JP2004045410A - Sample separation device and chemical analysis device - Google Patents

Sample separation device and chemical analysis device Download PDF

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Publication number
JP2004045410A
JP2004045410A JP2003206161A JP2003206161A JP2004045410A JP 2004045410 A JP2004045410 A JP 2004045410A JP 2003206161 A JP2003206161 A JP 2003206161A JP 2003206161 A JP2003206161 A JP 2003206161A JP 2004045410 A JP2004045410 A JP 2004045410A
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Japan
Prior art keywords
separation
sample
outlet
liquid
junction
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JP2003206161A
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Japanese (ja)
Inventor
Akira Miyake
三宅 亮
Yoshihiro Nagaoka
長岡 嘉浩
Shigeo Watabe
渡部 成夫
So Kato
加藤 宗
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Hitachi Ltd
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Hitachi Ltd
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/60Construction of the column
    • G01N30/6034Construction of the column joining multiple columns
    • G01N30/6043Construction of the column joining multiple columns in parallel
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/26Conditioning of the fluid carrier; Flow patterns
    • G01N30/38Flow patterns
    • G01N30/46Flow patterns using more than one column
    • G01N30/466Flow patterns using more than one column with separation columns in parallel
    • G01N30/467Flow patterns using more than one column with separation columns in parallel all columns being identical
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02Column chromatography
    • G01N30/60Construction of the column
    • G01N30/6095Micromachined or nanomachined, e.g. micro- or nanosize

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sample separation device and a chemical analysis device having a uniform flow in a clearance in a chromato column, capable of preventing once separated component from being mixed again with another separated component, and having high separability. <P>SOLUTION: This sample separation device is attained by forming on a flat plane an inlet of a sample liquid, a successive inlet passage, a plurality of separation passages having respectively the equal sectional shape and the equal length, an outlet of separated liquid, an outlet passage linking to the outlet, a branch part branched from the inlet passage to the plurality of separation passages, and a joining part for joining the plurality of separation passages into one outlet passage. <P>COPYRIGHT: (C)2004,JPO

Description

【0001】
【発明の属する技術分野】
本発明は試料液中に溶存する成分を分離する試料分離装置および、分離された各々の成分濃度を定量する化学分析装置に係わり、特に生体液や水などの成分分析を行うクロマトグラフに関する。
【0002】
【従来の技術】
本発明の化学分析装置に対応する従来技術としては、文献Gregor Ocvirk, ”Integration of a micro liquid chromatograph onto a silicon chip”, Proc.. of Transducers ’95 pp756−759 (1995)記載のシリコン基板上に形成されたクロマトカラムと光学測定用フローセルがある。
【0003】
本クロマトカラムはシリコン基板をエッチング加工により幅300μm、深さ100μm、長さ20mmに彫った溝の上から、ガラス板を接合した後、計5μmの微粒子(吸着物質のコート済み)を充填して形成されている。またクロマトカラムの出口直後には、光学測定用のフローセルが同じくエッチング加工により形成されている。このカラム内を試料液が通過する際に、試料液中の成分毎に微粒子表面への吸着の度合いが異なるため、カラム出口では、吸着の低い成分から順に出てくる。この分離成分をカラム直後に設けられた光学測定用のフローセルで検知する。本従来技術ではクロマトカラムとフローセルをエッチング加工により近接して設けることが可能となるため、その間の流路において分離成分の拡散が抑えられ、高い分離性能を維持できるとしている。
【0004】
【発明が解決しようとする課題】
各溶解成分を高感度に、迅速に分析するためには、検知部での各分離成分の検出ピークが相互に重なることなく十分に離れている必要がある。また分離能力を同等にして、クロマトカラムを短くした場合、計測時間の短縮、送液圧力の低減による送液ポンプの簡素化などの効果がある。しかし、この検知部での分離度を上げるためには、クロマトカラムでの分離能力をさらに向上させる必要があること、カラムから検知部に至る流路で各分離成分が再び混合しないようにする必要がある。
【0005】
上記従来技術では、分離性能を上げるためにクロマトカラムからフローセルに至る流路を短縮して、輸送中に起きる拡散による分離成分の再混合を極力抑えようとしている。その一方、分離性能を司るクロマトカラムに関しては、機能的には微粒子を詰める従来の管型カラムと大差なく、特に分離性能が向上しているわけではない。この微粒子を充填したクロマトカラムでの分離の原理を微視的に見ると次のようになる。
【0006】
クロマトカラム内に送液された試料液は、まずカラム断面一杯に広がり、各微粒子間の隙間に入り、流れ込む。この際に試料液内の溶解化学成分の分子は、隙間の中の局所的な流れや、分子拡散によって微粒子表面まで到達し、微粒子表面にコーティングされている吸着物質との間で吸着反応を起こす。この吸着の度合いが成分分子毎に異なるため、隙間を通過する際に成分毎に分離が起こる。しかしながら、この微粒子を用いた分離技術には以下の問題点がある。
【0007】
各隙間を流れ出た試料液は、その下流では別の隙間を流れてきた試料液と合流することになるが、別々の隙間を通過した試料液の分離状態は、各隙間の大きさ、距離が均一ではないため、同じ分離成分が同じタイミングで合流するとは限らず、異なる分離成分同士が再び合流し混合することになる。
【0008】
また、合流位置で淀むような流れがあれば、そこで分離成分が再び混合してしまう。このように微粒子を詰めたクロマトカラムでは微粒子同士の隙間の形状が不均一のため、分離能力向上には限界がある。この問題を解決するために、クロマトカラムの断面積を小さく、断面内での流れの偏在を小さくしたり、カラム内に充填する微粒子を小さくして、隙間の均一性を増すなどの改良が行われているが、根本的な解決には至っていない。
【0009】
本発明の目的は、クロマトカラム内において隙間の流れが均一で、一度分離した成分が再び他の分離成分と混合することのない、分離能力の高い試料分離装置および化学分析装置を提供することである。
【0010】
【課題を解決するための手段】
上記目的は、試料分離装置あるいは化学分析装置において、試料液の入口と、それに続く入口流路と、複数の等しい断面形状で、等しい長さの分離用流路と、分離液の出口と、出口に繋がる出口流路と、入口流路から複数の分離用流路に分岐させる分岐部と、複数の分離用流路を一本の出口流路に合流させる合流部を平板上に形成することにより解決される。
【0011】
【発明の実施の形態】
本発明の一実施例を図1〜図6を用いて説明する。図1は本発明の試料分離装置を備えた化学分析装置の全体構成図、図2は本発明の試料分離装置の詳細説明図、図3、4は本発明の別の試料分離装置の説明図、図5は本発明の別の化学分析装置の全体構成図を示す。図6は本発明の分離流路での分離の原理を説明する模式図である。
【0012】
図1において本発明の化学分析装置の構成について、上流から下流に向かって順に説明する。
【0013】
移動用の媒体として用いるキャリア液11がキャリア液槽10に保持されている。キャリア液槽10から試料分離装置40の間は配管12で繋がれており、この配管12の途中にはキャリア液11を汲み上げて試料分離装置へ送液するためのポンプ20、およびキャリア液11中に試料液30を注入するための注入バルブ31が、順に設けられている。注入バルブ31には、試料液30を注入するための孔があり、そこに注射器32が取り付けられるようになっている。注射器32の中は試料液30が吸引保持されている。
【0014】
試料分離装置40には配管12と接続された入口41、試料分離装置40で分離した試料液の出口42がある。この出口42から廃液槽70までは配管13で繋がれており、途中には液の吸収スペクトルを計測するためのフローセル50が設けられている。またフローセル50に光を照射するための光源51、フローセル50を透過した光を検知するための検知器52が設けられている。信号処理・動作制御部60からポンプ20、光源51に対しては制御信号を、また検知器52には検知信号用のケーブルが繋がれている。
【0015】
次に、図2を用いて試料分離装置40の構造について説明する。試料分離装置40には試料液30やキャリア液11を導入するための入口41、および分離した試料液30を排出するための出口42が設けられている。入口42から等しい断面形状、等しい長さの2つの分離用流路451、461が分岐している。各々の分離用流路451、461は、分岐部452、462を経て、それぞれ等しい断面形状、等しい長さの分離用流路453、454および463、464に別れている。この分岐用流路453、454および463、464は、再び合流部455、465を経てそれぞれ等しい断面形状、等しい長さの分離用流路456、466に統合される。更に、これらの流路456、466は一つに合流し、出口42へと連結している。これら全ての分離用流路の内壁には、分離用の吸着物質がコーティングされている。
【0016】
上記構成の化学分析装置は、以下のように動作する。
【0017】
まず、信号処理・動作制御部60からの制御信号を受けてポンプ20が送液を開始する。ポンプ20はキャリア液槽10からキャリア液11を一定流量で汲み上げ配管12を通して試料分離装置40へ供給を始める。流れが安定した時点で注入バルブ31に試料液30の入った注射器32を挿入し、一定量の試料液30を配管12中に注入する。試料液30はキャリア液11の流れに乗って試料分離装置40の入口41から内部に導入される。ここで各分離流路の断面形状、長さともに等しいので試料分離流路451に続く流路の圧力抵抗、461に続く流路の圧力抵抗は等しい。従って、試料液30を含むキャリア液11は流路451、461にそれぞれ等流量で均等に分岐して流れる。同じく流路451から分岐部452へ差し掛かった流れは、それに続く流路463、464共に流路抵抗が等しいため、均等の流量でそれぞれに分岐して流れる。以下の流路461−分岐部462−流路463、464においても同様であり、等流量で分岐する。
【0018】
図6は本発明の分離工程を示したものであるが、まずそれぞれの分離流路453,454において、流路壁面の吸着物質との相互作用で試料液中の成分が第1から第3までの3成分33、34、35に分離する。2つの流路で起こる分離パターンは2つの流路の形状、流動条件が同じであれば、図に示したように同じパターンを示す。また2つの流路の長さが同じであれば、同様に図に示すとおり合流部において同じタイミングで各成分同士が合流する。そのため、従来技術で顕著であった、微粒子間の隙間の不均一性による分離性能の低下は発生しない。各流路で分離した成分は、相互に混合することなく合流し、出口43より出て、フローセル50に送られる。フローセル50では信号処理・駆動制御部60からの信号を受けて光源が発光し、フローセル中の分離成分の吸収スペクトルの時間変化を検知器52が捉え、その信号を信号処理・駆動制御部60へ送りデータ処理を行う。
【0019】
以上のように本発明は、クロマトカラム内において均一な流れを形成させることが可能となり、一度分離した成分が再び他の分離成分と混合することのない、分離能力の高い試料分離装置および化学分析装置を提供することが可能となる。
【0020】
本発明の他の実施例について図3を用いて説明する。図3は、試料分離装置40の他の構造を示したものである。本実施例は、図2で示した試料液分離装置40の分離用流路を階層構造としたもので、図2と同じ部分は同じ番号を付した。図2の試料分離装置と同様に、同じ階層の各流路の断面形状、流路長さは等しくなっているので第1の実施例同様に高い分離能力が得られる。第1図の実施例の試料分離装置と比較すると、分離流路の数が多くなるため、試料液と吸着物質との接触確率は高まり、より短時間で高い分離性能が得られる。また本実施例の試料分離装置は2つの試料分離部71、72を直列に繋げているため、より細かに成分を分離することができる。
【0021】
図4は本発明の他の実施例の試料分離装置を示したものである。
図4では3枚の分離用流路プレート91、92、93を縦方向に積層したものであり、入口41から入った試料液は3枚の分離用流路プレートに均等に分散する。それぞれのプレート内の流路において、左から右に向かって試料液が流れて行くが、どの経路を辿っても入口から出口までの距離は同じとなるように格子状に流路が形成されている。格子の一辺に相当する単位流路要素94の断面形状を同じにしておけば、合流位置で異なる分離成分が混合することはない。さらに本実施例においては3つの分離用流路プレートを重ねて並列接続しているため、多量の分離成分を短時間に得ることができ、測定の感度も向上する。なお分離流路の形状は図2又は図3と同じ形状に構成していも良い。
【0022】
図2、図3、図4記載の試料分離装置内の分離流路を同じ断面形状で高精度に形成するためには、エッチング等の半導体製造技術を利用する。従来の微粒子を充填することにより、隙間に匹敵する幅の微細な流路を非常に容易に薄い板に多数形成でき、これを複数枚重ねることで小さな容積で高密度に分離流路が実装でき、小形化に寄与する。
【0023】
本発明の他の実施例を図5を用いて説明する。図5は高分離性能を得るために、図1に示すキャリア液と試料液が混合された状態で送液用のポンプ20で吸引送出して、その他の部品を直列に連結して構成した化学分析装置である。
【0024】
この構成の場合、各試料分離装置での圧力損失が積算されるため、駆動ポンプとして高圧で大型のポンプが必要となる。そこで、これらの問題を解決するために試料分離装置の各々の間に薄型の小形ポンプ20を設けたものである。本実施例のポンプ20はバイモルフ振動体21、逆止弁22、23から成る。最下部のポンプより吸引された試料およびキャリア液は順次下からフローセル50に向かって汲み上げられる。ひとつのポンプはひとつの試料分離装置内のみ試料液を送液するだけの圧力があれば良いから、図に示したようなダイヤフラム型の簡素なポンプであっても試料液の送液ができ、全体システムの小形化へ寄与する。
【0025】
【発明の効果】
本発明により、クロマトカラム内において隙間の流れが均一で、一度分離した成分が再び他の分離成分と混合することのない、分離能力の高い試料分離装置および化学分析装置を提供することが可能となる。
【図面の簡単な説明】
【図1】本発明の化学分析装置の構成図である。
【図2】本発明の試料分離装置の構成図である。
【図3】本発明の別の試料分離装置の構成図である。
【図4】本発明の別の試料分離装置の構成図である。
【図5】本発明の別の化学分析装置の構成図である。
【図6】本発明の分離流路での試料分離の状態の様子を示す説明図である。
【符号の説明】
10…キャリア液槽、11…キャリア液、12、13…配管、20…ポンプ、30…試料液、31…注入バルブ、32…注射器、40…試料分離装置、41…入口、42…出口、50…フローセル、51…光源、52…検知器、60…信号処理・動作制御部、451〜466…分離流路、71…第1試料分離部、72…第2試料分離部、91、92、93…分離用プレート、94…単位流路要素、21…バイモルフ振動体、22、23…逆止弁。
[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a sample separation device for separating components dissolved in a sample liquid and a chemical analyzer for quantifying the concentration of each separated component, and more particularly to a chromatograph for analyzing components such as biological fluids and water.
[0002]
[Prior art]
As a prior art corresponding to the chemical analyzer of the present invention, reference is made to Gregor Ocvirk, "Integration of micro liquid chromatography on a silicon chip", Proc. . of Transducers '95 pp756-759 (1995), there is a chromatography column and a flow cell for optical measurement formed on a silicon substrate.
[0003]
This chromatographic column is obtained by bonding a glass plate from above a groove formed by etching a silicon substrate to a width of 300 μm, a depth of 100 μm, and a length of 20 mm, and then filling a total of 5 μm fine particles (coated with an adsorbed substance). Is formed. Immediately after the exit of the chromatographic column, a flow cell for optical measurement is also formed by etching. When the sample solution passes through the column, the degree of adsorption on the surface of the fine particles differs for each component in the sample solution. This separated component is detected by a flow cell for optical measurement provided immediately after the column. According to this conventional technique, it is possible to provide a chromatographic column and a flow cell closer to each other by etching, so that diffusion of a separation component is suppressed in a flow path therebetween, and high separation performance can be maintained.
[0004]
[Problems to be solved by the invention]
In order to analyze each dissolved component with high sensitivity and speed, it is necessary that the detection peaks of each separated component in the detection unit are sufficiently separated without overlapping each other. Further, when the chromatographic column is shortened with the same separation capacity, there are effects such as shortening of measurement time and simplification of a liquid sending pump by reducing liquid sending pressure. However, in order to increase the degree of separation at this detector, it is necessary to further improve the separation capacity of the chromatographic column, and it is necessary to prevent the separation components from mixing again in the flow path from the column to the detector. There is.
[0005]
In the above prior art, the flow path from the chromatographic column to the flow cell is shortened in order to improve the separation performance, and the remixing of the separated components due to diffusion occurring during transportation is suppressed as much as possible. On the other hand, the chromatographic column controlling the separation performance is not much different from the conventional tubular column packed with fine particles in terms of function, and the separation performance is not particularly improved. Microscopically, the principle of the separation in a chromatography column filled with the fine particles is as follows.
[0006]
The sample liquid sent into the chromatographic column first spreads over the entire column cross section, enters gaps between the fine particles, and flows. At this time, the molecules of the dissolved chemical components in the sample liquid reach the fine particle surface by local flow in the gap or by molecular diffusion, and cause an adsorption reaction with the adsorbed substance coated on the fine particle surface. . Since the degree of adsorption differs for each component molecule, separation occurs for each component when passing through the gap. However, the separation technique using the fine particles has the following problems.
[0007]
The sample liquid that has flowed out of each gap will merge with the sample liquid that has flowed in another gap downstream of the gap.However, the separation state of the sample liquid that has passed through different gaps depends on the size and distance of each gap. Because they are not uniform, the same separated components do not always merge at the same timing, and different separated components will merge and mix again.
[0008]
In addition, if there is a flow that stagnates at the junction, the separated components are mixed again there. In a chromatographic column packed with fine particles as described above, the shape of the gap between the fine particles is not uniform, and thus there is a limit in improving the separation ability. In order to solve this problem, improvements were made such as reducing the cross-sectional area of the chromatographic column, minimizing the uneven distribution of flow in the cross-section, and reducing the size of fine particles packed in the column to increase the uniformity of the gap. However, it has not reached a fundamental solution.
[0009]
An object of the present invention is to provide a sample separation device and a chemical analysis device having a high separation ability, in which the flow of the gap is uniform in the chromatographic column, and the components separated once do not mix again with other separated components. is there.
[0010]
[Means for Solving the Problems]
The object is to provide a sample separation apparatus or a chemical analysis apparatus, in which a sample liquid inlet, a subsequent inlet flow path, a plurality of separation flow paths having the same cross-sectional shape and the same length, a separation liquid outlet, and an outlet are provided. By forming on a flat plate an outlet flow path, a branch portion that branches from the inlet flow path to a plurality of separation flow paths, and a junction that merges the plurality of separation flow paths into one outlet flow path. Will be resolved.
[0011]
BEST MODE FOR CARRYING OUT THE INVENTION
An embodiment of the present invention will be described with reference to FIGS. FIG. 1 is an overall configuration diagram of a chemical analysis device provided with a sample separation device of the present invention, FIG. 2 is a detailed explanatory diagram of the sample separation device of the present invention, and FIGS. 3 and 4 are explanatory diagrams of another sample separation device of the present invention. FIG. 5 shows an overall configuration diagram of another chemical analyzer according to the present invention. FIG. 6 is a schematic diagram for explaining the principle of separation in the separation channel of the present invention.
[0012]
In FIG. 1, the configuration of the chemical analyzer of the present invention will be described in order from upstream to downstream.
[0013]
A carrier liquid 11 used as a transfer medium is held in a carrier liquid tank 10. The carrier liquid tank 10 and the sample separation device 40 are connected by a pipe 12. In the middle of the pipe 12, a pump 20 for pumping up the carrier liquid 11 and sending it to the sample separation device, and An injection valve 31 for injecting the sample liquid 30 into the sample is provided in order. The injection valve 31 has a hole into which the sample liquid 30 is injected, and a syringe 32 is attached to the hole. The sample liquid 30 is suction-held in the syringe 32.
[0014]
The sample separator 40 has an inlet 41 connected to the pipe 12 and an outlet 42 for the sample liquid separated by the sample separator 40. The outlet 42 and the waste liquid tank 70 are connected by the pipe 13, and a flow cell 50 for measuring the absorption spectrum of the liquid is provided in the middle. Further, a light source 51 for irradiating light to the flow cell 50 and a detector 52 for detecting light transmitted through the flow cell 50 are provided. A signal processing / operation control unit 60 connects a control signal to the pump 20 and the light source 51, and a detector 52 is connected to a cable for a detection signal.
[0015]
Next, the structure of the sample separation device 40 will be described with reference to FIG. The sample separation device 40 is provided with an inlet 41 for introducing the sample liquid 30 and the carrier liquid 11 and an outlet 42 for discharging the separated sample liquid 30. Two separation channels 451 and 461 having the same cross-sectional shape and the same length are branched from the inlet 42. Each of the separation channels 451, 461 is divided into separation channels 453, 454 and 463, 464 having the same cross-sectional shape and the same length, respectively, via the branch portions 452, 462. The branching channels 453, 454 and 463, 464 are again integrated into separation channels 456, 466 having the same cross-sectional shape and the same length via the junctions 455, 465, respectively. Further, these channels 456, 466 join together and are connected to the outlet 42. The inner walls of all these separation channels are coated with an adsorbing substance for separation.
[0016]
The chemical analyzer having the above configuration operates as follows.
[0017]
First, the pump 20 starts liquid supply in response to a control signal from the signal processing / operation control unit 60. The pump 20 pumps the carrier liquid 11 from the carrier liquid tank 10 at a constant flow rate and starts supplying the carrier liquid 11 to the sample separation device 40 through the pipe 12. When the flow is stabilized, the syringe 32 containing the sample liquid 30 is inserted into the injection valve 31, and a fixed amount of the sample liquid 30 is injected into the pipe 12. The sample liquid 30 is introduced into the sample separation device 40 from the inlet 41 along with the flow of the carrier liquid 11. Here, since the cross-sectional shape and length of each separation channel are equal, the pressure resistance of the channel following the sample separation channel 451 and the pressure resistance of the channel following 461 are equal. Accordingly, the carrier liquid 11 containing the sample liquid 30 is equally branched and flows into the flow paths 451 and 461 at the same flow rate. Similarly, the flow approaching the branch portion 452 from the flow path 451 is branched and flows at an equal flow rate because the flow resistances of the subsequent flow paths 463 and 464 are equal. The same applies to the following flow channels 461-branch portions 462-channels 463, 464, and branches at an equal flow rate.
[0018]
FIG. 6 shows the separation step of the present invention. First, in each of the separation channels 453 and 454, the components in the sample liquid are changed from the first to the third by interaction with the adsorbed substance on the channel walls. Into three components 33, 34 and 35. The separation patterns occurring in the two flow paths show the same pattern as shown in the drawing if the shapes and flow conditions of the two flow paths are the same. If the lengths of the two flow paths are the same, the respective components merge at the same timing at the junction as shown in the figure. For this reason, the deterioration of the separation performance due to the unevenness of the gap between the fine particles, which is remarkable in the related art, does not occur. The components separated in the respective flow paths merge without being mixed with each other, and exit from the outlet 43 and are sent to the flow cell 50. In the flow cell 50, the light source emits light in response to a signal from the signal processing / drive control unit 60, and the detector 52 detects a temporal change in the absorption spectrum of the separated component in the flow cell, and sends the signal to the signal processing / drive control unit 60. Perform feed data processing.
[0019]
INDUSTRIAL APPLICABILITY As described above, the present invention makes it possible to form a uniform flow in a chromatographic column, and once separated components do not mix with other separated components again. A device can be provided.
[0020]
Another embodiment of the present invention will be described with reference to FIG. FIG. 3 shows another structure of the sample separation device 40. In the present embodiment, the separation channel of the sample liquid separation device 40 shown in FIG. 2 has a hierarchical structure, and the same parts as those in FIG. As in the sample separation apparatus of FIG. 2, the cross-sectional shapes and the flow path lengths of the flow paths in the same layer are equal, so that a high separation ability can be obtained as in the first embodiment. As compared with the sample separation device of the embodiment shown in FIG. 1, the number of separation channels is increased, so that the probability of contact between the sample liquid and the adsorbed substance is increased, and high separation performance can be obtained in a shorter time. In the sample separation device of the present embodiment, since the two sample separation units 71 and 72 are connected in series, the components can be separated more finely.
[0021]
FIG. 4 shows a sample separation apparatus according to another embodiment of the present invention.
In FIG. 4, three separation channel plates 91, 92, and 93 are vertically stacked, and the sample liquid entered from the inlet 41 is evenly dispersed in the three separation channel plates. The sample liquid flows from left to right in the flow path in each plate, but the flow path is formed in a grid so that the distance from the inlet to the outlet is the same regardless of the path. I have. If the cross-sectional shapes of the unit flow path elements 94 corresponding to one side of the lattice are the same, different separation components will not be mixed at the merging position. Further, in this embodiment, since three separation flow path plates are overlapped and connected in parallel, a large amount of separation components can be obtained in a short time, and the measurement sensitivity is improved. The shape of the separation channel may be the same as that of FIG. 2 or FIG.
[0022]
In order to form the separation flow paths in the sample separation device shown in FIGS. 2, 3 and 4 with the same cross-sectional shape with high precision, a semiconductor manufacturing technique such as etching is used. By filling with conventional microparticles, a large number of fine channels with a width comparable to the gap can be formed very easily on a thin plate, and by stacking a plurality of these, a high-density separation channel can be mounted with a small volume. , Contributes to miniaturization.
[0023]
Another embodiment of the present invention will be described with reference to FIG. FIG. 5 shows a chemical composition in which the carrier liquid and the sample liquid shown in FIG. 1 are mixed and suctioned and sent out by a pump 20 for feeding, and other parts are connected in series in order to obtain high separation performance. It is an analyzer.
[0024]
In the case of this configuration, since the pressure loss in each sample separation device is integrated, a large-sized high-pressure pump is required as a driving pump. In order to solve these problems, a thin small pump 20 is provided between each of the sample separation devices. The pump 20 according to the present embodiment includes a bimorph vibrator 21 and check valves 22 and 23. The sample and the carrier liquid sucked from the lowermost pump are sequentially pumped from below toward the flow cell 50. One pump only needs to have a pressure enough to send the sample liquid only in one sample separation device, so even a simple diaphragm type pump as shown in the figure can send the sample liquid. It contributes to downsizing of the whole system.
[0025]
【The invention's effect】
Advantageous Effects of Invention According to the present invention, it is possible to provide a sample separation device and a chemical analysis device having a high separation ability, in which the flow in the gap is uniform in the chromatographic column, and the components separated once do not mix with other separated components again. Become.
[Brief description of the drawings]
FIG. 1 is a configuration diagram of a chemical analyzer according to the present invention.
FIG. 2 is a configuration diagram of a sample separation device of the present invention.
FIG. 3 is a configuration diagram of another sample separation device of the present invention.
FIG. 4 is a configuration diagram of another sample separation device of the present invention.
FIG. 5 is a configuration diagram of another chemical analysis device of the present invention.
FIG. 6 is an explanatory diagram showing a state of sample separation in a separation channel of the present invention.
[Explanation of symbols]
DESCRIPTION OF SYMBOLS 10 ... Carrier liquid tank, 11 ... Carrier liquid, 12, 13 ... Piping, 20 ... Pump, 30 ... Sample liquid, 31 ... Injection valve, 32 ... Syringe, 40 ... Sample separator, 41 ... Inlet, 42 ... Outlet, 50 ... Flow cell, 51 ... Light source, 52 ... Detector, 60 ... Signal processing / operation control unit, 451-466 ... Separation channel, 71 ... First sample separation unit, 72 ... Second sample separation unit, 91, 92, 93 ... separation plate, 94 ... unit flow path element, 21 ... bimorph vibrator, 22, 23 ... check valve.

Claims (5)

試料液の入口と、それに続く入口流路と、複数の等しい断面形状で、等しい長さの分離用流路と、分離液の出口と、出口に繋がる出口流路と、入口流路から複数の分離用流路に分岐させる分岐部と、複数の分離用流路を一本の出口流路に合流させる合流部を平板上に形成したことを特徴とする試料分離装置。A sample liquid inlet, a subsequent inlet flow path, a plurality of equal cross-sectional shapes, separation flow paths having the same length, an outlet for the separated liquid, an outlet flow path connected to the outlet, and a plurality of A sample separation device, wherein a branch portion for branching into a separation channel and a junction for joining a plurality of separation channels to one outlet channel are formed on a flat plate. 請求項1において、前記分離用流路の合流部に、分岐部と複数の分離流路と合流部を備えた試料分離部を階層的に設けたことを特徴とする試料分離装置。2. The sample separation apparatus according to claim 1, wherein a sample separation section having a branch, a plurality of separation channels, and a junction is provided in a hierarchy at a junction of the separation flow paths. 請求項1において、前記分岐部から合流部に至る分離用流路は、格子状に交差しており、格子間の流路は、全て等断面、同じ長さであり、分岐部から合流部まで下流方向に沿ってどの経路を辿っても同じ距離となるように形成したことを特徴とする試料分離装置。In claim 1, the separation flow path from the branch to the junction intersects in a grid pattern, and all the channels between the lattices have the same cross-section and the same length, from the branch to the junction. What is claimed is: 1. A sample separation apparatus, wherein the distance is the same regardless of the path along the downstream direction. 試料液中の溶解化学成分を分離し、各分離成分の濃度を検出する化学分析装置において、
試料液の入口と、それに続く入口流路と、複数の等しい断面形状で、等しい長さの分離用流路と、分離液の出口と、出口に繋がる出口流路と、入口流路から複数の分離用流路に分岐させる分岐部と、複数の分離用流路を一本の出口流路に合流させる合流部を平板上に形成した試料分離装置を設けたことを特徴とする化学分析装置。
In a chemical analyzer that separates dissolved chemical components in a sample solution and detects the concentration of each separated component,
A sample liquid inlet, a subsequent inlet flow path, a plurality of separation flow paths having the same cross-sectional shape and the same length, an outlet for the separated liquid, an outlet flow path connected to the outlet, and a plurality of A chemical analyzer comprising: a sample separation device in which a branch portion for branching into a separation channel and a junction for joining a plurality of separation channels to one outlet channel are formed on a flat plate.
請求項4において、前記試料分離装置を複数積層して構成すると共に、前記各試料分離装置の間に試料送液手段を設けたことを特徴とする化学分析装置。5. The chemical analyzer according to claim 4, wherein a plurality of the sample separation devices are stacked, and a sample liquid sending means is provided between each of the sample separation devices.
JP2003206161A 2003-08-06 2003-08-06 Sample separation device and chemical analysis device Pending JP2004045410A (en)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006055770A (en) * 2004-08-20 2006-03-02 Tosoh Corp Microchannel structure
JP2007163459A (en) * 2005-11-18 2007-06-28 Sharp Corp Assay-use microchip
WO2008020593A1 (en) * 2006-08-14 2008-02-21 Tokyo Electron Limited Column for chromatography and method for producing the same
WO2013094322A1 (en) * 2011-12-22 2013-06-27 株式会社 島津製作所 Chip device for manipulating object component, and method using same
JP2017534840A (en) * 2014-09-05 2017-11-24 イマジン ティーエフ,エルエルシー Fine structure separation filter

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006055770A (en) * 2004-08-20 2006-03-02 Tosoh Corp Microchannel structure
JP2007163459A (en) * 2005-11-18 2007-06-28 Sharp Corp Assay-use microchip
WO2008020593A1 (en) * 2006-08-14 2008-02-21 Tokyo Electron Limited Column for chromatography and method for producing the same
WO2013094322A1 (en) * 2011-12-22 2013-06-27 株式会社 島津製作所 Chip device for manipulating object component, and method using same
JP2013130548A (en) * 2011-12-22 2013-07-04 Shimadzu Corp Chip device for manipulating object component, and method using the same
US9714445B2 (en) 2011-12-22 2017-07-25 Shimadzu Corporation Chip device for manipulating object component, and method using the same
JP2017534840A (en) * 2014-09-05 2017-11-24 イマジン ティーエフ,エルエルシー Fine structure separation filter

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