JP3881923B2 - Surface plasmon resonance sensor - Google Patents
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- JP3881923B2 JP3881923B2 JP2002094250A JP2002094250A JP3881923B2 JP 3881923 B2 JP3881923 B2 JP 3881923B2 JP 2002094250 A JP2002094250 A JP 2002094250A JP 2002094250 A JP2002094250 A JP 2002094250A JP 3881923 B2 JP3881923 B2 JP 3881923B2
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Description
【０００１】
【発明の属する技術分野】
本発明は、表面プラズモン共鳴センサの改良に関する。
【０００２】
【従来の技術】
表面プラズモン共鳴センサは、プリズムの裏面に金属薄膜を形成し、その金属薄膜の表面に試料液を直接接触させ、前記プリズムに前記金属薄膜と試料液との界面で全反射する条件で光を入射し、それにより生じる反射光や透過光の屈曲率や吸収率を光検出手段で検出して、その検出結果に基づいて試料液内の物質状態を分析するセンサとして知られている。
【０００３】
【発明が解決しようとする課題】
上記したように表面プラズモン共鳴センサでは、プリズム裏面に形成された金属薄膜の表面に試料液を直接接触させる必要があり、その方法は大きく２種類に分けられる。
一つは、金属薄膜上に試料液を垂らしたり、金属薄膜上に設けた収容部に試料液を入れたりする、所謂、金属薄膜上に直接試料液を供給する方法であり、
もう一つは、金属薄膜上を通過する試料液供給路を形成し、少なくとも金属薄膜とは外れた位置にある試料液供給口から試料液を注入又は吸引し、その試料液供給口から試料液を金属薄膜の上面を通るように流す方法である。
前者は、金属薄膜上に直接試料液を供給するので試料液の状態保持が簡単であり、また、不純物も入り難いという利点があるが、この方法では、金属薄膜を外部に晒された状態にしなければならないのでセンサ自体の保存や携帯が困難であるという欠点があり、さらに、試料液の供給量を使用者自身で調整しなければならないという欠点もある。また、反応が拡散に依存するものとなっているために安定するまでに十分な時間が必要である。従って、この前者の方法は実験等には適していても、実際に医療の現場や不特定多数の人が分析を目的として用いるのには適していない。
後者は、金属薄膜とは外れた位置にある試料液供給口から試料液を注入又は吸引し、その試料液供給口から試料液を金属薄膜の上面を通るように流すように構成されているので、金属薄膜が外部に晒されることなくセンサ自体の保存が容易であり、かつ、携帯も可能になり、さらに、金属薄膜上への試料液の供給量は試料液供給通路により適当に調整されるので実用性が高い。
しかし、この後者の方法は、試料液供給口から試料液を供給し、試料液供給通路を試料液が流れていく間に、試料液の内部に気泡が生じてしまうという問題がある。試料液の内部に気泡が生じると、それにより反射率が変わってしまうので測定精度の面で大きな問題となり、センサとしては致命的な欠点になりかねない。
本発明は、上記した従来の問題点を解決し、実用性の高い試料液供給口から試料液を金属薄膜の上面を通るように流すという構成をとりながら、かつ、内部に気泡が生じて測定精度が低下することのない表面プラズモン共鳴センサを提供することを目的としている。
【０００４】
【課題を解決するための手段】
上記した目的を達成するために、本発明に係る表面プラズモン共鳴センサは、プリズムの裏面に金属薄膜を形成し、該金属薄膜の表面に試料液を直接接触させると共に、前記プリズムに前記金属薄膜と試料液との界面で全反射する条件で光を入射し、その反射光に基づいて試料液内の物質状態の分析を行うことができるように構成された表面プラズモン共鳴センサにおいて、前記金属薄膜の上面を通過し、前記金属薄膜の表面に試料液が直接接触できるように試料液を供給する試料液供給通路を設け、前記試料液供給通路内における前記金属薄膜より上流の部分に、供給されてきた試料液中の気泡をトラップする凹所を少なくとも一つ設けたことを特徴とするものである。
【０００５】
【発明の実施の形態】
以下に添付図面に示した幾つかの実施例を参照しながら本発明に係る表面プラズモン共鳴センサの実施の形態について説明していく。
図１は、本発明に係る表面プラズモン共鳴センサの概略構造図である。
図中符号１はプリズムを示しており、このプリズム１の裏面には金属薄膜２が形成されている。
前記金属薄膜２の上には、その金属薄膜２の上面を通過するように試料液供給通路３が形成されており、この試料液供給通路３の一端には試料液供給口４が形成されている。
また、図１における符号１０及び１１は、光源及び光検出装置を示しており、試料液供給口４を介して試料液を試料液供給通路３内に供給し、試料液が金属薄膜２の上面に到達した時点で、光源１０からプリズム１に前記金属薄膜２と試料液との界面で全反射する条件で光を入射し、その反射光を光検出装置１１で検出する。
図２は、前記した試料液供給通路３の拡大断面図を示している。
図面に示すように、この試料液供給通路３は、金属薄膜２よりも上流側に複数の凹所５が形成されている。
これにより、試料液供給通路３を通過する間に試料液中に含まれている気泡は全て、凹所５に捕獲されるので、金属薄膜２に到達した試料液に気泡が含まれていることはなくなる。
【０００６】
次に、試料液に気泡が含まれていることによる測定結果への影響について確認した実験結果を示す。
実験に使用した表面プラズモン共鳴センサは、BK-7のシリンドリカルレンズの表面に、厚さ50μmの金属薄膜を形成し、金属薄膜の表面に抗体としてモノクローナル抗体を固定してある。
このように構成した表面プラズモン共鳴センサにサンプルとして血清希釈サンプルを一つは気泡の混入がない状態で、もう一つは気泡を混入させた状態で試料液として導入した。図３はそれらの実験結果である。この図面から明らかなように気泡の混入した試料液の場合には測定結果に異常を示す場合が有り、正しい測定結果を得ることが出来ない場合がある。
気泡の混入があっても表面プラズモン共鳴センサ部（金属薄膜）上へ気泡が流れないように構成した本発明に係る表面プラズモン共鳴センサにおいて、試料液供給通路を、その横断面形状が、長辺の長さが2ｍｍ、短辺の長さが0.5ｍｍの長方形になるように構成すると共に、その上壁の前記金属薄膜より上流側に凹所を、深さ0.2ｍｍ、断面形状が円錐形にして試料液の流れ方向に沿って5個設け、試料液供給通路に気泡の混入した試料液を導入すると凹部で気泡がトラップされて表面プラズモン共鳴センサ部へは流れないことを確認した。
【０００７】
上記した実験結果に加え、本発明に係る表面プラズモン共鳴センサの試験管供給通路の凹部形状を、三角形になるように構成して実験を行ったが、同様に良好な結果が得られた。
また、試験管供給通路に設ける凹所の数を、１〜5個まで変えて実験を行ったが、同様に良好が得られた。
さらに、前記試料液供給通路を、その横断面の長辺の長さが０．５ｍｍ以上の長方形になるように構成した結果も同様であり、さらにまた、前記試料液供給通路を、その横断面の直径が０．５ｍｍ以上の円形になるように構成した結果も同様であった。
【０００８】
【発明の効果】
以上説明したように、本発明に係る表面プラズモン共鳴センサは、プリズムの裏面に金属薄膜を形成し、該金属薄膜の表面に試料液を直接接触させると共に、前記プリズムに前記金属薄膜と試料液との界面で全反射する条件で光を入射し、その反射光に基づいて試料液内の物質状態の分析を行うことができるように構成された表面プラズモン共鳴センサにおいて、前記金属薄膜の上面を通過し、前記金属薄膜の表面に試料液が直接接触できるように試料液を供給する試料液供給通路を設け、前記試料液供給通路内における前記金属薄膜より上流の部分に、供給されてきた試料液中の気泡をトラップする凹所を少なくとも一つ設けているので、試料液供給通路に試料液を供給する時や試料液供給通路内を試料液が流れる間に試料液内に気泡が生じてしまったとしても、試料液内に生じた気泡は、金属薄膜に達する前に前記凹所で捕獲されるので金属薄膜上に達した試料液に気泡が残り測定精度を低下させることはないという効果を奏する。
【図面の簡単な説明】
【図１】 本発明に係る表面プラズモン共鳴センサの概略構造図
【図２】 試料液供給通路３の拡大断面図
【図３】 気泡入り血液希釈サンプルと気泡なし血液希釈サンプルを用いた測定結果を示すグラフである。
【符号の説明】
１ プリズム
２ 金属薄膜
３ 試料液供給通路
４ 試料液供給口
５ 凹所
１０ 光源
１１ 光検出装置[0001]
BACKGROUND OF THE INVENTION
The present invention relates to an improvement of a surface plasmon resonance sensor.
[0002]
[Prior art]
A surface plasmon resonance sensor forms a metal thin film on the back surface of a prism, makes a sample solution directly contact the surface of the metal thin film, and makes light incident on the prism under the condition of total reflection at the interface between the metal thin film and the sample solution. In addition, it is known as a sensor that detects the bending rate and absorption rate of reflected light and transmitted light generated thereby by a light detection means and analyzes the substance state in the sample liquid based on the detection result.
[0003]
[Problems to be solved by the invention]
As described above, in the surface plasmon resonance sensor, it is necessary to bring the sample solution into direct contact with the surface of the metal thin film formed on the back surface of the prism, and the method is roughly divided into two types.
One is a method of supplying the sample solution directly onto the metal thin film, such as suspending the sample solution on the metal thin film, or putting the sample solution into a container provided on the metal thin film,
The other is to form a sample liquid supply path that passes over the metal thin film, and injects or sucks the sample liquid from the sample liquid supply port located at least away from the metal thin film. Is made to flow through the upper surface of the metal thin film.
The former has the advantage that the sample liquid is supplied directly onto the metal thin film, so that the state of the sample liquid can be easily maintained and impurities are less likely to enter. However, in this method, the metal thin film is exposed to the outside. Therefore, there is a drawback that it is difficult to store and carry the sensor itself, and there is also a disadvantage that the supply amount of the sample solution must be adjusted by the user. In addition, since the reaction depends on diffusion, a sufficient time is required to stabilize the reaction. Therefore, although the former method is suitable for experiments and the like, it is not actually suitable for use in the medical field or an unspecified number of people for the purpose of analysis.
The latter is configured such that the sample liquid is injected or sucked from the sample liquid supply port located away from the metal thin film, and the sample liquid flows through the upper surface of the metal thin film from the sample liquid supply port. In addition, the sensor itself can be easily stored without being exposed to the metal thin film, and the sensor can be portable. Further, the amount of the sample liquid supplied onto the metal thin film is appropriately adjusted by the sample liquid supply passage. So practicality is high.
However, this latter method has a problem that bubbles are generated inside the sample solution while the sample solution is supplied from the sample solution supply port and the sample solution flows through the sample solution supply passage. If bubbles are generated inside the sample liquid, the reflectance changes accordingly, which causes a serious problem in terms of measurement accuracy, which may be a fatal defect for the sensor.
The present invention solves the above-described conventional problems, and measures the measurement by causing a sample solution to flow from the highly practical sample solution supply port so as to pass through the upper surface of the metal thin film. An object of the present invention is to provide a surface plasmon resonance sensor in which accuracy does not decrease.
[0004]
[Means for Solving the Problems]
In order to achieve the above-described object, a surface plasmon resonance sensor according to the present invention forms a metal thin film on the back surface of a prism, directly contacts a sample solution on the surface of the metal thin film, and the metal thin film and the prism. incident light under conditions of total reflection at the interface with the sample solution, the surface plasmon resonance sensor which is configured to be able to analyze the state of matter in the sample solution on the basis of the reflected light of the metal thin film A sample solution supply passage is provided for supplying the sample solution so that the sample solution can directly contact the surface of the metal thin film through the upper surface, and the sample solution supply passage is supplied to a portion upstream of the metal thin film in the sample solution supply passage . Further, at least one recess for trapping bubbles in the sample liquid is provided.
[0005]
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of a surface plasmon resonance sensor according to the present invention will be described below with reference to some embodiments shown in the accompanying drawings.
FIG. 1 is a schematic structural diagram of a surface plasmon resonance sensor according to the present invention.
In the figure,
A sample
FIG. 2 is an enlarged cross-sectional view of the sample
As shown in the drawing, the sample
As a result, all the bubbles contained in the sample solution while passing through the sample
[0006]
Next, the experimental result confirmed about the influence on the measurement result by the bubble being contained in a sample solution is shown.
In the surface plasmon resonance sensor used in the experiment, a metal thin film having a thickness of 50 μm is formed on the surface of a cylindrical lens of BK-7, and a monoclonal antibody is immobilized as an antibody on the surface of the metal thin film.
A serum-diluted sample was introduced as a sample solution into the surface plasmon resonance sensor configured as described above as a sample solution in a state where one was not mixed with bubbles and the other was mixed with bubbles. FIG. 3 shows the results of these experiments. As is clear from this drawing, in the case of a sample solution mixed with bubbles, there are cases where the measurement result shows an abnormality, and the correct measurement result may not be obtained.
In the surface plasmon resonance sensor according to the present invention configured so that bubbles do not flow onto the surface plasmon resonance sensor portion (metal thin film) even if bubbles are mixed, the cross-sectional shape of the sample liquid supply passage has a long side. It is configured to be a rectangle with a length of 2 mm and a short side length of 0.5 mm, and a recess is formed on the upper wall upstream of the metal thin film with a depth of 0.2 mm and a cross-sectional shape of a conical shape. It was confirmed that five bubbles were provided along the flow direction of the sample liquid, and when the sample liquid mixed with bubbles was introduced into the sample liquid supply passage, the bubbles were trapped in the recess and did not flow to the surface plasmon resonance sensor.
[0007]
In addition to the experimental results described above, the experiment was performed with the concave shape of the test tube supply passage of the surface plasmon resonance sensor according to the present invention configured to be a triangle, and good results were similarly obtained.
Moreover, although the number of the recesses provided in the test tube supply passage was changed from 1 to 5, an experiment was performed, and similarly good results were obtained.
Further, the result of configuring the sample solution supply passage so that the long side of the transverse section is a rectangle having a length of 0.5 mm or more is the same, and further, the sample solution supply passage is formed of the transverse section thereof. The result was also the same in the case where the diameter was 0.5 mm or more.
[0008]
【The invention's effect】
As described above, the surface plasmon resonance sensor according to the present invention has a metal thin film formed on the back surface of the prism, the sample liquid is brought into direct contact with the surface of the metal thin film, and the metal thin film and the sample liquid are placed on the prism. In a surface plasmon resonance sensor configured to allow light to be incident under the condition of total reflection at the interface and to analyze the substance state in the sample liquid based on the reflected light, it passes through the upper surface of the metal thin film. And providing a sample solution supply passage for supplying the sample solution so that the sample solution can be brought into direct contact with the surface of the metal thin film, and supplying the sample solution to a portion upstream of the metal thin film in the sample solution supply passage . Since there is at least one recess for trapping bubbles inside, bubbles are generated in the sample solution when the sample solution is supplied to the sample solution supply passage or while the sample solution flows in the sample solution supply passage. Even if it is, bubbles generated in the sample liquid are trapped in the recess before reaching the metal thin film, so that bubbles remain in the sample liquid reaching the metal thin film and the measurement accuracy is not reduced. There is an effect.
[Brief description of the drawings]
FIG. 1 is a schematic structural diagram of a surface plasmon resonance sensor according to the present invention. FIG. 2 is an enlarged sectional view of a sample
[Explanation of symbols]
DESCRIPTION OF
Claims (3)
前記プリズムに前記金属薄膜と試料液との界面で全反射する条件で光を入射し、その反射光に基づいて試料液内の物質状態の分析を行うことができるように構成された表面プラズモン共鳴センサにおいて、
前記金属薄膜の上面を通過し、前記金属薄膜の表面に試料液が直接接触できるように試料液を供給する試料液供給通路を設け、
前記試料液供給通路内における前記金属薄膜より上流の部分に、供給されてきた試料液中の気泡をトラップする凹所を少なくとも一つ設けた
ことを特徴とする表面プラズモン共鳴センサ。A metal thin film is formed on the back surface of the prism, and the sample liquid is brought into direct contact with the surface of the metal thin film.
Surface plasmon resonance is configured such that light is incident on the prism under the condition of total reflection at the interface between the metal thin film and the sample liquid, and the state of the substance in the sample liquid can be analyzed based on the reflected light. In the sensor
Providing a sample liquid supply passage that passes through the upper surface of the metal thin film and supplies the sample liquid so that the sample liquid can directly contact the surface of the metal thin film;
The surface plasmon resonance sensor characterized in that at least one recess for trapping bubbles in the supplied sample liquid is provided in a portion upstream of the metal thin film in the sample liquid supply passage.
ことを特徴とする請求項１に記載の表面プラズモン共鳴センサ。2. The surface plasmon resonance sensor according to claim 1, wherein the sample liquid supply passage is configured to be a rectangle having a long side of a cross section of 0.5 mm or more.
ことを特徴とする請求項１に記載の表面プラズモン共鳴センサ。2. The surface plasmon resonance sensor according to claim 1, wherein the sample liquid supply passage is configured to have a circular shape with a cross-sectional diameter of 0.5 mm or more.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002094250A JP3881923B2 (en) | 2002-03-29 | 2002-03-29 | Surface plasmon resonance sensor |
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|---|---|---|---|
| JP2002094250A JP3881923B2 (en) | 2002-03-29 | 2002-03-29 | Surface plasmon resonance sensor |
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| JP2003294613A JP2003294613A (en) | 2003-10-15 |
| JP3881923B2 true JP3881923B2 (en) | 2007-02-14 |
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| CN102735653B (en) * | 2011-04-14 | 2014-07-16 | 国家纳米科学中心 | Biological detection method by utilization of surface plasma resonance biosensor |
| JP5910772B2 (en) * | 2015-03-02 | 2016-04-27 | コニカミノルタ株式会社 | Measuring device and measuring method |
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