JP2007157353A - Imaging mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an imaging time-of-flight mass spectrometer capable of measuring both of spatial position information and mass information on atoms and molecules constituting a sample at the same time with a high resolution and at high speed. <P>SOLUTION: The imaging mass spectrometer 1 comprises: an ion source 10 having a lens system 60; an analyzing section 20; and a detecting section 30. At the ion source 10, a broad range of the sample is ionized at a time and the ion image of the sample is extracted as it is through the lens system 60. Then, at the analyzing section 20, the ion image of the sample is maintained as it is, and mass separation is performed on the ions of the sample. Next, at the detecting section 30, the arrival position and flight time of the sample ions are simultaneously detected. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to an imaging mass spectrometer, and more particularly to an imaging time-of-flight mass spectrometer that can simultaneously measure both spatial position information and mass information of atoms and molecules constituting a sample.

  Imaging mass spectrometry is a technique for observing a localized state of a substance on a sample surface by minimizing a site on the sample surface where ion generation is performed and arbitrarily controlling the site. Simply put, imaging mass spectrometry is a technique for simultaneously acquiring a fine two-dimensional spatial image of a sample and mass information of atoms and molecules constituting the sample.

  FIG. 10 shows a configuration example of a conventional imaging mass spectrometer. As shown in FIG. 10, the conventional imaging mass spectrometer 500 includes an ion source 100, an analysis unit 200, a detection unit 300, and a data processing unit 400. In the ion source 100, the sample is ionized using a laser, a fast charged particle, or a neutral particle sample. When a laser is used for ionization of the sample, the laser beam is finely focused and irradiated on the sample. Similarly, when ionizing a sample using a fast charged particle or neutral particle sample, the fast charged particle or neutral particle is converged and irradiated.

  In the ion source 100, ions desorbed / ionized from the micro spot of the sample are introduced into the analysis unit 200, and mass analysis is performed. As shown in FIG. 10B, a time-of-flight mass spectrometer is used as the analysis unit 200. When a time-of-flight mass spectrometer is used, mass spectrometry can be performed simultaneously for the entire mass range, so that imaging mass spectrometry can be performed efficiently. In this case, however, the beam diameter of the laser beam or charged particle beam limits the spatial resolution. For example, in the case of laser light, since it can be converged only to about the wavelength, the spatial resolution is limited to about 1 micron. In the case of a charged particle beam, there is a space charge effect, so about 0.1 microns is the limit.

  In addition, in order to acquire an image of a wide space using such a finely focused laser beam, it is necessary to continuously scan a finely focused beam in two dimensions, and to scan the entire range. Takes a lot of time.

  Furthermore, a magnetic field type mass spectrometer can be used as the analysis unit 200. When a magnetic field type mass spectrometer is used, the ion source 100 irradiates a charged particle beam to a wide range of the sample, ionizes the sample, selects the ions that have come out by mass selection using a magnetic field type mass spectrometer, The detection unit 300 (position detector) capable of acquiring information obtains ion intensity and position information. If the analysis unit 200 satisfies the spatial convergence, it reaches the detection unit 300 while maintaining the position information of the sample surface, so that imaging mass spectrometry can be performed.

By the way, in recent years, the present inventors have developed a mass spectrometer that has a high mass resolution and does not distort an ion image (see Non-Patent Document 1). Specifically, the mass spectrometer is configured by using a plurality of circular electric fields and a plurality of quadrupole lenses, and a multi-turn time-of-flight type in which ions can orbit the same flight space a plurality of times. It is a mass spectrometer. In the mass spectrometer, since the flight distance of ions is significantly longer than that of the conventional time-of-flight mass spectrometer, the mass resolution can be improved.
US Pat. No. 5,808,300 (registered September 15, 1998) Michisato Toyoda, Daisuke Okumura, Morio Ishihara and Itsuo Katakuse: Multi-turn Time-of-Flight Mass Spectrometers with Electrostatic Sectors, J. Mass Spectrom., 38 (2003), 1125-1142.

  In recent years, in the fields of biology, medicine, pharmacy, and the like, it has been required to perform imaging mass spectrometry on relatively large samples such as biological samples such as cells and tissues. In imaging mass spectrometry of a biological sample, the measurement target is a relatively large sample such as a tissue. Further, the resolution required for measurement is high resolution that enables measurement at the cell level. Furthermore, although a biological sample has very many components, it is required to measure these components as many as possible at the same time.

  However, a conventional imaging mass spectrometer cannot measure a wide range of a sample in a short time with high spatial resolution. Specifically, a conventional imaging mass spectrometer equipped with a time-of-flight mass spectrometer as a mass spectrometer scans a sample by irradiating it with a finely focused laser beam or charged particle beam, which limits spatial resolution. In addition, there is a problem that a wide range of measurement requires time.

  On the other hand, in an imaging mass spectrometer equipped with a magnetic field type mass spectrometer, only a specific mass is selected in the magnetic field, and others are excluded, so that there is a problem that the entire mass range cannot be measured at the same position.

  In addition, in the imaging mass spectrometer, in order to measure a wide range of samples in a short time with high spatial resolution, not only the mass spectrometer but also the ion source and detector are improved. There is a need. For this reason, although there is a mass spectrometer as described in Non-Patent Document 1, an imaging mass spectrometer that measures a wide range of a sample in a short time with high spatial resolution has not been developed.

  The present invention has been made in view of the above-mentioned problems, and its purpose is imaging capable of simultaneously measuring both spatial position information and mass information of atoms and molecules constituting a sample with high resolution and at high speed. It is to provide a time-of-flight mass spectrometer.

  In order to solve the above problems, an imaging mass spectrometer according to the present invention maintains an ion image of a sample that is ionized over a wide range of a sample at the same time, and a sample generated in the ion source, and mass-separates ions. And a detection unit that simultaneously detects the arrival position and time of flight of the ions, and the ion source includes a lens system that extracts the ion image of the sample as it is.

  According to the above configuration, in the ion source, a wide range of the sample is ionized simultaneously. Since the ion source includes a lens system that directly extracts the sample without destroying the ion image of the sample, the ion of the sample is sent to the analysis unit while maintaining the ion image. In the analysis unit, each ion of the sample is mass-separated while maintaining the ion image as it is without destroying the ion image of the sample generated in the ion source. Further, the detection unit detects the arrival position of each ion of the sample sent from the analysis unit and measures the flight time of the ions. For this reason, it is possible to capture an ion image as an image based on the position information of each ion of the sample, and it is possible to reflect the image on a detector as a detection unit with high position resolution. Furthermore, since the mass of the ion of the sample can be known, there is an effect that the imaging mass analysis of the sample can be performed by integrating the ion image detected by the detection unit and the mass information.

  In the ion source, since a wide range of the sample is ionized at the same time, even if the sample to be analyzed is large, the number of measurements (the number of scans) may be small. Therefore, there is an effect that imaging mass spectrometry of a wide range of a sample can be performed in a short time.

  In the imaging mass spectrometer according to the present invention, the ion source is preferably ionized by irradiating the sample with a laser beam, charged particle or neutral particle beam having a large beam diameter.

  According to the above configuration, the laser beam, charged particle, or neutral particle beam used for ionization of the sample is not focused finely and has a large beam diameter. A wide area is irradiated simultaneously. Therefore, there is an effect that a wide range of the sample can be ionized simultaneously.

  In addition, since the laser beam, charged particle or neutral particle beam is irradiated to a wide range of the sample, the position resolution is not limited by the diameter of the laser beam, charged particle or neutral particle beam. Therefore, there is an effect that a wide range image of the sample can be acquired simultaneously.

  In the imaging mass spectrometer according to the present invention, it is preferable that the lens system includes an extraction electrode and an electrostatic lens group.

  According to the above configuration, the sample stage provided in the ion source is maintained at a high direct current potential with the same sign as the desorbed ions to be analyzed, and the desorption ions from the sample are maintained by maintaining the extraction electrode at the ground potential. Accelerated by a high electric field between the sample stage and the extraction electrode, a large velocity component can be obtained in the normal direction of the sample stage. Furthermore, in order to increase the velocity component of the desorbed ions in the normal direction of the sample stage, it is preferable that the interval between the sample stage and the extraction electrode be sufficiently short so that no discharge is generated.

  Therefore, according to the above configuration, the velocity component is sufficiently larger than the isotropic initial velocity of the desorbed ions, and the dispersion of the emission angles of the desorbed ions is relatively compressed. There is an effect that it can be pulled out while being held as it is.

  In the lens system, an electrostatic lens group is disposed behind the extraction electrode. Therefore, the spread of the desorbed ion beam is suppressed, and the ion image of the sample can be extracted as it is.

  In order to solve the above-described problems, the imaging mass spectrometer according to the present invention preferably further includes a magnifying / reducing lens group for enlarging or reducing the ion image.

  According to the above configuration, since the ion image can be freely enlarged and reduced, the size of the ion image can be changed according to the size of the detector used as the detection unit. Therefore, even when the spatial resolution of the detector is insufficient, there is an effect that the necessary spatial resolution can be obtained by enlarging the image.

  In the imaging mass spectrometer according to the present invention, the magnifying / reducing lens group is preferably an electrostatic lens group.

  Since the electrostatic lens group has no mass aberration, the above configuration has an effect that analysis can be performed in the entire mass region.

  In the imaging mass spectrometer according to the present invention, the analysis unit is preferably a linear time-of-flight mass spectrometer.

  According to the said structure, since the time-of-flight mass spectrometer is provided as an analysis part, there exists an effect that the measurement of the whole mass range can also be performed simultaneously.

  In the imaging mass spectrometer according to the present invention, the analysis unit is preferably a time-of-flight mass spectrometer composed of a plurality of electric fields.

  According to the said structure, the flight distance of the ion of a sample becomes long. As a characteristic of the time-of-flight mass spectrometer, when the flight distance of ions is extended, the mass resolution tends to increase. Moreover, ion can be converged temporally by using the above-mentioned sector electric field. Therefore, according to the above configuration, the mass resolution can be improved.

  Further, in the imaging mass spectrometer according to the present invention, the analysis unit is composed of a linear time-of-flight mass spectrometer and a plurality of fan electric fields, and a multi-turn time-of-flight mass analysis that makes a round of the same flight space. It is preferable to consist of a total.

  According to the above configuration, the ions of the sample can circulate a plurality of times on the same orbit, so that the flight distance of the ions of the sample becomes long. Furthermore, since a sector electric field is used, ions can be converged in time. Therefore, there is an effect that the mass resolution can be improved. Further, since ions are spatially focused, the spatial resolution can be improved.

  As described above, the imaging mass spectrometer according to the present invention is configured to ionize a wide range of a sample at the same time, detect the ion image of the sample without destroying it, and measure the mass of each ion of the sample. . Therefore, the chemical fine structure on the sample surface can be analyzed at high speed with a spatial resolution of the order of submicrons.

[Embodiment 1]
An embodiment of the present invention will be described below with reference to FIGS. 1 and 2, but the present invention is not limited to this.

  As shown in FIG. 1, an imaging mass spectrometer 1 according to the present embodiment maintains an ion image of a sample generated in the ion source 10 as it is, which can ionize a wide range of the sample at the same time, and The analyzer 20 includes an analysis unit 20 that mass-separates ions, a detection unit 30 that can simultaneously detect the arrival position and flight time of ions, and a data processing unit 40. Further, as shown in FIG. 2, the ion source 10 is provided with a lens system 60 for extracting an ion image of the sample as it is.

  The ion source 10 only needs to be capable of ionizing a wide range of the sample at the same time, and the specific configuration is not particularly limited. Specifically, it is preferable to ionize a wide range of the sample simultaneously by irradiating the sample with a laser beam, charged particle or neutral particle beam having a large beam diameter. More specifically, the beam diameter is preferably 0.5 mm to 1 mm.

  In addition, since the sample is generally a solid phase (condensed phase), the ion source 10 may be capable of ionizing the sample by a desorption ionization method that can directly generate gaseous ions from the solid phase. preferable. Furthermore, it is preferable that the sample can be ionized by an ionization method capable of controlling the ion generation site.

  Examples of the ion source include secondary ion mass spectrometry (SIMS) for irradiating a sample with an ion beam, laser desorption / ionization (LDI) for irradiating a laser beam, Matrix-assisted lase desorption / ionization (MALDI), in which a matrix that assists ionization of polymer compounds is added to the sample surface and irradiated with a laser beam, and fast atom bombardment ions (fast atom) bombardment; FAB).

  By using the ion source as described above, the ion source 10 can be ionized by irradiating a wide range of the sample with a primary beam, that is, a laser beam or a charged particle beam.

  The ion source 10 will be described more specifically with reference to FIG. 2 as follows. However, the ion source according to the present invention is not limited to this.

  FIG. 2 schematically shows a main part of the ion source 10. As shown in FIG. 2, the ion source 10 is provided with a lens system 60 for extracting the ion image of the sample as it is. The lens system 60 includes an extraction electrode and an Einzel lens. The extraction electrode has a structure in which a plurality of electrodes are arranged so as not to interfere with the path of the primary beam.

  Further, in the ion source 10, as described above, a primary beam, that is, a laser beam or a charged particle beam is irradiated to a wide area of the sample to ionize the sample. At this time, if the optical component for the primary beam interferes with the orbit of the desorbed ions, the ion image of the sample is disturbed. Therefore, the ion source 10 needs to have a structure in which the primary beam optical components are arranged so that the primary beam optical components do not interfere with the orbit of the desorbed ions.

  The sample stage provided in the ion source 10 is maintained at a high DC potential having the same sign as the desorbed ions to be analyzed. The lead electrode is kept at the ground potential. Further, the interval between the sample stage and the extraction electrode is made sufficiently short to prevent discharge.

  With such a configuration, the desorbed ions are accelerated by a high electric field between the sample stage and the extraction electrode, and a large velocity component can be obtained in the normal direction of the sample stage. Further, the velocity component is sufficiently larger than the isotropic initial velocity of the desorbed ions, and the dispersion of the emission angles of the desorbed ions is relatively compressed. For this reason, the desorption ion image can be extracted while being held as it is.

  In the lens system 60, an acceleration type Einzel lens is disposed behind the extraction electrode. Therefore, the spread of the desorption ion beam can be suppressed, that is, the ion image can be prevented from being dispersed and the ion image being disturbed.

  The lens system 60 may further include a quadrupole immersion lens for collimating the desorbed ion beam behind the Einzel lens. Thereby, the spread of the desorption ion beam can be further suppressed.

  The lens system 60 includes an acceleration type Einzel lens. However, the present invention is not limited to this, and an electrostatic lens group other than the acceleration type Einzel lens can be used instead of the acceleration type Einzel lens. Can be used.

  The sample is not particularly limited, but is preferably a solid. For example, biological cells and tissues, semiconductors, and the like can be mentioned, but there is no limitation thereto.

  The “wide range of the sample” is not particularly limited in area or shape, but is a range of a square having a side of 0.5 mm to 1 mm, a circle, an ellipse, or a polygon having the same area. It is preferable.

  The analysis unit 20 maintains the ion image of the sample generated in the ion source without breaking it, and separates each ion based on the difference in ion mass. In the present embodiment, the analysis unit 20 is a linear time-of-flight mass spectrometer as shown in FIG. When a linear time-of-flight mass spectrometer is used as the analysis unit 20, it is preferable to arrange a plurality of multipole lenses. With the above configuration, the ion image can be maintained in the analysis unit 20, that is, (x | α) = (x | δ) = (y | β) = 0 can be satisfied. That is, the ion image at the ion source 10 can be made to reach the detection unit 30 as an image as it is.

  The detection unit 30 is not particularly limited as long as it can simultaneously detect the arrival position of ions and the flight time. The detection unit 30 measures the flight time of ions from the ion source 10. Thereby, the mass of the ion can be known.

  The detection unit 30 detects the arrival position of ions from the ion source 10. The position where the ions have reached corresponds to the starting position at the ion source 10, that is, the position on the sample surface. That is, the detection unit 30 detects spatial position information (in other words, an image of the sample) and mass information (in other words, a constituent material of the sample) of atoms and molecules constituting the sample. .

  Specifically, a high-speed MCP position / time detection system (manufactured by Tokyo Instruments Co., Ltd.) can be used as the detection unit 30. The detection unit 30 can also be realized by combining an MCP (microchannel plate), a fluorescent plate, and a high-speed CCD camera.

  The data processing unit 40 processes the relationship between the mass of the sample and the image, and its specific configuration is not particularly limited. For example, it can be realized by software. In this embodiment, the imaging mass spectrometer 1 includes the data processing unit 40. However, the imaging mass spectrometer according to the present invention may not include the data processing unit 40.

[Embodiment 2]
The following will describe another embodiment of the present invention with reference to FIG. For convenience of explanation, members having the same functions as those used in the first embodiment are denoted by the same member numbers, and description thereof is omitted.

  As shown in FIG. 3, the imaging mass spectrometer 2 according to the present embodiment includes an ion source 10, an analysis unit 20, an enlargement / reduction lens group 50 that enlarges or reduces an ion image, a detection unit 30, and data. And a processing unit 40. As described in the first embodiment, the data processing unit 40 may not be provided in the imaging mass spectrometer according to the present invention.

  The magnifying / reducing lens group 50 is not particularly limited as long as it can be enlarged or reduced without breaking the ion image. For example, it can be realized by an electrostatic lens group in which one or a plurality of electrostatic lenses are combined, for example, a triplet pair of quadrupole lenses.

  According to this, the image can be freely enlarged or reduced in accordance with the size of the detector used as the detection unit 30. Even when the spatial resolution of the detector used in the detection unit 30 is insufficient, the necessary spatial resolution can be obtained by enlarging the image.

[Embodiment 3]
The following will describe another embodiment of the present invention with reference to FIGS. For convenience of explanation, members having the same functions as those used in the first and second embodiments are given the same member numbers, and the description thereof is omitted.

  As shown in FIG. 4, the imaging mass spectrometer 3 according to the present embodiment includes an ion source 10, an analysis unit 21, a magnification / reduction lens group 50, a detection unit 30, and a data processing unit 40. Yes. As described in the first embodiment, the data processing unit 40 may not be provided in the imaging mass spectrometer according to the present invention.

  In the present embodiment, the analysis unit 21 is a time-of-flight mass spectrometer using a plurality of sector electric fields that satisfies temporal and spatial convergence as shown in FIG. However, the time-of-flight mass spectrometer using a plurality of sector electric fields used for the analysis unit 21 is not limited to the configuration shown in FIG. Specifically, any time-of-flight mass spectrometer may be used in which a plurality of electric electric fields are arranged so as to satisfy temporal and spatial convergence of ions and the traveling direction of the ions can be changed. For example, a time-of-flight mass spectrometer in which four electric sector fields are arranged so that ions meander as shown in FIG. 5 can be used. According to this, since the flight distance of the ions of the sample is extended, the mass resolution can be improved. Note that the term “ionic temporal / spatial convergence” will be described later, so please refer to it.

[Embodiment 4]
The following will describe another embodiment of the present invention with reference to FIGS. For convenience of explanation, members having the same functions as those used in Embodiments 1 to 3 are given the same member numbers, and explanation thereof is omitted.

  As shown in FIG. 6, the imaging mass spectrometer 4 according to the present embodiment includes an ion source 10, an analysis unit 22, a magnification / reduction lens group 50, a detection unit 30, and a data processing unit 40. Yes. As described in the first embodiment, the data processing unit 40 may not be provided in the imaging mass spectrometer according to the present invention.

  In this embodiment, as shown in FIG. 6B, the analysis unit 22 is a mass spectrometer that combines a multi-round time-of-flight mass spectrometer using a sector electric field and a linear time-of-flight mass spectrometer. is there. In this way, by combining the multi-round time-of-flight mass spectrometer and the linear time-of-flight mass spectrometer, in order to inject ions into the analysis unit 22 or send ions to the detection unit 30, the analysis unit 22 Ions can be taken out from.

  When the sample is a biological sample such as a cell, it is preferable to use a mass spectrometer having high mass resolution for the analysis unit. More specifically, higher mass resolution than the commonly used linear time-of-flight mass spectrometer, reflectron type time-of-flight mass spectrometer, and sector electric field type time-of-flight mass spectrometer. It is desirable to use a mass spectrometer having the same.

  The analysis unit 22 in the present embodiment is a mass spectrometer having a high mass resolution that satisfies the above requirements. In such a mass spectrometer, ions can be circulated a plurality of times on the same orbit, so that the flight distance can be increased. Therefore, mass resolution can be improved.

  Furthermore, the analysis unit 22 has an optical system that focuses ions in time and space.

  In this specification, “the ions are converged in time” is exactly the same except for the time of flight caused by the difference in mass before entering the analysis unit and after coming out of the analysis unit. That is, the same regardless of the difference in the initial conditions.

  In addition, “spatial convergence of ions” means that the position and angle of ions are the same before entering the analysis unit and after leaving the analysis unit. The ion image may be enlarged or reduced before entering and after coming out of the analysis unit.

  In other words, “to converge ions temporally and spatially” means to satisfy both the above temporal convergence and spatial convergence, and can also be referred to as “to completely converge ions”. .

  According to the above configuration, even if ions are circulated a plurality of times, the ions do not spread in time and space. That is, even if the same flight space is circulated a plurality of times, the image is not spatially distorted, and the flight time is not different due to differences other than the mass. Therefore, the mass resolution can be improved as the number of turns increases without lowering the sensitivity and resolution. As a result, it is possible to increase the flight distance (time) while maintaining the ion image of the ion source, and high-speed measurement can be performed with high spatial resolution and high mass resolution.

  The analysis unit 22 will be described in more detail with reference to FIG. 7 as follows. The analysis unit 22 includes a multi-turn time-of-flight mass spectrometer and a linear type time-of-flight mass analysis which will be described in detail below. It is not limited to a mass spectrometer combined with a meter. That is, the analysis unit 22 includes a multi-turn time-of-flight mass spectrometer in which a plurality of electric quadrupole lenses and a cylindrical electrostatic fan are arranged so that ions can be converged in time and space. Any mass spectrometer combined with a linear time-of-flight mass spectrometer may be used.

  As the multi-round time-of-flight mass spectrometer, the MULTITU disclosed in Non-Patent Document 1 can be used. MULTUM is composed of four separate units. Each unit is composed of two electrostatic quadrupole lenses and a cylindrical electrostatic sector. The cylindrical electrostatic sector has a deflection radius of 50 mm. The deflection angle is 156.87 °, and the gap between the electrodes is 7.5 mm. The applied voltage when the ion acceleration voltage is 1500 V is ± 225 V. The length of the quadrupole lens is 10 mm, and the radius of the inscribed circle of the electrode is 5 mm. The voltages applied to the four quadrupole lenses (Q4, Q5, Q12, and Q13 in FIG. 7) located near the intersection are ± 16.57 V, and the other lenses (Q2, Q7 in FIG. 7). , Q10, and Q15) are ± 49.04V. The flight distance of one round is 1.284m.

  The analysis unit 22 can be realized by combining the MULTUM and a linear time-of-flight mass spectrometer. In addition, the mass spectrometer which combined the said MULTUM and the linear type | mold time-of-flight mass spectrometer is also called "MULTUM Linear plus" below. By combining the above MULTUM with a linear time-of-flight mass spectrometer, it is possible to input ions into the analysis unit 22 or to extract ions from the analysis unit 22 in order to send ions to the detection unit 30. .

  In addition to the above-mentioned MULTUM Linear plus, a mass spectrometer in which MULTUM Linear plus is modified can also be used for the analysis unit 22. An example of such a mass spectrometer is MULTUM II described in Non-Patent Document 1. In this specification, details of the above MULTUM, MULTUM Linear plus, and MULTUM II will not be described, but refer to Non-Patent Document 1 for these.

  The method for controlling the operation of the imaging mass spectrometer described in the first to fourth embodiments is not particularly limited. Depending on the configuration of the imaging mass spectrometer, it is only necessary to control the operation so that both spatial position information and mass information of the atoms and molecules constituting the sample can be measured simultaneously with high resolution and at high speed. . For example, such control can be performed by software or the like.

  The present invention is not limited to the configurations described above, and various modifications can be made within the scope of the claims, and the technical means disclosed in different embodiments are appropriately combined. The obtained embodiment is also included in the technical scope of the present invention.

  The present invention will be described more specifically based on examples and FIG. 8 and FIG. 9, but the present invention is not limited to this. Those skilled in the art can make various changes, modifications, and alterations without departing from the scope of the present invention.

[Example 1: Simulation of spatial resolution and mass resolution of imaging mass spectrometer]
The spatial resolution and mass resolution obtained when the sample was measured were verified by simulation using an imaging mass spectrometer equipped with a time-of-flight mass spectrometer in which a sector electric field is arranged as shown in FIG. The result is shown in FIG.

  The simulation was performed by the transfer matrix method using the ion trajectory simulation program “TRIO-DRAW” developed at Osaka University (M. Toyoda and T. Matsuo, Computer Program “TRIO-DRAW” for Displaying Ion Trajectory and Flight Time, Nucl. Instr. and Meth. A, 427 375-381 (1999)). FIG. 8A is a simulation of what time-of-flight peak is observed after a lap when starting with an ion packet having the shape of a solid line on the graph under the initial conditions described on the lower left side of the graph. The broken line on the graph indicates the time-of-flight peak of the ion after the simulated lap. Fig. 8 (b) shows a simulation of how the spatial shape returns after circulation when ions are emitted in the spatial shape shown in the left panel (Initial profile) under the initial conditions described below the panel. It is. The right panel (Final profile) is the spatial shape of ions after circulation.

  As shown in FIG. 8 (a), the mass resolution was as high as 10367 in FWHM. Further, as shown in FIG. 8B, the ions were not dispersed even after flying in the mass spectrometer, and the ion image was hardly distorted.

[Example 2: Simulation of spatial resolution and mass resolution of imaging mass spectrometer]
Using an imaging mass spectrometer equipped with the above-described MULTUM II (see Non-Patent Document 1) in the analysis unit, the spatial resolution and mass resolution obtained when the sample was measured were verified by simulation. The result is shown in FIG.

  As in Example 1, the simulation was performed by the transfer matrix method using the ion orbit simulation program “TRIO-DRAW” developed at Osaka University (M. Toyoda and T. Matsuo, Computer Program “TRIO- DRAW "for Displaying Ion Trajectory and Flight Time, Nucl. Instr. And Meth. A, 427 375-381 (1999)). FIG. 9A is a simulation of what time-of-flight peak is observed after a lap when starting with an ion packet having a solid line shape on the graph under the initial conditions described on the lower left side of the graph. The broken line on the graph indicates the time-of-flight peak of the ion after the simulated lap. FIG. 9 (b) shows a simulation of how the spatial shape returns after circulation when ions are emitted in the spatial shape shown in the left panel (Initial profile) under the initial conditions described below the panel. It is. The right panel (Final profile) is the spatial shape of ions after circulation.

  As shown in FIG. 9 (a), the mass resolution was as high as 5592 in FWHM. Further, as shown in FIG. 9B, even when the ions flew around the mass spectrometer a plurality of times, they were not dispersed and the ion image was hardly distorted.

  Note that the present invention is not limited to the configurations described above, and various modifications are possible within the scope of the claims, and technical means disclosed in different embodiments and examples respectively. Embodiments and examples obtained by appropriately combining them are also included in the technical scope of the present invention. In addition, all of the academic literatures and patent literatures described in this specification are incorporated herein by reference.

  As described above, in the present invention, since a wide range of a sample is ionized at the same time, the ion image of the sample is detected without breaking, and the mass of each ion of the sample is simultaneously measured, The structure can be analyzed at high speed with submicron order spatial resolution. Therefore, the present invention is a device that performs high-speed imaging with a spatial resolution of submicron order for all biomolecules including proteins and metabolites such as cells and the like in the field of life science, as well as position detection devices for impurities and host atoms in semiconductors. Can be used as In addition to this, the present invention is not limited to such methods as pathological diagnosis methods, pharmacokinetic studies, basic research in regenerative medicine, quality control in tissue engineering, drug discovery research through proteome analysis and metabolome analysis, and biology such as system biology construction. It can be used for various applications in the medical field. Furthermore, the present invention can be widely applied to all industrial technical fields in which it is required to observe a substance distribution based on mass.

FIG. 1A is a block diagram showing an outline of an imaging mass spectrometer according to an embodiment of the present invention. FIG. 1B is a diagram schematically showing the operation of the imaging mass spectrometer of FIG. FIG. 2 is a diagram schematically illustrating a main part of the ion source of the imaging mass spectrometer according to the embodiment of the present invention. FIG. 3A is a block diagram showing an outline of an imaging mass spectrometer according to another embodiment of the present invention. FIG. 3B is a diagram schematically showing the operation of the imaging mass spectrometer shown in FIG. FIG. 4A is a block diagram showing an outline of an imaging mass spectrometer according to another embodiment of the present invention. FIG. 4B is a diagram schematically showing the operation of the imaging mass spectrometer shown in FIG. FIG. 5 is a diagram schematically showing the arrangement of the electric sector in the analysis unit of the imaging mass spectrometer according to the embodiment of the present invention. FIG. 6A is a block diagram showing an outline of an imaging mass spectrometer according to another embodiment of the present invention. FIG. 6B is a diagram schematically showing the operation of the imaging mass spectrometer shown in FIG. It is a schematic diagram which shows the principal part of the analysis part of the imaging mass spectrometer concerning embodiment of this invention. It is a figure which shows the result of having simulated the mass resolution (FIG. 8 (a)) and the spatial resolution (FIG.8 (b)) of the imaging mass spectrometer concerning embodiment of this invention. It is a figure which shows the result of having simulated the mass resolution (FIG. 9 (a)) and the spatial resolution (FIG.9 (b)) of the imaging mass spectrometer concerning another embodiment of this invention. FIG. 10A is a block diagram showing an outline of an imaging mass spectrometer according to the prior art. FIG. 10B is a diagram schematically showing the operation of the imaging mass spectrometer shown in FIG.

Explanation of symbols

1-4 Imaging Mass Spectrometer 10 Ion Source 20-22 Analysis Unit 30 Detection Unit 40 Data Processing Unit 50 Enlarging / Reducing Lens Group 60 Lens System

Claims (8)

An ion source that simultaneously ionizes a wide range of samples;
An analyzer that maintains the ion image of the sample generated in the ion source as it is, and mass-separates the ions;
A detection unit that simultaneously detects the arrival position and time of flight of ions,
An imaging mass spectrometer characterized in that the ion source is provided with a lens system for extracting an ion image of the sample as it is.   The imaging mass spectrometer according to claim 1, wherein the ion source ionizes the sample by irradiating the sample with a laser beam, a charged particle beam or a neutral particle beam having a large beam diameter.   The imaging mass spectrometer according to claim 1 or 2, wherein the lens system includes an extraction electrode and an electrostatic lens group.   The imaging mass spectrometer according to claim 1, further comprising a magnifying / reducing lens group for enlarging or reducing the ion image.   The imaging mass spectrometer according to claim 4, wherein the magnifying / reducing lens group is an electrostatic lens group.   The imaging mass spectrometer according to claim 1, wherein the analysis unit is a linear time-of-flight mass spectrometer.   The imaging mass spectrometer according to claim 1, wherein the analysis unit is a time-of-flight mass spectrometer configured with a plurality of sector electric fields. The analysis unit
A linear time-of-flight mass spectrometer,
The imaging mass spectrometer according to any one of claims 1 to 5, comprising a multi-turn time-of-flight mass spectrometer configured by a plurality of sector electric fields and rotating around the same flight space a plurality of times. .

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