Time-of-flight mass spectrometer and time-of-flight mass spectrometry method

Abstract

A scheme of the TOFMS of the present application has: a flight space forming electrode (11, 12) that forms a flight space in which ions are separated according to m / z; an ion detection section (13) that detects ions flying in the flight space; a voltage switching section (4, 2) that switches a voltage applied to the flight space forming electrode from a first voltage that makes ions of a first polarity fly to a second voltage that makes ions of a second polarity fly at a prescribed switching timing; an ion information acquisition section (30, 32) that obtains a flight time or m / z of the ions of the second polarity based on a detection result of the ions of the second polarity obtained by the ion detection section after the voltage is switched by the voltage switching section; a correction information storage section (31) that stores correction information corresponding to an elapsed time from the switching timing and information related to a deviation of the flight time or m / z; and a correction section (33) that corrects the flight time or m / z according to the elapsed time from the switching timing using the correction information stored in the correction information storage section.

Description

Technical Field

[0001] This invention relates to a Time of Flight Mass Spectrometry (TOFMS) device. Background Technology

[0002] Compounds can readily become positive ions or negative ions. Therefore, when analyzing unknown compounds in a sample using a mass analyzer, or when analyzing a variety of compounds in a sample, it is necessary to switch between positive and negative ion measurements simultaneously. In a mass analyzer, switching the polarity of the ions being measured is achieved by switching the polarity of the voltage applied to various components such as the ion source, ion delivery optical system, mass separator, and ion detector.

[0003] In Time-of-Flight Mass Analyzers (TOFMS) that use a time-of-flight mass separator as the mass separator, a high-voltage power supply is used to apply a high voltage of several kV to tens of kV to the flight tube or ion reflector contained in the mass separator. To achieve high quality accuracy in a TOFMS, the output voltage of this high-voltage power supply needs to be highly accurate (typically several ppm) (see Patent Document 1, etc.). In typical high-voltage power supplies, when switching the polarity of the output high voltage, time is required until the voltage stabilizes to the aforementioned high accuracy. Therefore, when switching the polarity of the target ion in a TOFMS, it is necessary to ensure sufficient waiting time from switching the polarities of multiple high-voltage power supplies until each voltage fully stabilizes; in typical TOFMS, this voltage stabilization waiting time is approximately several seconds.

[0004] Existing technical documents

[0005] Patent documents

[0006] Patent Document 1: International Publication No. 2018 / 066064

[0007] Patent Document 2: Japanese Patent No. 6485590

[0008] Patent Document 3: Japanese Patent No. 5915760

[0009] Patent Document 4: Japanese Patent No. 6596103 Summary of the Invention

[0010] The technical problem that the invention aims to solve

[0011] In other words, in TOFMS, if a sufficient waiting time of several seconds or more is not ensured before measurement and data acquisition when switching between positive and negative ion measurements, sufficient quality accuracy cannot be obtained. To achieve high quality accuracy in TOFMS, a sufficient waiting time needs to be set when switching the polarity of the ions being measured; however, there is a problem of difficulty in simultaneously measuring ions of both positive and negative polarities while rapidly switching polarities.

[0012] This invention was made to solve this technical problem. Its main purpose is to provide a time-of-flight mass analysis device and method that can shorten the waiting time after the polarity switching of the measured ions while ensuring high quality and accuracy.

[0013] Solution to the above technical problems

[0014] One solution to the time-of-flight mass analysis device of the present invention, which addresses the aforementioned technical problems, comprises:

[0015] The flight space forms an electrode, forming a flight space used to separate ions originating from components contained in the sample based on the mass-to-charge ratio;

[0016] An ion detection unit detects ions flying in the flight space.

[0017] The voltage switching unit switches the voltage applied to the flight space forming electrode from a first voltage that causes ions of the first polarity to fly to a second voltage that causes ions of the second polarity to fly at a predetermined switching time.

[0018] The ion information acquisition unit, based on the detection result of the second polarity ion obtained by the ion detection unit after the voltage is switched by the voltage switching unit, calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion.

[0019] The correction information storage unit stores correction information related to the deviation of flight time or mass-to-charge ratio, corresponding to the elapsed time since the switching time.

[0020] The calibration unit uses the calibration information stored in the calibration information storage unit to correct the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time since the switching time when the detection result of the ion is obtained.

[0021] Furthermore, one aspect of the time-of-flight mass analysis method of the present invention, which was developed to solve the aforementioned technical problems, includes:

[0022] The voltage switching step involves switching the voltage applied to the space-of-flight forming electrode at a predetermined switching time from a first voltage that causes ions of the first polarity to fly to a second voltage that causes ions of the second polarity to fly. The space-of-flight forming electrode forms a space for separating ions originating from components contained in the sample according to their mass-to-charge ratio.

[0023] The ion information acquisition step, based on the detection result of the second polarity ion obtained by the ion detection unit that detects ions flying in the flight space after the voltage is switched in the voltage switching step, calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion.

[0024] The correction step uses correction information to correct the flight time or mass-to-charge ratio calculated in the ion information acquisition step based on the elapsed time since the switching time when the detection result of the ion is obtained. The correction information corresponds the elapsed time since the switching time to information related to the deviation of the flight time or mass-to-charge ratio.

[0025] Invention Effects

[0026] In the time-of-flight mass analysis apparatus and method of the present invention described above, even during the period when the voltage applied to the electrode forming the flight space is switched to switch the polarity of the target ion, i.e., during the period when the voltage is fluctuating, even before the voltage is sufficiently stable, it is possible to correct for deviations in flight time or mass-to-charge ratio caused by these fluctuations, thereby obtaining a highly accurate flight time or mass-to-charge ratio. Therefore, the time-of-flight mass analysis apparatus and method of the present invention described above can shorten the measurement waiting time after switching the polarity of the target ion while ensuring high quality and accuracy. Thus, for example, it is possible to perform continuous measurements while rapidly switching between positive and negative ions.

[0027] Furthermore, according to the above-described solution of the present invention, even power supplies with poor response characteristics (voltage rise characteristics) that have been difficult to use until now, such as those that produce ringing after the voltage approaches the target value, can be used as power supplies for applying voltage to the space-forming electrodes. Therefore, a cheaper power supply can be selected, and the cost of the device can be reduced. Attached Figure Description

[0028] Figure 1 This is a schematic diagram of the TOFMS as one embodiment of the present invention.

[0029] Figure 2 This is a diagram illustrating an example of the relationship between elapsed time and quality deviation since the polarity switch of the power supply section.

[0030] Figure 3This is a schematic diagram of the structure of TOFMS as a variant.

[0031] Figure 4 This is a schematic diagram of the TOFMS as another variation.

[0032] Figure 5 It is Figure 1 The overall configuration diagram is shown when the implementation method is applied to Q-TOFMS.

[0033] Figure 6 This is a diagram showing a simplified circuit including the electrodes of the power supply section and the TOF section.

[0034] Figure 7 This is an illustrative diagram illustrating an example of the process for correcting quality deviations. Detailed Implementation

[0035] [The principle of eliminating quality deviation during polarity switching]

[0036] Figure 2 This is an example of a graph showing the change over time in the deviation (mass deviation) of the mass-to-charge ratio (strictly italicized "m / z", but referred to here as "mass-to-charge ratio" or "m / z") of the measured ion after a polarity switch in a typical TOFMS. Mass deviation is the error (deviation from the ideal value) of the m / z value of the ion peak originating from a certain component on the mass spectrum.

[0037] like Figure 2 As shown, from the point in time t = 0 when the polarity of the voltage applied to the electrodes of the TOFMS is switched to change the polarity of the target ion (approximately 0.4 seconds in this example) to a predetermined time Ta, the ions do not converge and no ion peak is observed because the power supply voltage deviates significantly from the target value. Afterward, if the power supply voltage approaches the target value, the ions converge, and an ion peak can be observed. However, during a certain period of time Tb, the m / z value of the ion peak deviates because the output voltage of the high-voltage power supply is not yet sufficiently stable; this deviation gradually decreases over time. Then, after a predetermined time Tc (approximately 5.7 seconds in this example), the output voltage of the high-voltage power supply stabilizes, resulting in a state without mass deviation.

[0038] TOFMS typically requires high-precision measurement of m / z values. Therefore, after switching the voltage polarity, the system usually waits until there is no m / z deviation, i.e., during the Tc period, before starting spectral data acquisition. If spectral data acquisition begins during the Tb period, although the waiting time after switching the voltage polarity can be shortened, the observed ion peak m / z values ​​will deviate from the ideal values ​​due to the unstable power supply voltage, thus failing to achieve high-precision measurement.

[0039] In contrast, in the TOFMS of the present invention described above, information related to mass deviation during the Tb period is pre-stored as correction information corresponding to the elapsed time from the voltage switching point (t=0). This correction information is used to correct deviations in the flight time or m / z value of each ion obtained from measured data. Therefore, even when measurements are performed during the Tb period, high-precision m / z values ​​can be obtained.

[0040] Here, the aforementioned "correction information related to deviations in flight time or mass-to-charge ratio" refers to any information that can be used to correct mass deviations caused by voltage variations. For example, it could be the deviation amount of flight time or m / z value itself, or it could be a correction coefficient used to correct mass deviations. Furthermore, as a correspondence to elapsed time, it could be a function (calculation formula) with the elapsed time as a variable, or it could be a data table with the elapsed time as an input.

[0041] Furthermore, in TOFMS, the flight time is measured and then converted into an m / z value. Therefore, it is possible to perform a correction operation on the m / z value after obtaining a value that assumes no mass deviation caused by power supply voltage fluctuations (i.e., the m / z value obtained during Tc), or to directly calculate the corrected m / z value based on the flight time value that assumes no mass deviation caused by power supply voltage fluctuations. That is, in the TOFMS of the above scheme, the "ion information acquisition unit" and the "correction unit" do not perform their respective processing or calculations sequentially, but can substantially perform processing or calculations with different technical meanings simultaneously.

[0042] [The structure and operation of TOFMS according to one embodiment]

[0043] Hereinafter, embodiments of the TOFMS of the present invention based on the above principles will be described with reference to the accompanying drawings.

[0044] Figure 1 This is a schematic diagram of one embodiment of the TOFMS of the present invention.

[0045] The TOFMS includes a measurement unit 1, a power supply unit 2, a data processing unit 3, and a control unit 4. The measurement unit 1 includes an ion source 10, an ion emission unit 11, an ion flight unit 12, and an ion detection unit 13. The specific configuration of the measurement unit 1 varies depending on the type of time-of-flight mass separator; several specific examples will be described later. The data processing unit 3 includes a time-of-flight data acquisition unit 30, a calibration information storage unit 31, an m / z value calculation unit 32, an m / z value correction unit 33, and a mass spectrometer generation unit 34 as functional modules.

[0046] The data processing unit 3 and the control unit 4 can be configured, for example, to use a personal computer as hardware, and can be configured to perform the functions of the aforementioned units by executing dedicated software installed on the computer. Of course, a portion of the data processing unit 3 and the control unit 4 can also be constructed using hardware circuitry.

[0047] The operation of TOFMS in this embodiment is as follows.

[0048] The power supply unit 2 applies a predetermined voltage to each part of the measuring unit 1 according to the control from the control unit 4. In the measuring unit 1, the ion source 10 ionizes the components contained in the introduced sample. The ion emission unit 11 imparts energy to the ions originating from the sample components at a predetermined time and ejects them into the ion flight unit 12. In addition, the term "ions originating from the sample components" here is not limited to ions generated by the ion source 10, but also includes ions generated through dissociation operations of those ions.

[0049] The ion flight section 12 includes one or more electrodes, and an electric field generated by a voltage applied to the electrodes forms a flight space for ions to pass through. Ions emitted from the ion emission section 11 travel within this flight space and reach the ion detection section 13. The flight velocity of the ions introduced into the ion flight section 12 depends on the m / z value of the ion. Therefore, the flight time of the ions from the ion emission section 11 to the ion detection section 13 depends on the m / z value of the ion. That is, ions with various m / z values ​​that depart from the ion emission section 11 almost simultaneously arrive at the ion detection section 13 with a time difference corresponding to their m / z values. The ion detection section 13 detects the arriving ions and outputs an ion intensity signal corresponding to the amount of ions as time passes.

[0050] In the data processing unit 3, the time-of-flight data acquisition unit 30 converts the aforementioned ion intensity signal into digital data and stores time-of-flight spectrum data showing the relationship between flight time and ion intensity with the ion emission time point set to zero. As described above, the flight time of an ion depends on its m / z value. Therefore, it is possible to use a conversion formula showing the relationship between flight time and m / z value to calculate the m / z value for each ion species based on the flight time. Here, this conversion formula (function) is set to f.

[0051] That is, in conventional TOFMS, the m / z value is calculated based on the time of flight (ttof) using the conversion formula f shown in equation (1). This conversion formula f can be calculated in advance or derived from measurements performed using standard samples with known precise m / z values.

[0052] m / z=f(ttof)…(1)

[0053] The conversion formula f in equation (1) above does not include the time-dependent variation of the output voltage of the power supply unit 2. Therefore, if the polarity of the output voltage in the power supply unit 2 is switched in order to switch the polarity of the ion to be measured, and the measurement is performed during the Tb period after the switch, the m / z value calculated using equation (1) includes... Figure 2 The quality deviation shown is as indicated.

[0054] In contrast, in the TOFMS of this embodiment, the measurement unit 1 performs measurements at predetermined times during the Tb period under the instruction of the control unit 4, and acquires time-of-flight spectrum data. Moreover, in the case where the polarity of the output voltage of the power supply unit 2 is switched in order to switch the polarity of the ion to be measured during the Tb period, the m / z value calculation unit 32 and the m / z value correction unit 33 calculate the m / z value using the following equation (2), which takes into account the mass deviation g(tpn) corresponding to the elapsed time tpn after the polarity switch.

[0055] m / z=f(ttof)×(1+g(tpn))…(2)

[0056] As described above, the primary cause of mass deviation after switching voltage polarity is the voltage variation until the voltage applied to the electrodes forming the flight space stabilizes. Essentially, the rate of mass deviation caused by this voltage variation is independent of the m / z value; any m / z value produces a mass deviation at the same rate. Therefore, by multiplying (1+g(tpn)) with f(ttof), which takes into account the amount of mass deviation corresponding to the time tpn elapsed after the polarity switch, it is possible to correct the mass deviation that occurs until the voltage applied to the electrodes stabilizes after the polarity switch with high precision. g(tpn) is a function showing the correction coefficients with the time tpn elapsed after the polarity switch as the variable.

[0057] Furthermore, since equation (2) is

[0058] m / z=f(ttof)+f(ttof)·g(tpn),

[0059] Therefore, even if we set it to use the following equation (3) with the quality deviation term G as the variable of the time tpn after polarity switching, it is essentially the same.

[0060] m / z=f(ttof)+G(tpn)…(3)

[0061] Equation (2) above can be considered as incorporating a correction term into the function (conversion formula) for calculating the m / z value. On the other hand, equation (3) indicates that after calculating the m / z value without considering voltage variations, the m / z value is corrected using a correction formula that shows the relationship between time tpn after polarity switching and quality deviation. They are essentially the same.

[0062] Figure 2 The relationship between time tpn and quality deviation after polarity switching, as shown, i.e., the function g(tpn) or G(tpn), largely depends on the configuration or structure of the device's electrical system. Therefore, for example, the manufacturer of this device, during the adjustment phase before shipping the device to the user, investigates g(tpn) or G(tpn) by measuring standard samples in advance and stores it in the calibration information storage unit 31. g(tpn) or G(tpn) can be a calculation formula, or it can be a data table that outputs a correction amount or correction coefficient if tpn or m / z value (or flight time) is input.

[0063] The m / z correction unit 33 receives information from the control unit 4 about the elapsed time tpn after the polarity switch during measurement. Using the correction information stored in the correction information storage unit 31, it calculates the corrected m / z value for each ion species, corrected for mass deviation. The mass spectrometry generation unit 34 generates a mass spectrum using the corrected m / z value. In this way, even when measurement is performed without sufficient waiting time after the polarity switch of the target ion, a high-quality, high-precision mass spectrum can be obtained.

[0064] Furthermore, if the control unit 4 controls the measurement unit 1 to always perform measurements after a time tpn elapsed following the same polarity switch (e.g., 1 second after the switch time), then the quality deviation or correction coefficient corresponding to the time tpn elapsed following the polarity switch can be stored in the correction information storage unit 31 in advance, and correction can be performed using this information.

[0065] Furthermore, the polarity switching of the measured ions can occur from positive to negative ions and from negative to positive ions. The response characteristics of the power supply unit 2 may differ depending on whether the voltage is switched from negative to positive or from positive to negative. Therefore, in cases where the response characteristics differ during voltage polarity switching, it is sufficient to store both positive-to-negative and negative-to-positive correction information in the correction information storage unit 31 beforehand and use them separately.

[0066] [Variation 1: Built-in function for acquiring calibration information]

[0067] Figure 3 This is a schematic diagram of a TOFMS as a variation of the above-described embodiment. Figure 3 In the middle, to and Figure 1 The same components of the TOFMS shown are assigned the same reference numerals.

[0068] In the TOFMS of the above embodiment, the correction information, such as the function g(tpn) in equation (2) or the function G(tpn) in equation (3), is specifically stored in the correction information storage unit 31 in advance at the time when the device is provided to the user. In contrast, the TOFMS of this modified example has the function of generating or changing the correction information such as the functions g(tpn) and G(tpn). That is, the data processing unit 3 includes a correction information acquisition unit 35 as a functional module, and the control unit 4 includes a correction information acquisition control unit 40 as a functional module. In addition, the measurement unit 1 includes a standard sample introduction unit 14, which introduces a standard sample different from the usual sample into the ion source 10. The standard sample is a sample containing one or more components with known ideal (or theoretical) m / z values.

[0069] The response characteristics until the voltage applied from the power supply unit 2 to the electrodes included in the ion flight unit 12 stabilizes vary not only according to individual differences in the power supply unit 2, but also according to resistance or inductance depending on factors such as the length of the wiring, or parasitic capacitance generated by the wiring. Therefore, although its response characteristics are generally dependent on the model as described above, each device has a certain degree of deviation, and if the device is repaired, it will also change before and after the repair.

[0070] In this TOFMS, for example, the user prepares a standard sample for measuring mass deviation specified by the manufacturer in the standard sample introduction unit 14, and performs mass deviation measurement through a prescribed operation instruction via an input unit (not shown). Then, in the control unit 4, the calibration information acquisition control unit 40 controls the measurement unit 1 to repeatedly perform measurements using the aforementioned standard sample after polarity switching. That is, the standard sample introduction unit 14 supplies the standard sample to the ion source 10, and the ion source 10 ionizes the known components in the standard sample. The ion emission unit 11, the ion flight unit 12, and the ion detection unit 13 repeatedly acquire time-of-flight spectrum data of ions originating from the known components. Based on the data obtained through this measurement, the calibration information acquisition unit 35 calculates the relationship between time elapsed after polarity switching and mass deviation (i.e., g(tpn) or G(tpn)), and saves this relationship in the calibration information storage unit 31.

[0071] In this way, in the TOFMS, calibration information reflecting the current configuration or structure of the device is stored in the calibration information storage unit 31. As a result, accurate correction of mass deviations that match the configuration or structure of the device can be performed, further improving the mass spectrometry's quality accuracy.

[0072] Alternatively, the aforementioned calibration information acquisition can be performed not by the user, but by the manufacturer's service representative during installation of the device at the customer's location, or during customer troubleshooting or maintenance. Furthermore, the aforementioned calibration information acquisition can be performed as part of an automatic tuning function that optimizes various parameters within the device, without relying on specific user operation.

[0073] [Variation Example 2: Modeling the Function Used for Correction]

[0074] The function g(tpn) representing the aforementioned quality deviation can be set as any expression, but if the function is modeled in advance, and one or more parameters included in the model function are changed to obtain a usable function g(tpn), the processing will be simplified. Specifically, the function can be modeled as follows.

[0075] Include Figure 1 Although the electrical system circuit of the power supply unit 2 used in the TOFMS shown varies depending on the model of the device, the circuit consisting of the power supply unit 2 and the electrodes from which voltage is applied can be used in many cases. Figure 6 The RLC series circuit shown is described simply. Figure 6 In this context, V is the output voltage of the power supply E, R is the output resistance, L is the inductance of the wiring, and C is the parasitic capacitance of the electrodes, etc.

[0076] Now, if we assume that the inductance L of the wiring is small enough to be negligible, then Figure 6 The RLC series circuit shown can be used as an RC series circuit. Generally, in an RC series circuit, V·e is generated. -t / RC The voltage error decreases over time. Therefore, under the assumption that the quality deviation is proportional to the voltage error, the function g(tpn) can be approximated as in equation (4).

[0077] g(tpn)=A·e -tpn / τ …(4)

[0078] As long as equation (4) is used as the model function, the two parameters A and τ can be determined respectively to match the composition and structure of the device.

[0079] On the other hand, Figure 6 When the inductance L of the wiring cannot be ignored, the circuit becomes an RLC series circuit, thus causing damped oscillations in the electrode voltage. In this case, the m / z value also causes a mass deviation equivalent to the damped oscillations. Therefore, the model function equivalent to the damped oscillations is determined as g(tpn), which can correct the oscillations in the m / z value.

[0080] Specifically, the model function can be determined as follows (5) to (7). Since the attenuation condition varies depending on the values ​​of R, L, and C, it is necessary to monitor the mass deviation of the standard sample during measurement and select an appropriate model function corresponding to the state of the device at that time.

[0081] Incomplete decay: g(tpn) = A·e -(tpn / τ) cos(ωtpn+α)…(5)

[0082] Excessive decay: g(tpn) = e -(tpn / τ) (Ae ηtpn +Be -ηtpn )cos(ωtpn+α)…(6)

[0083] Critical decay: g(tpn)=(A+Btpn)e -(tpn / τ) …(7)

[0084] As long as any one of equations (5) to (7) is used as the model function, the parameters A, B, τ, ω, α, η, etc. can be appropriately determined to match the composition and structure of the device.

[0085] [Variation Example 3: Rigorized time after polarity switching]

[0086] As mentioned above, since the mass deviation depends on the time elapsed after the polarity switch (tpn), it is necessary to accurately determine the time elapsed after the polarity switch at the measurement point in order to accurately correct the mass deviation. Generally, when using TOFMS to calculate mass spectrometry, multiple measurements are often performed repeatedly within a certain event time (data acquisition time), and the acquired spectral data are accumulated (or averaged) in the multiple measurements. When the event time is long, the difference between the voltage applied to the electrode at the start time of data acquisition and the voltage applied to the electrode at the end time of data acquisition is large, and sometimes the mass deviation at these two time points is different. Therefore, when the event time is long, or when a higher precision correction is required even when the event time is short, as shown in equation (8), the event time (teve) can be included in the variables of the mass deviation correction function g.

[0087] m / z=f(ttof)×(1+g(tpn,teve))…(8)

[0088] Therefore, even when the event duration is long, quality deviations can be corrected with high precision.

[0089] As an example, such as Figure 7As shown, half of the event time teve can be added to the start time tpn1 of the event, and the resulting value can be used as a variable that functions as a function of the quality deviation after the polarity switch and the elapsed time tpn.

[0090] g(tpn, teve) = A·e -(tpn1+teve / 2) / τ …(9)

[0091] [Variation Example 4: Utilization of Voltage Monitoring Values]

[0092] The main cause of the mass deviation is the error in the voltage applied to the electrode contained in the ion flight section 12. Due to factors such as the resistance of the wiring connecting the power supply section 2 and the electrode, there is sometimes a difference between the output voltage of the power supply section 2 and the voltage in the electrode. Therefore, in order to perform more accurate correction of the mass deviation, as shown in equation (10) below, the variable of the mass deviation correction function g can include the monitored value Vmon of the voltage in the electrode (or its equivalent voltage).

[0093] m / z=f(ttof)×(1+g(tpn,Vmon))…(10)

[0094] Figure 4 This is a schematic diagram of the TOFMS as a variant example. Figure 4 In the middle, to and Figure 1 The same components of the TOFMS shown are assigned the same reference numerals.

[0095] Voltage sensor 20 and voltage detection unit 37 detect the voltage generated by power supply unit 2 and applied to one of the electrodes contained in ion flight unit 12. The detected voltage is the monitoring value Vmon. m / z value correction unit 33 uses the time tpn elapsed after polarity switching and the monitoring value Vmon to calculate the correction amount based on the mass deviation correction function g, and corrects the m / z value. As a result, a correction with higher accuracy than that described in the above embodiment can be performed.

[0096] The following describes an example of the configuration of the measuring unit 1 in the TOFMS of the above embodiment in more detail.

[0097] [Concrete example 1: Q-TOFMS]

[0098] The following reference Figure 5 A four-pole-time-of-flight (Q-TOF) mass analyzer, which is a specific example of the present invention, will be described in detail.

[0099] Figure 5 This is an overall configuration diagram of a specific example of applying the above-described embodiments to a Q-TOF type mass analyzer. Figure 5 It is directly recorded in the middle Figure 1The components other than the measuring section 1 are included. Furthermore, the configuration of the measuring section in this Q-TOF type mass analyzer is a previously known configuration as described in Patent Document 2, etc., and can be appropriately modified or transformed.

[0100] In this Q-TOF mass analyzer, an ionization device 50 is installed inside an ionization chamber 500, connected to the front of a vacuum chamber 5. The vacuum chamber 5 is roughly divided into four chambers: a first intermediate vacuum chamber 51, a second intermediate vacuum chamber 52, a first analytical chamber 53, and a second analytical chamber 54. The ionization chamber 500 is at approximately atmospheric pressure, and the vacuum level increases in stages from the ionization chamber 500 in the order of the first intermediate vacuum chamber 51, the second intermediate vacuum chamber 52, the first analytical chamber 53, and the second analytical chamber 54. Furthermore, in... Figure 5 The description of the vacuum pump used for vacuum venting in each chamber is omitted, but generally, the first intermediate vacuum chamber 51 is vented by a rotary pump, and subsequent chambers are vented by a turbomolecular pump that uses a rotary pump as a roughing pump.

[0101] The ionization chamber 500 is equipped with an electrospray ionization (ESI) source 501 that ionizes compounds in the sample liquid by imparting a charge to the sample liquid and spraying it. However, the ionization method is not limited to this, and other ion sources such as atmospheric pressure chemical ionization sources can also be used. In addition, ion sources that ionize gaseous or solid samples instead of liquid samples can also be used.

[0102] The ionization chamber 500 is connected to the first intermediate vacuum chamber 51 via a narrow-diameter desolventizing tube 502. Ions and fine charged droplets generated in the ionization chamber 500, originating from the sample composition, are introduced into the desolventizing tube 502 and transported to the first intermediate vacuum chamber 51 primarily due to the pressure difference between the ionization chamber 500 (approximately atmospheric pressure) and the first intermediate vacuum chamber 51. The desolventizing tube 502 is heated to a suitable temperature, causing the charged droplets to pass through its interior, thus promoting the vaporization of the solvent within the droplets and further promoting ion generation.

[0103] A multi-polar ion guide 511 is disposed in the first intermediate vacuum chamber 51, which converges ions to the vicinity of the ion optical axis C1, and then directs them into the second intermediate vacuum chamber 52 through the opening at the top of the truncated cone 512. A multi-polar ion guide 521 is also disposed in the second intermediate vacuum chamber 52, which transports ions from the second intermediate vacuum chamber 52 to the first analysis chamber 53. The first analysis chamber 53 is disposed of a quadrupole mass filter 531 that separates ions according to m / z, a collision cell 533 containing a multi-polar ion guide 532, and a portion of a transfer electrode 534 for transporting ions ejected from the collision cell 533.

[0104] Ions incident into the first analysis chamber 53 are introduced into a quadrupole mass filter 531, where only ions with a specific m / z corresponding to the voltage applied to the quadrupole mass filter 531 pass through. Collision gases such as argon and nitrogen are continuously or intermittently supplied to the interior of the collision cell 533. Ions with a specified energy incident into the collision cell 533 come into contact with the collision gases and dissociate through collision-induced dissociation, generating various product ions.

[0105] Various product ions ejected from the collision cell 533 are converged by the transfer electrode 534 and simultaneously transported to the second analysis chamber 54. The second analysis chamber 54 is equipped with an orthogonal acceleration unit 540, an acceleration electrode unit 541, a flight tube 542, a reflector 543, a backplate 544, and an ion detector 545. The ions introduced into the second analysis chamber 54 via the transfer electrode 534 form a finer and more parallel ion stream, which is ejected in the orthogonal acceleration unit 540 in a direction approximately orthogonal to the incident direction of the ion stream.

[0106] Ions pulsedly emitted from the orthogonal acceleration section 540, i.e., as a single ion packet, are further accelerated by the accelerating electrode section 541 and guided into the flight space within the flight tube 542. In the flight space, the flight tube 542, reflector 543, and backplate 544 form a system that allows the ions to... Figure 5 The electric field of the path shown in C2 is used for the ion to fly back. As a result, the ion is deflected and flies again in the flight tube 542, reaching the ion detector 545.

[0107] The orthogonal acceleration section 540 and the acceleration electrode section 541 are equivalent to Figure 1 The electrodes included in the ion emission section 11. Furthermore, the flight tube 542, reflector 543, and backplate 544 correspond to... Figure 1The electrodes included in the ion flight section 12 are electrodes that form the electric field required for ions to fly along the flight path C2, and are therefore equivalent to the "flight space forming electrodes" in this invention. The power supply unit 2 applies a predetermined voltage to the orthogonal acceleration section 540, the acceleration electrode section 541, the flight tube 542, the reflector 543, and the backplate 544. For example, when the target ion changes from a positive ion to a negative ion, the power supply unit 2 switches the voltage applied to each electrode from a negative voltage to a positive voltage according to the instruction from the control unit 4. Furthermore, in Figure 5 The text omits the description, but of course, it also specifies the voltage to be applied to the ion guide or quadrupole mass filter plasma optical system.

[0108] In this Q-TOFMS, the orthogonal acceleration unit 540 repeatedly pulses ions at a predetermined period (e.g., 100 USEC). The emitted ions whirl back and forth within a flight space formed by voltages applied to the flight tube 542, reflector 543, and backplate 544, respectively, and are detected by the ion detector 545. In the data processing unit 3, the time-of-flight data acquisition unit 30 calculates the cumulative time-of-flight spectrum based on the ion intensity signals detected in multiple measurements performed within a predetermined event time. The m / z value calculation unit 32 and the m / z value correction unit 33 calculate, by performing the above processing, the m / z value after correcting for the mass deviation caused by voltage fluctuations after polarity switching, for the flight time of each peak observed in the cumulative time-of-flight spectrum. The mass spectrometry generation unit 34 uses the corrected m / z value to generate a mass spectrum.

[0109] In many cases, such Q-TOF mass analyzers equipped with atmospheric pressure ion sources are pre-connected to liquid chromatographs, or liquid samples are introduced into the ion source via flow injection analysis (FIA). Therefore, the time available for introducing certain components of the sample into the ion source is limited, but when the component is unknown, both positive and negative ion measurements need to be performed within this limited time. In conventional Q-TOFMS, the switching time between positive and negative ion measurements requires a waiting period, making it sometimes difficult to simultaneously perform positive and negative ion measurements on certain components. In contrast, in the Q-TOFMS utilizing this invention, the waiting time for switching between positive and negative ion measurements can be reduced to, for example, less than one second, thus enabling simultaneous positive and negative ion measurements on certain components. Furthermore, high-quality mass spectra can be obtained for both positive and negative ions separately.

[0110] [Specific Example 2: Multiple Surround TOFMS]

[0111] To improve mass accuracy and resolution in Time-of-Flight (TOF) systems, extending the ion flight distance is effective. One known method is the use of multiple-orbit TOF systems. For example, Patent Document 3 discloses a TOF system that allows ions to orbit multiple times along approximately the same trajectory, thereby extending the ion flight distance in a relatively narrow space. In this TOF system, the orbit for one revolution is approximately elliptical, and the orbit shifts slightly with each revolution of the ion. This increases the number of orbits while preventing ions from flying along the same trajectory, ensuring a longer flight distance.

[0112] Of course, the TOFMS described above and its variations can also be applied to such a multi-loop TOFMS. In the multi-loop TOFMS described in Patent Document 3, in order to make ions fly along a predetermined path, multiple fan-shaped electrodes forming a curved electric field to guide the ions or multiple ion lens electrodes forming an electric field that converges the ions are used, but these fan-shaped electrodes or ion lens electrodes are... Figure 1 The TOFMS shown includes electrodes in the ion flight section 12. Therefore, these electrodes correspond to the flight space formation electrodes in this invention.

[0113] [Specific Example 3: Multiple Reflections TOFMS]

[0114] As another method to extend the flight distance of ions, multiple-reflection TOFMS is known in the past. For example, Patent Document 4 discloses a TOFMS that repeatedly reflects ions between multiple reflective electrodes, thereby extending the flight distance of ions in a relatively narrow space. Of course, the TOFMS described above and its variations can also be applied to multiple-reflection TOFMS. In the multiple-reflection TOFMS described in Patent Document 4, multiple plate-shaped reflective electrodes arranged in a substantially parallel configuration are used to enable repeated ion flight; however, such reflective electrodes are... Figure 1 The TOFMS shown includes electrodes in the ion flight section 12. Therefore, such electrodes are equivalent to the flight space formation electrodes in this invention.

[0115] Furthermore, the present invention can be applied to all TOFMS, so in addition to Q-TOFMS and the like described above, the present invention can also be applied to ion trap TOFMS, matrix-assisted laser desorption / ionization (MALDI)-TOFMS and the like.

[0116] Furthermore, the above-described embodiments, various modifications, or specific examples are merely examples of the present invention. Within the scope of the spirit of the present invention, any appropriate modifications, alterations, additions, etc., are naturally included within the scope of the claims of this application.

[0117] [Various options]

[0118] Those skilled in the art will understand that the above exemplary embodiments and variations are specific examples of the following solutions.

[0119] (Item 1) One aspect of the time-of-flight mass analysis device of the present invention comprises:

[0120] The flight space forms an electrode, forming a flight space used to separate ions originating from components contained in the sample based on the mass-to-charge ratio;

[0121] An ion detection unit detects ions flying in the flight space.

[0122] The voltage switching unit switches the voltage applied to the flight space forming electrode from a first voltage that causes ions of the first polarity to fly to a second voltage that causes ions of the second polarity to fly at a predetermined switching time.

[0123] The ion information acquisition unit, based on the detection result of the second polarity ion obtained by the ion detection unit after the voltage is switched by the voltage switching unit, calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion.

[0124] The correction information storage unit stores correction information that corresponds to the elapsed time since the switching time and information related to the deviation of flight time or mass-to-charge ratio.

[0125] The calibration unit uses the calibration information stored in the calibration information storage unit to correct the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time since the switching time when the detection result of the ion is obtained.

[0126] (Item 18) One aspect of the time-of-flight mass analysis method of the present invention has the following features:

[0127] The voltage switching step involves switching the voltage applied to the space-of-flight forming electrode at a predetermined switching time from a first voltage that causes ions of the first polarity to fly to a second voltage that causes ions of the second polarity to fly. The space-of-flight forming electrode forms a space for separating ions originating from components contained in the sample according to their mass-to-charge ratio.

[0128] The ion information acquisition step, based on the detection result of the second polarity ion obtained by the ion detection unit that detects ions flying in the flight space after the voltage is switched in the voltage switching step, calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion.

[0129] The correction step uses correction information to correct the flight time or mass-to-charge ratio calculated in the ion information acquisition step based on the elapsed time since the switching time when the detection result of the ion is obtained. The correction information corresponds the elapsed time since the switching time to information related to the deviation of the flight time or mass-to-charge ratio.

[0130] According to the apparatus described in item 1 and the method described in item 18, it is possible to shorten the measurement waiting time after the polarity switching of the ion being measured while ensuring high quality and accuracy. Thus, for example, it is possible to perform measurements while rapidly switching between positive and negative ions.

[0131] Furthermore, according to the apparatus described in claim 1 and the method described in claim 18, even power supplies with poor response characteristics (voltage rise characteristics) that have been difficult to use until now, such as those that produce ringing after the voltage approaches the target value, can be used as power supplies for applying voltage to the forming electrodes in the flight space. Thus, inexpensive power supplies can be selected, and the cost of the apparatus can be reduced.

[0132] (Item 2) In the TOFMS described in Item 1, it can be set to,

[0133] The correction information is a correction value corresponding to the elapsed time since the switching point.

[0134] The correction unit adds the correction value stored in the correction information storage unit to the flight time or mass-to-charge ratio calculated by the ion information acquisition unit.

[0135] (Item 3) Furthermore, in the TOFMS described in Item 1, it is possible to set it to,

[0136] The correction information is a correction coefficient corresponding to the elapsed time since the switching point.

[0137] The correction unit multiplies the correction coefficient stored in the correction information storage unit with the flight time or mass-to-charge ratio calculated by the ion information acquisition unit.

[0138] The "correction value corresponding to the elapsed time since the switching point" in the TOFMS mentioned in item 2 and the "correction coefficient corresponding to the elapsed time since the switching point" in the TOFMS mentioned in item 3 are, for example, functions (calculation formulas) that take the elapsed time since the switching point as a variable, or data tables that take the elapsed time since the switching point as an input and output correction values ​​or correction coefficients.

[0139] According to the TOFMS described in item 2 or 3, if the elapsed time since the switching point is given, the flight time or mass-to-charge ratio can be easily corrected.

[0140] (Item 4) The TOFMS described in any one of items 1 to 3 can be configured to further include a correction information acquisition unit that generates or modifies the correction information.

[0141] (Item 5) The TOFMS described in Item 4 can be configured to further include: an ion source for generating ions derived from components contained in the sample; and a sample introduction unit for introducing a known sample into the ion source.

[0142] The correction information acquisition unit generates or modifies the correction information based on the change in flight time or mass-to-charge ratio over time since the switching moment, calculated from the intensity signal of ions originating from the known sample.

[0143] According to the TOFMS described in item 4 or 5, it is possible to perform high-precision correction of mass deviations that correspond to the configuration or structure of the device at that time point and reflect the voltage response characteristics after polarity switching. This further improves the mass spectrometer's mass accuracy. In particular, even when the device's state changes due to device malfunction repair or component replacement, high-precision correction of mass deviations is still possible.

[0144] (Item 6) In the TOFMS described in Item 4 or 5, the correction information acquisition unit can be configured to pre-store a model function corresponding to the correction information, and generate or change the correction information by changing the parameter values ​​contained in the model function, wherein the correction information is related to the elapsed time from the switching time or the deviation of the flight time or mass-to-charge ratio.

[0145] According to the TOFMS described in item 6, correction information can be easily generated or modified through relatively simple calculations.

[0146] (Item 7) In the TOFMS described in Item 6, the model function can be configured to include at least one value of resistance, inductance, or capacitance in a simplified circuit connected to a power supply unit that applies voltage to the flight space forming electrodes as a parameter.

[0147] The correction information acquisition unit acquires correction information by changing at least one of the parameter values ​​included in the model function.

[0148] (Item 8) In the TOFMS described in Item 7, the model function can be set to a voltage response function that includes the values ​​of the resistance and capacitance in the simplified circuit connected to the power supply unit as parameters.

[0149] In the TOFMS described in item 8, the model function is a simple function of the decrease in mass deviation over time. Therefore, according to the TOFMS described in item 8, correction information can be easily determined based on the results obtained from measuring known samples.

[0150] (Item 9) In the TOFMS described in Item 7, the model function can be configured to be a decay response function that includes at least the value of the inductance in the simplified circuit connected to the power supply as a parameter.

[0151] The correction information acquisition unit acquires the correction information by changing the attenuation response function through changing the value of the inductor.

[0152] In the TOFMS described in item 9, even when the target value is reached simultaneously with voltage overshoot or ringing applied to the forming electrode in the flight space after polarity switching, the quality deviation caused by such voltage fluctuation can be well corrected.

[0153] (Item 10) In any of the TOFMS described in items 1 through 9, it can be set to,

[0154] It also includes an ion ejection unit that is controlled to perform a measurement event of periodically and repeatedly ejecting ions derived from the sample composition into the flight space.

[0155] The ion information acquisition unit calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion based on the result of accumulating or averaging the intensity signal of the ion. The intensity signal of the ion is obtained for each of the multiple ion emission actions performed in the measurement event.

[0156] The correction unit corrects the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time from the switching point to the start of the measurement event and a predetermined delay time from the start of the measurement event.

[0157] (Item 11) In the TOFMS described in Item 10, it is possible to set the specified delay time to be 1 / 2 of the required time for the measurement event.

[0158] Multiple measurements are performed within a single measurement event, obtaining time-of-flight spectrum data within a specified mass-to-charge ratio range at each measurement. However, the voltage applied to the electrodes forming the flight space may vary during the execution of that single measurement event. In contrast, in the TOFMS described in items 10 and 11, the flight time or m / z value is corrected, for example, based on the time summed by the elapsed time and a specified delay time, or by a time calculated using a specified operation with the elapsed time and delay time as variables. Therefore, since a correction reflecting the delay time since the start of the measurement event can be performed, mass deviations can be corrected with higher accuracy.

[0159] (Item 12) In any of the TOFMS described in items 1 through 11, it can be set to,

[0160] It also includes a voltage monitoring unit to acquire a monitoring voltage corresponding to the voltage applied to at least one of the electrodes forming the flight space;

[0161] The correction unit corrects the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time since the switching time and the monitoring voltage.

[0162] According to the TOFMS described in item 12, even in cases where there is a difference between the output voltage from the power supply and the voltage actually applied to the forming electrodes in the flight space, corrections reflecting this difference can be performed, thus enabling the correction of quality deviations with higher accuracy.

[0163] (Item 13) In any of the TOFMS described in items 1 to 12, it can be set such that the elapsed time from the switching time is less than 5 seconds.

[0164] In conventional TOFMS, to achieve high-quality precision, at least 5 seconds are required to switch from the polarity of the target ion to the measurement. In contrast, the TOFMS described in item 13 can obtain high-quality precision mass spectrometry while shortening this waiting time.

[0165] In one embodiment of the TOFMS of the present invention, the flight space forming electrode is as described below and may include various electrodes for forming a flight space for causing ions to fly along a predetermined path.

[0166] (Item 14) In any of the TOFMS described in items 1 to 13, the flight space forming electrode may include a flight tube to which a high voltage of 1 kV or more is applied. Flight tubes are typically used in linear TOFMS or reflector-type TOFMS.

[0167] (Item 15) In any of the TOFMS described in items 1 to 14, the space-flying electrode may include a reflector to which a high voltage of 500V or more is applied. The reflector is used in a reflector-type TOFMS.

[0168] (Item 16) In any of the TOFMS described in items 1 to 13, the flight space forming electrode may include an electrode that forms multiple orbital orbits for ions to orbit multiple times or multiple reflection orbits for ions to reflect multiple times by forming an electric field.

[0169] (Item 17) In any of the TOFMS described in items 1 to 16, the space-of-flight forming electrode may include an ion ejection electrode, which is pulsedly subjected to a high voltage of 1 kV or more, thereby ejecting the second polarity ions toward the space-of-flight.

[0170] For example, in orthogonal acceleration TOFMS, the ion emission electrode includes at least one of a repulsion electrode and an introduction electrode in the orthogonal acceleration section. In ion trap type TOFMS, the ion emission electrode is the electrode constituting the ion trap; in a three-dimensional quadrupole ion trap, this electrode is an end cap electrode. Furthermore, in a linear ion trap, it consists of a rod electrode with an ion emission outlet and a rod electrode disposed opposite to the rod electrode along the ion optical axis. Additionally, in MALDI-TOFMS, the ion emission electrode includes an accelerating electrode for accelerating the extracted ions.

[0171] Explanation of reference numerals in the attached figures

[0172] 1. Measurement Department

[0173] 10 Ion Sources

[0174] 11 Ion Ejection Section

[0175] 12 Ion Flight Division

[0176] 13 Ion Detection Unit

[0177] 14 Standard Sample Inlet Section

[0178] 2 Power Supply Section

[0179] 20 Voltage Sensor

[0180] 3. Data Processing Department

[0181] 30 Flight Time Data Acquisition Department

[0182] 31. Correction Information Storage Department

[0183] 32 m / z value calculation section

[0184] 33 m / z value correction section

[0185] 34 Mass Spectrometry Generation Section

[0186] 35. Calibration Information Acquisition Department

[0187] 37 Voltage Detection Section

[0188] 4. Control Department

[0189] 40. Calibration Information Acquisition and Control Unit

[0190] 5. Vacuum Chamber

[0191] 50 Ionization Device

[0192] 500 Ionization Chamber

[0193] 501 ESI source

[0194] 502 solvent removal tube

[0195] 51 First Intermediate Vacuum Chamber

[0196] 511, 521, 532 Ion Directors

[0197] 512 Cutting cone

[0198] 52 Second Intermediate Vacuum Chamber

[0199] 53 Analytical Laboratory 1

[0200] 531 Quadruple Mass Filter

[0201] 533 Collision Pool

[0202] 534 Transfer Electrode

[0203] 54. Analytical Laboratory No. 2

[0204] 540 Orthogonal Accelerator

[0205] 541 Accelerating Electrode Section

[0206] 542 Flight Tube

[0207] 543 Reflector

[0208] 544 Backplate

[0209] 545 Ion Detector.

Claims

1. A time-of-flight mass analysis device, characterized in that, have: The flight space forms an electrode, forming a flight space used to separate ions originating from components contained in the sample based on the mass-to-charge ratio; An ion detection unit detects ions flying in the flight space. The voltage switching unit switches the voltage applied to the flight space forming electrode from a first voltage that causes ions of the first polarity to fly to a second voltage that causes ions of the second polarity to fly at a predetermined switching time. The ion information acquisition unit, based on the detection result of the second polarity ion obtained by the ion detection unit after the voltage is switched by the voltage switching unit, calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion. The correction information storage unit stores correction information that corresponds to the elapsed time since the switching time and information related to the deviation of flight time or mass-to-charge ratio. The calibration unit uses the calibration information stored in the calibration information storage unit to correct the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time since the switching time when the detection result of the ion is obtained.

2. The time-of-flight mass analysis device as described in claim 1, characterized in that, The correction information is a correction value corresponding to the elapsed time since the switching point. The correction unit adds the correction value stored in the correction information storage unit to the flight time or mass-to-charge ratio calculated by the ion information acquisition unit.

3. The time-of-flight mass analysis device as described in claim 1, characterized in that, The correction information is a correction coefficient corresponding to the elapsed time since the switching point. The correction unit multiplies the correction coefficient stored in the correction information storage unit with the flight time or mass-to-charge ratio calculated by the ion information acquisition unit.

4. The time-of-flight mass analysis device as described in claim 1, characterized in that, It also includes a correction information acquisition unit that generates or modifies the correction information.

5. The time-of-flight mass analysis device as described in claim 4, characterized in that, It also has: An ion source generates ions originating from components contained in the sample; a sample introduction section introduces a known sample into the ion source. The correction information acquisition unit generates or modifies the correction information based on the change in flight time or mass-to-charge ratio over time since the switching moment, calculated from the intensity signal of ions originating from the known sample.

6. The time-of-flight mass analysis device as described in claim 4, characterized in that, The correction information acquisition unit pre-stores model functions corresponding to the correction information, and generates or modifies the correction information by changing the parameter values ​​contained in the model function. The correction information is related to the elapsed time and the deviation of the flight time or mass-to-charge ratio from the switching time.

7. The time-of-flight mass analysis device as described in claim 6, characterized in that, The model function includes at least one value of resistance, inductance, or capacitance in a simplified circuit connected to a power source that applies voltage to the electrodes forming the flight space as a parameter. The correction information acquisition unit acquires correction information by changing at least one of the parameter values ​​contained in the model function.

8. The time-of-flight mass analysis device as described in claim 7, characterized in that, The model function is a voltage response function that includes the values ​​of resistance and capacitance in a simplified circuit connected to the power supply unit as parameters.

9. The time-of-flight mass analysis device as described in claim 7, characterized in that, The model function is a decay response function that includes at least the value of the inductance in the simplified circuit connected to the power supply as a parameter. The correction information acquisition unit acquires the correction information by changing the attenuation response function through changing the value of the inductor.

10. The time-of-flight mass analysis device as described in claim 1, characterized in that, It also includes an ion ejection unit that is controlled to perform a measurement event of periodically and repeatedly ejecting ions originating from the sample component into the flight space. The ion information acquisition unit calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion based on the result of accumulating or averaging the intensity signal of the ion. The intensity signal of the ion is obtained for each of the multiple ion emission actions performed in the measurement event. The correction unit corrects the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time from the switching point to the start of the measurement event and a predetermined delay time from the start of the measurement event.

11. The time-of-flight mass analysis device as described in claim 10, characterized in that, The specified delay time is half the time required for the measurement event.

12. The time-of-flight mass analysis device as described in claim 1, characterized in that, It also includes a voltage monitoring unit to acquire a monitoring voltage corresponding to the voltage applied to at least one of the electrodes forming the flight space; The correction unit corrects the flight time or mass-to-charge ratio calculated by the ion information acquisition unit based on the elapsed time since the switching time and the monitoring voltage.

13. The time-of-flight mass analysis device as described in claim 1, characterized in that, The elapsed time from the switching point is less than 5 seconds.

14. The time-of-flight mass analysis device as described in claim 1, characterized in that, The flight space forming electrode includes a flight tube to which a high voltage of more than 1 kV is applied.

15. The time-of-flight mass analysis device as described in claim 1, characterized in that, The flight space forming electrode includes a reflector to which a high voltage of 500V or more is applied.

16. The time-of-flight mass analysis device as described in claim 1, characterized in that, The flight space forming electrode includes an electrode that forms multiple orbital paths for ions to circulate multiple times or multiple reflection paths for ions to reflect multiple times through an electric field.

17. The time-of-flight mass analysis device as described in claim 1, characterized in that, The flight space forming electrode includes an ion ejection electrode that ejects ions of the second polarity toward the flight space by being pulsedly applied with a high voltage of 1 kV or more.

18. A time-of-flight mass analysis method, characterized in that, have: The voltage switching step involves switching the voltage applied to the space-of-flight forming electrode at a predetermined switching time from a first voltage that causes ions of the first polarity to fly to a second voltage that causes ions of the second polarity to fly. The space-of-flight forming electrode forms a space for separating ions originating from components contained in the sample according to their mass-to-charge ratio. The ion information acquisition step, based on the detection result of the second polarity ion obtained by the ion detection unit that detects ions flying in the flight space after the voltage is switched in the voltage switching step, calculates the flight time of the ion in the flight space or the mass-to-charge ratio of the ion. The correction step uses correction information to correct the flight time or mass-to-charge ratio calculated in the ion information acquisition step based on the elapsed time since the switching time when the detection result of the ion is obtained. The correction information corresponds the elapsed time since the switching time to information related to the deviation of the flight time or mass-to-charge ratio.

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