JPH09281077A - Capillary electrophoretic apparatus - Google Patents
Capillary electrophoretic apparatusInfo
- Publication number
- JPH09281077A JPH09281077A JP8093827A JP9382796A JPH09281077A JP H09281077 A JPH09281077 A JP H09281077A JP 8093827 A JP8093827 A JP 8093827A JP 9382796 A JP9382796 A JP 9382796A JP H09281077 A JPH09281077 A JP H09281077A
- Authority
- JP
- Japan
- Prior art keywords
- capillary
- pump
- electrophoresis
- flow
- separation
- 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.)
- Pending
Links
Abstract
Description
【０００１】[0001]
【発明の属する技術分野】本発明は生体中の蛋白質、ペ
プチド、アミノ酸、神経伝達物質、ホルモン、核酸、食
品、薬品、環境物質等広範に亘る物質の微量分離分析に
用いられるキャピラリ−電気泳動装置に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a capillary electrophoresis apparatus used for micro-separation analysis of a wide variety of substances such as proteins, peptides, amino acids, neurotransmitters, hormones, nucleic acids, foods, drugs, environmental substances, etc. in a living body. About.
【０００２】[0002]
【従来の技術】キャピラリ−電気泳動法は、電解液を充
填したキャピラリ−に試料注入後キャピラリ−両端に電
圧を印加し、電場における試料粒子の易動度の差に基づ
いて分離する方法である。 易動度は、粒子がもつ荷電
量と電場の大きさに由来する駆動力と、粒子の移動に伴
い泳動媒体との間に生ずる摩擦力、の相互作用できま
り、粒子の電場における動きを電気泳動と言い、泳動粒
子はキャピラリ−末端にある検出器で検出される。 印
加電圧にはキャピラリ−内に発生するジュ−ル熱に基づ
く限界、および電源装置の限界約30kVがある。 キャピ
ラリ−電気泳動法における分離効率および分解能は、後
述の様に泳動距離および電界強度に依存するが、装置の
コンパクト性、取扱い易さ、および電源電圧限界などか
ら使用出来るキャピラリ−の長さには制約がある。 分
離用電気泳動の流れに、向流の送液をおこなうシリンジ
ポンプを組み合わせることによって、実効的な電気泳動
距離を長くする試みは、テフロン細管（内径0.5mm程
度）を用いた電気泳動の例があり、文献 分析化学 29、
11、pp728, 1972に、またフロ−トで向流をおこなうイソ
タコフォレ−シス（等速電気泳動）が特開昭47-162に開
示されている。2. Description of the Related Art A capillary electrophoresis method is a method in which a sample is injected into a capillary filled with an electrolytic solution and a voltage is applied to both ends of the capillary to separate them based on a difference in mobility of sample particles in an electric field. . The mobility is defined by the interaction of the driving force derived from the amount of electric charge and the magnitude of the electric field possessed by the particle and the frictional force generated between the particle and the electrophoretic medium, and the movement of the particle in the electric field The term "electrophoresis" means that electrophoretic particles are detected by a detector at the end of the capillary. The applied voltage has a limit based on Joule heat generated in the capillary and a limit of about 30 kV for the power supply. The separation efficiency and resolution in the capillary electrophoresis method depend on the migration distance and the electric field strength as described below, but the length of the usable capillary depends on the compactness of the device, the ease of handling, and the power supply voltage limit. There are restrictions. An example of electrophoresis using a Teflon thin tube (inner diameter of about 0.5 mm) is an attempt to increase the effective electrophoresis distance by combining the flow of separation electrophoresis with a syringe pump that carries a countercurrent solution. Yes, literature analytical chemistry 29 ,
11, pp728, 1972, and isotachophoresis (constant velocity electrophoresis) in which a countercurrent flows in the float are disclosed in JP-A-47-162.
【０００３】[0003]
（１）現在一般に使用されている市販の石英キャピラリ
−電気泳動装置には、後述の電気浸透流の影響で、分離
成分はテフロン細管を用いた場合の数倍の速さで移動し
て検出器に到達する。 これには、分析時間を短縮する
利点がある反面、充分な分離や分解能が得られず、した
がって、多成分混合試料、特に易動度の差の小さい成分
の分離が難しいというあらたな問題がある。 石英キャ
ピラリ−電気泳動の場合も、電界強度の兼ね合いで使用
できるキャピラリ−の長さには制約があるため、分離、
分解性能を向上させるためには実効的な泳動距離をのば
す手段が必要とされる。 （２）石英キャピラリ−電気泳動装置をポンプなど他の
システムと結合する場合には、キャピラリ−サイズ（内
径10乃至100μm, 外径50乃至400μm）が小さいことに付
随して低流量制御が可能で、且つ、分離能を損なうこと
のないポンプ性能が要求される。上記シリンジポンプに
は始動時および停止時に流体に不均一な力が発生し、ポ
ンプ流に乱れを生じ、また連続作動には複数のシリンジ
を交互に動かすため、始動時および停止時の影響は大き
いという問題点がある。 （３）キャピラリ−電気泳動装置をポンプなど他のシス
テムと結合する場合、密閉して用いるカソ−ド部で発生
するガスが泳動流路遮断あるいは泳動の流れを乱す原因
になることがある。(1) In a commercially available quartz capillary electrophoresis apparatus that is currently in general use, due to the effect of electroosmotic flow described below, the separated component moves at a speed several times faster than that in the case of using a Teflon thin tube, and then a detector. To reach. This has the advantage of shortening the analysis time, but on the other hand, it does not provide sufficient separation and resolution, and therefore has the new problem that it is difficult to separate multi-component mixed samples, especially those with small mobility differences. . In the case of quartz capillary electrophoresis as well, there is a limit to the length of the capillary that can be used depending on the balance of the electric field strength.
In order to improve the decomposition performance, a means for extending the effective migration distance is required. (2) When the quartz capillary electrophoresis device is connected to another system such as a pump, low flow rate control is possible due to the small capillary size (inner diameter 10 to 100 μm, outer diameter 50 to 400 μm). In addition, the pump performance that does not impair the separability is required. In the above syringe pump, a non-uniform force is generated in the fluid at the time of starting and stopping, turbulence occurs in the pump flow, and a plurality of syringes are alternately moved for continuous operation, so the influence at the time of starting and stopping is large. There is a problem. (3) When the capillary electrophoresis device is connected to another system such as a pump, the gas generated in the cathode part which is used in a sealed manner may block the migration channel or disturb the migration flow.
【０００４】[0004]
【課題を解決するための手段】キャピラリ−（ゾ−ン）
電気泳動法の性能は以下の式で説明されるように、分離
効率は印加する電解強度と泳動距離に比例し、分解能は
電解強度の1/2乗、と泳動距離の1/2乗に比例する。 キ
ャピラリ−電気泳動中のバンド幅の拡散は[Means for Solving the Problem] Capillary (zone)
As described in the following equation, the performance of the electrophoresis method is that the separation efficiency is proportional to the applied electrolytic strength and the migration distance, and the resolution is proportional to the electrolytic strength 1/2 power and the migration distance 1/2 power. To do. Bandwidth diffusion during capillary-electrophoresis
【０００５】[0005]
【数１】 [Equation 1]
【０００６】σ2/L で定義される理論段高さHはThe theoretical plate height H defined by σ 2 / L is
【０００７】[0007]
【数２】 [Equation 2]
【０００８】となる。 この式は v＝μ・Eの関係から[0008] This formula is based on the relationship of v = μ ・ E
【０００９】[0009]
【数３】 (Equation 3)
【００１０】となり、分離効率を示す理論段数NはThe theoretical plate number N indicating the separation efficiency is
【００１１】[0011]
【数４】 (Equation 4)
【００１２】すなわち、泳動距離L および電界強度E に
比例する。他方、易動度の異なる二つの成分の分解能R
はThat is, it is proportional to the migration distance L and the electric field strength E. On the other hand, the resolution R of two components with different mobilities
Is
【００１３】[0013]
【数５】 (Equation 5)
【００１４】t1:成分1の泳動時間、t2:成分2の泳動時
間、w1:成分1のピ−ク幅、w2:成分2のピ−ク幅として計
算され、T 1 is the component 1 migration time, t 2 is the component 2 migration time, w 1 is the component 1 peak width, and w 2 is the component 2 peak width.
【００１５】[0015]
【数６】 (Equation 6)
【００１６】となり、分解能も泳動距離L と電界強度E
に依存する（参考;"Capillary Electrophoresis", R.Ku
hn, S.H.Kuhn, Springer Verlag, pp32乃至34, 199
3)。 限られたキャピラリ−長で実効的な電気泳動距離
を長くするためには、大きく分けて二つの方法が考えら
れる。 一つにはポンプ結合により見掛けの泳動速度を
遅くするもので、泳動末端すなわち検出器側に結合した
ポンプから向流の送液をおこなうか、または泳動先端す
なわち試料注入側に結合したポンプでキャピラリ−内の
液を排出して、分離成分が検出器に到達するまでの時間
をかせぐ。 他の一つは、泳動末端に流量調節用の手段
を結合して上記同様実効的な泳動距離をのばす。 以
下、(１)から(４)はポンプ、(５)、(６)は流量調節手
段、(７)、(８)は電極で発生するガスの処理法に関する
ものである。Therefore, the resolution is also the migration distance L and the electric field strength E.
(Reference; "Capillary Electrophoresis", R.Ku
hn, SHKuhn, Springer Verlag, pp32-34, 199
3). In order to increase the effective electrophoretic distance with a limited capillary length, there are roughly two methods. One is to slow down the apparent migration speed by binding to a pump.Therefore, the pump connected to the migration end, that is, the detector side, performs countercurrent flow, or the pump connected to the migration tip, that is, the sample injection side, is used for the capillary. -Drain the liquid inside and allow time for the separated components to reach the detector. In the other one, a means for flow rate adjustment is attached to the migration end to extend the effective migration distance as described above. Hereinafter, (1) to (4) relate to a pump, (5) and (6) relate to a flow rate adjusting means, and (7) and (8) relate to a method of treating gas generated in an electrode.
【００１７】（１）無脈流且つ微少流量の送液ポンプと
して電気浸透流ポンプを用いる。(1) An electroosmotic flow pump is used as a pulse-free and minute flow rate liquid feed pump.
【００１８】（２）無脈流あるいは低脈流の微少流量の
送液ポンプとして電磁流ポンプ、たとえば回転磁場を発
生させるコイル中に、溶液を充填した細管を配置して、
極性を持つ液体の送りだしをおこなうポンプを用いる。(2) An electromagnetic flow pump as a liquid-feeding pump with a small flow rate of non-pulsating flow or low pulsating flow, for example, a coil for generating a rotating magnetic field is arranged with a thin tube filled with a solution,
A pump that pumps out polar liquid is used.
【００１９】（３）低脈流で微少流量の送液ポンプとし
て平板形および円筒形圧電素子をアクチュエ−タに利用
したポンプを用いる。 いずれも電気制御による息つき
運動によりノズルから液を噴出させる。素子に印加する
電圧及び周波数によって流量と脈動率の制御ができる。
平板形素子は積層化によるコンパクトな多チャンネル
化が容易であり、円筒形素子は形状、サイズ共キャピラ
リ−と近い特徴がある。(3) A pump using a flat plate type and a cylindrical type piezoelectric element as an actuator is used as a liquid feed pump having a low pulsating flow and a very small flow rate. In each case, the liquid is ejected from the nozzle by the breathing motion by electric control. The flow rate and pulsation rate can be controlled by the voltage and frequency applied to the element.
The flat plate element can easily be made into a compact multi-channel by stacking, and the cylindrical element has characteristics similar to capillaries in both shape and size.
【００２０】（４）更に集積化キャピラリ−電気泳動法
には電気浸透流ポンプの他、静電形マイクロポンプを使
用することも考えられる。(4) In addition to the electroosmotic flow pump, it is also possible to use an electrostatic micropump for the integrated capillary electrophoresis method.
【００２１】（５）泳動末端に結合する流量調節手段
に、電気的制御が可能な圧電素子を利用した流路調節弁
を用いる。(5) A flow path control valve using an electrically controllable piezoelectric element is used as the flow rate control means connected to the migration end.
【００２２】（６）泳動末端に結合する流量調節部手段
に、オリフィス、キャピラリ−、フィルタ−類の中から
サイズ、長さ、厚さ等泳動条件に適合するものを選択し
て用いる、または多チャンネル切り替え方式で流量調節
条件を選択する。(6) For the means for controlling the flow rate, which is connected to the electrophoretic terminal, one selected from orifices, capillaries, filters, etc., which is suitable for electrophoretic conditions such as size, length and thickness, or is used Select the flow rate adjustment condition by the channel switching method.
【００２３】（７）カソ−ドで発生するガスの処理法の
一つは電極材料に水素吸蔵体を用いる。例えば、パラジ
ウム、チタンなどの金属単体、あるいはＡＢ5型、ＡＢ2
型（Ａ：希土類、チタン、ジルコニウム、マグネシウ
ム、カルシウム等、Ｂ：鉄、コバルト、ニッケル、マン
ガン等）に代表される水素吸蔵合金を用いて、水素金属
間化合物、あるいは固溶体とする。(7) One of the methods for treating the gas generated by the cathode uses a hydrogen storage material as an electrode material. For example, simple metals such as palladium and titanium, AB 5 type, AB 2 type
A hydrogen storage alloy represented by a type (A: rare earth, titanium, zirconium, magnesium, calcium, etc., B: iron, cobalt, nickel, manganese, etc.) is used to form a hydrogen intermetallic compound or a solid solution.
【００２４】（８）他方発生水素ガス消費法としてニッ
ケル、パラジウムのような水素透過性のある材料をカソ
−ド兼隔離板として用い、カソ−ドで発生する水素をこ
の隔離板に接して設けた補助電解セルに導入して消費す
る方法がある。 電気泳動部に面したカソ−ドで発生し
た水素ガスは、隔離板の中を透過して補助電解セル側に
達し、この面でイオン化して補助電解セル内の対極に移
動して消費される。 この補助電解セルの電位はイオン
化反応が起こる様調整しておく。(8) On the other hand, as a method for consuming the generated hydrogen gas, a material having hydrogen permeability such as nickel and palladium is used as a cathode / separator, and hydrogen generated in the cathode is provided in contact with the separator. There is a method of introducing it into an auxiliary electrolysis cell and consuming it. The hydrogen gas generated by the cathode facing the electrophoretic section permeates through the separator and reaches the auxiliary electrolysis cell side, is ionized on this surface and moves to the counter electrode in the auxiliary electrolysis cell for consumption. . The potential of this auxiliary electrolysis cell is adjusted so that an ionization reaction occurs.
【００２５】[0025]
【発明の実施の形態】図１に本発明に基づくキャピラリ
−電気泳動装置の基本構成を示す。 分離用キャピラリ
−電気泳動部Ａ，ポンプ部Ｂ，分離用キャピラリ−電気
泳動用カソ−ド部Ｃで構成されている。 電解液（緩衝
液）を満たした分離用石英キャピラリ−管１の両端はそ
れぞれ電極室２および３と液絡をはかり、一端から試料
溶液を導入したのち、キャピラリ−両端に高電圧を印加
して電気泳動をおこなう。 試料中の各成分は、電場に
おける易動度の差に基づいて分離される。 この電気泳
動分離成分は、電圧印加時キャピラリ−管内に生ずる電
気浸透流の影響をうけて、通常カソ−ド９に向かって移
動し、検出器４で検出される。 この分離用キャピラリ
−電気泳動部に結合したポンプ部Ｂでは、分離バンドを
乱さぬ無脈流あるいは低脈流のポンプ５が液槽６から緩
衝液を汲みだして、上記分離バンドが移動する流れに対
して向流の送液をおこない、実効泳動距離をのばす。
石英キャピラリ−電気泳動および実施例で示す電気浸透
流は以下の様に説明される。 石英キャピラリ−は、溶
液と接すると石英表面のシラノ−ル基が解離して−の電
荷を持ち、これに溶液中の＋イオンが引き寄せられ電気
二重層（ζ電位）を形成する。 電場に置くと、この可
動の＋イオンがカソ−ドに向かって動き、このような界
面の動きに伴いキャピラリ−内の溶液内部も粘性で動
く。 電気浸透流速度（Veo)に影響をおよぼすパラメ−
タは、FIG. 1 shows the basic structure of a capillary-electrophoresis device according to the present invention. It is composed of a separation capillary electrophoresis section A, a pump section B, and a separation capillary electrophoresis cathodic section C. Both ends of the separation quartz capillary tube 1 filled with an electrolytic solution (buffer solution) have a liquid junction with the electrode chambers 2 and 3, respectively, and after introducing the sample solution from one end, a high voltage is applied to both ends of the capillary. Perform electrophoresis. Each component in the sample is separated based on the difference in mobility in the electric field. This electrophoretic separation component is usually moved toward the cathode 9 under the influence of the electroosmotic flow generated in the capillary tube when a voltage is applied, and detected by the detector 4. In the pump section B coupled to this separation capillary-electrophoresis section, a pulse-free or low-pulsation pump 5 that does not disturb the separation band pumps out a buffer solution from the liquid tank 6 and the separation band moves. The solution is counter-currently flown to increase the effective migration distance.
The quartz capillary-electrophoresis and the electroosmotic flow shown in the examples are explained as follows. When contacting with the solution, the silica capillary dissociates the silanol groups on the surface of the quartz and has a negative charge, and + ions in the solution are attracted to this to form an electric double layer (ζ potential). When placed in an electric field, the movable + ions move toward the cathode, and with the movement of such an interface, the solution inside the capillary also moves viscously. Parameters affecting electroosmotic flow velocity (Veo)
Is
【００２６】[0026]
【数７】 (Equation 7)
【００２７】で表わされるように、電界強度（E）、ゼ
−タ電位（ζ）、溶液の誘電率（ε）、粘度（η）のほ
かゼ−タ電位に影響をおよぼす溶液のｐＨやイオン強
度、さらに温度、キャピラリ−体の形状、内表面の状
態、溶液への添加物などがある。（参考;”Capillary
Electrophoresis", R.Kuhn, S.H.Kuhn, Springer Verl
ag,pp22乃至29, 1993)。 電気浸透流ポンプは上記条件
を選択して構成し、分離用キャピラリ−電気泳動装置と
の結合をはかる。ポンプ流速は、印加電圧に依存するた
め、電気的制御が可能である。流体速度のプロファイル
は通常の圧力ポンプの場合が放物線状であるのに比し均
一な平面をもっている。 また、電気浸透流ポンプに用
いるキャピラリ−は、１本、複数本のキャピラリ−の集
合体または多孔質体でもよい。As shown by, the electric field strength (E), the zeta potential (ζ), the dielectric constant (ε) and the viscosity (η) of the solution, as well as the pH and ions of the solution that affect the zeta potential. Strength, temperature, shape of capillaries, state of inner surface, additives to solution, etc. (Reference; “Capillary
Electrophoresis ", R. Kuhn, SHKuhn, Springer Verl
Ag, pp 22-29, 1993). The electroosmotic flow pump is constructed by selecting the above-mentioned conditions and is connected to the separation capillary-electrophoresis device. Since the pump flow velocity depends on the applied voltage, it can be electrically controlled. The fluid velocity profile has a uniform flat surface as compared to the parabolic shape in the case of a normal pressure pump. Further, the capillaries used for the electroosmotic pump may be an assembly of one or a plurality of capillaries or a porous body.
【００２８】（第１の実施例）図２に本発明の一実施例
に基づく電気浸透流ポンプの断面図、図３にこれを結合
したキャピラリ−電気泳動装置の構成図を示す。 送液
ポンプは、キャピラリ−体１０、液槽６およびキャピラ
リ−体前後に設けた電極１１、１２からなり、ポンプの
送液量、流速はキャピラリ−体の種類（１本のキャピラ
リ−、複数のキャピラリ−および多孔体）、形状、サイ
ズ、印加電圧、溶液の種類、濃度、ｐＨ、添加物等を選
択して最適化する。 ポンプ部の電圧印加は、分離用電
気泳動と逆向き、すなわちカソ−ド１１およびアノ−ド
１２になるが、図３のように分離用カソ−ド９およびポ
ンプ用カソ−ド１１は共用にして三極構造にもできる。
カソ−ド液槽は電極近辺の液組成変化などが問題になる
場合必要に応じた容量にすることができる。 分離用キ
ャピラリ−泳動部に検出器４の他に設けた補助検出器２
０からの予備情報は、電気泳動条件コントロ−ラ２１に
フィ−ドバックされ、分離用印加電圧あるいはポンプ用
印加電圧を制御に用いられる。 図４にPTH-アミノ酸混
合試料分離への効果を示す。 トリス−グリシン、50mM
−SDS緩衝液を満した内径50μm、長さ30cmの石英キャピ
ラリ−、電界強度0.38kV/cmの泳動条件で得られたエレ
クトロフェログラム上のピ−ク5は易動度の近いPTH-ト
リプトファンとPTH-フェニルアラニンの混合ピ−クであ
るが、内径50μm、長さ20cm、電界強度0.20kV/cmのキャ
ピラリ−を用いた電気浸透流ポンプの作動によりピ−ク
6（PTH−トリプトファン)、ピ−ク7（PTH-フェニルアラ
ニン）への分離がみられる。 図５に本発明を用いて生
体試料を直接採取、オンラインで分析する例を示す。
マイクロダイアリシスのような微小のプロ−ブ２７、あ
るいは極細のキャピラリ−を生体の細胞間あるいは血管
内に挿入して、コントロ−ラ−２８を介して採取した試
料をフラクションコレクタ−２９に分取、随時これをオ
ンラインで本発明のキャピラリ−電気泳動システムで分
離分析する。(First Embodiment) FIG. 2 shows a cross-sectional view of an electroosmotic flow pump according to an embodiment of the present invention, and FIG. 3 shows a block diagram of a capillary-electrophoresis device having the electroosmotic flow pump connected thereto. The liquid feed pump is composed of a capillary body 10, a liquid tank 6, and electrodes 11 and 12 provided before and after the capillary body. The liquid feed amount and flow rate of the pump are determined by the type of the capillary body (one capillary, a plurality of capillaries). Capillary and porous body), shape, size, applied voltage, type of solution, concentration, pH, additives, etc. are selected and optimized. The voltage applied to the pump is in the opposite direction to the separation electrophoresis, that is, the cathode 11 and the anode 12, but as shown in FIG. 3, the separation cathode 9 and the pump cathode 11 are shared. It can also have a tripolar structure.
The cathode liquid tank can be made to have a capacity as necessary when a change in liquid composition near the electrodes becomes a problem. Auxiliary detector 2 provided in addition to the detector 4 in the separation capillary migration section
Preliminary information from 0 is fed back to the electrophoretic condition controller 21 and used for controlling the separation applied voltage or the pump applied voltage. Figure 4 shows the effect on the separation of PTH-amino acid mixed samples. Tris-glycine, 50 mM
-A quartz capillary with an inner diameter of 50 μm and a length of 30 cm filled with SDS buffer, and a peak 5 on the electropherogram obtained under the electrophoretic conditions of an electric field strength of 0.38 kV / cm was PTH-tryptophan with a similar mobility. It is a mixed peak of PTH-phenylalanine, but the peak is generated by the operation of an electroosmotic pump using a capillary with an inner diameter of 50 μm, a length of 20 cm and an electric field strength of 0.20 kV / cm.
Separation into 6 (PTH-tryptophan) and peak 7 (PTH-phenylalanine) is observed. FIG. 5 shows an example of directly collecting and online analyzing a biological sample using the present invention.
A microprobe 27 such as microdialysis, or an ultrafine capillary is inserted into cells or blood vessels of a living body, and a sample collected via a controller 28 is collected in a fraction collector 29. At any time, this is separated and analyzed online by the capillary-electrophoresis system of the present invention.
【００２９】（第２の実施例）図６に本発明の第２の実
施例に基づくキャピラリ−電気泳動装置における電磁流
ポンプの構成図を示す。３相電流を流して３個のコイル
１３の中に回転磁場を発生させ中心部に配置したプラス
チック細管内の液体を動かし、分離用キャピラリ−電気
泳動部に結合して用いる。 （第３の実施例）図７に本発明の第２の実施例に基づく
キャピラリ−電気泳動装置における圧電素子ポンプの断
面図を示す。 平板形圧電素子１５をアクチュエ−タと
して用いた本ポンプは、溶液と接する素子表面の凸型シ
リコンゴムにテフロンコ−ティングを施こしてあり、印
加する電圧、周波数により流速、脈流を制御する。 （第４の実施例）図８に本発明の第４の実施例に基づく
キャピラリ−電気泳動装置におけるカソ−ド部Ｃの構成
図を示す。 カソ−ドで発生するガスをカソ−ド液槽の
外に導く事を目的としたもので、例えばニッケルのよう
な水素透過性の材料を分離用電気泳動のカソ−ド兼隔離
板１８として用いて、これに接して補助電解セル１７を
設ける。 分離用電気泳動部のカソ−ドで発生する水素
は隔離板を透過したのち、補助電解セル側でイオン化し
て消費されるよう、対極１９はニッケル極より低い電位
に調整しておく。(Second Embodiment) FIG. 6 is a block diagram of an electromagnetic flow pump in a capillary electrophoresis apparatus according to a second embodiment of the present invention. A three-phase current is passed to generate a rotating magnetic field in the three coils 13 to move the liquid in the plastic tube arranged at the center, and the liquid is coupled to the separation capillary-electrophoresis section for use. (Third Embodiment) FIG. 7 shows a sectional view of a piezoelectric element pump in a capillary electrophoresis apparatus according to a second embodiment of the present invention. This pump using the flat plate type piezoelectric element 15 as an actuator has Teflon coating on the convex silicone rubber on the surface of the element which is in contact with the solution, and controls the flow velocity and pulsating flow by the applied voltage and frequency. (Fourth Embodiment) FIG. 8 shows the construction of a cathode section C in a capillary electrophoresis apparatus according to the fourth embodiment of the present invention. The purpose is to guide the gas generated in the cathode to the outside of the cathode liquid tank. For example, a hydrogen permeable material such as nickel is used as the cathode / separator 18 for the separation electrophoresis. Then, the auxiliary electrolytic cell 17 is provided in contact with this. The counter electrode 19 is adjusted to have a potential lower than that of the nickel electrode so that hydrogen generated in the cathode of the separation electrophoretic section passes through the separator and is ionized and consumed on the auxiliary electrolysis cell side.
【００３０】（第５の実施例）図９に本発明の第５の実
施例に基づくキャピラリ−電気泳動部と質量分析計の複
合化システムを示す。 実効的な泳動距離を制御するポ
ンプは泳動部先端にキャピラリ−内の溶液（緩衝液）を
排出する向きに結合してある。 電気泳動分離用のキャ
ピラリ−の末端はインタ−フェイスＤの金属パイプに装
填され、泳動してきた分離成分は噴霧補助溶液２３と共
に噴霧、イオン化されて質量分析部２６に導入され、イ
オン検出、デ−タ処理がおこなわれる。 このシステム
では泳動分離された成分のオンラインでの同定が可能に
なる。(Fifth Embodiment) FIG. 9 shows a combined system of a capillary-electrophoresis unit and a mass spectrometer according to a fifth embodiment of the present invention. The pump for controlling the effective migration distance is connected to the tip of the migration section in the direction for discharging the solution (buffer solution) in the capillary. The ends of the capillaries for electrophoretic separation are loaded into the metal pipe of the interface D, and the separated components that have migrated are sprayed and ionized with the spray auxiliary solution 23 and introduced into the mass spectrometric section 26 for ion detection and desorption. Data processing is performed. This system allows on-line identification of electrophoretically separated components.
【００３１】（第６の実施例）図１０に本発明の第６の
実施例に基づく流量調節弁を泳動末端に結合したキャピ
ラリ−電気泳動システムの装置構成を示す。 連続的な
流量調節が可能な流量調節弁３０は、目的に合わせて泳
動の出口で流れを絞り、実効的な泳動距離を制御する。(Sixth Embodiment) FIG. 10 shows a device configuration of a capillary-electrophoresis system in which a flow control valve according to a sixth embodiment of the present invention is connected to an electrophoretic terminal. The flow rate control valve 30 capable of continuously controlling the flow rate controls the effective migration distance by narrowing the flow at the migration outlet according to the purpose.
【００３２】[0032]
（１）前述のいずれのポンプも電気制御ができるため、
取扱いおよび自動化が容易、さらに、泳動条件最適化の
シミュレ−ションが容易となるため、目的、分析対象に
応じた多様の対応とプログラム制御が可能となる。(1) Since any of the above pumps can be electrically controlled,
It is easy to handle and automate, and simulation of optimizing electrophoretic conditions is easy. Therefore, various correspondences and program control depending on the purpose and analysis target are possible.
【００３３】（２）泳動部のキャピラリ−長を短縮でき
る上、電気制御系であるため装置をコンパクトにでき
る。このことは、分析系の温度制御を容易にして再現性
の良い結果をもたらす、と同時にパ−ムトップサイズの
環境計測やベッドサイドの臨床検査に適した計測器とし
ての応用分野もある。(2) The capillary length of the electrophoretic section can be shortened, and the device can be made compact due to the electric control system. This facilitates the temperature control of the analytical system and brings reproducible results, and at the same time, it has an application field as a measuring instrument suitable for environment measurement of the palm top size and bedside clinical examination.
【００３４】（３）血清、脳脊髄液、ＤＮＡをはじめと
する生体成分や医薬品、環境物質に含まれる各種イオン
などわずかな易動度差をもつ混合成分の分離を容易に
し、泳動距離依存性の高い等速電気泳動分離モ−ドにお
いても、リ−デイングイオンとタ−ミナルイオンにはさ
まれた試料各成分の分離性能向上に貢献する。(3) It facilitates the separation of mixed components having a slight mobility difference such as serum, cerebrospinal fluid, biological components such as DNA, pharmaceuticals, and various ions contained in environmental substances, and has migration distance dependency. Even in high-speed isotachophoresis separation mode, it contributes to the improvement of the separation performance of each component of the sample sandwiched between the reading ion and the terminal ion.
【図１】本発明のキャピラリ−電気泳動装置の基本構成
図。FIG. 1 is a basic configuration diagram of a capillary-electrophoresis device of the present invention.
【図２】第１の実施例に基づくキャピラリ−電気泳動装
置における電気浸透流ポンプの断面図。FIG. 2 is a sectional view of an electroosmotic flow pump in the capillary-electrophoresis device according to the first embodiment.
【図３】第１の実施例に基づく電気浸透流ポンプ結合キ
ャピラリ−電気泳動装置の構成図。FIG. 3 is a block diagram of an electroosmotic pump-coupled capillary-electrophoresis device according to the first embodiment.
【図４】第１の実施例に基づく電気泳動パタ−ンを示す
図。FIG. 4 is a diagram showing an electrophoretic pattern according to the first embodiment.
【図５】第１の実施例に基づく生体試料オンライン採
取、オンライン分析の概念図。FIG. 5 is a conceptual diagram of biological sample online collection and online analysis based on the first embodiment.
【図６】第２の実施例に基づくキャピラリ−電気泳動装
置における電磁流ポンプの模式図。FIG. 6 is a schematic diagram of an electromagnetic flow pump in the capillary-electrophoresis device according to the second embodiment.
【図７】第３の実施例に基づくキャピラリ−電気泳動装
置における圧電素子ポンプの断面図。FIG. 7 is a sectional view of a piezoelectric element pump in a capillary-electrophoresis device according to a third embodiment.
【図８】第４の実施例に基づくキャピラリ−電気泳動装
置おけるカソ−ド部および補助電解セルの構成図。FIG. 8 is a configuration diagram of a cathode part and an auxiliary electrolysis cell in a capillary electrophoresis apparatus according to a fourth embodiment.
【図９】第５の実施例に基づくキャピラリ−電気泳動部
と質量分析計の複合化システムを示す図。FIG. 9 is a diagram showing a combined system of a capillary-electrophoresis unit and a mass spectrometer based on a fifth embodiment.
【図１０】第６の実施例に基づく流量調節弁結合キャピ
ラリ−電気泳動装置の構成図。FIG. 10 is a block diagram of a capillary electrophoresis system combined with a flow control valve according to a sixth embodiment.
1…電気泳動分離用キャピラリ−、２、３…電極液槽、
４…検出器、５…送液ポンプ、６…液槽、７…オ−トサ
ンプラ−、８、９…電気泳動分離用電極、１０…ポンプ
用キャピラリ−体、１１、１２…ポンプ駆動用電極、１
３…電磁コイル１４…プラスチック細管、１５…圧電素
子、１６…ポンプ駆動ユニット、１７…補助電解セル、
１８…電極兼隔離板、１９…対極、２０…補助検出器、
２１…電気泳動条件コントロ−ラ−、２２…金属パイ
プ、２３…噴霧補助溶液、 ２４、２５…排気系、２
６…質量分析部、２７…マイクロダイアリシス微小プロ
−ブ、２８…サンプリングコントロ−ラ−、２９…フラ
クションコレクタ−、３０…流量調節弁、３１…流量調
節弁コントロ−ラ。1 ... Capillary for electrophoretic separation-2, 3 ... Electrode solution tank,
4 ... Detector, 5 ... Liquid feed pump, 6 ... Liquid tank, 7 ... Autosampler, 8, 9 ... Electrophoretic separation electrode, 10 ... Pump capillary body, 11, 12 ... Pump drive electrode, 1
3 ... Electromagnetic coil 14 ... Plastic thin tube, 15 ... Piezoelectric element, 16 ... Pump drive unit, 17 ... Auxiliary electrolysis cell,
18 ... Electrode / separator, 19 ... Counter electrode, 20 ... Auxiliary detector,
21 ... Electrophoresis condition controller, 22 ... Metal pipe, 23 ... Spraying auxiliary solution, 24, 25 ... Exhaust system, 2
6 ... Mass spectrometric section, 27 ... Microdialysis microprobe, 28 ... Sampling controller, 29 ... Fraction collector, 30 ... Flow control valve, 31 ... Flow control valve controller.
───────────────────────────────────────────────────── フロントページの続き (72)発明者 高田 安章 東京都国分寺市東恋ケ窪１丁目280番地 株式会社日立製作所中央研究所内 (72)発明者 奥村 昭彦 東京都国分寺市東恋ケ窪１丁目280番地 株式会社日立製作所中央研究所内 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ansho Takada 1-280 Higashi Koigokubo, Kokubunji, Tokyo Inside the Central Research Laboratory, Hitachi, Ltd. (72) Akihiko Okumura 1-280 Higashi Koikeku, Kokubunji, Tokyo Hitachi Ltd. Central Research Laboratory
Claims (25)
供給手段と、分離された試料成分を検出する少なくとも
１個の検出手段と、電気泳動を発生させる電圧供給手
段、とからなる電気泳動装置であって、該分離用石英キ
ャピラリ−内の液体の流れを制御する電気浸透流ポンプ
又は流量調節手段のいずれか一方を付加したことを特徴
とするキャピラリ−電気泳動装置。1. An electrophoretic device comprising a quartz capillary for electrophoretic separation, a sample supply means, at least one detection means for detecting separated sample components, and a voltage supply means for generating electrophoresis. A capillary electrophoresis apparatus, characterized in that either one of an electroosmotic flow pump for controlling the flow of the liquid in the separation quartz capillary or a flow rate adjusting means is added.
ャピラリ−の泳動末端、又は試料注入側のどちらか一方
に取り付けられたことを特徴とする請求項１のキャピラ
リ−電気泳動装置。2. The capillary electrophoresis apparatus according to claim 1, wherein the electroosmotic pump is attached to either the migration end of the quartz capillary for electrophoretic separation or the sample injection side.
ピラリ−体が電場で生ずる電気浸透流を利用したポンプ
であるが、前記キャピラリ−体は少なくとも１本から成
ることを特徴とする請求項１のキャピラリ−電気泳動装
置。3. The electroosmotic flow pump is a pump that utilizes an electroosmotic flow generated by an electric field in a capillary body containing a solution, and the capillary body is composed of at least one. 1. Capillary-electrophoresis device.
ピラリ−体が電場で生ずる電気浸透流を利用したポンプ
であるが、前記キャピラリ−体は多孔質体から成ること
を特徴とする請求項１のキャピラリ−電気泳動装置。4. The electroosmotic flow pump is a pump that uses an electroosmotic flow generated by an electric field in a capillary body containing a solution, and the capillary body is made of a porous body. 1. Capillary-electrophoresis device.
路を調節する弁を備えたことを特徴とする請求項１のキ
ャピラリ−電気泳動装置。5. The capillary electrophoresis apparatus according to claim 1, wherein the flow rate adjusting means is provided with a valve for adjusting a flow path by using a piezoelectric element.
ラリ−体を単独で又は多チャンネル化して用いることを
特徴とする請求項１のキャピラリ−電気泳動装置。6. The capillary electrophoresis apparatus according to claim 1, wherein an orifice or a capillary body is used alone or in a multi-channel form for the flow rate adjusting means.
独で又は多チャンネル化して用いることを特徴とする請
求項１のキャピラリ−電気泳動装置。7. The capillary electrophoresis apparatus according to claim 1, wherein a porous filter is used alone or in a multi-channel form as the flow rate adjusting means.
供給手段と、分離された試料成分を検出する少なくとも
１個の検出手段と、電気泳動を発生させる電圧供給手
段、とからなる電気泳動装置であって、該分離用石英キ
ャピラリ−内の液体の流れを制御する電磁流ポンプを付
加したことを特徴とするキャピラリ−電気泳動装置。8. An electrophoretic device comprising a quartz capillary for electrophoretic separation, a sample supply means, at least one detection means for detecting separated sample components, and a voltage supply means for generating electrophoresis. The capillary electrophoresis apparatus, further comprising an electromagnetic flow pump for controlling the flow of the liquid in the separation quartz capillary.
英キャピラリ−の泳動末端、又は試料注入側のどちらか
一方に取り付けられたことを特徴とする請求項８のキャ
ピラリ−電気泳動装置。9. The capillary electrophoresis apparatus according to claim 8, wherein the electromagnetic flow pump is attached to either one of the migration end of the quartz capillary for electrophoretic separation and the sample injection side.
料供給手段と、分離された試料成分を検出する少なくと
も１個の検出手段と、電気泳動を発生させる電圧供給手
段、とからなる電気泳動装置であって、該分離用石英キ
ャピラリ−内の液体の流れを制御する、圧電素子をアク
チュエ−タ−に利用したポンプを付加したことを特徴と
するキャピラリ−電気泳動装置。10. An electrophoretic device comprising a quartz capillary for electrophoretic separation, sample supply means, at least one detection means for detecting separated sample components, and voltage supply means for generating electrophoresis. A capillary electrophoresis apparatus, wherein a pump using a piezoelectric element as an actuator is added to control the flow of the liquid in the separation quartz capillary.
利用したポンプが前記電気泳動分離用石英キャピラリ−
の泳動末端、又は試料注入側のいずれか一方に取り付け
られたことを特徴とする請求項１０のキャピラリ−電気
泳動装置。11. A quartz capillary for electrophoretic separation is a pump using the piezoelectric element as an actuator.
The capillary-electrophoresis device according to claim 10, wherein the capillary-electrophoresis device is attached to either one of the migration end and the sample injection side.
料供給手段と、分離された試料成分を検出する少なくと
も１個の検出手段と、電気泳動を発生させる電圧供給手
段、とからなる電気泳動装置であって、該分離用石英キ
ャピラリ−内の液体の流れを制御する静電形マイクロポ
ンプを付加したことを特徴とするキャピラリ−電気泳動
装置。12. An electrophoretic device comprising a quartz capillary for electrophoretic separation, a sample supply means, at least one detection means for detecting separated sample components, and a voltage supply means for generating electrophoresis. A capillary electrophoresis apparatus, characterized in that an electrostatic micropump for controlling the flow of the liquid in the separation quartz capillary is added.
動分離用石英キャピラリ−の泳動末端、又は試料注入側
のいずれか一方に取り付けられたことを特徴とする請求
項１２のキャピラリ−電気泳動装置。13. The capillary electrophoresis apparatus according to claim 12, wherein the electrostatic micropump is attached to either the migration end of the quartz capillary for electrophoretic separation or the sample injection side. .
給手段と、分離された試料成分を検出する少なくとも１
個の検出手段と、電気泳動を発生させる電圧供給手段、
とからなる電気泳動装置であって、該分離用石英キャピ
ラリ−内の液体の流れを制御するポンプを付加した電気
泳動分離用キャピラリ−を結合したことを特徴とする質
量分析装置。14. A capillary for electrophoretic separation, sample supply means, and at least one for detecting separated sample components.
Individual detection means, voltage supply means for generating electrophoresis,
A mass spectrometric apparatus comprising: an electrophoretic separation capillary having a pump for controlling a flow of a liquid in the separation quartz capillary, the electrophoretic separation capillary including:
ャピラリ−体が電場で生ずる電気浸透流を利用したポン
プであるが、前記キャピラリ−体は少なくとも１本から
成ることを特徴とする請求項１４の質量分析装置。15. The electroosmotic flow pump is a pump utilizing an electroosmotic flow generated by an electric field in a capillary body containing a solution, wherein the capillary body is composed of at least one. 14 mass spectrometers.
ことを特徴とする請求項１４の質量分析装置。16. The mass spectrometer according to claim 14, wherein the capillary body is made of a porous body.
給手段と、分離された試料成分を検出する少なくとも１
個の検出手段と、電気泳動を発生させる電圧供給手段、
とから成る電気泳動装置に前記分離用キャピラリ−内の
液体の流れを制御するポンプ、又は流量調節手段のいず
れか一方を付加したキャピラリ−電気泳動装置であっ
て、カソ−ドで発生する水素ガスを吸蔵あるいは消費す
るカソ−ド部を備えたことを特徴とするキャピラリ−電
気泳動装置。17. A capillary for electrophoretic separation, sample supply means, and at least one for detecting separated sample components.
Individual detection means, voltage supply means for generating electrophoresis,
A capillary electrophoresis apparatus in which either a pump for controlling the flow of the liquid in the separation capillary or a flow rate adjusting means is added to the electrophoresis apparatus comprising hydrogen gas generated by a cathode. A capillary electrophoresis device comprising a cathode part for occluding or consuming oxygen.
するポンプが電気浸透流ポンプである請求項１７のキャ
ピラリ−電気泳動装置。18. The capillary electrophoresis apparatus according to claim 17, wherein the pump that controls the flow of the liquid in the capillary is an electroosmotic pump.
するポンプが電磁流ポンプである請求項１７のキャピラ
リ−電気泳動装置。19. The capillary-electrophoresis device according to claim 17, wherein the pump for controlling the flow of the liquid in the capillary is an electromagnetic flow pump.
流路を調節する弁である請求項１７のキャピラリ−電気
泳動装置。20. The capillary-electrophoresis device according to claim 17, wherein the flow rate adjusting means is a valve for adjusting a flow path by using a piezoelectric element.
キャピラリ−のいずれか一方である請求項１７のキャピ
ラリ−電気泳動装置。21. The capillary electrophoresis apparatus according to claim 17, wherein the flow rate adjusting means is either an orifice or a capillary.
ある請求項１７のキャピラリ−電気泳動装置。22. The capillary electrophoresis apparatus according to claim 17, wherein the flow rate adjusting means is a porous filter.
ドが、パラジウム、チタン、ニッケル、白金などの金属
単体、あるいはＡＢ5型、ＡＢ2型（Ａ：希土類、チタ
ン、ジルコニウム、マグネシウム、カルシウム等、Ｂ：
鉄、コバルト、ニッケル、マンガン等）に代表される水
素吸蔵体からなる請求項１７のキャピラリ−電気泳動装
置。23. The personal computer built in the personal computer.
Is a simple metal such as palladium, titanium, nickel, platinum, or AB 5 type, AB 2 type (A: rare earth, titanium, zirconium, magnesium, calcium, etc., B:
18. The capillary-electrophoresis device according to claim 17, comprising a hydrogen storage material represented by iron, cobalt, nickel, manganese, etc.).
給手段と、分離された試料成分を検出する少なくとも１
個の検出手段と、電気泳動を発生させる電圧供給手段、
とから成る電気泳動装置であって、ニッケル、パラジウ
ム、白金などの水素透過性材料を、カソ−ド兼隔離板と
して用い、この隔離板に接して泳動部とは独立して設け
た電解セル内の対極で、前記カソ−ドで発生して透過し
てくる水素を消費する手段を備えたキャピラリ−電気泳
動装置。24. A capillary for electrophoretic separation, sample supply means, and at least one for detecting separated sample components.
Individual detection means, voltage supply means for generating electrophoresis,
In an electrolysis cell using a hydrogen-permeable material such as nickel, palladium, or platinum as a cathode / separator and in contact with the separator and provided independently of the electrophoretic section. Capillary-electrophoresis device equipped with a means for consuming the hydrogen generated and permeated by the cathode at the opposite electrode.
隔離板を透過してくる水素を消費する電位に設定されて
いる請求項２４のキャピラリ−電気泳動装置。25. The capillary-electrophoresis device according to claim 24, wherein in the cell, the counter electrode is set to a potential that consumes hydrogen that permeates the separator.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8093827A JPH09281077A (en) | 1996-04-16 | 1996-04-16 | Capillary electrophoretic apparatus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8093827A JPH09281077A (en) | 1996-04-16 | 1996-04-16 | Capillary electrophoretic apparatus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH09281077A true JPH09281077A (en) | 1997-10-31 |
Family
ID=14093234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP8093827A Pending JPH09281077A (en) | 1996-04-16 | 1996-04-16 | Capillary electrophoretic apparatus |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH09281077A (en) |
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