Orthogonal acceleration time-of-flight mass spectrometer and adjustment method thereof

Abstract

To obtain both of high measurement sensitivity and high mass resolution in an orthogonal acceleration time-of-flight mass spectrometer.SOLUTION: An orthogonal acceleration time-of-flight mass spectrometer 1 comprises: an ion source 201; an orthogonal acceleration electrode 242 which deflects the flight direction of ions; flight path regulation electrodes 244, 246, 247 which regulate a flight path of the deflected ions; an ion detection unit 245 which detects the ions flying in the flight path; a voltage application unit 3 which applies voltage to the orthogonal acceleration electrode and the flight path regulation electrodes; a measurement control unit 43 which acquires mass spectral data by measuring a prescribed known ion generated from a prescribed amount of a known sample under a plurality of measurement conditions with different values of the voltage applied to the orthogonal acceleration electrode from the voltage application unit; and a score value calculation unit 44 which calculates a score value on the basis of a prescribed calculating formula by using the intensity of a mass peak and the mass resolution in the mass spectral data acquired in each of the plurality of measurement conditions.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to an orthogonal acceleration time-of-flight mass spectrometer. [Background technology]

[0002] Mass spectrometers are used to identify unknown compounds in samples and quantify known compounds. Mass spectrometers ionize various compounds in a liquid sample, for example by imparting an electric charge to the liquid sample and spraying it. Then, the ions are separated according to their mass-to-charge ratio and the intensity of the ions is measured for each mass-to-charge ratio. Based on the measurement data obtained in this way, a mass spectrum is created by plotting a graph with the mass-to-charge ratio of the ions and the measured intensity on two axes. Unknown compounds are then identified based on the mass-to-charge ratios of the mass peaks in the mass spectrum, and known compounds are quantified based on the intensities of the mass peaks.

[0003] A mass spectrometer is composed of units such as an ionization unit, an ion transport optical system, a mass separation unit, and an ion detection unit, each of which is equipped with electrodes for forming an electric field to focus ions. Immediately after installing a mass spectrometer or before measuring trace amounts of target compounds contained in a sample, the voltages applied to the electrodes in each unit of the mass spectrometer are adjusted and optimized. Patent Document 1 describes a method for automatically adjusting the voltages applied to each electrode. In this autotuning method, a sample containing a predetermined amount of a standard substance is introduced into the mass spectrometer, and the intensity of a predetermined known ion generated from the standard substance is measured while varying the voltage applied to each electrode. The voltage applied to each electrode is then determined to maximize the measured ion intensity (maximize measurement sensitivity).

[0004] Orthogonal acceleration time-of-flight mass spectrometers are used to separate compounds contained in a sample with high mass resolution. In an orthogonal acceleration time-of-flight mass spectrometer, ions generated in an ion source are deflected orthogonally by an orthogonal acceleration unit, imparting a certain amount of kinetic energy to the ions, leading to a predetermined flight path. The intensities of the ions traveling along the measurement flight path are then measured sequentially. Multiple ions are supplied from the ion source to the orthogonal acceleration unit as a group of ions, and the ions in each group enter the orthogonal acceleration unit with a certain degree of spread. Because the multiple ions are deflected in a direction perpendicular to the direction of incidence in the orthogonal acceleration unit and fly within the measurement flight space, high mass resolution can be achieved without being affected by the spread of ions within the group with respect to the direction of incidence into the orthogonal acceleration unit. Patent documents 2 and 3 describe adjusting the voltage applied to each electrode in such an orthogonal acceleration time-of-flight mass spectrometer to maximize the ion detection intensity or maximize the ion mass resolution. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Publication No. 2018-120804 [Patent Document 2] International Publication No. 2004 / 030025 [Patent Document 3] U.S. Patent Application Publication No. 2021 / 0111013 Summary of the Invention [Problem to be solved by the invention]

[0006] In mass analyzers that separate ions by mass using a quadrupole electric field, and in ion trap time-of-flight mass analyzers that release ions captured in an ion trap into flight space, high mass resolution can be achieved by adjusting the voltage applied to each electrode to maximize ion detection intensity. Alternatively, high sensitivity can be achieved by adjusting the measurement parameters to maximize mass resolution. However, in orthogonal acceleration time-of-flight mass analyzers, optimizing the measurement parameters to maximize ion measurement sensitivity does not necessarily optimize mass resolution, and it has been found that optimizing the measurement parameters to maximize ion mass resolution does not necessarily optimize measurement sensitivity.

[0007] The problem to be solved by the present invention is to provide a technique that can obtain both high measurement sensitivity and high mass resolution in an orthogonal acceleration time-of-flight mass spectrometer. [Means for solving the problem]

[0008] The method for adjusting an orthogonal acceleration time-of-flight mass spectrometer according to the present invention, which has been made to solve the above problems, comprises: generating predetermined known ions from a sample in an ion source; applying a voltage to an orthogonal acceleration electrode to deflect the flight direction of ions incident from the ion source, causing the ions to fly along a flight path defined by a flight path defining electrode; detecting mass-separated ions while they fly along the flight path to obtain mass spectrum data; calculating a score value based on a predetermined calculation formula using the intensity and mass resolution of the mass peak of the known ion in the mass spectrum data; Including, calculating the score value for each of a plurality of measurement conditions in which the voltage applied to the orthogonal acceleration electrodes is different; A value of a voltage to be applied to the orthogonal acceleration electrodes is determined based on the score value calculated for each of the plurality of measurement conditions. It is something.

[0009] Furthermore, the orthogonal acceleration time-of-flight mass spectrometer according to the present invention comprises: an ion source; an orthogonal acceleration electrode for deflecting the flight direction of ions incident from the ion source; a flight path defining electrode for defining a flight path of the ions deflected by the orthogonal acceleration electrode; an ion detection unit that detects ions that have flown along the flight path; a voltage application unit that applies voltages to the orthogonal acceleration electrodes and the flight path defining electrodes; a measurement control unit that acquires mass spectrum data by measuring predetermined known ions generated from a predetermined amount of a known sample under a plurality of measurement conditions in which the voltage applied from the voltage application unit to the orthogonal acceleration electrode is different; and a score calculation unit that calculates a score based on a predetermined formula using the intensities and mass resolutions of mass peaks in the mass spectrum data acquired under each of the plurality of measurement conditions; Equipped with. [Effects of the Invention]

[0010] The orthogonal acceleration time-of-flight mass spectrometer according to the present invention includes an ion source, orthogonal acceleration electrodes that deflect the flight direction of ions incident from the ion source, flight path defining electrodes that define the flight path of ions deflected by the orthogonal acceleration electrodes, and an ion detector that detects ions that have traveled along the flight path. The orthogonal acceleration electrodes include, for example, a push electrode that is located on the opposite side of the flight space across the central axis of the flight path of ions incident from the ion source, and a pull electrode that is located on the flight space side. The flight path defining electrodes also include, for example, a flight tube that is located on the outer edge of the flight space. In a reflectron-type mass spectrometer, the flight path defining electrodes also include, for example, a reflectron or backplate that folds back the flight path of ions.

[0011] Assuming that the same amount of ions generated in the ion source are all detected by the ion detector, the area of ​​the mass peak in the mass spectrum data will always be constant, and the peak width of the mass peak will be narrowest when the mass peak is at its highest. In other words, both the highest measurement intensity and the highest mass resolution can be obtained. However, in an orthogonal acceleration time-of-flight mass spectrometer, for example, if the mass resolution is increased by changing the value of the voltage applied to the orthogonal acceleration electrodes, a situation may arise in which some of the ions incident on the orthogonal acceleration electrodes are not introduced into the flight space, resulting in a decrease in the measurement intensity. Conversely, if an attempt is made to increase the measurement intensity by introducing more ions into the flight space, the mass resolution may decrease. Therefore, even if the same amount of ions are generated in the ion source, the orthogonal acceleration voltage Extremely The amount of ions that reach the ion detector can vary greatly depending on the applied voltage. Therefore, in an orthogonal acceleration time-of-flight mass spectrometer, optimizing the measurement parameters to maximize ion measurement sensitivity can result in poor mass resolution, and vice versa.

[0012] In the present invention, mass spectrum data is obtained by measuring predetermined known ions generated from a predetermined amount of a known sample under a plurality of measurement conditions in which the voltage applied to the orthogonal acceleration electrodes is different. Then, a score value is calculated based on a predetermined formula using the intensities and mass resolution of the mass peaks in the mass spectrum data obtained under each of the plurality of measurement conditions. In this way, the score value is calculated taking into account both the intensities and mass resolution of the known ions, and therefore, by determining the value of the voltage applied to the orthogonal acceleration electrodes based on the calculated score value, both high measurement sensitivity and high mass resolution can be obtained. [Brief explanation of the drawings]

[0013] [Figure 1] 1 is a diagram showing the configuration of a main part of an embodiment of an orthogonal acceleration time-of-flight mass spectrometer according to the present invention; [Figure 2]FIG. 2 is a diagram for explaining the potential of each electrode arranged in the analysis chamber in the orthogonal acceleration time-of-flight mass spectrometer of the present embodiment. [Figure 3] FIG. 10 is a diagram illustrating the flight paths of ions when the axis of the ion lens is misaligned. [Figure 4] An example of the flight path of ions in the orthogonal acceleration space. [Figure 5] Another example of the flight path of ions in the orthogonal acceleration space. [Figure 6] 10 is a graph showing the relationship between the voltage applied to the second accelerating electrode and the measured values ​​of mass peak intensity and mass resolution. [Figure 7] 10 is a graph showing the relationship between the voltage applied to the second accelerating electrode and the normalized values ​​of mass peak intensity and mass resolution. [Figure 8] 10 is a graph showing the relationship between the voltage applied to the second accelerating electrode and the score value obtained according to the present embodiment. DETAILED DESCRIPTION OF THE INVENTION

[0014] An embodiment of an orthogonal acceleration time-of-flight mass spectrometer and an adjustment method thereof according to the present invention will be described below with reference to the drawings.

[0015] 1 shows a schematic configuration of an orthogonal acceleration time-of-flight mass spectrometer (OA-TOF-MS) 1 of this embodiment. The OA-TOF-MS 1 of this embodiment roughly comprises a mass analysis unit 2, a voltage application unit 3, and a control and processing unit 4 that controls the operations of these units.

[0016] The mass spectrometric section 2 includes an ionization chamber 20 and a vacuum chamber, which are at approximately atmospheric pressure. Inside the vacuum chamber, in order from the ionization chamber 20 side, there are a first intermediate vacuum chamber 21, a second intermediate vacuum chamber 22, a third intermediate vacuum chamber 23, and an analysis chamber 24. Each of these chambers is evacuated by a vacuum pump (not shown), and has a multi-stage differential pumping system configuration in which the degree of vacuum increases stepwise from the first intermediate vacuum chamber 21 to the analysis chamber 24.

[0017] An electrospray ionization probe (ESI probe) 201 that imparts an electric charge to a liquid sample and sprays it as charged droplets is placed in the ionization chamber 20. The ionization chamber 20 and first intermediate vacuum chamber 21 are connected via a desolvation tube 202, which is a thin-diameter capillary. A curtain of gas heated from a gas source (not shown) is sprayed onto the desolvation tube 202, and the charged droplets sprayed from the ESI probe 201 are desolvated and ionized as they pass from the ionization chamber 20 through the desolvation tube 202 and enter the first intermediate vacuum chamber 21.

[0018] An ion guide 211 consisting of a plurality of ring electrodes is disposed in the first intermediate vacuum chamber 21. Ions that enter the first intermediate vacuum chamber 21 are converged by the ion guide 211 so that they fly along the ion optical axis C. 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. Ions converged by the ion guide 211 pass through the skimmer 212 and enter the second intermediate vacuum chamber 22.

[0019] An ion guide 221 made up of a plurality of rod electrodes is disposed in the second intermediate vacuum chamber 22. Ions that enter the second intermediate vacuum chamber 22 are focused by the ion guide 221 so that they fly along the ion optical axis C. The second intermediate vacuum chamber 22 and the third intermediate vacuum chamber 23 are separated by a partition wall having an opening located on the ion optical axis C. Ions focused by the ion guide 221 enter the third intermediate vacuum chamber 23 through this opening.

[0020] The third intermediate vacuum chamber 23 is equipped with a quadrupole mass filter 231 that separates ions according to their mass-to-charge ratio, a collision cell 232 equipped with a multipole ion guide 233 therein, and an ion guide 234 made up of multiple ring electrodes. Collision-induced dissociation (CID) gas such as argon or nitrogen is supplied to the interior of the collision cell 232 from a gas source (not shown) as needed. For example, in MS / MS analysis, ions having a specific mass-to-charge ratio among the ions that have entered the third intermediate vacuum chamber 23 are selected as precursor ions by the quadrupole mass filter 231 and enter the collision cell 232. In the collision cell 232, the precursor ions collide with the CID gas, and the ions are separated into precursor ions. Tips The product ions generated in the collision cell 232 are converged by the ion guide 234 to fly along the ion optical axis C and enter the analysis chamber 24.

[0021] The analysis chamber 24 is equipped with an ion lens 241 composed of multiple ring electrodes, an orthogonal acceleration electrode 242 composed of a pusher electrode 2421 and a puller electrode 2422, a second acceleration electrode 243, a reflectron 244, a flight tube 246, a back plate 247, and an ion detector 245. The pusher electrode 2421 is a plate-shaped electrode, and the puller electrode 2422 is a plate-shaped electrode overall with an ion passage formed in the center. The second acceleration electrode 243 has multiple ring-shaped electrodes and a slit located behind it. The reflectron 244 is composed of a first reflectron 2441 and a second reflectron 2442, both of which are multiple ring-shaped electrodes. The flight tube 246 is a cylindrical electrode, and the back plate 247 is a plate-shaped electrode.

[0022] Ions that have entered the analysis chamber 24 are focused along the ion optical axis C by the ion lens 241, and then enter the space between the push electrode 2421 and the pull electrode 2422 (orthogonal acceleration space).

[0023] A pulse voltage is applied to the pusher electrode 2421 at a constant cycle. The application of this pulse voltage creates an electric field in the orthogonal acceleration space that deflects the flight direction of the ions in an orthogonal direction (from the pusher electrode 2421 toward the puller electrode 2422). The ions whose flight direction is deflected by the orthogonal acceleration electrode 242 are given a certain amount of kinetic energy by an acceleration electric field formed by a voltage applied to the second acceleration electrode 243, and then travel along a return flight path defined by the reflectron 244, flight tube 246, and back plate 247 and enter the ion detector 245. Since ions with smaller mass-to-charge ratios fly faster, the ions are separated according to their respective mass-to-charge ratios while flying along their flight path, and are incident on the ion detector 245 and detected in order of decreasing mass-to-charge ratio.

[0024] The voltage application unit 3 applies a predetermined voltage to each electrode of the mass analysis unit 2 based on a control signal sent from the control / processing unit 4 .

[0025] The control and processing unit 4 has a memory unit 41 and, as functional blocks, a tuning condition setting unit 42, a measurement control unit 43, a score value calculation unit 44, and a voltage determination unit 45. The actual entity of the control and processing unit 4 is a personal computer, and the above functional blocks operate by executing a mass analysis program pre-installed in the computer. Also connected to the control and processing unit 4 are an input unit 6 including a keyboard, a mouse, etc., and a display unit 7 consisting of a liquid crystal display, etc.

[0026] The memory unit 41 stores measurement conditions for various compounds (precursor ions in MRM measurement and product It stores information such as the mass-to-charge ratio of the ions (e.g., mass-to-charge ratio of MRM transitions), and information (formulas, tables, etc.) that shows the relationship between the flight time of the ions in the measurement flight space and their mass-to-charge ratio. In addition, it stores information such as the initial setting of the voltage applied to each electrode during tuning, the step width during voltage scanning (e.g., 1 V), the scanning range (e.g., ±50 V), and the intensity and resolution during voltage scanning.

[0027] The OA-TOF-MS1 of this embodiment is characterized by the adjustment of the voltages applied to each electrode disposed within the analysis chamber 24. In mass analyzers that separate ions by mass using a quadrupole electric field or ion trap time-of-flight mass analyzers that release ions captured in an ion trap into flight space, adjusting the voltages applied to each electrode to maximize ion detection intensity simultaneously achieves high mass resolution. Alternatively, adjusting measurement parameters to maximize mass resolution also achieves high sensitivity. However, in orthogonal acceleration time-of-flight mass analyzers, optimizing measurement parameters to maximize ion measurement sensitivity does not necessarily optimize mass resolution, and optimizing measurement parameters to maximize ion mass resolution does not necessarily optimize measurement sensitivity. This point will be explained below.

[0028] First, the voltages applied to each electrode in the analysis chamber 24 of the OA-TOF-MS1 will be described with reference to FIG. 2. Here, the case where ions exhibit ideal behavior will be described as an example. The initial setting values ​​during tuning described above may be the voltage values ​​applied to each electrode when ions exhibit ideal behavior, or values ​​entered specifically for the device by an engineer may be used as the initial setting values. The following explanation will explain the voltages applied to each electrode when the measurement target is positive ions. When the measurement target is negative ions, the magnitude relationship of the voltage values ​​applied to each electrode can be reversed.

[0029] Ions that have entered the analysis chamber 24 pass through the centers (on the ion optical axis C) of the plurality of lens electrodes that make up the ion lens 241 and enter the orthogonal acceleration space formed between the push electrode 2421 and the pull electrode 2422. As shown schematically in Figures 1 and 2, all ions that have entered the orthogonal acceleration space enter a single point at the center of the orthogonal acceleration space when a pulse voltage, which will be described later, is applied to the push electrode 2421.

[0030] A voltage V2 is constantly applied to the pull-in electrode 2422, and a pulse voltage V1 (V1>V2) is periodically applied to the push-out electrode 2421. This creates a potential gradient that descends from the push-out electrode 2421 toward the pull-in electrode 2422, thereby deflecting the flight direction of ions entering the orthogonal acceleration space in the orthogonal direction. During the time period (hereinafter referred to as the "standby time period") other than the time period when the pulse voltage is applied (hereinafter referred to as the "acceleration time period"), the same voltage V2 as that of the pull-in electrode 2422 is also applied to the push-out electrode 2421, and no potential gradient is formed between them.

[0031] In the second acceleration electrode 243, a voltage V3 (V2>V3) is applied to the electrode located closest to the pull-in electrode 2422, and a voltage is applied to each electrode so as to form a downward potential gradient toward the reflectron 244. As a result, the ions whose flight direction has been deflected by the orthogonal acceleration electrode 242 are accelerated toward the flight space surrounded by the flight tube 246, the reflectron 244, and the backplate 247.

[0032] A voltage V4 (V3>V4) is applied to the flight tube 246. Furthermore, a voltage is applied to the first reflectron 2441 located on the side facing the flight space, the second reflectron 2442 located on the backplate 247 side, and the backplate 247 so as to form an upward potential gradient from the flight tube 246 toward the backplate 247. A voltage V5 (V5>V4) is applied to the backplate 247.

[0033] Ions introduced into the flight space by the second acceleration electrode 243 fly through a substantially field-free space (field-free space) surrounded by the flight tube 246, and then enter a space (turn-around flight space) surrounded by the reflectron 244. Because an upward potential gradient is formed in the turn-around flight space, the ions gradually decelerate, reverse their flight direction, and head back toward the field-free space. After flying through the field-free space, they enter the ion detector 245.

[0034] If all ions behave ideally as described above, all ions entering the center of the orthogonal acceleration space will travel the same flight path and enter the ion detector 245. Furthermore, all ions with the same mass-to-charge ratio will travel this flight path for the same flight time and enter the ion detector 245 at the same time. However, in reality, due to the Coulomb repulsion between ions, a group of ions enters the orthogonal acceleration space with a certain degree of spatial spread. Furthermore, there is some variation in the flight direction and flight speed of each ion. Furthermore, depending on the assembly precision of the mass analyzer, some deviation may occur in the ion optical axis C.

[0035] When ions enter the orthogonal acceleration space in a spatially spread state, applying pulse voltage V1 to pusher electrode 2421 to form an electric field causes ions that are closer to pusher electrode 2421 to be imparted with more energy by the electric field and then to be incident on second acceleration electrode 243. In other words, the amount of energy imparted to an ion varies depending on the position of the ion at the time pulse voltage V1 is applied, resulting in variations in the kinetic energy of each ion after being accelerated by second acceleration electrode 243. In the case of a time-of-flight mass spectrometer that does not include reflectron 244 and causes ions to fly in a straight line, variations in the kinetic energy of ions directly result in variations in flight time, resulting in a decrease in mass resolution.

[0036] In an OA-TOF-MS1 such as this embodiment, the variation in ion kinetic energy due to the spatial spread of ions can be eliminated by appropriately setting the return electric field formed by the reflectron 244. Ions accelerated by the second acceleration electrode 243 fly through a field-free space surrounded by the flight tube 246 and then enter the return flight space surrounded by the reflectron 244. Because voltages are applied to the multiple electrodes constituting the reflectron 244 to form an upward potential gradient toward the back plate 247, ions entering the return flight space gradually lose kinetic energy and are then accelerated in the opposite direction. Ions with greater kinetic energy upon entering the return flight space penetrate deeper into the return flight space (closer to the back plate 247). In other words, ions with greater kinetic energy will travel a longer distance. Therefore, by appropriately setting the voltage applied to the reflectron 244, the OA-TOF-MS1 can compensate for differences in ion kinetic energy.

[0037] On the other hand, variations in the flight direction and flight speed of ions cannot be eliminated by the reflectron 244. When a pulse voltage V1 is applied to the push electrode 2421, ions flying along the ion optical axis C and ions flying toward the pull electrode 2422 are instantly accelerated toward the pull electrode 2422. On the other hand, ions flying toward the push electrode 2421 require time to change their flight direction toward the pull electrode 2422. This time is called the turnaround time. Thus, depending on the flight components of the ions, a time difference occurs before the ions start flying toward the second acceleration electrode 243. This time difference is not eliminated until the ions enter the ion detector 245, which causes a decrease in mass resolution.

[0038] If there is a deviation in the center positions of the multiple ring electrodes that make up the ion lens 241, the ions will enter the orthogonal acceleration space with a spatial spread centered on an axis C' that is tilted from the ion optical axis C, which is assumed to be ideally positioned. For example, as shown in FIG. 3, if the centers of the multiple ring electrodes that make up the ion lens 241 are shifted more toward the pusher electrode 2421 as the ring electrodes located further back are shifted, an ion group will enter the orthogonal acceleration space with a spatial spread centered on the axis C' that points toward the pusher electrode 2421, as shown in FIG. 4. Furthermore, most of the ions in this ion group will fly toward the pusher electrode 2421.

[0039] 4 shows the flight path of ions up to the time when pulse voltage V1 is applied to the pusher electrode 2421 when voltage V2 is applied to the pusher electrode 2421 during the standby period. The voltage V2 applied to the pusher electrode 2421 during the standby period is the same as the voltage V2 applied to the puller electrode 2422, and the orthogonal acceleration space is a field-free space. Therefore, ions that pass through the ion lens 241 and enter the acceleration flight space continue to fly while maintaining the flight direction and flight speed at the time of entry into the acceleration flight space until pulse voltage V1 is applied to the pusher electrode 2421. Therefore, the angular spread of the ion beam when it enters the orthogonal acceleration space almost directly results in variations in flight direction and flight speed, and the turnaround time caused by these variations reduces the mass resolution.

[0040] FIG. 5 shows the flight path of ions until a pulse voltage V1 is applied to the extrusion electrode 2421 when a voltage V6 (V6 < V2) is applied to the extrusion electrode 2421 during the standby period. Since the voltage V6 applied to the extrusion electrode 2421 during the standby period is lower than the voltage V2 applied to the retraction electrode 2422, the ions that pass through the ion lens 241 and enter the acceleration flight space fly while being gradually attracted toward the extrusion electrode 2421 until the pulse voltage V1 is applied to the extrusion electrode 2421. As a result, some of the ions included in the ion group collide with the extrusion electrode 2421 and disappear. However, on the other hand, the angular spread of the ions at the time when the pulse voltage V1 is applied to the extrusion electrode 2421 becomes smaller than when they enter the orthogonal acceleration space. As a result, the variations in the flight direction and flight speed become smaller, the mass resolution is improved compared to the case shown in FIG. 4, and the ion detection sensitivity decreases.

[0041] Thus, in the OA-TOF-MS1, depending on the positional relationship of each part in the apparatus and the behavior of ions, even if the value of the voltage applied to the orthogonal acceleration electrode 242 (particularly the extrusion electrode 2421) is tuned, both the ion sensitivity and the mass resolution may not necessarily be optimized under the same conditions. The explanation using FIGS. 4 and 5 is an example, and the same situation as above may occur due to other factors such as when the ion optical axis C' is shifted toward the retraction electrode 2422 side. Also, here, the situation caused by the voltage applied to the extrusion electrode 2421 during the standby period has been explained, but the behavior of ions may also change depending on the magnitude of the potential gradient formed by the voltages applied to the extrusion electrode 2421 and the retraction electrode 2422 during the acceleration period.

[0042] Similarly, in the second acceleration electrode 243, even if the value of the voltage applied to the second acceleration electrode 243 is tuned, both the ion sensitivity and the mass resolution may not necessarily be optimized. This point will be explained below.

[0043] For example, if the potential formed on the second acceleration electrode 243 is far from the high potential side from the potential gradient connecting the potentials of the pull-in electrode 2422 and the flight tube 246, the ions flying in the space (second acceleration space) surrounded by the second acceleration electrode 243 are likely to spread. This phenomenon is called the lens effect. Therefore, when the lens effect is generated, the ions are likely to collide with and disappear at the lens electrodes constituting the second acceleration electrode 243 or the slit at the exit thereof before reaching the exit of the second acceleration space. Therefore, the ion detection sensitivity is higher when the lens effect is not generated.

[0044] Flight by applying a single pulse voltage direction There is also some variation in the timing when each ion included in one ion group whose flight is changed enters the orthogonal acceleration space. Therefore, the ions that enter the orthogonal acceleration space earlier enter deeper along the central axis C' in the orthogonal acceleration space. At this time, for example, if a voltage V6 (V6 < V2) is applied in the standby time zone as shown in FIG. 5, prioritizing the mass resolution over the ion detection sensitivity, the ions that enter the orthogonal acceleration space earlier fly through the orthogonal acceleration space for a longer time. As a result, they enter deep into the orthogonal acceleration space and are attracted to the push-out electrode 2421. These ions are located in the upper right region A of the orthogonal acceleration space shown in FIG. 5 and have a large flight speed on the side opposite to the orthogonal acceleration direction. Since these ions have a long turnaround time during orthogonal acceleration, the mass resolution decreases when they enter and are detected by the ion detector 245.

[0045] The ions that have entered deep into the orthogonal acceleration space enter a position close to the side of the ion detector 245 in the second acceleration space. Therefore, if the lens effect is generated in the second acceleration space by the voltage applied to the second acceleration electrode 243, the ions are likely to collide with the lens electrodes or the slit constituting the second acceleration electrode 243. Therefore, when the lens effect is generated in the second acceleration electrode 243, the ions with a large turnaround time disappear and the mass resolution is improved.

[0046] In this embodiment, tuning is performed in consideration of the above circumstances. The procedure for tuning will be described below.

[0047] When the user instructs the start of tuning, the tuning condition setting unit 42 displays a screen on the display unit 7 that prompts the user to input tuning conditions. This screen prompts the user to set weighting coefficients to be applied to the value calculated from the ion detection sensitivity and the value calculated from the mass resolution in the calculation of the score value, which will be described later. When the user inputs a value X greater than 0 and less than 1 for the ion detection sensitivity, the mass resolution is automatically set to the value 1-X. As a result, the following mathematical formula (1) for calculating the score value Z is created and stored in the memory unit 41. Z=X*I+(1-X)*R …(1) where I is the normalized intensity of the mass peak of an ion derived from a standard substance with a given mass-to-charge ratio, R is quality This is a normalized value of the mass resolution. Of course, the user may input a value X greater than 0 and less than 1 for the mass resolution, and the ion detection sensitivity may be automatically set to the value 1-X.

[0048] When the user sets a predetermined standard sample and issues a command to start measurement, the measurement control unit 43 reads out the initial setting values ​​stored in the memory unit 41 for each of the electrodes constituting the OA-TOF-MS1, and performs measurement with those voltages applied to each electrode. In this measurement, a standard sample containing a predetermined amount of standard substance is continuously introduced into the ESI probe 201 to generate ions, and voltages are applied to each electrode including the orthogonal acceleration electrode 242 to make the ions fly along a predetermined flight path, and mass spectrum data is obtained by detecting the ions that have flown along that flight path. Next, the mass peaks of known ions having a predetermined mass-to-charge ratio are identified from the obtained mass spectrum data. Then, the identified known ions are analyzed. stomach The mass peak intensity is calculated from the height and area of ​​the mass peak of the ion, and the mass resolution is calculated from the mass-to-charge ratio value of the known ion and the peak width.

[0049] Once the mass spectrum data has been calculated for the initial setting, the measurement control unit 43 sets a plurality of measurement conditions, each with a different applied voltage to at least one electrode, by varying the voltage applied to each electrode located between the ESI probe 201 and the ion lens 241 by a predetermined value (e.g., 5% of the initial setting). Then, in the same manner as above, ions with a predetermined mass-to-charge ratio generated from the standard substance in the standard sample are measured to obtain mass spectrum data. The reason for initially tuning the voltage applied to each electrode located between the ESI probe 201 and the ion lens 241 is that slight changes in the voltage applied to each electrode do not result in a large loss of ions.

[0050] Assuming that all ions generated in the ionization chamber 20 are always detected by the ion detector 245 regardless of the measurement conditions, the area of ​​the mass peak in the mass spectrum data is always constant, and the peak width of the mass peak is narrowest when the mass peak is highest. In other words, both the highest measurement intensity and the highest mass resolution can be obtained. However, as described above, changing the voltages applied to the orthogonal acceleration electrode 242 and the second acceleration electrode 243 can result in the loss of many ions, significantly changing the ion measurement sensitivity and / or mass resolution. Furthermore, changing the voltages applied to these electrodes can also change the flight path of ions accelerated by the second acceleration electrode 243. Therefore, in this embodiment, the voltages applied to each electrode located between the ESI probe 201 and the ion lens 241 are first tuned, and the voltages to be applied to these electrodes are then determined. After this, the voltages to be applied to each electrode in the analysis chamber 24 are tuned.

[0051] After acquiring mass spectrum data for each of the multiple measurement conditions, the intensity and mass resolution of the mass peak of the known ion in each mass spectrum data are calculated. Next, the score calculation unit 44 normalizes the intensity values ​​of the mass peaks in the other mass spectrum data using the intensity value of the highest mass peak among all the mass spectrum data as a reference. This calculates the value I in the above formula (1). Similarly, for the mass resolution, the mass resolution values ​​of the other mass spectrum data are normalized using the highest mass resolution among all the mass spectrum data as a reference. The score value for each measurement condition is calculated by substituting the calculated mass peak intensity value I and mass resolution value R into the above formula (1). Then, based on the measurement condition with the highest score value, the value of the voltage applied to each electrode located between the ESI probe 201 and the ion lens 241 is determined.

[0052] Next, the voltages applied to the reflectron 244, flight tube 246, and back plate 247 located within the analysis chamber 24 are tuned. The voltages determined as described above are applied to each electrode located between the ESI probe 201 and the ion lens 241, and initial voltage values ​​are applied to the orthogonal acceleration electrode 242 and the second acceleration electrode 243. Then, multiple measurement conditions with different combinations of applied voltages are set for the reflectron 244, flight tube 246, and back plate 247, and mass spectrum data is acquired under each measurement condition. Next, the mass peak intensity and mass resolution of ions with the specified mass-to-charge ratio are calculated from each mass spectrum data. The score calculation unit 44 then normalizes the mass peak intensity and mass resolution values, respectively, using the same method as described above to calculate a score. Finally, the voltages applied to the reflectron 244, flight tube 246, and back plate 247 are determined based on the measurement condition with the highest score.

[0053] These electrodes located within the analysis chamber 24 define the ion's return flight path, and the voltage applied to the reflectron 244 and back plate 247 is related to the height of the potential gradient along the return flight path. The height of the potential gradient along the return flight path affects the ion's penetration depth, but slight changes in this potential gradient are unlikely to result in ion loss. Furthermore, the flight tube 246 is designed to create a flight space essentially free of electric fields, and the applied voltage is unlikely to result in ion loss. Therefore, the voltages applied to these electrodes are tuned before tuning the voltages applied to the orthogonal acceleration electrode 242 and the second acceleration electrode 243. Here, as described above, for each of the mass spectrum data obtained under multiple measurement conditions, a value I normalized to the mass peak intensity and a value R normalized to the mass resolution are calculated, and a score is calculated using the above formula (1). The voltages to be applied to the reflectron 244, flight tube 246, and back plate 247 are then determined based on the measurement condition that yielded the highest score.

[0054] Then, similarly to the above, multiple measurement conditions with different combinations of voltage values ​​are set for the orthogonal acceleration electrode 242 and the second acceleration electrode 243, and mass spectrum data is acquired under each measurement condition. Then, from each mass spectrum data, the mass peak intensity and mass resolution of ions with the predetermined mass-to-charge ratio are calculated. The score value calculation unit 44 then normalizes the mass peak intensity value and mass resolution value, respectively, using the same method as above, to calculate a score value. Finally, the values ​​of the voltages applied to the orthogonal acceleration electrode 242 and the second acceleration electrode 243 are determined based on the measurement condition with the highest score value.

[0055] The above process completes tuning of the voltages applied to the electrodes constituting the OA-TOF-MS1. However, as described above, changing the voltages applied to the orthogonal acceleration electrode 242 and the second acceleration electrode 243 changes the flight path of the ions. Therefore, the previously tuned voltages applied to the reflectron 244, flight tube 246, and backplate 247 may not necessarily be optimal. Therefore, it is preferable to re-tune the voltages applied to these electrodes.

[0056] Therefore, for the voltage values ​​to be applied to the reflectron 244, flight tube 246, and back plate 247, multiple voltage values ​​are set again around the previously determined voltage value, each differing by a predetermined value (for example, 3% of the previously determined voltage value), and multiple measurement conditions are set with different combinations of voltage values ​​to be applied to the reflectron 244, flight tube 246, and back plate 247.Once again, as above, the measurement condition that results in the highest score value is identified, and the voltage values ​​to be applied to the reflectron 244, flight tube 246, and back plate 247 are determined.

[0057] In the OA-TOF-MS1 of this embodiment, the voltages applied to the electrodes are tuned by performing the above processes, thereby determining the optimal combination of applied voltages that satisfies tuning conditions that are weighted by the user for ion detection sensitivity and mass resolution.

[0058] Here, an actual example in which the voltage applied to the second accelerating electrode 243 is tuned will be described.

[0059] 6 is a graph showing the results of obtaining mass spectrum data under a plurality of measurement conditions in which different voltages are applied to the second accelerating electrode 243, and determining the mass peak intensity and mass resolution of ions with a predetermined mass-to-charge ratio. In the example shown in Fig. 6, the applied voltage value at which the mass peak intensity is maximized is different from the applied voltage value at which the mass resolution is maximized.

[0060] Therefore, as shown in Figure 7, the mass peak intensity and mass resolution in each mass spectrum data are normalized using the maximum mass peak intensity and maximum mass resolution value obtained from multiple mass spectrum data as the reference values, respectively. In Figure 7, the normalized values ​​I and R are referred to as normalization parameters.

[0061] The score value is then calculated using the above formula (1) with the weighting coefficient set by the user. Figure 8 is a graph plotting score values ​​(scoring parameters) when the coefficient X for the normalized value I of the mass peak intensity is set to 0.3 and the coefficient 1-X for the normalized value R of the mass resolution is set to 0.7. By calculating the score value in this way and determining the applied voltage that maximizes the score value, the user can determine the optimal applied voltage value for balancing ion detection sensitivity and mass resolution. In Figure 8, the normalized values ​​I, R, and score value Z are referred to as normalization parameters.

[0062] The above embodiment is merely an example and can be modified as appropriate in accordance with the spirit of the present invention.

[0063] In the above embodiment, the electrodes located between the ESI probe 201 and the ion lens 241 are grouped as one electrode group, the reflectron 244, the flight tube 246, and the back plate 247 are grouped as another electrode group, and the orthogonal acceleration electrode 242 and the second acceleration electrode 243 are grouped as another electrode group, and the voltage values ​​applied to each electrode group are tuned in order, and then the voltage values ​​applied to the reflectron 244, the flight tube 246, and the back plate 247 are tuned again. However, the combination of electrodes included in one electrode group can be changed as appropriate. For example, the orthogonal acceleration electrode 242 and the second acceleration electrode 243 may be grouped as separate electrode groups, and the voltages applied to them may be tuned individually.

[0064] In the above embodiment, the score values ​​were calculated for all three electrode groups using the above formula (1). However, in cases where ions are unlikely to disappear even when different applied voltages are applied, such as in the case of electrodes located between the ESI probe 201 and the ion lens 241, tuning may be performed to optimize either the ion detection sensitivity (mass peak intensity) or the mass separation function.

[0065] In the above embodiment, the intensity of the highest mass peak and the highest mass resolution among all mass spectrum data are used as the reference values ​​to normalize the intensity and mass resolution of the mass peaks in the other mass spectrum data, but normalization may also be performed using a preset reference value. In this case, a score value can be calculated each time a piece of mass spectrum data is acquired.

[0066] In the above embodiment, the ESI probe 201 is used as the ion source, but other ion sources may be provided. Furthermore, the sample to be measured is not limited to a liquid, and may be a gas or solid. Furthermore, in the OA-TOF-MS1 of the above embodiment, it is essential that the analysis chamber 24 is provided with the orthogonal acceleration electrode 242, and that electrodes that define the flight path of ions deflected by the orthogonal acceleration electrode 242 are provided, but other components such as the electrodes may be changed as appropriate.

[0067] [Aspect] It will be apparent to those skilled in the art that the above-described exemplary embodiments are examples of the following aspects.

[0068] (Section 1) An orthogonal acceleration time-of-flight mass spectrometer according to one aspect of the present invention comprises: an ion source; an orthogonal acceleration electrode for deflecting the flight direction of ions incident from the ion source; a flight path defining electrode for defining a flight path of the ions deflected by the orthogonal acceleration electrode; an ion detection unit that detects ions that have flown along the flight path; a voltage application unit that applies voltages to the orthogonal acceleration electrodes and the flight path defining electrodes; a measurement control unit that acquires mass spectrum data by measuring predetermined known ions generated from a predetermined amount of a known sample under a plurality of measurement conditions in which the voltage applied from the voltage application unit to the orthogonal acceleration electrode is different; and a score calculation unit that calculates a score based on a predetermined formula using the intensities and mass resolutions of mass peaks in the mass spectrum data acquired under each of the plurality of measurement conditions; Equipped with.

[0069] (Section 6) A method for adjusting an orthogonal acceleration time-of-flight mass spectrometer according to one aspect of the present invention includes the steps of: generating predetermined known ions from a sample in an ion source; applying a voltage to an orthogonal acceleration electrode to deflect the flight direction of ions incident from the ion source, causing the ions to fly along a flight path defined by a flight path defining electrode; detecting mass-separated ions while they fly along the flight path to obtain mass spectrum data; calculating a score value based on a predetermined calculation formula using the intensity and mass resolution of the mass peak of the known ion in the mass spectrum data; Including, calculating the score value for each of a plurality of measurement conditions in which the voltage applied to the orthogonal acceleration electrodes is different; A value of a voltage to be applied to the orthogonal acceleration electrodes is determined based on the score value calculated for each of the plurality of measurement conditions. It is something.

[0070] The orthogonal acceleration time-of-flight mass spectrometer according to paragraph 1 includes an ion source, orthogonal acceleration electrodes that deflect the flight direction of ions incident from the ion source, flight path defining electrodes that define the flight path of ions deflected by the orthogonal acceleration electrodes, and an ion detector that detects ions that have traveled along the flight path. The method for adjusting an orthogonal acceleration time-of-flight mass spectrometer according to paragraph 6 adjusts such an orthogonal acceleration time-of-flight mass spectrometer. The orthogonal acceleration electrodes include, for example, a pusher electrode located on the opposite side of the flight space across the central axis of the flight path of ions incident from the ion source, and a pull-in electrode located on the flight space side. The flight path defining electrodes include, for example, a flight tube located on the outer edge of the flight space. In a reflectron-type mass spectrometer, the flight path defining electrodes also include, for example, a reflectron that turns back the flight path of ions.

[0071] Assuming that the same amount of ions generated in the ion source are all detected by the ion detector, the area of ​​the mass peak in the mass spectrum data will always be constant, and the peak width of the mass peak will be narrowest when the mass peak is highest. In other words, both the highest measurement intensity and the highest mass resolution can be obtained. However, in an orthogonal acceleration time-of-flight mass spectrometer, for example, if the value of the voltage applied to the orthogonal acceleration electrodes is changed to increase the mass resolution, a situation may arise in which some of the ions incident on the orthogonal acceleration electrodes are not introduced into the flight space, or vice versa. Therefore, even if the same amount of ions are generated in the ion source, the orthogonal acceleration voltage Extremely The amount of ions that reach the ion detector can vary greatly depending on the applied voltage. Therefore, in an orthogonal acceleration time-of-flight mass spectrometer, optimizing the measurement parameters to maximize ion measurement sensitivity can result in poor mass resolution, and vice versa.

[0072] In the orthogonal acceleration time-of-flight mass spectrometer according to paragraph 1 and the adjustment method according to paragraph 6, The value isMass spectrum data is obtained by measuring predetermined known ions generated from a predetermined amount of a known sample under a plurality of different measurement conditions. Then, score values ​​are calculated based on a predetermined calculation formula using the intensities and mass resolution of the mass peaks in the mass spectrum data obtained under each of the plurality of measurement conditions. In the orthogonal acceleration time-of-flight mass spectrometer according to paragraph 1 and the adjustment method according to paragraph 6, the score values ​​are calculated taking into account both the intensities and mass resolution of the known ions, and therefore the orthogonal acceleration energy is adjusted based on the calculated score values. Extremely By determining the value of the applied voltage, both high measurement sensitivity and high mass resolution can be obtained.

[0073] (Section 2) The orthogonal acceleration time-of-flight mass spectrometer according to paragraph 2 is the orthogonal acceleration time-of-flight mass spectrometer according to paragraph 1, the voltage application unit applies a pulse voltage to the orthogonal acceleration electrode at a predetermined cycle to deflect the flight direction of the ions, and applies a standby voltage during other time periods; The measurement control unit acquires the mass spectrum data under a plurality of measurement conditions with different standby voltage values.

[0074] According to the orthogonal acceleration time-of-flight mass spectrometer according to the second aspect, the mass resolution can be improved by tuning the value of the standby voltage.

[0075] (Section 3) The orthogonal acceleration time-of-flight mass spectrometer according to paragraph 3 is an orthogonal acceleration time-of-flight mass spectrometer according to paragraph 1 or 2, The measurement control unit acquires mass spectrum data by measuring the known ions under a plurality of measurement conditions in which different values ​​of voltage are applied to the flight path defining electrodes.

[0076] According to the orthogonal acceleration time-of-flight mass spectrometer of the third aspect, even if the flight path changes depending on the value of the voltage applied to the orthogonal acceleration electrode, a voltage appropriate for the changed flight path can be applied to the flight path defining electrode.

[0077] (Section 4) The orthogonal acceleration time-of-flight mass spectrometer according to paragraph 4 is the orthogonal acceleration time-of-flight mass spectrometer according to any one of paragraphs 1 to 3, further comprising: a tuning condition setting unit that receives input of a coefficient for the intensity of the mass peak and a coefficient for the mass resolution; Equipped with The score value calculation unit calculates the score value as the sum of an intensity parameter value calculated from the intensity of the mass peak multiplied by a coefficient for the intensity of the mass peak and a resolution parameter value calculated from the mass resolution multiplied by a coefficient for the mass resolution.

[0078] According to the orthogonal acceleration time-of-flight mass spectrometer according to the fourth aspect, the user can arbitrarily adjust the balance between ion detection sensitivity and mass resolution.

[0079] (Section 5) The orthogonal acceleration time-of-flight mass spectrometer according to paragraph 5 is 4 In the orthogonal acceleration time-of-flight mass spectrometer according to the paragraph, The intensity parameter value is a value normalized based on the intensity value of the largest mass peak among the mass spectrum data acquired under the plurality of measurement conditions, and the resolution parameter value is a value normalized based on the value of the highest mass resolution among the mass spectrum data acquired under the plurality of measurement conditions.

[0080] According to the orthogonal acceleration time-of-flight mass spectrometer according to the fifth aspect, it is possible to calculate a score value that appropriately reflects the measured value of the intensity of the mass peak actually measured and the value of the mass resolution. [Explanation of symbols]

[0081] 1...Orthogonal acceleration time-of-flight mass spectrometer 2...Mass spectrometry section 20...Ionization chamber 201...ESI probe 202...Desolvation tube 21...First intermediate vacuum chamber 211...Ion Guide 212...Skimmer 22...Second intermediate vacuum chamber 221...Ion Guide 23...Third intermediate vacuum chamber 231...Quadrupole mass filter 232...Collision cell 233...Multipole ion guide 234...Ion Guide 24…Analysis room 241...Ion lens 242...Orthogonal acceleration electrode 2421...Extrusion electrode 2422...Pull-in electrode 243…Second acceleration electrode 244...Reflectron 2441...Reflectron No. 1 2442...Reflectron No. 2 245...Ion detector 246...Flight tube 247...Backplate 3...Voltage application section 4...Control and processing section 41...Storage section 42...Tuning condition setting section 43...Measurement control section 44...Score calculation unit 45...Voltage determination unit 6...Input section 7…Display section C...Ion optical axis C': The central axis of the ion actually entering the orthogonal acceleration space

Claims

1. an ion source; an orthogonal acceleration electrode for deflecting the flight direction of ions incident from the ion source; a flight path defining electrode for defining a flight path of the ions deflected by the orthogonal acceleration electrode; an ion detection unit that detects ions that have flown along the flight path; a voltage application unit that applies voltages to the orthogonal acceleration electrodes and the flight path defining electrodes; a measurement control unit that acquires mass spectrum data by measuring predetermined known ions generated from a predetermined amount of a known sample under a plurality of measurement conditions in which the voltage applied from the voltage application unit to the orthogonal acceleration electrode is different; and a score calculation unit that calculates a score based on a predetermined formula using the intensities and mass resolutions of mass peaks in the mass spectrum data acquired under each of the plurality of measurement conditions; Equipped with the voltage application unit applies a pulse voltage to the orthogonal acceleration electrode at a predetermined cycle to deflect the flight direction of the ions, and applies a standby voltage during other time periods; the measurement control unit acquires a plurality of mass spectrum data sets with different mass peak intensities and mass resolutions by changing the standby voltage in the measurement of the known ions using the plurality of measurement conditions.

2. An orthogonal acceleration time-of-flight mass spectrometer as described in claim 1, wherein the plurality of measurement conditions include a measurement condition in which a standby voltage value is set such that at least a portion of ions incident on the orthogonal acceleration electrode that have a flight component in a direction opposite to the direction deflected by the orthogonal acceleration electrode collide with the orthogonal acceleration electrode and are lost.

3. Furthermore, the measurement control unit acquires mass spectrum data by measuring the known ions under a plurality of measurement conditions in which the voltage applied to the flight path defining electrodes is different.

2. The orthogonal acceleration time-of-flight mass spectrometer according to claim 1,

4. moreover, a tuning condition setting unit that receives input of a coefficient for the intensity of the mass peak and a coefficient for the mass resolution; Equipped with The score calculation unit calculates the score as the sum of a value obtained by multiplying an intensity parameter value calculated from the intensity of the mass peak by a coefficient for the intensity of the mass peak and a value obtained by multiplying a resolution parameter value calculated from the mass resolution by a coefficient for the mass resolution.

2. The orthogonal acceleration time-of-flight mass spectrometer according to claim 1,

5. 5. The orthogonal acceleration time-of-flight mass spectrometer according to claim 4, wherein the intensity parameter value is a value normalized based on the intensity value of the largest mass peak among the mass spectrum data acquired under the plurality of measurement conditions, and the resolution parameter value is a value normalized based on the value of the highest mass resolution among the mass spectrum data acquired under the plurality of measurement conditions.

6. generating predetermined known ions from a sample in an ion source; applying a voltage to an orthogonal acceleration electrode to deflect the flight direction of ions incident from the ion source, causing the ions to fly along a flight path defined by a flight path defining electrode; detecting mass-separated ions while they fly along the flight path to obtain mass spectrum data; calculating a score value based on a predetermined calculation formula using the intensity and mass resolution of the mass peak of the known ion in the mass spectrum data; Including, calculating the score value for each of a plurality of measurement conditions in which the voltage applied to the orthogonal acceleration electrodes is different; A value of a voltage to be applied to the orthogonal acceleration electrodes is determined based on the score value calculated for each of the plurality of measurement conditions. It is something, the voltages applied to the orthogonal acceleration electrodes include a pulse voltage that is applied at a predetermined period to deflect the flight direction of the ions, and a standby voltage that is applied during other time periods; A method for adjusting an orthogonal acceleration time-of-flight mass spectrometer, wherein, in measuring the known ions using the plurality of measurement conditions, the standby voltage is changed to obtain a plurality of mass spectrum data sets with different mass peak intensities and mass resolutions.

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