JP4405883B2 - Target substance detection device - Google Patents

Description

The present invention relates to an apparatus for detecting a target substance by detecting a wavelength characteristic of light transmittance or light reflectance in the presence of a target substance.

In recent years, with increasing awareness of health problems, environmental problems, and safety problems, a method for detecting trace amounts of biological substances and chemical substances involved in these problems has been desired. As this detection method, many methods for measuring changes in optical characteristics caused by the interaction between a liquid specimen containing a detection target substance and a reagent or a sensor element have been proposed. As an optical detection method for these detection target substances,
(1) A technique for detecting a change in the absorption spectrum or a change in the absorbance at a specific wavelength due to a reaction product generated by a chemical reaction including an enzyme reaction, and (2) fixing a capturing body that specifically binds to the detection target substance. A method of forming agglomerates of fine particles via a detection target substance using the activated microparticles, and detecting a change in absorbance spectrum of the aggregate or absorbance at a specific wavelength,
Many methods for detecting spectral changes have been proposed and developed.

  Since these methods rely on spectrum detection using a spectroscope, there is a problem that it takes time to scan the wavelength region for spectrum detection. This problem can be improved by using a polychromator and an array-type detection method that does not require wavelength scanning, but there are restrictions on the arrangement of the light source, specimen detector, polychromator, and detector. The problem remains that it is difficult to reduce the size.

Further, as an example of solving the above-described miniaturization problem by a detection technique that does not rely on an absorption spectrum, there is a sensor based on a surface plasmon resonance method as described in Patent Document 1. The invention described in Patent Document 1 is characterized in that the mechanism for detecting the resonance angle, which is a problem of the conventional surface plasmon resonance method, is solved by the spread of incident light and a photodiode array. As an advantage of this sensor, the configuration of the detection device can be simplified because the light emitting and light receiving elements are formed in the same plane. However, the length corresponding to the resonance angle is required at the site where the specimen comes into contact , that is, the size of the sensor surface required for detecting one type of detection target substance is increased, so that multiple detection target substances can be detected simultaneously. There are limitations.

As a technique for solving the problem of the sensor area of the detection of the one kind of detection target substance by the technique using plasmon resonance, there is a sensor based on the localized plasmon resonance method using metal fine particles described in Patent Document 2. Since the sensor element based on this localized plasmon resonance uses metal fine particles, there is an advantage that the area of the detection portion is small. However, since it is necessary to detect a transmission or reflection spectrum, the same problem as the method using spectrum detection described above remains.
JP-A-10-212245 Japanese Patent No. 3452837

  The present invention has been made in view of the above-described problems of the prior art. The purpose is to reduce the size of both the sensor element unit and the detection device in the detection method of the target substance based on the wavelength spectrum characteristics. Furthermore, it aims at simplification of the structure of a detection apparatus simultaneously.

In order to achieve the above object, the present invention uses, as a sensor element, a sensing element provided with a substance whose optical physical properties change upon contact with a target substance. A light source for irradiating the sensor element part with light for detection and a plurality of light receiving means for receiving light transmitted through the sensor element are formed on the same substrate. Further, a spectroscopic unit is provided on the optical path from the light source to the light receiving unit so that the dispersed light is incident on each of the plurality of light receiving units for each wavelength band. With the above configuration, the spectral transmission characteristics of the sensor element can be detected .

That is, the detection location of a target substance according to the present invention has a surface capable of fixing the target substance, in accordance with the fixed state of the target substance to the surface, by plasmon resonance, the wavelength characteristics of irradiation light is A sensing element that changes, a light source, a light irradiation means for irradiating the detection element with light from the light source, and a light receiving means for receiving light emitted from the light source and obtained through the detection element , A target substance detection device using plasmon resonance,
The sensing element comprises a plurality of fine metal particles capable of causing localized plasmon resonance,
The light emitted from the light source disposed on the same substrate as the light receiving means passes through the detection element, and then is dispersed by the spectroscopic means, whereby light in a different wavelength range has a plurality of light receiving elements. A target substance detection apparatus using plasmon resonance, which is configured to receive light by an element array .

  As an effect of the present invention, it is possible to contribute to downsizing of an apparatus for analyzing the amount of a substance to be detected in a specimen by the wavelength spectrum characteristics. Furthermore, since there is no need for mechanical driving when acquiring the wavelength spectrum, it contributes to shortening the time required for acquiring the spectrum, that is, the analysis time. Further, since the electrical elements of the light emitting element and the light receiving element exist on a single substrate, the electrical interface is simplified, the apparatus configuration is simplified, and the workability during maintenance is improved.

  The best mode for carrying out the present invention will be described. Here, the detection element portion of the present invention and other optical components will be described separately.

[Optical configuration]
The optical configuration will be described with reference to FIG.
(Configuration of FIG. 1)
Reference numeral 101 denotes a substrate. This substrate may be a printed circuit board or a semiconductor substrate. Reference numeral 102 denotes a light emitting element as a light source configured on a substrate. The light emitting element is not particularly limited as long as it has a sufficient amount of light in the target wavelength range, but a light emitting diode and a semiconductor laser are preferable. Reference numeral 103 denotes a light receiving element array in which a plurality of light receiving elements as light receiving means are arranged in an array. Here, the sensor array is configured in a straight line, and there is no particular limitation as long as it has sufficient sensitivity in the target wavelength range.

  Reference numeral 104 denotes a detection element. In FIG. 1, the detection element is configured between the light emitting element 102 and the diffraction grating 107, but may be configured between the spectroscopic means and the light receiving means as shown in FIG. The configuration of the detection element will be described later. Reference numeral 105 denotes a light shielding plate for narrowing light from the light emitting element. Reference numeral 106 denotes a collimating lens for converting light from the light emitting element into parallel light. Reference numeral 107 denotes a diffraction grating which is a spectroscopic means for splitting light from the light emitting element. Although a reflection type diffraction grating is used in FIG. 1, a transmission type optical system may be configured. However, depending on the diffraction efficiency, a blazed reflection diffraction grating is used and a free spectral region of the first-order diffracted light is used. It is desirable to detect them. Further, as the spectroscopic means, a prism may be used instead of the diffraction grating. Although not shown in FIG. 1, it is more preferable to configure a filter for limiting the wavelength on the light emitting element in order to avoid stray light due to light having a wavelength outside the free spectrum. Reference numeral 108 denotes a concave mirror for guiding and focusing the light dispersed by the diffraction grating onto the light receiving element 103, thereby narrowing the detection wavelength range for each light receiving element and improving the spectral accuracy. In FIG. 1, 108 is a concave mirror and 107 is a flat diffraction grating, but 107 may be a concave diffraction grating and 108 may be a plane mirror.

The wavelength (wavelength range) of the light incident on the plurality of light receiving elements is made different by the spectroscopic means, and the light receiving wavelengths of the plurality of optical elements are thereby made different so that the detection element for each wavelength (or wavelength range). Each light receiving element receives each of a plurality of wavelengths (or wavelength ranges) obtained by dividing a predetermined wavelength range necessary for forming a wavelength absorption spectrum. By providing it, an absorption spectrum over a predetermined wavelength range can be obtained.
Note that, when the substrate 101 is formed on the same semiconductor substrate, Si (silicon) and GaAs (gallium arsenide) substrates are suitable as the substrate material 101. In addition, the light-emitting element 102 may be formed using a compound containing at least one of Ga (gallium), N (nitrogen), In (indium), Al (aluminum), and P (phosphorus). desirable. The light receiving element 103 is preferably a photodiode made of Si if the target wavelength is in the visible light region, and is preferably a photodiode made of GaAsP if the visible light is only in the blue region. In the infrared region, an InGaAs photodiode is desirable. It is desirable that the substrate material 101, the light emitting element 102, and the light receiving element 103 have a suitable combination according to the target wavelength region. However, for the substrate 101, it is more desirable to use a Si substrate in consideration of the cost of the substrate.

[Detecting element section]
The configuration of the detection element unit will be described with reference to FIGS. FIG. 5 shows an example of a sensing element by a localized plasmon resonance method using metal fine particles. FIG. 5A shows an example in which metal fine particles are fixed on the surface of a flat plate. Reference numeral 401 denotes a substrate, and reference numeral 402 denotes metal fine particles fixed on the 401 substrate. The substrate material 401 is optically transparent . The metal element 402 is composed of any metal element that can cause a localized plasmon resonance phenomenon, and gold and silver are particularly preferable.
FIGS. 5B and 5C show a state in which metal fine particles are fixed in a flow channel through which a liquid sample as a specimen can flow. 401 and 402 are similarly a board | substrate and metal microparticles | fine-particles, and are the same as that of the content mentioned above, However, The flow-path part 403 is provided in the board | substrate of 401. FIG. Reference numeral 403 denotes a formed flow path, which is a portion through which a specimen containing a detection target substance flows. Reference numeral 404 denotes a lid on the upper surface of the flow path. The 404 parts are preferably optically transparent. The example shown here is an example in which metal fine particles are fixed to the groove portion of the substrate in which the groove 401 is formed, but the metal fine particles may be fixed to the flow path portion of the lid 404.

  FIG. 5 (d) is an enlarged view of the vicinity of the fine particles in FIGS. 5 (a), (b), and (c), and is an explanatory view of a site that recognizes an actual detection target substance. A capture body that specifically binds to the detection target substance indicated by 405 is fixed to the metal fine particle 402. Reference numeral 406 denotes a detection target substance. FIG. 5D shows a state where the substance is captured by a capturing body 405. A suitable example of the 405 capturing body will be described later.

  In the detection method using localized plasmon resonance, it is known that absorption is increased at a specific wavelength due to localized plasmon resonance of metal fine particles. Since this absorption peak wavelength changes depending on the refractive index in the vicinity of the metal fine particles, the absorption peak wavelength shifts because the refractive index in the vicinity of the metal fine particles changes when the detection target substance is captured by the capturing body. Therefore, by detecting this shift amount, the amount of the detection target substance can be obtained. The fixed state of the detection target substance, that is, the presence / absence of the detection target substance and its fixed amount can be obtained. The reaction between the detection target substance and the metal fine particles having the capturing body can be performed by adding a liquid sample containing the detection target substance to the metal fine particles having the capturing body fixed to the flow path.

FIG. 6 shows an example of a sensing element using surface plasmon resonance as a reference example . Reference numeral 501 denotes a substrate. This substrate is preferably made of a material that is optically transparent to a degree sufficient for measurement with transmitted light, and is preferably made of the same material as that of a prism 503 described later or a material having a refractive index close to each other. Reference numeral 502 denotes a metal thin film. The metal element constituting the metal thin film may be any metal element as long as it can cause a plasmon resonance phenomenon, and gold and silver are particularly preferable. Reference numeral 505 denotes a capturing body that specifically binds to the detection target substance, and is fixed to the metal thin film 502. 506 is a substance to be detected, and shows a state where it is captured by a capturing body 505. Reference numeral 503 denotes a prism which is present for making incident light 507 for detection incident on a metal thin film at a total reflection angle and extracting reflected light 508 on the surface of the metal thin film. This prism is not included in the detection element, but is shown for convenience of explanation. Reference numeral 504 denotes an index matching oil. This is used to prevent reflection on the contact surface when the detection element is set on the prism 503 of the apparatus side component. In the detection method using surface plasmon resonance, it is known that the absorption at a specific wavelength increases and the reflected light intensity decreases due to the surface plasmon resonance of the metal thin film. Since this absorption peak wavelength changes depending on the refractive index in the vicinity of the metal thin film, the absorption peak wavelength shifts because the refractive index in the vicinity of the metal thin film changes when the detection target substance is captured by the capturing body. Therefore, by detecting this shift amount, the amount of the detection target substance can be obtained.

FIG. 7 shows a detection method using an enzyme label as a reference example . Reference numeral 601 denotes a substrate. The substrate is not particularly limited as long as it is optically transparent enough to measure with transmitted light. Reference numeral 602 denotes a capturing body that specifically binds to the detection target substance. In this example, an antibody is used and is fixed to a substrate 601. Reference numeral 603 denotes a detection target substance. Reference numeral 604 denotes a capturing body that specifically binds to the detection target substance labeled with the enzyme 605. Reference numeral 606 denotes an enzyme substrate corresponding to the enzyme 605, and reference numeral 607 denotes an enzyme reaction product generated by the action of the enzyme on the enzyme substrate. Although 605 enzymes are preferred, horseradish peroxidase, alkaline phosphatase, and β-galactosidase are preferred. There is no particular limitation as long as it has optical characteristics such as absorption at the wavelength. As the substrate, those usually used in combination with these enzymes can be used. For example, an antibody capable of binding to a target substance labeled with horseradish peroxidase (labeled antibody) is used, and a capture body composed of an antibody specific to the target substance is immobilized on a substrate by a conventional method. An enzyme reaction product having an absorption wavelength at 491 nm can be obtained by capturing a target substance, binding a labeled antibody, and adding 1,2-phenylenediamine as a substrate.

  Thus, when the enzyme reaction product has absorption at a specific wavelength, the absorption spectrum resulting from the enzyme reaction product can be obtained in the absorption spectrum of the transmitted light, and the detection element surface of the detection target substance can be obtained from this absorption spectrum. In other words, the presence or absence of the substance to be detected on the surface of the sensing element and the amount of the substance to be immobilized can be obtained.

FIG. 8 shows a detection method using a fluorescent label as a reference example . Reference numeral 701 denotes a substrate. When measuring transmitted light, the substrate may be a substrate having sufficient transparency for measuring transmitted light. When measuring reflected light, the substrate should be a substrate having a reflective surface sufficient for measuring reflected light. I just need it. Reference numeral 702 denotes a capturing body that specifically binds to the detection target substance. In this example, an antibody is used and is fixed to a substrate 701. Reference numeral 703 denotes a detection target substance. Reference numeral 704 denotes a capturing body that specifically binds to the detection target substance labeled with the fluorescent dye 705. In this example, it is an antibody labeled with a fluorescent dye. As the fluorescent dye, FITC, Cy3, and Cy5 are often used. Reference numeral 706 denotes excitation light corresponding to the fluorescent dye 705, and reference numeral 707 denotes fluorescence emitted from the fluorescent dye 705. Fluorescence is generated according to the fixed state of the detection target substance, so that the emission spectrum intensity of the fluorescence from the detection element changes, and thereby, the fixed state of the detection target substance on the detection element surface, i.e. The presence or absence of the detection target substance and its fixed amount can be determined. When a detection system in which excitation light affects the light receiving element side is used, a wavelength limiting filter that blocks the excitation light is provided at an appropriate position so that the excitation light does not reach the light receiving element side.

(Captured body)
The target substance capturing body fixed on the surface of the metal fine particle is not particularly limited as long as it forms a specific binding pair with the target substance. Examples of combinations of binding pairs that specifically bind to the detection target substance include antigen / antibody, complementary DNA, receptor / ligand, and enzyme / substrate.

  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. Biological materials include biological materials selected from nucleic acids, proteins, sugar chains, lipids, and complexes thereof, and more specifically, biomolecules selected from nucleic acids, proteins, sugar chains, and lipids. Specifically, it is selected from DNA, RNA, aptamer, gene, chromosome, cell membrane, virus, antigen, antibody, lectin, hapten, hormone, receptor, enzyme, peptide, sphingosaccharide, sphingolipid The present invention can be applied to any substance as long as it contains any other substance. 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.

  Hereinafter, the present invention will be described with other examples, but these do not limit the scope of the present invention.

Example 1
A first embodiment will be described with reference to FIG. 102 light emitting elements are placed on 101 substrate material. Here, a printed circuit board is used as the substrate 101, and a white light emitting diode is surface-mounted on the printed circuit board as a light emitting element. As the light receiving element 103, a photodiode array is used. Reference numeral 104 denotes a sensing element unit. Here, a sensing element based on localized plasmon resonance shown in FIG. 5 is used. This sensing element uses an optically transparent glass flow cell. The detection region on the inner surface of the flow cell is subjected to an aminosilane coupling treatment to form an inner surface from which an amino group has come out. Fix it.

  Subsequently, the antibody is immobilized on the gold fine particles as a capturing body. In the immobilization method, the gold fine particles are surface-modified with an ethanol solution of 11-mercaptodecanoic acid having a thiol group having a high affinity for gold in the detection region of the flow cell to which the gold fine particles are fixed. Thereby, the carboxyl group is exposed on the surface of the gold fine particles. In this state, an aqueous solution of N-Hydroxysulfuccinimide (manufactured by Dojindo Laboratories) and an aqueous solution of 1-Ethyl-3- [3-dimethylamino] propyl] carbohydrate hydrate (manufactured by Dojindo Laboratories) are dropped into the detection region. Thereby, the succinimide group is exposed on the surface of the gold fine particles. Subsequently, as an antibody to be immobilized, a rabbit anti-mouse IgG antibody / phosphate buffer (pH 8.0) specific for the target substance is placed in the flow cell. By reacting the succinimide group arranged on the gold surface with the amino group of the rabbit anti-mouse IgG antibody, the rabbit anti-mouse IgG antibody is immobilized on the gold surface. The above is the method for creating the sensing element.

  Reference numeral 105 denotes a light shielding plate, which is used to limit the divergence angle from the light emitting diode 102. The light passing through the light shielding plate is collimated by 106 collimating lenses. The parallel light is incident on 107 diffraction gratings. The longest wavelength light beam is diffracted to 111 and the short wavelength light beam is diffracted to 112 by the diffraction grating 107. The light split here is focused into the shape of the photodiode array 103 by the concave mirror 108, and the detection wavelength range for each light receiving element is narrowed to improve the spectral accuracy. As a result, light in different wavelength ranges is incident on each photodiode of the 103 photodiode array. Therefore, by detecting the output signals of all the pixels of the photodiode array 103, the absorption spectrum of the localized plasmon resonance of the detection unit 104 can be acquired. A signal processing method from the photodiode will be described with reference to FIG. Assume that the output of each photodiode 1011 has already been converted to a voltage by a current-voltage conversion circuit. Here, a current-voltage conversion circuit is not shown, but a circuit using an operational amplifier is generally used. The output of each photodiode is held by a 1010 hold circuit. The role of the hold circuit is to sample and hold each photodiode simultaneously. The output held by the hold circuit is input to the AD converter 1008 by the multiplexer 1009. Although a multiplexer is used here, a shift register may be used. The value converted into digital data by the AD converter is processed by the central processing unit 1001 and processed as spectrum data. In this embodiment, since detection using localized plasmon resonance is performed, spectrum data as shown in FIG. 9 can be acquired. This processing method will be described below.

  Here, the change of the detection unit 104 will be described. A capturing body 405 is fixed to the surface of the metal fine particle 402 in FIG. In this example, an antibody that specifically binds to the detection target substance is used for this capturing body. When the detection target substance 406 is captured by this antibody, the refractive index near the metal fine particle 402 changes. As a result, as shown in FIG. 9, the absorption peak wavelength due to localized plasmon resonance in the metal fine particles 402 is shifted. The amount of the detection target substance in the unknown sample can be obtained based on a calibration curve obtained in advance from the shift amount of the absorption peak and a known amount of the detection target substance.

( Reference Example 1 )
A first reference example will be described with reference to FIG. 102 light emitting elements are placed on 101 substrate material. Here, a printed circuit board is used as the substrate 101, and a white light emitting diode is surface-mounted on the printed circuit board as a light emitting element. As the light receiving element 103, a photodiode array is used. Reference numeral 105 denotes a light shielding plate, which is used to limit the divergence angle from the light emitting diode 102. The light passing through the light shielding plate is collimated by 106 collimating lenses. The parallel light is incident on 107 diffraction gratings. The longest wavelength light beam is diffracted to 111 and the short wavelength light beam is diffracted to 112 by the diffraction grating 107. The light split here is focused into the shape of the photodiode array 103 by the concave mirror 108, and the detection wavelength range for each light receiving element is narrowed to improve the spectral accuracy. As a result, light in different wavelength ranges is incident on each photodiode of the 103 photodiode array.

Reference numeral 104 denotes a detection element unit. Here, as in the first embodiment, the detection element based on localized plasmon resonance shown in FIG. 5 is used. What is indicated by 11X is a detection site in the detection element. Absorption spectrum of the localized plasmon can be acquired by detecting the light after the spectrum passing through the detection part by the photodiode array 103. Since the signal processing is the same as in the first embodiment, it is omitted here. However, when the detection site is smaller than the photodiode array 103 as shown in FIG. 2, the entire spectrum of the detection site cannot be acquired. Therefore, the spectrum of the entire target wavelength range of the 11X detection region can be acquired by acquiring the photodiode signal while moving the detection element 104 in the direction of the photodiode. Since the change of the detection unit 104 is the same as that of the first embodiment, the description thereof is omitted here.
(Reference Example 2)
The second reference example will be described with reference to FIG . 102 light emitting elements are placed on 101 substrate material. Here, a printed circuit board is used as the substrate 101, and a white light emitting diode is surface-mounted on the printed circuit board as a light emitting element. As the light receiving element 103, a photodiode array is used. Reference numeral 105 denotes a light shielding plate, which is used to limit the divergence angle from the light emitting diode 102. The light passing through 105 is reflected by the concave mirror 108 and placed on the sensing element 104 so as to be focused. Here, the sensing element 104 uses an enzyme label shown in FIG. The light reflected from the detection element enters the concave diffraction grating 107. With the 107 diffraction grating, the longest wavelength light beam is diffracted to 111 and the short wavelength light beam is diffracted to 112. The light split here is focused on the 103 photodiode array with the power of the concave surface of the 107 diffraction grating, thereby narrowing the detection wavelength range for each light receiving element and improving the spectral accuracy. As a result, light in different wavelength ranges is incident on each photodiode of the 103 photodiode array. Since the signal processing of the photodiode array is the same as in the first embodiment, it is omitted here.

Reference numeral 104 denotes a detection element unit. Here, the detection label element using the enzyme shown in FIG. 7 is used. Reference numeral 601 in FIG. 7 denotes a substrate of the detection element. This is an antibody that is a capturing body that specifically binds to the detection target substance 602 on this substrate. This antibody captures 603 detection target substances. An antibody, which is a capture body labeled with an enzyme, indicated by 604 is bound to the substance to be detected that is captured. In this state, 606 enzyme substrates are introduced to generate 607 enzyme products. As the enzyme used here, horseradish peroxidase is used, and 1,2-phenylenediamine is used as an enzyme substrate. The resulting enzyme product has an absorption at 491 nm. The amount of detection target substance can be determined by measuring the absorption at 491 nm. In other words, the signal of the specific element portion of the 103 photodiode array may be detected. Since each detection signal processing of the photodiode array is the same as that of the first embodiment, description thereof is omitted.
In addition, although the detection element 104 is used, a detection element using fluorescence as shown in FIG. 8 may be used instead of the label with the enzyme.

( Reference Example 3 )
A third reference example will be described with reference to FIG. 102 light emitting elements are placed on 101 substrate material. Here, a printed circuit board is used as the substrate 101, and a white light emitting diode is surface-mounted on the printed circuit board as a light emitting element. As the light receiving element 103, a photodiode array is used. Reference numeral 105 denotes a light shielding plate, which is used to limit the divergence angle from the light emitting diode 102. The light passing through the light shielding plate is collimated by 106 collimating lenses. The parallel light is incident on the 301 prism. By the prism 301, the detection element 104 is made incident on the metal thin film 302 at a total reflection angle. Details of this sensing element are shown in FIG. Details will be described later.

  The light reflected on the surface of the detection element passes through the prism again and enters the concave diffraction grating 107. As for the light incident on the diffraction grating, the longest wavelength light beam is diffracted to 111 and the short wavelength light beam is diffracted to 112. The light dispersed here is focused into the shape of the photodiode array 103 by the power of the concave diffraction grating 107, thereby narrowing the detection wavelength range for each light receiving element and improving the spectral accuracy. As a result, light in different wavelength ranges is incident on each photodiode of the 103 photodiode array. Since the signal processing of the photodiode array is the same as in the first embodiment, it is omitted here.

  Here, the detection element unit will be described with reference to FIG. Incident light 507 is introduced at a total reflection angle into a metal thin film formed on the detection element 501 by a prism 503. The light reflected by the surface of the metal thin film passes through the prism again to become 508 outgoing light. Here, an index matching oil 504 is provided between the detection element substrate 501 and the prism 503 so as to prevent reflection at the interface. On the metal thin film 502, an antibody 505 that is a capturing body for capturing the detection target substance 506 is fixed.

  When the detection target substance 506 is captured by the antibody 505, the refractive index near the metal thin film 502 changes. As a result, the peak wavelength of reflected light attenuation due to surface plasmon resonance in the metal thin film 502 is shifted. The amount of the detection target substance in the unknown sample can be obtained based on the calibration curve obtained from the shift amount of the peak of attenuation and the detection target substance of a known amount in advance.

It is a detection device block diagram of a 1st embodiment. It is a detection device block diagram of the first reference embodiment. It is a detection apparatus block diagram of 2nd reference embodiment. It is a detection apparatus block diagram of 3rd reference embodiment. It is a figure which shows the detection element of a localized plasmon resonance. It is a figure which shows the detection element of surface plasmon resonance. It is a figure which shows the detection element of an enzyme label. It is a figure which shows the detection element of a fluorescent label. It is a figure which shows the spectrum change by local plasmon resonance. It is a block diagram which shows the apparatus structure of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 101 Substrate 102 Light emitting element 103 Light receiving element array 104 Detection element 105 Light shielding plate 106 Collimating lens 107 Diffraction grating 108 Reflecting mirror 109 Optical path center line 110 Line indicating the range of the light beam 111 Line indicating the optical path of the diffracted light on the long wavelength side 112 Short Line indicating optical path of diffracted light on wavelength side 113 Wavelength limiting filter 114 Detection site 301 Prism 302 Metal thin film 401 Detection element substrate 402 Metal fine particle 403 Flow path 404 Cover material 405 Captured body 406 Detection target substance 501 Detection element substrate 502 Metal thin film 503 Prism 504 Index matching oil 505 Capture body 506 Detection target substance 507 Incident light 508 Reflected light 601 Detection element substrate 602 Capture body 603 Detection target substance 604 Enzyme label capture body 605 Enzyme 606 Enzyme substrate 607 Enzyme life Composition 701 Detection element substrate 702 Capture body 703 Detection target substance 704 Fluorescent label capture body 705 Fluorescent dye 706 Excitation light 707 Fluorescence 1001 Central processing unit 1002 Memory 1003 Fixed disk 1004 Display device 1005 Keyboard 1006 LED lighting circuit 1007 LED
1008 AD converter 1009 Multiplexer 1010 Hold circuit 1011 Photodiode array

Claims (3)

Has a surface capable of fixing the target substance, in accordance with the fixed state of the target substance to the surface, by plasmon resonance, and detection device wavelength characteristics of irradiation light is changed, and the light source, from a light source Detection of a target substance using plasmon resonance comprising light irradiating means for irradiating light to the sensing element and light receiving means for receiving light emitted from the light source and obtained through the sensing element A device,
The sensing element comprises a plurality of fine metal particles capable of causing localized plasmon resonance,
The light emitted from the light source disposed on the same substrate as the light receiving means passes through the detection element, and then is dispersed by the spectroscopic means, whereby light in a different wavelength range has a plurality of light receiving elements. An apparatus for detecting a target substance using plasmon resonance, wherein the apparatus is configured to receive light by an element array. The target substance detection apparatus using plasmon resonance according to claim 1, further comprising reflection means for guiding light from the light source to the light receiving means via the detection element. The apparatus for detecting a target substance using plasmon resonance according to claim 2, wherein the reflecting means is configured by using a concave mirror, and the concave mirror focuses light split by the spectroscopic means on the light receiving means.

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