JP5292034B2 - Biosensor device - Google Patents

Biosensor device Download PDF

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JP5292034B2
JP5292034B2 JP2008240799A JP2008240799A JP5292034B2 JP 5292034 B2 JP5292034 B2 JP 5292034B2 JP 2008240799 A JP2008240799 A JP 2008240799A JP 2008240799 A JP2008240799 A JP 2008240799A JP 5292034 B2 JP5292034 B2 JP 5292034B2
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pump
solution
switching valve
cell
sample solution
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JP2010071851A (en
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俊 田中
良太 嶽
友海 水谷
敦 伊藤
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Ulvac Inc
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Ulvac Inc
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a flow-through cell type biosensor device which sucks at least two kinds of solutions by a pump, by switching a selector valve and promptly and accurately measuring, without having a gas phase penetrate a passage, when switching the solutions. <P>SOLUTION: The flow-through cell type biosensor device is provided with the selector valve on the suction side of the pump for supplying a cell with at least two kinds of solutions by switching the valve. The selector valve is configured so as to hold a second solution which is not sucked into the pump in the selector valve in an airtight state, when the pump sucks a first solution. <P>COPYRIGHT: (C)2010,JPO&amp;INPIT

Description

本発明は、溶液中の物質の検知又は質量等の測定に用いるためのフロースルーセル式のバイオセンサ装置に関する。   The present invention relates to a flow-through cell type biosensor device for use in detecting a substance in a solution or measuring a mass or the like.

従来、フロースルーセル式のバイオセンサ装置は、測定対象である試料溶液を測定環境溶液(以下、移動相溶液とする。)を満たした流路に注入乃至流動させることにより測定を行うようにしている。この際、移動相溶液を主ポンプにより流動させ、その下流にサンプルインジェクタを配置するようにしている(例えば、非特許文献1参照)。
上記構成とすることにより、ポンプ内を試料により汚染することなく計測が可能となる。
しかしながら、長時間の測定を要する吸着反応等の測定の場合には、流速を極端に遅くするか、或いは、大量の試料溶液を流通させるために巨大なサンプルループを装着する必要がある。前者の場合、結合反応に対して試料供給量が追いつかなくなる可能性があり、後者の場合には、試料溶液が多量に必要となるだけでなく、サンプルループ自体の寸法が大きくなり、試料溶液の温度調整のためにも装置の小型化ができないという問題があった。
このような問題を解決するために、フロースルーセル式の廃液を、試料溶液を収容するための溶液に戻すことが提案されている(特許文献1参照)。
Conventionally, a flow-through cell type biosensor device performs measurement by injecting or flowing a sample solution to be measured into a flow path filled with a measurement environment solution (hereinafter referred to as a mobile phase solution). Yes. At this time, the mobile phase solution is caused to flow by the main pump, and a sample injector is arranged downstream thereof (see, for example, Non-Patent Document 1).
With the above configuration, measurement can be performed without contaminating the inside of the pump with the sample.
However, in the case of measurement such as an adsorption reaction that requires long-time measurement, it is necessary to extremely slow the flow rate or to attach a huge sample loop to distribute a large amount of sample solution. In the former case, there is a possibility that the sample supply amount cannot catch up with the binding reaction. In the latter case, not only a large amount of sample solution is required, but also the size of the sample loop itself increases, There was also a problem that the device could not be downsized for temperature adjustment.
In order to solve such a problem, it has been proposed to return a flow-through cell type waste liquid to a solution for containing a sample solution (see Patent Document 1).

しかしながら、特許文献1において提案されている発明によっても、セルに溶液を送るポンプにおいて、ポンプが複数の溶液を切り換えて吸入を行う場合には、切換直後の吸入時に配管内に空気を吸引するために、正確な測定ができないという問題があった。
この問題に対して、測定前に、ポンプにより、移動相溶液や試料溶液をある程度吸入し、その後、測定を開始するという方法を採用することもできるが、移動相溶液を予め吸入する場合には、移動相溶液が安定して流路内を移動するまで待つ必要があり、試料溶液を予め吸入する場合には、セル内に試料溶液が達してしまうことがあるため、測定の正確さが得られないという問題があった。特に、検知器が、QCMを利用する場合には、結合や解離反応が進行してしまうために、測定自体が有効でなくなるという問題があった。
However, even with the invention proposed in Patent Document 1, in a pump that sends a solution to a cell, when the pump switches a plurality of solutions and performs suction, air is sucked into the pipe at the time of suction immediately after switching. However, there is a problem that accurate measurement cannot be performed.
To solve this problem, it is possible to adopt a method in which a mobile phase solution or sample solution is inhaled to some extent by a pump before measurement, and then the measurement is started. Therefore, it is necessary to wait until the mobile phase solution stably moves in the flow path. When the sample solution is sucked in advance, the sample solution may reach the cell, so that the measurement accuracy can be obtained. There was a problem that it was not possible. In particular, when the detector uses QCM, there is a problem that the measurement itself becomes ineffective because the binding and dissociation reactions proceed.

「JIS K-0124 2002,高速液体クロマトグラフィー通則 日本工業規格」"JIS K-0124 2002, General Rules for High Performance Liquid Chromatography, Japanese Industrial Standards" 特開平11−183479号公報(第8頁及び第1図)Japanese Patent Laid-Open No. 11-183479 (page 8 and FIG. 1)

そこで、本発明は、少なくとも2種類の溶液を切換弁により切り換えてポンプにより吸入するフロースルーセル式のバイオセンサ装置において、切換時に気相が流路内に入り込むことがなく、迅速且つ正確な測定が可能なバイオセンサ装置を提供することを目的とする。   Therefore, the present invention is a flow-through cell type biosensor device that switches at least two kinds of solutions with a switching valve and sucks them with a pump. It is an object of the present invention to provide a biosensor device capable of performing

上記課題を解決するために、本発明者等は鋭意検討の結果下記の通り解決手段を見出した。
即ち、本発明のバイオセンサ装置は、請求項1に記載の通り、少なくとも2種類の溶液を切り換えてセルに供給するための切換弁を、ポンプの吸入側に備えたフロースルーセル型のバイオセンサ装置であって、前記切換弁は、前記ポンプが一の溶液を吸入している際に、前記ポンプに吸入されていない他の溶液を前記切換弁内に気密状態で保持できるように構成し、前記切換弁は、前記ポンプが前記一の溶液を吸入している際に前記一の溶液を収容する容器のみが前記ポンプと接続され、前記ポンプが前記他の溶液を吸入している際に前記他の溶液を収容する容器のみが前記ポンプと接続されるように構成し、前記切換弁は、前記ポンプに吸入されていない溶液を前記切換弁内に気密状態で保持するために、該溶液側と気密に接続された吸入手段を備えたことを特徴とする。
また、請求項2に記載の本発明は、請求項1に記載のバイオセンサ装置において、前記セル内の検出器を、水晶振動子としたことを特徴とする。
In order to solve the above-mentioned problems, the present inventors have found a solving means as follows as a result of intensive studies.
That is, the biosensor device of the present invention is a flow-through cell type biosensor having a switching valve for switching at least two types of solutions to supply to a cell, as described in claim 1. The switching valve is configured such that when the pump is sucking one solution, the other valve not sucked into the pump can be held in the switching valve in an airtight state. The switching valve is connected to the pump only when the pump is sucking the one solution, and the pump is sucking the other solution. Only a container for storing another solution is connected to the pump, and the switching valve is arranged on the solution side in order to keep the solution not sucked into the pump in an airtight state in the switching valve. And airtightly connected inhalation Characterized by comprising a stage.
The invention according to claim 2 is the biosensor device according to claim 1 , wherein the detector in the cell is a crystal resonator.

本発明によれば、切換弁を切り換える際に気相が流路内に生じることがないため正確な測定が可能となる。また、試料溶液をタンクに戻す構成とした場合であっても、流路内で気泡を生じることがない。更に、QCMにより測定を行う場合には、計測値を安定させることが可能となる。   According to the present invention, when the switching valve is switched, no gas phase is generated in the flow path, so that accurate measurement is possible. Moreover, even if it is a case where it is the structure which returns a sample solution to a tank, a bubble is not produced in a flow path. Furthermore, when the measurement is performed by the QCM, the measurement value can be stabilized.

次に、本発明の実施の形態につき、図面を参照して説明する。
図1は、本発明のバイオセンサ装置の一実施の形態を示すものであり、切換弁として4方切換弁を使用したものである。図中、試料溶液及び移動相溶液はそれぞれ容器1,2内に収容され、容器1は切換弁3のポート3aに接続され、容器2は同ポート3dに接続されている。また、ポート3cは、図示しないが、ポンプ及びその下流に続くセルへと接続され、ポート3bは、吸入手段4に接続される。切換弁3は、同図(a)で示す状態では、ポート3aと3bとを接続し、且つ、ポート3cと3dとを接続する。また、同図(b)で示す状態では、ポート3aと3cとを接続し、且つ、ポート3bと3dとを接続する。
そして、ポンプにより移動相溶液が吸入されている状態(同図(a))において、吸入手段4により試料溶液が切換弁3内(少なくともポート3aと3bの間)に吸入され気密状態にて保持し、ポンプにより試料溶液が吸入されている状態(同図(b))において、ポンプに保持された試料溶液が送出されることになる。
上記構成によれば、測定前に同図(a)のように移動相溶液をセル内に供給しておき、その間に、切換弁内には、試料溶液が気密状態にて保持されることになるので、切換弁を同図(b)の状態に切り換えても、気相が流路内に入ることがなく、セル内の検出器の測定に影響を与えることがない。
Next, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 shows an embodiment of a biosensor device of the present invention, in which a four-way switching valve is used as a switching valve. In the figure, the sample solution and the mobile phase solution are stored in containers 1 and 2, respectively, container 1 is connected to port 3a of switching valve 3, and container 2 is connected to port 3d. Further, although not shown, the port 3c is connected to a pump and a cell downstream thereof, and the port 3b is connected to the suction means 4. The switching valve 3 connects the ports 3a and 3b and connects the ports 3c and 3d in the state shown in FIG. In the state shown in FIG. 5B, the ports 3a and 3c are connected, and the ports 3b and 3d are connected.
In the state where the mobile phase solution is sucked by the pump ((a) in the figure), the sample solution is sucked into the switching valve 3 (at least between the ports 3a and 3b) by the suction means 4 and kept in an airtight state. In the state where the sample solution is inhaled by the pump (FIG. 5B), the sample solution held by the pump is sent out.
According to the above configuration, the mobile phase solution is supplied into the cell before the measurement as shown in FIG. 5A, and the sample solution is kept in an airtight state in the switching valve during that time. Therefore, even if the switching valve is switched to the state shown in FIG. 5B, the gas phase does not enter the flow path, and the measurement of the detector in the cell is not affected.

図2は、本発明の第2の実施の形態を示すもので、図1の4方切換弁3の代わりに、6方切換弁5を採用したものである。図中、試料溶液及び移動相溶液はそれぞれ容器1,2内に収容され、容器1は切換弁5のポート5aに接続され、容器2は同ポート5dに接続されている。また、ポート5cは、図示しないが、ポンプ及びその下流に続くセルへと接続される。ポート5bは、吸入手段4に接続される。切換弁5は、同図(a)で示す状態では、ポート5aと5bとを接続し、且つ、ポート5cと5dとを接続する。また、同図(b)で示す状態では、ポート5aと5cとを接続し、且つ、ポート5bと5dとを接続する。尚、本実施の形態では、ポート5aとポート5bとの間には、ポート5e及び5bで示されるループ接続がされており、このループ内において、他の試料溶液を入れることができるようになっている。
そして、ポンプにより移動相溶液が吸入されている状態(同図(a))において、吸入手段4により試料溶液が切換弁5内(少なくともポート5aと5bの間)に吸入され気密状態にて保持される。ポンプにより試料溶液が吸入されている状態(同図(b))において、ポンプに保持された試料溶液が送出されることになる。
上記構成によれば、測定前に同図(a)のように移動相溶液をセル内に供給しておき、その間に、切換弁5内には、試料溶液が気密状態にて保持されることになるので、切換弁を同図(b)の状態に切り換えても、気相が流路内に入ることがななく、セル内の検出器の測定に影響を与えることがない。
FIG. 2 shows a second embodiment of the present invention, which employs a six-way switching valve 5 instead of the four-way switching valve 3 of FIG. In the figure, the sample solution and the mobile phase solution are stored in containers 1 and 2, respectively, container 1 is connected to port 5a of switching valve 5, and container 2 is connected to port 5d. Further, although not shown, the port 5c is connected to a pump and a cell subsequent to the pump. The port 5 b is connected to the suction means 4. The switching valve 5 connects the ports 5a and 5b and connects the ports 5c and 5d in the state shown in FIG. Further, in the state shown in FIG. 5B, the ports 5a and 5c are connected, and the ports 5b and 5d are connected. In the present embodiment, a loop connection indicated by the ports 5e and 5b is provided between the port 5a and the port 5b, and other sample solutions can be put in the loop. ing.
Then, in the state where the mobile phase solution is sucked by the pump ((a) in the figure), the sample solution is sucked into the switching valve 5 (at least between the ports 5a and 5b) by the suction means 4 and kept in an airtight state. Is done. In a state where the sample solution is inhaled by the pump ((b) in the same figure), the sample solution held by the pump is sent out.
According to the above configuration, the mobile phase solution is supplied into the cell before the measurement as shown in FIG. 5A, and the sample solution is held in the switching valve 5 in an airtight state during that time. Therefore, even if the switching valve is switched to the state shown in FIG. 5B, the gas phase does not enter the flow path, and the measurement of the detector in the cell is not affected.

次に、図1の装置において、セル内に検出器として27MHzの水晶振動子を配置し、切換弁3を移動相溶液から試料用溶液へと切り換えた際の発振周波数の測定を行い、その結果を図3のグラフの実線として示す。上記した通り、試料溶液を切換弁3内に気密状態にて保持していたため、切り換えの前後において水晶振動子の発振周波数の変化はなかった。
比較のために、移動相溶液の次に試料溶液をセルに連続して供給する、即ち、移動相溶液をセルに供給している際に、試料溶液を切換弁3内に保持させなかった例を、同図の破線として示す。この破線で示されたものでは、切り替えの際に水晶振動子の発振周波数の変化があり、これは、切換弁3内の気泡によるものと考えられる。
従って、本実施の形態のバイオセンサ装置による測定の場合には、切換弁3の切換時に発振周波数の変化が見られることなく安定した測定が可能となることがわかった。
Next, in the apparatus of FIG. 1, a 27 MHz crystal resonator is arranged as a detector in the cell, and the oscillation frequency when the switching valve 3 is switched from the mobile phase solution to the sample solution is measured. Is shown as a solid line in the graph of FIG. As described above, since the sample solution was kept airtight in the switching valve 3, there was no change in the oscillation frequency of the crystal unit before and after switching.
For comparison, an example in which the sample solution is continuously supplied to the cell next to the mobile phase solution, that is, the sample solution is not held in the switching valve 3 when the mobile phase solution is supplied to the cell. Is shown as a broken line in FIG. In the case indicated by the broken line, there is a change in the oscillation frequency of the crystal resonator at the time of switching, which is considered to be due to bubbles in the switching valve 3.
Therefore, in the case of measurement by the biosensor device of the present embodiment, it has been found that stable measurement can be performed without a change in oscillation frequency when the switching valve 3 is switched.

図4は、本発明の第3の実施の形態を示すもので、第1の実施の形態の装置の構成に対して、切換弁3の下流側に、ポンプ6とセル7を順に接続し、セル7の下流側に、他の切換弁8を配置し、この切換弁8のポート8a及び8b間で切り換えることにより、試料溶液の容器1とタンク9にそれぞれ切り換えできるように構成されている。
そして、試料溶液が収容された容器1とポンプ6とを接続する流路の内径を0.5mmとし、他の流路の内径を1mmとする。
上記構成において、測定開始前に、まず、切換弁3を移動相溶液の入った容器2に接続し、ポンプ6により移動相溶液をセル7、切換弁8を介して、タンク9へと送る。その際に、切換弁3内に吸入手段4により試料溶液が入った容器1から気密状態で試料溶液を保持するようにしておく。次に、切換弁3を試料溶液の入った容器1に切り替えて、試料溶液が収容された容器1から試料溶液をポンプ6により吸入して、セル7により計測を行い、試料溶液を切換弁8を切り換えて、容器1に戻すようにする。
上記操作の中で、試料溶液は、切換弁8から容器1までの間に大気と接触して、試料溶液には、気体が溶存することになる。
本実施の形態では、この試料溶液が、再度、ポンプ6により吸入されても、ポンプ6の吸入側の流路の内径が0.5mm以上としているので、ポンプ6の吸入側の流路内に気泡が生じることがない。
FIG. 4 shows a third embodiment of the present invention, in which the pump 6 and the cell 7 are sequentially connected to the downstream side of the switching valve 3 with respect to the configuration of the apparatus of the first embodiment. The other switching valve 8 is disposed downstream of the cell 7 and is switched between the ports 8a and 8b of the switching valve 8 so that the sample solution can be switched to the container 1 and the tank 9 respectively.
And the internal diameter of the flow path which connects the container 1 in which the sample solution was accommodated, and the pump 6 is 0.5 mm, and the internal diameter of another flow path is 1 mm.
In the above configuration, before starting the measurement, first, the switching valve 3 is connected to the container 2 containing the mobile phase solution, and the mobile phase solution is sent to the tank 9 via the cell 7 and the switching valve 8 by the pump 6. At that time, the sample solution is kept in an airtight state from the container 1 containing the sample solution by the suction means 4 in the switching valve 3. Next, the switching valve 3 is switched to the container 1 containing the sample solution, the sample solution is sucked from the container 1 containing the sample solution by the pump 6, measurement is performed by the cell 7, and the sample solution is switched to the switching valve 8. To switch back to the container 1.
In the above operation, the sample solution comes into contact with the atmosphere between the switching valve 8 and the container 1, and gas is dissolved in the sample solution.
In the present embodiment, even if the sample solution is sucked again by the pump 6, the inner diameter of the flow path on the suction side of the pump 6 is 0.5 mm or more. No bubbles are generated.

次に、図4の装置のセル内に検出器として27MHzの水晶振動子を配置し、測定を行った結果を、図5のグラフの実線として示す。尚、ポンプ6の吸入速度(流量)は、200μl/minとした。このグラフから、本実施の形態の装置では、気泡が生じることがなく、水晶振動子の発振周波数の変化がなく、安定した測定ができることがわかった。
比較のために、容器1からポンプ6までの流路内径を0.25mmとし、他の流路内径を1mmとして、同様の測定を行った結果を図5のグラフの破線として示す。このグラフから、ポンプ6から試料溶液を吸入する際に気泡が生じ、正確な測定ができないことがわかった。
Next, a measurement result obtained by arranging a 27 MHz crystal resonator as a detector in the cell of the apparatus of FIG. 4 is shown as a solid line in the graph of FIG. The suction speed (flow rate) of the pump 6 was 200 μl / min. From this graph, it was found that in the apparatus of the present embodiment, bubbles are not generated, the oscillation frequency of the crystal resonator is not changed, and stable measurement can be performed.
For comparison, the result of the same measurement with the inner diameter of the channel from the container 1 to the pump 6 being 0.25 mm and the inner diameter of the other channel being 1 mm is shown as a broken line in the graph of FIG. From this graph, it was found that bubbles were generated when the sample solution was sucked from the pump 6 and accurate measurement could not be performed.

更に、図4の装置を使用して、ポンプ6からの吐出流量を100μl/min〜1508μl/minに変化させて、水晶振動子の発振周波数の変化を測定した結果を図6(a)〜(e)に示す。尚、同装置において、試料溶液が収容された容器1とポンプ6とを接続する流路の内径は0.5mmとし、他の流路の内径を1mmとしている。同図から、ポンプ6からの吐出流量を変化させても周波数の急激な変動がなく測定できることがわかった。   Furthermore, using the apparatus shown in FIG. 4, the discharge flow rate from the pump 6 was changed from 100 μl / min to 1508 μl / min, and the change in the oscillation frequency of the crystal resonator was measured. e). In the same apparatus, the inner diameter of the flow path connecting the container 1 containing the sample solution and the pump 6 is 0.5 mm, and the inner diameter of the other flow path is 1 mm. From the figure, it was found that even if the discharge flow rate from the pump 6 is changed, the measurement can be performed without abrupt frequency fluctuation.

本発明のバイオセンサ装置の構成については以上の通りであるが、次に、同装置を構成する部材等について説明する。
本発明において、切換弁に供給される少なくとも2種類の溶液は、試料溶液と、それ以外の溶液をいうものとする。後者の溶液の具体例としては、例えば、緩衝液等の移動相溶液が挙げられる。
また、切換弁内に保持される溶液は気密状態にて保持されるものであり、この気密状態とは具体的には、切換弁に保持されることになる溶液を、切換弁の外部まで導出し、導出された管路内において気泡等が目視で入っていない程度のものをいうものとする。
尚、切換弁内に溶液を保持させる手段としては、切換弁内に溶液を搬送できるものであれば特に制限するものではなく、例えば、図1や図2で示したような切換弁の上流側に設けられたシリンジやポンプ等の吸入手段、或いは、切換弁の上流側に設けられたポンプ等を使用することができる。
The configuration of the biosensor device of the present invention is as described above. Next, members and the like constituting the device will be described.
In the present invention, the at least two types of solutions supplied to the switching valve refer to a sample solution and other solutions. Specific examples of the latter solution include a mobile phase solution such as a buffer solution.
Further, the solution held in the switching valve is held in an airtight state. Specifically, the airtight state means that the solution to be held in the switching valve is led out to the outside of the switching valve. In addition, it shall be such that no bubbles or the like are visually present in the derived pipe line.
The means for holding the solution in the switching valve is not particularly limited as long as it can transport the solution into the switching valve. For example, the upstream side of the switching valve as shown in FIGS. Inhalation means such as a syringe and a pump provided in the above, or a pump provided on the upstream side of the switching valve can be used.

また、切換弁やポンプ等の部材を接続して流路を形成する部材としては、テフロン(登録商標)管やPEEK管等を使用することができる。また、図4で説明した容器1からポンプ6までの流路内径は、0.5mm以上とし、好ましくは、0.5mm〜1.58mmとする。この場合に、装置を構成する他の流路の内径を1.0mm以上、好ましくは、1.0mm〜1.58mmとする。尚、この0.5mm〜1.58mmは、他の流路の内径を1.0mm〜1.58mmとした場合において、実測上、気泡が生じないことを確認した範囲である。
また、セル内に配置される検出器としては、水晶振動子や表面弾性波素子等が挙げられるが、その中でも、水晶振動子を検出器とすれば、気相が接触して測定結果を乱すことがなく、安定した測定が可能となる。
また、試料溶液が収容された容器から溶液を吸引するポンプについても特に制限はないが、例えば、ペリスタポンプや圧電式ダイヤフラムポンプ等を使用することができる。
Moreover, a Teflon (trademark) pipe | tube, a PEEK pipe | tube, etc. can be used as a member which connects members, such as a switching valve and a pump, and forms a flow path. Further, the inner diameter of the flow path from the container 1 to the pump 6 described in FIG. 4 is 0.5 mm or more, and preferably 0.5 mm to 1.58 mm. In this case, the inner diameter of the other flow path constituting the apparatus is 1.0 mm or more, preferably 1.0 mm to 1.58 mm. In addition, this 0.5 mm-1.58 mm is the range which confirmed that a bubble was not produced on measurement, when the internal diameter of another flow path was 1.0 mm-1.58 mm.
In addition, examples of the detector disposed in the cell include a crystal resonator and a surface acoustic wave device. Among them, if the crystal resonator is used as a detector, the gas phase contacts and disturbs the measurement result. And stable measurement is possible.
There is no particular limitation on the pump for sucking the solution from the container in which the sample solution is stored. For example, a peristaltic pump, a piezoelectric diaphragm pump, or the like can be used.

本発明は、分子間相互作用が弱く、長時間を要する反応の測定をより少量のサンプルによって実施できることで、計測可能な物質が広がり、創薬、食品衛生、環境ホルモン評価等の分野において、より有効且つ安全な製品開発の促進に対して評価手段として寄与できるため、広く産業上の利用可能性を有する。   The present invention has a weak intermolecular interaction and can measure a reaction that takes a long time with a smaller amount of sample, so that a measurable substance spreads, and in fields such as drug discovery, food hygiene, and environmental hormone evaluation, Since it can contribute as an evaluation means to the promotion of effective and safe product development, it has wide industrial applicability.

本発明の第1の実施の形態のバイオセンサ装置の説明図Explanatory drawing of the biosensor apparatus of the 1st Embodiment of this invention 本発明の第2の実施の形態のバイオセンサ装置の説明図Explanatory drawing of the biosensor apparatus of the 2nd Embodiment of this invention 本発明の第1の実施の形態のバイオセンサ装置の切換弁を切り換えた際の周波数変動を示すグラフThe graph which shows the frequency fluctuation at the time of switching the switching valve of the biosensor apparatus of the 1st Embodiment of this invention 本発明の第3の実施の形態のバイオセンサ装置の説明図Explanatory drawing of the biosensor apparatus of the 3rd Embodiment of this invention 本発明の第3の実施の形態のバイオセンサ装置の周波数変動を示すグラフThe graph which shows the frequency fluctuation of the biosensor apparatus of the 3rd Embodiment of this invention 本発明の第3の実施の形態のバイオセンサ装置においてポンプからの吐出流量を変化させた場合の周波数変動を示すグラフThe graph which shows the frequency fluctuation at the time of changing the discharge flow rate from a pump in the biosensor apparatus of the 3rd Embodiment of this invention.

符号の説明Explanation of symbols

1 試料溶液を収容した容器
2 移動相溶液を収容した容器
3 切換弁
4 吸入手段
5 切換弁
6 ポンプ
7 セル
8 切換弁
9 タンク
DESCRIPTION OF SYMBOLS 1 Container containing sample solution 2 Container containing mobile phase solution 3 Switching valve 4 Suction means 5 Switching valve 6 Pump 7 Cell 8 Switching valve 9 Tank

Claims (2)

ポンプの吸入側に、少なくとも2種類の溶液を切り換えてセルに供給するための切換弁を備えたフロースルーセル型のバイオセンサ装置であって、
前記切換弁は、前記ポンプが一の溶液を吸入している際に、前記ポンプに吸入されていない他の溶液を前記切換弁内に気密状態で保持できるように構成し、
前記切換弁は、前記ポンプが前記一の溶液を吸入している際に前記一の溶液を収容する容器のみが前記ポンプと接続され、前記ポンプが前記他の溶液を吸入している際に前記他の溶液を収容する容器のみが前記ポンプと接続されるように構成し
前記切換弁は、前記ポンプに吸入されていない溶液を前記切換弁内に気密状態で保持するために、該溶液側と気密に接続された吸入手段を備えたことを特徴とするバイオセンサ装置。
A flow-through cell type biosensor device comprising a switching valve for switching and supplying at least two kinds of solutions to the cell on the suction side of the pump,
The switching valve is configured so that when the pump is sucking one solution, the other solution not sucked into the pump can be kept in an airtight state in the switching valve,
The switching valve is connected to the pump only when the pump is sucking the one solution, and the pump is sucking the other solution. Only the container containing the other solution is configured to be connected to the pump ,
The biosensor device according to claim 1, wherein the switching valve is provided with suction means that is airtightly connected to the solution side in order to keep the solution not sucked into the pump in an airtight state in the switching valve .
前記セル内の検出器を、水晶振動子としたことを特徴とする請求項1に記載のバイオセンサ装置。 The biosensor device according to claim 1, wherein the detector in the cell is a crystal resonator.
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