mass spectrometer

Abstract

Provided is an apparatus capable of performing both mass analysis and electron beam diffraction measurement for identifying isomers by a single measurement. Further, provided is a technique capable of performing electron beam diffraction measurement more efficiently than ever before in such an apparatus. A mass analysis apparatus (1) includes: an ionization section (201) that generates ions from a sample; a mass separation section (231, 235) that mass separates the ions generated by the ionization section; an ion detector (237) that detects the ions mass separated by the mass separation section; an ion trapping section (31) that traps the ions mass separated by the mass separation section; and an electron beam detection section (32) that detects an electron beam diffracted by the ions trapped by the ion trapping section.

Description

TECHNICAL FIELD

[0001] The present application relates to a mass spectrometer. BACKGROUND

[0002] A mass spectrometer is widely used for identification and quantification of components contained in a sample. In a mass spectrometer, ions generated from components of a sample are mass-separated, and the intensity of ions of each mass-to-charge ratio is measured. Then, a mass spectrum in which the mass-to-charge ratio and the intensity of ions are axes is generated, and the components are identified based on the degree of coincidence with a mass spectrum of a known substance or the like. Furthermore, the components are quantified based on the intensity of a mass spectral peak on the mass spectrum.

[0003] In a case where the components of a sample are relatively large molecules, it is difficult to identify the components from the ions generated from the components of the sample as they are. Therefore, MS / MS analysis is performed, which is an analysis in which ions having a specific mass-to-charge ratio are selected as precursor ions from ions generated from components of a sample, product ions generated by cleavage of the precursor ions are mass-separated, and the intensity of ions of each mass-to-charge ratio is measured. In MS / MS analysis, the components of a sample are identified by deducing the partial structure of the components of the sample from the mass-to-charge ratios of various product ions.

[0004] Since mass spectrometry separates ions according to the mass-to-charge ratio, it is not possible to separate ions having the same mass-to-charge ratio. For example, butane and isobutane are structural isomers in which the bonding position of a methyl group is different, but the mass of both is the same, and therefore it is not possible to separate their ions. Furthermore, in the case of structural isomers, even if product ions are generated by cleavage of a precursor ion, since only product ions of the same kind are generated in many cases, it is difficult to distinguish between the two.

[0005] Therefore, in the past, other measurement methods have been used in order to obtain information on the geometry (interatomic distance or bond angle) of molecules that cannot be obtained by mass spectrometry. In such measurement methods, for example, there are rotational spectroscopy measurement, electron beam diffraction measurement, and X-ray diffraction measurement. In rotational spectroscopy measurement, a microwave is irradiated to a sample gas to measure absorbance (absorption measurement), or light emitted from a sample gas is spectrometrically measured, but compared to diffraction methods such as electron beam diffraction measurement or X-ray diffraction measurement, the sensitivity is poor. Furthermore, the elastic scattering cross section of X-ray diffraction measurement is small, and is only about 10 -5 ~ 10 -4 times the elastic scattering cross section of electron beam diffraction (for example, Non-Patent Literature 1), and in measurement of a sample gas, the sensitivity is poor compared to electron beam diffraction. From these viewpoints, in the past, there have been proposals for obtaining the geometry of molecules by electron beam diffraction measurement described in Non-Patent Literatures 2 to 5.

[0006] Electron beam diffraction devices are described in non-patent documents 2 and 3. In these devices, neutral gas molecules are introduced into an ion trap and irradiated with a laser for ionization (photoionization). After the generated multiple ions are captured in the ion trap, mass screening is performed in the ion trap to capture only the ions of the analysis target. The ions captured in the ion trap are then irradiated with an electron beam to obtain an electron beam diffraction image. By analyzing this electron beam diffraction image, information on the geometric structure of the molecule is obtained.

[0007] Non-Patent Document 4 describes a device that combines an apparatus for performing electron beam diffraction measurements with a mass spectrometer. This device includes a deflection unit downstream of the ionization unit that deflects the flight direction of ions. This deflection unit switches the deflection direction, thereby directing ions generated by the ionization unit into either an ion trap or a time-of-flight mass separation unit. In the ion trap, similar to the devices of Non-Patent Documents 2 and 3, a diffraction image is obtained by irradiation with an electron beam, providing information on the molecular structure of the ions. Meanwhile, in the time-of-flight mass separation unit, the status of ion generation in the ion source is monitored by obtaining a mass spectrum.

[0008] Prior art literature

[0009] Patent Literature

[0010] Non-patent document 1: Masaki Haneda, “Observation of Ultrahigh-Speed ​​Structural Dynamics Using Desktop Femtosecond Electron Beam Diffraction,” Journal of the Vacuum Society of Japan, Vol. 59 (2016), No. 2

[0011] Non-Patent Literature 2: Keiko Kato, Abstract of the Dissertation "Development of an Ion Trap Electron Diffraction Apparatus and Its Application in Molecular Ion Structure Determination and Reaction Tracking," 2006, Graduate School of Science, University of Tokyo, [Online], [Retrieved December 21, 2020], URL<URL:http: / / gakui.dl.itc.u-tokyo.ac.jp / cgi-bin / gazo.cgi?no=121041>

[0012] Non-Patent Document 3: Tanaka Hideaki et al., Abstracts of the 9th Analytical Science Symposium 2015 Tokyo Lecture, "Ion Trap Electron Diffraction Apparatus for Determining the Geometric Structure of Molecular Ions," [Online], [Retrieved December 21, 2020], URL<URL:http: / / molsci.center.ims.ac.jp / area / 2015 / PDF / pdf / 1P012_w.pdf>

[0013] Non-patent document 4: D. Schooss, MN Blom, JH Parks, BV Irsendorff, H. Haberland, MMKappes, The structure of Ag 55 + and Ag 55 - :Trapped ions electron diffractionand density functional theory(Ag 55 + and Ag 55 - Structure of trapped ions: electron diffraction and density functional theory), Nano Lett. 5 (2005) 1972.

[0014] Non-patent document 5: M. Marier-Brost, DB Cameron, M. Rokni, JH Parks, “Electron diffraction of trapped cluster ions”, Phys. Rev. A 59 (1999) R3162. Summary of the Invention

[0015] Technical problem to be solved by the invention

[0016] By combining a structure for performing electron beam diffraction measurement as described in non-patent documents 2-5 with a mass spectrometer, a single device can be used to obtain information on the geometric structure of the molecule (interatomic distances or bond angles) with a sensitivity higher than that of rotational spectroscopy or X-ray diffraction measurement, based on mass analysis, when identifying structural isomers that are difficult to identify by mass analysis, thereby identifying the sample components. However, in electron beam diffraction devices proposed in the past, in order to obtain a diffraction image with an intensity sufficient for analysis, it is necessary to continuously irradiate the electron beam for a long period of time, such as 5 to 6 hours. On the other hand, mass analysis can be performed in a short time of about a few minutes. Thus, in the previous structure, the time required for auxiliary electron beam diffraction measurement becomes much longer than the time required for mass analysis as the main measurement. Therefore, a technology that can perform electron beam diffraction measurement more efficiently is required.

[0017] Here, the case where measurements for obtaining information on the geometric structure of a molecule are performed in addition to mass analysis is described as an example. However, the same problem as described above also exists when various auxiliary measurements are performed in addition to mass analysis to obtain information that cannot be obtained by mass analysis.

[0018] The present application addresses the problem of providing an apparatus that can perform both mass analysis and a sub-measurement for obtaining information that cannot be obtained by mass analysis in one measurement. Furthermore, the present application addresses the problem of providing a technique that enables a sub-measurement to be performed more efficiently than ever before in such an apparatus.

[0019] Solution to the problem

[0020] A mass analysis apparatus of the present application, which has been completed in order to solve the above problem, is provided with:

[0021] an ionization section that generates ions from a sample;

[0022] a mass separation section that mass separates ions generated by the ionization section;

[0023] an ion detector that detects ions mass separated by the mass separation section;

[0024] an ion trapping section that traps ions mass separated by the mass separation section;

[0025] a sub-measurement section that measures a physical quantity other than a mass-to-charge ratio of ions trapped by the ion trapping section.

[0026] Effects of the Invention

[0027] In the mass analysis apparatus of the present application, mass analysis can be performed by mass separating ions generated by the ionization section by the mass separation section and detecting by the ion detector. Furthermore, it is also possible to measure (sub-measure) a physical quantity other than a mass-to-charge ratio by trapping ions mass separated by the ionization section by the mass separation section and selecting ions of interest after the mass separation and trapping by the ion trapping section. The sub-measurement can be, for example, irradiation of electromagnetic waves (light, etc.) or a particle beam to ions trapped by the ion trapping section and detection of electromagnetic waves (light, etc.) or particles emitted from the ion trapping section. Specifically, for example, electron beam diffraction measurement can be performed by accumulating ions of interest in the ion trapping section and irradiating them with an electron beam for a predetermined time and detecting an electron beam diffracted by the ions in the ion trapping section. Although it is not possible to identify isomers, etc. having the same mass-to-charge ratio by mass analysis alone, in the mass analysis apparatus of the present application, it is possible to identify isomers, etc. by performing electron beam diffraction measurement as described above as a sub-measurement to obtain information on molecular structure. Furthermore, in the mass analysis apparatus of the present application, it is possible to perform both mass analysis of mass separating and detecting ions generated by the ionization section and sub-measurement of trapping the mass-separated ions and measuring a physical quantity other than a mass-to-charge ratio of the ions in one measurement by appropriately changing a flight path of the ions.

[0028] If an ion capture unit (typically a three-dimensional ion trap) is used to capture an excess amount of ions and then perform mass separation in the ion capture unit, the electric field in the ion capture unit is distorted by the charge of the ions themselves (space charge), making it impossible to perform mass separation normally. Therefore, in a configuration in which mass separation is performed in the ion capture unit as in the past, there is a limit to the amount of ions that can be captured in the ion capture unit. In addition, using a conventional device, even if the ions generated from the sample are captured in maximum quantity, the amount of ions will decrease due to the subsequent mass separation. In contrast, in the mass analysis device of the present invention, the ions of the analysis object are screened by the mass separation unit and only the ions of the analysis object are introduced into the ion capture unit. Therefore, the maximum amount of ions of the analysis object can be captured and provided for secondary measurement, and high-intensity measurement data can be obtained in a shorter time and more efficiently than before.

[0029] Alternatively, the ion capture unit can be positioned between the mass separation unit and the ion detector, or a deflection unit can be provided between the mass separation unit and the ion detector to deflect the ion's flight direction, with the ion capture unit positioned along the flight path of the ions deflected by the deflection unit. In the former case, the ion capture unit can be inactivated, allowing the ions, after mass separation by the mass separation unit, to pass through untouched and be detected by the ion detector for mass analysis, or the ions, after mass separation by the mass separation unit, can be captured in the capture unit for secondary measurement. Furthermore, in the latter case, the ion flight path during mass analysis differs from the ion flight path during the secondary measurement, allowing both measurements to be performed in parallel. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a schematic diagram of the configuration of an embodiment of a mass spectrometer according to the present invention.

[0031] Figure 2 These are the measurement conditions for the target compound in the measurement example using the mass spectrometer of this embodiment.

[0032] Figure 3 3 is a diagram illustrating the content of measurement performed in this embodiment.

[0033] Figure 4 This is a diagram illustrating the rectangular voltage applied to the ion trap in this embodiment.

[0034] Figure 5 This is the ion trap used in the mass spectrometer of this embodiment.

[0035] Figure 6 These are simulation results regarding the diffusion of ions in the X-axis direction within the ion trap when the phase of the rectangular voltage applied to the ion trap is 0°.

[0036] Figure 7is a simulation result on diffusion in the X-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 270°.

[0037] Figure 8 is a simulation result on diffusion in the X-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 180°.

[0038] Figure 9 is a simulation result on diffusion in the X-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 270°.

[0039] Figure 10 is a simulation result on diffusion in the Z-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 0°.

[0040] Figure 11 is a simulation result on diffusion in the Z-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 90°.

[0041] Figure 12 is a simulation result on diffusion in the Z-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 180°.

[0042] Figure 13 is a simulation result on diffusion in the Z-axis direction of ions in an ion trap when the phase of a rectangular voltage applied to the ion trap is 270°.

[0043] Figure 14 is a diagram explaining electron beam diffraction measurement.

[0044] Figure 15 is a chromatograph mass spectrometer using the mass spectrometer of the present embodiment.

[0045] Figure 16 is an ion mobility analysis-mass spectrometer using the mass spectrometer of the present embodiment.

[0046] Figure 17 is a chromatograph-ion mobility analysis-mass spectrometer using the mass spectrometer of the present embodiment.

[0047] Figure 18 is a configuration example of each part in the mass spectrometer of the modified example.

[0048] Figure 19 is an example of a sub measurement that can be implemented in the mass spectrometer of the present embodiment.

[0049] Figure 20 is a schematic configuration example of the mass spectrometer that performs various sub measurements.

[0050] Figure 21 is another schematic configuration example of a quality analysis device that performs various sub-measurements. DETAILED DESCRIPTION

[0051] Hereinafter, an embodiment of a quality analysis device of the present application will be described with reference to the drawings.

[0052] Figure 1 is a schematic configuration diagram of a quality analysis device 1 of the present embodiment. The quality analysis device 1 of the present embodiment is configured of a device main body 10 and a control and processing section 4. An ionization chamber 20, a first intermediate vacuum chamber 21, a second intermediate vacuum chamber 22, and an analysis chamber 23 are provided in the device main body 10. Further, an electron beam irradiation section 30 is connected to the analysis chamber 23. Based on the control performed by the control and processing section 4, appropriate voltages are applied to each section in the device main body 10 from a voltage application section 5 in measurement execution.

[0053] The ionization chamber 20 is at substantially atmospheric pressure, the first intermediate vacuum chamber 21 is a low vacuum chamber that is vacuumed by a rotary pump (omitted from the drawing), and the second intermediate vacuum chamber 22 and the analysis chamber 23, the electron beam irradiation section 30 are high vacuum chambers that are vacuumed by a turbo molecular pump (omitted from the drawing). The vacuum degrees of the first intermediate vacuum chamber 21, the second intermediate vacuum chamber 22, and the analysis chamber 23 are configured as a multi-stage differential evacuation system in which the vacuum degree is made higher in stages in this order.

[0054] In the ionization chamber 20, an electrospray ionization probe (ESI probe) 201 that imparts an electric charge to a sample solution and performs spraying is provided. The ionization chamber 20 is communicated with the first intermediate vacuum chamber 21 through a heated capillary 202 of a small diameter. In the present embodiment, the ESI probe 201 is used as an ionization section, but an appropriate ionization section can be used according to the characteristics of the sample.

[0055] In the first intermediate vacuum chamber 21, an ion lens 211 is provided, which is configured of a plurality of ring-shaped electrodes and which converges ions while transporting them to the next stage. The first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 are separated by a skimmer 212 having a small hole in the top portion.

[0056] In the second intermediate vacuum chamber 22, a first ion guide 221 and a second ion guide 222 are provided, which are each configured of a plurality of rod electrodes and which converge ions while transporting them to the next stage. The second intermediate vacuum chamber 22 and the analysis chamber 23 are communicated through a small hole formed in a partition wall.

[0057] The analysis chamber 23 is provided with a front-stage quadrupole mass filter (Q1) 231, a collision cell 232, a rear-stage quadrupole mass filter (Q3) 235, a deflection unit 236, and an ion detector 237. The front-stage quadrupole mass filter 231 is composed of a front rod electrode 2311, a main rod electrode 2312, and a rear rod electrode 2313. A quadrupole rod electrode 234 is arranged inside the collision cell 232. In addition, a gas inlet for introducing collision-induced dissociation gas (CID gas) such as argon and nitrogen is provided in the collision cell 232. The rear-stage quadrupole mass filter 235 is composed of a front rod electrode 2351, a main rod electrode 2352, and a rear rod electrode 2353. Four rod electrodes 2361 are arranged in the deflection unit 236. In this embodiment, the flight direction of ions is deflected by the deflection unit 236 as described later. However, a member having an appropriate structure that can deflect the flight direction of ions can be used as the deflection unit.

[0058] In addition, an ion trap 31 and an electron beam detection unit 32 are arranged in the analysis chamber 23. The ion trap 31 is composed of a ring electrode 311, an entrance-side end cap electrode 312, and an exit-side end cap electrode 313 arranged to sandwich the ring electrode 311. An opening 314 for introducing ions and electron beams is provided in the entrance-side end cap electrode 312. In addition, an opening 315 for discharging ions and electron beams is provided in the exit-side end cap electrode 313. The ion trap 31 is arranged in a vacuum chamber 316. In addition to openings corresponding to the above-mentioned openings 314 and 315, a gas inlet 317 for introducing cooling gas into the ion trap 3 is provided on the wall surface of the vacuum chamber 316. In addition, the interior of the vacuum chamber 316 is exhausted to a high vacuum by a turbomolecular pump (not shown).

[0059] The electron beam detection unit 32 includes a Faraday cup 321, a microchannel plate 322, a fluorescent screen 323, and a CCD camera 324. The microchannel plate 322 is positioned outside the exit-side end cap electrode 313 within the ion trap 31. The Faraday cup 321 is positioned near the surface of the microchannel plate 322, on the electron beam irradiation axis C2. The fluorescent screen 323 is mounted on the back of the microchannel plate 322. The CCD camera 324 is positioned on the back side of the fluorescent screen 323, where it can capture images of the back side.

[0060] An electron gun 301 and an electron lens 302 are provided in the electron beam irradiation unit 30. In the electron beam irradiation unit 30, the incident energy of the electron beam irradiated to the ions can be changed when performing electron beam diffraction measurement.

[0061] The control and processing section 4 has, in addition to the storage section 41, a measurement condition setting section 43, a measurement control section 44, an analysis processing section 45, an electron beam diffraction image estimation section 46, and a molecular structure estimation section 47 as functional modules. The compound database 411 is stored in the storage section 41. Further, the molecular structure estimation section 47 includes a first molecular structure estimation section 471, a second molecular structure estimation section 472, and a third molecular structure estimation section 473. The entity of the control and processing section 4 is a general personal computer, and the processor of the personal computer functions as each of the above sections by executing a mass spectrometry program 42 installed in advance in the computer. Further, the input section 6 and the display section 7 are connected to the control and processing section 4.

[0062] The measurement conditions, analysis results, and the like related to a large number of known compounds are included in the compound database 411. As the measurement conditions, for example, the time (retention time) from the elution of the column of the liquid chromatograph, and the mass-to-charge ratio of a precursor ion and a product ion (MRM transition) that characterizes the compound are included. Further, as the information of the analysis results, for example, the MS / MS spectral data of each compound, and the data of the electron beam diffraction image are included. The data of the electron beam diffraction image can be obtained experimentally by measurement of a standard sample, or can be calculated theoretically based on the molecular structure of the compound. In such a theoretical calculation, for example, a first principle calculation can be used.

[0063] Next, the measurement of a sample using the mass spectrometry apparatus 1 of the present embodiment will be described. Here, the case will be described by way of example in which a liquid chromatograph is arranged in front of the mass spectrometry apparatus 1 (see FIG. 1) (refer to Figure 15 ), and the sample is introduced into the liquid chromatograph, and the components contained in the sample are separated from each other in the column of the liquid chromatograph and measured by the mass spectrometry apparatus 1. However, in the present application, it is not necessary to have a component separation mechanism such as a chromatograph. For example, even in the case of measuring a sample containing a plurality of compounds, when the ions derived from the compounds that are the measurement targets can be separated from the ions derived from other compounds by mass separation alone, the component separation mechanism can not be used, and the sample can be introduced directly into the mass spectrometry apparatus 1.

[0064] First, the measurement condition setting unit 43 reads a list of compounds included in the compound database 411 and displays it on the display unit 7. When the user selects a compound to be measured from this list, the measurement condition setting unit 43 generates a method file that describes the measurement conditions listed in the compound database 411. Then, based on this method file, a batch file is generated for executing the measurement. In this embodiment, the user selecting a compound to be measured from the compound database 411 corresponds to inputting information on molecular structure candidates in the present invention. The measurement condition setting unit 43 in this embodiment functions as a molecular structure candidate input receiving unit in the present invention (see [Protocol] described below).

[0065] As a specific example, Figure 2 The case where compounds A to D shown are used as measurement objects is described. Compound C and compound D among compounds A to D are structural isomers. Among structural isomers, there are structural isomers that can be separated from each other by the chromatographic column of a liquid chromatograph or a gas chromatograph, but what is considered here is the case where the retention time, precursor ions and product ions of compound C and compound D flowing out of the chromatographic column of the liquid chromatograph are the same (that is, compound C and compound D cannot be identified by liquid chromatography mass analysis alone). Therefore, in this example, MRM measurement is performed on all of compounds A to D, and electron beam diffraction measurement is further performed on compounds C and D. That is, as Figure 3 As shown, a batch file is generated with the following contents: MRM measurement of compound A is performed in time slot 1; MRM measurements of compounds A and B are performed alternately in time slot 2; MRM measurement of compound B is performed in time slot 3; and MRM measurements and electron beam diffraction measurement of compounds C and D are performed in time slot 4. The presence or absence of electron beam diffraction measurement can be specified by the user, or the measurement condition setting unit 43 can automatically set electron beam diffraction measurement for a group of compounds with the same retention time, precursor ion mass-to-charge ratio, and product ion mass-to-charge ratio. For ease of explanation, only one MRM transition is measured for each compound here, but multiple MRM transitions can also be measured.

[0066] After the batch file is generated, if the user instructs measurement execution through a predetermined input operation, the measurement control unit 44 performs measurement according to the following steps.

[0067] First, a sample is introduced into a liquid chromatograph, and sample components separated by the chromatographic column of the chromatograph are sequentially introduced into the ESI probe 201 and ionized.

[0068] Upon reaching the first time zone (time zone 1) recorded in the batch file after the start of measurement, measurement of the compound recorded in the time zone is performed. In time zone 1, MRM measurement of Compound A is performed. Then, in each time zone, MRM measurement and electron beam diffraction measurement are performed based on the contents recorded in the batch file.

[0069] The MRM measurement performed in time zones 1 to 4 will be described simply. The measurement conditions of the MRM measurement are the same as in the past.

[0070] The sample components flowing out from the column of the liquid chromatograph are ionized by the ESI probe 201, introduced into the 1st intermediate vacuum chamber 21 through the heated capillary 202, and then converged on the ion optical axis Cl by the ion lens 211. The ions converged by the ion lens 211 are introduced into the 2nd intermediate vacuum chamber 22 through the cone hole body 212. The ions introduced into the 2nd intermediate vacuum chamber 22 are converged on the ion optical axis Cl by the 1st ion guide 221 and the 2nd ion guide 222, and introduced into the analysis chamber 23.

[0071] In the analysis chamber 23, first, the precursor ions of the measurement target compound are selected by the pre-stage quadrupole filter 231, and introduced into the collision cell 232. A prescribed amount of a prescribed kind of inert gas (typically argon) is sealed in the collision cell 232 in advance as a collision gas. A potential difference is provided between the rear electrode 2313 of the pre-stage quadrupole filter 231 and the entrance of the collision cell 232, and the precursor ions of the measurement target compound are given energy (collision energy) by this potential difference to be introduced into the collision cell. Inside the collision cell 232, product ions are generated from the precursor ions by collision with the molecules of the inert gas.

[0072] Next, in the post-stage quadrupole filter 235, only the product ions having a mass-to-charge ratio (recorded in the method file) decided in advance are selected. The ions selected by the post-stage quadrupole filter 235 are introduced as they are into the deflection section 236, and detected by the ion detector 237. The output signal from the ion detector 237 is sent and saved to the storage section 41 in order.

[0073] Next, the electron beam diffraction measurement performed in time zone 4 will be described.

[0074] In electron beam diffraction measurement, similar to the MRM measurement described above, ions of a predetermined mass-to-charge ratio are selected in the front-stage quadrupole mass filter 231 as precursor ions, 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 in the rear-stage quadrupole mass filter 235 as ions to be analyzed. In electron beam diffraction measurement, product ions having the same mass-to-charge ratio as the ions of the predetermined mass-to-charge ratio selected in the rear-stage quadrupole mass filter 235 but containing portions with different molecular structures are used as the targets of analysis.

[0075] When performing electron beam diffraction measurement, the interior of the vacuum chamber 316 is evacuated to a high vacuum in advance, and the neutral gas molecules remaining in the ion trap 31 are exhausted. Then, one of the four rod electrodes 2361 of the deflection unit 236 ( Figure 1 A voltage with a polarity opposite to that of the product ions is applied to the rod electrode 2361 at the lower left of the center, and a voltage with the same polarity as that of the product ions is applied to the other rod electrodes 2361. By applying voltages of appropriate magnitude to these four rod electrodes 2361, the flight direction of the ions that have passed through the post-stage quadrupole mass filter 235 is deflected by 90 degrees (at Figure 1 (center is downward direction).

[0076] The product ions, whose flight direction is deflected by the deflection unit 236, are captured by the ion trap 31 and cooled by collision with cooling gas (typically helium) temporarily introduced into the ion trap 31 through the gas inlet 317. The product ions are then concentrated in the center of the ion trap 31. After the product ions are accumulated and cooled in the ion trap 31 for a predetermined period of time, the interior of the ion trap 31 is irradiated with an electron beam from the electron beam irradiation unit 30.

[0077] In previously proposed electron beam diffraction measurements, ions generated by the sample are directly accumulated in an ion trap, and then mass separation is performed within the ion trap to screen the ions to be measured. When accumulating ions generated by the sample, if an excessive amount of ions is attempted to be accumulated, the electric field inside the ion trap is distorted by the ions' own charge (called "space charge"), and normal mass separation cannot be performed. Therefore, first, during the stage of accumulating ions generated by the sample, there is a limit to the amount that can be accumulated in the ion trap. In addition, in the past, ions generated by the sample were introduced into the ion trap, and the ions to be measured were mass separated and screened within the ion trap. Therefore, even if the maximum amount of ions that can be accumulated is initially assumed, the amount of ions to be analyzed contained therein is less than that amount.

[0078] In contrast, in the mass spectrometer of this embodiment, the product ions of the target ion are filtered by the front-stage quadrupole mass filter 231, the collision cell 232, and the rear-stage quadrupole filter 235 before being 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 of the target ion are introduced into the ion trap 31 without limiting the amount of ions accumulated in the ion trap 31.

[0079] In addition, in the past, ions were captured in an ion trap by applying a high-frequency sinusoidal voltage to the annular electrode with the inlet-side end cap electrode and the outlet-side end cap electrode as the ground potential. The mass-to-charge ratio (range) of the captured ions was increased or decreased by varying the amplitude while maintaining the frequency of the sinusoidal voltage constant (voltage drive). In the previous method, the larger the mass-to-charge ratio of the ion to be captured, the larger the amplitude of the sinusoidal voltage had to be. To achieve this, a large and expensive power supply capable of outputting high voltage was required. In addition, there were the following problems: discharge was easily generated due to the application of high voltage, and the application of high voltage that varied over time had an adverse effect on the flight path of the electron beam.

[0080] On the other hand, in this embodiment, the inlet side end cap electrode 312 and the outlet side end cap electrode 313 are set to ground potential, and a digital circuit is used to apply the rectangular voltage generated by the voltage application unit 5 to the annular electrode 311 of the ion trap 31. An ion trap that captures ions by applying a rectangular voltage in this way is also called a digital ion trap (DIT). In a DIT, while keeping the amplitude of the rectangular voltage constant, the frequency is varied within a wide range (frequency driving is performed), thereby changing the mass-to-charge ratio (range) of the ions captured in the ion trap 31. In a digital ion trap, regardless of the mass-to-charge ratio of the captured ions, since the amplitude of the rectangular voltage is constant, there is no need to use a large and expensive power supply. In addition, there is no need to worry about discharge. Furthermore, in frequency driving, the frequency can be changed within a wide range, so compared with the previous voltage-driven type, a wider mass-to-charge ratio range can be covered and more types of ions can be captured. For example, by reducing the frequency, it is possible to capture ions with a large mass-to-charge ratio that were difficult to capture in conventional voltage-driven ion traps, or to capture tiny charged particles that are much larger than ions. Furthermore, by applying a low-frequency rectangular voltage to capture precursor ions with a large mass-to-charge ratio, the captured precursor ions can be fragmented (i.e., dissociated) using a laser or the like, and the frequency of the rectangular voltage can be instantaneously switched to a higher frequency (by causing the frequency to jump), so that the fragment ions with a smaller mass-to-charge ratio generated by the fragmentation of the precursor ions can be captured in the ion trap. In addition, by injecting an electron beam at the timing when the rectangular voltage (high-frequency voltage) reaches a specified phase, as described later, the possibility of adversely affecting the flight path of the electron beam can be eliminated.

[0081] In the mass spectrometer 1 of this embodiment, the rectangular voltage is applied to the annular electrode 311 for a predetermined time to trap the product ions in the ion trap 31. At this time, as the phase of the rectangular voltage applied to the annular electrode 311 changes, the spatial distribution of ions inside the ion trap 31 changes. In the following description, Figure 4 As shown in FIG, the phase at the moment when the applied voltage changes from negative to positive is set to 0°, and the phase at the moment when the applied voltage changes from positive to negative is set to 180°. Figure 5 As shown, the symmetry axis of the ion trap 31 (the axis passing through the opening 314 of the entrance-side end cap electrode 312 and the opening 315 of the exit-side end cap electrode 313 ) is defined as the Z axis, and a direction perpendicular thereto is defined as the X axis.

[0082] The results of simulations conducted by the present inventors on the correlation between the phase of the rectangular voltage and the motion state (spatial distribution and velocity distribution) of ions will be described.

[0083] Figures 6 to 9 The following are simulation results for the X-axis diffusion (X) and X-axis velocity (Vx) of ions within the ion trap 31 when the phase of the rectangular voltage is 0°, 90°, 180°, and 270°, respectively. These results show that even when the phase of the rectangular voltage applied to the annular electrode 311 is changed, no significant change in the X-axis diffusion of ions is observed.

[0084] Figures 10 to 13 The results are respectively simulated for the diffusion (Z) of the position of ions in the ion trap 31 along 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°. Unlike the X-axis direction, according to these results, if the phase of the rectangular voltage applied to the annular electrode 311 changes, the diffusion of the position of ions along the Z-axis direction also changes. It can be seen that among these, especially when the phase is 270°, the ions diffuse in the most elongated state in the Z-axis direction, and the distribution in the X-axis direction is the narrowest. Since the electron beam from the electron beam irradiation part 30 irradiates along the Z-axis direction (the negative direction of the Z-axis), if the electron beam is irradiated to the inside of the ion trap 31 at this time, the ions captured in the ion trap 31 can be irradiated with the electron beam most efficiently. That is, the spatial overlap between the cloud of ions and the electron beam becomes larger. Therefore, in this embodiment, before and after the phase of the rectangular voltage applied to the annular electrode 311 becomes 270° (at Figure 4 At the timing indicated by the hatching in the middle), the electron beam from the electron beam irradiation unit 30 is irradiated into the ion trap 31.

[0085] Furthermore, conventionally, ions trapped in an ion trap are continuously irradiated with an electron beam. However, because the high-frequency sinusoidal voltage applied to the annular electrode varies with time, the direction and magnitude of the electron beam deflection also vary with time. As a result, the background, which is detrimental to diffraction, increases, blurring the electron beam diffraction image.

[0086] In contrast, the mass spectrometer 1 of this embodiment emits a pulsed electron beam at a time when the phase of the rectangular voltage is approximately 270°. That is, the electric field formed within the ion trap 31 remains constant at the time of electron beam emission. Therefore, the effect of this electric field on the electron beam path can be considered in advance, and measurement conditions such as the electron beam emission direction can be determined to compensate for this effect.

[0087] The electron beam that has passed through the ion trap 31 without being diffracted by the product ions enters 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.

[0088] The electron beam diffracted by the product ions trapped in the ion trap 31 is incident on the microchannel plate 322. Electron multiplier tubes are arranged two-dimensionally in the microchannel plate 322. Electrons incident on the electron multiplier tubes are amplified and emitted from the opposite side. Electrons emitted from the electron multiplier tubes are incident on the fluorescent screen 323. The surface of the fluorescent screen 323 is pre-coated with a fluorescent substance. Electrons incident on the fluorescent screen 323 generate fluorescence from the fluorescent substance at the incident position. A CCD camera 324 is arranged on the back side of the fluorescent screen 323. The fluorescence emitted from the fluorescent screen 323 is captured at a predetermined period and the captured data is sequentially transmitted to the control and processing unit 4. The received captured data is stored in the storage unit 41 by the control and processing unit 4.

[0089] Once all time band measurements are complete, the analysis processing unit 45 reads the MRM measurement data obtained for each compound. The presence of the compound is then determined based on the ion intensity during the MRM measurement. Furthermore, the compound is quantified as needed. Compound quantification can be performed by pre-storing information about a calibration curve for the target compound and comparing the ion intensity during the MRM measurement with the calibration curve.

[0090] The analysis processing section 45 reads the data of the electron beam diffraction image acquired in the time zone 4. Further, with reference to the compound database 411, the data of the electron beam diffraction images of the compounds C and D that are the measurement targets in the time zone 4 is read. At this time, in the case where the data of the electron beam diffraction image of either of the compounds C and D is not included in the compound database 411, the electron beam diffraction image estimation section 46 theoretically estimates the electron beam diffraction image based on the molecular structure information of the compound (for example, the molecular structure is estimated by first principle calculation, and the electron beam diffraction image is theoretically calculated from the contribution of each atom), and generates the data of the electron beam diffraction image.

[0091] Next, the analysis processing section 45 collates the measurement data of the electron beam diffraction image obtained by the measurement with the data of the electron beam diffraction images of the compounds C and D. Then, based on the degree of agreement of both, it is determined whether or not the compounds C and D are present (only the compound C, only the compound D, or both the compounds C and D).

[0092] Here, as an example, reference is made to Figure 14 An electron beam diffraction image of carbon tetrachloride (CCl4) is described. In carbon tetrachloride, a carbon atom (C) is bonded to four chlorine atoms (Cl) at an interatomic distance r. If an electron beam is irradiated thereto, electrons are scattered in various directions, but the waves (de Broglie waves) of the electrons scattered from C and the electrons scattered from Cl are mutually reinforced in a certain direction θ. On the other hand, they are mutually canceled in an angle θ'. Since the orientation of the molecule is random, concentric circular fringes due to interference can be formed on the detection plane. The radius of the concentric circles has a correlation with the distance r, and by comparing the theoretically calculated interference fringes with the observed interference fringes with the distance r as a parameter, the distance r can be calculated. In the case of carbon tetrachloride (CCl4), two peaks corresponding to the C-Cl equilibrium distance and the Cl-Cl equilibrium distance are calculated on the radial distribution function.

[0093] However, the number of atoms of the compound measured by liquid chromatography mass analysis and the like is generally more than that of carbon tetrachloride. In the electron beam diffraction image of such a compound, the peaks corresponding to the interatomic distances overlap with each other. Therefore, it is difficult to determine the interatomic distance of each bond within the molecule only from the electron beam diffraction image.

[0094] In contrast to this, in the present embodiment, the mass-to-charge ratio of the ion can be known by performing mass analysis in advance, and therefore the functional group included in the molecular structure of the compound can be assumed in advance based on the mass-to-charge ratio, and it can be estimated whether or not the functional group is included based on the presence or absence of a unique interference fringe in the functional group. Further, with respect to structural isomers, it can be estimated which one of a plurality of structural isomers the measured compound is based on the difference in the interference fringes due to the positional relationship of the molecular structure of the structural isomers and the position of the functional group.

[0095] Furthermore, the recent improvement in the accuracy of molecular structures (the positions of atoms within a molecule) determined through first-principles calculations has made it possible to accurately infer the interference fringes that appear in electron beam diffraction images based on the molecular structure. By comparing electron diffraction images obtained through simulations based on theoretical calculations with those obtained through actual measurements, structural isomers can be identified or the ratio of these mixtures can be determined.

[0096] The mass spectrometer 1 of this embodiment can perform various measurements in addition to the above-described example. While the above-described example combines MRM measurement with electron beam diffraction measurement, it is also possible to combine product ion scanning measurement with electron beam diffraction measurement. For example, it is also possible to first perform product ion scanning measurement on a target compound to measure a product ion spectrum, and then perform electron beam diffraction measurement to analyze the structure of the ions corresponding to the peaks appearing in this spectrum.

[0097] In addition, in the above example, although the product ions generated by dissociating precursor ions of a specified mass-to-charge ratio generated from the sample in the collision cell 232 are measured (mass analysis and electron beam diffraction measurement), it is also possible to measure the ions obtained by mass separation of the ions generated from the sample by the front-stage quadrupole mass filter 231 or the rear-stage quadrupole mass filter 233 without dissociating the ions in the collision cell 232 (mass analysis and electron beam diffraction measurement).

[0098] In the above example, the case where electron beam diffraction is performed on compounds C and D that are not separated (holding time is the same) in the chromatographic column of the liquid chromatograph is described. However, even in the case of isomers that can be separated in the chromatographic column, the compounds are only separated in the chromatographic column of the liquid chromatograph and the molecular structure information of the compounds cannot be obtained. Therefore, by performing electron beam diffraction measurement in the same manner as in the above example, the molecular structure information of the compounds is obtained at the same time, and each compound separated by the liquid chromatograph can be analyzed with higher accuracy. In addition, the above example is not limited to the combination of liquid chromatograph (LC) in the mass spectrometer 1 of this embodiment, and can also be combined with gas chromatograph (GC) ( Figure 15 ).

[0099] Furthermore, it is also possible to use the mass spectrometer 1 of this embodiment in combination with an ion mobility spectrometer (IMS) ( Figure 16 ) or a configuration in which a chromatographic device (liquid chromatograph, gas chromatograph), an ion mobility analyzer, and the mass spectrometer 1 of this embodiment are sequentially combined from the upstream side ( Figure 17 ) device to perform measurements.

[0100] In an ion mobility analysis device, ions are separated according to the size of the collision cross section of the ions, and isomers can be identified. However, there are many cases in which the theoretical value of the size of the collision cross section of the ions does not match the measured value. Furthermore, the measured value of the collision cross section of the ions also varies depending on the configuration of the device (for example, for each manufacturer), the type of gas that causes the ions to collide, and the like. Therefore, sometimes even if the size of the collision cross section of the ions obtained by measurement is compared with the values included in a database, the molecular structure cannot be identified. That is, as with a chromatographic device, even in cases in which the compound can be separated, information on the molecular structure of the compound cannot be obtained. As shown in Figure 16 and Figure 17 By combining the ion mobility analysis device with the mass spectrometry device 1 of the present embodiment, not only the size of the collision cross section of the ions is obtained, but also molecular structure information is obtained by electron diffraction measurement, and thus the compound contained in the sample can be analyzed with higher precision. In addition, in the case of combining the ion mobility analysis device, the ionization section of the mass spectrometry device 1 is separated from the other configurations (in the figure, the electron beam irradiation section and the like are included in the mass spectrometry section), and an ion mobility analysis section is disposed therebetween.

[0101] As described above, in an electron diffraction image, concentric circular fringes appear due to the interference of the waves (de Broglie waves) of the electrons, and thus by changing the wavelength, different electron diffraction images can be obtained from the same molecule. If the wavelength of the electron beam used for electron diffraction measurement is changed, the interatomic distance at which the wavelength of the electron beam is mutually strengthened changes, and thus the observed interference fringes differ. In the present method in which the degree of agreement of the overall pattern of the interference fringes is determined, the energy of the incident electrons becomes an important parameter. Therefore, in the mass spectrometry device 1 of the present embodiment, for example, in cases in which the component contained in the sample cannot be specified as which of the structural isomers with sufficient accuracy by measurement using only the above-described example, electron diffraction measurement using electron beams having different energies can be performed. The user sets, using the measurement condition setting section 43, electron beams having different energies as the conditions for electron diffraction measurement as the measurement conditions, and performs measurement using a plurality of electron beams having different wavelengths (a plurality of electron beams having different energies) respectively when measurement is performed by the measurement control section 44, and thus a plurality of electron diffraction images are obtained. After the measurement, the 2nd molecular structure estimation section 472 analyzes the difference in the interference fringes appearing in the plurality of electron diffraction images, and estimates the molecular structure.

[0102] In addition, the electron beam is scattered by both the nucleus and the electrons. For both the nucleus and the electrons, the larger the atomic number, the more atoms there are. That is, the larger the atomic number, the greater the scattering intensity. Thus, in the mass spectrometer 1 of the present embodiment, it is also possible to prepare a sample in which atoms with larger atomic numbers (or functional groups including atoms with larger atomic numbers) are pre-attached or replaced at or near positions where the molecular structures differ between structural isomers, and perform electron beam diffraction measurement using the sample. In this case, after the measurement is completed, the third molecular structure inference unit 473 extracts interference fringes corresponding to the attached atoms or functional groups from the electron beam diffraction image, thereby inferring the molecular structure.

[0103] The above-described embodiment is merely an example and can be modified appropriately based on the spirit of the present invention.

[0104] In the above embodiment, the ESI probe 201 is used as the ionization unit, but an atmospheric pressure chemical ionization device or the like can also be used. Furthermore, when measuring a gas sample, an electron ionization device or a chemical ionization device can also be used.

[0105] In the above embodiment, a triple quadrupole mass spectrometer is used as the mass spectrometer, but other mass spectrometers such as a quadrupole-time-of-flight type can be used. In addition, when an ionization unit such as an electron ionizer is used that generates fragment ions during ionization, a mass spectrometer having only a single mass separation unit (e.g., only a single quadrupole mass filter) can also be used.

[0106] In the above embodiment, the deflection unit 236 is provided, but the deflection unit 236 may be omitted. For example, Figure 18 The structure is as shown in the middle block diagram. In this structure, when performing mass analysis (solid line), no voltage is applied to the ion trap, and ions separated by mass in the mass analysis unit pass through the ion trap and are detected by the ion detector. When performing electron beam diffraction measurement (dashed line), voltage is applied to the ion trap to accumulate ions, an electron beam is applied from the electron beam irradiation unit, and a diffraction image is obtained by the electron beam detection unit.

[0107] Furthermore, the mass spectrometer 1 of the above embodiment also performs electron beam diffraction to obtain information on molecular structure. Based on the same concept, the mass spectrometer 1 can also perform rotational spectrometry and X-ray diffraction measurement.

[0108] In addition, although NMR is also used to estimate molecular structure, its sensitivity is significantly lower than that of mass analysis, with a sensitivity of about two decimal places or more. Therefore, when measuring the same sample, a separate sample must be prepared that is more concentrated in the components of the measurement object than the sample used for mass analysis. Depending on the sample, there are also samples that are difficult to synthesize and adjust, making it impossible to measure the product ions described above. In addition, the measurement itself needs to be performed separately from the mass analysis. In contrast, the mass spectrometer of the above embodiment can perform both mass analysis and electron beam diffraction measurement at a single time and with higher sensitivity through a series of measurements.

[0109] While electron beam diffraction measurement is performed in conjunction with mass analysis in the aforementioned embodiments and variations, various secondary measurements can be performed in addition to electron beam diffraction measurement. In the present invention, after mass separation, only ions with a specific mass-to-charge ratio (or within a specific mass-to-charge ratio range) are captured in large quantities into an ion trap as the target ions for measurement, enabling measurement of various physical quantities (acquisition of physical property information) related to these target ions.

[0110] exist Figure 19 In the embodiment, as an example of a secondary measurement that can be implemented in the mass spectrometer of the present invention, the following measurement method (including the electron beam diffraction measurement in the above embodiment) is shown: an electromagnetic wave (light, etc.) or a particle beam is incident on an ion trap, and after interacting with the ions (trapped ions) captured in the ion trap, the electromagnetic wave (light, etc.) or particles emitted from the ion trap are detected. Here, as an example of interaction, in the case of incident electromagnetic waves, the absorption or scattering of the electromagnetic wave caused by the trapped ions can be cited. The ions that absorb the electromagnetic wave and migrate to an excited state emit electromagnetic waves with a wavelength different from that of the incident electromagnetic wave, or emit a particle beam, thereby returning to the ground state. In addition, there are also cases where the electromagnetic wave is not absorbed by the ions and is elastically or inelastically scattered (including diffraction). In the case of an incident particle beam, scattering can be cited as an example of interaction with the trapped ions. The ions that obtain energy from the incident particles and migrate to an excited state emit electromagnetic waves, or emit a particle beam, thereby returning to the ground state. In addition, there are also cases where the incident particles are elastically or inelastically scattered (including diffraction). Other examples of secondary measurements include methods that inject electromagnetic waves (light, etc.) or particle beams into an ion trap and detect the electromagnetic waves (light, etc.) or particles that are emitted from the ion trap without interacting with trapped ions. In absorbance measurements, electromagnetic waves that pass through the ion trap without interacting with trapped ions are detected. Furthermore, secondary measurements can also include methods that vary the type of trapped ions and compare the differences in measurement results.

[0111] Figure 20 as well as Figure 21 An example of the configuration of a device that can be commonly used among these is shown. Figure 20 The structure is similar to the above embodiment and includes a deflection unit. Figure 21 This is a configuration that does not use a deflection unit, similar to the above-mentioned modification. Figure 20 as well as Figure 21 In FIG. 1 , the solid lines indicate components for performing mass analysis, and the dotted lines indicate components for performing sub-measurement.

[0112] For example, by irradiating trapped ions with an electron beam and measuring the electron beam diffracted by the ions to perform electron beam diffraction measurement, information on the molecular structure of the ions can be obtained. In addition, by exciting the trapped ions with an electron beam and measuring the electrons scattered by the ions to perform electron energy loss spectroscopy, information on the electronic state of the ions can be obtained. In addition, by using an electron beam microprobe analyzer (EPMA) that excites trapped ions with an electron beam and measures the light emitted from the ions, electronic structure analysis and elemental analysis of the ions can be performed. In addition, by exciting the trapped ions with a beam (ion beam) of ions different from the ions and detecting the ions scattered by the ions, ion scattering spectroscopy can be performed to perform elemental analysis. In addition, by exciting the trapped ions with an ion beam and detecting the light emitted from the ions, particle induced fluorescence spectroscopy can be performed to perform elemental analysis. In addition, by exciting the trapped ions with light and detecting the light emitted from the ions, atomic absorption spectroscopy can be performed to perform elemental analysis. Furthermore, by irradiating trapped ions with light and detecting the light diffracted by the ions, laser diffraction or X-ray diffraction measurements can be performed to obtain information about the ions' shape or molecular structure. Furthermore, by irradiating trapped ions with light and detecting the light transmitted through the ions, X-ray absorption edge measurements or Fourier transform infrared spectroscopy, which measure the amount of light absorbed by the ions, can be performed to obtain information about the ions' intramolecular bonding. Furthermore, by irradiating trapped ions with light and detecting the light scattered by the ions, Raman spectroscopy can be performed to obtain information about the ions' intramolecular bonding. Furthermore, by irradiating trapped ions with light and measuring the electrons emitted from the ions, photoelectron spectroscopy can be performed to obtain information about the ions' electronic or bonding states.

[0113] [plan]

[0114] Those skilled in the art will appreciate that the above-mentioned exemplary embodiments are specific examples of the following schemes.

[0115] (Item 1)

[0116] The mass analysis device of the first embodiment has:

[0117] an ionization unit for generating ions from a sample;

[0118] a mass separation unit for separating the masses of ions generated by the ionization unit;

[0119] an ion detector for detecting ions separated by mass by the mass separation section;

[0120] an ion trapping section for trapping ions separated by mass by the mass separation section;

[0121] The auxiliary measuring unit measures physical quantities other than the mass-to-charge ratio of the ions trapped by the ion trapping unit.

[0122] In the mass spectrometer of item 1, mass analysis can be performed by mass-separating ions generated by the ionization section in a mass separation section and detecting them with an ion detector. Furthermore, it is also possible to mass-separate ions generated by the ionization section in a mass separation section, screen out the ions to be analyzed, and then capture them in an ion capture section to measure (secondary measurement) physical quantities other than mass-to-charge ratio. Secondary measurements can include, for example, irradiating the ions captured in the ion capture section with electromagnetic waves (light, etc.) or a particle beam and detecting the electromagnetic waves (light, etc.) or particles emitted from the ion capture section. Specifically, for example, electron beam diffraction measurement can be performed by accumulating the ions to be analyzed in the ion capture section, irradiating them with an electron beam for a predetermined period of time, and detecting the electron beam diffracted by the ions in the ion capture section. Although isomers with the same mass-to-charge ratio cannot be identified by mass analysis alone, the mass spectrometer of item 1 can, for example, obtain information on the molecular structure by performing the electron beam diffraction measurement described above as a secondary measurement, thereby identifying isomers. In addition, in the mass spectrometer of item 1, by appropriately changing the flight path of the ions, it is possible to perform both mass analysis of mass separation and detection of ions generated by the ionization unit and secondary measurement of physical quantities other than the mass-to-charge ratio of the ions by capturing the mass-separated ions.

[0123] If an ion capture unit (typically a three-dimensional ion trap) has captured an excess of ions and an attempt is made to perform mass separation in the ion capture unit, the electric field inside the ion capture unit is distorted by the charge (space charge) of the ions themselves, and mass separation cannot be performed normally. In addition, in previously proposed devices, ions generated from a sample are introduced into the ion capture unit, and the ions to be analyzed are screened within the ion capture unit. Therefore, there is a limit to the amount of ions that can be captured in the ion capture unit. Moreover, even if a maximum amount of ions is initially captured, the amount of ions to be analyzed contained therein is less than the maximum amount. In contrast, in the mass spectrometer of item 1, the ions to be analyzed are screened by a mass separation unit located outside the ion capture unit. Since only the ions to be analyzed are introduced into the ion capture unit, the maximum amount of ions to be analyzed can be captured and provided to the electron beam diffraction measurement, and a high-intensity diffraction image can be obtained more efficiently than before.

[0124] (Item 2)

[0125] In the mass spectrometer described in Item 1,

[0126] The mass separation unit comprises:

[0127] a front-stage mass separation section for selecting ions with a specific mass-to-charge ratio from the ions generated by the ionization section as precursor ions;

[0128] a dissociation unit for dissociating the precursor ions to generate product ions;

[0129] The post-stage mass separation section selects ions with a specific mass-to-charge ratio from the product ions.

[0130] In the mass spectrometer described in Item 2, by selecting precursor ions and product ions in the front-stage mass separation section and the rear-stage mass separation section, respectively, mass analysis using ions characteristic of the compound to be measured can be performed, or product ions of structural isomers having local partial structures including positions with different molecular structures can be selected to perform electron beam diffraction measurement.

[0131] (Item 3)

[0132] The mass spectrometer according to item 1 or 2 further comprises

[0133] a deflection unit, provided between the mass separation unit and the ion detector, for deflecting the flight direction of ions emitted from the mass separation unit;

[0134] The ion trapping portion is provided on a flight path of the ions whose flight directions are deflected by the deflecting portion.

[0135] In the mass spectrometer described in Item 3, ions separated by the mass separation section are deflected and introduced into the ion trapping section. This separates ions from neutral molecules and introduces only the ions to be analyzed into the ion trapping section, thereby reducing the background of the electron beam diffraction image caused by electron scattering by neutral molecules. Furthermore, in the mass spectrometer described in Item 3, ions generated from a sample and having a predetermined mass-to-charge ratio are captured in the ion trapping section, and electron beam diffraction measurements can be performed by irradiating these ions with an electron beam, while simultaneously performing mass analysis of ions newly generated by the ionization section.

[0136] (Item 4)

[0137] The mass spectrometer according to any one of items 1 to 3 further includes a voltage application unit that applies a rectangular wave voltage for trapping ions in the ion trapping unit.

[0138] In the mass spectrometer described in Item 4, the frequency can be varied while maintaining the amplitude of the rectangular wave voltage constant, thereby varying the mass-to-charge ratio (range) of ions captured by the ion trapping unit. Therefore, a large power supply is not required. Furthermore, there is no need to worry about discharge or deflection of the electron beam's flight path due to the application of high voltage.

[0139] (Item 5)

[0140] In the mass spectrometer according to any one of items 1 to 4, the auxiliary measurement unit includes:

[0141] an irradiation unit for irradiating the ions captured in the ion capture unit with electromagnetic waves or particle beams;

[0142] The detection unit detects the electromagnetic wave or particle beam emitted from the ion trapping unit.

[0143] In the mass spectrometer of item 5, various measurements as described below can be performed. For example, by irradiating ions captured in the ion capture section (trapped ions) with an electron beam and measuring the electron beam diffracted by the ions to perform electron beam diffraction measurement, information on the molecular structure of the ions can be obtained. Alternatively, by exciting the trapped ions with an electron beam and measuring the electrons scattered by the ions to perform electron energy loss spectroscopy, information on the electronic state of the ions can be obtained. Alternatively, by exciting the trapped ions with an electron beam and using it as an electron beam microprobe analyzer (EPMA) that measures the light emitted from the ions, electronic structure analysis and elemental analysis of the ions can be performed. Alternatively, by exciting the trapped ions with an ion beam and detecting the ions scattered by the ions, ion scattering spectroscopy can be performed to perform elemental analysis. Alternatively, by exciting the trapped ions with an ion beam and detecting the light emitted from the ions, particle induced fluorescence spectroscopy can be performed to perform elemental analysis. Alternatively, by exciting the trapped ions with light and detecting the light emitted from the ions, atomic absorption spectroscopy can be performed to perform elemental analysis. Alternatively, by irradiating trapped ions with light and detecting the light diffracted by the ions, laser diffraction measurement or X-ray diffraction measurement can be performed to obtain information on the ion's shape or molecular structure. Alternatively, by irradiating trapped ions with light and detecting the light transmitted through the ions, X-ray absorption edge measurement or Fourier transform infrared spectroscopy, which measures the amount of light absorbed by the ions, can be performed to obtain information on the ion's intramolecular bonding. Alternatively, by irradiating trapped ions with light and detecting the light scattered by the ions, Raman spectroscopy can be performed to obtain information on the ion's intramolecular bonding. Alternatively, by irradiating trapped ions with light and performing photoelectron spectroscopy, which measures the electrons emitted from the ions, information on the ion's electronic state or bonding state can also be obtained.

[0144] (Item 6)

[0145] In the mass spectrometers described in Items 4 and 5,

[0146] When a rectangular wave voltage of a predetermined phase is applied from the voltage applying unit to the ion trapping unit, the irradiating unit irradiates the interior of the ion trapping unit with a pulsed electromagnetic wave or a particle beam.

[0147] In the mass spectrometer described in Item 5, by pre-simulating or conducting preliminary tests, the phase of the rectangular wave voltage that causes ions in the ion trap to be in a diffuse state along the irradiation path of the electromagnetic wave or particle beam is predetermined to the above-specified phase, thereby enabling more ions to be irradiated with the electromagnetic wave or particle beam, thereby obtaining a high-intensity signal intensity. In a mass spectrometer constructed by applying a high-frequency sinusoidal voltage to an annular electrode to capture ions inside an ion trap as in the past, a phase difference occurs between the voltage driving the resonant circuit and the output voltage of the resonant circuit actually applied to the electrode. This phase difference depends on the load impedance of the electrode and therefore varies depending on the electrode shape, its holding method, etc. Therefore, it is difficult to irradiate the electromagnetic wave or particle beam at the moment when the high-frequency sinusoidal voltage reaches a specific phase. Even if it is assumed that the phase can be made consistent, the amplitude of the high-frequency sinusoidal voltage needs to be changed according to the mass-to-charge ratio of the ion being measured, and thus the voltage setting value of the incident optical system of the electromagnetic wave or particle beam needs to be changed accordingly. In contrast, the mass spectrometer described in Item 5 applies the drive voltage directly to the electrodes without passing through a resonant circuit. This allows control to be performed so that the electromagnetic wave or particle beam is irradiated at the optimal phase. Furthermore, even if the mass-to-charge ratio of the ions being measured changes, the amplitude can be kept constant simply by changing the frequency of the rectangular wave voltage, eliminating the need to change the voltage setting of the incident optical system for the electromagnetic wave or particle beam.

[0148] (Item 7)

[0149] In the mass spectrometer according to item 5 or 6,

[0150] The irradiation unit is an electron beam irradiation unit that irradiates the ion trapping unit with an electron beam.

[0151] The detection unit detects the electron beam diffracted by the ions.

[0152] In the mass spectrometer described in Item 7, electron beam diffraction measurement is performed on ions of a specific mass-to-charge ratio (or a mass-to-charge ratio range) trapped in an ion trapping unit, thereby obtaining information on the molecular structure of the ions.

[0153] (Item 8)

[0154] The mass spectrometer according to item 7, further comprising:

[0155] a molecular structure candidate input reception unit that receives input of information of a molecular structure candidate;

[0156] a first molecular structure estimation unit that estimates a molecular structure of a molecule contained in a sample by comparing an electron beam diffraction image obtained by measuring the sample with an electron beam diffraction image prepared in advance for the molecular structure candidate.

[0157] In the mass spectrometer described in item 8, by using an electron beam diffraction image prepared in advance (for example, an electron beam diffraction image obtained by electron beam diffraction of a standard sample, an electron beam diffraction image estimated based on theoretical calculation described below), it is possible to more easily analyze the electron beam diffraction image obtained by measurement. Further, in the mass spectrometer described in item 7, instead of a diffraction peak acquired by general electron beam diffraction measurement, it is possible to obtain data of concentric circle-shaped interference fringes as a diffraction image. Such data can be processed as one kind of image data. Then, as the first molecular structure estimation unit, for example, it is possible to use an identifier generated by machine learning of the pattern of the entire diffraction image obtained by electron beam diffraction measurement and / or theoretical calculation of various compounds.

[0158] (item 9)

[0159] In the mass spectrometer described in item 8, further provided with

[0160] 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 molecular structure candidate input reception unit.

[0161] In the mass spectrometer described in item 9, it is also possible to estimate an electron beam diffraction image for a compound not included in the compound database.

[0162] (item 10)

[0163] In the mass spectrometer described in any one of items 7 to 9,

[0164] The energy of the electron beam irradiated by the electron beam irradiation unit can be variable.

[0165] (item 11)

[0166] In the mass spectrometer described in item 10, further provided with

[0167] a second molecular structure estimation unit that estimates the structure of the molecule of the sample based on an electron beam diffraction image obtained by irradiation of the sample with an electron beam of a different energy.

[0168] In the mass spectrometers described in Items 10 and 11, by performing electron beam diffraction measurement using electron beams of different energies, different electron beam diffraction images can be obtained for the same molecule, which can be used for molecular structure analysis.

[0169] (Item 12)

[0170] The mass spectrometer according to any one of items 7 to 11 further comprising

[0171] The third molecular structure estimating unit 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.

[0172] In the mass spectrometer described in Item 12, an atom having a larger atomic number and scattering more electrons is added as the above-mentioned predetermined type of atom to a position of interest within the molecule (for example, at or near a position where the structures between isomers are different), thereby making the scattering of the electron beam caused by the atom larger, and enabling interference fringes reflecting the structure of interest to be obtained with high intensity.

[0173] (Item 13)

[0174] The mass spectrometer according to any one of items 1 to 12 further comprising

[0175] The separation mechanism separates compounds contained in the sample before mass separation of the ions in the mass separation section.

[0176] (Item 14)

[0177] In the mass spectrometer described in Item 13,

[0178] The separation mechanism is a chromatography device and / or an ion mobility analyzer.

[0179] In the mass spectrometer described in the 13th item, since the compounds contained in the sample are separated from each other and introduced into the ion source, only the compounds to be measured are screened, and the influence of other compounds can be eliminated, thereby performing mass analysis and electron beam diffraction measurement with higher accuracy. As such a separation mechanism, a chromatographic device (such as a liquid chromatograph, a gas chromatograph) or an ion mobility spectrometer can be used as described in the 14th item. In addition, when the separation mechanism is a chromatographic device, after the compounds contained in the sample are separated, each compound is introduced into the ionization unit for ionization. In this case, the separation mechanism is configured in the front stage of the mass spectrometer. On the other hand, when the separation mechanism is an ion mobility spectrometer, after the compounds contained in the sample are ionized in the ionization unit, the ions derived from each compound are separated by the ion mobility spectrometer and introduced into the mass separation unit. In this case, the separation mechanism is configured between the ionization unit and the mass separation unit of the mass spectrometer. In this way, the separation of the above-mentioned compounds also includes the formation of the ions derived from each compound.

[0180] Depending on the type of isomers, separation may be possible using a chromatographic column in a chromatographic apparatus. However, since information on the molecular structure of the compound cannot be obtained through separation using a chromatographic apparatus alone, electron beam diffraction measurement is also performed to obtain information on the molecular structure of the compound, thereby enabling analysis of the compounds contained in the sample with higher accuracy.

[0181] In addition, although isomers can be identified in the ion mobility analysis device, there are many cases where the theoretical value of the size of the collision cross-sectional area of ​​the ion is inconsistent with the measured value. In addition, the measured value of the collision cross-sectional area also varies according to the composition of the device (e.g., each manufacturer) and the type of gas that ions collide with. Therefore, it is sometimes difficult to compare the size of the collision cross-sectional area of ​​the ion obtained by measurement with the value included in the database and it is impossible to identify the molecular structure. By combining the ion mobility analysis device with the mass spectrometer of the present invention, it is possible not only to obtain the size of the collision cross-sectional area of ​​the ion, but also to obtain molecular structure information by electron beam diffraction measurement, thereby being able to parse the compound contained in the sample with higher accuracy.

[0182] Description of Reference Numerals

[0183] 1. Mass analysis device

[0184] 10 Device body

[0185] 20 Ionization chamber

[0186] 21. The 1st intermediate vacuum chamber

[0187] 22. Second intermediate vacuum chamber

[0188] 23 Analysis Room

[0189] 231 Front stage quadrupole mass filter

[0190] 232 Collision Cell

[0191] 234 quadrupole electrode

[0192] 235 Post-stage quadrupole mass filter

[0193] 236 Deflection Unit

[0194] 2361 Rod Electrode

[0195] 237 Ion Detector

[0196] 30 Electron beam irradiation unit

[0197] 301 electron gun

[0198] 302 electron lens

[0199] 31 Ion Trap

[0200] 311 Ring Electrode

[0201] 312 Inlet side end cover electrode

[0202] 313 outlet side end cover electrode

[0203] 316 Vacuum Tank

[0204] 317 Gas inlet

[0205] 32 Electron beam detection unit

[0206] 321 Faraday Cup

[0207] 322 Microchannel Plate

[0208] 323 fluorescent screen

[0209] 324 CCD camera

[0210] 4 Control and processing department

[0211] 41 Storage

[0212] 411 Compound Database

[0213] 42 Quality Analysis Procedures

[0214] 43 Measurement condition setting section

[0215] 44 Measurement Control Department

[0216] 45 Analysis Processing Unit

[0217] 46 electron beam diffraction image estimation unit

[0218] 47 molecular structure estimation unit

[0219] 471 first molecular structure estimation unit

[0220] 472 second molecular structure estimation unit

[0221] 473 third molecular structure estimation unit

[0222] 5 voltage application unit

[0223] 6 input unit

[0224] 7 display unit

Claims

1. A mass analysis device, characterized in that have: an ionization unit for generating ions from a sample; a mass separation unit for performing mass separation on the ions generated by the ionization unit; an ion detector for detecting ions separated by mass by the mass separation section; an ion trapping section for capturing ions separated by mass by the mass separation section; a sub-measuring unit for measuring physical quantities other than the mass-to-charge ratio of the ions trapped by the ion trapping unit, The mass separation unit comprises: a front-stage mass separation section for selecting ions having a specific mass-to-charge ratio from the ions generated by the ionization section as precursor ions; a dissociation unit for dissociating the precursor ions to generate product ions; The post-stage mass separation section selects ions with a specific mass-to-charge ratio from the product ions.

2. The mass spectrometer according to claim 1, wherein further comprising a deflection unit provided between the mass separation unit and the ion detector, for deflecting the flight direction of ions emitted from the mass separation unit, The ion trapping portion is provided on a flight path of the ions whose flight directions are deflected by the deflecting portion.

3. The mass spectrometer according to claim 1, wherein The device further includes a voltage application unit configured to apply a rectangular wave voltage for trapping ions in the ion trapping unit.

4. The mass spectrometer according to claim 1, wherein The auxiliary measuring unit includes: an irradiation unit for irradiating the ions captured in the ion capture unit with electromagnetic waves or particle beams; The detection unit detects electromagnetic waves or particles emitted from the ion trapping unit.

5. The mass spectrometer according to claim 1, wherein A voltage applying unit is further provided for applying a rectangular wave voltage for trapping ions to the ion trapping unit. The auxiliary measuring unit includes: an irradiation unit for irradiating the ions captured in the ion capture unit with electromagnetic waves or particle beams; a detection unit for detecting electromagnetic waves or particles emitted from the ion trapping unit, When a rectangular wave voltage of a predetermined phase is applied from the voltage applying unit to the ion trapping unit, the irradiating unit irradiates the interior of the ion trapping unit with a pulsed electromagnetic wave or a particle beam.

6. The mass spectrometer according to claim 4, wherein 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.

7. The mass spectrometer according to claim 6, wherein Further possess: a molecular structure candidate input accepting unit for accepting input of information on molecular structure candidates; The first molecular structure estimating unit compares an electron beam diffraction image obtained by measuring a sample with an electron beam diffraction image prepared in advance for the molecular structure candidate, thereby estimating the molecular structure of a molecule contained in the sample.

8. The mass spectrometer according to claim 7, wherein The device further includes an electron beam diffraction image estimating unit that estimates an electron beam diffraction image by theoretical calculation based on the molecular structure accepted by the molecular structure candidate input accepting unit.

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

10. The mass spectrometer according to claim 9, wherein The device further includes a second molecular structure estimating unit for estimating the structure of the sample molecule based on electron beam diffraction images obtained by irradiation with electron beams of different energies.

11. The mass spectrometer according to claim 6, wherein The method further includes a third molecular structure estimating unit for estimating 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.

12. The mass spectrometer according to claim 11, wherein The device further includes a separation mechanism for separating compounds contained in the sample before mass separation of the ions in the mass separation unit.

13. The mass spectrometer according to claim 12, wherein The separation mechanism is a chromatography device and / or an ion mobility analyzer.

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