JP2005283391A - Liquid chromatograph mass spectrometer - Google Patents

Liquid chromatograph mass spectrometer Download PDF

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JP2005283391A
JP2005283391A JP2004099014A JP2004099014A JP2005283391A JP 2005283391 A JP2005283391 A JP 2005283391A JP 2004099014 A JP2004099014 A JP 2004099014A JP 2004099014 A JP2004099014 A JP 2004099014A JP 2005283391 A JP2005283391 A JP 2005283391A
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JP4400284B2 (en
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Kazuo Kouhata
和男 向畑
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Shimadzu Corp
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Abstract

<P>PROBLEM TO BE SOLVED: To complementarily detect information for a compound such that it cannot be properly ionized, causing an analysis omission in a mass spectrometric part, by adding a simple structure. <P>SOLUTION: This mass spectrometer comprises a light emission part 25 emitting a measuring light across an atomized flow 27 of sample droplets from a sample liquid tube 221 of an atmospheric ionization interface into an ionization chamber, and a photomultiplier 26 for detecting scattered light or absorbed light in the atomized flow, which are arranged on the tip side of the atomized flow 27. The sample is ionized in the process of evaporating a mobile phase from the atomized droplets, and the ions are sucked to a desolvating tube 23. A number of fine particles of the sample from which the mobile phase is simply evaporated are present in the atomized flow. The scattered light or absorbed light corresponding to the measuring light emitted from the light emission part 25 is detected by the photomultiplier 26, whereby an easy evaporation light scattering detection can be performed, and this detection result can be used to complement a mass analytic result. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

本発明は、液体クロマトグラフの検出器として質量分析装置を用いた液体クロマトグラフ質量分析装置に関する。   The present invention relates to a liquid chromatograph mass spectrometer using a mass spectrometer as a detector of a liquid chromatograph.

液体クロマトグラフでは分析目的や試料の種類などに応じて様々な検出器が利用されているが、近年、高い成分選択性と定性分析能力を有する質量分析装置を検出器とした液体クロマトグラフ質量分析装置（以下「ＬＣ／ＭＳ」と称す）が盛んに利用されるようになってきている。ＬＣ／ＭＳでは、ＬＣ部のカラムから溶出する液体試料に含まれる試料成分を気体イオンにするために大気圧イオン化インタフェイスが用いられる。代表的な大気圧イオン化法としては、エレクトロスプレイイオン化法（ＥＳＩ）や大気圧化学イオン化法（ＡＰＣＩ）などが知られている。   Various detectors are used in liquid chromatographs depending on the purpose of analysis and the type of sample. In recent years, liquid chromatograph mass spectrometry using a mass spectrometer with high component selectivity and qualitative analysis capability as a detector. An apparatus (hereinafter referred to as “LC / MS”) has been actively used. In LC / MS, an atmospheric pressure ionization interface is used to convert sample components contained in a liquid sample eluted from the column of the LC section into gas ions. As typical atmospheric pressure ionization methods, an electrospray ionization method (ESI), an atmospheric pressure chemical ionization method (APCI), and the like are known.

ＥＳＩでは、液体試料を導入したノズルの先端部に数ｋＶ程度の高電圧を印加し、強い不平等電界を発生させる。液体試料はノズル中を流れる際にこの電界により電荷分離し、クーロン引力により引きちぎられるように霧化する。そして、周囲の乾燥空気に触れて液滴中の溶媒が蒸発する過程で気体イオンが発生する。こうした原理から、ＥＳＩは高極性化合物や熱に不安定な化合物のイオン化に適しているが、低極性又は無極性の化合物には適さない。他方、ＡＰＣＩでは、ノズルの先端の前方に針電極を配置しておき、ノズルにおいて加熱により霧化した液体試料の液滴に、針電極からのコロナ放電により生成したキャリアガスイオンを化学反応させてイオン化を行う。こうした原理から、ＡＰＣＩは比較的低極性である化合物から極性化合物などのイオン化に適するが、高極性化合物や熱に不安定な化合物には適さない。   In ESI, a high voltage of about several kV is applied to the tip of a nozzle into which a liquid sample is introduced to generate a strong unequal electric field. When the liquid sample flows through the nozzle, the electric field is separated by this electric field and atomized so as to be torn off by the Coulomb attractive force. Gas ions are generated in the process of evaporating the solvent in the droplets by touching the surrounding dry air. Based on these principles, ESI is suitable for ionization of highly polar compounds and thermally unstable compounds, but is not suitable for low polarity or nonpolar compounds. On the other hand, in APCI, a needle electrode is disposed in front of the tip of a nozzle, and carrier gas ions generated by corona discharge from the needle electrode are chemically reacted with liquid sample droplets atomized by heating at the nozzle. Perform ionization. From such a principle, APCI is suitable for ionization of a compound having a relatively low polarity to a polar compound, but is not suitable for a highly polar compound or a thermally unstable compound.

従来のＬＣ／ＭＳでは、大気圧イオン化インタフェイスをＥＳＩとＡＰＣＩとで切り替えて（例えばプローブを交換して）分析を行えるようになっているが、上述したようにイオン化に適した化合物が異なるため、物質の種類が全く未知であるような試料を分析する際には、いずれか一方の大気圧イオン化インタフェイスのみで分析を行った場合には、分析漏れが生じる可能性がある。しかしながら、大気圧イオン化インタフェイスを切り替えて２回の測定を行うのは大変に面倒であり、試料の量も余分に必要となる。また、無極性化合物や低極性の中でも特に極性の低いほうの化合物ではＡＰＣＩでもイオン化できないか、イオン化できても感度が非常に低く実用的でなくなる。   In conventional LC / MS, analysis can be performed by switching the atmospheric pressure ionization interface between ESI and APCI (for example, by exchanging probes). However, as described above, the compounds suitable for ionization are different. When analyzing a sample whose kind of substance is completely unknown, if analysis is performed only with one of the atmospheric pressure ionization interfaces, there is a possibility that an analysis leakage may occur. However, it is very troublesome to perform the measurement twice by switching the atmospheric pressure ionization interface, and an extra amount of sample is required. In addition, nonpolar compounds and low polarity compounds, particularly those with lower polarity, cannot be ionized even by APCI, or even if ionized, the sensitivity is very low and impractical.

こうした質量分析装置での分析漏れを補うために、従来知られている液体クロマトグラフの他の検出器を併用するという手法も考えられる。すなわち、液体クロマトグラフのカラムから溶出した液体試料を分岐して一方を質量分析装置に導入し、他方を紫外可視分光光度計や蒸発光散乱検出器などに導入し、同時に検出を行うようにする。こうした装置として特許文献１に記載のＬＣ／ ＭＳが知られている。このＬＣ／ＭＳでは、大気圧イオン化インタフェイスのノズルから噴霧された微小液滴の一部を蒸発管の中に吸引し、蒸発管を通過する際に液滴中の溶媒の気化を促進させ、微粒子化した目的化合物にレーザ光を照射してその散乱光を検出している。これによって、質量分析部による試料の分析と蒸発光散乱検出器による分析とを並行して行うことができる。   In order to make up for the analysis omission in such a mass spectrometer, a method of using another detector of a conventionally known liquid chromatograph in combination is also conceivable. That is, a liquid sample eluted from a column of a liquid chromatograph is branched and one is introduced into a mass spectrometer, and the other is introduced into an ultraviolet-visible spectrophotometer or an evaporative light scattering detector so that detection can be performed simultaneously. . An LC / MS described in Patent Document 1 is known as such an apparatus. In this LC / MS, a part of the fine droplet sprayed from the nozzle of the atmospheric pressure ionization interface is sucked into the evaporation tube, and the vaporization of the solvent in the droplet is promoted when passing through the evaporation tube, The scattered light is detected by irradiating a laser beam to the target compound. Thereby, the analysis of the sample by the mass analyzer and the analysis by the evaporative light scattering detector can be performed in parallel.

しかしながら、こうした構成では、装置が大掛かりになることが避けられず、装置の小型化が困難になるとともに価格も高価になる。また、本来は試料分子をイオン化するためにノズルから噴霧された液滴の一部を強制的に吸引してしまうことによって、質量分析部に導入されるイオンの量が減少し分析感度が下がるという危惧もある。   However, in such a configuration, it is inevitable that the apparatus becomes large, and it is difficult to reduce the size of the apparatus, and the price is high. In addition, forcibly sucking a part of the droplet sprayed from the nozzle in order to ionize the sample molecules reduces the amount of ions introduced into the mass analyzer and lowers the analysis sensitivity. There are also concerns.

特開２００２−３７２５１６号公報JP 2002-372516 A

本発明は上記課題を解決するために成されたものであり、その主な目的は、ＬＣ／ＭＳを基本とする簡単な構成の変更・追加によって、質量分析部では検出が困難であるような成分についての情報を質量分析と並行して簡便に取得することができる液体クロマトグラフ質量分析装置を提供することにある。   The present invention has been made to solve the above-mentioned problems, and its main object is to make it difficult for the mass spectrometer to detect by changing / adding a simple configuration based on LC / MS. An object of the present invention is to provide a liquid chromatograph mass spectrometer capable of easily acquiring information about components in parallel with mass spectrometry.

上記課題を解決するために成された本発明は、液体クロマトグラフのカラムから溶出した試料液に含まれる試料成分を大気圧イオン化インタフェイスによりイオン化して質量分析する液体クロマトグラフ質量分析装置において、
a)略大気圧雰囲気にあるイオン化室内へ試料液を噴霧する噴霧手段と、
b)該噴霧手段により噴霧された試料液滴から発生するイオンを収集して後段へと輸送するためのイオン輸送手段と、
c)前記噴霧手段により噴霧された試料液の噴霧流に向けて測定光を照射する光照射手段と、
d)該光照射手段より照射された測定光が噴霧流に当たって散乱した光及び／又は吸収を受けた後の光を検出する光検出手段と、
を備えることを特徴としている。 In order to solve the above-mentioned problems, the present invention provides a liquid chromatograph mass spectrometer that ionizes a sample component contained in a sample solution eluted from a liquid chromatograph column by an atmospheric pressure ionization interface and performs mass spectrometry.
a) a spraying means for spraying the sample liquid into an ionization chamber in an atmosphere of substantially atmospheric pressure;
b) ion transporting means for collecting and transporting ions generated from the sample droplet sprayed by the spraying means to the subsequent stage;
c) a light irradiation means for irradiating the measurement light toward the spray flow of the sample liquid sprayed by the spray means;
d) light detecting means for detecting the light scattered by the measurement light emitted from the light irradiating means upon being sprayed and / or the light after being absorbed;
It is characterized by having.

大気圧イオン化インタフェイスでは、略大気圧雰囲気にあるイオン化室内に例えばネブライズガスの助けを受けて試料液を噴霧する。大気圧化学イオン化法による場合には、加熱によって液滴中の移動相（溶媒）を気化させ、コロナ放電で生成したキャリアガスイオンを試料分子と反応させてイオン化を行う。一方、エレクトロスプレイイオン化法による場合には、液滴を噴霧する際に電荷を付与し、液滴から移動相が蒸発する過程でイオンを発生させる。こうして発生したイオンは微小液滴が入り混じった状態でイオン輸送手段により収集されて後段へと輸送されるが、噴霧流の先端部に近い部分では、液滴中の移動相が気化した状態である試料（化合物）の微粒子が多数存在する。光照射手段から出射した測定光がこうした微粒子に当たると散乱や吸収が生じるから、光検出手段により散乱光や吸収を受けた後の光を検出することにより試料を検出することができる。すなわち、光照射手段と光検出手段とにより簡易的な蒸発光散乱検出器を構成することができる。   In the atmospheric pressure ionization interface, a sample liquid is sprayed with the help of, for example, a nebulization gas in an ionization chamber in an atmosphere of substantially atmospheric pressure. In the case of the atmospheric pressure chemical ionization method, the mobile phase (solvent) in the droplets is vaporized by heating, and carrier gas ions generated by corona discharge are reacted with sample molecules to perform ionization. On the other hand, in the case of the electrospray ionization method, an electric charge is applied when the droplet is sprayed, and ions are generated in the process of evaporating the mobile phase from the droplet. The ions generated in this way are collected by the ion transport means in a state where micro droplets are mixed and transported to the subsequent stage, but in the portion near the tip of the spray flow, the mobile phase in the droplet is in a vaporized state. There are many fine particles of a sample (compound). When the measurement light emitted from the light irradiating means hits such fine particles, scattering or absorption occurs. Therefore, the sample can be detected by detecting the light after receiving the scattered light or absorption by the light detecting means. That is, a simple evaporative light scattering detector can be configured by the light irradiation means and the light detection means.

こうした蒸発光散乱による検出では、噴霧手段からの噴霧流において液滴中の移動相の蒸発が不十分である場合には十分な感度が得られない。一般的に、噴霧流の中で中心軸に近い部分では液滴の密度が高いために液滴同士が接触して大きな液滴を生じ易く、上記のような蒸発光散乱検出の条件にはあまり適さない。そこで、好ましくは、前記噴霧手段から噴霧され略円錐形状に拡がる噴霧流の周縁部に測定光が当たるように前記光照射手段により光を照射する構成とするとよい。この構成によれば、相対的に試料の微粒子が多い部分に測定光が照射されるので、蒸発光散乱検出の感度を上げるのに有利である。   In such detection by evaporation light scattering, sufficient sensitivity cannot be obtained when the evaporation of the mobile phase in the droplets is insufficient in the spray flow from the spray means. In general, the density of droplets is high in the portion near the central axis in the spray flow, so that the droplets are likely to come into contact with each other to form large droplets. Not suitable. Therefore, it is preferable that the light irradiating unit irradiates light so that the measurement light strikes the peripheral portion of the spray flow sprayed from the spraying unit and spreading in a substantially conical shape. According to this configuration, the measurement light is irradiated to a portion where the sample has a relatively large amount of fine particles, which is advantageous in increasing the sensitivity of the evaporative light scattering detection.

本発明に係る液体クロマトグラフ質量分析装置によれば、大気圧イオン化インタフェイスによってイオン化されにくい試料成分について蒸発光散乱検出により補完的な情報を得ることができるので、分析漏れを軽減することができ、分析の正確性を向上させることができる。また、本発明に係る液体クロマトグラフ質量分析装置では、イオン化室内に蒸発光散乱検出のための光照射手段及び光検出手段を設ければよく、別途、蒸発管やアスピレータなどを設ける必要がないので、装置構成が簡単であり、装置のサイズが大きくならずに済みコスト的にも有利である。さらにまた、蒸発光散乱検出によって質量分析に利用されるイオンの収集や輸送を妨害することがないので、質量分析部の分析感度に影響を及ぼすこともない。   According to the liquid chromatograph mass spectrometer according to the present invention, it is possible to obtain complementary information by evaporative light scattering detection for sample components that are difficult to be ionized by the atmospheric pressure ionization interface. Can improve the accuracy of analysis. Further, in the liquid chromatograph mass spectrometer according to the present invention, it is only necessary to provide light irradiation means and light detection means for detecting evaporated light scattering in the ionization chamber, and it is not necessary to separately provide an evaporation tube or an aspirator. The apparatus configuration is simple, and the size of the apparatus is not increased, which is advantageous in terms of cost. Furthermore, since the evaporative light scattering detection does not interfere with the collection and transport of ions used for mass analysis, the analysis sensitivity of the mass analyzer is not affected.

以下、本発明の一実施例であるＬＣ／ＭＳについて図面を参照して説明する。図１は本実施例によるＬＣ／ＭＳの要部の構成図、図２は本実施例の特徴である大気圧イオン化インタフェイスの構成図である。   Hereinafter, an LC / MS according to an embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a configuration diagram of a main part of the LC / MS according to the present embodiment, and FIG. 2 is a configuration diagram of an atmospheric pressure ionization interface which is a feature of the present embodiment.

ＬＣ部１にあっては、送液ユニット１２が移動相容器１１から移動相（溶離液）を吸引し、一定の送液量を維持しつつ試料注入部１３へと送給する。試料注入部１３では所定のタイミングで試料液を移動相中に注入する。試料液が混入された移動相はカラム１４に送られ、カラム１４を通過する間に成分毎に分離され、それぞれ時間的にずれてカラム１４から溶出して大気圧イオン化インタフェイス２に到達する。   In the LC unit 1, the liquid feeding unit 12 sucks the mobile phase (eluent) from the mobile phase container 11 and feeds it to the sample injection unit 13 while maintaining a constant liquid feeding amount. The sample injection unit 13 injects the sample liquid into the mobile phase at a predetermined timing. The mobile phase mixed with the sample solution is sent to the column 14 and separated for each component while passing through the column 14. Each mobile phase is eluted with a time lag and reaches the atmospheric pressure ionization interface 2.

大気圧イオン化インタフェイス２はイオン化室２１を含み、イオン化室２１内にはカラム１４の末端に接続されたイオン化プローブ２２の先端部が突設されている。イオン化室２１内部の構成については後で詳細に説明する。   The atmospheric pressure ionization interface 2 includes an ionization chamber 21, and a tip portion of an ionization probe 22 connected to the end of the column 14 protrudes from the ionization chamber 21. The configuration inside the ionization chamber 21 will be described in detail later.

ＭＳ部３にあっては、質量分析室３７と、上記イオン化室２１との間にそれぞれ隔壁で隔てられた第１中間真空室３１及び第２中間真空室３４が設けられている。質量分析室３７内には質量分離部としての四重極フィルタ３８とイオン検出器３９とが設けられ、それらの中間にある第１中間真空室３１及び第２中間真空室３４にはそれぞれ第１イオンレンズ３２及び第２イオンレンズ３５が設けられている。イオン化室２１と第１中間真空室３１との間は細径の脱溶媒管２３を介して、第１中間真空室３１と第２中間真空室３４との間は極小径の通過穴を頂部に有する円錐形状のスキマー３３を介して連通している。   In the MS unit 3, a first intermediate vacuum chamber 31 and a second intermediate vacuum chamber 34 are provided between the mass spectrometry chamber 37 and the ionization chamber 21, respectively, separated by a partition wall. In the mass analysis chamber 37, a quadrupole filter 38 and an ion detector 39 as a mass separation unit are provided, and the first intermediate vacuum chamber 31 and the second intermediate vacuum chamber 34 in the middle thereof are respectively provided with the first intermediate vacuum chamber 31 and the second intermediate vacuum chamber 34. An ion lens 32 and a second ion lens 35 are provided. Between the ionization chamber 21 and the first intermediate vacuum chamber 31, a small-diameter solvent removal tube 23 is provided, and between the first intermediate vacuum chamber 31 and the second intermediate vacuum chamber 34, a very small diameter passage hole is formed at the top. It communicates through a conical skimmer 33.

イオン化室２１内は、イオン化プローブ２２からほぼ連続的に供給される液体試料の気化分子によってほぼ大気圧雰囲気になっている。また、第１中間真空室３１内はロータリポンプ４０により約１０2[Pa]まで、第２中間真空室３４内はターボ分子ポンプ４１により約１０-1〜１０-2[Pa]まで真空排気され、さらに質量分析室３７内はターボ分子ポンプ４２により約１０-3〜１０-4[Pa]の高真空状態まで真空排気される。このようにイオン化室２１、第１中間真空室３１、第２中間真空室３４、質量分析室３７と、段階的に真空度を上げるような多段差動排気系の構成とすることにより、質量分析室３７内の高い真空度を維持するようにしている。 The inside of the ionization chamber 21 is almost at atmospheric pressure by vaporized molecules of the liquid sample supplied from the ionization probe 22 almost continuously. Further, the first intermediate vacuum chamber 31 up to about 10 2 [Pa] by a rotary pump 40, the second intermediate vacuum chamber 34 is evacuated to about 10 -1 ~10 -2 [Pa] by a turbo molecular pump 41 Further, the inside of the mass analysis chamber 37 is evacuated to a high vacuum state of about 10 −3 to 10 −4 [Pa] by the turbo molecular pump 42. In this way, the ionization chamber 21, the first intermediate vacuum chamber 31, the second intermediate vacuum chamber 34, the mass analysis chamber 37, and the multistage differential exhaust system that increases the degree of vacuum stepwise can be used for mass analysis. A high degree of vacuum in the chamber 37 is maintained.

大気圧イオン化インタフェイス２及びＭＳ部３における分析動作を説明すると、試料液はイオン化プローブ２２の先端からイオン化室２１内に噴霧され、後述するように噴霧流中の試料分子はイオン化される。発生したイオンは未だイオン化していない微小液滴とともに、イオン化室２１と第１中間真空室３１との差圧により脱溶媒管２３中に引き込まれる。第１イオンレンズ３２は、その電場により脱溶媒管２３を介してのイオンの引き込みを助けるとともに、イオンをスキマー３３の通過孔近傍に収束させる。スキマー３３の通過孔を通って第２中間真空室３４に導入されたイオンは、第２イオンレンズ３５により収束及び加速された後、小孔３６を通って質量分析室３７へと送られる。質量分析室３７では、特定の質量数を有するイオンのみが四重極フィルタ３８を通り抜け、イオン検出器３９に到達しイオン電流として検出される。   The analysis operation in the atmospheric pressure ionization interface 2 and the MS unit 3 will be described. The sample liquid is sprayed into the ionization chamber 21 from the tip of the ionization probe 22, and the sample molecules in the spray flow are ionized as described later. The generated ions are drawn into the desolvation tube 23 by the differential pressure between the ionization chamber 21 and the first intermediate vacuum chamber 31 together with fine droplets that have not yet been ionized. The first ion lens 32 helps the ions to be drawn through the desolvation tube 23 by the electric field and converges the ions in the vicinity of the passage hole of the skimmer 33. The ions introduced into the second intermediate vacuum chamber 34 through the passage hole of the skimmer 33 are converged and accelerated by the second ion lens 35, and then sent to the mass analysis chamber 37 through the small hole 36. In the mass analysis chamber 37, only ions having a specific mass number pass through the quadrupole filter 38, reach the ion detector 39, and are detected as an ion current.

この実施例のＬＣ／ＭＳでは、イオン化プローブ２２を交換することによってＥＳＩ又はＡＰＣＩを選択的に行うことができる。
ＥＳＩの場合、図２（ａ）に示すように、試料液を噴霧するイオン化プローブ２２は、試料液が供給される試料液管２２１と、試料液管２２１と同軸であって外筒として取り囲むように配設されたネブライズガス管２２２とを有し、ネブライズガス管２２２又はその周囲に設けられた金属筒に直流電源２２３より高電圧が印加される。この電圧による電場の影響で、試料液管２２１を流れて来る試料液は片寄って帯電しており、その状態でネブライズガス管２２２から噴出するネブライズガス（通常Ｎ2ガス）の助けを受けて微小液滴となって噴出する。噴出した微小液滴は周囲の乾燥窒素ガスに接触し、液滴中の移動相や溶媒が急速に蒸発し液滴のサイズは小さくなる。すると、帯電電荷の斥力によって液滴は細かく***し、その過程で試料分子に由来する気体イオンが発生する。 In the LC / MS of this embodiment, ESI or APCI can be selectively performed by exchanging the ionization probe 22.
In the case of ESI, as shown in FIG. 2A, an ionization probe 22 for spraying a sample solution is coaxial with the sample solution tube 221 to which the sample solution is supplied and surrounds the sample solution tube 221 as an outer cylinder. A high voltage is applied from the DC power source 223 to the nebulization gas pipe 222 or a metal cylinder provided around the nebulization gas pipe 222. Under the influence of the electric field due to this voltage, the sample liquid flowing through the sample liquid pipe 221 is biased to be charged, and in this state, with the help of the nebulization gas (usually N 2 gas) ejected from the nebulization gas pipe 222, a fine droplet And erupts. The ejected microdroplets come into contact with the surrounding dry nitrogen gas, and the mobile phase and solvent in the droplets rapidly evaporate, reducing the size of the droplets. Then, the droplets are finely divided by the repulsive force of the charged charges, and gas ions derived from the sample molecules are generated in the process.

イオン化プローブ２２は脱溶媒管２３の入口開口の中心軸に対してほぼ直交する方向に試料液を噴霧し、その噴霧流２７はほぼ円錐形状に広がりながら進行する。その進行の過程で上述したように試料イオンが生成され、イオンは液滴が入り混じった状態で脱溶媒管２３に吸い込まれる。但し、噴霧流２７では全ての試料がイオン化されて脱溶媒管２３に吸引されるわけではないから、噴霧流２７中には液滴から単に移動相が蒸発した状態である試料の微粒子も多数含まれる。また、試料にはイオン化されにくい化合物もあるから、こうした化合物ではその多くが微粒子の状態で噴霧流２７の先端部に近い部分に存在する。   The ionization probe 22 sprays the sample liquid in a direction substantially perpendicular to the central axis of the inlet opening of the desolvation tube 23, and the spray flow 27 proceeds while spreading in a substantially conical shape. In the process of progress, sample ions are generated as described above, and the ions are sucked into the desolvation tube 23 in a state where droplets are mixed. However, in the spray flow 27, not all samples are ionized and sucked into the desolvation tube 23. Therefore, the spray flow 27 includes a large number of sample fine particles in which the mobile phase is simply evaporated from the droplets. It is. In addition, since there are compounds that are difficult to ionize in the sample, many of these compounds are present in the vicinity of the tip of the spray flow 27 in the form of fine particles.

このＬＣ／ＭＳでは、こうした試料を検出するために、噴霧流２７の先端部に近い側で噴霧流２７を横切るように測定光を照射する発光源２５と、測定光に対して噴霧流２７中で散乱された光や吸収を受けた光を検出するための光電子増倍管２６とが適宜の位置に配置されている。図３は、図２（ａ）の構成を噴霧流２７の中心軸Ｃに直交する面内でみたときの概略図である。発光源２５から照射される測定光は噴霧流２７の周縁部を横切るようにその光路が設定されている。噴霧流２７の中心軸Ｃ近傍は液滴の密度が高いために液滴同士が接触する確率が高く、液滴が大きくなって移動相が蒸発しにくい。逆に噴霧流２７の周縁部では液滴のサイズが小さく移動相の蒸発が促進されて、相対的に試料の微粒子が存在する確率が高い。そこで、このように噴霧流２７の周縁部に測定光を当てることによって、ここでの測定対象である試料の微粒子に効率良く測定光を照射して検出感度を高めることができる。   In this LC / MS, in order to detect such a sample, a light emitting source 25 that irradiates the measurement light so as to cross the spray flow 27 on the side close to the tip of the spray flow 27, and in the spray flow 27 with respect to the measurement light. And a photomultiplier tube 26 for detecting light scattered or absorbed light are arranged at appropriate positions. FIG. 3 is a schematic view of the configuration shown in FIG. 2A when viewed in a plane perpendicular to the central axis C of the spray flow 27. The optical path of the measurement light emitted from the light emission source 25 is set so as to cross the peripheral edge of the spray flow 27. In the vicinity of the central axis C of the spray flow 27, since the density of the droplets is high, there is a high probability that the droplets are in contact with each other, and the droplets are large and the mobile phase is difficult to evaporate. Conversely, at the peripheral edge of the spray flow 27, the droplet size is small and the evaporation of the mobile phase is promoted, so that there is a relatively high probability that sample fine particles are present. Thus, by applying the measurement light to the peripheral edge of the spray flow 27 in this manner, the measurement light can be efficiently irradiated to the fine particles of the sample that is the measurement target here, and the detection sensitivity can be increased.

なお、脱溶媒管２３に吸い込まれた以外の試料液やガスは、最終的に噴霧流２７の前方に設けられているドレイン２４からイオン化室２１外に排出される。   Note that sample liquids and gases other than those sucked into the desolvation tube 23 are finally discharged out of the ionization chamber 21 from the drain 24 provided in front of the spray flow 27.

図１に示すように、光電子増倍管２６の検出出力はＭＳ部３のイオン検出器３９の検出出力とともにデータ処理部４３に送られ、データ処理部４３で演算処理が行われて例えばマススペクトル、マスクロマトグラム、トータルイオンクロマトグラムのほか、散乱光の強度変化を示すクロマトグラムなどが作成される。発光源２５と光電子増倍管２６との組み合わせにより、ＭＳ部３では検出できない又は検出できても非常に感度の低いような化合物を検出することができるので、ＭＳ部３による結果を補完して、より分析精度を高めることができる。   As shown in FIG. 1, the detection output of the photomultiplier tube 26 is sent to the data processing unit 43 together with the detection output of the ion detector 39 of the MS unit 3, and the data processing unit 43 performs arithmetic processing, for example, a mass spectrum. In addition to the mass chromatogram and the total ion chromatogram, a chromatogram showing the intensity change of the scattered light is generated. Since the combination of the light emission source 25 and the photomultiplier tube 26 can detect a compound that cannot be detected by the MS unit 3 or that can be detected, but has a very low sensitivity, the result of the MS unit 3 is complemented. , Analysis accuracy can be improved.

ＡＰＣＩの場合には、図２（ｂ）に示すように、試料液管２２１、ネブライズガス管２２２に、試料液管２２１開口の前方空間を囲繞するヒータ２２４、及びさらにその前方に設けられた針状の放電電極２２５を一体化したイオン化プローブ２２を使用する。試料液管２２１の先端に達した試料液（ＥＳＩと異なり帯電はしていない）はネブライズガス管２２２から噴き出すネブライズガスの助けを受けて微小液滴となって噴出する。その前方空間はヒータ２２４で囲繞されているから、このヒータ２２４の加熱によって液滴中の溶媒は気化して溶媒ガスとなる。放電電極２２５に図示しない高電圧源から高電圧が印加されるとコロナ放電を生じ、溶媒ガス分子は溶媒イオンとなる。この溶媒イオンと液滴中の試料分子とが化学反応し、試料分子はイオン化されて試料イオンとなる。この場合でも、略円錐状に広がる噴霧流２７の先端部に近い位置を測定光が横切るように発光源２５と光電子増倍管２６とを配置することは上記ＥＳＩの場合と同じである。このＡＰＣＩの場合、ヒータ２２４による加熱によって液滴からの移動相の気化はＥＳＩの場合よりも効率的に行われる。したがって、ＥＳＩの場合よりも検出感度が上がることが期待できる。   In the case of APCI, as shown in FIG. 2 (b), a sample liquid pipe 221, a nebulization gas pipe 222, a heater 224 surrounding the front space of the sample liquid pipe 221 opening, and a needle-like shape provided in front of the heater 224 are provided. The ionization probe 22 in which the discharge electrode 225 is integrated is used. The sample liquid that has reached the tip of the sample liquid tube 221 (uncharged unlike ESI) is ejected as fine droplets with the help of the nebulizing gas ejected from the nebulizing gas tube 222. Since the front space is surrounded by the heater 224, the solvent in the droplets is vaporized by the heating of the heater 224 to become solvent gas. When a high voltage is applied to the discharge electrode 225 from a high voltage source (not shown), corona discharge occurs, and the solvent gas molecules become solvent ions. The solvent ions and the sample molecules in the droplets chemically react, and the sample molecules are ionized to become sample ions. Even in this case, the emission source 25 and the photomultiplier tube 26 are arranged in the same manner as in the above ESI so that the measurement light crosses a position near the tip of the spray flow 27 spreading in a substantially conical shape. In the case of this APCI, the vaporization of the mobile phase from the droplets by heating by the heater 224 is performed more efficiently than in the case of ESI. Therefore, the detection sensitivity can be expected to be higher than in the case of ESI.

なお、上記実施例は本発明の一例にすぎず、本発明の趣旨の範囲で適宜変更や修正を加えることができることは明らかである。例えば、上記実施例では大気圧イオン化インタフェイスとして代表的なＥＳＩとＡＰＣＩとについてのみ説明したが、他のイオン化手法、例えば噴霧流中にレーザを照射する等の方法によるイオン化にも本発明を適用することができる。   Note that the above embodiment is merely an example of the present invention, and it is obvious that changes and modifications can be made as appropriate within the scope of the gist of the present invention. For example, in the above embodiment, only ESI and APCI which are typical as atmospheric pressure ionization interfaces have been described, but the present invention is also applied to ionization by other ionization methods, for example, a method of irradiating a laser in a spray flow. can do.

本発明の一実施例である液体クロマトグラフ質量分析装置の要部の構成図。The block diagram of the principal part of the liquid chromatograph mass spectrometer which is one Example of this invention. 本実施例のＬＣ／ＭＳにおける大気圧イオン化インタフェイスの概略図。The schematic of the atmospheric pressure ionization interface in LC / MS of a present Example. 本実施例のＬＣ／ＭＳにおける大気圧イオン化インタフェイスを軸Ｃに直交する面でみたときの概略図。The schematic when the atmospheric pressure ionization interface in LC / MS of a present Example is seen in the surface orthogonal to the axis | shaft C. FIG.

符号の説明Explanation of symbols

１…ＬＣ部
１４…カラム
２…大気圧イオン化インタフェイス
２１…イオン化室
２２…イオン化プローブ
２２１…試料液管
２２２…ネブライズガス管
２２３…直流電源
２２４…ヒータ
２２５…放電電極
２３…脱溶媒管
２５…発光源
２６…光電子増倍管
２７…噴霧流
３…ＭＳ部 DESCRIPTION OF SYMBOLS 1 ... LC part 14 ... Column 2 ... Atmospheric pressure ionization interface 21 ... Ionization chamber 22 ... Ionization probe 221 ... Sample liquid tube 222 ... Nebulize gas tube 223 ... DC power supply 224 ... Heater 225 ... Discharge electrode 23 ... Desolvation tube 25 ... Light emission Source 26 ... Photomultiplier tube 27 ... Spray flow 3 ... MS section

Claims (2)

液体クロマトグラフのカラムから溶出した試料液に含まれる試料成分を大気圧イオン化インタフェイスによりイオン化して質量分析する液体クロマトグラフ質量分析装置において、
a)略大気圧雰囲気にあるイオン化室内へ試料液を噴霧する噴霧手段と、
b)該噴霧手段により噴霧された試料液滴から発生するイオンを収集して後段へと輸送するためのイオン輸送手段と、
c)前記噴霧手段により噴霧された試料液の噴霧流に向けて測定光を照射する光照射手段と、
d)該光照射手段より照射された測定光が噴霧流に当たって散乱した光及び／又は吸収を受けた後の光を検出する光検出手段と、
を備えることを特徴とする液体クロマトグラフ質量分析装置。 In a liquid chromatograph mass spectrometer that performs mass spectrometry by ionizing a sample component contained in a sample solution eluted from a liquid chromatograph column by an atmospheric pressure ionization interface,
a) a spraying means for spraying the sample liquid into an ionization chamber in an atmosphere of substantially atmospheric pressure;
b) ion transporting means for collecting and transporting ions generated from the sample droplet sprayed by the spraying means to the subsequent stage;
c) a light irradiation means for irradiating the measurement light toward the spray flow of the sample liquid sprayed by the spray means;
d) light detecting means for detecting the light scattered by the measurement light emitted from the light irradiating means upon being sprayed and / or the light after being absorbed;
A liquid chromatograph mass spectrometer comprising: 前記噴霧手段から噴霧され略円錐形状に拡がる噴霧流の周縁部に測定光が当たるように前記光照射手段により光を照射することを特徴とする請求項１に記載の液体クロマトグラフ質量分析装置。   2. The liquid chromatograph mass spectrometer according to claim 1, wherein the light irradiating means irradiates light so that the measurement light strikes a peripheral portion of a spray flow sprayed from the spraying means and spreading in a substantially conical shape.
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