【０００１】[0001]
【産業上の利用分野】本発明は、キャピラリ電気泳動チ
ップに関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a capillary electrophoresis chip.
【０００２】[0002]
【従来の技術】キャピラリ電気泳動法（ＣＥ）は、ペプ
チド、タンパク質、核酸、糖等の生体成分の分析の他、
光学分割、同位体の分離等、極めて近い成分を高速で分
離するに適した方法であり、臨床診断や医薬品、環境物
質のモニタリング等に広く利用される。2. Description of the Related Art Capillary electrophoresis (CE) is used for the analysis of biological components such as peptides, proteins, nucleic acids and sugars.
This method is suitable for high-speed separation of extremely close components such as optical resolution and isotope separation, and is widely used for clinical diagnosis, pharmaceuticals, monitoring of environmental substances and the like.
【０００３】細管を利用したキャピラリ電気泳動法は分
離度が高く、しかも、溶媒や試料の消費量が極めて少な
いという利点がある一方、このように試料の量が微量で
あるため、濃度感度が高速液体クロマトグラフ（ＨＰＬ
Ｃ）の１／１０〜１／１００程度と低く、検出感度がキ
ャピラリの内径に依存するという欠点がある。また、キ
ャピラリの内表面の状態は泳動液によって敏感に変化す
るため、泳動液を交換する際には十分なコンディショニ
ング作業が必要である。このような泳動液の交換作業を
行なわなくても済むように、泳動液毎にキャピラリを準
備しておくことも可能であるが、この場合にはキャピラ
リ毎にその履歴を管理しておく必要がある。The capillary electrophoresis method using a thin tube has an advantage that the separation degree is high and the consumption amount of the solvent and the sample is extremely small. On the other hand, since the sample amount is small, the concentration sensitivity is high. Liquid chromatograph (HPL
It is as low as about 1/10 to 1/100 of C), and has a drawback that the detection sensitivity depends on the inner diameter of the capillary. Moreover, since the state of the inner surface of the capillary changes sensitively depending on the electrophoretic liquid, it is necessary to perform sufficient conditioning work when exchanging the electrophoretic liquid. It is possible to prepare a capillary for each electrophoretic liquid so that such an electrophoretic liquid exchange operation need not be performed, but in this case, it is necessary to manage the history for each capillary. is there.
【０００４】このような問題点を解決するため、キャピ
ラリ電気泳動チップが開発された。これは図５に示すよ
うに、１対の透明平板（通常、ガラス板）５１、５２か
ら成り、一方の透明平板５２の表面に泳動用のキャピラ
リ溝５４、５５を形成し、他方の透明平板５１のその溝
５４、５５の端に対応する位置にリザーバ５３を設けた
ものである。その使用法は次の通りである。両透明平板
５１、５２を図５（ｃ）に示すように重ね、いずれかの
リザーバ５３から泳動液を溝５４、５５の中に注入す
る。そして、短い方の溝５４の一方の端のリザーバ５３
に試料を注入し、その溝５４の両端のリザーバ５３に電
極を差し込んで所定時間だけ高電圧を印加する。これに
より、試料は溝５４の中に分散される。次に、長い方の
溝５５の両端のリザーバに電極を差し込み、泳動電圧を
印加する。これにより、両溝５４、５５の交差部分５６
に存在する試料が溝５５内を電気泳動する。従って、溝
５５の適当な位置に紫外可視光分光光度計、傾向光度
計、電気化学検出器等の検出器を配置しておき（この部
分が検出セルとなる）、分離成分の検出を行なうことに
より、試料の分析を行なうことができる。In order to solve such problems, a capillary electrophoresis chip has been developed. As shown in FIG. 5, this is composed of a pair of transparent flat plates (usually glass plates) 51, 52. Capillary grooves 54, 55 for migration are formed on the surface of one transparent flat plate 52, and the other transparent flat plate is formed. The reservoir 53 is provided at a position corresponding to the ends of the grooves 54 and 55 of the 51. Its usage is as follows. Both transparent flat plates 51 and 52 are overlapped as shown in FIG. 5C, and the migration liquid is injected into the grooves 54 and 55 from either reservoir 53. Then, the reservoir 53 at one end of the shorter groove 54
The sample is injected into the chamber, electrodes are inserted into the reservoirs 53 at both ends of the groove 54, and a high voltage is applied for a predetermined time. As a result, the sample is dispersed in the groove 54. Next, electrodes are inserted into the reservoirs at both ends of the longer groove 55, and a migration voltage is applied. As a result, the intersection 56 of the grooves 54, 55
The sample existing in the groove electrophores in the groove 55. Therefore, a detector such as an ultraviolet-visible light spectrophotometer, a trend photometer, and an electrochemical detector is arranged at an appropriate position of the groove 55 (this portion becomes a detection cell) to detect the separated component. By this, the sample can be analyzed.
【０００５】このように、キャピラリ電気泳動チップ
は、２枚のガラス板にマイクロマシニングで溝や孔を形
成するのみで、電極、検出セル、リザーバ等が一体化さ
れた電気泳動装置が構成されるため、大量生産が可能で
あり、非常に低コストで製造することができる。このた
め、各泳動液、或いは各試料・各分析条件毎にチップを
用意しておくことができ、分析条件の変更等が極めて簡
単に且つ短時間で行なえるという特長を有する。また、
溝はチップ上に比較的自由に形成することができるため
並列多流路ＣＥが可能であり、更に、夾雑成分を系外に
排出したり、サンプル濃縮用の流路を分離流路に加えた
複合チップを容易にデザインすることも可能である。As described above, the capillary electrophoresis chip is an electrophoretic device in which electrodes, detection cells, reservoirs and the like are integrated only by forming grooves and holes in two glass plates by micromachining. Therefore, it can be mass-produced and can be manufactured at a very low cost. Therefore, a chip can be prepared for each electrophoretic solution, or for each sample and each analysis condition, and the change of the analysis condition can be performed very easily and in a short time. Also,
Since the grooves can be formed relatively freely on the chip, parallel multi-channel CE is possible. Further, contaminant components are discharged to the outside of the system, and a channel for sample concentration is added to the separation channel. It is also possible to easily design the composite chip.
【０００６】[0006]
【発明が解決しようとする課題】キャピラリ電気泳動チ
ップは上記のように数多くの利点を持つが、次のような
欠点を有する。まず、拡散用の電圧や泳動用の電圧を印
加するために溝の両端のリザーバに電極を差し込まなけ
ればならないが、リザーバが非常に小さい（通常、１ｍ
ｍφ程度）ことや、差し込んだ電極を確実に固定してお
くための手段が用意されていないこと等のため、操作性
が悪い。次に、チップ表面の濡れや汚れにより電極間の
絶縁不良が生じるおそれがある。さらに、チップ自体が
小さい（通常、１〜２ｃｍ角程度）ため、取り扱いに不
便であるとともに、チップの識別（すなわち、試験条件
等の識別）を行なうための表示が困難である。The capillary electrophoresis chip has many advantages as described above, but has the following drawbacks. First, the electrodes have to be inserted into the reservoirs at both ends of the groove in order to apply the diffusion voltage or the migration voltage, but the reservoir is very small (usually 1 m).
(about mφ), and means for securely fixing the inserted electrode are not prepared, and the operability is poor. Next, there is a possibility that insulation failure between electrodes may occur due to wetting or dirt on the chip surface. Furthermore, since the chip itself is small (usually about 1 to 2 cm square), it is inconvenient to handle, and it is difficult to make a display for identifying the chip (that is, identifying test conditions and the like).
【０００７】本発明はこれらの課題を解決するために成
されたものであり、その目的とするところは、操作性を
大きく改善したキャピラリ電気泳動チップを提供するこ
とにある。The present invention has been made to solve these problems, and an object thereof is to provide a capillary electrophoresis chip with greatly improved operability.
【０００８】[0008]
【課題を解決するための手段】上記課題を解決するため
に成された本発明に係るキャピラリ電気泳動チップは、
１対の略同形の透明平板を備え、少なくとも一方の透明
平板の表面に泳動液が流れる溝が形成され、他方の透明
平板の該溝の端に略対応する位置にそれぞれ貫通孔が設
けられ、両透明平板が溝を内側にして張り合わされて成
るキャピラリ電気泳動チップにおいて、 a)各貫通孔と外周の側面とをそれぞれ電気的に接続する
ように、少なくとも一方の透明平板に形成された導電性
薄膜と、 b)張り合わされた両透明平板の周囲を囲う絶縁材料製の
フレームと、 c)フレームと透明平板の上記導電性薄膜との接触部分毎
に設けられた内部接触電極と、 d)フレームの外側に設けられた複数の端子と、 e)フレームの内部に設けられ、内部接触電極と各端子と
をそれぞれ接続するリード線と、 を備えることを特徴とするものである。SUMMARY OF THE INVENTION A capillary electrophoresis chip according to the present invention made to solve the above problems,
A pair of transparent plates of substantially the same shape, at least one of the transparent plates has a groove on which the electrophoretic liquid flows, and the other transparent plate has through holes at positions substantially corresponding to the ends of the grooves; In a capillary electrophoresis chip in which both transparent flat plates are stuck together with their grooves inside, a) a conductive plate formed on at least one transparent flat plate so as to electrically connect each through hole to the outer side surface. A thin film, b) a frame made of an insulating material that surrounds both laminated transparent flat plates, c) an internal contact electrode provided at each contact portion between the frame and the transparent thin film, and d) a frame A) a plurality of terminals provided on the outside of the frame, and e) a lead wire provided inside the frame and connecting the internal contact electrode and each terminal, respectively.
【０００９】[0009]
【作用】まず、いずれかの貫通孔から泳動液を注入して
溝に泳動液を満たし、いずれか一方の貫通孔から試料を
注入する。各貫通孔は導電性薄膜−内部接触電極−リー
ド線の経路により各端子と電気的に接続しているため、
溝の両端の貫通孔に対応する端子に高電圧を印加するこ
とにより、その溝における電気泳動が行なわれる。First, the electrophoretic liquid is injected from any of the through holes to fill the groove with the electrophoretic liquid, and the sample is injected from any one of the through holes. Since each through hole is electrically connected to each terminal by the path of the conductive thin film-internal contact electrode-lead wire,
Electrophoresis in the groove is performed by applying a high voltage to the terminals corresponding to the through holes at both ends of the groove.
【００１０】なお、フレームは、ゴム等の弾性材料を用
いた一体型とし、弾性的に２枚の透明平板を保持するよ
うにしてもよいし、複数のパーツから成る分割型として
（一般的には２個に分割するのが好ましい）、２枚の透
明平板の周囲を囲ったパーツを適当な係合手段により固
定するようにしてもよい。The frame may be an integral type using an elastic material such as rubber and may elastically hold two transparent flat plates, or may be a divided type composed of a plurality of parts (generally, Is preferably divided into two pieces), and the parts surrounding the two transparent flat plates may be fixed by an appropriate engaging means.
【００１１】[0011]
【発明の効果】本発明に係るキャピラリ電気泳動チップ
では、電極が予めチップに形成されているため、小さい
孔に電極を差し込むという面倒な作業が不要である。ま
た、各薄膜電極は接触電極と内部リード線によりフレー
ムの外側の端子に確実に接続されているため、操作性が
向上するとともに、絶縁不良を生じることがなく、安定
した分析を行なうことができる。更に、フレームを適度
な大きさにしておくことにより、キャピラリ電気泳動チ
ップの取り扱いが便利になるとともに、フレームにバー
コード等を付けることが可能となり、チップの識別が容
易になる。In the capillary electrophoresis chip according to the present invention, since the electrodes are formed on the chip in advance, the troublesome work of inserting the electrodes into the small holes is unnecessary. Further, since each thin film electrode is securely connected to the terminal on the outside of the frame by the contact electrode and the internal lead wire, operability is improved and insulation failure does not occur, and stable analysis can be performed. . Furthermore, by making the frame an appropriate size, handling of the capillary electrophoresis chip becomes convenient, and a bar code or the like can be attached to the frame, so that the chip can be easily identified.
【００１２】[0012]
【実施例】本発明の一実施例であるキャピラリ電気泳動
チップを図１〜図４により説明する。図１に示すよう
に、本実施例のキャピラリ電気泳動チップ１０はチップ
本体１１とフレーム１２とから成る。チップ本体１１の
基本的構成は図５に示した従来のものと同様であり、そ
れぞれ溝５４、５５及びリザーバ５３が形成された２枚
の透明平板（本実施例の場合、ガラス板）２１、２２か
ら成る。ただし、本実施例のチップ本体１１では、各リ
ザーバ２３の箇所に、各リザーバ２３と透明平板２２
（他方の透明平板２１でも構わない）の直近の端面とを
接続する薄膜電極２７が形成されている。薄膜電極２７
は、金属の蒸着等により形成することにより、両透明平
板２１、２２の間に隙間を作らないようにすることがで
きる。EXAMPLE A capillary electrophoresis chip which is an example of the present invention will be described with reference to FIGS. As shown in FIG. 1, the capillary electrophoresis chip 10 of this embodiment comprises a chip body 11 and a frame 12. The basic structure of the chip body 11 is the same as that of the conventional one shown in FIG. 5, and two transparent flat plates (in this embodiment, glass plates) 21 in which grooves 54, 55 and a reservoir 53 are formed, It consists of 22. However, in the chip body 11 of the present embodiment, each reservoir 23 and the transparent flat plate 22 are provided at each reservoir 23.
A thin film electrode 27 is formed to connect with the nearest end face of the transparent plate 21 (other transparent plate 21 may be used). Thin film electrode 27
Can be formed by vapor deposition of metal or the like so that no gap is formed between the transparent flat plates 21 and 22.
【００１３】本実施例ではフレーム１２はゴム製であ
り、図２に示すように内周側端縁には、チップ本体１１
の周縁部の上下面を僅かに覆ってチップ本体１１を保持
するための保持部１２ａが形成されている。各薄膜電極
２７に対応する箇所には内部接触電極部１３が設けられ
ており、バネ等の適当な付勢手段（フレーム１２自体の
弾性を利用してもよい）により接触電極が薄膜電極２７
に押し付けられるようになっている。一方、フレーム１
２の一方の辺の外側にはコネクタ１４が設けられ、ここ
には少なくとも薄膜電極２７の数の端子１５が設けられ
ている。フレーム１２の内部にはリード線１６用の孔が
設けられており、各内部接触電極部１３はこのリード線
１６により各端子１５に接続されている。In this embodiment, the frame 12 is made of rubber, and as shown in FIG.
A holding portion 12a for holding the chip body 11 is formed by slightly covering the upper and lower surfaces of the peripheral edge portion of the. An internal contact electrode portion 13 is provided at a position corresponding to each thin film electrode 27, and the contact electrode is formed by a suitable biasing means such as a spring (the elasticity of the frame 12 itself may be used).
It can be pressed against. On the other hand, frame 1
A connector 14 is provided on the outer side of one side of 2, and at least terminals 15 corresponding to the thin film electrodes 27 are provided therein. A hole for a lead wire 16 is provided inside the frame 12, and each internal contact electrode portion 13 is connected to each terminal 15 by this lead wire 16.
【００１４】図３に示すように、このキャピラリ電気泳
動チップ１０のコネクタ１４に対応した形状のコネクタ
２０を用意し、これを高電圧源に接続することにより、
図４に示すような泳動用電圧印加回路が構成される。As shown in FIG. 3, a connector 20 having a shape corresponding to the connector 14 of the capillary electrophoresis chip 10 is prepared and is connected to a high voltage source.
A migration voltage application circuit as shown in FIG. 4 is configured.
【００１５】本実施例のキャピラリ電気泳動チップ１０
では上記のように、電極が一切外部に露出しないため、
安全な作業が行なえるとともに、絶縁不良のない確実な
泳動を行なうことができる。また、フレーム１２の表面
に例えば図１に示すようなバーコードラベル１７等を付
することにより、各キャピラリ電気泳動チップ１０の識
別が可能となり、多数のキャピラリ電気泳動チップ１０
の管理が容易となる。The capillary electrophoresis chip 10 of this embodiment
Then, as mentioned above, since the electrodes are not exposed to the outside,
Not only can safe work be performed, but reliable migration without insulation failure can be performed. Further, by attaching a barcode label 17 or the like as shown in FIG. 1 on the surface of the frame 12, it is possible to identify each capillary electrophoresis chip 10, and a large number of capillary electrophoresis chips 10 can be identified.
Management becomes easier.
【００１６】上記実施例ではフレーム１２はゴム製の一
体型のものとしたが、樹脂又はゴム製の２分割型として
もよい。この場合、一方のパーツを「コ」の字型とし、
他方のパーツを一直線型として、一直線型のパーツをス
ライダ式にはめ込む方法や、双方のパーツとも「コ」の
字型にして、フレーム材料である樹脂又はゴムの弾性を
利用したスナップ式係合手段により両パーツを固定する
方法等が考えられる。いずれの場合にも、両パーツの内
部のリード線１６の十分な接触及び導通を確保するよう
に、適切な内部接続手段を形成しておくことが望まし
い。In the above-mentioned embodiment, the frame 12 is made of rubber, but it may be made of resin or rubber. In this case, one of the parts has a "U" shape,
A method in which the other part is a straight line type and the straight line type parts are fitted in a slider type, or both parts are "U" shaped and snap type engagement means utilizing the elasticity of resin or rubber which is a frame material Therefore, a method of fixing both parts can be considered. In any case, it is desirable to form appropriate internal connecting means so as to ensure sufficient contact and conduction of the lead wires 16 inside both parts.
【図１】 本発明の一実施例であるキャピラリ電気泳動
チップの平面図。FIG. 1 is a plan view of a capillary electrophoresis chip which is an embodiment of the present invention.
【図２】 実施例のキャピラリ電気泳動チップの一部断
面図。FIG. 2 is a partial cross-sectional view of a capillary electrophoresis chip of an example.
【図３】 外部コネクタとの接続の様子を示す斜視図。FIG. 3 is a perspective view showing a state of connection with an external connector.
【図４】 外部コネクタとの接続により高電圧源と接続
されたときに構成される電気回路の回路図。FIG. 4 is a circuit diagram of an electric circuit configured when connected to a high voltage source by being connected to an external connector.
【図５】 従来のキャピラリ電気泳動チップの構成を示
す平面図及び側面図。FIG. 5 is a plan view and a side view showing a configuration of a conventional capillary electrophoresis chip.
１０…キャピラリ電気泳動チップ １１…チップ本体 １２…フレーム １２ａ…保持部 １３…内部接触電極部 １４…フレームコネクタ １５…端子 １６…リード線 １７…識別ラベル ２０…外部コネクタ ２１、２２…透明平板 ２３…リザーバ ２７…薄膜電極 DESCRIPTION OF SYMBOLS 10 ... Capillary electrophoresis chip 11 ... Chip main body 12 ... Frame 12a ... Holding part 13 ... Internal contact electrode part 14 ... Frame connector 15 ... Terminal 16 ... Lead wire 17 ... Identification label 20 ... External connector 21, 22 ... Transparent flat plate 23 ... Reservoir 27 ... Thin film electrode
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7066768AJP2937064B2 (en) | 1995-02-28 | 1995-02-28 | Capillary electrophoresis chip |
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7066768AJP2937064B2 (en) | 1995-02-28 | 1995-02-28 | Capillary electrophoresis chip |
| Publication Number | Publication Date |
|---|---|
| JPH08233778Atrue JPH08233778A (en) | 1996-09-13 |
| JP2937064B2 JP2937064B2 (en) | 1999-08-23 |
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7066768AExpired - Fee RelatedJP2937064B2 (en) | 1995-02-28 | 1995-02-28 | Capillary electrophoresis chip |
| Country | Link |
|---|---|
| JP (1) | JP2937064B2 (en) |
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