen lamp. The objective lens 603 has no problem as long as incident light from the light source can be made substantially parallel. Here, it is more preferable to use one having no chromatic aberration. As the light receiving means 604 for receiving the transmitted light as the emitted light, a spectroscopic measurement apparatus having a wavelength resolution of about 1 nm is desirable. In the present invention, it is preferable to use a multi-channel detector or a spectrophotometer. As the reaction well 601, it is preferable to use a reaction well 601 made of a material with less non-specific adsorption of the target substance. As the target substance detection element 605, the plasmon optical element shown in FIGS.

(Measurement device using microchannel)
This will be described with reference to FIG. The light source 701 is not particularly limited as long as it is a stable light source. In the present invention, it is preferable to use a halogen lamp. As the light receiving means 702 for receiving transmitted light as outgoing light, a spectroscopic measurement device having a wavelength resolution of about 1 nm is desirable. In the present invention, it is preferable to use a multi-channel detector or a spectrophotometer. As the specimen reservoir 703, a reservoir made of a material with less non-specific adsorption of the target substance, or a reservoir may be built in the chip. In the present invention, it is preferable to use an Eppendorf tube coated with non-specific adsorption prevention. The cleaning liquid reservoir 704 is not particularly limited. Here, it is preferable to use a glass or plastic tube for biochemistry. The flow path switching valve 705 is not particularly limited as long as the fluid tube can be switched. In the present invention, it is preferable to use a three-way valve. As the liquid feeding means 706, a syringe pump, a tube pump, a diaphragm pump, or the like can be appropriately selected and used. As the waste liquid tank 707, when a syringe pump is used as a pump, the syringe becomes a waste liquid tank as it is. When a tube pump or a diaphragm pump is used, a beaker or a bottle can be used as a waste tank. If there is only a small amount of sample, the sample may be circulated using a circulation channel or tube instead of using waste liquid. As the liquid feeding and waste liquid tubes 708 and 709, tubes made of a material having as little as possible adsorption of the target substance are preferable. As the target substance detection element 710, the plasmon optical element shown in FIGS. The flow path 711 is preferably minute so that the amount of the sample can be reduced as much as possible. In addition, it is preferable that the surface of the channel is coated so that the target substance is not adsorbed as much as possible. The cover 712 is preferably a transparent material and a material that can form a flow path with the substrate 713.

  Examples of the present invention will be described below, but the present invention is not limited only to the contents described herein.

Example 1
<Target substance detection element>
This will be described with reference to FIG. A quartz wafer with a thickness of 525 μm is used as the support 202, gold is used as the material of the metal dots 201, and antibodies are used as the capture body 203.
(Element fabrication by electron beam (EB) drawing process)
As the metal dot array, an open ring metal structure having a gap in part is used as shown in FIG. The diameter of the ring is 200 nm, the band width is 50 nm, and the gap interval is 20 nm. The period of the array is 450 nm and the thickness of Au is 50 nm.

Next, an example of a method for manufacturing a detection element is described with reference to FIGS. After 5 nm of Ti is deposited as a binder on the quartz substrate 801, 50 nm of Au ₈ 0 ₂ is continuously deposited. Next, a negative resist 803 (Shipley Far East, SAL601) is spin-coated. After pre-baking, it is introduced into a chamber of an electron beam drawing apparatus and a desired pattern is drawn. After drawing, post-exposure bake is performed and cooled rapidly. Then, it develops with a developing solution and performs resist patterning. Using the patterned resist as a mask, dry etching is performed to transfer the pattern to the gold layer. When the gold is patterned, finally, the resist is removed by performing a process such as a remover. Through the above process, a gold dot pattern can be formed.

<Target substance measuring device>
This will be described with reference to FIG. A halogen lamp is used as the light source 701, and a multi-channel detector (Hamamatsu Photonics) is used as the spectroscope 702. An Eppendorf tube is used as the specimen reservoir 703, and a glass bottle for biochemistry is used as the cleaning liquid reservoir 704. A three-way valve (GL Science) is used as the flow path switching valve 705, and a syringe pump (kd Scientific KDS200) is used as the liquid feeding means 706. A syringe is used as the waste liquid tank 707, and a Teflon tube is used as the liquid feeding and waste liquid tubes 708 and 709. As the target substance detection element 710, an element in which an open ring structure of gold is arranged as shown in FIG. 1 by the above-described patterning method is used. As the flow path 711, a 1 mm width formed on the cover (PDMS substrate) 712 is used. 100 μm width and 40 mm length are used. Quartz glass is used as the substrate 713, and a plano-convex cylinder lens (Sigma light machine, 20 mm × 40 mm) is used as the collimating lens.

<Evaluation of refractive index response>
A localized surface plasmon (LSPR) sensor immobilizes a capturing body that specifically reacts with a specific antigen on the sensor surface, and captures a target substance by the antibody. Since the target substance generally has a higher refractive index than the solution in the visible light region, the refractive index of the gold dot surface is increased by capturing the target substance. Then, the refractive index change is sensed by LSPR. Therefore, if the responsiveness to the refractive index is evaluated, the sensitivity of the sensor can be evaluated. According to the invention disclosed in the present invention, an element composed of a ring-shaped metal nanostructure having a gap of a part or a plurality of parts effectively acts on the plasmon resonance caused by the gap part and the ring part, and has a high refractive index response. It can confirm that it shows sex.

<Measurement of target substance>
In the apparatus of FIG. 7, the target substance detection element 710 on which the anti-PSA antibody is immobilized is set in the apparatus and the following protocol is performed.
(1) The three-way valve is switched to the cleaning liquid side, and a buffer solution whose pH is adjusted to 7.4 is allowed to flow at a flow rate of 0.1 (ml / min.) For 10 minutes to thoroughly wash the target substance detection element.
(2) The valve is switched to the sample side, and the sample is allowed to flow at a flow rate of 0.1 (ml / min.) For 10 minutes to cause an antigen-antibody reaction.
(3) Measure the reflection spectrum at regular intervals while feeding the specimen.
(4) Switch the valve to the washing solution side again, and flow the buffer solution at a flow rate of 0.1 (ml / min.) For 10 minutes to wash away the non-specifically adsorbed antigen.

  With the above protocol, the spectrum shown in FIG. 5C is obtained at each reaction time. By fitting this spectrum with graph software and obtaining the peak value of the spectrum, the time course of the antigen-antibody reaction is obtained as shown in FIG.

(Example 2)
<Target substance detection element>
Four target substance detection elements shown in FIG. 1 are arranged in series, and different types of antibodies are immobilized on the target substance detection elements.
(Element fabrication by nanoimprint process)
An example of a method for manufacturing a detection element will be described with reference to FIGS. After 5 nm of Ti is deposited as a binder on the quartz substrate 901, 50 nm of Au _{90 2} is continuously deposited. Next, a UV curable resin (acrylic or epoxy) 903 is spin-coated. Then, using a template 904 prepared in advance, the resin is patterned by an imprint method. Next, by etching process, Au is etched using the resin film as a resist, and the resist film is then ashed. Through the above process, a desired gold dot pattern can be formed.

<Target substance measuring device>
This will be described with reference to FIG. A halogen lamp is used as the light source 1001, a multi-channel detector capable of simultaneous measurement of 4ch is used as the spectroscope 1002, and an Eppendorf tube is used as the specimen reservoir 1003. A glass bottle for biochemistry is used as the cleaning liquid reservoir 1004, and a three-way valve (GL Science) is used as the flow path switching valve 1005. As the pump 1006, a syringe pump (kd Scientific KDS200) is used, and as the waste liquid tank 1007, a syringe is used. As the liquid feeding and waste liquid tubes 1008 and 1009, Teflon tubes are used, and as the target substance detection element 1010, a chip in which four elements shown in FIG. 1 are arranged in series is used. As the flow path 1011, a 1 mm width, 100 μm width and 40 mm length formed on the PDMS substrate 1012 is used, quartz glass is used as the substrate 1013, and a plano-convex cylinder lens (Sigma light machine, 20 mm × 40 mm) is used as the collimating lens. ) Is used. The optical fiber 1016 is not particularly limited as long as a sufficient amount of light from the light source can be obtained in each wavelength band. Here, it is preferable to use a fiber having a visible light wavelength band.

<Measurement of target substance>
In the apparatus of FIG. 10, a target substance detection element on which an anti-CEA antibody, anti-AFP antibody, anti-PSA antibody and anti-PAP antibody are immobilized is set in the apparatus, and the following protocol is performed.
(1) The three-way valve is switched to the cleaning liquid side, and a buffer solution whose pH is adjusted to 7.4 is allowed to flow at a flow rate of 0.1 (ml / min.) For 10 minutes to thoroughly wash the target substance detection element.
(2) The valve is switched to the sample side, and the sample is allowed to flow at a flow rate of 0.1 (ml / min.) For 10 minutes to cause an antigen-antibody reaction.
(3) Measure the reflection spectrum at regular intervals while feeding the specimen.
(4) Switch the valve to the washing solution side again, and flow the buffer solution at a flow rate of 0.1 (ml / min.) For 10 minutes to wash away the non-specifically adsorbed antigen.

  According to the above protocol, a spectrum as shown in FIG. 5C is obtained for each reaction field. By fitting this spectrum with graph software and obtaining the peak value of the spectrum, the kinetics of the reaction can be measured for each marker protein as shown in FIG. As described above, by measuring the reaction profile of a plurality of disease marker proteins and their antibodies, it becomes possible to investigate the cause of the disease with higher accuracy than the measurement of one protein.

It is a figure for demonstrating the example of the target substance detection element of this invention. It is a figure for demonstrating the example of the target substance detection element (separate structure) of this invention. It is a figure for demonstrating the example of the target substance detection element (separate structure) of this invention. It is a figure for demonstrating the example of the target substance detection element (separate structure) of this invention. It is a figure for demonstrating embodiment of this invention. It is a figure for demonstrating embodiment of this invention. It is a figure for demonstrating embodiment and Example 1 of this invention. It is a figure for demonstrating the preparation process of the target substance detection element of this invention. It is a figure for demonstrating the preparation process of the target substance detection element of this invention. It is a figure for demonstrating Example 2 of this invention. It is a figure for demonstrating Example 1 of this invention. It is a figure for demonstrating Example 2 of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 101 Metal structure 102 Support body 103 Capture body 104 Target substance 201 Metal structure 202 Support body 301 Metal structure 302 Support body 401 Metal structure 402 Support body 501 Incident light 502 Transmitted light 601 Reaction well 602 Light source 602 Objective lens 604 Light reception Means 605 Target substance detection element 701 Light source 702 Spectrometer 703 Sample reservoir 704 Cleaning liquid reservoir 705 Flow path switching valve 706 Liquid supply means 707 Waste liquid tank 708 Liquid supply tube 709 Waste liquid tube 710 Target substance detection element 711 Flow path 712 Cover 713 Substrate 714 Target Substance detection chip 715 Collimate lens 801 Quartz substrate 802 Gold (Au)
803 resist 901 quartz substrate 902 gold (Au)
903 UV curable resin 904 Mold 1001 Light source 1002 Spectrometer 1003 Sample reservoir 1004 Cleaning liquid reservoir 1005 Channel switching valve 1006 Pump 1007 Waste liquid tank 1008 Liquid feeding tube 1009 Waste liquid tube 1010 Target substance detection element 1011 Channel 1012 Cover 1013 Substrate 1014 Target substance Detection chip 1015 Coupler 1016 Optical fiber

Claims (5)

An element for detecting a target substance in a sample,
The target substance detection element is
A support and a metal structure present on the surface of the support;
A target substance capturing body present on the surface of the metal structure,
The element for detecting a target substance, wherein the metal structure has a ring structure in which a part of the metal structure is opened.   The target substance detection element according to claim 1, comprising a unit composed of a plurality of the metal structures. A target substance detection device comprising:
Holding means for holding the target substance detection element according to claim 1 or 2,
Light irradiation means for irradiating the target substance detection element with incident light for detection;
A light receiving means for receiving outgoing light composed of transmitted light or reflected light obtained by irradiating the target substance detection element with the incident light;
A reading means for reading a change in the emitted light caused by the presence of the target substance in the specimen;
A target substance detection device comprising:   A kit for detecting the presence or absence or amount of a target substance in a specimen, the target substance detection element according to claim 1 or 2, the detection apparatus according to claim 3, and the target substance to the element And a reagent for detecting the target substance. A method for detecting a target substance in a sample using the target substance detection element according to claim 1, comprising:
Contacting the specimen with the target substance detection element;
And a step of detecting an optical change that occurs when the target substance is captured by the target substance detection element.

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