JP2008281470A - Device for measuring multichannel type surface plasmon resonance phenomenon - Google Patents

Device for measuring multichannel type surface plasmon resonance phenomenon Download PDF

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JP2008281470A
JP2008281470A JP2007126575A JP2007126575A JP2008281470A JP 2008281470 A JP2008281470 A JP 2008281470A JP 2007126575 A JP2007126575 A JP 2007126575A JP 2007126575 A JP2007126575 A JP 2007126575A JP 2008281470 A JP2008281470 A JP 2008281470A
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prism
light source
plasmon resonance
surface plasmon
optical system
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JP2007126575A
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Hiromitsu Ogata
浩光 小形
Keiichi Kafuku
慶一 加福
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Andes Electric Co Ltd
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Andes Electric Co Ltd
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a device for measuring multichannel type surface plasmon resonance phenomenon that forms a prism on a sensor substrate by chemical etching to solve the botheration on operation caused by the introduction of the interface between the sensor substrate and the prism, and enter, by eliminating the affect of reflected light from places other than a sensing point and dividing beams emitted from a light source to improve an S/N ratio into N divisions equally with a beam splitter, them into only a sensing spot. <P>SOLUTION: The device for measuring multichannel type surface plasmon resonance phenomenon includes the light source for emitting beams, an optical system for dividing the light source into N divisions of the same light intensity and equal beams, an optical system for entering each beams divided into the N divisions simultaneously so as to line-focus on a substrate where a metallic thin film and the prism are formed and each sensing point on the substrate at a fixed angle, and a calculation section for extracting an electric signal of a detector to perform an operation and a comparison, which is small-sized and enables simultaneous multipoint-measurement. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

本発明は、多点において同時計測が可能な表面プラズモン共鳴現象測定装置(以下、SPR測定装置という)に関するものである。   The present invention relates to a surface plasmon resonance phenomenon measuring apparatus (hereinafter referred to as an SPR measuring apparatus) capable of simultaneous measurement at multiple points.

SPR測定装置は、生体分子間相互作用解析装置(ビアコア製、日本レ−ザ−製)として生化学関連の研究においては必要不可欠な装置となっている。しかし,現状のものはあくまでも研究目的のもので、on site・フィールドユースを指向しておらず高価な卓上型理化学機器の範疇である。   The SPR measuring device is an indispensable device for biochemical research as a biomolecular interaction analyzer (manufactured by Biacore, manufactured by Nippon Laser Co., Ltd.). However, the current ones are for research purposes only, and are not intended for on-site / field use, but are a category of expensive desktop physics and chemistry equipment.

前記SPR測定装置において、試料の温度変化による屈折率変化を排除するため、試料の温度を一定に保つための温度コントロールユニットを組み込んでおり、装置が大型で高額となる1つの要因となっていた。   In the SPR measuring apparatus, in order to eliminate the refractive index change due to the temperature change of the sample, a temperature control unit for keeping the temperature of the sample constant is incorporated, which is one factor that makes the apparatus large and expensive. .

この改善策として、例えば、特開2004-340922などの様な差動式のSPRが供されている。ここでは、センシングポイントをブランクと対象物の2つに分け、それらのシグナルの差を算出する事で、試料の温度変化による誤差を排除している。   As an improvement measure, for example, a differential SPR as disclosed in Japanese Patent Application Laid-Open No. 2004-340922 is provided. Here, the sensing point is divided into a blank and an object, and the difference between the signals is calculated to eliminate the error due to the temperature change of the sample.

しかしながら、センサー基板とプリズムのインターフェースとしてPVC膜を用いてセンサー基板をPVC膜へ押し付けて使用しており、操作に於いては勘と熟練を要するものであった。さらに、この押し付け度合いにより、計測されるシグナルにバラツキが生じるといた問題があった。   However, a PVC film is used as an interface between the sensor substrate and the prism and the sensor substrate is pressed against the PVC film, and the operation requires skill and skill. Furthermore, there is a problem that the measured signal varies depending on the degree of pressing.

また、センシングポイント以外にも光源が入射されるために、その反射光の影響によりバックグラウンドが高くなってしまうといった問題があった。   Further, since the light source is incident other than the sensing point, there is a problem that the background becomes high due to the influence of the reflected light.

特開2004-340922JP2004-340922

本発明が解決しようとする問題点は、センサー基板とプリズム間のインターフェース導入による操作上の煩わしさを解消し、誰でもが簡単に操作できるSPRを提供することである。また、従来の様にセンシングポイント以外からの反射光の影響を排除し、S/N比の向上を図る。   The problem to be solved by the present invention is to eliminate the troublesome operation due to the introduction of the interface between the sensor substrate and the prism, and to provide an SPR that anyone can easily operate. In addition, the influence of reflected light from other than the sensing point is eliminated as before, and the S / N ratio is improved.

本発明では、センサー基板とプリズム間のインターフェース導入による操作上の煩わしさを解消するため、化学的エッチングによりセンサー基板上にプリズムを形成する。また、光源から発せられたビームをビームスプリッタにより均等にN分割し、センシングスポットだけに入射させることで、従来のようなノイズを排除し、S/N比を向上させる。   In the present invention, the prism is formed on the sensor substrate by chemical etching in order to eliminate the troublesome operation due to the introduction of the interface between the sensor substrate and the prism. Further, the beam emitted from the light source is equally divided into N by the beam splitter and incident only on the sensing spot, thereby eliminating noise as in the prior art and improving the S / N ratio.

本発明のSPR測定装置は、インターフェースを必要としないプリズム一体型のセンサー基板を製作し、これを用いることで、操作性が格段に向上する。
また、光源を均等にN分割可能なビームスプリッタにより、センシングスポットだけに光を入射させることができ、これによりノイズとなるセンシングポイント以外からの反射光がなくなり、得られるシグナルのS/N比は向上する。
The SPR measurement device of the present invention can be manufactured with a prism-integrated sensor substrate that does not require an interface, and by using this, the operability is greatly improved.
In addition, the beam splitter that can divide the light source equally into N allows light to be incident only on the sensing spot, which eliminates the reflected light from other than the sensing point that causes noise, and the S / N ratio of the signal obtained is improves.

ビームを発生する光源と、前記光源を同じ光強度で均等なビームにN分割する光学系と、N分割された各々のビームを同時に、金属薄膜とプリズムが形成された基板と、基板上の各センシングポイントに一定の角度で線焦点を結ぶように入射させる光学系と、金属薄膜面からの反射光を検出器に結像するための光学系と、検出器の電気信号を取り出して演算および比較を行うための演算部を有し、小型で多点における同時計測を可能とした表面プラズモン共鳴現象測定装置。     A light source that generates a beam, an optical system that divides the light source into N equal beams with the same light intensity, a substrate on which a metal thin film and a prism are formed, and each of the N divided beams, Computation and comparison by taking out the electrical signal of the detector and the optical system that makes the sensing point incident at a certain angle to form a line focus, the optical system that forms the reflected light from the metal thin film surface on the detector A surface plasmon resonance phenomenon measuring apparatus that has a calculation unit for performing the measurement and is small and capable of simultaneous measurement at multiple points.

図1は、本発明装置の各部の配置である。光源1より発せられたビームはコリメートレンズ2を通り、ここで平行光となる。   FIG. 1 is an arrangement of each part of the device of the present invention. The beam emitted from the light source 1 passes through the collimating lens 2 and becomes parallel light here.

前記の平行光は、ビームスプリッタ3で同じ強度をもち、且つ、無偏光の3つの平行光に分割される。   The parallel light is split into three non-polarized parallel lights having the same intensity by the beam splitter 3.

これらのビームはミラー4を介してシリンドリカルレンズ5により、プリズム一体型のセンサー基板6上に形成された金属薄膜面上で線焦点を結び、反射される。   These beams are reflected by the cylindrical lens 5 through the mirror 4 so as to form a line focus on the metal thin film surface formed on the prism-integrated sensor substrate 6.

前記金属薄膜上で反射されたビームはミラー7で進路を変更され、シリンドリカルレンズ8で平行光となる。次に、偏光板9でP偏光のだけを透過し、レンズアレイ10により各々の検出器11に集光される。   The path of the beam reflected on the metal thin film is changed by the mirror 7 and becomes parallel light by the cylindrical lens 8. Next, only the P-polarized light is transmitted through the polarizing plate 9 and is condensed on each detector 11 by the lens array 10.

各々の検出器のシグナルは、演算部12において処理され、モニタに曲線を出力する。   The signal of each detector is processed in the calculation unit 12 and a curve is output to the monitor.

前述したように、金属薄膜はN個のドットのパターンニングが施されており、その各々のドット面に、ビームスプリッタにより分割された各々の前記ビームが線焦点を結ぶ。このビームは金属薄膜面で反射されるが、反射光のうち、ある入射角度における反射光強度が著しく減少するといった現象が起こる。この現象を、表面プラズモン共鳴現象といい、この時の入射角度を共鳴角度という。   As described above, the metal thin film is patterned with N dots, and each of the beams divided by the beam splitter forms a line focus on each dot surface. Although this beam is reflected by the metal thin film surface, a phenomenon occurs in which the intensity of the reflected light at a certain incident angle is significantly reduced. This phenomenon is called a surface plasmon resonance phenomenon, and the incident angle at this time is called a resonance angle.

例えば、N個の金属薄膜ドット表面には、種々の感染症病原体に対する特異抗体が種類別に固定化されている。また、その内1つはどの病原体にも反応しない抗体が固定化されており、ブランクとして用いる。ここで、金属箔膜面に未知の病原体を含む検体をのせておけば、抗原抗体反応により、未知の病原体は金属箔膜ドット面に固定化された抗体の何れかと特異的に結合する。その後、検体を取り除き、代わりにリン酸緩衝液などの媒質をのせ、病原体が結合された抗体が固定化された金属薄膜ドット面だけ共鳴角度が大きな値となる。これをブランクの共鳴角度と比較すれば、共鳴角度のシフト量が得られ、このシフト量が大きい程、抗体に病原体が結合したことになる。   For example, specific antibodies against various infectious disease pathogens are immobilized on the surfaces of N metal thin film dots by type. One of them is immobilized with an antibody that does not react with any pathogen, and is used as a blank. Here, if a specimen containing an unknown pathogen is placed on the metal foil membrane surface, the unknown pathogen specifically binds to any of the antibodies immobilized on the metal foil membrane dot surface by the antigen-antibody reaction. Thereafter, the specimen is removed, and a medium such as a phosphate buffer is placed instead, and the resonance angle becomes a large value only on the metal thin film dot surface on which the antibody to which the pathogen is bound is immobilized. If this is compared with the resonance angle of the blank, a shift amount of the resonance angle is obtained, and the larger the shift amount, the more the pathogen is bound to the antibody.

つまり、金属薄膜ドットパターン上の、どの病原体に特異的に結合する抗体が固定化されているかは既知であるため、検体に含まれる未知の病原体を特定する事ができる。   That is, since it is already known which pathogen on the metal thin film dot pattern is immobilized, an unknown pathogen contained in the specimen can be identified.

例えば、感染症病原体の検出および特定する事ができることから、感染症診断としての用途で使用する事が可能である。   For example, since an infectious disease pathogen can be detected and identified, it can be used for infectious disease diagnosis.

マルチチャンネル型表面プラズモン共鳴現象測定装置における各部の配置図である。(実施例1)FIG. 3 is a layout diagram of each part in a multi-channel surface plasmon resonance phenomenon measuring apparatus. Example 1

符号の説明Explanation of symbols

1 光源
2 コリメートレンズ
3 ビームスプリッタ
4 ミラー
5 シリンドリカルレンズ
6 プリズム一体型センサー基板
7 ミラー
8 シリンドリカルレンズ
9 偏光板
10 レンズアレイ
11 検出器
12 演算部
DESCRIPTION OF SYMBOLS 1 Light source 2 Collimating lens 3 Beam splitter 4 Mirror 5 Cylindrical lens 6 Prism integrated sensor board 7 Mirror 8 Cylindrical lens 9 Polarizing plate 10 Lens array 11 Detector 12 Calculation part

Claims (1)

ビームを発生する光源と、前記光源を同じ光強度で均等なビームにN分割する光学系と、金属薄膜とプリズムが形成されたプリズム一体型のセンサー基板と、N分割された各々のビームを基板上の各センシングポイントに一定の角度で線焦点を結ぶように入射させる光学系と、金属薄膜面からの反射光を検出器に結像するための光学系と、検出器の電気信号を取り出して演算および比較を行うための演算部を有し、小型で多点における同時計測を可能とした表面プラズモン共鳴現象測定装置。   A light source that generates a beam; an optical system that divides the light source into equal beams with the same light intensity; a prism-integrated sensor substrate on which a metal thin film and a prism are formed; and each N-divided beam as a substrate An optical system that allows each of the sensing points above to enter a line focus at a fixed angle, an optical system that forms an image of reflected light from the metal thin film surface on the detector, and an electrical signal from the detector is extracted. A surface plasmon resonance phenomenon measuring apparatus that has a calculation unit for performing calculation and comparison, and is small and capable of simultaneous measurement at multiple points.
JP2007126575A 2007-05-11 2007-05-11 Device for measuring multichannel type surface plasmon resonance phenomenon Pending JP2008281470A (en)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102346143A (en) * 2011-11-02 2012-02-08 中国广州分析测试中心 Optical scanning device for laser surface plasma resonance system
JP2014531038A (en) * 2011-10-26 2014-11-20 メルセー,ティボーMERCEY,Thibaut Fine structure chip for surface plasmon resonance analysis, analysis apparatus including the fine structure chip, and use of the apparatus

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2014531038A (en) * 2011-10-26 2014-11-20 メルセー,ティボーMERCEY,Thibaut Fine structure chip for surface plasmon resonance analysis, analysis apparatus including the fine structure chip, and use of the apparatus
CN102346143A (en) * 2011-11-02 2012-02-08 中国广州分析测试中心 Optical scanning device for laser surface plasma resonance system

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