JP2008053020A - Mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To improve SN ratio of detection signals by stabilizing ionization with APCI for reduced noise level. <P>SOLUTION: A current that flows is detected with a current value monitor 48 when a needle electrode 12 for APCI is applied with a high voltage. An error is acquired between the actual current value and a target current value indicated by a control part 34 using a comparator 46. A voltage generator 47 adjusts a high voltage V2 that is applied to the needle electrode 12 so that the error becomes zero. Since the current value depends on a solvent ion amount present in an APCI region 17, the target component in the APCI region 17 is ionized stably by controlling the voltage so that the current value becomes constant. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a mass spectrometer, and more particularly to a mass spectrometer that uses an ion source by an atmospheric pressure chemical ionization method to ionize a liquid sample.

  In a liquid chromatograph mass spectrometer, an interface using atmospheric pressure ionization is used to ionize and introduce a liquid sample that is separated and eluted from a liquid chromatograph column into the mass spectrometer. Yes. Typical atmospheric pressure ionization methods that are widely used include atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI).

  In APCI, for example, a nozzle connected to the end of a column of a liquid chromatograph is opened and arranged in an ionization chamber in a substantially atmospheric pressure atmosphere, and a needle-like discharge electrode is arranged in front of the nozzle tip, The analysis target component is ionized by chemically reacting the analysis target component in the droplet of the liquid sample atomized by heating at the nozzle with a solvent ion (buffer ion) generated by corona discharge from the discharge electrode (Patent Document 1). Etc.)

  On the other hand, in ESI, a strong unequal electric field is generated in a liquid sample by applying a high voltage of about several kV to the tip of a nozzle for introducing the liquid sample. The liquid sample has a charge which is separated by charge separation by this electric field, and is atomized so as to be torn off by Coulomb attractive force. The solvent in the generated charged droplets evaporates by touching the surrounding air, and in the process, ions of the analysis target component are generated.

  As described above, since the ionization mechanism is different between APCI and ESI, components easily ionized by the respective ionization methods are not the same. Therefore, an ionization probe that can execute APCI and ESI in parallel is also available for analyzing a liquid sample containing unknown components or for analyzing a liquid sample containing many types of components at once. Has been developed.

  As described above, in APCI, ionization is performed by applying a high voltage to the discharge electrode to cause corona discharge. At that time, in the conventional mass spectrometer, the voltage value of the applied voltage is controlled to be constant, so that corona discharge can be stably performed. However, the space potential in the ionization chamber varies depending on the amount of ions generated, and the ionization efficiency of the solvent gas by corona discharge is affected by the space potential. For this reason, even if the voltage value of the voltage applied to the discharge electrode is kept constant, the ionization state of the analysis target component is not always optimal. In practice, the ionization becomes unstable. This contributes to a decrease in detection sensitivity.

  In particular, in the configuration in which APCI and ESI can be performed simultaneously as described above, since the ionization efficiency of both needs to be balanced, the position of the discharge electrode is not necessarily arranged at the optimal position for APCI. As a result, the variation in the amount of solvent ions generated by corona discharge tends to increase, and the problem that ionization of APCI tends to become unstable becomes significant.

JP 2002-181783 A

  The present invention has been made to solve the above-mentioned problems, and the main object thereof is mass spectrometry capable of improving the S / N ratio by stably performing ionization with APCI. To provide an apparatus.

In order to solve the above problems, the present invention comprises a spraying means for spraying a liquid sample in a substantially atmospheric pressure atmosphere, and ionizing solvent molecules in the liquid sample in the forward direction of the spray flow by the spraying means. In a mass spectrometer having an ion source comprising: a discharge electrode that performs atmospheric pressure chemical ionization of a component to be analyzed by a reaction between a component to be analyzed in a sprayed liquid sample and solvent ions generated by discharge from the discharge electrode ,
a) current detection means for detecting a current flowing in the discharge electrode when a voltage is applied to the discharge electrode;
b) voltage control means for adjusting the voltage applied to the discharge electrode so that the current value detected by the current detection means becomes a target value;
It is characterized by having.

  In the mass spectrometer according to the present invention, the current detection unit detects the current flowing through the discharge electrode, and the voltage control unit adjusts the voltage value of the applied voltage so that the detected current value is maintained at the target value. The value of the current flowing through the discharge electrode correlates with the amount of ions generated by corona discharge. The current value increases as the ion amount increases, and the current value decreases as the ion amount decreases. Therefore, by controlling the current value to be constant as described above, the amount of ions generated can be kept substantially constant. As a result, ionization of the analysis target component can be performed stably, and the detection signal can also be stably reduced to reduce the noise level and thus improve the SN ratio.

  In addition, as described above, in the ion source that serves as both APCI and ESI, when the voltage applied to the discharge electrode is constant, the fluctuation of the current flowing through the electrode tends to be larger than that of the ion source of APCI alone (this application). In the study by the inventor, there is a fluctuation of twice or more), so that the effect of constant current value control is particularly large as in the present invention. That is, the spraying means has a charge applying portion for applying a charge to the liquid sample to be sprayed, and the ion source is sprayed in a substantially atmospheric pressure atmosphere while applying a charge to the liquid sample by the charge applying portion. Therefore, the mass spectrometer according to the present invention is particularly suitable for a mass spectrometer that is an ion source capable of performing electrospray ionization that ionizes an analysis target component in parallel with atmospheric pressure chemical ionization.

  Further, in the mass spectrometer having such a configuration, a storage unit is provided that previously examines and stores, for each analysis target component, a relationship between a voltage applied to the charge applying unit and the target value to be set in the voltage control unit, It is preferable that the control unit obtains the target value based on the storage information of the storage unit and adjusts the voltage applied to the discharge electrode.

  That is, since the ease of ionization in each of APCI and ESI depends on characteristics such as the polarity of the component to be analyzed, the optimal ionization conditions differ for each component. Therefore, the optimum conditions (the applied voltage to the charge applying portion of the spraying means and the target value of the current for determining the applied voltage to the discharge electrode) are determined beforehand by a preliminary experiment or the like. In the actual analysis, the target value corresponding to the component to be analyzed is set based on the information stored in the storage means, so that each of the APCI and ESI is optimal or close to the state. Ionization can be achieved.

  Hereinafter, a mass spectrometer which is an embodiment of the present invention will be described with reference to the drawings. FIG. 1 is an overall configuration diagram of the main part of the mass spectrometer.

  In FIG. 1, an ionization probe (corresponding to a spraying means in the present invention) 11 and an APCI needle electrode (corresponding to a discharge electrode in the present invention) 12 connected to a column outlet end of a liquid chromatograph (not shown) are disposed. A first intermediate vacuum chamber 20 separated by a partition wall between the ionization chamber 10 and an analysis chamber 27 in which a pre-quadrupole mass filter 28, a main quadrupole mass filter 29, and a detector 30 are disposed. And a second intermediate vacuum chamber 24 are provided. The ionization chamber 10 and the first intermediate vacuum chamber 20 communicate with each other via a thin solvent removal pipe 13, and the top portion of the skimmer 22 is between the first intermediate vacuum chamber 20 and the second intermediate vacuum chamber 24. The second intermediate vacuum chamber 24 and the analysis chamber 27 communicate with each other through a small opening provided in the partition wall 26. .

The inside of the ionization chamber 10 as an ion source is in an almost atmospheric pressure atmosphere (about 10 ⁵ [Pa]) due to vaporized molecules of the liquid sample continuously supplied from the ionization probe 11, and the first intermediate in the next stage. The inside of the vacuum chamber 20 is evacuated by a rotary pump 31 to a low vacuum state of about 10 ² [Pa]. Further, the inside of the second intermediate vacuum chamber 24 at the next stage is evacuated to a medium vacuum state by a turbo molecular pump 32 to about 10 ⁻¹ to 10 ⁻² [Pa], and the inside of the analysis chamber 27 at the final stage is separated. The turbo molecular pump 33 is evacuated to a high vacuum state of about 10 ⁻³ to 10 ⁻⁴ [Pa]. In other words, a multi-stage differential exhaust system in which the degree of vacuum is increased stepwise from the ionization chamber 10 toward the analysis chamber 27 to maintain the inside of the final analysis chamber 27 in a high vacuum state. ing.

  Although the structures of the first intermediate vacuum chamber 20 and the second intermediate vacuum chamber 24 are different from each other, an ion optical system is provided for efficiently transporting ions to the subsequent stage. That is, the first intermediate vacuum chamber 20 is provided with a first lens electrode 21 having a plurality of (four) plate-like electrodes arranged in three rows in an inclined manner, and the solvent is removed by an electric field formed by the electrodes 21. While helping the drawing of the ions through the pipe 13, the ions are converged in the vicinity of the orifice 23 of the skimmer 22. The second intermediate vacuum chamber 24 is provided with an octopole-type second lens electrode 25 in which eight rod electrodes are arranged so as to surround the ion optical axis C, whereby ions are converged and analyzed. Sent to chamber 27.

  Predetermined voltages are applied to the first lens electrode 21, the second lens electrode 25, and the quadrupole mass filters 28 and 29 from the first to third power supply units 35, 36, and 37, respectively. A voltage ± (U + V · cosωt) obtained by adding a predetermined high-frequency voltage Vcosωt and a predetermined DC voltage U is applied to 28 and 29 in accordance with the mass-to-charge ratio to be selected. The operations of these power supply units 35, 36, 37 and the like are controlled in a centralized manner by a control unit 34 mainly composed of a CPU. In addition to the one shown in FIG. 1, a predetermined voltage (mainly DC voltage) is applied to each part, but the description is omitted because the drawing becomes complicated.

  The operation of this mass spectrometer will be schematically described. The liquid sample supplied almost continuously is sprayed into the ionization chamber 10 from the tip of the ionization probe 11, and the sample molecules are ionized by either ESI or APCI as described later. Fine droplets mixed with ions are drawn into the desolvation pipe 13 due to the differential pressure between the ionization chamber 10 and the first intermediate vacuum chamber 20, and further vaporize the solvent in the process of passing through the heated desolvation pipe 13. Is promoted and ionization proceeds. With the help of the electric field formed by the first lens electrode 21, the ions enter the first intermediate vacuum chamber 20, converge, and are sent to the second intermediate vacuum chamber 24 through the orifice 23.

  In the second intermediate vacuum chamber 24, ions are further converged and sent to the analysis chamber 27 by the action of an electric field formed by the octopole-type second lens electrode 25. In the analysis chamber 27, only ions having a specific mass-to-charge ratio determined by the voltage applied to each rod electrode pass through the space in the long axis direction of the quadrupole mass filters 28 and 29, and the other mass charges. Ions with a ratio diverge on the way. The ions passing through the quadrupole mass filters 28 and 29 reach the detector 30, and the detector 30 outputs a current signal corresponding to the amount of ions as a detection signal.

  Next, the configuration and operation of the ion source, which is a feature of the mass spectrometer of the present embodiment, will be described with reference to FIGS. FIG. 2 is a detailed configuration of the ion source and a configuration diagram of a control system related thereto.

The tip of the ionization probe 11 has a coaxial double tube structure in which a capillary tube 11a through which a liquid sample flows inside and a nebulization gas tube 11c to which nebulization gas is supplied are arranged on the outside, and around the capillary tube 11a. Is provided with an electrode (corresponding to a charge applying portion in the present invention) 11b for applying a biased charge to the liquid sample. A needle electrode 12 is disposed in front of the traveling direction of the spray flow of the liquid sample from the ionization probe 11, and an inlet 13a corresponding to the inlet of the desolvation pipe 13 so as to be substantially orthogonal to the central axis of the spray flow. Is provided. Around the suction port 13a is a dry gas jet port 14, and dried N ₂ gas is blown toward the ions and charged droplets sucked into the suction port 13a, thereby further promoting the evaporation of the solvent. The A drain 15 is provided further in front of the spray flow, and the vaporized solvent and the droplets that have not been refined are discharged outside the ionization chamber 10.

  A fourth power supply unit 40 for applying a high voltage V1 (usually about several kV) to the electrode 11b of the ionization probe 11 and a fifth power supply unit 44 for applying a high voltage V2 to the needle electrode 12 are provided independently. Are respectively controlled by the control unit 34. The fourth power supply unit 40 includes a D / A conversion unit 41 that converts a target voltage value (digital value) given from the control unit 34 into an analog value, and a drive amplifier 42 that outputs a voltage corresponding to the analog value. . Therefore, the high voltage V <b> 1 corresponding to the target voltage value set by the control unit 34 is applied from the fourth power supply unit 40 to the electrode 11 b of the ionization probe 11.

  When the high voltage V1 is applied to the electrode 11b, an unequal electric field is applied to the liquid sample flowing in the capillary tube 11a, and the liquid sample is given a biased charge. The liquid sample is sprayed into the ionization chamber 10 as fine charged droplets with the help of the nebulizing gas ejected from the nebulizing gas pipe 11c in addition to the Coulomb force due to the electric charge in the liquid sample. Charged droplets collide with residual gas molecules in the ionization chamber 10 or break up due to Coulomb repulsion, and the solvent gradually evaporates and becomes finer. In such a process, the analysis target component (component that is easily ionized by ESI) is mainly ionized in the ESI region 16.

  On the other hand, the fifth power supply unit 44 includes a D / A conversion unit 45 that converts a current target value (digital value) given from the control unit 34 into an analog value, and a current value that flows due to the high voltage V2 applied to the needle electrode 12. The current value monitor 48 (corresponding to the current detection means in the present invention) 48 is compared with the analog value (target value) output from the D / A converter 45 and the monitor value obtained by the current value monitor 48. It includes a comparator 46, a voltage generator 47 that adjusts the output voltage so that the error caused by the comparator 46 becomes zero, and an output voltage monitor 49 that monitors this output voltage and outputs it as a digital value. Here, the comparator 46 and the voltage generator 47 correspond to the voltage control means in the present invention. When the control unit 34 sets a current target value for the fifth power supply unit 44, the output high voltage V2 is adjusted so that the actual current value flowing through the needle electrode 12 matches the target value.

  When this high voltage V2 is applied to the needle electrode 12, corona discharge is generated, and solvent molecules in the liquid sample sprayed from the ionization probe 11 are ionized to generate a large number of solvent ions. The solvent ions cause a chemical reaction with the sample component molecules, so that the sample components (components that are easily ionized by APCI) are mainly ionized in the APCI region 17 near the tip of the needle electrode 12. Although the current flowing through the needle electrode 12 mainly depends on the amount of solvent ions present in the APCI region 17, the fifth power supply unit 44 does not maintain the voltage constant but makes this current value constant (the current target value is Therefore, the amount of solvent ions in the APCI region 17 is stable without largely changing, and ionization by APCI is also stably performed.

  During the ionization as described above, the high voltage V2 applied to the needle electrode 12 changes. Since this voltage value is also one of the ionization conditions, it is necessary to be able to confirm the voltage applied to the needle electrode 12 in the analysis when the validity of the analysis is later examined or the analysis conditions are reviewed. There is. Therefore, when the analysis is started, the control unit 34 receives the output voltage value from the output voltage monitor 49 of the fifth power supply unit 44 every moment, and stores this as a log of the analysis conditions. The analysis condition log stored in this manner is associated with the data acquired by the analysis, whereby the analysis condition corresponding to the actual data can be verified.

  Specifically, the control unit 34 can achieve the above-described control as follows. That is, in both ESI and APCI, since the ease of ionization of various components depends on the polarity of the components, the optimum ionization conditions are usually different for different components. Therefore, by preliminary experiments and the like, the probe applied voltage and the set current value of the needle electrode that optimize each ionization when ESI and APCI are simultaneously performed for various components that may be analyzed. Check the relationship. For example, the relationship is as shown in FIG. Then, a table is created based on this relationship, a database is created so that it can be read out in correspondence with the sample components, and stored in a storage device attached to the control unit 34. Of course, an appropriate modification such as obtaining an approximate calculation formula without storing it and storing it is possible.

  When the component to be analyzed can be specified for the actual analysis, the table corresponding to the component is read from the storage device, and the needle setting current with respect to the probe applied voltage set from the outside or set by the automatic adjustment function The target current value is set in the fifth power supply unit 44 by obtaining the value. When the sample components introduced into the mass spectrometer change over time as in the case of a liquid chromatograph mass spectrometer, the change in the component is examined in advance by qualitative analysis, and then the change in the component is detected. The current target value may be changed according to the above. If the component is unknown, a standard current target value may be set.

  As described above, in the mass spectrometer of the present embodiment, even when ESI and APCI are executed simultaneously in parallel, ionization is performed in an optimal state or close to the ESI region 16 and the APCI region 17, respectively. The voltage applied to the electrode 11b and the needle electrode 12 of the ionization probe 11 can be controlled.

  Although the above description is about a case where an ion source having both ESI and ACPI functions is provided, it is possible to ionize APCI in an optimum or near state by the same control even with an ion source of APCI alone. Of course.

  Moreover, since the said Example is an example of this invention, even if it changes suitably, amends, and is added in the range of the meaning of this invention, it is clear that it is included by the claim of this application.

The whole block diagram of the principal part of the mass spectrometer by one Example of this invention. FIG. 3 is a detailed configuration diagram of an ion source in the mass spectrometer of the present embodiment and a configuration diagram of a control system related thereto. The figure which shows the relationship between a probe applied voltage and a needle electric current value.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 ... Ionization chamber 11 ... Ionization probe 11a ... Capillary tube 11b ... Electrode 11c ... Nebulization gas tube 12 ... Needle electrode 13 ... Desolvation pipe 13a ... Suction port 14 ... Outlet 15 ... Drain 16 ... ESI region 17 ... APCI region 20 ... No. DESCRIPTION OF SYMBOLS 1 Intermediate vacuum chamber 21 ... 1st lens electrode 22 ... Skimmer 23 ... Orifice 24 ... 2nd intermediate vacuum chamber 25 ... 2nd lens electrode 26 ... Partition 27 ... Analysis chamber 28 ... Pre quadrupole mass filter 29 ... Main quadrupole Mass filter 30 ... Detector 31 ... Rotary pump 32, 33 ... Turbo molecular pump 34 ... Control unit 35, 36, 37, 40, 44 ... Power supply unit 41, 45 ... D / A conversion unit 42 ... Drive amplifier 46 ... Comparator 47 ... Voltage generator 48 ... Current value monitor 49 ... Output voltage monitor

Claims (3)

A sprayed liquid sample comprising spraying means for spraying a liquid sample into a substantially atmospheric pressure atmosphere, and a discharge electrode for ionizing solvent molecules of the liquid sample in front of the traveling direction of the spray flow by the spraying means In a mass spectrometer having an ion source for chemical-ionizing an analysis target component at atmospheric pressure by a reaction between the analysis target component and solvent ions generated by discharge from a discharge electrode,
a) current detection means for detecting a current flowing in the discharge electrode when a voltage is applied to the discharge electrode;
b) voltage control means for adjusting the voltage applied to the discharge electrode so that the current value detected by the current detection means becomes a target value;
A mass spectrometer comprising:   The spraying means has a charge applying unit for applying a charge to the liquid sample to be sprayed, and the ion source is sprayed in a substantially atmospheric pressure atmosphere while applying a charge to the liquid sample by the charge applying unit. The mass spectrometer according to claim 1, wherein the ion source is capable of performing electrospray ionization for ionizing an analysis target component in parallel with atmospheric pressure chemical ionization. Storage means for preliminarily examining and storing the relationship between the voltage applied to the charge applying unit and the target value to be set in the voltage control means for each component to be analyzed, the control means storing the storage means The mass spectrometer according to claim 2, wherein the target value is obtained based on the information, and the voltage applied to the discharge electrode is adjusted.

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