JP4627744B2 - Time-of-flight mass spectrometer - Google Patents

Description

  The present invention relates to a time-of-flight mass spectrometer, and more particularly to a time-of-flight mass spectrometer that can be manufactured at low cost and has high resolution.

  In order to advance research into tailor-made medicine in recent years, structural analysis of proteins that are generated using genetic information and high-molecular substances that are functionally modified after translation in cells based on proteins becomes important. One of the methods for structural analysis of these substances is mass spectrometry. The mass spectrometry is a method of identifying a substance by examining a mass number (m / Z: m is mass and Z is electric charge), and an apparatus for examining the mass number includes a mass spectrometer. A mass spectrometer is a device that flies an ionized sample in a vacuum, separates ions having different masses in the course of flight, and records them as a spectrum. There are various types of mass spectrometers that realize this, but time-of-flight mass spectrometers are suitable for mass spectrometers that can examine the structure and arrangement of high molecular weight and high-molecular substances such as proteins. ing. FIG. 1 schematically shows a configuration example of a time-of-flight mass spectrometer. In FIG. 1, two differential exhaust spaces in which exhaust is regulated by two orifices on the wall surface in order to guide ions generated at atmospheric pressure from one ion source into a mass spectrometer maintained at a high vacuum. Pass through. Thereafter, the ions are converged on the flight trajectory by the ring lens 3, energized by the electrode plates 4, accelerated and emitted in a direction perpendicular to the traveling direction so far. The trajectory of ions is controlled by 5 grid electrodes and 6 reflectors, and finally ions are detected by 7 detectors. In the flight of ions, regardless of the mass of the ions, the ions start acceleration by receiving an equal voltage, so the lighter ions have a higher speed and the slower ions have a lower speed. As a result, the ions are separated due to the difference in mass, and there is a difference in the time from the start of flight after being ejected by the electrode plate until reaching the detector 7. This arrival time is detected and recorded as a mass spectrum. Since the measurable mass number region is wider than that of a conventional quadrupole mass spectrometer or the like, it has been widely used for the measurement of a sample having a large mass number such as a protein in recent years. In a time-of-flight mass spectrometer, various developments have been made to measure larger molecules with high resolution. Japanese Patent Application Laid-Open No. 2004-133867 has devised a method of suppressing the spread of ion trajectories and improving resolution by adding an intermediate electrode to an electrode plate that gives energy to ions. In Patent Document 2, a heating means is provided in an electrode plate, a grid electrode, a lens, or the like, and a remnant of a measurement sample is heated to prevent charging due to the influence of an electric field, to stabilize ion trajectories, and to improve resolution. Has been devised. There is also a tandem mass spectrometer that improves accuracy by providing a mass spectrometer such as a quadrupole mass spectrometer or an ion trap mass spectrometer in the front stage of the time-of-flight mass spectrometer.

Patent Registration No. 3626969 JP 2004-172070 A

  In the mass spectrometers described in Patent Document 1 and Patent Document 2, when ions undergo vertical acceleration, the mounting angle of each electrode plate is very important in controlling the ion trajectory. In order to obtain high resolution, the ion trajectory must be an ideal trajectory. When deviating greatly from the ideal trajectory, ions are not efficiently incident on the detector, so that the analysis sensitivity may be reduced or the worst measurement may not be performed. As shown in FIG. 5, the conventional grid electrode and plate electrode of the mass spectrometer have a structure in which a plurality of plate electrode plates 4 and grid electrode plates 5 are attached to a support column 9 by inserting high-precision spacers with small dimensional errors and stacking them. It was. However, in the structure of FIG. 5, as the number of stacked electrodes increases, the dimensional errors of the components are accumulated. In the conventional structure, it is necessary to assemble the electrode plate or grid electrode and the spacer to cancel the dimensional error when stacking the spacers as a countermeasure against the stacking of the dimensional errors. There was a problem that the nature was bad.

  An object of the present invention is to provide a mass spectrometer having a structure capable of ensuring the trajectory of ions with high accuracy even if there is a dimensional error in spacers, electrode plates, and the like.

  The configuration of the present invention for achieving the above object is as follows.

  In a time-of-flight mass spectrometer that ejects an ionized sample and measures the time of flight of the ejected ions to analyze the mass, in order to eject the ions, an electrode plate that accelerates by applying a potential difference to the ions to be measured, A time-of-flight mass spectrometer in which grid electrodes for controlling the direction of emission of ions emitted by an electrode plate are supported by different supports.

  A known technique such as atmospheric pressure chemical ionization (APCI) or electrospray (ESI) can be used for ionization of the sample. The ions are preferably ejected in a direction perpendicular to the ion introduction direction, but may be ejected in any direction as long as the difference in flight time can be measured by the difference in mass. The electrode plate and the grid electrode are each made of a plate-like member having a hole through which ions pass at the center. The outer shape can be any shape such as a circle or square. The support is a member for fixing the positions of the plate electrode plate and the grid electrode plate. Any shape can be used as long as the position can be fixed, but it is preferably a rod-like member extending in a direction perpendicular to the plate electrode plate and the grid electrode plate. The cross section of the rod may be any shape such as circular or square.

  As described above, according to the present invention, in order to eject ions inside the ion reservoir, an electrode plate that accelerates by applying a potential difference to ions to be measured and a grid electrode that controls the ejection direction of the ions ejected by the electrode plate are provided. When installing the electrode plate or grid electrode in the mass spectrometer, the dimensional error of the electrode plate or grid electrode and the spacer is not accumulated by dividing the column and installing it independently, and the electrode plate or grid It is possible to assemble the electrodes with a precision parallelism of micrometer order. The parallelism on the order of micrometers, which was difficult with a stacked stack structure, can be easily realized, and a voltage can be applied symmetrically with respect to the incident direction of ions. Therefore, the spread of ion energy into the space is reduced, and an accurate ion trajectory can be realized, thereby improving the resolution.

  In addition, the effect of stricter plate surface accuracy relaxation and cost reduction by improving the assemblability can be obtained.

  In the time-of-flight mass spectrometer, when the electrode plate and the grid electrode are mounted with an inclination, an asymmetric voltage distribution is generated, which causes bending of the ion trajectory and spreading of the ions into the space. As shown in FIG. 2, the resolution was simulated when the electrode plate was mounted with an inclination of several tens of microns. Of the two electrode plates that give the potential difference, the one with the higher potential is the electrode plate 1 and the one with the lower potential than the electrode plate 1 is the electrode plate 2, and the results are shown in FIGS. From these, it can be seen that the inclination of the electrode plate affects the ion trajectory, which causes the measurement resolution of mass spectrometry to deteriorate. Therefore, it is necessary to attach the electrode plate exactly perpendicular to the ion launch direction, and in the attachment, the parallelism of each electrode plate is required to be attached with an accuracy of micrometer order.

  A generally adopted electrode plate structure is shown in FIG. FIG. 5 shows that a high-precision spacer 8 with a small dimensional error is inserted so that a plate electrode made up of a plurality of electrode plates and a grid electrode made up of a plurality of electrode plates are spaced apart from each other by a predetermined interval. Defines the parallelism between the electrode plates. However, in the shape of FIG. 5, the dimensional errors of the components are accumulated as the number of stacked stages increases. The main cause of the inclination of the electrode plate is that the dimensional error of the electrode plate or grid electrode and the dimensional error of the spacer are integrated. To deal with stacking of dimensional errors, it is necessary to assemble electrode plates or grid electrodes and spacers to offset the dimensional error when stacking spacers, but this method is difficult in practice and poor in productivity. . FIG. 6 shows a first embodiment according to the present invention. In this embodiment, in order to eject ions inside the ion reservoir, a mass spectrometer having an electrode plate that accelerates by applying a potential difference to ions that are symmetrical to the measurement and a grid electrode that controls the ejection direction of the ions ejected by the electrode plate, This is for the case where there are three types of struts. Two of the electrode plates are joined to separate independent columns, and the grid electrode is installed on the third column. There may be an intermediate electrode between the two electrode plates. In the case of having an intermediate electrode, it is possible to join the intermediate electrode to one or two support plates of the same type as the electrode plate, and it is also possible to make only the intermediate electrode independent. It is also possible to install the intermediate electrode and the electrode plate on independent columns. In the first embodiment, the number of grid electrodes is one or more, and the number of pillars to which the grid electrodes are attached can be increased to one or more. The arrow indicates the ion launch direction. Further, in the first embodiment, when the ion launching direction is reverse upward, the structure is such that the positions of the 4 electrode plates and the 5 grid electrodes are reversed, and at this time, the number of intermediate electrodes and grid electrodes, The types are the same as described above.

  A second embodiment of the present invention is shown in FIG. In this embodiment, in order to eject ions inside the ion reservoir, a mass spectrometer having an electrode plate that accelerates by applying a potential difference to ions that are symmetrical to the measurement and a grid electrode that controls the ejection direction of the ions ejected by the electrode plate, FIG. 7 shows an embodiment in which two types of support columns are used. Two electrode plates are joined to the same column. There may be an intermediate electrode between the electrode plates. In the case of having an intermediate electrode, the intermediate electrode can be joined to one or two of the electrode plates and the same type of support, or only the intermediate electrode can be made independent as a separate body. Also, each of the two electrode plates and the intermediate electrode can be installed on separate independent columns. One or more grid electrodes are used. In the second embodiment, when the ion launching direction is reversed upward, 4 electrode plates are arranged in the lower part, and 5 grid electrodes are arranged in the upper part. At this time, the number of intermediate electrodes and grid electrodes and the type of support are the same as described above.

  In addition to the above-described embodiments, various modifications can be made to the embodiment of the present invention. For example, only one of the voltage plates may be joined to another column. At this time, the separate voltage plate may be an electrode plate having a high voltage or a low electrode plate among the two electrode plates giving a potential difference. Similarly, one grid electrode or two or more grid electrodes may be joined to another support. At this time, an arbitrary grid electrode can be separated.

  As described above, there are various methods for preventing the accumulation of dimensional errors of components and easily realizing the attachment of the electrode plate or the grid electrode in the micrometer order.

It is a figure which shows the basic composition of the vertical acceleration type | mold time-of-flight mass spectrometer of this invention. It is an enlarged view of an inclination object electrode plate. It is a figure of the simulation result which changed the direction of the electrode plate. It is a figure of the simulation result which changed the direction of the electrode plate. It is a figure which shows installation of the conventional electrode plate. FIG. 3 is an electrode plate installation configuration diagram of Example 1. 6 is an electrode plate installation configuration diagram of Embodiment 2. FIG.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 ... Ion source, 2 ... Working exhaust space regulated by orifice, 3 ... Ring lens, 4 ... Electrode plate, 5 ... Grid electrode, 6 ... Reflector, 7 ... Detector, 8 ... Spacer, 9 ... Post.

Claims (10)

In a time-of-flight mass spectrometer that injects an ionized sample, measures the time of flight of the ejected ions, and analyzes the mass,
In order to eject ions, an electrode plate that accelerates by applying a potential difference to ions to be measured ;
A grid electrode for controlling the emission direction of ions emitted by the electrode plate;
A first support for supporting the electrode plate;
A time-of-flight mass spectrometer comprising a second support for supporting the grid electrode. In claim 1,
The said electrode plate is comprised from the some electrode, The time-of-flight mass spectrometer characterized by the above-mentioned. In claim 2 ,
A time-of-flight mass spectrometer having two or more types of the first support. In claim 3,
The time-of-flight mass spectrometer according to claim 1, wherein the first support is provided for each of the plurality of electrodes. In any one of Claim 1-4,
The said grid electrode is comprised from the some electrode, The time-of-flight mass spectrometer characterized by the above-mentioned. In claim 5,
A time-of-flight mass spectrometer characterized in that two or more types of the second support are provided. In claim 6,
The time-of-flight mass spectrometer is characterized in that the second support is provided for each of the plurality of electrodes. In claim 2,
A time-of-flight mass spectrometer having an intermediate electrode between the electrodes. In claim 8,
The intermediate electrode is supported by the first support, and a time-of-flight mass spectrometer. In claim 8,
A time-of-flight mass spectrometer further comprising a third support for supporting the intermediate electrode.

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