JP6044715B2 - Time-of-flight mass spectrometer - Google Patents

Description

  The present invention relates to a time-of-flight mass spectrometer (hereinafter abbreviated as “TOFMS”), and more particularly, to an orthogonal acceleration type TOFMS.

  In TOFMS, a constant kinetic energy is applied to ions derived from a sample component to fly in a space of a fixed distance, the time required for the flight is measured, and the mass-to-charge ratio of the ions is obtained from the flight time. For this reason, when ions are accelerated and flight is started, if there are variations in the position of ions or the initial energy of ions, variations in the flight time of ions with the same mass-to-charge ratio will result in a decrease in mass resolution and mass accuracy. It leads to. One of the techniques to solve these problems is the orthogonal acceleration (also called “vertical acceleration” or “orthogonal extraction”) method that accelerates ions in the direction perpendicular to the incident direction of the ion beam and sends them to the flight space. It has been.

  In the orthogonal acceleration method TOFMS, if there is an angular spread of incident ions in the acceleration direction of the ions in the orthogonal acceleration portion (the direction substantially perpendicular to the incident direction of the ions to the orthogonal acceleration portion), this causes variations in initial energy. This contributes to a decrease in mass resolution. Therefore, in the conventional general orthogonal acceleration type TOFMS, in order to suppress the angular spread of ions incident on the orthogonal acceleration unit, an incident beam limiting mechanism composed of two or more slits arranged separated by a predetermined distance. Is used.

FIG. 5 is a schematic configuration diagram in the vicinity of the orthogonal acceleration unit of the orthogonal acceleration type TOFMS using such an incident beam limiting mechanism (see Non-Patent Document 1 and the like).
In FIG. 5, the orthogonal acceleration unit 4 includes a flat plate electrode 41 and a mesh electrode 42 in which a large number of openings through which ions can pass are formed. An incident beam limiting mechanism 300 including two slit plates 301 and 302 arranged in parallel is arranged. In this figure, the initial beam direction of the ion beam incident on the acceleration region sandwiched between the plate electrode 41 and the mesh electrode 42 is the X-axis direction, and the acceleration direction, that is, the time-of-flight analysis direction is the Z-axis orthogonal to the X-axis. Direction.

  When ions are incident on the orthogonal acceleration unit 4 from the incident beam limiting mechanism 300, the electrodes 41 and 42 are at the same potential (for example, ground potential), and there is no electric field in the acceleration region. When a high voltage pulse having the same polarity as the ions is applied to the plate electrode 41 when a sufficient amount of ions are incident, an accelerating electric field is formed in the acceleration region, and the ions are given large kinetic energy, and the mesh electrode The flight starts through 42 openings.

In the orthogonal acceleration unit 4, the initial energy Ez of the ions in the time-of-flight analysis direction (Z-axis direction) is given by Ez = Esin ² α. Here, E and α are the energy of the ion beam incident on the acceleration region and the angle formed with the X axis. The greater the initial energy Ez, the longer the flight time due to the turnaround time (the time it takes for an ion having a velocity component in the direction opposite to the time-of-flight analysis direction to start and return to the starting point). The spread increases. In order to reduce the initial energy Ez, it is necessary to reduce the energy E and the angle α. The incident beam limiting mechanism 300 is for limiting the angle α to be small. In the configuration shown in FIG. 5, the beam angle spread α with respect to the interval L between the two slit plates 301 and 302 and the opening width H of the slit plate 302. Is given by tan ^-1 (H / L). Therefore, by appropriately setting the distance L and the opening width H, the angle α of the ion beam can be suppressed, and variations in the initial energy of ions can be within an allowable range.

  However, in the conventional incident beam limiting mechanism as described above, when the interval L is increased or the aperture width H is decreased in order to increase the mass resolution, the amount of ions passing through the incident beam limiting mechanism 300 is reduced. Measurement sensitivity will decrease. On the other hand, in Non-Patent Document 1, an ion lens is arranged in a space between two slit plates, and the ion converging action by the ion lens is used, so that the ion transmittance is inferior, so the sensitivity is so high. It is possible to switch between a high-resolution mode in which the parallelism of the ion beam is high but a high-sensitivity mode in which the ion transmittance is good although the mass resolution is not so high because the parallelism of the ion beam is relatively poor. An ion optical system for adjusting the beam shape is disclosed.

Michael Ugarov and one other person, “New Method of Ion Beam Formation for Increasing Sensitivity and Performance Stability of Tofu MS beam formation for increased sensitivity and performance stability of TOF MS), Agilent Technologies, 59th ASMS (2011), poster presentation MP 097 (Internet <URL: http://www.chem.agilent.com /Library/posters/Public/ASMS_2011_MP_97.pdf>)

  However, in the conventional ion optical system for beam shape adjustment described above, the difference in sensitivity between the high-sensitivity mode and the high-resolution mode is not so large, and the ion transmittance in the high-sensitivity mode is 1. It is only about 5 to 2 times. Usually, the high-resolution mode is used for qualitative analysis, and the high-sensitivity mode is used for quantitative analysis. However, if the sensitivity difference is such a level, for example, the content is very small, so the high-resolution mode cannot be sufficiently observed. Even if the component is observed by switching to the high sensitivity mode, it often happens that the component cannot be observed with sufficient sensitivity.

  The present invention has been made to solve the above-described problems, and is an orthogonal acceleration method that can switch between a high-resolution mode that emphasizes mass resolution and a high-sensitivity mode that emphasizes measurement sensitivity in accordance with the purpose of analysis and the like. The purpose of the time-of-flight mass spectrometer is to perform analysis with sufficiently high sensitivity and analysis with sufficiently high mass resolution.

The present invention made to solve the above problems comprises an orthogonal acceleration unit that accelerates incident ions in a direction orthogonal to the incident axis, and an ion optical system that sends ions to the orthogonal acceleration unit. An orthogonal acceleration time-of-flight mass spectrometer,
The ion optical system is
a) an incident beam restricting portion in which a plurality of slits for restricting the width of the ion beam in the acceleration direction in the orthogonal acceleration portion are provided in the acceleration direction, the two or more being arranged at predetermined intervals in the ion optical axis direction;
b) Ions that are disposed between two adjacent incident beam restricting portions of the two or more incident beam restricting portions, and have passed through at least one of a plurality of slits provided in the incident beam restricting portion in the preceding stage. A beam deflecting unit that deflects the ion beam so that the beam does not reach the slit provided in the incident beam regulating unit in the subsequent stage;
It is characterized by having.

  In the orthogonal acceleration time-of-flight mass spectrometer according to the present invention, when the ion beam is not deflected by the beam deflecting unit, for example, the same as the conventional incident beam restricting mechanism using a plurality of slit plates as shown in FIG. In addition, an ion beam whose parallelism is increased by a plurality of incident beam restricting units arranged apart from each other in the ion optical axis direction is emitted from the ion optical system and introduced into the orthogonal acceleration unit. At this time, in the ion optical system, since the ion beam is emitted through a plurality of slits provided in the incident beam restricting portion, the beam cross-sectional area (beam diameter) is large and the amount of ions is large. That is, since a large amount of ions are subjected to mass spectrometry, the measurement sensitivity is increased.

  On the other hand, when the ion beam is deflected by the beam deflecting unit, the ion beam that has passed through at least one of the plurality of slits provided in the preceding incident beam restricting unit passes through the slit provided in the subsequent incident beam restricting unit. Cannot pass. When the beam is blocked by such beam deflection at the slit located on the end side among the plurality of slits arranged in the acceleration direction, the beam cross-sectional area is reduced accordingly. That is, since the width of the ion beam in the acceleration direction is narrowed, variations in the initial position of ions during acceleration are suppressed, and the spread of the flight time of the same ion species is suppressed, so that mass resolution is improved.

  Thus, in the time-of-flight mass spectrometer according to the present invention, it is possible to switch between high-sensitivity measurement and high-resolution measurement depending on the presence or absence of deflection by the beam deflection unit. In particular, a plurality of slits are provided, and all of these slits are used for high-sensitivity measurement, and part of the slits are not substantially used (no ions are allowed to pass) for high-resolution measurement. This amount can be changed greatly, and a sufficient sensitivity difference can be secured.

In the time-of-flight mass spectrometer according to the present invention, it is possible to use a magnetic field to deflect the ion beam. However, in general, the configuration is simpler and easier to control by using an electric field. .
That is, as a preferable aspect of the present invention, the beam deflection unit includes a deflection electrode disposed between two incident beam regulating units, and a deflection voltage generation unit that applies a deflection voltage to the deflection electrode. It is good to do.

  In this aspect, the high resolution mode that prioritizes mass resolution and the high sensitivity mode that prioritizes sensitivity can be switched. When the high resolution mode is designated, a deflection voltage is applied to the deflection electrode, It is preferable to further include a control unit that controls the deflection voltage generation unit so as to stop the application of the deflection voltage to the deflection electrode when the sensitivity mode is designated.

  According to this configuration, it is possible to switch between the high sensitivity mode and the high resolution mode in a short time by the control by the control unit. Therefore, for example, a comparison in which a specific component separated by a liquid chromatograph is introduced It is also possible to switch between high-resolution measurement and high-sensitivity measurement within a short time and obtain the results (mass spectrum) for each measurement.

  According to the time-of-flight mass spectrometer according to the present invention, for example, when performing high-sensitivity measurement with an emphasis on measurement sensitivity, such as quantitative analysis of trace components, although the mass resolution is low, high-resolution measurement with an emphasis on mass resolution. Measurement can be performed with sufficiently high sensitivity. On the other hand, if you want to perform high-resolution measurement with an emphasis on mass resolution, such as qualitative analysis of components with a relatively high content, the sensitivity is low, but the measurement should be performed with sufficiently high mass resolution compared to high-sensitivity measurement. Can do. As described above, since it is possible to clearly switch the measurement with emphasis on sensitivity or mass resolution, it is possible to obtain an accurate result according to the analysis purpose.

1 is an overall configuration diagram of an orthogonal acceleration TOFMS that is an embodiment of the present invention. FIG. The schematic block diagram of the ion optical system for beam shape adjustments in FIG. The schematic perspective view of the ion incident part of the ion optical system for beam shape adjustments in FIG. The figure which shows the result of having simulated the ion orbit in the ion optical system for beam shape adjustments in FIG. The schematic block diagram of the orthogonal acceleration part of the conventional orthogonal acceleration type TOFMS, and the incident beam limiting mechanism of the front stage.

  An orthogonal acceleration type TOFMS which is an embodiment of the present invention will be described with reference to the accompanying drawings. FIG. 1 is an overall configuration diagram of the orthogonal acceleration type TOFMS of the present embodiment. In FIG. 1, the same components as those already described with reference to FIG.

  The orthogonal acceleration type TOFMS of this embodiment includes an ion source 1 that ionizes a target sample, a TOF analyzer 5 that includes a reflector 51, an orthogonal acceleration unit 4 that accelerates ions and sends them to the TOF analyzer 5, and an ion source. An ion guide 2 for guiding ions emitted from 1, an ion optical system 3 for adjusting the shape of the ion beam guided by the ion guide 2 and feeding it to the orthogonal acceleration unit 4, and TOF analysis A detector 6 for detecting ions flying in the flight space of the detector 5, a data processor 16 for processing data obtained by the detector 6 to create, for example, a mass spectrum, and the like for beam shape adjustment A deflection voltage generator 12 that applies a predetermined voltage to the electrodes included in the ion optical system 3, and an orthogonal acceleration power supply unit 13 that applies a predetermined voltage to the electrodes 41 and 42 included in the orthogonal acceleration unit 4. Comprises a reflector power unit 14 for applying a predetermined voltage to the reflector 51, a control unit 10 which controls the operation of each unit, and the analysis condition input unit 15 for a user to specify, the. The control unit 10 includes an analysis mode switching unit 11 as a functional block.

  The ionization method in the ion source 1 is not particularly limited. For example, when the sample is in a liquid state, an atmospheric pressure ionization method such as an electrospray ionization (ESI) method or an atmospheric pressure chemical ionization (APCI) method is used. When the sample is in a solid state, a matrix-assisted laser desorption ionization (MALDI) method or the like is used.

The basic analysis operation in the orthogonal acceleration type TOFMS of the present embodiment is as follows.
For example, various ions generated in the ion source 1 by the ESI method are introduced into the ion optical system 3 for beam shape adjustment through the ion guide 2 and introduced into the orthogonal acceleration unit 4 in the X-axis direction through the ion optical system 3 for beam shape adjustment. Is done. When ions are introduced into the orthogonal acceleration unit 4, an acceleration electric field is not formed in the orthogonal acceleration unit 4, and when a sufficient amount of ions are introduced into the orthogonal acceleration unit 4, the orthogonal acceleration power supply unit An accelerating electric field is formed by applying a predetermined voltage from 13 to the plate electrode 41 and the mesh electrode 42. Ions are given kinetic energy in the Z-axis direction by the action of this acceleration electric field, and are sent into the flight space of the TOF analyzer 5.

  As shown by a two-dot chain line in FIG. 1, ions that have started flying from the acceleration region of the orthogonal acceleration unit 4 are folded back by an electric field formed by a voltage applied from the reflector power supply unit 14 to the reflector 51. Automatically reaches the detector 6. The detector 6 sequentially generates a detection signal corresponding to the amount of ions that have reached with time. The data processing unit 16 obtains a time-of-flight spectrum from this detection signal, and further obtains a mass spectrum by converting the flight time to a mass-to-charge ratio m / z.

  FIG. 2 is a schematic configuration diagram of a beam shape adjusting ion optical system 3 disposed between the ion guide 2 and the orthogonal acceleration unit 4. FIG. 2A schematically shows an ion trajectory in the high sensitivity mode, and FIG. 2B schematically shows an ion trajectory in the high resolution mode. FIG. 3 is a schematic perspective view of an ion incident portion of the ion optical system 3 for beam shape adjustment. The right side of the ion incident portion is shown by a cross section cut along a plane including the X axis and the Z axis.

  The beam shape adjusting ion optical system 3 includes two slit plates 31 and 32 arranged in parallel with a predetermined distance in the X-axis direction which is the ion optical axis direction. The slit plate 31 at the front stage has three slit openings 31a, 31b, 31c that are narrow in the Z-axis direction, which is the acceleration direction of ions in the orthogonal acceleration unit 4, and extend in the Y-axis direction orthogonal to the Z-axis. Are provided along the Z-axis direction. Similarly, the slit plate 32 at the rear stage is provided with three slit openings 32a, 32b, and 32c along the Z-axis direction.

  Between the slit openings 31a and 32a and the slit openings 31b and 32b, and between the slit openings 31b and 32b and the slit openings 31c and 32c, conductors that connect between the front and rear slit plates 31, 32, respectively. Certain partition walls 33 and 34 are provided. A flat electrode 35 is disposed behind the upper edge of the slit opening 31a of the front slit plate 31 so as to face each other across the partition wall 33, and the lower edge of the slit opening 31c of the front slit plate 31 is also provided. A flat plate electrode 36 is arranged behind the unit so as to face each other with the partition wall 34 interposed therebetween.

  Here, the partition wall 33 and the electrode 35 constitute a pair of deflection electrodes, and the partition wall 34 and the electrode 36 constitute another pair of deflection electrodes. For example, the partition wall 33 and the partition wall 34 are grounded, and a predetermined DC deflection voltage is applied to the electrode 35 and the electrode 36 from the deflection voltage generator 12.

  In the TOFMS of the present embodiment, a high sensitivity mode and a high resolution mode are prepared as analysis modes. For example, measurement in any analysis mode is possible by an instruction from the analyst via the input unit 15. ing. In addition, when the analysis is automatically performed according to the method file in which the analysis conditions are set in advance, the measurement can be performed while automatically switching between the high sensitivity mode and the high resolution mode. In any case, in the control unit 10, the analysis mode switching unit 11 instructs the deflection voltage generation unit 12 in the analysis mode. In the high sensitivity mode, the deflection voltage generation unit 12 does not generate the deflection voltage, and in the high resolution mode, the deflection voltage. The generator 12 generates a predetermined deflection voltage.

In the high sensitivity mode, since no deflection voltage is applied to the two pairs of deflection electrodes, no deflection electric field is formed between the partition wall 33 and the electrode 35 and between the partition wall 34 and the electrode 36. As shown in FIGS. 2A and 3, ions are incident from the previous stage so as to substantially cover the entire slit openings 31 a to 31 c of the slit plate 31. The ions that have reached the slit openings 31a to 31c on the surface of the front slit plate 31 pass through the slit openings 31a to 31c and go straight. And it passes through slit opening 32a-32c of the slit plate 32 of a back | latter stage, respectively, and comes out.
In FIG. 2 (a), only ions having a trajectory parallel to the X axis are drawn, but even if ions entering at an angle greater than a predetermined angle with respect to the X axis pass through the slit openings 31a to 31c. Since they do not pass through the slit openings 32a to 32c (contact with the partition walls 33 and 34 and the slit plate 32 on the way and disappear), an ion beam having a certain degree of parallelism is emitted from the slit openings 32a to 32c.

  In this case, since ions are emitted from all of the three slit openings 32a to 32c, the ion beam introduced into the orthogonal acceleration unit 4 is wide in the Z-axis direction. For this reason, the initial position variation when ions are accelerated by the orthogonal acceleration unit 4 is large, and this causes a decrease in the mass resolution. Therefore, the mass resolution is not so high. On the other hand, the amount of ions blocked by the ion optical system 3 for adjusting the beam shape is small, and a larger amount of ions are introduced into the orthogonal acceleration unit 4 and used for mass analysis, so that high sensitivity can be realized.

  On the other hand, in the high resolution mode, a deflection voltage is applied to the two pairs of deflection electrodes, and a deflection electric field is formed between the partition wall 33 and the electrode 35 and between the partition wall 34 and the electrode 36, respectively. As in the high-sensitivity mode, ions that have entered the slit openings 31a to 31c on the surface of the previous slit plate 31 out of the ions that have substantially entered the slit openings 31a to 31c of the slit plate 31. Passes through the slit openings 31a to 31c. The ions that have passed through the slit opening 31b travel straight without being influenced by the deflection electric field, and pass through the slit opening 32b of the slit plate 32 at the subsequent stage and exit. On the other hand, the ions that have passed through the upper and lower slit openings 31a and 31c receive a force in the Z-axis direction due to the deflection electric field immediately after that, and bend their trajectories as shown in FIG. As a result, the ions do not reach the slit openings 32a and 32c of the subsequent slit plate 32, and ions are not emitted from the slit openings 32a and 32c.

  In this case, since ions are emitted from only the central slit opening 32b among the three slit openings 32a to 32c, the ion beam introduced into the orthogonal acceleration unit 4 is narrow in the Z-axis direction. For this reason, variations in the initial position when ions are accelerated by the orthogonal acceleration unit 4 are reduced, and high mass resolution can be achieved. On the other hand, since the amount of ions blocked by the ion optical system 3 for beam shape adjustment is large, the amount of ions introduced into the orthogonal acceleration unit 4 and used for mass analysis is small, and the sensitivity is low.

  FIG. 4 is a diagram showing the result of simulating ion trajectories in the beam shape adjusting ion optical system 3. According to FIG. 4B, in the high resolution mode, it can be confirmed that some orbits of ions that have passed through the front slit plate 31 are greatly bent and blocked by the rear slit plate 32. When the ion transmittance in each analysis mode is calculated, the ion transmittance in the high sensitivity mode is about 3.4 times that in the high resolution mode. This becomes a difference in sensitivity almost as it is. From this, it can be confirmed that the orthogonal acceleration method TOFMS of the present embodiment can sufficiently increase the sensitivity difference between the high sensitivity mode and the high resolution mode as compared with the case of using the conventional ion optical system for beam shape adjustment. It was.

It should be noted that the above embodiment is an example of the present invention, and it is obvious that any changes, modifications, additions, etc. within the scope of the present invention are included in the claims of the present application.
For example, the number of slit plates, the number of slit openings formed in one slit plate, or the shape of the slit openings can be determined as appropriate. Further, the position and shape of the deflection electrode can be appropriately changed. It is also possible to deflect ions by a magnetic field instead of a deflection electric field.

DESCRIPTION OF SYMBOLS 1 ... Ion source 2 ... Ion guide 3 ... Ion optical system 4 for beam shape adjustment ... Orthogonal acceleration part 41 ... Flat plate electrode 42 ... Mesh electrode 5 ... TOF analyzer 51 ... Reflector 6 ... Detector 10 ... Control part 11 ... Analysis mode switching unit 12 ... deflection voltage generation unit 13 ... orthogonal acceleration power supply unit 14 ... reflector power supply unit 15 ... input unit 16 ... data processing units 31 and 32 ... slit plates 31a to 31c, 32a to 32c ... slit openings 33 and 34 ... Partition wall (deflection electrode)
35, 36 ... Electrode (deflection electrode)

Claims (3)

An orthogonal acceleration type time-of-flight mass spectrometer comprising: an orthogonal acceleration unit that accelerates incident ions in a direction orthogonal to the incident axis; and an ion optical system that sends ions to the orthogonal acceleration unit,
The ion optical system is
a) an incident beam restricting portion in which a plurality of slits for restricting the width of the ion beam in the acceleration direction in the orthogonal acceleration portion are provided in the acceleration direction, the two or more being arranged at predetermined intervals in the ion optical axis direction;
b) Ions that are disposed between two adjacent incident beam restricting portions of the two or more incident beam restricting portions, and have passed through at least one of a plurality of slits provided in the incident beam restricting portion in the preceding stage. A beam deflecting unit that deflects the ion beam so that the beam does not reach the slit provided in the incident beam regulating unit in the subsequent stage;
A time-of-flight mass spectrometer. The time-of-flight mass spectrometer according to claim 1,
The beam deflection unit includes a deflection electrode disposed between two incident beam restricting units, and a deflection voltage generation unit that applies a deflection voltage to the deflection electrode. . The time-of-flight mass spectrometer according to claim 2,
The high resolution mode giving priority to mass resolution and the high sensitivity mode giving priority to sensitivity can be switched. When the high resolution mode is designated, a deflection voltage is applied to the deflection electrode, and when the high sensitivity mode is designated. A time-of-flight mass spectrometer further comprising a control unit that controls the deflection voltage generation unit so as to stop application of the deflection voltage to the deflection electrode.

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