JP2003057172A - Surface plasmon resonance sensor apparatus - Google Patents
Surface plasmon resonance sensor apparatusInfo
- Publication number
- JP2003057172A JP2003057172A JP2001243773A JP2001243773A JP2003057172A JP 2003057172 A JP2003057172 A JP 2003057172A JP 2001243773 A JP2001243773 A JP 2001243773A JP 2001243773 A JP2001243773 A JP 2001243773A JP 2003057172 A JP2003057172 A JP 2003057172A
- Authority
- JP
- Japan
- Prior art keywords
- optical system
- plasmon resonance
- address
- surface plasmon
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
Landscapes
- Investigating Or Analysing Materials By Optical Means (AREA)
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は、生化学計測の対象
となる液体試料の微少質量変化を検出するために、表面
プラズモン共鳴現象を利用した表面プラズモン共鳴セン
サ装置に関し、特に、多数の試料を同時に計測処理する
ことのできる表面プラズモン共鳴センサ装置に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a surface plasmon resonance sensor device utilizing a surface plasmon resonance phenomenon to detect a minute mass change of a liquid sample which is an object of biochemical measurement, and particularly to a large number of samples. The present invention relates to a surface plasmon resonance sensor device that can perform measurement processing at the same time.
【０００２】[0002]
【従来の技術】従来より、生化学的反応の進行に伴う物
質の物理化学的な変化量を検出する方法として、表面プ
ラズモン共鳴現象を用いた表面プラズモン共鳴センサ装
置が知られている。これは、例えば、図３に示すよう
に、回折格子を備えた平行ガラス基板（またはガラスプ
リズム）１の表面に金や銀等の金属薄膜２を真空蒸着等
の成膜技術を用いて形成し、ガラス基板１の側から金属
薄膜２との界面に向かって全反射条件を満足する角度で
レーザ光３を照射すると、特定の入射角θの時に、金属
薄膜２に表面プラズモン共鳴が励起されるというもので
ある。2. Description of the Related Art Conventionally, a surface plasmon resonance sensor device using a surface plasmon resonance phenomenon has been known as a method for detecting the amount of physicochemical change of a substance with the progress of biochemical reaction. For example, as shown in FIG. 3, a metal thin film 2 such as gold or silver is formed on the surface of a parallel glass substrate (or glass prism) 1 having a diffraction grating by using a film forming technique such as vacuum deposition. When the laser light 3 is irradiated from the glass substrate 1 side toward the interface with the metal thin film 2 at an angle satisfying the total reflection condition, surface plasmon resonance is excited in the metal thin film 2 at a specific incident angle θ. That is.
【０００３】表面プラズモン共鳴が励起されると、金属
薄膜２上のプラズモン波に光エネルギが吸収されるた
め、ガラス基板１と金属薄膜２との界面で全反射する反
射光５の強度が鋭く低下する。図４に、入射角θと反射
光５の強度との関係を示す。ここで、表面プラズモン共
鳴が生じる入射角θは、金属薄膜２と接触している測定
部４の試料溶液など媒質の密度（すなわち、金属薄膜表
面の質量）に依存するという関係がある。When surface plasmon resonance is excited, optical energy is absorbed by plasmon waves on the metal thin film 2, so that the intensity of the reflected light 5 totally reflected at the interface between the glass substrate 1 and the metal thin film 2 sharply decreases. To do. FIG. 4 shows the relationship between the incident angle θ and the intensity of the reflected light 5. Here, there is a relation that the incident angle θ at which the surface plasmon resonance occurs depends on the density of the medium such as the sample solution of the measurement unit 4 in contact with the metal thin film 2 (that is, the mass of the metal thin film surface).
【０００４】従って、この光学系から反射され反射光５
が特異的に低下する反射角を求めることにより、表面プ
ラズモン共鳴現象の有無、並びに、表面プラズモン共鳴
現象が生じている時の入射角θを求めることができ、結
果として媒質の密度、すなわち、金属薄膜表面の質量の
変化を求めることが可能となる。Therefore, the reflected light 5 reflected from this optical system
By specifically determining the reflection angle at which the surface plasmon resonance phenomenon occurs, and the incident angle θ when the surface plasmon resonance phenomenon occurs, the density of the medium, that is, the metal It is possible to obtain the change in mass on the surface of the thin film.
【０００５】このように、金属薄膜表面の質量の微少変
化は、金属薄膜の表面プラズモン共鳴吸収による大きな
光量変化として鋭敏に検知することができるようにな
る。従って、この表面プラズモン共鳴現象を応用した計
測法では、非常に微少な量を対象として計測が可能とな
り、通常、１ピコグラムの質量変化をも検出できる。そ
れゆえ、一般的な計測方法では計測できない微少量を扱
う生化学計測にも応用されている。例えば、図４に示す
２つの特性のように、測定部４（図３参照）におけるＤ
ＮＡ結合の有無が、反射光５の強度が低下する入射角θ
の違いとなって現れるので、ＤＮＡの結合による質量の
微少変化を検知することができる。As described above, a minute change in the mass of the surface of the metal thin film can be sensitively detected as a large change in the amount of light due to surface plasmon resonance absorption of the metal thin film. Therefore, according to the measurement method to which the surface plasmon resonance phenomenon is applied, it is possible to measure an extremely small amount, and a mass change of 1 picogram can usually be detected. Therefore, it is also applied to biochemical measurement that handles minute amounts that cannot be measured by general measurement methods. For example, as in the two characteristics shown in FIG. 4, D in the measurement unit 4 (see FIG. 3) is
Incident angle θ at which the intensity of the reflected light 5 decreases with or without NA coupling
Therefore, it is possible to detect a minute change in mass due to the binding of DNA.
【０００６】一般に、上述した表面プラズモン共鳴セン
サ装置は、一つの検出部位で行われる生化学反応を対象
として、個々に計測を行なうものであり、計測の作業効
率が悪いため、多数の試料を計測するための装置が開発
されている。例えば、特開２０００−６５７２９号公報
に記載されているように、多種類の試料成分の表面プラ
ズモン共鳴角を効率的に検出する装置が開発されてい
る。図５を用いて簡単に説明すると、この装置は、試料
溶液が吸着されるセンサーチップ８に密着したプリズム
７の入射側に所要角度幅の光を光源９から照射して、セ
ンサーチップ８からの反射光の強度を受光装置１０で検
出する光学系を備えている。Generally, the above-mentioned surface plasmon resonance sensor device individually measures a biochemical reaction carried out at one detection site, and since the measurement work efficiency is low, a large number of samples are measured. Devices have been developed to do so. For example, as described in Japanese Patent Application Laid-Open No. 2000-65729, an apparatus has been developed for efficiently detecting the surface plasmon resonance angle of many kinds of sample components. To briefly explain with reference to FIG. 5, this device irradiates the incident side of the prism 7 that is in close contact with the sensor chip 8 on which the sample solution is adsorbed, with light of a required angle width from the light source 9 to emit light from the sensor chip 8. An optical system for detecting the intensity of the reflected light with the light receiving device 10 is provided.
【０００７】ここで、プリズム７は、取付ブロック６
に、上面が面一状になるように取付けられている。ま
た、多検体用のセンサーチップ８は、下面が開口１２ｂ
した列方向及び行方向へマトリクス状に配列された多数
のセル１２ａを設けたセルプレート１２の下面に、上面
に金属薄膜が成膜されたガラス基板１１を各セル１２ａ
の開口１２ｂを閉鎖するように取付けて構成されてい
る。Here, the prism 7 is attached to the mounting block 6
Is mounted so that the upper surface is flush. The lower surface of the sensor chip 8 for multiple specimens has an opening 12b.
Each of the cells 12a is provided with a glass substrate 11 having a metal thin film formed on the lower surface of a cell plate 12 provided with a large number of cells 12a arranged in a matrix in the column and row directions.
Is configured so as to close the opening 12b.
【０００８】このように構成された装置を用いて多種類
の試料成分の表面プラズモン共鳴角を検出する手順を説
明すると、まず、センサーチップ８の所望のセル１２ａ
をプリズム７の上面の所定位置に配置して、上記の光学
系を用いて当該セル１２ａにおける共鳴角を検出する。
その後、取付ブロック６に固定されたプリズム７の上面
に対して、センサーチップ８を行方向及び列方向の二次
元方向へ選択的に移動することにより、順次所望のセル
１２ａをプリズム７の上面の所定位置に配置させ、その
共鳴角を検出するようになっている。A procedure for detecting the surface plasmon resonance angles of various kinds of sample components using the apparatus configured as described above will be described. First, a desired cell 12a of the sensor chip 8 is described.
Is arranged at a predetermined position on the upper surface of the prism 7 and the resonance angle in the cell 12a is detected by using the above optical system.
After that, by selectively moving the sensor chip 8 in the two-dimensional direction of the row direction and the column direction with respect to the upper surface of the prism 7 fixed to the mounting block 6, the desired cells 12a are sequentially arranged on the upper surface of the prism 7. It is arranged at a predetermined position and its resonance angle is detected.
【０００９】[0009]
【発明が解決しようとする課題】しかしながら、マトリ
クス状に配列された任意のセル１２ａにおける共鳴角の
検出精度を一定に保つには、接触しながら相対的に移動
するセンサーチップ８を構成するガラス基板１１の下面
とプリズム７の上面との間を、光学的に密な結合状態に
維持したまま、両者を機械的に移動させなければならな
い。光学的な結合を維持するためには、ガラス基板１１
とプリズム７との間に、屈折率がプリズム７及びガラス
基板１１とほぼ等しいマッチングオイル或いはシリコン
ゴムシートを介在させ、気泡の混入がない状態で密着さ
せる必要があり、そのため、構成が複雑になると共に、
相対移動が非常に困難であるという問題点があった。However, in order to keep the detection accuracy of the resonance angle in the arbitrary cells 12a arranged in a matrix constant, the glass substrate forming the sensor chip 8 which moves relatively while making contact. The lower surface of 11 and the upper surface of the prism 7 must be mechanically moved while maintaining an optically tight coupling state. In order to maintain the optical coupling, the glass substrate 11
Between the prism 7 and the prism 7, it is necessary to interpose a matching oil or a silicon rubber sheet whose refractive index is almost the same as that of the prism 7 and the glass substrate 11 and to bring them into close contact with each other without inclusion of bubbles, which complicates the structure. With
There is a problem that relative movement is very difficult.
【００１０】また、ガラス基板１１をプリズム７に対し
て、接触させながら移動させるため、多数試料の総合的
な分析速度も遅く、測定精度も劣るという欠点があっ
た。さらに、試料毎にセル１２ａが必要であり、且つこ
のセル１２ａは各々分離独立しているので、センサーチ
ップ８が大型化し、多数試料を取扱うことが現実的では
ないという不具合があった。Further, since the glass substrate 11 is moved in contact with the prism 7, the total analysis speed of a large number of samples is slow and the measurement accuracy is poor. Further, since the cell 12a is required for each sample and the cells 12a are separated and independent, the sensor chip 8 becomes large, and it is not practical to handle a large number of samples.
【００１１】従って、本発明は、上述した従来の技術の
問題を解決するためになされたもので、多数の試料を計
測処理することができると共に、光学系を相対移動させ
る必要が無く、信頼性の高い構成で、測定精度の高い表
面プラズモン共鳴センサ装置を提供することを目的とす
る。Therefore, the present invention has been made in order to solve the above-mentioned problems of the prior art, and it is possible to measure and process a large number of samples, and it is not necessary to move the optical system relatively, and the reliability is improved. It is an object of the present invention to provide a surface plasmon resonance sensor device having a high configuration and high measurement accuracy.
【００１２】[0012]
【課題を解決するための手段】本発明の表面プラズモン
共鳴センサ装置は、一方の面に生化学反応測定用の複数
の試料を２次元的に配列した第１アドレスに基づいて搭
載し、反射面を構成する他方の面で表面プラズモン共鳴
を生じさせる薄膜を形成した第１光学系と、前記薄膜の
反射面に照射するためのレーザ光を出射する光源と、２
次元的に配列された第２アドレスに基づいて配設された
複数の反射面を有し、前記光源から出射されるレーザ光
を前記薄膜の前記複数の試料が搭載された試料搭載領域
に導く第２光学系と、前記光源と前記第２光学系との間
に設けられ、前記光源から出射されるレーザ光を前記第
２光学系の第２アドレス内の所望の反射面に選択的に照
射するための２次元シャッタ手段と、前記第１光学系の
試料搭載領域で反射された反射光の強度を検出する光検
出手段とを備え、前記第１光学系の前記第１アドレス内
の所望のアドレスにある試料に対応する試料搭載領域に
前記レーザ光を照射させるために、前記２次元シャッタ
手段の一部を選択的に開閉すると共に前記第２光学系の
反射面を角度調整して前記第２光学系の前記第２アドレ
ス内の所望の反射面に前記レーザ光を照射させることに
より、前記試料における生化学反応を検出できる構成で
あり、また、前記第２光学系の前記第２アドレス内の所
望の反射面の角度を制御することにより、前記第１項額
手段に搭載された複数の試料を順次計測することができ
る構成であり、また、前記第２光学系は、デジタルマイ
クロデバイスである構成であり、さらに、前記２次元シ
ャッタ手段は、液晶シャッタ、空間光変調器またはデジ
タルマイクロデバイスである構成である。A surface plasmon resonance sensor device of the present invention has a plurality of samples for biochemical reaction measurement mounted on one surface based on a first address which is two-dimensionally arranged, and has a reflective surface. A first optical system in which a thin film that causes surface plasmon resonance is formed on the other surface of the first optical system, a light source that emits laser light for irradiating the reflecting surface of the thin film, and 2
A plurality of reflecting surfaces arranged based on the second addresses arranged in a dimension, and guiding laser light emitted from the light source to a sample mounting region of the thin film on which the plurality of samples are mounted. Two optical systems, provided between the light source and the second optical system, the laser light emitted from the light source is selectively applied to a desired reflecting surface within the second address of the second optical system. Two-dimensional shutter means for detecting the intensity of reflected light reflected by the sample mounting area of the first optical system, and a desired address in the first address of the first optical system. In order to irradiate the sample mounting area corresponding to the sample with the laser beam, a part of the two-dimensional shutter means is selectively opened and closed, and the reflection surface of the second optical system is angle-adjusted. Desired reflection in the second address of the optical system By irradiating the laser beam on the sample, a biochemical reaction in the sample can be detected, and by controlling an angle of a desired reflecting surface in the second address of the second optical system, A structure capable of sequentially measuring a plurality of samples mounted on the first frame means, the second optical system being a digital microdevice, and the two-dimensional shutter means being The configuration is a liquid crystal shutter, a spatial light modulator, or a digital micro device.
【００１３】[0013]
【発明の実施の形態】以下、図面と共に本発明による表
面プラズモン共鳴センサ装置の好適な実施の形態につい
て詳細に説明する。なお、従来装置と同一または同等部
分には同一符号を付し、その説明を省略する。BEST MODE FOR CARRYING OUT THE INVENTION Preferred embodiments of a surface plasmon resonance sensor device according to the present invention will be described in detail below with reference to the drawings. The same or equivalent parts as those of the conventional device are designated by the same reference numerals, and the description thereof will be omitted.
【００１４】実施の形態１．図１は、本発明の実施の形
態１に係る表面プラズモン共鳴センサ装置の構成を概略
的に示す図である。図１において、符号１５で示される
ものは、一方の面である搭載面１７Ａに生化学反応測定
用の複数の試料１６を２次元的（図１中左右方向及び紙
面を貫通する方向）に配列した第１アドレスに基づいて
搭載し、反射面１７Ｂを構成する他方の面で表面プラズ
モン共鳴を生じさせる薄膜１７を形成したシリンドリカ
ルレンズである。このシリンドリカルレンズ１５と薄膜
１７とは第１光学系を構成し、また、反射面１７Ｂのう
ち試料１６の真下の領域は試料搭載領域を構成する。Embodiment 1. FIG. 1 is a diagram schematically showing a configuration of a surface plasmon resonance sensor device according to a first embodiment of the present invention. In FIG. 1, reference numeral 15 denotes a plurality of samples 16 for biochemical reaction measurement arranged two-dimensionally (in the left-right direction and the direction penetrating the paper in FIG. 1) on the mounting surface 17A which is one surface. The cylindrical lens is mounted on the basis of the first address described above, and the thin film 17 that causes surface plasmon resonance is formed on the other surface of the reflective surface 17B. The cylindrical lens 15 and the thin film 17 constitute a first optical system, and a region of the reflecting surface 17B directly below the sample 16 constitutes a sample mounting region.
【００１５】即ち、前記シリンドリカルレンズ１５は、
図１中紙面を貫通する方向に長手方向を有する断面半円
状の半円柱状のレンズであり、このシリンドリカルレン
ズ１５の上部は、金(Au)または銀(Ag)等で構成される薄
膜１７で被覆されている。この薄膜１７の上には、生化
学反応計測用の試料１６が搭載されている。That is, the cylindrical lens 15 is
1 is a semi-cylindrical lens having a semi-circular cross-section having a longitudinal direction passing through the plane of the paper in FIG. 1, and the upper part of this cylindrical lens 15 is a thin film 17 made of gold (Au) or silver (Ag) or the like. It is covered with. A sample 16 for biochemical reaction measurement is mounted on the thin film 17.
【００１６】また、光源であるレーザ装置１８から出射
されたレーザ光１８Ａは、２次元シャッタ手段である液
晶シャッタ１９を介してＤＭＤ(Digital Micro Device)
２０に導かれる。なお、ＤＭＤは日本テキサスインスツ
ルメンツ（株）の登録商標である。A laser beam 18A emitted from a laser device 18 which is a light source is DMD (Digital Micro Device) via a liquid crystal shutter 19 which is a two-dimensional shutter means.
Guided to 20. DMD is a registered trademark of Texas Instruments Japan, Ltd.
【００１７】前記ＤＭＤ２０は、図１中左右方向及び紙
面を貫通する方向による２次元的な第２アドレスの各ア
ドレスに複数の反射面が配列された構成であり、前記第
２アドレス内の任意のアドレスの反射面の角度を１軸を
中心に−１０度から＋１０度にまで角度調整することが
できるデバイスである。The DMD 20 has a structure in which a plurality of reflecting surfaces are arranged at each address of a two-dimensional second address in the left-right direction in FIG. 1 and a direction penetrating the paper surface, and any of the second addresses is arranged. It is a device that can adjust the angle of the reflecting surface of the address from -10 degrees to +10 degrees about one axis.
【００１８】また、前記液晶シャッタ１９は、前記第２
アドレスの内の所望のアドレスにレーザ光を導けるよう
に、２次元的に構成されるシャッタの任意の部分を選択
的に開閉制御可能に構成されている。なお、２次元アレ
イセンサ２１は、前記反射面１７Ｂの試料搭載領域で反
射された反射光の強度を検出する光検出手段である。Further, the liquid crystal shutter 19 has the second
In order to guide the laser beam to a desired address among the addresses, it is possible to selectively control the opening and closing of an arbitrary portion of the two-dimensionally configured shutter. The two-dimensional array sensor 21 is a light detecting unit that detects the intensity of the reflected light reflected by the sample mounting area of the reflecting surface 17B.
【００１９】このような構成により、本発明の実施の形
態１に係る表面プラズモン共鳴センサ装置によれば、前
記薄膜１７上の第１アドレス内の所望のアドレスにある
試料１６にレーザ光１８Ａを照射させるために、液晶シ
ャッタ１９の一部を選択的に開閉してＤＭＤ２０の第２
アドレス内の所望の反射面にレーザ光１８Ａを照射させ
ることができる。With such a configuration, according to the surface plasmon resonance sensor device according to the first embodiment of the present invention, the laser beam 18A is applied to the sample 16 at the desired address within the first address on the thin film 17. In order to allow the liquid crystal shutter 19 to partially open and close, the second part of the DMD 20 is opened.
The desired reflection surface in the address can be irradiated with the laser light 18A.
【００２０】この結果、所望の試料１６の真下の反射面
１７Ｂ内の試料搭載領域にレーザ光１８Ａを照射するこ
とができ、さらにレーザ光１８Ａを反射しているＤＭＤ
２０の反射面の角度を調整することにより、図１に示す
ようにレーザ光１８Ａを他の試料１６に照射できるの
で、入射角をθ1やθ2等の任意の角度に調整することが
でき、２次元アレイセンサ２１で反射光の光強度を検出
することにより、表面プラズモン共鳴が励起される入射
角度を特定することによって各試料１６における生化学
反応の発生の有無を判定できる。As a result, the laser beam 18A can be irradiated to the sample mounting area in the reflecting surface 17B directly below the desired sample 16, and the DMD that reflects the laser beam 18A can be further irradiated.
Since the laser beam 18A can be irradiated to the other sample 16 as shown in FIG. 1 by adjusting the angle of the reflecting surface of 20, the incident angle can be adjusted to an arbitrary angle such as θ 1 or θ 2. By detecting the light intensity of the reflected light with the two-dimensional array sensor 21, it is possible to determine the occurrence of the biochemical reaction in each sample 16 by specifying the incident angle at which the surface plasmon resonance is excited.
【００２１】以上、本発明の実施の形態１に係る表面プ
ラズモン共鳴センサ装置によれば、簡単で信頼性の高い
構成で、複数試料におけるプラズモン共鳴の発生条件を
精度良く検出でき、生化学反応の発生の有無を高精度に
判定することのできる表面プラズモン共鳴センサ装置を
提供することができる。なお、以上の説明では、２次元
シャッタ手段として液晶シャッタ１９を用いた場合につ
いて説明したが、液晶シャッタ１９の代わりに空間光変
調器を用いても同様に本発明を実施することができる。As described above, according to the surface plasmon resonance sensor device according to the first embodiment of the present invention, the plasmon resonance generation condition in a plurality of samples can be accurately detected with a simple and highly reliable structure, and the biochemical reaction It is possible to provide a surface plasmon resonance sensor device capable of highly accurately determining the presence or absence of occurrence. In the above description, the case where the liquid crystal shutter 19 is used as the two-dimensional shutter means has been described, but the present invention can be similarly implemented by using a spatial light modulator instead of the liquid crystal shutter 19.
【００２２】実施の形態２．図２は、本発明の実施の形
態２に係る表面プラズモン共鳴センサ装置の構成を概略
的に示す構成図である。この実施の形態２に係る表面プ
ラズモン共鳴センサ装置では、２次元シャッタ手段とし
てＤＭＤ２２を用いていること以外は実施の形態１に係
る表面プラズモン共鳴センサ装置に準ずるものである。Embodiment 2. FIG. 2 is a configuration diagram schematically showing the configuration of the surface plasmon resonance sensor device according to the second embodiment of the present invention. The surface plasmon resonance sensor device according to the second embodiment is similar to the surface plasmon resonance sensor device according to the first embodiment except that the DMD 22 is used as the two-dimensional shutter means.
【００２３】このように２次元シャッタ手段としてＤＭ
Ｄ２２を用いた場合でも、ＤＭＤ２２の任意の部分を選
択的に開閉制御することにより、前記ＤＭＤ２０の第２
アドレスの内の所望のアドレスにレーザ光１８Ａを導く
ことができ、薄膜１７上の第１アドレス内の所望のアド
レスにある試料１６にレーザ光１８Ａを照射させて、試
料１６における生化学反応を検出できるように構成され
ている。As described above, the DM is used as the two-dimensional shutter means.
Even when the D22 is used, the second part of the DMD 20 is controlled by selectively opening / closing the arbitrary part of the DMD 22.
The laser light 18A can be guided to a desired address among the addresses, and the laser light 18A is irradiated to the sample 16 located at the desired address within the first address on the thin film 17 to detect the biochemical reaction in the sample 16. It is configured to be able to.
【００２４】[0024]
【発明の効果】本発明の表面プラズモン共鳴センサ装置
は、一方の面に生化学反応測定用の複数の試料を２次元
的に配列した第１アドレスに基づいて搭載し、反射面を
構成する他方の面で表面プラズモン共鳴を生じさせる薄
膜を形成した第１光学系と、前記薄膜の反射面に照射す
るためのレーザ光を出射する光源と、２次元的に配列さ
れた第２アドレスに基づいて配設された複数の反射面を
有し、前記光源から出射されるレーザ光を前記薄膜の前
記複数の試料が搭載された試料搭載領域に導く第２光学
系と、前記光源と前記第２光学系との間に設けられ、前
記光源から出射されるレーザ光を前記第２光学系の第２
アドレス内の所望の反射面に選択的に照射するための２
次元シャッタ手段と、前記第１光学系の試料搭載領域で
反射された反射光の強度を検出する光検出手段とを備
え、前記第１光学系の前記第１アドレス内の所望のアド
レスにある試料に対応する試料搭載領域に前記レーザ光
を照射させるために、前記２次元シャッタ手段の一部を
選択的に開閉すると共に前記第２光学系の反射面を角度
調整して前記第２光学系の前記第２アドレス内の所望の
反射面に前記レーザ光を照射させることにより、前記試
料における生化学反応を検出できるので、簡単で信頼性
の高い構成で、複数試料におけるプラズモン共鳴の発生
条件を精度良く検出でき、生化学反応の発生の有無を高
精度に判定することのできる表面プラズモン共鳴センサ
装置を提供することができる。また、前記第２光学系の
前記第２アドレス内の所望の反射面の角度を制御するこ
とにより、前記第１項額手段に搭載された複数の試料を
順次計測することができるので、複数試料における生化
学反応の発生の有無を高精度に判定することのできる表
面プラズモン共鳴センサ装置を提供することができる。
また、前記第２光学系は、デジタルマイクロデバイスで
あるので、信頼性及び検出精度の高い表面プラズモン共
鳴センサ装置を提供することができる。さらに、前記２
次元シャッタ手段は、液晶シャッタ、空間光変調器また
はデジタルマイクロデバイスであるので、信頼性及び検
出精度の高い表面プラズモン共鳴センサ装置を提供する
ことができる。According to the surface plasmon resonance sensor device of the present invention, a plurality of samples for biochemical reaction measurement are mounted on one surface based on a first address which is two-dimensionally arranged, and the other constitutes a reflecting surface. Based on a first optical system in which a thin film that causes surface plasmon resonance is formed on the surface of the light source, a light source that emits laser light for irradiating the reflecting surface of the thin film, and a second address that is two-dimensionally arranged. A second optical system having a plurality of reflecting surfaces provided and guiding the laser light emitted from the light source to a sample mounting region of the thin film on which the plurality of samples are mounted; and the light source and the second optical system. A laser beam emitted from the light source, which is provided between the second optical system and the second optical system.
2 to selectively illuminate the desired reflecting surface in the address
A sample located at a desired address within the first address of the first optical system, including a three-dimensional shutter means and a light detection means for detecting the intensity of the reflected light reflected by the sample mounting area of the first optical system. In order to irradiate the laser beam onto the sample mounting area corresponding to, the part of the two-dimensional shutter means is selectively opened and closed, and the reflection surface of the second optical system is angle-adjusted. By irradiating the desired reflection surface in the second address with the laser light, the biochemical reaction in the sample can be detected, so that the plasmon resonance generation condition in a plurality of samples can be accurately determined with a simple and highly reliable configuration. It is possible to provide a surface plasmon resonance sensor device that can be well detected and can highly accurately determine whether or not a biochemical reaction has occurred. In addition, by controlling the angle of the desired reflecting surface within the second address of the second optical system, it is possible to sequentially measure a plurality of samples mounted on the first forehead device, so that a plurality of samples can be measured. It is possible to provide a surface plasmon resonance sensor device capable of highly accurately determining whether or not a biochemical reaction has occurred in (3).
Further, since the second optical system is a digital micro device, it is possible to provide a surface plasmon resonance sensor device having high reliability and high detection accuracy. Further, the above 2
Since the dimensional shutter means is a liquid crystal shutter, a spatial light modulator or a digital micro device, it is possible to provide a surface plasmon resonance sensor device with high reliability and detection accuracy.
【図１】 本発明の実施の形態１に係る表面プラズモン
共鳴センサ装置の構成を概略的に示す図である。FIG. 1 is a diagram schematically showing a configuration of a surface plasmon resonance sensor device according to a first embodiment of the present invention.
【図２】 本発明の実施の形態２に係る表面プラズモン
共鳴センサ装置の構成を概略的に示す図である。FIG. 2 is a diagram schematically showing a configuration of a surface plasmon resonance sensor device according to a second embodiment of the present invention.
【図３】 表面プラズモン共鳴を利用して質量変化を検
出するための検出原理を概念的に示す図である。FIG. 3 is a diagram conceptually showing a detection principle for detecting a mass change using surface plasmon resonance.
【図４】 表面プラズモン共鳴を利用した質量変化の検
出における入射角θと反射光の強度との関係を示す特性
図である。FIG. 4 is a characteristic diagram showing a relationship between an incident angle θ and the intensity of reflected light in detecting a mass change using surface plasmon resonance.
【図５】 従来の多種類の試料成分の表面プラズモン共
鳴角を効率的に検出する装置を概略的に示す構成図であ
る。FIG. 5 is a configuration diagram schematically showing a conventional device for efficiently detecting surface plasmon resonance angles of various kinds of sample components.
１５ シリンドリカルレンズ １６ 試料 １７ 薄膜 １７Ａ 搭載面 １７Ｂ 反射面 １８ レーザ装置 １８Ａ レーザ光 １９ 液晶シャッタ ２０ ＤＭＤ ２１ ２次元アレイセンサ 15 Cylindrical lens 16 samples 17 thin film 17A mounting surface 17B reflective surface 18 Laser device 18A laser light 19 LCD shutter 20 DMD 21 Two-dimensional array sensor
───────────────────────────────────────────────────── フロントページの続き (72)発明者 後藤 崇之 神奈川県横浜市金沢区幸浦一丁目８番地１ 三菱重工業株式会社基盤技術研究所内 (72)発明者 犬塚 博誠 神奈川県横浜市金沢区幸浦一丁目８番地１ 三菱重工業株式会社基盤技術研究所内 (72)発明者 田原 諭 神奈川県横浜市金沢区幸浦一丁目８番地１ 三菱重工業株式会社基盤技術研究所内 Ｆターム(参考） 2G059 AA01 BB12 CC16 DD13 EE02 FF03 GG01 GG07 JJ11 JJ23 JJ30 KK04 ─────────────────────────────────────────────────── ─── Continued front page (72) Inventor Takayuki Goto 1-8 Koura, Kanazawa-ku, Yokohama-shi, Kanagawa Mitsubishi Heavy Industries, Ltd. Basic Technology Research Center (72) Inventor Hiromitsu Inuzuka 1-8 Koura, Kanazawa-ku, Yokohama-shi, Kanagawa Mitsubishi Heavy Industries, Ltd. Basic Technology Research Center (72) Inventor Satoshi Tahara 1-8 Koura, Kanazawa-ku, Yokohama-shi, Kanagawa Mitsubishi Heavy Industries, Ltd. Basic Technology Research Center F term (reference) 2G059 AA01 BB12 CC16 DD13 EE02 FF03 GG01 GG07 JJ11 JJ23 JJ30 KK04
Claims (4)
料を２次元的に配列した第１アドレスに基づいて搭載
し、反射面を構成する他方の面で表面プラズモン共鳴を
生じさせる薄膜が形成された第１光学系と、 前記薄膜の反射面に照射するためのレーザ光を出射する
光源と、 ２次元的に配列された第２アドレスに基づいて配設され
た複数の反射面を有し、前記光源から出射されるレーザ
光を前記薄膜の前記複数の試料が搭載された試料搭載領
域に導く第２光学系と、 前記光源と前記第２光学系との間に設けられ、前記光源
から出射されるレーザ光を前記第２光学系の第２アドレ
ス内の所望の反射面に選択的に照射するための２次元シ
ャッタ手段と、 前記第１光学系の試料搭載領域で反射された反射光の強
度を検出する光検出手段とを備え、 前記第１光学系の前記第１アドレス内の所望のアドレス
にある試料に対応する試料搭載領域に前記レーザ光を照
射させるために、前記２次元シャッタ手段の一部を選択
的に開閉すると共に前記第２光学系の反射面を角度調整
して前記第２光学系の前記第２アドレス内の所望の反射
面に前記レーザ光を照射させることにより、前記試料に
おける生化学反応を検出できることを特徴とする表面プ
ラズモン共鳴センサ装置。1. A thin film in which a plurality of samples for biochemical reaction measurement are mounted on one surface based on a first address arranged two-dimensionally, and surface plasmon resonance is generated on the other surface constituting a reflecting surface. A first optical system in which a plurality of reflective surfaces are formed, a light source that emits laser light for irradiating the reflective surface of the thin film, and a plurality of reflective surfaces that are arranged based on second addresses that are two-dimensionally arranged. A second optical system for guiding laser light emitted from the light source to a sample mounting area of the thin film on which the plurality of samples are mounted; and a second optical system provided between the light source and the second optical system. Two-dimensional shutter means for selectively irradiating a desired reflecting surface in the second address of the second optical system with laser light emitted from the light source, and a sample mounting area of the first optical system. And a light detection means for detecting the intensity of the reflected light, The part of the two-dimensional shutter means is selectively opened and closed and the sample mounting area corresponding to the sample located at a desired address within the first address of the first optical system is selectively opened and closed. A biochemical reaction in the sample can be detected by adjusting the angle of the reflecting surface of the second optical system and irradiating the desired reflecting surface in the second address of the second optical system with the laser light. Surface plasmon resonance sensor device.
所望の反射面の角度を制御することにより、前記第１項
額手段に搭載された複数の試料を順次計測することがで
きることを特徴とする請求項１記載の表面プラズモン共
鳴センサ装置。2. A plurality of samples mounted on the forehead means can be sequentially measured by controlling an angle of a desired reflecting surface within the second address of the second optical system. The surface plasmon resonance sensor device according to claim 1, which is characterized in that.
バイスであることを特徴とする請求項１または２記載の
表面プラズモン共鳴センサ装置。3. The surface plasmon resonance sensor device according to claim 1, wherein the second optical system is a digital micro device.
タ、空間光変調器またはデジタルマイクロデバイスであ
ることを特徴とする請求項１ないし３のいずれか記載の
表面プラズモン共鳴センサ装置。4. The surface plasmon resonance sensor device according to claim 1, wherein the two-dimensional shutter means is a liquid crystal shutter, a spatial light modulator or a digital micro device.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001243773A JP2003057172A (en) | 2001-08-10 | 2001-08-10 | Surface plasmon resonance sensor apparatus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001243773A JP2003057172A (en) | 2001-08-10 | 2001-08-10 | Surface plasmon resonance sensor apparatus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003057172A true JP2003057172A (en) | 2003-02-26 |
Family
ID=19073813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001243773A Withdrawn JP2003057172A (en) | 2001-08-10 | 2001-08-10 | Surface plasmon resonance sensor apparatus |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2003057172A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006104183A1 (en) * | 2005-03-29 | 2006-10-05 | National University Corporation, Hamamatsu University School Of Medicine | Dlp type evanescent microscope |
| JP2007078488A (en) * | 2005-09-13 | 2007-03-29 | Hokkaido Univ | Electrochemical infrared spectroscope |
| WO2014017433A1 (en) * | 2012-07-23 | 2014-01-30 | コニカミノルタ株式会社 | Optical specimen detection device |
-
2001
- 2001-08-10 JP JP2001243773A patent/JP2003057172A/en not_active Withdrawn
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006104183A1 (en) * | 2005-03-29 | 2006-10-05 | National University Corporation, Hamamatsu University School Of Medicine | Dlp type evanescent microscope |
| JP2007078488A (en) * | 2005-09-13 | 2007-03-29 | Hokkaido Univ | Electrochemical infrared spectroscope |
| WO2014017433A1 (en) * | 2012-07-23 | 2014-01-30 | コニカミノルタ株式会社 | Optical specimen detection device |
| JPWO2014017433A1 (en) * | 2012-07-23 | 2016-07-11 | コニカミノルタ株式会社 | Optical specimen detector |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0442921B1 (en) | Optical biosensor system | |
| FI96722C (en) | Biological detectors | |
| JP2731591B2 (en) | Biological sensor | |
| FI94805C (en) | Sensor for biological, biochemical and chemical testing | |
| US9829434B2 (en) | Optical detection system for liquid samples | |
| GB2273772A (en) | Detection of macromolecules utilising light diffraction | |
| JP3399804B2 (en) | Surface plasmon sensor | |
| US20180340940A1 (en) | Systems and methods for high throughput analysis of conformation in biological entities | |
| JP3343086B2 (en) | Surface plasmon sensor | |
| JP3468091B2 (en) | Biochemical measurement device | |
| US7846396B2 (en) | Sample holder for surface plasmon resonance measuring instruments | |
| JP4382339B2 (en) | Measuring chip | |
| JPH06500636A (en) | Optical method for selectively detecting specific substances in chemical, biochemical, and biological measurement samples | |
| JP3903432B2 (en) | measuring device | |
| JP2002372490A (en) | Sensor utilizing total reflection attenuation and measurement chip assembly | |
| JP2003057172A (en) | Surface plasmon resonance sensor apparatus | |
| US6788415B2 (en) | Turntable measuring apparatus utilizing attenuated total reflection | |
| JP2003075337A (en) | Integrated surface plasmon resonance sensor | |
| JP3945636B2 (en) | measuring device | |
| JP2003042945A (en) | Surface plasmon resonance sensor system | |
| JP2003042944A (en) | Surface plasmon resonace sensor system | |
| JP2002048707A (en) | Measuring method and device using total reflection decay | |
| JP2003194712A (en) | Apparatus and chip for measurement making use of attenuated total reflection | |
| CN112630194A (en) | Angle modulation type SPR sensor based on scanning galvanometer and SPR detection equipment | |
| JP2005098793A (en) | Sensor well unit and measuring apparatus |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20061208 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20070606 |
|
| A300 | Withdrawal of application because of no request for examination |
Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 20081104 |