JP2003075336A - Spr analyzer for multipoint sample analysis - Google Patents
Spr analyzer for multipoint sample analysisInfo
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- JP2003075336A JP2003075336A JP2001265219A JP2001265219A JP2003075336A JP 2003075336 A JP2003075336 A JP 2003075336A JP 2001265219 A JP2001265219 A JP 2001265219A JP 2001265219 A JP2001265219 A JP 2001265219A JP 2003075336 A JP2003075336 A JP 2003075336A
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- voltage
- thin film
- metal thin
- medium
- sample
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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
ことのできる多点試料分析用ＳＰＲ(Surface Plasmon R
esonance)分析装置に関する。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 a target of biochemical measurement, and particularly to a large number of samples. SPR (Surface Plasmon R) for multi-point sample analysis that can perform simultaneous measurement processing
esonance) analyzer.
【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４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. 4, a metal thin film 2 of 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５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. 5 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５に示す
２つの特性のように、測定部４（図４参照）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. 5, D in the measurement unit 4 (see FIG. 4) 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多点検出装
置が開発されている。例えば、米国特許第５６２９２１
３号明細書に記載されているようなバイオセンサ装置が
ある。図６を用いて簡単に説明すると、このバイオセン
サ装置１０は、試料部１５を多数に分割して検査部１１
のガラス基板１３に蒸着された金属薄膜１４上の同一平
面に配置し、光源１７からの光ビームをコリメーティン
グレンズ１８を介して平行光としてプリズム１６に入射
させ、検査部１１で反射した反射光を光検出器１９で検
出することにより、一度に試料部１５の個数だけ計測で
きるようになっている。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. Multi-point detectors have been developed. For example, US Pat. No. 5,629,921.
There are biosensor devices as described in US Pat. To briefly explain with reference to FIG. 6, in the biosensor device 10, the sample part 15 is divided into a plurality of parts and the inspection part 11 is divided.
Are arranged on the same plane on the metal thin film 14 deposited on the glass substrate 13, and the light beam from the light source 17 is incident on the prism 16 as parallel light through the collimating lens 18 and reflected by the inspection unit 11. By detecting the light with the photodetector 19, it is possible to measure the number of sample portions 15 at one time.
【０００７】[0007]
【発明が解決しようとする課題】しかしながら、上述の
ように複数の試料に一様に光を照射し、反射光強度分布
を求めて測定部に試料が付着した場合の光強度分布との
差分を求めることにより予測値であるＳＰＲの共鳴曲線
から屈折率変化量を求めていたが、この方法では共鳴曲
線をあらかじめ求めておく必要があることと、アレイセ
ンサの感度ムラ等により各点のデータの精度の信頼性に
問題が生じるという課題があった。However, as described above, a plurality of samples are uniformly irradiated with light, the reflected light intensity distribution is obtained, and the difference from the light intensity distribution when the sample adheres to the measurement part is calculated. The refractive index change amount was obtained from the resonance curve of the SPR that is the predicted value by obtaining it. However, in this method, it is necessary to obtain the resonance curve in advance, and due to the sensitivity unevenness of the array sensor, etc. There was a problem in that there was a problem in the reliability of accuracy.
【０００８】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、多数の試料を一
度に計測できると共に測定精度が良く、高感度かつ高速
処理可能な２次元配列の多点試料分析用ＳＰＲ分析装置
を提供することを主な目的とするものである。Therefore, the present invention has been made in order to solve the above-mentioned problems of the conventional technique, and it is possible to measure a large number of samples at a time, and the measurement accuracy is good, and the two-dimensional array is capable of high sensitivity and high-speed processing. The main purpose of the present invention is to provide an SPR analyzer for analyzing multipoint samples.
【０００９】[0009]
【課題を解決するための手段】本発明の多点試料分析用
ＳＰＲ分析装置は、電界が印加されることにより屈折率
が変化し、生化学反応測定用の試料を複数搭載する媒質
と、前記媒質を搭載する一方の面及び反射面を構成する
他方の面を有する金属薄膜と、前記金属薄膜の前記反射
面が入射光に対する反射面を構成するように前記金属薄
膜が形成され、前記入射光を前記金属薄膜の前記反射面
に誘導すると共に、前記反射面で反射された反射光を出
力面から出力する光学系と、前記出力面から出力された
前記反射光の強度を各試料毎に同時測定する光検出手段
と、前記媒質に対向配置され、前記金属薄膜と対をなす
測定用電極と、前記金属薄膜及び前記測定用電極の間に
電界を印加するための電界印加手段とを備え、前記電界
印加手段から直流電圧に交流電圧を重畳した測定用電圧
を前記金属薄膜及び前記測定用電極の間に印加し、前記
交流電圧を制御して前記媒質の屈折率を変化させ、前記
金属薄膜で表面プラズモン共鳴を生じさせることによ
り、複数の試料における生化学反応を同時に分析できる
構成であり、また、前記直流電圧の値を生化学反応が生
じる前の試料において表面プラズモン共鳴が生じる電圧
値に設定しておき、前記直流電圧に比べて微弱な前記交
流電圧の電圧値を制御して前記媒質の屈折率を変化させ
ることにより、生化学反応が生じた試料において生じる
表面プラズモン共鳴を検出して、複数試料における生化
学反応の有無を同時分析できる構成である。The SPR analyzer for multipoint sample analysis of the present invention has a medium in which a plurality of samples for biochemical reaction measurement are mounted, the refractive index of which changes when an electric field is applied. A metal thin film having one surface on which a medium is mounted and the other surface forming a reflection surface; and the metal thin film is formed so that the reflection surface of the metal thin film forms a reflection surface for incident light, An optical system that guides to the reflection surface of the metal thin film and outputs the reflected light reflected by the reflection surface from the output surface, and the intensity of the reflected light output from the output surface for each sample simultaneously. A photodetection means for measurement, a measurement electrode that is arranged to face the medium and forms a pair with the metal thin film, and an electric field application means for applying an electric field between the metal thin film and the measurement electrode, DC from the electric field applying means A measurement voltage in which an AC voltage is superimposed on the pressure is applied between the metal thin film and the measurement electrode, the AC voltage is controlled to change the refractive index of the medium, and surface plasmon resonance is generated in the metal thin film. By doing so, biochemical reactions in a plurality of samples can be simultaneously analyzed, and the value of the direct current voltage is set to a voltage value at which surface plasmon resonance occurs in the sample before the biochemical reaction occurs, By controlling the voltage value of the AC voltage, which is weaker than the DC voltage, and changing the refractive index of the medium, surface plasmon resonance generated in the sample in which the biochemical reaction occurs is detected, and biochemistry in a plurality of samples is detected. It is a configuration that can simultaneously analyze the presence or absence of reaction.
【００１０】[0010]
【発明の実施の形態】以下、図面と共に本発明による多
点試料分析用ＳＰＲ分析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 the SPR analyzer for multipoint sample analysis 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.
【００１１】図１は、本発明の多点試料分析用ＳＰＲ分
析装置の構成を概略的に示す図である。図１に示すよう
に、本発明の多点試料分析用ＳＰＲ分析装置は、プリズ
ムからなる基板２１にＳＰＲ励起光Ｌ１が入射面２２よ
り入射し、格子状に形成された金属薄膜２３の部分に全
反射条件で一様に照射し表面プラズモン共鳴（ＳＰＲ）
を生じさせる測定系を構成している。FIG. 1 is a diagram schematically showing the structure of an SPR analyzer for analyzing multipoint samples according to the present invention. As shown in FIG. 1, in the SPR analyzer for analyzing a multipoint sample of the present invention, SPR excitation light L1 is incident on a substrate 21 made of a prism from an incident surface 22, and a metal thin film 23 formed in a lattice shape is formed. Surface plasmon resonance (SPR) with uniform irradiation under total reflection conditions
Constitutes a measurement system that causes
【００１２】金属薄膜２３の上部には電界の印加により
屈折率が変化する媒質２４が装荷されており、測定試料
２５は媒質２４の上に直接もしくは結合用修飾分子によ
り固定される。試料上部にはカバーガラス２６が一定の
間隙を設けて固定されており、カバーガラス２６側には
試料２５が固定される金属電極として機能する金属薄膜
２３と対向するように測定用電極２７が配設されてい
る。A medium 24 whose refractive index changes by application of an electric field is loaded on the upper part of the metal thin film 23, and the measurement sample 25 is fixed directly on the medium 24 or by a modifying molecule for binding. A cover glass 26 is fixed to the upper part of the sample with a certain gap, and a measuring electrode 27 is arranged on the cover glass 26 side so as to face the metal thin film 23 functioning as a metal electrode to which the sample 25 is fixed. It is set up.
【００１３】金属薄膜２３の反射面２３Ａによって反射
された光は、ＣＣＤ等で構成される２次元アレイセンサ
２８で検出される。試料２５を付着する前の状態で２次
元アレイセンサ２８に入射する光量が最低点を通って一
様になるように金属薄膜２３上の非線形電気感受率を有
する高分子（ＭＮＡ:Methyl Nitro Aniline）等で構成
される媒質２４に電圧印加装置２９から出力される電圧
Ｖｘ（＝Ｖ＋ｖsinωt）を印加する。このように、直流
電圧Ｖに微弱な交流電圧（ｖsinωt）を重畳したものを
媒質２４に印加し、電圧の印加による媒質２４の屈折率
の変化を利用して、直流電圧Ｖの値を調整して２次元ア
レイセンサ２８の出力信号を信号処理装置３０で観測す
ることにより生化学反応の発生の有無を測定する。The light reflected by the reflecting surface 23A of the metal thin film 23 is detected by the two-dimensional array sensor 28 composed of CCD or the like. A polymer (MNA: Methyl Nitro Aniline) having a non-linear electric susceptibility on the metal thin film 23 so that the amount of light incident on the two-dimensional array sensor 28 becomes uniform through the lowest point before the sample 25 is attached. The voltage Vx (= V + vsinωt) output from the voltage applying device 29 is applied to the medium 24 composed of the above. As described above, a DC voltage V superposed with a weak AC voltage (vsinωt) is applied to the medium 24, and the value of the DC voltage V is adjusted by utilizing the change in the refractive index of the medium 24 due to the voltage application. By observing the output signal of the two-dimensional array sensor 28 with the signal processor 30, the presence or absence of the biochemical reaction is measured.
【００１４】具体的には、複数の試料において生化学反
応を生じさせる前の段階において、直流電圧Ｖが図２に
おける特性Ａのように表面プラズモン共鳴が生じる電圧
値（図２における反射強度が最小の電圧値：以下電圧Ｖ
0と称す）になるように直流電圧Ｖを調整し、２次元ア
レイセンサ２８の出力信号を信号処理装置３０で観測す
る。なお、このように表面プラズモン共鳴が生じている
ときは、図２に示す特性Ａのように交流成分ｖの周期が
２倍（２ω）になるが、直流電圧Ｖの値がＶ0以外の値
である場合は、図２に示す特性Ｂのように２次元アレイ
センサ２８の出力信号の周期は原信号の周期と同一
（ω）となる。Specifically, at a stage before a biochemical reaction is caused in a plurality of samples, a DC voltage V causes a voltage value at which surface plasmon resonance occurs as shown by a characteristic A in FIG. 2 (the reflection intensity in FIG. 2 is minimum. Voltage value: below voltage V
The DC voltage V is adjusted so as to be 0 ), and the output signal of the two-dimensional array sensor 28 is observed by the signal processing device 30. When the surface plasmon resonance occurs in this way, the period of the AC component v is doubled (2ω) as in the characteristic A shown in FIG. 2, but the value of the DC voltage V is a value other than V 0. In the case of, the cycle of the output signal of the two-dimensional array sensor 28 is the same as the cycle of the original signal (ω) as the characteristic B shown in FIG.
【００１５】次に各試料に試薬を滴下し、２次元アレイ
センサ２８の出力信号を観測する。図３に示すように、
試薬を滴下することによって生化学反応が生じた場合に
は試料の屈折率が変化するため、交流電圧ｖのみを調整
して金属薄膜２３及び測定用電極２７の間における電界
を調整し（Ｅ０→Ｅ０−Ｅｄ）、媒質２４の屈折率を調
整することにより、試薬滴下後の試料における表面プラ
ズモン共鳴の発生の有無を分析する。Next, a reagent is dropped on each sample and the output signal of the two-dimensional array sensor 28 is observed. As shown in FIG.
When a biochemical reaction occurs by dropping the reagent, the refractive index of the sample changes. Therefore, only the AC voltage v is adjusted to adjust the electric field between the metal thin film 23 and the measurement electrode 27 (E0 → E0-Ed), by adjusting the refractive index of the medium 24, the presence or absence of occurrence of surface plasmon resonance in the sample after dropping the reagent is analyzed.
【００１６】信号処理装置３０で２次元アレイセンサ２
８の出力信号を観測することによって、前述のような分
析を複数試料について同時に行えば、いずれの試料にお
いて表面プラズモン共鳴が励起されたか否かを判定する
ことができ、この結果、いずれの試料において生化学反
応が発生したのかを分析することができる。The signal processing device 30 is used for the two-dimensional array sensor 2
By observing the output signal of 8 at the same time, it is possible to determine in which sample the surface plasmon resonance was excited by performing the above-mentioned analysis simultaneously for a plurality of samples. As a result, in any sample It is possible to analyze whether a biochemical reaction has occurred.
【００１７】上述のような測定の際には、初期条件（直
流電圧Ｖ、交流電圧ｖ等）を第１メモリ２９Ａに記憶保
持させておき、また、その際の各電極への直流電界印加
データを試料の識別データと共に第２メモリ２９Ｂに記
憶保持させておく。２次元的に配列した測定部に試料２
５が付着することによりＳＰＲ条件が変化すると、２次
元アレイセンサ２８の出力信号が変化する（周期が２ω
からωへと変化する）。これを初期条件と同じ均一な光
量分布になるように電界強度を変化させ第２メモリ２９
Ｂに保存する。電界強度の強さに接地電極として機能す
る金属薄膜２３と試料２５の間にある媒質２４の屈折率
の変化量が比例関係にあるため、印加する電圧値に基づ
いて媒質２４の屈折率の変化を制御することができる。At the time of the above-described measurement, the initial conditions (DC voltage V, AC voltage v, etc.) are stored and held in the first memory 29A, and the DC electric field application data to each electrode at that time is stored. Is stored and held in the second memory 29B together with the identification data of the sample. Sample 2 on the measuring section arranged two-dimensionally
When the SPR condition changes due to the adhesion of No. 5, the output signal of the two-dimensional array sensor 28 changes (the cycle is 2ω).
Changes from to ω). The electric field intensity is changed so that the light intensity distribution is the same as that in the initial condition.
Save to B. Since the change amount of the refractive index of the medium 24 between the metal thin film 23 functioning as a ground electrode and the sample 25 is proportional to the strength of the electric field, the change of the refractive index of the medium 24 based on the applied voltage value. Can be controlled.
【００１８】ＳＰＲが生じる条件は、基板２１、金属薄
膜２３、媒質２４、試料２５およびその周辺の媒質の各
部の屈折率と光の波長、光の入射角によって決定される
ため、第１メモリ２９Ａ及び第２メモリ２９Ｂに保存し
た電界データから得られる各位置における媒質２４の屈
折率の変化量に基づき、試料２５の屈折率変化または密
度変化を高速でかつ精密に求めることが可能となる。以
上、本発明の多点試料分析用ＳＰＲ分析装置によれば、
交流電界を印加することにより共鳴曲線を得ることが可
能であり、計測データの信頼性を向上させた多点分析用
ＳＰＲ分析装置を提供することができる。The conditions under which SPR occurs are determined by the refractive index of each part of the substrate 21, the metal thin film 23, the medium 24, the sample 25, and the surrounding medium, the wavelength of light, and the incident angle of light. Also, based on the amount of change in the refractive index of the medium 24 at each position obtained from the electric field data stored in the second memory 29B, the change in the refractive index or the density change of the sample 25 can be obtained at high speed and precisely. As described above, according to the SPR analyzer for multipoint sample analysis of the present invention,
It is possible to obtain a resonance curve by applying an alternating electric field, and it is possible to provide an SPR analyzer for multipoint analysis with improved reliability of measurement data.
【００１９】[0019]
【発明の効果】本発明の多点試料分析用ＳＰＲ分析装置
によれば、電界印加手段から直流電圧に交流電圧を重畳
した測定用電圧を前記金属薄膜及び前記測定用電極の間
に印加し、前記交流電圧を制御して前記媒質の屈折率を
変化させ、前記金属薄膜で表面プラズモン共鳴を生じさ
せることにより、複数の試料における生化学反応を同時
に分析できるので、多数の試料を一度に計測できると共
に分析精度が良く、高感度かつ高速処理可能な２次元配
列の多点試料分析用ＳＰＲ分析装置を提供することがで
きる。また、前記直流電圧の値を生化学反応が生じる前
の試料において表面プラズモン共鳴が生じる電圧値に設
定しておき、前記直流電圧に比べて微弱な前記交流電圧
の電圧値を制御して前記媒質の屈折率を変化させること
により、生化学反応が生じた試料において生じる表面プ
ラズモン共鳴を検出して、複数試料における生化学反応
の有無を同時分析できるので、極めて分析精度の高い多
点試料分析用ＳＰＲ分析装置を提供することができる。According to the SPR analyzer for multipoint sample analysis of the present invention, a measuring voltage in which an AC voltage is superimposed on a DC voltage is applied from the electric field applying means between the metal thin film and the measuring electrode, By controlling the AC voltage to change the refractive index of the medium and causing surface plasmon resonance in the metal thin film, biochemical reactions in a plurality of samples can be analyzed at the same time, so that a large number of samples can be measured at one time. At the same time, it is possible to provide an SPR analyzer for analyzing a multipoint sample in a two-dimensional array, which has a high analysis accuracy and can be processed with high sensitivity and high speed. Further, the value of the DC voltage is set to a voltage value at which surface plasmon resonance occurs in a sample before a biochemical reaction occurs, and the voltage value of the AC voltage, which is weaker than the DC voltage, is controlled to control the medium. By changing the refractive index of, it is possible to detect the surface plasmon resonance generated in the sample in which the biochemical reaction has occurred and simultaneously analyze the presence or absence of the biochemical reaction in multiple samples. An SPR analyzer can be provided.
【図１】 本発明の多点試料分析用ＳＰＲ分析装置の構
成を概略的に示す図である。FIG. 1 is a diagram schematically showing the configuration of an SPR analyzer for analyzing multipoint samples of the present invention.
【図２】 本発明の多点試料分析用ＳＰＲ分析装置にお
ける印加電圧と反射光強度の関係を表す特性図である。FIG. 2 is a characteristic diagram showing the relationship between applied voltage and reflected light intensity in the SPR analyzer for multipoint sample analysis of the present invention.
【図３】 本発明の多点試料分析用ＳＰＲ分析装置にお
ける電界と屈折率の変化の様子を表す特性図である。FIG. 3 is a characteristic diagram showing changes in electric field and refractive index in the SPR analyzer for multipoint sample analysis of the present invention.
【図４】 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. 4 is a diagram conceptually showing a detection principle for detecting a mass change using surface plasmon resonance.
【図５】 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. 5 is a characteristic diagram showing a relationship between an incident angle θ and the intensity of reflected light in detection of a mass change using surface plasmon resonance.
【図６】 米国特許第５６２９２１３号明細書に記載さ
れているバイオセンサ装置を示す構成図である。FIG. 6 is a configuration diagram showing a biosensor device described in US Pat. No. 5,629,213.
２１ 基板、２２ 入射面、２３ 金属薄膜、２３Ａ
反射面、２４ 媒質、２５ 試料、２６ カバーガラ
ス、２７ 測定用電極、２８ ２次元アレイセンサ、２
９ 電圧印加装置、２９Ａ 第１メモリ、２９Ｂ 第２
メモリ、３０ 信号処理装置。21 substrate, 22 incident surface, 23 metal thin film, 23A
Reflective surface, 24 medium, 25 sample, 26 cover glass, 27 measuring electrode, 28 two-dimensional array sensor, 2
9 voltage application device, 29A first memory, 29B second
Memory, 30 Signal processing device.
─────────────────────────────────────────────────────
─────────────────────────────────────────────────── ───
【手続補正書】[Procedure amendment]
【提出日】平成１３年１０月２日（２００１．１０．
２）[Submission date] October 2, 2001 (2001.10.
2)
【手続補正１】[Procedure Amendment 1]
【補正対象書類名】明細書[Document name to be amended] Statement
【補正対象項目名】００１５[Name of item to be corrected] 0015
【補正方法】変更[Correction method] Change
【補正内容】[Correction content]
【００１５】次に各試料に試薬を滴下し、２次元アレイ
センサ２８の出力信号を観測する。図３に示すように、
試薬を滴下することによって生化学反応が生じた場合に
は試料の屈折率が変化するため、交流電圧ｖのみを調整
して金属薄膜２３及び測定用電極２７の間における電界
を調整し（Ｅ０→Ｅ０−ｄＥ）、媒質２４の屈折率を調
整することにより、試薬滴下後の試料における表面プラ
ズモン共鳴の発生の有無を分析する。Next, a reagent is dropped on each sample and the output signal of the two-dimensional array sensor 28 is observed. As shown in FIG.
When a biochemical reaction occurs by dropping the reagent, the refractive index of the sample changes. Therefore, only the AC voltage v is adjusted to adjust the electric field between the metal thin film 23 and the measurement electrode 27 (E0 → E0- dE), by adjusting the refractive index of the medium 24, to analyze the occurrence of surface plasmon resonance in the sample after the reagent dropwise.
───────────────────────────────────────────────────── フロントページの続き (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 (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 中山 博之 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 Ｆターム(参考） 2G059 AA01 BB04 BB12 CC16 EE02 EE04 FF11 FF12 GG01 JJ12 KK04 MM10 PP01 ─────────────────────────────────────────────────── ─── Continued front page (72) Inventor Satoshi Tahara 1-8 Koura, Kanazawa-ku, Yokohama-shi, Kanagawa Mitsubishi Heavy Industries, Ltd. Basic Technology Research Center (72) Inventor Takayuki Goto 1-8 Koura, Kanazawa-ku, Yokohama-shi, Kanagawa Mitsubishi Heavy Industries, Ltd. Basic Technology Research Center (72) Inventor Hiroyuki Nakayama 1-8 Koura, Kanazawa-ku, Yokohama-shi, Kanagawa Mitsubishi Heavy Industries, Ltd. Basic Technology Research Center F term (reference) 2G059 AA01 BB04 BB12 CC16 EE02 EE04 FF11 FF12 GG01 JJ12 KK04 MM10 PP01
Claims (2)
化し、生化学反応測定用の試料を複数搭載する媒質と、 前記媒質を搭載する一方の面及び反射面を構成する他方
の面を有する金属薄膜と、 前記金属薄膜の前記反射面が入射光に対する反射面を構
成するように前記金属薄膜が形成され、前記入射光を前
記金属薄膜の前記反射面に誘導すると共に、前記反射面
で反射された反射光を出力面から出力する光学系と、 前記出力面から出力された前記反射光の強度を各試料毎
に同時測定する光検出手段と、 前記媒質に対向配置され、前記金属薄膜と対をなす測定
用電極と、 前記金属薄膜及び前記測定用電極の間に電界を印加する
ための電界印加手段とを備え、 前記電界印加手段から直流電圧に交流電圧を重畳した測
定用電圧を前記金属薄膜及び前記測定用電極の間に印加
し、前記交流電圧を制御して前記媒質の屈折率を変化さ
せ、前記金属薄膜で表面プラズモン共鳴を生じさせるこ
とにより、複数の試料における生化学反応を同時に分析
できることを特徴とする多点試料分析用ＳＰＲ分析装
置。1. A medium on which a plurality of samples for biochemical reaction measurement are mounted, the refractive index of which changes when an electric field is applied, and a surface on which the medium is mounted and another surface which constitutes a reflecting surface are formed. With the metal thin film, the metal thin film is formed so that the reflection surface of the metal thin film constitutes a reflection surface for incident light, and guides the incident light to the reflection surface of the metal thin film, and at the reflection surface. An optical system that outputs the reflected light reflected from the output surface, a photodetector that simultaneously measures the intensity of the reflected light output from the output surface for each sample, and the metal thin film that is arranged to face the medium. And a measuring electrode paired with, and an electric field applying means for applying an electric field between the metal thin film and the measuring electrode, and a measuring voltage obtained by superimposing an AC voltage on a DC voltage from the electric field applying means. The metal thin film and A biochemical reaction in a plurality of samples can be analyzed at the same time by applying the voltage between the measurement electrodes, controlling the AC voltage to change the refractive index of the medium, and causing surface plasmon resonance in the metal thin film. An SPR analyzer for multipoint sample analysis, characterized by:
前の試料において表面プラズモン共鳴が生じる電圧値に
設定しておき、前記直流電圧に比べて微弱な前記交流電
圧の電圧値を制御して前記媒質の屈折率を変化させるこ
とにより、生化学反応が生じた試料において生じる表面
プラズモン共鳴を検出して、複数試料における生化学反
応の有無を同時分析できることを特徴とする請求項１記
載の多点試料分析用ＳＰＲ分析装置。2. The value of the DC voltage is set to a voltage value at which surface plasmon resonance occurs in a sample before a biochemical reaction occurs, and the voltage value of the AC voltage, which is weaker than the DC voltage, is controlled. 2. The surface plasmon resonance generated in the sample in which the biochemical reaction has occurred is detected by changing the refractive index of the medium so that the presence or absence of the biochemical reaction in a plurality of samples can be simultaneously analyzed. SPR analyzer for multi-point sample analysis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001265219A JP2003075336A (en) | 2001-09-03 | 2001-09-03 | Spr analyzer for multipoint sample analysis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001265219A JP2003075336A (en) | 2001-09-03 | 2001-09-03 | Spr analyzer for multipoint sample analysis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2003075336A true JP2003075336A (en) | 2003-03-12 |
Family
ID=19091718
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001265219A Withdrawn JP2003075336A (en) | 2001-09-03 | 2001-09-03 | Spr analyzer for multipoint sample analysis |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2003075336A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005064317A1 (en) * | 2003-12-26 | 2005-07-14 | Matsushita Electric Industrial Co., Ltd. | Method of analyzing ligand in sample and apparatus for analyzing ligand in sample |
| JP2007057293A (en) * | 2005-08-23 | 2007-03-08 | Shimadzu Corp | Particle measuring instrument |
| JP2007078488A (en) * | 2005-09-13 | 2007-03-29 | Hokkaido Univ | Electrochemical infrared spectroscope |
-
2001
- 2001-09-03 JP JP2001265219A patent/JP2003075336A/en not_active Withdrawn
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005064317A1 (en) * | 2003-12-26 | 2005-07-14 | Matsushita Electric Industrial Co., Ltd. | Method of analyzing ligand in sample and apparatus for analyzing ligand in sample |
| US7312069B2 (en) | 2003-12-26 | 2007-12-25 | Matsushita Electric Industrial Co., Ltd. | Method of analyzing ligand in sample and apparatus for analyzing ligand in sample |
| JP2007057293A (en) * | 2005-08-23 | 2007-03-08 | Shimadzu Corp | Particle measuring instrument |
| JP4517980B2 (en) * | 2005-08-23 | 2010-08-04 | 株式会社島津製作所 | Particle measuring device |
| JP2007078488A (en) * | 2005-09-13 | 2007-03-29 | Hokkaido Univ | Electrochemical infrared spectroscope |
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