Quality analysis equipment

Abstract

To provide a device capable of performing both mass spectrometry and electron beam diffraction measurement for identifying an isomer in a single measurement, and to provide a technique that enables electron beam diffraction measurement to be performed more efficiently than conventionally in such a device.SOLUTION: A mass spectroscope 1 includes an ionization unit 201 that generates ions from a sample, mass separation units 231 and 235 that mass-separate the ions generated in the ionization unit, an ion detection unit 237 that detects ions mass-separated by the mass separation unit, an ion capture unit 31 that captures ions mass-separated by the mass separation unit, and an electron beam detection unit 32 that detects an electron beam diffracted by ions captured by the ion capture unit.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a mass spectrometer. [Background technology]

[0002] Mass spectrometers are widely used to identify and quantify components contained in samples. In mass spectrometers, ions generated from sample components are mass-separated and the ion intensity for each mass-to-charge ratio is measured. A mass spectrum with two axes of mass-to-charge ratio and ion intensity is then created, and the component is identified based on the degree of agreement with mass spectra of known substances. The component is also quantified based on the intensity of the mass peaks in the mass spectrum.

[0003] When a sample component is a relatively large molecule, it is difficult to identify the component from the ions generated from the sample component itself. Therefore, MS / MS analysis is performed in which ions with a specific mass-to-charge ratio are selected as precursor ions from the ions generated from the sample component, and the precursor ions are fragmented to generate product ions, which are mass-separated and the intensity of the ions for each mass-to-charge ratio is measured. In MS / MS analysis, the partial structure of the sample component is estimated from the mass-to-charge ratios of various product ions to identify the sample component.

[0004] Mass spectrometry separates ions according to their mass-to-charge ratio, and therefore cannot separate ions with the same mass-to-charge ratio. For example, butane and isobutane are structural isomers with different bonding positions of the methyl group, but since the two have the same mass, these ions cannot be separated. In addition, in the case of structural isomers, even if precursor ions are cleaved to generate product ions, only the same type of product ions are often generated, making it difficult to distinguish between the two.

[0005] Therefore, other measurement methods have been used to obtain information on the geometric structure of molecules (atomic distances and bond angles) that cannot be obtained by mass spectrometry. Examples of such measurement methods include rotational spectrometry, electron diffraction measurement, and X-ray diffraction measurement. In rotational spectrometry, microwaves are irradiated onto the sample gas to measure the absorbance (light absorption measurement), or light emission from the sample gas is spectroscopically measured, but the sensitivity is lower than that of diffraction methods such as electron diffraction measurement and X-ray diffraction measurement. In addition, the elastic scattering cross section in X-ray diffraction measurement is 10 times that of electron diffraction. -5 ~10 -4 The diffraction efficiency is only 100 times smaller than that of electron diffraction (see, for example, Non-Patent Document 1), and the sensitivity of the diffraction efficiency is poorer than that of electron diffraction when measuring sample gases. For these reasons, it has been proposed to obtain the geometric structure of molecules by electron diffraction measurements as described in Non-Patent Documents 2-5.

[0006] Non-Patent Documents 2 and 3 describe electron beam diffraction devices. In these devices, neutral gas molecules are introduced into an ion trap and ionized (photoionized) by irradiating them with laser light, and the multiple types of ions generated are trapped in the ion trap, after which mass selection is performed in the ion trap to trap only the ions to be analyzed. An electron beam is then irradiated onto the ions trapped in the ion trap to obtain an electron beam diffraction image. Information on the geometric structure of the molecule is obtained by analyzing this electron beam diffraction image.

[0007] Non-Patent Document 4 describes an apparatus that combines an apparatus for performing electron beam diffraction measurement with a mass analyzer. This apparatus is equipped with a deflection section downstream of the ionization section that deflects the flight direction of ions, and the deflection section switches the deflection direction to introduce ions generated in the ionization section into either an ion trap or a time-of-flight mass separator. In the ion trap, a diffraction image is obtained by irradiating an electron beam as in the apparatuses of Non-Patent Documents 2 and 3, and information on the molecular structure of the ions is obtained. Meanwhile, the time-of-flight mass separator obtains a mass spectrum to monitor the state of ion generation in the ion source. [Prior art documents] [Non-patent literature]

[0008] [Non-Patent Document 1] M. Haneda, "Observation of ultrafast structural dynamics using tabletop femtosecond electron diffraction," Journal of the Vacuum Society of Japan, Vol. 59 (2016), No. 2 [Non-Patent Document 2] Keiko Kato, Dissertation Abstract "Development of an Ion Trap Electron Diffraction Apparatus and Its Application to Determining the Structure of Molecular Ions and Tracking Their Reactions", 2006, Graduate School of Science, The University of Tokyo, [online], [Retrieved December 21, 2020], Internet<URL:http: / / gakui.dl.itc.u-tokyo.ac.jp / cgi-bin / gazo.cgi?no=121041> [Non-Patent Document 3] Hidetaka Tanaka and 3 others, Abstract of the 9th Molecular Science Symposium 2015 Tokyo Lecture "Ion trap electron diffraction apparatus for determining the geometric structure of molecular ions", [online], August 31, 2015, Molecular Science Society, [Retrieved December 21, 2020], Internet<URL:http: / / molsci.center.ims.ac.jp / area / 2015 / PDF / pdf / 1P012_w.pdf> [Non-Patent Document 4] D. Schooss, MN Blom, JH Parks, BV Issendorff, H. Haberland, and MM Kappes, "The structure of Ag55+ and Ag55-: Trapped ions electron diffraction and density functional theory", Nano Lett. 5 (2005) 1972. [Non-Patent Document 5] M. Marier-Brost, DB Cameron, M. Rokni, and JH Parks, "Electron diffraction of trapped cluster ions", Phys. Rev. A 59 (1999) R3162. Summary of the Invention [Problem to be solved by the invention]

[0009] By combining a configuration for performing electron beam diffraction measurement as described in Non-Patent Documents 2-5 with a mass spectrometer, it is possible to obtain information on the geometric structure of molecules (atomic distances and bond angles) with higher sensitivity than rotational spectrum measurement or X-ray diffraction measurement when identifying structural isomers that are difficult to identify by mass analysis, and identify sample components with a single device based on mass analysis. However, in the electron beam diffraction devices proposed in the past, in order to obtain a diffraction image with sufficient intensity for analysis, it is necessary to continue irradiating the electron beam for a long period of time, for example, 5 to 6 hours. On the other hand, mass analysis can be performed in a short time of about several minutes. Thus, in the conventional configuration, the time required for auxiliary electron beam diffraction measurement is significantly longer than the time required for mass analysis, which is the main measurement. Therefore, a technology that can perform electron beam diffraction measurement more efficiently is required.

[0010] Here, an example has been described in which measurements are performed to obtain information on the geometric structure of molecules in addition to mass spectrometry. However, similar problems to those described above arise when various secondary measurements are performed in addition to mass spectrometry to obtain information that cannot be obtained by mass spectrometry.

[0011] The problem to be solved by the present invention is to provide an apparatus capable of performing both mass spectrometry and a secondary measurement for obtaining information that cannot be obtained by mass spectrometry in a single measurement, and to provide a technique for performing the secondary measurement in such an apparatus more efficiently than ever before. [Means for solving the problem]

[0012] In order to solve the above problems, the mass spectrometer according to the present invention is an ionization unit for generating ions from a sample; The ions generated in the ionization section are mass-produced. Depending on the charge ratio A mass separation unit for separating the particles; The mass separation section In minutes an ion detector for detecting the released ions; The mass separation section In minutes an ion trapping unit that traps the released ions; a sub-measurement unit for measuring a physical quantity of the ions trapped in the ion trapping unit other than the mass-to-charge ratio; Equipped with. Effect of the Invention

[0013] In the mass spectrometer according to the present invention, mass analysis can be performed by mass-separating ions generated in the ionization section in the mass separation section and detecting them with an ion detector. In addition, after mass-separating ions generated in the ionization section in the mass separation section to select ions to be analyzed, the ions can be trapped in the ion trapping section and a physical quantity other than the mass-to-charge ratio can be measured (secondary measurement). The secondary measurement can be, for example, irradiating the ions trapped in the ion trapping section with an electromagnetic wave (light beam, etc.) or a particle beam, and detecting the electromagnetic wave (light, etc.) or particles emitted from the ion trapping section. Specifically, for example, after accumulating ions to be analyzed in the ion trapping section, an electron beam can be irradiated thereon for a predetermined time, and the electron beam diffracted by the ions in the ion trapping section can be detected to perform electron beam diffraction measurement. Although mass analysis alone cannot distinguish isomers having the same mass-to-charge ratio, the mass spectrometer according to the present invention can obtain information on molecular structure and distinguish isomers by performing, for example, the above-mentioned electron beam diffraction measurement as a secondary measurement. Furthermore, in the mass spectrometer of the present invention, by appropriately changing the flight path of the ions, it is possible to perform, in a single measurement, both mass analysis, in which the ions generated in the ionization section are mass-separated and detected, and a secondary measurement, in which the ions after mass separation are trapped and a physical quantity of the ions other than the mass-to-charge ratio is measured.

[0014] If mass separation is performed in an ion trapping section (typically a three-dimensional ion trap) with an excessive amount of ions trapped in the ion trapping section, the electric field in the ion trapping section is distorted by the electric charge (space charge) of the ions themselves, making it impossible to perform normal mass separation. Therefore, in a conventional configuration in which mass separation is performed in an ion trapping section, the amount of ions that can be trapped in the ion trapping section is limited. Furthermore, even if the maximum amount of ions generated from a sample is trapped using a conventional device, the amount of ions decreases due to the subsequent mass separation. In contrast, in the mass spectrometer according to the present invention, the mass separation section selects ions to be analyzed and introduces only the ions to be analyzed into the ion trapping section, so that the maximum amount of ions to be analyzed can be captured and used for secondary measurement, and high-intensity measurement data can be obtained more efficiently and in a shorter time than in the past.

[0015] The ion trapping section may be disposed between the mass separation section and the ion detector, for example, or a deflection section for deflecting the flight direction of ions may be provided between the mass separation section and the ion detector, and the ion trapping section may be disposed on the flight path of ions deflected by the deflection section. In the former case, the ion trapping section is not operated, and ions that have been mass-separated in the mass separation section are allowed to pass through as is and detected by the ion detector for mass analysis, and the ions that have been mass-separated in the mass separation section are trapped in the ion trapping section for secondary measurement. In the latter case, the flight path of ions during mass analysis and the flight path of ions during secondary measurement are different, so that both measurements can be performed in parallel. [Brief description of the drawings]

[0016] [Figure 1] 1 is a schematic diagram of an embodiment of a mass spectrometer according to the present invention; [Diagram 2] 4 shows measurement conditions for target compounds in measurement examples using the mass spectrometer of this embodiment. [Diagram 3] FIG. 4 is a diagram for explaining the measurement content executed in the present embodiment. [Figure 4] FIG. 4 is a diagram for explaining a rectangular voltage applied to an ion trap in this embodiment. [Diagram 5]2 shows an ion trap used in the mass spectrometer of this embodiment. [Figure 6] Simulation results for the spread of ions in the X-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 0°. [Figure 7] Simulation results for the spread of ions in the X-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 90°. [Figure 8] Simulation results for the spread of ions in the X-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 180°. [Figure 9] Simulation results for the spread of ions in the X-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 270°. [Figure 10] Simulation results for the spread of ions in the Z-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 0°. [Figure 11] Simulation results for the spread of ions in the Z-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 90°. [Figure 12] Simulation results for the spread of ions in the Z-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 180°. [Figure 13] Simulation results for the spread of ions in the Z-axis direction inside the ion trap when the phase of the rectangular voltage applied to the ion trap is 270°. [Figure 14] FIG. 2 is a diagram for explaining electron beam diffraction measurement. [Figure 15] 1 is a chromatographic mass spectrometer using the mass spectrometer of this embodiment. [Figure 16] An ion mobility spectrometry-mass spectrometry apparatus using the mass spectrometry apparatus of this embodiment. [Figure 17] Chromatograph-ion mobility analysis-mass analyzer using the mass analyzer of this embodiment. [Figure 18] 13 shows an example of the arrangement of each part in a mass spectrometer according to a modified example. [Figure 19] 4 shows examples of sub-measurements that can be performed in a mass spectrometer according to the present invention. [Figure 20] 1 shows an example of the schematic configuration of a mass spectrometer that performs various secondary measurements. [Figure 21] 3 shows another schematic configuration example of a mass spectrometer for performing various secondary measurements. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0017] An embodiment of a mass spectrometer according to the present invention will now be described with reference to the drawings.

[0018] 1 is a schematic diagram of a mass spectrometer 1 according to the present embodiment. The mass spectrometer 1 according to the present embodiment is composed of an apparatus body 10 and a control and processing unit 4. The apparatus body 10 is provided with an ionization chamber 20, a first intermediate vacuum chamber 21, a second intermediate vacuum chamber 22, and an analysis chamber 23. An electron beam irradiation unit 30 is connected to the analysis chamber 23. An appropriate voltage is applied from a voltage application unit 5 to each unit in the apparatus body 10 during measurement, based on the control by the control and processing unit 4.

[0019] The ionization chamber 20 is at approximately atmospheric pressure, the first intermediate vacuum chamber 21 is a low vacuum chamber evacuated by a rotary pump (not shown), and the second intermediate vacuum chamber 22, the analysis chamber 23, and the inside of the electron beam irradiation unit 30 are high vacuum chambers evacuated by a turbo molecular pump (not shown). The first intermediate vacuum chamber 21, the second intermediate vacuum chamber 22, and the analysis chamber 23 have a multi-stage differential pumping system configuration in which the degree of vacuum increases in stages in this order.

[0020] An electrospray ionization probe (ESI probe) 201 that applies an electric charge to a sample solution and sprays it is installed in the ionization chamber 20. The ionization chamber 20 and the first intermediate vacuum chamber 21 are connected through a thin-diameter heated capillary 202. In this embodiment, the ESI probe 201 is used as the ionization unit, but an appropriate ionization unit can be used depending on the characteristics of the sample.

[0021] An ion lens 211 consisting of a plurality of annular electrodes that focuses ions and transports them to a subsequent stage is disposed in the first intermediate vacuum chamber 21. The first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 are separated by a skimmer 212 having a small hole at the top.

[0022] A first ion guide 221 and a second ion guide 222, each of which is composed of a plurality of rod electrodes and which focus ions while transporting them to the rear stage, are disposed in the second intermediate vacuum chamber 22. The second intermediate vacuum chamber 22 and the analysis chamber 23 are communicated with each other through a small hole formed in the partition wall.

[0023] In the analysis chamber 23, a front quadrupole mass filter (Q1) 231, a collision cell 232, a rear quadrupole mass filter (Q3) 235, a deflection unit 236, and an ion detector 237 are arranged. The front quadrupole mass filter 231 is composed of a pre-rod electrode 2311, a main rod electrode 2312, and a post rod electrode 2313. A quadrupole rod electrode 234 is arranged inside the collision cell 232. In addition, the collision cell 232 is provided with a gas inlet for introducing a collision induced dissociation gas (CID gas) such as argon gas or nitrogen gas. The rear quadrupole mass filter 235 is composed of a pre-rod electrode 2351, a main rod electrode 2352, and a post rod electrode 2353. In the deflection unit 236, four rod electrodes 2361 are arranged. In this embodiment, the flight direction of the ions is deflected by the deflection section 236 as described below, and the deflection section may be of any suitable configuration capable of deflecting the flight direction of the ions.

[0024] In addition, an ion trap 31 and an electron beam detector 32 are disposed in the analysis chamber 23. The ion trap 31 is composed of a ring electrode 311, an entrance end cap electrode 312 and an exit end cap electrode 313 disposed on either side of the ring electrode 311. The entrance end cap electrode 312 is provided with an opening 314 for introducing ions and an electron beam. The exit end cap electrode 313 is provided with an opening 315 for discharging ions and an electron beam. The ion trap 31 is disposed in a vacuum chamber 316, and in addition to openings corresponding to the openings 314 and 315, a gas inlet 317 for introducing a cooling gas into the ion trap 31 is provided on the wall of the vacuum chamber 316. The inside of the vacuum chamber 316 is evacuated to a high vacuum by a turbo molecular pump (not shown).

[0025] The electron beam detection unit 32 includes a Faraday cup 321, Micro It is equipped with a channel plate 322 , a fluorescent screen 323 , and a CCD camera 324 . Micro The channel plate 322 is disposed outside the exit end cap electrode 313 in the ion trap 31. The Faraday cup 321 is Micro The fluorescent screen 323 is disposed on the irradiation axis C2 of the electron beam near the surface of the channel plate 322. Micro It is attached to the rear surface of the channel plate 322. The CCD camera 324 is disposed on the rear surface side of the fluorescent screen 323 at a position where it can image the rear surface.

[0026] The electron beam irradiation unit 30 is provided with an electron gun 301 and an electron lens 302. In the electron beam irradiation unit 30, the incident energy of the electron beam irradiated onto the ions when performing electron beam diffraction measurement can be changed.

[0027] The control / processing unit 4 includes, as functional blocks, a measurement condition setting unit 43, a measurement control unit 44, an analysis processing unit 45, an electron beam diffraction image estimation unit 46, and a molecular structure estimation unit 47, in addition to a storage unit 41. A compound database 411 is stored in the storage unit 41. The molecular structure estimation unit 47 includes a first molecular structure estimation unit 471, a second molecular structure estimation unit 472, and a third molecular structure estimation unit 473. The actual entity of the control / processing unit 4 is a general personal computer, and the processor of the personal computer functions as each of the above units by executing a mass analysis program 42 pre-installed in the computer. An input unit 6 and a display unit 7 are also connected to the control / processing unit 4.

[0028] The compound database 411 stores information such as measurement conditions and analysis results for a large number of known compounds. The measurement conditions include, for example, the time (retention time) at which the compound flows out of a column of a liquid chromatograph, and the mass-to-charge ratio of a pair of precursor ions and product ions (MRM transitions) that characterize the compound. The analysis result information includes, for example, MS / MS spectrum data and electron diffraction image data for each compound. The electron diffraction image data may be experimentally obtained by measuring a standard sample, or may be theoretically calculated based on the molecular structure of the compound. For such theoretical calculations, for example, first-principles calculations may be used.

[0029] Next, the measurement of a sample using the mass spectrometer 1 of this embodiment will be described. Here, an example will be described in which a liquid chromatograph is placed in front of the mass spectrometer 1 (see FIG. 15), a sample is introduced into the liquid chromatograph, and components contained in the sample are separated from each other in the column of the liquid chromatograph and measured by the mass spectrometer 1. However, the provision of a component separation means such as a chromatograph is not essential to the present invention. For example, even when a sample containing multiple compounds is measured, if ions derived from the compound to be measured can be separated from ions derived from other compounds by mass separation alone, the sample may be directly introduced into the mass spectrometer 1 without using a component separation means.

[0030] First, the measurement condition setting unit 43 reads out a list of compounds stored in the compound database 411 and displays it on the display unit 7. When the user selects a compound to be measured from the list, the measurement condition setting unit 43 creates a method file describing the measurement conditions described in the compound database 411. Then, a batch file for executing the measurement is created from these method files. Note that in this embodiment, the process in which the user selects a compound to be measured from the compound database 411 corresponds to inputting information on molecular structure candidates in the present invention, and the measurement condition setting unit 43 in this embodiment functions as a molecular structure candidate input receiving unit in the present invention (see [Aspects] described later).

[0031] As a specific example, a case where compounds A to D shown in FIG. 2 are the measurement targets will be described here. Among compounds A to D, compounds C and D are structural isomers. Some structural isomers can be separated from each other using a liquid chromatograph or gas chromatograph column, but here, the retention time, precursor ion, and product ion effluent from the liquid chromatograph column for compounds C and D are the same (that is, compounds C and D cannot be distinguished from each other using liquid chromatograph mass spectrometry alone). Therefore, in this example, MRM measurement is performed for all compounds A to D, and electron beam diffraction measurement is further performed for compounds C and D. That is, as shown in FIG. 3, a batch file is created in which MRM measurement of compound A is performed in time zone 1, MRM measurement of compounds A and B is alternately performed in time zone 2, MRM measurement of compound B is performed in time zone 3, and MRM measurement and electron beam diffraction measurement of compounds C and D are performed in time zone 4. The user may specify whether or not to perform electron diffraction measurement, or the measurement condition setting unit 43 may automatically set electron diffraction measurement for a pair of compounds having the same retention time, mass-to-charge ratio of precursor ion, and mass-to-charge ratio of product ion. For ease of explanation, only one MRM transition is measured for one compound here, but multiple MRM transitions may be measured.

[0032] After the batch file is created, when the user issues an instruction to execute a measurement by a predetermined input operation, the measurement control unit 44 performs the measurement in the following procedure.

[0033] First, a sample is introduced into a liquid chromatograph. The sample components separated in the column of the chromatograph are sequentially introduced into the ESI probe 201 and ionized.

[0034] After the measurement starts, when the first time slot (time slot 1) described in the batch file is reached, the compound described in that time slot is measured. In time slot 1, MRM measurement of compound A is performed. After that, in each time slot, MRM measurement and electron beam diffraction measurement are performed based on the contents described in the batch file.

[0035] A brief explanation will be given of the MRM measurements performed in time periods 1 to 4. The measurement conditions for the MRM measurements are the same as in the conventional method.

[0036] The sample components flowing out from the liquid chromatograph column are ionized by the ESI probe 201, then introduced into the first intermediate vacuum chamber 21 through the heated capillary 202, and then focused onto the ion optical axis C1 by the ion lens 211. The ions focused by the ion lens 211 pass through the skimmer 212 and enter the second intermediate vacuum chamber 22. The ions that enter the second intermediate vacuum chamber 22 are focused onto the ion optical axis C1 by the first ion guide 221 and the second ion guide 222, and enter the analysis chamber 23.

[0037] In the analysis chamber 23, first, precursor ions of the compound to be measured are selected by the front-stage quadrupole mass filter 231 and introduced into the collision cell 232. A predetermined amount of a predetermined type of inert gas (typically argon gas) is sealed in the collision cell 232 as a collision gas. A potential difference is provided between the post rod electrode 2313 of the front-stage quadrupole mass filter 231 and the inlet of the collision cell 232, and this potential difference provides energy (collision energy) to the precursor ions of the compound to be measured, causing them to enter the collision cell. In the collision cell 232, product ions are generated from the precursor ions by collision with molecules of the inert gas.

[0038] Subsequently, only product ions having a predetermined mass-to-charge ratio (described in the method file) are selected in the post-quadrupole mass filter 235. The ions selected by the post-quadrupole mass filter 235 pass directly through the deflection unit 236 and are detected by the ion detector 237. Output signals from the ion detector 237 are sequentially transmitted to the memory unit 41 and stored therein.

[0039] Next, the electron diffraction measurement performed in time period 4 will be described.

[0040] In the electron diffraction measurement, as in the MRM measurement, ions of a predetermined mass-to-charge ratio are selected as precursor ions in the front-stage quadrupole mass filter 231, and the precursor ions are dissociated in the collision cell 232 to generate product ions. Then, ions of a predetermined mass-to-charge ratio are selected as ions to be analyzed in the rear-stage quadrupole mass filter 235. In the electron diffraction measurement, product ions that have the same mass-to-charge ratio but contain portions with different molecular structures are used as the ions of the above-mentioned predetermined mass-to-charge ratio selected by the rear-stage quadrupole mass filter 235 as the ions to be analyzed.

[0041] When performing electron beam diffraction measurement, the inside of the vacuum chamber 316 is evacuated to a high vacuum in advance to discharge neutral gas molecules remaining inside the ion trap 31. Then, a voltage of the opposite polarity to that of the product ions is applied to one of the four rod electrodes 2361 of the deflection unit 236 (the rod electrode 2361 located at the lower left in FIG. 1), and a voltage of the same polarity as that of the product ions is applied to the other rod electrodes 2361. By applying a voltage of an appropriate magnitude to these four rod electrodes 2361, the flight direction of the ions that have passed through the rear-stage quadrupole mass filter 235 is deflected by 90 degrees (downward in FIG. 1).

[0042] The product ions, whose flight direction has been deflected by the deflection unit 236, are captured in the ion trap 31, cooled by collision with a cooling gas (typically helium gas) that is temporarily introduced into the ion trap 31 through the gas inlet 317, and collected in the center of the ion trap 31. After the product ions are accumulated and cooled for a predetermined time in the ion trap 31, an electron beam is irradiated from the electron beam irradiation unit 30 into the inside of the ion trap 31.

[0043] In the conventional electron diffraction measurement, ions generated from a sample are directly stored in an ion trap, and then mass separation is performed in the ion trap to select the ions to be measured. When storing ions generated from a sample, if an excessive amount of ions are stored, the electric field inside the ion trap is distorted by the electric charge of the ions themselves (called "space charge"), and normal mass separation cannot be performed. Therefore, at the stage of storing ions generated from a sample, there is a limit to the amount of ions that can be stored in the ion trap. In addition, since ions generated from a sample are introduced into the ion trap and the ions to be measured are mass separated and selected in the ion trap in the conventional method, even if the maximum amount of ions that can be stored is stored at the beginning, the amount of ions to be analyzed contained therein is less than that.

[0044] In contrast, in the mass spectrometer of this embodiment, product ions to be analyzed are selected by the front-stage quadrupole mass filter 231, the collision cell 232, and the rear-stage quadrupole mass filter 235, and then introduced into the ion trap 31. Therefore, there is no need to perform mass separation within the ion trap 31, and only the product ions to be analyzed can be introduced into the ion trap 31 without limiting the amount of ions accumulated in the ion trap 31.

[0045] In addition, conventionally, the entrance end cap electrode and the exit end cap electrode are held at ground potential, and a high-frequency sinusoidal voltage is applied to the ring electrode to trap ions in the ion trap, and the mass-to-charge ratio (range) of the trapped ions is increased or decreased by increasing or decreasing the amplitude (voltage driving) while keeping the frequency of the sinusoidal voltage constant. In the conventional method, the amplitude of the sinusoidal voltage must be increased as the mass-to-charge ratio of the ions to be trapped increases, which requires the use of a large and expensive power supply capable of outputting high voltages. In addition, there are problems in that the application of high voltages makes discharges more likely to occur, and the application of time-varying high voltages has a negative effect on the flight path of the electron beam.

[0046] On the other hand, in this embodiment, the entrance end cap electrode 312 and the exit end cap electrode 313 are set to ground potential, and a rectangular voltage generated by the voltage application unit 5 using a digital circuit is applied to the ring electrode 311 of the ion trap 31. An ion trap that applies a rectangular voltage to trap ions in this way is also called a digital ion trap (DIT). In the DIT, the frequency is changed over a wide range (frequency drive) while keeping the amplitude of the rectangular voltage constant to change the mass-to-charge ratio (range) of ions to be trapped in the ion trap 31. In the digital ion trap, the amplitude of the rectangular voltage is constant regardless of the mass-to-charge ratio of the ions to be trapped, so there is no need to use a large and expensive power supply. There is also no risk of discharge. Furthermore, since the frequency drive can change the frequency over a wide range, it is possible to cover a wider mass-to-charge ratio range and trap more types of ions than conventional voltage-driven ion traps. For example, by lowering the frequency, it is possible to trap ions with a large mass-to-charge ratio that is difficult to trap in conventional voltage-driven ion traps, or to trap fine charged particles that are much larger than ions. Furthermore, while a low-frequency rectangular voltage is applied to capture precursor ions with a large mass-to-charge ratio, the captured precursor ions are fragmented (i.e., dissociated) using laser light or the like, and the frequency of the rectangular voltage can be instantly switched to a higher frequency (frequency jump) so that the fragment ions with a small mass-to-charge ratio generated by the fragmentation of the precursor ions are captured in the ion trap. In addition, by injecting the electron beam at a timing when the rectangular voltage (high-frequency voltage) reaches a predetermined phase, as described below, the possibility of adversely affecting the flight path of the electron beam can be eliminated.

[0047] In the mass spectrometer 1 of this embodiment, this rectangular voltage is applied to the ring electrode 311 for a predetermined time to trap product ions in the ion trap 31. electrodeThe spatial distribution of ions inside the ion trap 31 changes with the change in phase of the rectangular voltage applied to 311. In the following description, the phase at the point when the applied voltage changes from negative to positive is set to 0°, and the phase at the point when it changes from positive to negative is set to 180°, as shown in Fig. 4. Also, as shown in Fig. 5, the axis of symmetry of the ion trap 31 (the axis passing through the opening 314 of the entrance end cap electrode 312 and the opening 315 of the exit end cap electrode 313) is set to the Z axis, and the direction perpendicular to that is set to the X axis.

[0048] The results of a simulation performed by the present inventor regarding the correlation between the phase of the rectangular voltage and the motion state of ions (spatial distribution and velocity distribution) will be described.

[0049] 6 to 9 show simulation results of the spread (X) of ion positions in the X-axis direction and the velocity (Vx) in the X-axis direction in the ion trap 31 when the phase of the rectangular voltage is 0°, 90°, 180°, and 270°, respectively. These results show that even if the phase of the rectangular voltage applied to the ring electrode 311 is changed, there is no significant change in the spread of ion positions in the X-axis direction.

[0050] 10 to 13 show the results of simulating the spread (Z) of the ion position in the ion trap 31 in the Z-axis direction and the velocity (Vz) in the Z-axis direction when the phase of the rectangular voltage is 0°, 90°, 180°, and 270°, respectively. Unlike the X-axis direction, these results show that the spread of the ion position in the Z-axis direction also changes when the phase of the rectangular voltage applied to the ring electrode 311 changes. Among these, it can be seen that when the phase is particularly 270°, the ions spread in the most elongated state in the Z-axis direction and are most narrowly distributed in the X-axis direction. Since the electron beam from the electron beam irradiation unit 30 is irradiated in the Z-axis direction (negative direction of the Z axis), if the electron beam is irradiated to the inside of the ion trap 31 at this timing, the electron beam can be irradiated most efficiently to the ions trapped in the ion trap 31. In other words, the spatial overlap between the ion cloud and the electron beam becomes large. Therefore, in this embodiment, the electron beam from the electron beam irradiation unit 30 is irradiated into the ion trap 31 around the timing when the phase of the rectangular voltage applied to the ring electrode 311 becomes 270° (the timing indicated by hatching in Figure 4).

[0051] Furthermore, in the conventional ion trap, the electron beam is continuously irradiated to the ions trapped in the ion trap, but the high-frequency sinusoidal voltage applied to the ring electrode changes over time, which causes the direction and magnitude of the electron beam deflection to change over time, resulting in an increase in the background that does not contribute to diffraction, making the electron diffraction image unclear.

[0052] In contrast, in the mass spectrometer 1 of this embodiment, a pulsed electron beam is irradiated at a timing around when the phase of the rectangular voltage is 270°. In other words, since the electric field formed inside the ion trap 31 at the timing of irradiating the electron beam is always the same, it is possible to consider in advance the effect of the electric field on the path of the electron beam and determine measurement conditions such as the irradiation direction of the electron beam so as to compensate for this effect.

[0053] The electron beam that passes through the ion trap 31 without being diffracted by the product ions is incident on the Faraday cup 321. A current corresponding to the amount of the incident electron beam is generated in the Faraday cup 321, and the amount of the electron beam irradiated from the electron beam irradiation unit 30 is estimated based on the magnitude of the current.

[0054] An electron beam diffracted by product ions trapped in the ion trap 31 enters a microchannel plate 322. Electron multipliers are arranged two-dimensionally in the microchannel plate 322, and electrons entering the electron multipliers are amplified and emitted from the opposite side. The electrons emitted from the electron multipliers enter a fluorescent screen 323. A fluorescent material is applied to the surface of the fluorescent screen 323 in advance, and electrons entering the fluorescent screen 323 cause the fluorescent material to emit fluorescence at the position of incidence. A CCD camera 324 is arranged on the back side of the fluorescent screen 323, which captures the fluorescence emitted from the fluorescent screen 323 at a predetermined cycle and sequentially transmits the captured data to a control and processing unit 4. The control and processing unit 4 stores the received captured data in a memory unit 41.

[0055] When the measurements for all time periods are completed, the analysis processing unit 45 reads out the MRM measurement data obtained for each compound. Then, the presence or absence of the compound is determined from the ion intensity in the MRM measurement. In addition, the compound is quantified as necessary. The compound can be quantified by storing information on a calibration curve for the target compound in advance and comparing the ion intensity in the MRM measurement with the calibration curve.

[0056] The analysis processing unit 45 reads out data of the electron beam diffraction image acquired in time zone 4. Also, by referring to the compound database 411, the analysis processing unit 45 reads out data of the electron beam diffraction images of compounds C and D, which are the measurement targets in time zone 4. At this time, if the data of the electron beam diffraction image of either compound C or D is not recorded in the compound database 411, the electron beam diffraction image estimation unit 46 theoretically estimates the electron beam diffraction image based on the molecular structure information of the compound (for example, estimating the molecular structure by first-principles calculation and theoretically determining the electron beam diffraction image from the contribution of each atom) to create the data of the electron beam diffraction image.

[0057] Next, the analysis processing unit 45 converts the measurement data of the electron beam diffraction image obtained by the measurement into the compound C and D. Then, based on the degree of agreement between the two, the presence or absence of compounds C and D (only compound C, only compound D, or both compounds C and D) is determined.

[0058] As an example, the electron diffraction pattern of carbon tetrachloride (CCl4) will be described with reference to FIG. 14. In carbon tetrachloride, a carbon atom (C) and four chlorine atoms (Cl) are bonded with an interatomic distance r. When an electron beam is irradiated onto this, the electrons are scattered in various directions, but at a certain direction θ, the waves (de Broglie waves) of electrons scattered from C and from Cl reinforce each other. On the other hand, at an angle θ', they cancel each other out. Since the orientation of the molecules is random, concentric stripes are formed on the detection surface due to interference. The radius of these concentric circles is related to the distance r, and the distance r can be obtained by comparing the theoretical interference stripes and the observed interference stripes when the distance r is changed as a parameter. In the case of carbon tetrachloride (CCl4), two peaks corresponding to the C-Cl equilibrium distance and the Cl-Cl equilibrium distance are obtained on the radial distribution function.

[0059] However, the number of atoms in compounds measured by liquid chromatography-mass spectrometry is generally greater than that of carbon tetrachloride. In the electron diffraction patterns of such compounds, the peaks corresponding to interatomic distances overlap each other. Therefore, it is difficult to determine the interatomic distances of each bond in a molecule from the electron diffraction pattern alone.

[0060] In contrast, in this embodiment, since the mass-to-charge ratio of the ions can be known by performing mass spectrometry in advance, the functional group contained in the molecular structure of the compound can be assumed based on the mass-to-charge ratio, and whether or not the functional group is contained can be estimated based on the presence or absence of interference fringes specific to the functional group. In addition, for structural isomers, it can be estimated which of multiple structural isomers the measured compound is from the difference in interference fringes that appear due to the positional relationship between the functional group and the different positions of the molecular structures of the structural isomers.

[0061] Recently, the accuracy of molecular structures (the positions of each atom in a molecule) calculated by first-principles calculations has improved, and it is now possible to estimate with high accuracy the interference fringes that appear in electron diffraction patterns from those molecular structures. By comparing electron diffraction patterns obtained by simulations based on these theoretical calculations with those obtained by actual measurements, it is possible to identify structural isomers and determine the proportions of their mixtures.

[0062] In the mass spectrometer 1 of this embodiment, various measurements can be performed in addition to the above-mentioned example. In the above example, MRM measurement and electron diffraction measurement are combined, but product ion scan measurement and electron diffraction measurement can also be combined. For example, it is conceivable to first perform a product ion scan measurement on a compound to be measured to measure a product ion spectrum, and then perform electron diffraction measurement to analyze the structure of ions corresponding to peaks that appear on the spectrum.

[0063] In the above example, precursor ions having a predetermined mass-to-charge ratio generated from the sample are dissociated in the collision cell 232 to generate product ions, which are then measured (mass spectrometry and electron diffraction measurements). However, it is also possible to measure (mass spectrometry and electron diffraction measurements) ions that are generated from the sample and are mass-separated in the front quadrupole mass filter 231 or rear quadrupole mass filter 233 without dissociating ions in the collision cell 232.

[0064] In the above example, the case of performing electron beam diffraction on compounds C and D, which are not separated (have the same retention time) in a liquid chromatograph column, has been described. However, even in the case of isomers that can be separated in a column, the liquid chromatograph column only separates the compounds, and cannot obtain information on the molecular structure of the compounds. Therefore, by performing electron beam diffraction measurement as in the above example and also obtaining information on the molecular structure of the compounds, it is possible to analyze each compound separated by liquid chromatograph with higher accuracy. In addition, in the above example, the mass spectrometer 1 of this embodiment can be combined with not only a liquid chromatograph (LC) but also a gas chromatograph (GC) (FIG. 15).

[0065] Furthermore, it is also possible to combine the mass spectrometer 1 of this embodiment with an ion mobility spectrometer (IMS) (FIG. 16), or to perform measurements using an apparatus configured by combining, from the upstream side, a chromatograph (liquid chromatograph or gas chromatograph), an ion mobility spectrometer, and the mass spectrometer 1 of this embodiment (FIG. 17).

[0066] In an ion mobility analyzer, ions are separated according to the size of the collision cross section of the ions, and it is said that it is possible to distinguish isomers. However, the theoretical value of the size of the collision cross section of the ions often does not match the actual value. In addition, the measured value of the collision cross section of the ions also varies depending on the configuration of the device (for example, by manufacturer) and the type of gas with which the ions are collided. Therefore, even if the size of the collision cross section of the ions obtained by measurement is compared with the value recorded in the database, it may not be possible to identify the molecular structure. In other words, as with a chromatograph device, even if a compound can be separated, information on the molecular structure of the compound cannot be obtained. As shown in Figures 16 and 17, by combining an ion mobility analyzer with the mass spectrometer 1 of this embodiment, not only the size of the collision cross section of the ions but also molecular structure information can be obtained by electron beam diffraction measurement, and the compounds contained in the sample can be analyzed with higher accuracy. In addition, when an ion mobility analyzer is combined, the ionization section of the mass spectrometer 1 and other components (in the figure, the electron beam irradiation section and the like are described as the mass analysis section) are separated, and the ion mobility analysis section is placed between them.

[0067] As described above, concentric stripes appear in an electron diffraction image due to the interference of electron waves (de Broglie waves), and different electron diffraction images can be obtained from the same molecule by changing the wavelength. When the wavelength of the electron beam used in the electron diffraction measurement is changed, the interatomic distance that reinforces the electron beam of that wavelength changes, and thus differences occur in the observed interference stripes. In this method for determining the degree of agreement of the overall pattern of interference stripes, the energy of the incident electrons is an important parameter. Therefore, in the mass spectrometer 1 of this embodiment, when it is not possible to identify with sufficient accuracy which of the structural isomers a component contained in a sample is, for example, only by the measurement in the above example, the user can perform electron diffraction measurement by irradiating electron beams with different energies. The user sets the measurement conditions for the electron diffraction measurement through the measurement condition setting unit 43 to irradiate electron beams with different energies, and obtains multiple electron diffraction images by performing measurements using electron beams with multiple different wavelengths (multiple different energies) during measurement by the measurement control unit 44. After the measurement is completed, the second molecular structure estimation unit 472 analyzes the difference in the interference fringes appearing in the multiple electron beam diffraction images to estimate the molecular structure.

[0068] In addition, the electron beam is scattered by both the atomic nuclei and the electrons, and the number of both the atomic nuclei and the electrons is greater in atoms with larger atomic numbers. In other words, the scattering intensity is greater for atoms with larger atomic numbers. Therefore, in the mass spectrometer 1 of this embodiment, a sample can be prepared in which an atom with a large atomic number (or a functional group containing an atom with a large atomic number) is added or substituted in advance at or near a position where the molecular structure differs between structural isomers, and electron diffraction measurement can be performed using the sample. In this case, after the measurement is completed, the third molecular structure estimation unit 473 extracts interference fringes corresponding to the added atom or functional group from the electron diffraction image to estimate the molecular structure.

[0069] The above embodiment is merely an example and can be modified appropriately in accordance with the spirit of the present invention. In the above embodiment, the ESI probe 201 is used as the ionization unit, but an ionization unit such as an atmospheric pressure chemical ionization device can be used. Also, when measuring a gas sample, an electron ionization device or a chemical ionization device can be used.

[0070] In the above embodiment, a triple quadrupole type mass analyzer was used, but other mass analyzers such as a quadrupole time-of-flight type may be used. In addition, when an ionization unit that generates fragment ions during ionization, such as an electron ionization device, is used, a mass analyzer having only one mass separation unit (e.g., having only one quadrupole mass filter) may be used.

[0071] Although the above embodiment is configured with the deflection unit 236, it may be configured without using the deflection unit 236. For example, it may be configured as shown in the block diagram of FIG. 18. In this configuration, when performing mass analysis (solid line), no voltage is applied to the ion trap, and ions that have been mass-separated in the mass analysis unit are passed through the ion trap and detected by the ion detector. When performing electron beam diffraction measurement (dashed line), a voltage is applied to the ion trap to accumulate ions, an electron beam is irradiated from the electron beam irradiation unit, and the resulting diffraction image is obtained by the electron beam detection unit.

[0072] Furthermore, the mass spectrometer 1 of the above embodiment is also equipped with a configuration for performing electron beam diffraction to obtain information on molecular structure, but based on a similar concept, it is also possible to configure a mass spectrometer that is also equipped with a configuration for performing rotational spectrum measurement or X-ray diffraction measurement.

[0073] Although NMR is sometimes used to estimate molecular structures, the sensitivity of NMR is significantly lower than that of mass spectrometry, by more than two orders of magnitude, so when measuring the same sample, a separate sample must be prepared in which the components to be measured are concentrated in a more concentrated form than the sample used for mass spectrometry. Some samples are difficult to synthesize or prepare, and furthermore, the product ions described above cannot be measured. In addition, the measurement itself must be performed separately from mass spectrometry. In contrast, the mass spectrometer of the above embodiment can perform both mass spectrometry and electron beam diffraction measurement at the same time and with high sensitivity in a series of measurements.

[0074] In the above-mentioned embodiment and modified example, electron diffraction measurement was performed together with mass analysis, but various secondary measurements other than electron diffraction measurement can be performed. In the present invention, after mass separation, only ions having a specific mass-to-charge ratio (or a mass-to-charge ratio within a specific range) are captured in an ion trap as ions to be measured, and various physical quantities related to the ions to be measured can be measured (physical property information can be obtained).

[0075] FIG. 19 shows a measurement method (including the electron beam diffraction measurement in the above embodiment) in which an electromagnetic wave (light beam, etc.) or a particle beam is incident on an ion trap, and the electromagnetic wave (light, etc.) or particle emitted from the ion trap is detected after interacting with the ion trapped in the ion trap (trapped ion) as an example of a secondary measurement that can be performed in the mass spectrometer according to the present invention. In this case, when an electromagnetic wave is incident, the interaction may be, for example, absorption or scattering of the electromagnetic wave by the trapped ion. Ions that have absorbed an electromagnetic wave and transitioned to an excited state return to the ground state by emitting an electromagnetic wave having a wavelength different from that of the incident electromagnetic wave or emitting a particle beam. In addition, the electromagnetic wave may not be absorbed by the ion and may undergo elastic or inelastic scattering (including diffraction). In addition, when a particle beam is incident, scattering may be an example of an interaction with the trapped ion. Ions that have obtained energy from the incident particle and transitioned to an excited state return to the ground state by emitting an electromagnetic wave or a particle beam. In addition, the incident particle may undergo elastic or inelastic scattering (including diffraction). Other examples of secondary measurements include a measurement method in which an electromagnetic wave (e.g., a light beam) or a particle beam is incident on an ion trap and the electromagnetic wave (e.g., a light beam) or particle emitted from the ion trap is detected without interacting with the trapped ions. In absorbance measurements, electromagnetic waves that have passed through the ion trap without interacting with the trapped ions are detected. Secondary measurements may also include a method in which the type of ion trapped is changed and the measurement results are compared.

[0076] An example of the configuration of an apparatus that can be commonly used for these is shown in Figures 20 and 21. Figure 20 shows a configuration with a deflection unit as in the above embodiment, and Figure 21 shows a configuration without a deflection unit as in the above modified example. In Figures 20 and 21, solid lines indicate components for performing mass analysis, and dashed lines indicate components for performing secondary measurements.

[0077] For example, information on the molecular structure of the ion can be obtained by performing electron beam diffraction measurement by irradiating the trapped ion with an electron beam and measuring the electron beam diffracted by the ion. Information on the electronic state of the ion can be obtained by performing electron energy loss spectroscopy by irradiating the trapped ion with an electron beam to excite it and measuring the electrons scattered by the ion. Furthermore, electronic structure analysis and elemental analysis of the ion can be performed by using the device as an electron microprobe analyzer (EPMA) in which the trapped ion is irradiated with an electron beam to excite it and the light emitted from the ion is measured. Furthermore, elemental analysis can be performed by performing ion scattering spectroscopy by irradiating the trapped ion with a beam of ions other than the ion to excite it and detecting the ions scattered by the ion. Furthermore, particle analysis can be performed by irradiating the trapped ion with an ion beam to excite it and detecting the light emitted from the ion. Induction Elemental analysis can be performed by performing fluorescence spectroscopy. Elemental analysis can be performed by performing atomic absorption spectroscopy by irradiating the trapped ions with a light beam to excite them and detecting the light emitted from the ions. Information on the shape and molecular structure of the ions can be obtained by performing laser diffraction measurement or X-ray diffraction measurement by irradiating the trapped ions with a light beam and detecting the light diffracted by the ions. Information on the shape and molecular structure of the ions can also be obtained by performing X-ray absorption edge measurement or Fourier transform measurement, in which the trapped ions are irradiated with light and the amount of light absorbed by the ions is measured by detecting the light transmitted through the ions. conversion Information on the intramolecular bonds of ions can be obtained by infrared spectroscopy. Information on the intramolecular bonds of ions can also be obtained by irradiating the trapped ions with light and detecting the light scattered by the ions, thereby performing Raman spectroscopy. Information on the electronic state and bonding state of ions can also be obtained by irradiating the trapped ions with light and measuring the electrons released from the ions, thereby performing photoelectron spectroscopy.

[0078] [Aspects] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0079] (Section 1) A mass spectrometer according to one embodiment comprises: an ionization unit for generating ions from a sample; The ions generated in the ionization section are mass-produced. Depending on the charge ratio A mass separation unit for separating the particles; The mass separation section In minutes an ion detector for detecting the released ions; The mass separation section In minutes an ion trapping unit that traps the released ions; a sub-measurement unit for measuring a physical quantity of the ions trapped in the ion trapping unit other than the mass-to-charge ratio; Equipped with.

[0080] In the mass spectrometer of the first paragraph, mass analysis can be performed by mass-separating ions generated in the ionization section in the mass separation section and detecting them with an ion detector. In addition, after mass-separating ions generated in the ionization section in the mass separation section to select ions to be analyzed, the ions can be trapped in the ion trapping section and a physical quantity other than the mass-to-charge ratio can be measured (secondary measurement). The secondary measurement can be, for example, irradiating the ions trapped in the ion trapping section with an electromagnetic wave (light beam, etc.) or a particle beam, and detecting the electromagnetic wave (light, etc.) or particles emitted from the ion trapping section. Specifically, for example, after accumulating ions to be analyzed in the ion trapping section, an electron beam can be irradiated thereon for a predetermined time, and the electron beam diffracted by the ions in the ion trapping section can be detected to perform electron beam diffraction measurement. Although it is not possible to distinguish isomers having the same mass-to-charge ratio by mass analysis alone, the mass spectrometer of the first paragraph can obtain information on molecular structure and distinguish isomers by performing, for example, the above-mentioned electron beam diffraction measurement as a secondary measurement. In addition, in the mass spectrometer of paragraph 1, by appropriately changing the flight path of the ions, it is possible to perform, in a single measurement, both mass analysis, in which the ions generated in the ionization section are mass-separated and detected, and a secondary measurement, in which the ions after mass separation are captured and a physical quantity of the ions other than the mass-to-charge ratio is measured.

[0081] When an excessive amount of ions are trapped in an ion trap (typically a three-dimensional ion trap), mass separation is performed in the ion trap. The ions are separated by their own charges (space charges). Capture unit The internal electric field is distorted, making it impossible to perform normal mass separation. In addition, in the conventionally proposed devices, ions generated from the sample are introduced into the ion trapping section, and the ions to be analyzed are selected within the ion trapping section, so there is a limit to the amount of ions that can be captured in the ion trapping section. Even if the maximum amount of ions is captured at the beginning, the amount of ions to be analyzed contained therein is less than the maximum amount. In contrast, in the mass spectrometer of paragraph 1, the ions to be analyzed are selected by a mass separation section outside the ion trapping section, and only the ions to be analyzed are introduced into the ion trapping section, so that the maximum amount of ions to be analyzed can be captured and used for electron diffraction measurement, and a high-intensity diffraction image can be obtained more efficiently than in the past.

[0082] (Section 2) 2. The mass spectrometer according to claim 1, The mass separation unit is a mass pre-separation section for selecting ions having a specific mass-to-charge ratio as precursor ions from the ions generated in the ionization section; a dissociation unit that dissociates the precursor ions to generate product ions; a post-stage mass separator for selecting ions having a specific mass-to-charge ratio from among the product ions; Equipped with.

[0083] In the mass spectrometer described in paragraph 2, by selecting precursor ions and product ions in the front-stage mass separation section and rear-stage mass separation section, respectively, it is possible to perform mass analysis using ions characteristic of the compound to be measured, or to select product ions having local partial structures including positions of different molecular structures of structural isomers and perform electron beam diffraction measurements.

[0084] (Section 3) The mass spectrometer according to claim 1 or 2, further comprising: a deflection section that is provided between the mass separation section and the ion detector and that deflects the flight direction of the ions emitted from the mass separation section; Equipped with The ion trapping section is provided on a flight path of the ions whose flight direction has been deflected by the deflection section.

[0085] In the mass spectrometer described in paragraph 3, ions separated in the mass separation section are deflected and introduced into the ion trapping section, so that the ions are separated from the neutral molecules and only the ions to be analyzed are introduced into the ion trapping section, thereby reducing the background of the electron diffraction image caused by scattering of electrons by neutral molecules. In addition, in the mass spectrometer described in paragraph 3, ions having a predetermined mass-to-charge ratio generated from a sample are trapped in the ion trapping section, and an electron beam is irradiated thereon to perform electron diffraction measurement, while at the same time performing mass analysis of ions newly generated in the ionization section.

[0086] (Section 4) The mass spectrometer according to any one of claims 1 to 3, further comprising: A voltage application unit that applies a square wave voltage to the ion trapping unit to trap ions. Equipped with.

[0087] In the mass spectrometer described in paragraph 4, the mass-to-charge ratio (range) of the ions trapped in the ion trapping section can be changed by changing the frequency while keeping the amplitude of the square wave voltage constant, so a large power supply is not required. In addition, there is no need to worry about discharge caused by application of a high voltage or deflection of the flight path of the electron beam.

[0088] (Section 5) 5. The mass spectrometer according to claim 1, wherein the sub-measurement unit: an irradiation unit that irradiates the ions trapped in the ion trapping unit with an electromagnetic wave or a particle beam; a detection unit for detecting electromagnetic waves or particles emitted from the ion capture unit; Equipped with.

[0089] The mass spectrometer of paragraph 5 can perform various measurements as described below. For example, an electron beam diffraction measurement can be performed by irradiating an ion trapped in an ion trapping section (trapped ion) with an electron beam and measuring the electron beam diffracted by the ion, thereby obtaining information on the molecular structure of the ion. Also, an electron beam can be irradiated with an electron beam to excite the trapped ion, and electrons scattered by the ion can be measured to perform electron energy loss spectroscopy, thereby obtaining information on the electronic state of the ion. Also, an electron beam can be irradiated with an electron beam to excite the trapped ion, and the device can be used as an electron microprobe analyzer (EPMA) that measures the light emitted from the ion, thereby performing electronic structure analysis and elemental analysis of the ion. Furthermore, an ion beam can be irradiated with an ion beam to excite the trapped ion, and ions scattered by the ion can be detected to perform ion scattering spectroscopy and elemental analysis. Alternatively, an ion beam can be irradiated with an ion beam to excite the trapped ion, and the light emitted from the ion can be detected to obtain particle size distribution. Induction Elemental analysis can be performed by performing fluorescence spectroscopy. Elemental analysis can be performed by performing atomic absorption spectroscopy by irradiating the trapped ions with a light beam to excite them and detecting the light emitted from the ions. Information on the shape and molecular structure of the ions can be obtained by performing laser diffraction measurement or X-ray diffraction measurement by irradiating the trapped ions with a light beam and detecting the light diffracted by the ions. Information on the shape and molecular structure of the ions can also be obtained by performing X-ray absorption edge measurement or Fourier transform measurement, in which the trapped ions are irradiated with light and the amount of light absorbed by the ions is measured by detecting the light transmitted through the ions. conversion Information on the intramolecular bonds of ions can be obtained by infrared spectroscopy. Information on the intramolecular bonds of ions can also be obtained by irradiating the trapped ions with light and detecting the light scattered by the ions, thereby performing Raman spectroscopy. Information on the electronic state and bonding state of ions can also be obtained by irradiating the trapped ions with light and measuring the electrons released from the ions, thereby performing photoelectron spectroscopy.

[0090] (Section 6) 4. The mass spectrometer according to claim 1, moreover, A voltage application unit that applies a square wave voltage to the ion trapping unit to trap ions. Equipped with The sub-measurement unit, an irradiation unit that irradiates the ions trapped in the ion trapping unit with an electromagnetic wave or a particle beam; a detection unit for detecting electromagnetic waves or particles emitted from the ion capture unit; Equipped with When a rectangular wave voltage of a predetermined phase is applied from the voltage application unit to the ion-trapping unit, the irradiation unit irradiates the inside of the ion-trapping unit with a pulsed electromagnetic wave or particles.

[0091] In the mass spectrometer described in paragraph 5, by performing simulations and preliminary experiments in advance, the phase of the square wave voltage that causes ions to spread on the irradiation path of the electromagnetic wave or particle beam in the ion trapping unit is determined as the above-mentioned predetermined phase, so that more ions can be irradiated with the electromagnetic wave or particle beam and a high signal intensity can be obtained. In a mass spectrometer configured to apply a high frequency sine voltage to a ring electrode to trap ions inside an ion trap as in the past, a phase difference occurs between the voltage that drives the resonant circuit and the output voltage of the resonant circuit that is actually applied to the electrode. This depends on the load impedance of the electrode and varies depending on the electrode shape and the method of holding it. Therefore, it is difficult to irradiate the electromagnetic wave or particle beam at the moment when the high frequency sine voltage reaches a specific phase. Even if the phase can be adjusted, the amplitude of the high frequency sine voltage needs to be changed according to the mass-to-charge ratio of the ions to be measured, and the voltage setting value of the entrance optical system for the electromagnetic wave or particle beam needs to be changed accordingly. In contrast, in the mass spectrometer described in paragraph 5, the drive voltage is applied directly to the electrodes without going through a resonant circuit, so that the electromagnetic waves or particle beams can be controlled to be irradiated in accordance with the optimal phase. Furthermore, even if the mass-to-charge ratio of the ions to be measured changes, only the frequency of the square wave voltage changes, and the amplitude remains constant, so there is no need to change the voltage setting value of the incidence optical system for the electromagnetic waves or particle beams.

[0092] (Section 7) 7. The mass spectrometer according to claim 5 or 6, the irradiation unit is an electron beam irradiation unit that irradiates the ion trapping unit with an electron beam, The detection unit detects the electron beam diffracted by the ions.

[0093] In the mass spectrometer described in item 7, information on the molecular structure of an ion can be obtained by performing electron diffraction measurement on the ion of a specific mass-to-charge ratio (or mass-to-charge ratio range) trapped in the ion trapping section.

[0094] (Section 8) 8. The mass spectrometer according to claim 7, further comprising: a molecular structure candidate input receiving unit that receives input of information on the molecular structure candidate; a first molecular structure estimation unit that estimates a molecular structure of a molecule contained in the sample by comparing an electron beam diffraction image obtained by measuring the sample with an electron beam diffraction image previously prepared for the molecular structure candidate; Equipped with.

[0095] In the mass spectrometer described in paragraph 8, by using a previously prepared electron beam diffraction image (for example, an electron beam diffraction image obtained by electron beam diffraction of a standard sample or an electron beam diffraction image estimated based on theoretical calculation as described in the next paragraph), the electron beam diffraction image obtained by measurement can be more easily analyzed. 7 In the mass spectrometer described in the paragraph, data of concentric interference fringes is obtained as a diffraction image, unlike the diffraction peaks obtained in general electron diffraction measurements. Such data can be processed as a type of image data. Therefore, as the first molecular structure estimation unit, for example, a classifier created by machine learning the overall pattern of diffraction images obtained by electron diffraction measurements and / or theoretical calculations of various compounds can be used.

[0096] (Section 9) 9. The mass spectrometer according to claim 8, further comprising: The molecular structure candidate an electron beam diffraction image estimation unit that estimates an electron beam diffraction image by theoretical calculation based on the molecular structure received by the input reception unit; Equipped with.

[0097] The mass spectrometer described in paragraph 9 can estimate an electron beam diffraction pattern even for a compound that is not recorded in the compound database.

[0098] (Section 10) 10. The mass spectrometer according to any one of claims 7 to 9, The energy of the electron beam irradiated by the electron beam irradiating unit is variable.

[0099] (Section 11) 11. The mass spectrometer according to claim 10, further comprising: A second molecular structure estimation section that estimates the structure of a sample molecule based on electron diffraction images obtained by irradiating the sample with electron beams of different energies. Equipped with.

[0100] In the mass spectrometer described in items 10 and 11, by performing electron diffraction measurements using electron beams of different energies, different electron diffraction images can be obtained for the same molecule and can be used for analyzing the molecular structure.

[0101] (Section 12) 12. The mass spectrometer according to any one of claims 7 to 11, further comprising: a third molecular structure estimation unit that estimates the molecular structure of the sample molecule based on an electron beam diffraction image obtained by measuring a compound in which a predetermined type of atom is bonded to a specific position of the sample molecule; Equipped with.

[0102] In the mass spectrometer described in paragraph 12, an atom having a large atomic number and scattering more electrons is set as the above-mentioned predetermined type of atom at a position of interest in a molecule (for example, a position where the structure differs between isomers or in the vicinity thereof), thereby increasing the scattering of the electron beam by the atom, and making it possible to obtain high-intensity interference fringes that reflect the structure of interest.

[0103] (Section 13) 13. The mass spectrometer according to any one of claims 1 to 12, further comprising: A separation means for separating compounds contained in a sample before the ions are mass-separated in the mass separation section. Equipped with.

[0104] (Section 14) 14. The mass spectrometer according to claim 13, The separation means is a chromatographic device and / or an ion mobility spectrometer.

[0105] In the mass spectrometer described in paragraph 13, compounds contained in a sample are separated from each other and introduced into the ion source, so that only the compounds to be measured are selected, and the influence of other compounds is eliminated, so that mass analysis and electron beam diffraction measurement can be performed with higher accuracy. As such a separation means, as described in paragraph 14, a chromatograph (for example, a liquid chromatograph or a gas chromatograph) or an ion mobility analyzer can be used. When the separation means is a chromatograph, the compounds contained in the sample are separated, and then each compound is introduced into the ionization section for ionization. In this case, the separation means is disposed in the upstream of the mass spectrometer. On the other hand, when the separation means is an ion mobility analyzer, the compounds contained in the sample are ionized in the ionization section, and then ions derived from each compound are separated in the ion mobility analyzer and introduced into the mass separation section. In this case, the separation means is disposed between the ionization section and the mass separation section of the mass spectrometer. In this way, the separation of the compounds includes a configuration for separating ions derived from each compound.

[0106] Depending on the type of isomer, it may be possible to separate them using a chromatographic column. However, as it is not possible to obtain information about the molecular structure of the compound through chromatographic separation alone, it is necessary to also perform electron diffraction measurements to obtain information about the compound's molecular structure, thereby enabling the compounds contained in the sample to be analyzed with greater precision.

[0107] In addition, although it is said that it is possible to distinguish isomers using ion mobility spectrometers, the theoretical and actual values ​​of the collision cross section of ions often do not match, and MeasurementsThe cross section of the ions measured varies depending on the configuration of the device (e.g., by manufacturer) and the type of gas with which the ions collide. Therefore, it is difficult to compare the size of the collision cross section of the ions obtained by measurement with the values ​​recorded in the database, and it may not be possible to identify the molecular structure. invention By combining this with a mass spectrometer, it is possible to obtain not only the size of the ion collision cross section but also molecular structure information through electron diffraction measurement, enabling the analysis of the compounds contained in the sample with greater precision. [Explanation of symbols]

[0108] 1...Mass spectrometer 10...Device body 20…Ionization chamber 21…First intermediate vacuum chamber 22…Second intermediate vacuum chamber 23…Analysis room 231...Pre-quadrupole mass filter 232…Collision cell 234...Quadrupole rod electrode 235...Post-quadrupole mass filter 236...Deflection section 2361...Rod electrode 237…Ion detector 30...Electron beam irradiation unit 301...Electron gun 302...Electron lens 31...Ion trap 311...Ring electrode 312: Inlet end cap electrode 313: Exit end cap electrode 316...Vacuum chamber 317…Gas inlet 32...Electron beam detector 321…Faraday cup 322...Microchannel plate 3 23...Fluorescent screen 324…CCD camera 4. Control and processing section 41...Storage section 411...Compound database 42…Mass spectrometry program 43...Measurement condition setting section 44...Measurement control section 45...Analysis processing section 46…Electron beam diffraction image estimation section 47…Molecular structure estimation department 471...1st molecular structure estimation section 472…Second molecular structure estimation section 473...Third molecular structure estimation section 5…Voltage application section 6. Input section 7…Display section

Claims

1. an ionization unit for generating ions from a sample; a mass separation unit that separates the ions generated in the ionization unit according to their mass-to-charge ratio; an ion detector that detects ions separated by the mass separation unit; an ion trapping unit that traps the ions separated by the mass separation unit; a sub-measurement unit for measuring a physical quantity of the ions trapped in the ion trapping unit other than the mass-to-charge ratio; Equipped with The mass separation unit is a mass pre-separation section for selecting ions having a specific mass-to-charge ratio as precursor ions from the ions generated in the ionization section; a dissociation unit that dissociates the precursor ions to generate product ions; a post-stage mass separator for selecting ions having a specific mass-to-charge ratio from among the product ions; A mass spectrometer comprising:

2. moreover, a deflection section that is provided between the mass separation section and the ion detector and that deflects the flight direction of the ions emitted from the mass separation section; Equipped with 2. The mass spectrometer according to claim 1, wherein the ion trapping section is provided on a flight path of ions whose flight direction has been deflected by the deflection section.

3. moreover, A voltage application unit that applies a square wave voltage to the ion trapping unit to trap ions. The mass spectrometer according to claim 1 or 2, comprising:

4. The sub-measurement unit, an irradiation unit that irradiates the ions trapped in the ion trapping unit with an electromagnetic wave or a particle beam; a detection unit for detecting electromagnetic waves or particles emitted from the ion capture unit; The mass spectrometer according to claim 1 , comprising:

5. An ionization unit for generating ions from a sample; a mass separation unit that separates the ions generated in the ionization unit according to their mass-to-charge ratio; an ion detector that detects ions separated by the mass separation unit; an ion trapping unit that traps the ions separated by the mass separation unit; a sub-measurement unit for measuring a physical quantity of the ions trapped in the ion trapping unit other than the mass-to-charge ratio; a voltage application unit that applies a square wave voltage to the ion trapping unit to trap ions; Equipped with The sub-measurement unit, an irradiation unit that irradiates the ions trapped in the ion trapping unit with an electromagnetic wave or a particle beam; a detection unit for detecting electromagnetic waves or particles emitted from the ion capture unit; Equipped with A mass spectrometer, wherein when a rectangular wave voltage of a predetermined phase is applied from the voltage application unit to the ion trapping unit, the irradiation unit irradiates an inside of the ion trapping unit with a pulsed electromagnetic wave or particle beam.

6. the irradiation unit is an electron beam irradiation unit that irradiates the ion trapping unit with an electron beam, 6. The mass spectrometer according to claim 4, wherein the detection section detects an electron beam diffracted by the ions.

7. moreover, a molecular structure candidate input receiving unit that receives input of information on the molecular structure candidate; a first molecular structure estimation unit that estimates a molecular structure of a molecule contained in the sample by comparing an electron beam diffraction image obtained by measuring the sample with an electron beam diffraction image previously prepared for the molecular structure candidate; The mass spectrometer of claim 6 , comprising:

8. moreover, an electron beam diffraction image estimation unit that estimates an electron beam diffraction image by theoretical calculation based on the molecular structure accepted by the molecular structure candidate input acceptance unit; The mass spectrometer of claim 7 , comprising:

9. 9. The mass spectrometer according to claim 6, wherein the energy of the electron beam irradiated by the electron beam irradiating unit is variable.

10. moreover, A second molecular structure estimation unit that estimates the structure of a sample molecule based on electron beam diffraction images obtained by irradiating the sample with electron beams of different energies. The mass spectrometer of claim 9 , comprising:

11. moreover, a third molecular structure estimation unit that estimates the molecular structure of the sample molecule based on an electron beam diffraction image obtained by measuring a compound in which a predetermined type of atom is bonded to a specific position of the sample molecule; A mass spectrometer according to any one of claims 6 to 10, comprising:

12. moreover, A separation means for separating compounds contained in a sample before the ions are mass-separated in the mass separation section. A mass spectrometer according to claim 1 , comprising:

13. 13. A mass spectrometer as claimed in claim 12, wherein the separation means is a chromatographic device and / or an ion mobility spectrometer.

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