JP6443262B2 - Time-of-flight mass spectrometer - Google Patents

Description

  The present invention relates to a time-of-flight mass spectrometer, and more particularly to a reflectron type time-of-flight mass spectrometer using an ion reflector (reflector).

  A time-of-flight mass spectrometer (hereinafter sometimes referred to as “TOFMS” according to common usage) gives a constant energy to various ions derived from a sample and accelerates the flight speed of each ion to a mass-to-charge ratio m / Utilizing the dependence on z, the flight time of each ion when these ions are allowed to fly a certain distance is measured, and the mass-to-charge ratio for each ion is calculated from the flight time. In TOFMS, the flight speed of ions depends on the initial energy given by an electric field or the like, and therefore, the group of ions having the same mass-to-charge ratio, that is, the spread (variation) of the initial energy of the ion packet affects the mass resolution of the apparatus. .

  One way to improve ion beam time-of-flight energy convergence to improve mass resolution is to use a reflectron-type configuration in which ions are reciprocated using an ion reflector that reflects ions by an electric field. . In the ion reflector, even if the ions have the same mass-to-charge ratio, the ions with higher energy (that is, higher flight speed) take a trajectory that enters further and turns back. Therefore, ions with the same mass-to-charge ratio and high energy are substantially longer in flight distance than ions with low energy, thereby compensating for the time-of-flight shift due to energy differences. That is, the energy convergence of the flight time of ions is improved.

  However, since there is a limit to the energy convergence by the ion reflector described above, if the variation of the initial energy is large to some extent and the flight trajectory is greatly deviated, it also contributes to a decrease in resolution. In the reflectron type TOFMS, the forward path trajectory in which ions fly from the ion ejection part that accelerates and sends ions to the flight space to the ion reflector, and the return path trajectory in which the ions returned by the ion reflector go to the detector. Is ideally on the same straight line, but it is actually impossible to arrange the ion ejection part and the detector on the same straight line. Therefore, in general, as in the apparatus described in Patent Document 1 and the like, the ion ejection unit, the ion reflector, and the detection are performed so that the forward path and the backward path are substantially symmetric with respect to the central axis of the ion reflector. A container is arranged. For this reason, even if ions of the same species, that is, the same mass-to-charge ratio, are different in the initial position when they are accelerated, the flight trajectory is different, and the flight time varies, which causes a reduction in resolution.

  In response to such a problem, the TOFMS described in Patent Document 1 has a trajectory in which a slit diaphragm having a slit opening of a predetermined shape and size is arranged in a free flight space in front of the detector, leading to a reduction in resolution. This prevents the ions that have deviated from reaching the detector. Since the spatial spread of the ion packet is the largest in front of the detector, the influence of the mechanical error of the slit opening on the resolution can be reduced if a shielding plate is arranged immediately in front of the detector. However, when ions are shielded by such a shielding plate to increase the resolution, the ions reach the detector more than necessary, that is, ions that do not actually reduce the resolution. The problem arises that the amount of ions decreases and the analytical sensitivity decreases.

  The TOFMS described in Patent Document 1 is an orthogonal acceleration type reflectron type TOFMS, but other than the orthogonal acceleration type, for example, a type of reflectron that emits ions simultaneously from an ion trap capable of accumulating ions. Also in the type TOFMS, since the ion trap, the ion reflector, the detector, etc. are usually arranged so that the outward track and the return track are substantially symmetric with respect to the central axis of the ion reflector, the above problem is caused. What happens is similar.

US Pat. No. 6,717,132

  The present invention has been made to solve the above-described problems, and the object of the present invention is to achieve a high resolution and a high sensitivity while avoiding a decrease in analytical sensitivity while ensuring a high resolution. It is to provide a reflectron type time-of-flight mass spectrometer.

In order to solve the above-mentioned problems, the present invention provides a time-of-flight mass separator having a free flight space with no electric field and an ion reflector for reflecting ions, and ion acceleration for accelerating ions and sending them to the free flight space. A reflectron type time-of-flight mass spectrometry comprising: a detector; and a detector that detects ions that have returned in the free flight space after flying in the free flight space and reflected by the ion reflector In the device
A shield plate having a forward-side opening on the forward-side ion trajectory from the ion accelerator to the ion reflector and a return-side opening on the backward-side ion trajectory from the ion reflector to the detector is the free flight. Arranged in space,
The width of the forward-side opening in the spreading direction of the plane on which both the central axis of the ion trajectory on the forward path and the central axis of the ion trajectory on the backward path are placed is the width of the return-side opening in the same direction. It is characterized by being more narrowly defined.

  When the time-of-flight mass spectrometer according to the present invention is an orthogonal acceleration type time-of-flight mass spectrometer, the ion acceleration unit accelerates the incident ions in a direction substantially orthogonal to the incident axis. It is an orthogonal acceleration part. Further, when the time-of-flight mass spectrometer according to the present invention is an ion trap time-of-flight mass spectrometer, the ion acceleration unit accumulates ions once and then accelerates and ejects ions (three-dimensional four-dimensional). A bipolar ion trap or a linear ion trap). In the case of a time-of-flight mass spectrometer that flies ions generated by an ion source using a matrix-assisted laser desorption / ionization (MALDI) method, the ion acceleration unit moves ions generated by the ion source near the sample. It is an accelerating electrode that is pulled out and accelerated.

  In the time-of-flight mass spectrometer according to the present invention, there is a risk that the resolution is greatly reduced on both the outward path side where ions travel from the ion accelerator to the ion reflector and on the outbound path side where ions travel from the ion reflector to the detector. Ions are shielded by a common shielding plate arranged in free flight space. Ions emitted from the ion accelerating portion vary in their emission angles mainly due to variations in their initial energies, and the ion packets travel while gradually spreading spatially. However, the spread of the ion packets is smaller on the forward path side than on the return path side. Therefore, at a stage where the spatial spread of the ion packet is relatively small, ions passing through the trajectory that may greatly reduce the resolution are shielded by a shielding plate having a relatively small opening width. Then, on the forward path side where the spatial expansion of the ion packet after being reflected by the ion reflector is relatively large, ions passing through the trajectory that may greatly reduce the resolution are shielded by a shielding plate having a relatively large opening width. .

  It should be noted that the opening width between the forward-side opening and the return-side opening formed in one shielding plate may be determined based on ion orbit simulation calculation using a computer. In recent years, the trajectory that can be taken by an ion that has a certain initial energy and jumped from a certain initial position can be calculated fairly precisely. Therefore, based on the calculation result of the ion trajectory, the trajectory of ions passing through the reference trajectory can be calculated. What is necessary is just to determine the opening width of an outward path side opening and a return path side opening so that passage of the ion which exceeds a predetermined allowable range with respect to flight time may be prevented.

  When a shielding plate having a slit opening is disposed only on the return path side as in the conventional TOFMS described above, it is necessary to narrow the opening width of the slit opening in order to increase the resolution. On the other hand, in the time-of-flight mass spectrometer according to the present invention, it is possible to widen the opening width of the slit opening on the return path compared to the above-described conventional TOFMS by shielding ions that are largely out of orbit on the outward path side. it can. This is because in the above-described conventional apparatus, when ions having a large deviation from the trajectory are reflected by the ion reflector on the forward path side, the trajectory may be modified to approach the reference trajectory. This is because, in the time-of-flight mass spectrometer according to the present invention, ions taking such a trajectory are excluded on the forward path side, and thus need not be considered on the return path side.

  According to the time-of-flight mass spectrometer according to the present invention, ions that cause a reduction in resolution can be accurately eliminated while flying in free flight space, while ensuring high resolution. By increasing the amount of ions that reach the detector, high analytical sensitivity can be achieved. In addition, since a single shielding plate is used to limit the range in which ions pass through both the outward path and the return path, the cost of the shielding plate itself and the manufacturing of the device for attaching the shielding plate are limited. Cost can be reduced.

BRIEF DESCRIPTION OF THE DRAWINGS The schematic block diagram of the reflectron type | mold TOFMS which is one Example of this invention. The top view of the shielding board in the reflectron type | mold TOFMS of a present Example. The figure which shows the time-of-flight spectrum calculated | required by the simulation calculation in the reflectron type | mold TOFMS of a present Example, and the conventional reflectron type | mold TOFMS.

Hereinafter, a reflectron type TOFMS according to an embodiment of the present invention will be described with reference to the accompanying drawings.
FIG. 1 is a schematic configuration diagram of the reflectron type TOFMS of this embodiment.

  The reflectron type TOFMS of the present embodiment is an orthogonal acceleration type TOFMS, and includes an orthogonal acceleration unit 1 including a plate-like extruded electrode 11 and a grid-like grid electrode 12, an ion focusing lens 2 that is an Einzel lens, an electric field, and the like. A free flight space 3, an ion reflector 4 including a plurality of reflective electrodes 41 and a back plate 42, and a detector 5 for detecting ions. Although not shown, the free flight space 3 and the ion reflector 4 are arranged inside a drift tube maintained in a high vacuum atmosphere.

  The reflection electrode 41 is a flat electrode having a rectangular opening, for example, as in the device described in Patent Document 1, and a plurality of reflection electrodes 41 are separated along the center line C by a predetermined distance (in FIG. The back plate 42 is arranged in the farthest position as viewed from the ion incident side. A different direct current voltage is applied to each reflective electrode 41 and back plate 42 from a voltage source (not shown), so that it enters the rectangular tube-like space virtually connecting the rectangular openings of the reflective electrode 41. A reflected electric field is formed which decelerates incoming ions and further reflects and accelerates the ions.

  The detector 5 is an ion detector using, for example, a microchannel plate or a secondary electron multiplier, and has a wide detection surface in order to efficiently detect ions arriving in a spatially widened state.

  In the reflectron type TOFMS of the present embodiment, a shield plate 6 having a characteristic structure is used in order to eliminate ions that cause a reduction in resolution due to initial energy when the ions are accelerated, a deviation in initial position, and the like during flight. Is provided in the free flight space 3. FIG. 2A is a plan view of the shielding plate 6 used in the TOFMS of this embodiment. In the shielding plate 6, rectangular slit openings 61 and 62 having opening widths L 1 and L 2 that are asymmetrical about the axis P are formed in the plate-like member 63. A slit opening 61 having an opening width L1 is an outward path opening, and a slit opening 62 having an opening width L2 is a return path opening. In other words, the opening width of the forward path side opening 61 is narrower than that of the return path side opening 62. The shielding plate 6 is disposed so that the axis P coincides with the center line C of the reflective electrode 41.

  The opening widths L1 and L2 of the slit openings 61 and 62 of the shielding plate 6 are determined based on ion trajectory calculation by simulation using a computer. In other words, in ion trajectory calculation by simulation, ions that fly in a specific trajectory from a certain position with a certain initial energy reach the detector with a time difference from ions passing through the reference trajectory. Can be calculated with considerably high accuracy. Therefore, the initial position, initial energy, mass-to-charge ratio range, etc. of the ion packet are defined based on rough estimates obtained from preliminary experiments and preliminary simulation calculation results. The correct ion trajectory. Based on the result, the ion trajectory whose time difference is greater than or equal to the predetermined time with respect to the flight time when passing through the reference trajectory is blocked, and the ion whose time difference falls below the predetermined value passes through the slit opening and finally The installation position of the shielding plate 6 and the opening widths L1 and L2 of the slit openings 61 and 62 are determined so as to reach the detector 5. What is necessary is just to set the tolerance value of the time difference of flight time according to the target resolution.

  In the reflectron type TOFMS of the present embodiment, the ions incident on the orthogonal acceleration unit 1 are formed by DC voltages applied to the extrusion electrode 11 and the grid electrode 12 as indicated by thick arrows in FIG. The DC electric field is accelerated almost simultaneously in a direction substantially perpendicular to the ion incident axis. That is, an ion packet including ions in a predetermined mass-to-charge ratio range is emitted from the orthogonal acceleration unit 1. The ion packet is converged by the ion focusing lens 2 and then sent out into the free flight space 3 to reach the shielding plate 6. If the initial energy at the time of ion acceleration deviates greatly from the initial energy that is the reference, or if the initial position deviates significantly from the initial position that is the reference, the trajectory becomes the reference from the beginning of the flight of ions. Deviate from orbit. Therefore, such ions cannot be passed through the forward path opening 61 having a relatively narrow opening width L1, and are excluded.

  The ion packet whose spatial extent is limited by passing through the forward-side opening 61 is incident on the ion reflector 41 and is folded by the reflected electric field formed therein. At this time, even if the mass-to-charge ratio is the same, ions with higher energy penetrate deeper and are reflected. The ions reflected and re-flighted in the free flight space 3 reach the shielding plate 6, and this may cause a reduction in resolution, so that ions whose trajectory is deviated from the reference trajectory do not pass through the return-side opening 62. Eliminated.

  In the case where ions are not eliminated at all on the outward path, the ions enter the ion reflector 41 through a trajectory greatly deviating from the reference ion trajectory on the outward path, and the trajectory is slightly modified when reflected there. It is necessary to exclude ions directed to 5 with a shielding plate arranged on the return path side. Therefore, it is necessary to narrow the width of the slit opening on the return path side. On the other hand, in the reflectron type TOFMS of the present embodiment, ions taking a specific trajectory that may cause a reduction in resolution can be eliminated to some extent by the forward-side opening 61. Therefore, the opening width L2 of the return-side opening 62 is reduced. It can be relatively wide. Therefore, it is possible to increase the transmission efficiency of ions that do not substantially cause a decrease in resolution, and it is possible to realize a high analytical sensitivity by introducing more ions into the detector 5.

  The present inventor performed a simulation calculation in order to confirm the difference in analysis sensitivity between the reflectron type TOFMS of the present example and the conventional reflectron type TOFMS. FIG. 3 is a time-of-flight spectrum obtained by the simulation calculation. The horizontal axis of this spectrum is the time of flight, and the vertical axis is the number of ions that have reached the detector 5.

FIG. 3B is not a left-right asymmetrical slit opening centered on the axis P as shown in FIG. 2A, but a shield having a left-right symmetrical (ie, L1 = L2) slit opening. It is a time-of-flight spectrum when using a plate. The shielding plate having the left and right symmetrical slit openings has a shape determined based on the result of ion trajectory calculation by simulation so as to achieve a resolution of 21000. According to the calculation, the ion transmittance in this case is 35.8%, and the resolution is R = 21,700.
On the other hand, FIG. 3A is a time-of-flight spectrum in the reflectron type TOFMS of the present embodiment. According to the calculation, the ion transmittance in this case is 46.7%, and the resolution is R = 21400. As described above, in the reflectron type TOFMS of this embodiment, the ion transmittance can be improved by about 30% while maintaining the resolution substantially the same as in the case of using a shielding plate having a symmetrical slit opening. it can. Since the difference in ion transmittance is almost the same as the difference in analysis sensitivity, it can be said that the reflectron type TOFMS of the present embodiment has an effect of improving the analysis sensitivity by about 30% compared to the conventional apparatus.

  In the reflectron type TOFMS of the above embodiment, the forward path side opening 61 and the return path side opening 62 of the shielding plate 6 are completely separated. However, as shown in FIG. You may use the shielding board in which the one left-right asymmetric type slit opening 65 was formed.

The above-described embodiment is an example of the present invention, and it is a matter of course that modifications, corrections, and additions as appropriate within the scope of the present invention are included in the scope of the claims of the present application.
For example, although the above embodiment is an orthogonal acceleration type TOFMS, a configuration in which ions once accumulated in an ion trap are ejected from the ion trap to fly, and ions generated from a sample by an ion source by a MALDI method or the like are adjacent to the sample. It is clear that the present invention can be applied to a TOFMS having a configuration in which it is pulled out from the vehicle and accelerated to fly.

DESCRIPTION OF SYMBOLS 1 ... Orthogonal acceleration part 11 ... Extrusion electrode 12 ... Grid electrode 2 ... Ion focusing lens 3 ... Free flight space 4 ... Ion reflector 41 ... Reflective electrode 42 ... Back plate 5 ... Detector 6 ... Shielding plate 61 ... Outward side opening (slit Opening)
62 ... Return way opening (slit opening)
63 ... plate-like member 65 ... slit opening C ... center line

Claims (1)

A time-of-flight mass separation unit having a free flight space with no electric field and an ion reflector for reflecting ions, an ion acceleration unit for accelerating ions and sending them to the free flight space, and the ion reflector flying in the free flight space A reflectron type time-of-flight mass spectrometer comprising: a detector that detects ions returned after flying in free flight space after being reflected by
A shield plate having a forward-side opening on the forward-side ion trajectory from the ion accelerator to the ion reflector and a return-side opening on the backward-side ion trajectory from the ion reflector to the detector is the free flight. Arranged in space,
The width of the forward-side opening in the spreading direction of the plane on which both the central axis of the ion trajectory on the forward path and the central axis of the ion trajectory on the backward path are placed is the width of the return-side opening in the same direction. A time-of-flight mass spectrometer characterized by being narrower than that.

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