JP2007242426A - Time-of-flight mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To solve problems that mass spectrometry is limited in a certain mass number or more by resolution determined by flight time, flight distance, and response time of a detector or the like, and on the other hand, that changing the flight time and the flight distance or the like reduces Duty Cycle and sensitivity in measurement in a time-of-flight mass spectrometer. <P>SOLUTION: This is the high resolution time-of-flight mass spectrometer which is provided with a deflecting electrode to deflect ions and a position detector, and in which the resolution of a specific mass number is improved by obtaining mass distribution constituted of distribution of the flight time and the detector. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a mass spectrometer that performs mass separation according to time of flight, and more particularly, to a mass spectrometer that has higher sensitivity and resolution than conventional techniques.

  Now that the analysis of human DNA sequences has been completed, structural analysis of proteins that are generated using this genetic information and macromolecules that are modified and function in cells based on the proteins becomes important. One method for analyzing the structure of biomolecules is mass spectrometry. In mass spectrometry, identification is performed based on the mass number of substances constituting a biomolecule. Further, in this field, an ion trap mass spectrometer that can obtain biopolymer sequence information that cannot be obtained by a single mass separation, or a time-of-flight mass called a Q-TOF (Time of flight) type. Analyzing devices are mainstream. Recently, in order to confirm this sequence information with high accuracy, a device combining a TOF and an ion trap capable of measuring the mass number with high accuracy is also on the market. Similar to the apparatus, a MALDI method using a laser and an Electro Spray method for performing ionization under atmospheric pressure are used as a method for ionizing a biological sample. In each method, it is expected that the demand for measuring ions with a high mass number with high sensitivity and high accuracy will increase in the future because the amount of information related to the structure increases.

Currently, time-of-flight mass spectrometers that are widely used determine the mass number based on the time-of-flight difference of ions. In this case, in order to measure the mass number difference with higher accuracy, a detection system capable of high-speed processing and having high time accuracy is required. As a method of improving resolution in a conventional time-of-flight mass spectrometer, a flight-type mass spectrometer using laser ionization is delayed.
Excitation has been used. Delayed Excitation improves the resolution by improving the initial ion distribution by re-acceleration of the ions once launched. In the atmospheric pressure Electro-Spray ionization method, high resolution is achieved by limiting incoming ions and deflecting and converging an incident ion beam by a lens. Although the resolution can be improved by using these methods, it is difficult to achieve both sensitivity and sensitivity.

  Patent Document 1 describes a method of deflecting in a direction different from the launch direction in which the incident energy is changed. In Patent Document 1, the sensitivity is improved by having a plurality of detection mechanisms. However, when this method is used, the sensitivity is improved by increasing the number of launches, but when changing the energy of incident ions or deflecting ions with different mass numbers, The initial distribution changes. As a result, the resolution and sensitivity change in each detector. That is, the resolution detected by a plurality of detectors changes for each detector, and as a result, the resolution of the signal detected as a whole decreases.

  In Patent Document 3, the resolution is improved by calculating the shape of the TOF. Although the resolution is improved by improving the calculation accuracy, it is difficult to reduce the influence of the initial distribution of ions. When the voltage of each electrode fluctuates due to the temperature of the ionization region, the ambient temperature, etc., complicated control such as changing the set voltage is required.

  In this method, when a plurality of ion beams are launched, an error occurs in the flight time of ions, and the flight time changes, resulting in a decrease in mass number accuracy and resolution.

  As a method of deflecting ions in flight, Patent Document 4 is raised. In Patent Document 4, a method of adjusting the deflection of ions in flight and the mounting direction of the detector is used. In this method, the resolution is improved by creating a convergence point on the detector surface by the deflection. Yes. However, when the sensitivity is improved by increasing the number of launches, it is necessary to detect a large number of ions at the same time.

  In normal TOF, it is important to reduce the energy spread when launching the initial distribution of ions. In order to reduce this energy spread, the optical system is optimized so that the energy spread is minimized in the launch space. However, it is difficult to improve the resolution without reducing the sensitivity.

JP 2002-367558 A US Patent No. 5869829 US Patent No. 6621073 US Pat. No. 5,654,544

  Conventionally, as means for improving the resolution, the acceleration voltage is increased in order to reduce the influence of the initial distribution, the entire flight time is shortened, and a slit is used to suppress the spread of the initial distribution to converge. For example, a method for measuring only the ions has been used. However, even after improving the resolution and sensitivity by shortening the flight time, there was a problem of sensitivity reduction due to the spread of the initial distribution and limiting the amount of ions. For this reason, mass spectrometers having a function of adjusting and deflecting the ion optical system have been considered as in Patent Documents 2, 3, and 4. Even in this method, the low sensitivity of the low mass number incident in the flight time interval and the undetected high mass number ions cannot be solved. Recently, since the detection system has been increased in speed and a large amount of data can be processed, it has become possible to measure multi-channel ions as in Patent Document 1. However, when a multi-channel detector is used, it is necessary to solve both of the difference in resolution between channels and the decrease in sensitivity due to the resolution improvement measures by limiting the amount of ions and correcting ion trajectories.

  In a normal TOF, a spatial distribution occurs with respect to position and energy in the launch region as shown in FIG. The analysis of the ion launch direction and the ion incidence direction is performed in Patent Document 2, but generating and operating the electric field obtained in the patent is effective only under ideal conditions. When operating, it is considered that the beam trajectory slightly changes depending on the valence, mass, etc. of the ions, and it is necessary to optimize the incident beam shape. In addition, in order to improve sensitivity, even when the ion beam is bent, calibration according to the detection point by the position detector enables measurement in accordance with actual use conditions. In the present invention, the position detector is used, and the resolution is improved by taking into account the distribution of incident ions on the detector. Specifically, the distribution generated by actual ion incidence is corrected by the distribution obtained by measurement. When performing this correction, the incident ion beam is not limited to a certain condition. For example, by changing the shape of the incident ion beam by changing the incident energy and creating a shape function corresponding to the change, the correction is made according to the actual measurement conditions. Is possible.

  Regarding sensitivity improvement by a plurality of launches described in Patent Document 1, the sensitivity is improved by actually increasing the number of launches. However, when the incident energy is changed to improve sensitivity, the resolution changes depending on the incident energy. When this resolution is changed, the measurement accuracy is determined under the worst condition when the operation is performed simultaneously and integration is performed. In order to perform measurement without reducing the resolution, it is necessary to perform measurement in each detection unit using position detection. In addition, by performing position detection, it is possible to monitor the detector corresponding to the ion ejection, so it is possible to increase the number of times of TOF ejection, and high sensitivity due to a high number of repetitions without reducing the resolution. Can be measured.

  By using this detector, it is possible to correct the beam spread caused by bending incident ions. First, by calibrating the detector, an address to be used for detection is determined, which is utilized when obtaining a final mass spectrum. Moreover, it can correct | amend with respect to the incident position to a detector changing depending on the mass number which generate | occur | produces when bending a beam.

  It is an object of the present invention to achieve both a reduction in resolution, which is a problem with a sensitivity improvement measure using a multi-channel detector, and a sensitivity reduction due to a resolution improvement measure based on ion amount limitation or ion trajectory correction.

  It is possible to provide a mass spectrometer that can improve resolution reduction in a multi-channel detector and sensitivity reduction due to ion amount limitation and ion trajectory correction.

  FIG. 2 shows a first embodiment of the present invention. Second ion deflecting means for deflecting the beam in a direction substantially parallel to a plane orthogonal to the emitting direction is provided. The ion emitting means capable of ejecting ions vertically and the second ion deflecting means emit the beam in the emitting direction. In order to detect an ion beam deflected in a direction substantially parallel to a plane perpendicular to the plane, a two-dimensional detector is provided instead of a conventional position-dimensional detector. By providing an ion deflection electrode facing the launch immediately before the region, ions are deflected two-dimensionally in accordance with the mass-to-charge ratio of the ions. That is, those with a large mass-to-charge ratio are hardly deflected and those with a small mass-to-charge ratio are deflected more greatly. Due to such deflection, the position where ions are launched differs. The position where the ions are ejected can be expressed as an ion deflection shape function whose elements are the velocity of the ions when they enter the deflection electrode, the voltage applied to the deflection electrode, and the like. The ejected ions basically enter the detector while maintaining the same relationship as the ejected position. In a conventional time-of-flight mass spectrometer that detects ions launched without being deflected as in the present invention, a one-dimensional detector is sufficient. However, in the present invention, ions ejected with a two-dimensional spread are detected. A detector capable of detecting ions on a two-dimensional plane is required so that the shape can be detected as it is. In other words, the time of flight is measured like a conventional time-of-flight mass spectrometer, the difference in launch position according to the mass-to-charge ratio is detected, and the measurement results are combined and calculated. The resolution can be improved without reducing the sensitivity.

  However, when performing measurement in a wide range, it is necessary to determine the shape function of the detection position by deflection in advance and correct the distribution at the detector position. In this case, it is necessary to set launch conditions that do not cause overlap.

  In Example 2, the time-of-flight mass spectrometer having the position detector of this example includes an electrospray ion source, a matrix-assisted laser ion source, an atmospheric pressure chemical ion source, an atmospheric pressure photoion source, and an atmospheric pressure matrix-assisted laser. Ions ionized by an ion source or the like are introduced into a time-of-flight mass spectrometer. A position detector is used for the detection unit of the time-of-flight mass spectrometer. In this method, by performing position detection, the convergence point and the spread of the ion beam can be measured. Therefore, the shape function can be obtained by calculating the original beam spread from the slit shape, the detected position and spread information with respect to time. It is possible to reproduce a high-resolution spectrum in which the influence of the original spread is reduced as compared with the conventional detection method. Conventionally, the number of launches has been limited by the overlap of ions during flight. On the other hand, the method of the present invention is characterized in that the position is detected and the sensitivity is improved by correcting the time and position with respect to the launch position flight time. The present invention also relates to a flight mass spectrometer having a position detector that simultaneously improves the sensitivity without degrading the resolution by obtaining the beam shape function.

Spatial spread of ions. Normal orthogonal time-of-flight mass spectrometer. Example 1 Orthogonal time-of-flight mass spectrometer. Shape function. Difference in flight time due to ion distribution in the acceleration section.

Claims (3)

Ion ejection means for ejecting ionized molecules in a direction substantially perpendicular to the incident direction;
Ion deflecting means for deflecting the ions ejected by the ion ejecting means so that the time of flight differs according to the mass-to-charge ratio;
A detector for detecting ions deflected by the ion deflection means;
In a time-of-flight mass spectrometer equipped with
Second ion deflecting means for deflecting an ion beam incident on the ion ejecting means in a direction substantially parallel to a plane orthogonal to the ejecting direction;
The mass spectrometer is a two-dimensional detector capable of detecting positional information on a plane orthogonal to the ion ejection direction. The mass spectrometer according to claim 1,
The mass spectrometer according to claim 2, wherein the second deflecting unit is a counter electrode facing each other across a flight trajectory of an ion beam incident on the ion ejecting unit. The time-of-flight mass spectrometer according to claim 1 or 2,
A storage unit that stores a deflection shape function of the ion beam by the second deflection unit; and a function of analyzing a detection result of the detector based on the deflection shape function stored in the storage unit. Characteristic mass spectrometer.

Images