JP2003247935A - Surface plasmon resonance sensor chip and analysis method of sample using it - Google Patents

Surface plasmon resonance sensor chip and analysis method of sample using it

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Publication number
JP2003247935A
JP2003247935A JP2002050937A JP2002050937A JP2003247935A JP 2003247935 A JP2003247935 A JP 2003247935A JP 2002050937 A JP2002050937 A JP 2002050937A JP 2002050937 A JP2002050937 A JP 2002050937A JP 2003247935 A JP2003247935 A JP 2003247935A
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JP
Japan
Prior art keywords
resonance
surface plasmon
sensor chip
sample
metal layer
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.)
Granted
Application number
JP2002050937A
Other languages
Japanese (ja)
Other versions
JP3858726B2 (en
Inventor
Kanako Tsuboya
奏子 坪谷
Masahiro Nakajima
昌宏 中島
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mitsubishi Chemical Corp
Original Assignee
Mitsubishi Chemical Corp
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Priority to JP2002050937A priority Critical patent/JP3858726B2/en
Publication of JP2003247935A publication Critical patent/JP2003247935A/en
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Publication of JP3858726B2 publication Critical patent/JP3858726B2/en
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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/55Specular reflectivity
    • G01N21/552Attenuated total reflection
    • G01N21/553Attenuated total reflection and using surface plasmons

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  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

<P>PROBLEM TO BE SOLVED: To provide a surface plasmon resonance sensor chip capable of a low-cost and accurate analysis and having high corrosion resistance. <P>SOLUTION: In this surface plasmon resonance sensor chip, an optical prism, a diffraction grating and a metal layer are formed in the vicinity of a sensor surface in contact with a sample, and a resonance region capable of generating a resonance phenomenon between a surface plasmon wave induced on the surface of the metal surface by irradiation of light and an evanescent wave generated by the action of the optical prism or the diffraction grating is formed on the sensor surface. In the surface plasmon resonance sensor chip, the chip is fabricated by forming the metal layer on a resin board, the metal layer contains 95-99.7 wt.% of Ag, and contains 0.3-5 wt.% of noble metal elements other than Ag. <P>COPYRIGHT: (C)2003,JPO

Description

【発明の詳細な説明】Detailed Description of the Invention

【0001】[0001]

【発明の属する技術分野】本発明は、表面プラズモン共
鳴(SPR)を利用した試料分析のためのセンサチップ
(表面プラズモン共鳴センサチップ)の構造に関し、特
に、エバネッセント波を誘起する光学構造として光学プ
リズム又は回折格子を備えたセンサチップの構造及びそ
れを用いた試料の分析方法に関する。
BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a structure of a sensor chip (surface plasmon resonance sensor chip) for sample analysis using surface plasmon resonance (SPR), and more particularly to an optical prism as an optical structure for inducing an evanescent wave. Alternatively, the present invention relates to a structure of a sensor chip provided with a diffraction grating and a sample analysis method using the same.

【0002】[0002]

【従来の技術】従来、生化学や医療検査等の分野におい
ては、化学種,生化学種又は生物種等の検出種を含む試
料流体の定量的及び/又は定性的な分析方法として、表
面プラズモン共鳴(SPR)を利用した分析方法が知ら
れている。表面プラズモン共鳴は、金属層に光が入射し
た場合に金属表面に誘起される表面プラズモン波が入射
光により生成されたエバネッセント波に共鳴して励起さ
れる現象である。表面プラズモン共鳴は入射光の波長及
び角度に依存しており、表面プラズモン共鳴が励起され
たときには、特定の入射角又は特定の波長を有する光成
分の光エネルギーが表面プラズモン波へ移行することに
より、対応する入射角又は波長を有する反射光が減少す
るという特徴がある。
2. Description of the Related Art Conventionally, in the field of biochemistry, medical examination, etc., surface plasmon has been used as a quantitative and / or qualitative analysis method for a sample fluid containing a detected species such as a chemical species, a biochemical species or a biological species. An analysis method utilizing resonance (SPR) is known. Surface plasmon resonance is a phenomenon in which, when light is incident on a metal layer, a surface plasmon wave induced on the metal surface resonates with an evanescent wave generated by the incident light and is excited. Surface plasmon resonance depends on the wavelength and angle of incident light, and when surface plasmon resonance is excited, the light energy of a light component having a specific incident angle or a specific wavelength is transferred to a surface plasmon wave, The feature is that reflected light having a corresponding incident angle or wavelength is reduced.

【0003】表面プラズモン共鳴を起こすためには、特
定の表面プラズモン波を有する金属と、表面プラズモン
波と共鳴するエバネッセント波を誘起する光学構造とが
必要となる。エバネッセント波を誘起する光学構造とし
ては現在二つの構造が知られている。一つは光学プリズ
ム(以下、単にプリズムと称する。)の全反射を利用し
た光学構造であり、もう一つは回折格子を利用した光学
構造である。なお、上記の金属にこれらの光学構造を組
み合わせた素子は一般に表面プラズモン共鳴センサチッ
プ(以下、単にセンサチップという)と呼ばれている。
In order to cause surface plasmon resonance, a metal having a specific surface plasmon wave and an optical structure for inducing an evanescent wave resonating with the surface plasmon wave are required. At present, two structures are known as optical structures that induce an evanescent wave. One is an optical structure that uses total reflection of an optical prism (hereinafter, simply referred to as a prism), and the other is an optical structure that uses a diffraction grating. An element obtained by combining the above metals with these optical structures is generally called a surface plasmon resonance sensor chip (hereinafter, simply referred to as a sensor chip).

【0004】通常、センサチップは基体に金属層を積層
した構造を有し、金属層上には、特定の検出種と相互作
用して特異的に結合する結合物質(リガンド、分子認識
素子)が塗布されて固定化される。このリガンドが固定
化された金属層の表面に試料を接触させることにより、
リガンドに試料中の検出種が捕捉される。表面プラズモ
ン共鳴は金属層の表面における媒質の屈折率にも依存し
ており、媒質の屈折率が変化すれば波長一定の場合には
共鳴角が変化し、また、入射角度一定の場合には共鳴波
長が変化する。したがって、反射光の強度に基づき共鳴
角或いは共鳴波長を調べることで金属層の表面における
媒質の屈折率を分析することができる。この場合、金属
層の表面の媒質の屈折率の変化は、リガンドに捕捉され
る検出種の物質量、すなわち試料中の検出種の濃度の変
化に対応していることから、表面プラズモン共鳴が起き
る共鳴角或いは共鳴波長を調べることで、試料中の検出
種の濃度等を分析することができる。
Usually, a sensor chip has a structure in which a metal layer is laminated on a substrate, and a binding substance (ligand, molecular recognition element) that interacts with a specific detection species and specifically binds is formed on the metal layer. It is applied and fixed. By bringing the sample into contact with the surface of the metal layer on which this ligand is immobilized,
The detection species in the sample are captured by the ligand. Surface plasmon resonance also depends on the refractive index of the medium on the surface of the metal layer.If the refractive index of the medium changes, the resonance angle changes when the wavelength is constant, and when the incident angle is constant, resonance occurs. The wavelength changes. Therefore, the refractive index of the medium on the surface of the metal layer can be analyzed by examining the resonance angle or the resonance wavelength based on the intensity of the reflected light. In this case, since the change in the refractive index of the medium on the surface of the metal layer corresponds to the change in the amount of the detection species trapped by the ligand, that is, the change in the concentration of the detection species in the sample, surface plasmon resonance occurs. By examining the resonance angle or the resonance wavelength, the concentration of the detection species in the sample can be analyzed.

【0005】[0005]

【発明が解決しようとする課題】このようなセンサチッ
プに求められる性能としては、各共鳴スポットでの共鳴
曲線のピークがシャープで強度が大きいこと、つまり共
鳴角のずれ(シフト)に対する感度がよいことが挙げら
れる。また多点(多スポット)で同時検出を行う場合に
は、各スポットでの感度のばらつきが小さいことが好ま
しい。このようなチップの特性を評価するためには、上
記のようなリガンドを付着させない状態で共鳴曲線を取
り、その共鳴曲線のピークの半値幅を測定することによ
って、ある程度の指標とすることができる。その場合、
チップ表面に接する物質の屈折率を揃えるという意味
で、一定の温度に保たれた水をチップ表面に接触させな
がら行うと、良好に評価することができる。半値幅が狭
いほど、共鳴角のずれ(シフト)に対する感度がよいこ
ととなり好ましい。更に、本センサチップの主用途のひ
とつは生化学や医療検査等の分野であるため、測定試料
は生体材料由来の塩を含む場合が多く、従って耐腐食性
が高いことが好ましい。このような特性を評価する方法
としては、所定濃度の塩水に接触した状態での腐食の度
合いを観察する塩水試験がある。以上述べたセンサチッ
プに用いられる金属層は、まず、測定波長の付近で十分
高い反射率を有している必要があるため、高反射率金属
が望ましいとされている。中でも、Auは共鳴曲線の半
値幅が小さく、共鳴角のシフト量が大きく、耐腐食性も
高く、優れた材料である。しかしながらAuは非常に高
価であるため、Auと同等の性質を有し、かつ低コスト
な金属材料が求められていた。
The performance required for such a sensor chip is that the peak of the resonance curve at each resonance spot is sharp and the intensity is large, that is, the sensitivity to the shift of the resonance angle is good. It can be mentioned. Further, when performing simultaneous detection at multiple points (multiple spots), it is preferable that the variations in sensitivity among the spots are small. In order to evaluate the characteristics of such a chip, a resonance curve is taken without attaching the ligand as described above, and the full width at half maximum of the peak of the resonance curve is measured, which can be used as an index to some extent. . In that case,
In order to make the refractive indexes of the substances in contact with the chip surface uniform, it is possible to make a good evaluation when the water is kept at a constant temperature while being brought into contact with the chip surface. The narrower the full width at half maximum is, the better the sensitivity to the shift of the resonance angle is, which is preferable. Further, since one of the main uses of the present sensor chip is in the fields of biochemistry, medical examinations, etc., the measurement sample often contains a salt derived from a biomaterial, and therefore it is preferable that it has high corrosion resistance. As a method for evaluating such characteristics, there is a salt water test for observing the degree of corrosion in contact with salt water having a predetermined concentration. First, the metal layer used for the sensor chip described above is required to have a sufficiently high reflectance in the vicinity of the measurement wavelength, and thus a high reflectance metal is said to be desirable. Among them, Au is an excellent material because it has a narrow half width of the resonance curve, a large shift amount of the resonance angle, and a high corrosion resistance. However, since Au is extremely expensive, there has been a demand for a metal material that has the same properties as Au and is low in cost.

【0006】本発明は、このような課題に鑑み創案され
たもので、低コストで精度の高い分析ができ、かつ耐腐
食性の高い表面プラズモン共鳴センサチップ、及びそれ
を用いた試料の分析方法を提供することを目的とする。
The present invention was devised in view of such problems, and a surface plasmon resonance sensor chip having low cost, high-accuracy analysis and high corrosion resistance, and a sample analysis method using the same. The purpose is to provide.

【0007】[0007]

【課題を解決するための手段】鋭意検討した結果、発明
者らは、樹脂基板上に特定の銀合金からなる金属層が積
層されてなるセンサチップによれば上記の課題を解決で
きることを見出した。即ち本発明の要旨は、試料と接す
るセンサ面の近傍に、光学プリズム又は回折格子と金属
層とが設けられて、光の照射により上記金属層の表面に
誘起される表面プラズモン波と上記光学プリズム又は回
折格子の作用により生じるエバネッセント波との共鳴現
象が生じうる共鳴領域が上記センサ面に形成された表面
プラズモン共鳴センサチップであって、該チップは、樹
脂基板上に該金属層が形成されてなり、該金属層がAg
を95重量%以上99.7重量%以下含み、Ag以外の
貴金属元素を0.3重量%以上5重量%以下含むことを
特徴とする、表面プラズモン共鳴センサチップに存す
る。
As a result of earnest studies, the inventors have found that a sensor chip in which a metal layer made of a specific silver alloy is laminated on a resin substrate can solve the above problems. . That is, the gist of the present invention is that an optical prism or a diffraction grating and a metal layer are provided in the vicinity of the sensor surface in contact with the sample, and the surface plasmon wave induced on the surface of the metal layer by irradiation of light and the optical prism. Alternatively, there is provided a surface plasmon resonance sensor chip in which a resonance region capable of causing a resonance phenomenon with an evanescent wave caused by the action of a diffraction grating is formed on the sensor surface, wherein the chip has a metal layer formed on a resin substrate. And the metal layer is Ag
In a surface plasmon resonance sensor chip characterized by containing 95 wt% or more and 99.7 wt% or less and a noble metal element other than Ag in an amount of 0.3 wt% or more and 5 wt% or less.

【0008】本発明の別の要旨は、上記表面プラズモン
共鳴センサチップを用いて試料の定量的及び/又は定性
的な分析を行うための分析方法であって、上記センサ面
に上記試料を接触させるステップと、上記共鳴領域を照
らすように照射光を照射するステップと、上記表面プラ
ズモン共鳴センサチップからの反射光を検出するステッ
プと、検出した反射光の強度に基づき試料の定量的及び
/又は定性的な分析を行うステップとを備えたことを特
徴とする、分析方法に存する。
Another subject matter of the present invention is an analysis method for performing a quantitative and / or qualitative analysis of a sample using the surface plasmon resonance sensor chip, wherein the sample is brought into contact with the sensor surface. A step of irradiating irradiation light so as to illuminate the resonance region, a step of detecting reflected light from the surface plasmon resonance sensor chip, and a quantitative and / or qualitative analysis of the sample based on the intensity of the detected reflected light. And a step of performing a dynamic analysis.

【0009】[0009]

【発明の実施の形態】以下、本発明について詳細に説明
する。本発明においては、上述のセンサチップが、樹脂
基板上に金属層が形成されてなり、その金属層が、Ag
を95重量%以上99.7重量%以下含み、Ag以外の
貴金属元素を0.3重量%以上5重量%以下含むことを
特徴とする。これにより、低コストで精度の高い分析が
でき、かつ耐腐食性の高い表面プラズモン共鳴センサチ
ップを提供することができる。金属層の主成分をAgと
する。表面プラズモン共鳴を起こすためには、金属層の
複素誘電率の実部と虚部の比が大きく、実部の係数が負
であることが望ましい。通常使用するレーザー波長付近
で、Au以外にAgがこれを満たす。ただしAgは単独
で用いると耐腐食性に劣るという問題点があり、他の金
属との合金とする必要があるが、いずれの金属との合金
でもよいわけではない。本発明者らの検討の結果、Ag
に所定量の貴金属元素を含むことにより、耐酸化性、耐
硫化性、耐アルカリ性を増すことができることが分かっ
た。ひいては、低コストで精度の高い分析ができ、かつ
耐腐食性の高い表面プラズモン共鳴センサチップが得ら
れる。本発明において貴金属元素とは、Au、Ag、P
t、Pd、Ru、Rh、Os、Irを指す。好ましくは
貴金属元素がAu、Pt又はPdのいずれかである。貴
金属以外の元素、例えばCuを単独で添加すると耐酸化
性、耐ガス性等に問題がある。組成割合については、A
gを95重量%以上99.7重量%以下含み、Ag以外
の貴金属元素を0.3重量%以上5重量%以下含むこと
とする。貴金属元素量が少なすぎると耐腐食性の改善効
果が小さく、一方あまり多すぎると金属層の複素誘電率
の実部と虚部の比が小さくなり、表面プラズモン共鳴セ
ンサチップとしての性能が低下する。例えば、共鳴曲線
ピークがブロードになり半値幅が大きくなってしまう。
また、これら金属の他に、必要に応じて更に他の金属を
0.3〜5重量%程度含んでも良い。希土類元素を添加
すると、成膜時におけるAgの結晶粒の成長を抑制し、
膜の結晶構造の安定性を高め、膜の均質性が良くなり好
ましい。特に好ましくはNd、Yのいずれかである。
BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described in detail below. In the present invention, the above-described sensor chip has a metal layer formed on a resin substrate, and the metal layer is Ag.
Is contained in an amount of 95 wt% or more and 99.7 wt% or less, and a noble metal element other than Ag is included in an amount of 0.3 wt% or more and 5 wt% or less. As a result, it is possible to provide a surface plasmon resonance sensor chip that can perform highly accurate analysis at low cost and has high corrosion resistance. The main component of the metal layer is Ag. In order to cause surface plasmon resonance, it is desirable that the ratio of the real part to the imaginary part of the complex permittivity of the metal layer is large and the coefficient of the real part is negative. In addition to Au, Ag satisfies this in the vicinity of the normally used laser wavelength. However, when Ag is used alone, it has a problem that it is inferior in corrosion resistance, and it is necessary to form an alloy with another metal. However, an alloy with any metal is not necessarily required. As a result of the study by the present inventors, Ag
It has been found that the oxidation resistance, the sulfidation resistance and the alkali resistance can be increased by including a predetermined amount of a noble metal element in the. As a result, it is possible to obtain a surface plasmon resonance sensor chip that can perform highly accurate analysis at low cost and has high corrosion resistance. In the present invention, the noble metal element means Au, Ag, P
Refers to t, Pd, Ru, Rh, Os, and Ir. Preferably, the noble metal element is Au, Pt or Pd. If an element other than a noble metal, such as Cu, is added alone, there is a problem in oxidation resistance and gas resistance. For composition ratio, see A
g is contained in an amount of 95% by weight or more and 99.7% by weight or less, and a noble metal element other than Ag is included in an amount of 0.3% by weight or more and 5% by weight or less. If the amount of the precious metal element is too small, the effect of improving the corrosion resistance is small, while if it is too large, the ratio of the real part and the imaginary part of the complex permittivity of the metal layer becomes small, and the performance as a surface plasmon resonance sensor chip deteriorates. . For example, the peak of the resonance curve becomes broad and the half-width becomes large.
In addition to these metals, if necessary, other metals may be contained in an amount of about 0.3 to 5% by weight. Addition of a rare earth element suppresses the growth of Ag crystal grains during film formation,
This is preferable because it improves the stability of the crystal structure of the film and improves the homogeneity of the film. Particularly preferred is either Nd or Y.

【0010】本発明のセンサチップは、樹脂基板上に金
属層を有する構造であれば、回折格子型、プリズム型の
いずれのセンサチップにも適用することができる。ただ
し、好ましくは回折格子型センサチップとする。プリズ
ム型のセンサチップは、一般にセンサチップ本体(透明
基体上に金属層が積層されたもの)とプリズムとから構
成されている。センサチップは基本的には使い捨てであ
るが、プリズムは高価であるため、センサチップ本体だ
けでなくプリズムまでも使い捨てにすると測定コストが
非常に高くなってしまう。このため、この型のセンサチ
ップでは、一般にセンサチップ本体とプリズムが別で、
使用時にプリズムをセンサチップ本体に密着させてプリ
ズムに光を入射し、反射光を検出し測定するようになっ
ている。
The sensor chip of the present invention can be applied to any diffraction grating type or prism type sensor chip as long as it has a structure having a metal layer on a resin substrate. However, a diffraction grating type sensor chip is preferable. The prism type sensor chip is generally composed of a sensor chip body (a transparent substrate on which a metal layer is laminated) and a prism. The sensor chip is basically disposable, but since the prism is expensive, the measurement cost becomes very high if not only the sensor chip body but also the prism is disposable. Therefore, in this type of sensor chip, the sensor chip body and the prism are generally different,
At the time of use, the prism is brought into close contact with the main body of the sensor chip, light is incident on the prism, and reflected light is detected and measured.

【0011】このようにセンサチップ本体とプリズムと
が別の場合、使用時には、センサチップ本体とプリズム
との密着性を上げるためにマッチングオイルを間に挟ん
で密着させる場合が多い。しかし毎回同じ状態に密着さ
せるのは非常に困難で、測定の度に密着度合いのばらつ
きが大きく、したがって測定値のばらつきが大きいとい
う課題がある。この対策例として、特開2000-12
1551号公報に開示されているように補正用の標準液
を測定することでセンサチップ間の測定値のばらつきを
補正する方法が提案されている。しかしながら、この場
合、標準液を供給するための新たな送液系が必要にな
り、また、センサチップ本体も標準液の供給をうけるこ
とができるように特別な構造を必要とする。
As described above, when the sensor chip body and the prism are separate from each other, in use, matching oil is often sandwiched between the sensor chip body and the prism in order to improve the adhesion. However, it is very difficult to bring the same state into close contact with each other every time, and there is a problem that the degree of close contact varies greatly at each measurement, and therefore the variation of the measured values is large. As an example of this measure, Japanese Patent Laid-Open No. 2000-12
As disclosed in Japanese Patent No. 1551, a method has been proposed in which a standard solution for correction is measured to correct variations in measured values between sensor chips. However, in this case, a new liquid supply system for supplying the standard solution is required, and the sensor chip body also needs a special structure so that the standard solution can be supplied.

【0012】一方、回折格子型のセンサチップは、表面
に凹凸形状(グレーティング)を有する透明基体上に金
属層を積層された構造になっている。凹凸形状上に金属
層が積層されることで金属層の表面にも凹凸形状が現
れ、この金属層の表面の凹凸形状が回折格子として機能
する。この型のセンサチップは、プリズム型のように高
価なプリズムを使用しないため安価であり、使い捨てが
可能である。また、プリズム型のようにプリズムとセン
サチップ本体を密着させる作業が不要のため、密着度合
いのばらつきといった不具合もなく測定値の再現性が良
いという利点もある。
On the other hand, the diffraction grating type sensor chip has a structure in which a metal layer is laminated on a transparent substrate having an uneven shape (grating) on the surface. By stacking the metal layer on the uneven shape, the uneven shape appears on the surface of the metal layer, and the uneven shape of the surface of the metal layer functions as a diffraction grating. This type of sensor chip is inexpensive and disposable as it does not use an expensive prism unlike the prism type. Further, unlike the prism type, there is no need to bring the prism and the sensor chip main body into close contact with each other, so that there is an advantage that the reproducibility of measured values is good without a problem such as a variation in the degree of close contact.

【0013】また、プリズム型のセンサチップではプリ
ズムを入射光及び反射光の経路とするという構造上、ビ
ームの径やビームを照射できる領域に制約があるが、回
折格子型のセンサチップにはこのような制約はなく、大
径のビームを使用することができ、また任意の位置にビ
ームを照射することができる。したがって、回折格子型
によればプリズム型に比較して一度に大面積を検査する
ことができ、またセンサチップ上の任意の位置について
検査することができるという利点がある。
Further, in the prism type sensor chip, there are restrictions on the diameter of the beam and the area where the beam can be irradiated due to the structure that the prism is used as the path of the incident light and the reflected light. There is no such limitation, a large-diameter beam can be used, and the beam can be irradiated to any position. Therefore, the diffraction grating type has an advantage that a large area can be inspected at once and an arbitrary position on the sensor chip can be inspected as compared with the prism type.

【0014】今日では、分析処理の高速化のため、一つ
のセンサチップ上において多数の測定点(スポット)につ
いて測定を行う多項目測定が行われ、さらに、全スポッ
トについて同時に測定を行う多点同時測定が要望されて
いるが、このような要望に鑑みても、一度に大面積の検
査が可能であり、また、金属表面上の任意の位置につい
て検査が可能な回折格子型のセンサチップの有用性は高
い。
Today, in order to speed up the analysis process, multi-item measurement is performed in which a large number of measurement points (spots) are measured on one sensor chip, and moreover, simultaneous measurement is performed for all spots. Measurement is demanded, but even in view of such demand, it is possible to inspect a large area at once, and it is also useful to use a diffraction grating type sensor chip that can inspect any position on the metal surface. The nature is high.

【0015】回折格子型のセンサチップの作成方法とし
ては、基板材料として紫外線硬化性樹脂を用いた2P法
によるもの、熱可塑性樹脂を用いるものがある。前者の
方式では、所望の回折格子パターンと凹凸逆(陰画)の
パターンを持ったスタンパーを作成し、透明な支持基盤
(ガラスあるいはプラスチック)上に紫外線硬化性樹脂
を均一に塗布し、その上にスタンパーを圧着し、透明支
持基盤側から紫外線を照射する。紫外線硬化性樹脂が硬
化した後スタンパーを剥離すると、所望の回折格子パタ
ーンを持った、紫外線硬化性樹脂層付き基盤が得られ
る。さらにこの上に、薄い金属膜を蒸着やスパッタリン
グで形成する。これを検出装置のサイズに合うように加
工して、センサチップが得られる。しかしながら、代表
的な紫外線硬化性樹脂である、アクリル系紫外線硬化性
樹脂やポリエステル系紫外線硬化性樹脂には、一般に金
属膜との密着性が不十分な樹脂が多い。この対策として
は、紫外線硬化性樹脂の上に直接金属膜を形成するので
はなく、両者の間にクロムなど密着性の良い材料からな
る中間層を形成したり、下処理して密着性を上げたりす
ることが考えられる。ただしそのためにチップの表面性
が悪化したりコストが高くなる虞がある。
As a method for producing a diffraction grating type sensor chip, there are a method using a 2P method using an ultraviolet curable resin as a substrate material and a method using a thermoplastic resin. In the former method, a stamper having a desired diffraction grating pattern and a pattern with a concavo-convex reverse (negative image) is created, and an ultraviolet curable resin is evenly applied on a transparent support base (glass or plastic), and then it is applied. The stamper is pressure-bonded and the transparent support base side is irradiated with ultraviolet rays. When the stamper is peeled off after the ultraviolet curable resin is cured, a substrate with an ultraviolet curable resin layer having a desired diffraction grating pattern is obtained. Further, a thin metal film is formed thereon by vapor deposition or sputtering. A sensor chip is obtained by processing this so as to match the size of the detection device. However, the acrylic UV-curable resin and the polyester UV-curable resin, which are typical UV-curable resins, generally have insufficient adhesion to the metal film. As a measure against this, instead of forming a metal film directly on the ultraviolet curable resin, form an intermediate layer made of a material with good adhesion such as chromium between them, or prepare a middle layer to improve the adhesion. It is possible that However, this may deteriorate the surface properties of the chip and increase the cost.

【0016】一方、熱可塑性樹脂は一般に、従来の紫外
線硬化性樹脂に比べて金属膜との密着性にも優れるの
で、クロム層を挟んだり密着性を向上させるための下処
理をすることなく、上述の金属層を直接積層できる。従
ってチップの表面性も良く、良好な表面プラズモン共鳴
シグナルを得ることができる。また、製造時に工程を増
やすことなく低コストで作製できる。また、熱可塑性樹
脂を用いることで、スタンパーを用いた射出成形法や圧
着法などの各種成形法、転写法によって、表面に回折格
子が形成された表面プラズモン共鳴センサチップを短時
間で多数得ることができる。熱可塑性樹脂からなる基板
は、一旦精密な金型及びスタンパーを作ってしまえばパ
ターンの配置や基板の厚みを正確に制御できるので、回
折格子の位置も正確であるばかりでなく、また基板表面
に傾斜が生じることもないので、このようなセンサチッ
プを用いた試料の分析方法によれば、より精度の高い分
析が可能である。
On the other hand, since the thermoplastic resin is generally superior in adhesiveness to the metal film as compared with the conventional ultraviolet-curing resin, it is possible to sandwich the chrome layer or to perform the pretreatment for improving the adhesiveness. The metal layers mentioned above can be laminated directly. Therefore, the surface property of the chip is good, and a good surface plasmon resonance signal can be obtained. Further, it can be manufactured at low cost without increasing the number of steps during manufacturing. Further, by using a thermoplastic resin, it is possible to obtain a large number of surface plasmon resonance sensor chips each having a diffraction grating formed on the surface in a short time by various molding methods such as injection molding method using a stamper, pressure bonding method, and transfer method. You can For a substrate made of thermoplastic resin, once the precise mold and stamper are made, the pattern arrangement and the thickness of the substrate can be controlled accurately, so not only the position of the diffraction grating is accurate, but also on the substrate surface. Since no inclination occurs, the sample analysis method using such a sensor chip enables more accurate analysis.

【0017】更に、熱可塑性樹脂を用いた基板は、基板
そのものに回折格子が形成されるので、2P法のように
支持基盤と紫外線硬化性樹脂層との界面が存在せず、従
って衝撃等により剥離することがなく、より耐衝撃性及
び耐環境性に優れた表面プラズモン共鳴センサチップが
得られる。
Further, in the substrate using the thermoplastic resin, since the diffraction grating is formed on the substrate itself, there is no interface between the support base and the UV-curable resin layer as in the 2P method, and therefore, there is no impact due to impact or the like. It is possible to obtain a surface plasmon resonance sensor chip which is free from peeling and is more excellent in impact resistance and environment resistance.

【0018】基板に用いる熱可塑性樹脂としては、表面
に回折格子パターンが転写できるものであれば種類は問
わないが、例えば、ポリカーボネート樹脂、アクリル樹
脂、ポリスチレン樹脂、塩化ビニル樹脂、エポキシ樹
脂、ポリエステル樹脂、アモルファスポリオレフィン等
が使用できる。ポリカーボネート系樹脂は、吸湿性が低
く、寸法安定性に優れ、表面への金属膜への密着性も良
好で、各種光学部品への応用が広がっていることから他
の樹脂に比べて高品質なものを低価格で入手することが
可能なため望ましい。
The thermoplastic resin used for the substrate may be of any type as long as it can transfer the diffraction grating pattern to the surface, and examples thereof include polycarbonate resin, acrylic resin, polystyrene resin, vinyl chloride resin, epoxy resin and polyester resin. , Amorphous polyolefin and the like can be used. Polycarbonate resin has low hygroscopicity, excellent dimensional stability, good adhesion to the metal film on the surface, and is widely used in various optical parts, so it has higher quality than other resins. It is desirable because it can be obtained at a low price.

【0019】好ましくは熱可塑性樹脂を射出成形するこ
とよりSPRチップ用基板を作製する。すなわち、所望
の回折格子パターンと凹凸逆(陰画)のパターンを持っ
たスタンパーを用いて、回折格子パターンを表面に有す
る透明なプラスチック基板を射出成形によって形成し、
その上に金属膜を形成してSPRチップとする。これに
よれば、特に寸法安定性が良い、即ち個々のチップの寸
法の違いが非常に小さい、優れた特性のチップが得られ
る。従って1チップ上に複数、例えば400個(400
セル)以上もの微小な共鳴領域を有するチップであって
も、個々の共鳴領域から良好なSPRシグナルが得られ
る優れたチップが作製できるという利点がある。更に、
低コストで、短時間に多数のチップが作製できるという
利点もある。
Preferably, the SPR chip substrate is manufactured by injection molding a thermoplastic resin. That is, a transparent plastic substrate having a diffraction grating pattern on its surface is formed by injection molding using a stamper having a desired diffraction grating pattern and a concavo-convex pattern (negative image).
A metal film is formed thereon to form an SPR chip. According to this, it is possible to obtain a chip having particularly excellent dimensional stability, that is, a difference in size between individual chips is very small and having excellent characteristics. Therefore, a plurality of chips, for example 400 (400
Even if the chip has a minute resonance region of a cell or more, there is an advantage that an excellent chip that can obtain a good SPR signal from each resonance region can be manufactured. Furthermore,
There is also an advantage that many chips can be manufactured in a short time at low cost.

【0020】次に、本発明のセンサチップの作製方法に
ついて詳しく説明する。まず、常法に従い、所望の回折
格子パターンと凹凸逆(陰画)のパターンを持ったスタ
ンパーを作成する。例えばガラス基盤上にフォトレジス
トを塗布した後、レーザ光等で露光、現像して所定の凹
凸パターンを形成し、これを原盤としてスパッタリン
グ、メッキ法等によりニッケルなど金属からなる回折格
子スタンパーを作製する。
Next, a method of manufacturing the sensor chip of the present invention will be described in detail. First, according to a conventional method, a stamper having a desired diffraction grating pattern and a pattern of concavo-convex reverse (negative image) is prepared. For example, after applying a photoresist on a glass substrate, it is exposed to laser light and developed to form a predetermined uneven pattern, and using this as a master, a diffraction grating stamper made of metal such as nickel is produced by sputtering, plating, etc. .

【0021】次に、このスタンパーをもとに熱可塑性樹
脂の射出成形を行う。射出成形条件について詳細に説明
する。各樹脂の性質によって条件は異なるが、ポリカー
ボネート樹脂を例にすると以下の通りである。用いられ
る射出成形機としては、スタンパー及び金型(可動側、
固定側)を用いてスタンパーの形状を成形物に転写する
ことが可能なものであればよく、平面性や転写精度の面
から光ディスク用に一般的に用いられている装置を用い
ることができる。チップの表面に形成すべき凹凸形状が
非常に微細であることから、金型温度は可動側、固定側
ともに125〜130度、樹脂温度は360〜390
度、型締め厚は30〜70トンとすることが望ましい。
Next, injection molding of a thermoplastic resin is carried out based on this stamper. The injection molding conditions will be described in detail. Although the conditions vary depending on the properties of each resin, the polycarbonate resin is as follows as an example. The injection molding machine used includes a stamper and a mold (movable side,
Any device can be used as long as it can transfer the shape of the stamper to the molded product by using the (fixed side), and a device generally used for optical disks can be used in terms of flatness and transfer accuracy. Since the uneven shape to be formed on the surface of the chip is extremely fine, the mold temperature is 125 to 130 degrees on both the movable side and the fixed side, and the resin temperature is 360 to 390.
It is desirable that the mold clamping thickness is 30 to 70 tons.

【0022】射出成形により得る成形片の形状として
は、最初からチップ基板の大きさに成形してもよいし、
チップより大きく成形して、成形後、または金属膜の形
成後にカッターや超音波、熱などを用いた方法で打ち抜
きを行ってもよい。成形片(基板)の厚みは、SPRチ
ップとして表面プラズモン共鳴測定装置に取り付け可能
な厚さであればよく、使用される測定装置に合わせて設
計すればよいが、平面度や射出成形速度の確保などから
考えると0.4〜3mm程度の厚みが望ましい。
The shape of the molded piece obtained by injection molding may be molded to the size of the chip substrate from the beginning,
It may be molded to be larger than the chip, and may be punched by a method using a cutter, ultrasonic waves, heat or the like after the molding or after the metal film is formed. The thickness of the molded piece (substrate) may be any thickness as long as it can be attached to the surface plasmon resonance measuring device as an SPR chip, and may be designed according to the measuring device used, but the flatness and the injection molding speed are ensured. Considering the above, a thickness of 0.4 to 3 mm is desirable.

【0023】成形の後、成形片(基板)表面に金属層を
形成する。金属層は、蒸着法、スパッタリング法、イオ
ンプレーティング法などによって成膜される。金属の材
料としては前述のとおりである。なお、金属層と基板の
間に層間の密着力をより向上させるため、または、反射
率や共鳴ピークの強度を高める等の目的で第1の中間層
を設けてもよい。
After molding, a metal layer is formed on the surface of the molded piece (substrate). The metal layer is formed by a vapor deposition method, a sputtering method, an ion plating method, or the like. The metal material is as described above. A first intermediate layer may be provided between the metal layer and the substrate for the purpose of further improving the adhesion between the layers or for the purpose of increasing the reflectance or the intensity of the resonance peak.

【0024】金属層の厚さは、形成された膜の厚さが均
一になること、基板樹脂への光の透過を少なくすること
等の目的で、40nm以上が好ましく、より好ましくは
70nm以上である。また、それ以上厚さが厚くなって
も金属層の屈折率は殆ど変化せず、SPR共鳴曲線への
寄与は小さいので、コストの面から考えると300nm
以下が好ましく、更に好ましくは200nm以下であ
る。
The thickness of the metal layer is preferably 40 nm or more, more preferably 70 nm or more for the purpose of making the thickness of the formed film uniform and reducing the transmission of light to the substrate resin. is there. Further, even if the thickness is further increased, the refractive index of the metal layer hardly changes and the contribution to the SPR resonance curve is small.
The following is preferable, and 200 nm or less is more preferable.

【0025】必要に応じて、金属層の上に直接、又は付
着性、安定性を高めるための第2の中間層を介してチッ
プの表面に検出したい物質と特異的に結合を行う物質
(リガンド)を付着させる。リガンドの付着はスポッタ
ーなどを用いて、数十〜数百μm径のスポット状に行わ
れる。本発明に係るSPRチップを用いた測定装置によ
るSPR測定法の一例について説明する。
If necessary, a substance (ligand that specifically binds to the substance to be detected on the surface of the chip directly on the metal layer or via the second intermediate layer for enhancing the adhesiveness and stability (ligand) ) Is attached. The attachment of the ligand is performed using a spotter or the like in the form of spots having a diameter of several tens to several hundreds of μm. An example of the SPR measuring method by the measuring device using the SPR chip according to the present invention will be described.

【0026】回折格子上の所定の位置にリガンドを均一
に付着させ、その状態でのSPR共鳴曲線を測定する。
入射光の波長を変える方法と、入射光の角度を変える場
合があるが、以下は入射光の角度を変える場合について
説明する。表面プラズモン共鳴(SPR)が起こり、回
折格子からの回折光の強度が減少していき、最大に強度
が減少した位置の入射光角度を「共鳴角」と呼ぶ。共鳴
角の前後で入射光角度―強度曲線(以下「共鳴曲線」と
呼ぶ)を描くと、共鳴角の周辺でピークが生じ、ピーク
の深さが深く、半値幅が狭いほど良好な検出が行われる
とされる。
A ligand is uniformly attached to a predetermined position on the diffraction grating, and the SPR resonance curve in that state is measured.
There are a method of changing the wavelength of the incident light and a case of changing the angle of the incident light. Below, a case of changing the angle of the incident light will be described. The surface plasmon resonance (SPR) occurs, the intensity of the diffracted light from the diffraction grating decreases, and the incident light angle at the position where the intensity decreases to the maximum is called the “resonance angle”. When an incident light angle-intensity curve (hereinafter referred to as "resonance curve") is drawn before and after the resonance angle, peaks occur around the resonance angle, and the deeper the peak depth and the narrower the half width, the better the detection. It is supposed to be done.

【0027】まずリガンドのみの状態で共鳴曲線を描
き、共鳴角を求める。次にそこに検出したい物質を含む
水、バッファー、溶媒などを接触させ、チップ上のリガ
ンドと結合させる。その後共鳴曲線を取ると、リガンド
と検出種が結合したときに、共鳴角がずれるという現象
がみられ、ずれの有無によって結合が起こったこと、ま
たずれの量によって結合した検出種の量も知ることがで
きる。
First, a resonance curve is drawn in the state of only the ligand to obtain the resonance angle. Then, water, a buffer, a solvent, etc. containing the substance to be detected are brought into contact therewith to bond with the ligand on the chip. When the resonance curve is taken after that, when the ligand and the detection species bind, the phenomenon that the resonance angle shifts is seen, and the binding occurred depending on the presence or absence of the deviation, and the amount of the detection species bound depending on the amount of the deviation. be able to.

【0028】多点同時測定の場合は、入射光のスポット
内に多数の検出スポットを配置させて、回折光をCCD
カメラで分割して検出することにより、数十〜数百のス
ポットを同時に検出することが可能である。チップに求
められる性能としては、上記各スポットでの共鳴曲線の
ピークがシャープで強度が大きいこと、つまり共鳴角の
ずれに対する感度がよいことに加え、多点に分割したと
きの、各スポットでの感度のばらつきが小さいことが上
げられる。共鳴曲線は図1に示すようなガウシアン分布
に似た曲線となる。図において(最大)信号振幅をAと
し、振幅Aが得られる角度を共鳴角θmax(deg)
とし、信号値がA/eとなる領域の幅を半値幅σ(de
g)とする。一般に、半値幅σが小さく、振幅Aが大き
いほど角度分解能が高いので好ましいとされる。実際の
共鳴曲線は必ずしもガウシアン分布とならないため、ガ
ウシアン関数によってカーブフィッティングを行い、ガ
ウシアン曲線に近似して、上記振幅A、共鳴角θmax
(deg)、半値幅σ(deg)を得る。
In the case of multipoint simultaneous measurement, a large number of detection spots are arranged in the spot of incident light to diffract the diffracted light.
It is possible to detect several tens to several hundreds of spots at the same time by dividing and detecting with a camera. As the performance required for the chip, the peak of the resonance curve at each spot is sharp and the intensity is large, that is, the sensitivity to the deviation of the resonance angle is good, and when divided into multiple points, The small variation in sensitivity can be raised. The resonance curve becomes a curve similar to the Gaussian distribution as shown in FIG. In the figure, the (maximum) signal amplitude is A, and the angle at which the amplitude A is obtained is the resonance angle θmax (deg)
And the width of the region where the signal value is A / e is the half width σ (de
g). Generally, the smaller the half-value width σ and the larger the amplitude A, the higher the angular resolution, which is preferable. Since an actual resonance curve does not necessarily have a Gaussian distribution, curve fitting is performed using a Gaussian function to approximate the Gaussian curve to obtain the amplitude A and the resonance angle θmax.
(Deg) and half-width σ (deg) are obtained.

【0029】このようなチップの特性の評価のために
は、リガンドを付着させない状態で、共鳴曲線のみを取
ることによってある程度の指標とすることができる。そ
の場合、チップ表面に接する物質の屈折率を揃えるとい
う意味で、一定の温度に保たれた水をチップ表面に接触
させながら行うと、良好に評価することが出来る。
In order to evaluate the characteristics of such a chip, it is possible to obtain a certain index by taking only the resonance curve in the state where the ligand is not attached. In that case, in order to make the refractive indexes of the substances in contact with the chip surface uniform, it is possible to make a good evaluation if the water is kept at a constant temperature while being brought into contact with the chip surface.

【0030】[0030]

【実施例】本発明を実施例に従い詳細に説明する。ただ
し、本発明はその要旨を越えない限り以下の実施例に限
定されるものではない。 [センサチップの作製]ポリカーボネート樹脂を用いて
射出成形を行った。金型は直径130mm、厚さ1.2
mmの円盤が成形できる成形金型を用いた。スタンパー
は直径130mmの円盤状で中心に直径35.4mmの
穴をもち、その一部にレーザ露光装置により、15mm
×25mmの範囲に、ピッチ0.8μm、長さ25m
m、深さ40nmの平行な溝からなる回折格子パターン
を形成したものを用いた。
EXAMPLES The present invention will be described in detail with reference to examples. However, the present invention is not limited to the following examples unless it exceeds the gist. [Production of Sensor Chip] Polycarbonate resin was used for injection molding. The mold has a diameter of 130 mm and a thickness of 1.2
A molding die capable of molding a mm disk was used. The stamper has a disk shape with a diameter of 130 mm and has a hole with a diameter of 35.4 mm at the center.
Pitch 0.8 μm, length 25 m in the range of × 25 mm
A diffraction grating pattern formed of parallel grooves having a depth of m and a depth of 40 nm was used.

【0031】射出成形条件は、固定側金型温度127〜
128℃、可動側金型(スタンパー取り付け)温度12
5℃、樹脂温度360〜370℃であった。圧縮圧力は
最大で140kgf/cm2、保圧時間1秒、冷却時間
10秒、射出速度105mm/secとした。この成形
により、直径130mm、厚さ1.2mmの透明基板上
に、上記の回折格子パターンを持つポリカーボネート製
の円盤が得られた。
The injection molding conditions are fixed mold temperature 127-
128 ℃, movable mold (stamper attached) temperature 12
It was 5 degreeC and the resin temperature was 360-370 degreeC. The compression pressure was 140 kgf / cm 2 at the maximum, the pressure holding time was 1 second, the cooling time was 10 seconds, and the injection speed was 105 mm / sec. By this molding, a polycarbonate disc having the above diffraction grating pattern was obtained on a transparent substrate having a diameter of 130 mm and a thickness of 1.2 mm.

【0032】次に、円盤の回折格子パターンを有する側
に、到達真空度:2.0×10-3Pa以下、スパッタリ
ングガス:Ar、ガス圧:0.45〜0.55Pa、電
圧405〜445V、電流値0.8A、成膜時間3〜4
分の条件下で、表−1に示す金属層をDCマグネトロン
スパッタリングにより、膜厚がいずれも100nm〜1
10nmの間となるように形成した。このように金属層
を形成した円盤から、回折格子を含む25mm×25m
mの部分を切り出し、センサチップとした。
Next, on the side of the disk having the diffraction grating pattern, the ultimate vacuum: 2.0 × 10 −3 Pa or less, sputtering gas: Ar, gas pressure: 0.45 to 0.55 Pa, voltage 405 to 445 V. , Current value 0.8A, film formation time 3-4
Under a condition of 1 minute, the metal layers shown in Table 1 were each subjected to DC magnetron sputtering to have a film thickness of 100 nm to 1
It was formed to have a thickness of 10 nm. From the disk with the metal layer formed in this way, 25 mm x 25 m including the diffraction grating
The portion of m was cut out and used as a sensor chip.

【0033】[0033]

【表1】 [Table 1]

【0034】[共鳴曲線の半値幅の測定]表面プラズモ
ン共鳴測定装置(HTS社製)に、チップの測定領域の
周囲にシリコン製のガスケットを介して上記チップを取
り付けた。チップ表面に、30℃の水が均一に接してい
る状態で、波長876nmのレーザ光を直径約10mm
のスポット状に照射する。レーザ光の入射角の角度を共
鳴角付近で走査しつつ回折光の強度を測定することによ
って、共鳴曲線を得た。共鳴曲線の半値幅の評価結果を
表−1に示す。半値幅は小さいほど共鳴角シフトに対す
る感度が鋭敏になるため望ましく、0.6以下であれば
分析に適している。
[Measurement of full width at half maximum of resonance curve] The above chip was attached to a surface plasmon resonance measuring device (manufactured by HTS) via a silicon gasket around the measurement region of the chip. Laser light with a wavelength of 876 nm is about 10 mm in diameter, with water at 30 ° C uniformly contacting the chip surface.
Irradiate in spot form. A resonance curve was obtained by measuring the intensity of the diffracted light while scanning the incident angle of the laser light near the resonance angle. Table 1 shows the evaluation results of the full width at half maximum of the resonance curve. The smaller the full width at half maximum is, the more sensitive the resonance angle shift is to sensitivity, which is desirable, and a value of 0.6 or less is suitable for analysis.

【0035】[塩水試験]次いで、本センサチップにつ
いて耐腐食性を評価した。表面に表1に示す金属膜を形
成したセンサチップを、5%のNaCl水溶液に12時
間浸せきした。取り出して水道水で洗浄し、乾燥させて
から表面を観察した。塩水試験による耐腐食性の評価結
果を表−1に示す。○は腐食、膜の剥がれが全く見られ
なかったもの、△は腐食は見られなかったが、一部膜が
剥がれていた物、×は腐食が起こり、金属膜が基板から
剥がれてしまったものである。 [総合判定]総合判定の結果を表−1に示す。共鳴曲線
の半値幅が0.6以下で、塩水試験で△以上であるもの
を、実使用に耐えうるチップとみなす。
[Salt Water Test] Next, the corrosion resistance of this sensor chip was evaluated. The sensor chip having the metal film shown in Table 1 formed on the surface was immersed in a 5% NaCl aqueous solution for 12 hours. It was taken out, washed with tap water, dried, and then the surface was observed. Table 1 shows the evaluation results of the corrosion resistance by the salt water test. ○: No corrosion, no peeling of the film was observed, △: No corrosion, but the film was partially peeled, ×: Corrosion occurred and the metal film was peeled from the substrate Is. [Comprehensive judgment] Table-1 shows the result of the comprehensive judgment. A chip having a resonance curve with a half width of 0.6 or less and a salt water test of Δ or more is regarded as a chip that can withstand actual use.

【0036】[0036]

【発明の効果】以上のように、本発明により、低コスト
で精度の高い分析ができ、かつ耐腐食性の高い表面プラ
ズモン共鳴センサチップを提供することができる。ま
た、これを用いた試料の分析方法によれば、精度の高い
分析ができ、多点同時測定の場合にもばらつきのない均
一なSPR曲線を得ることができる。
As described above, according to the present invention, it is possible to provide a surface plasmon resonance sensor chip capable of performing highly accurate analysis at low cost and having high corrosion resistance. Further, according to the sample analysis method using this, it is possible to perform highly accurate analysis, and it is possible to obtain a uniform SPR curve without variations even in the case of multipoint simultaneous measurement.

【図面の簡単な説明】[Brief description of drawings]

【図1】 表面プラズモン共鳴装置により測定される共
鳴曲線の模式図
FIG. 1 is a schematic diagram of a resonance curve measured by a surface plasmon resonance device.

───────────────────────────────────────────────────── フロントページの続き Fターム(参考) 2G059 AA01 AA05 BB12 CC16 EE02 FF11 GG01 HH01 HH06 JJ05 JJ12 KK01    ─────────────────────────────────────────────────── ─── Continued front page    F term (reference) 2G059 AA01 AA05 BB12 CC16 EE02                       FF11 GG01 HH01 HH06 JJ05                       JJ12 KK01

Claims (7)

【特許請求の範囲】[Claims] 【請求項1】 試料と接するセンサ面の近傍に、光学プ
リズム又は回折格子と金属層とが設けられて、光の照射
により上記金属層の表面に誘起される表面プラズモン波
と上記光学プリズム又は回折格子の作用により生じるエ
バネッセント波との共鳴現象が生じうる共鳴領域が上記
センサ面に形成された表面プラズモン共鳴センサチップ
であって、 該チップは、樹脂基板上に該金属層が形成されてなり、
該金属層がAgを95重量%以上99.7重量%以下含
み、Ag以外の貴金属元素を0.3重量%以上5重量%
以下含むことを特徴とする、表面プラズモン共鳴センサ
チップ。
1. An optical prism or a diffraction grating and a metal layer are provided in the vicinity of a sensor surface in contact with a sample, and a surface plasmon wave induced on the surface of the metal layer by irradiation of light and the optical prism or diffraction. A surface plasmon resonance sensor chip in which a resonance region in which a resonance phenomenon with an evanescent wave caused by the action of a lattice can occur is formed on the sensor surface, wherein the chip is formed by forming the metal layer on a resin substrate,
The metal layer contains Ag in an amount of 95 wt% or more and 99.7 wt% or less, and a noble metal element other than Ag in an amount of 0.3 wt% or more and 5 wt% or less.
A surface plasmon resonance sensor chip comprising:
【請求項2】 該貴金属元素がAu、Pt及びPdのい
ずれかである、請求項1に記載の表面プラズモン共鳴セ
ンサチップ。
2. The surface plasmon resonance sensor chip according to claim 1, wherein the noble metal element is any one of Au, Pt and Pd.
【請求項3】 該チップは、回折格子が形成された樹脂
基板上に該金属層が形成されてなり、光の照射により該
金属層の表面に誘起される表面プラズモン波と該回折格
子の作用により生じるエバネッセント波との共鳴現象が
生じうる共鳴領域が該センサ面に形成されてなる、請求
項1または2かに記載の表面プラズモン共鳴センサチッ
プ。
3. The chip has the metal layer formed on a resin substrate on which a diffraction grating is formed, and the action of the surface plasmon wave induced on the surface of the metal layer by light irradiation and the action of the diffraction grating. The surface plasmon resonance sensor chip according to claim 1 or 2, wherein a resonance region in which a resonance phenomenon with an evanescent wave caused by is generated is formed on the sensor surface.
【請求項4】 該基板が熱可塑性樹脂からなる請求項1
乃至3のいずれかに記載の表面プラズモン共鳴センサチ
ップ。
4. The substrate according to claim 1, which is made of a thermoplastic resin.
4. A surface plasmon resonance sensor chip according to any one of 3 to 3.
【請求項5】 請求項1乃至4の何れかの項に記載の表
面プラズモン共鳴センサチップを用いて試料の定量的及
び/又は定性的な分析を行うための分析方法であって、 上記センサ面に上記試料を接触させるステップと、 上記共鳴領域を照らすように照射光を照射するステップ
と、 上記表面プラズモン共鳴センサチップからの反射光を検
出するステップと、 検出した反射光の強度に基づき試料の定量的及び/又は
定性的な分析を行うステップとを備えたことを特徴とす
る、分析方法。
5. An analysis method for quantitatively and / or qualitatively analyzing a sample using the surface plasmon resonance sensor chip according to claim 1. The step of bringing the sample into contact with the sample, the step of irradiating the sample with irradiation light so as to illuminate the resonance region, the step of detecting the reflected light from the surface plasmon resonance sensor chip, and the step of measuring the sample based on the intensity of the detected reflected light. And a step of performing a quantitative and / or qualitative analysis.
【請求項6】 請求項5記載の分析方法であって、 上記チップは複数の共鳴領域が形成されてなり、 上記センサ面に上記試料を接触させるステップと、 上記複数の共鳴領域の全体を照らすように照射光を照射
するステップと、 上記表面プラズモン共鳴センサチップからの反射光を検
出するステップと、 検出した反射光から各共鳴領域からの反射光を抽出する
ステップと、 抽出した各共鳴領域からの反射光の強度に基づき試料の
定量的及び/又は定性的な分析を行うステップとを備え
たことを特徴とする、分析方法。
6. The analysis method according to claim 5, wherein the chip is formed with a plurality of resonance regions, the step of bringing the sample into contact with the sensor surface, and illuminating the whole of the plurality of resonance regions. Irradiating light as described above, detecting reflected light from the surface plasmon resonance sensor chip, extracting reflected light from each resonance region from the detected reflected light, and extracting from each resonance region And a step of quantitatively and / or qualitatively analyzing the sample based on the intensity of the reflected light.
【請求項7】 請求項5または6に記載の分析方法であ
って、 上記共鳴領域を覆うように上記試料中の検出種と特異的
に結合する結合物質を上記センサ面に固定化するステッ
プと、 上記センサ面に上記試料を接触させるステップと、 上記共鳴領域を照らすように照射光を照射するステップ
と、 上記表面プラズモン共鳴センサチップからの反射光を検
出するステップと、 検出した反射光から各共鳴領域からの反射光を抽出する
ステップと、 抽出した各共鳴領域からの反射光の強度に基づき試料の
定量的及び/又は定性的な分析を行うステップとを備え
たことを特徴とする、分析方法。
7. The analysis method according to claim 5, wherein a binding substance that specifically binds to the detection species in the sample is immobilized on the sensor surface so as to cover the resonance region. , Contacting the sample with the sensor surface, irradiating irradiation light so as to illuminate the resonance region, detecting reflected light from the surface plasmon resonance sensor chip, and detecting reflected light An analysis comprising: a step of extracting reflected light from the resonance region; and a step of performing a quantitative and / or qualitative analysis of the sample based on the intensity of the reflected light extracted from each resonance region. Method.
JP2002050937A 2002-02-27 2002-02-27 Surface plasmon resonance sensor chip and sample analysis method using the same Expired - Fee Related JP3858726B2 (en)

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009145189A (en) * 2007-12-13 2009-07-02 Fujifilm Corp Biosensor
WO2011155435A1 (en) * 2010-06-07 2011-12-15 コニカミノルタホールディングス株式会社 Near field-enhanced fluorescence sensor chip
JPWO2012070175A1 (en) * 2010-11-26 2014-05-19 コニカミノルタ株式会社 Prism portion of analysis chip, analysis chip including this prism portion, and method of manufacturing prism portion of analysis chip
CN106525769A (en) * 2016-11-08 2017-03-22 上纬(上海)精细化工有限公司 Method of detecting mixing ratio of composite material matrix resin

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009145189A (en) * 2007-12-13 2009-07-02 Fujifilm Corp Biosensor
WO2011155435A1 (en) * 2010-06-07 2011-12-15 コニカミノルタホールディングス株式会社 Near field-enhanced fluorescence sensor chip
JPWO2011155435A1 (en) * 2010-06-07 2013-08-01 コニカミノルタ株式会社 Near-field enhanced fluorescence sensor chip
JP5958339B2 (en) * 2010-06-07 2016-07-27 コニカミノルタ株式会社 Near-field enhanced fluorescence sensor chip
JPWO2012070175A1 (en) * 2010-11-26 2014-05-19 コニカミノルタ株式会社 Prism portion of analysis chip, analysis chip including this prism portion, and method of manufacturing prism portion of analysis chip
CN106525769A (en) * 2016-11-08 2017-03-22 上纬(上海)精细化工有限公司 Method of detecting mixing ratio of composite material matrix resin

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