JP6835360B2 - Flight time measurement type mass spectrometer and method - Google Patents

Description

The present invention relates to time-of-flight mass spectrometry, and in particular, high accuracy without impairing efficiency even for long-term measurement using time-of-flight mass spectrometry. It is related to the method of making measurements.

Multi-Reflection Time-of-Flight Mass Spectrometry (MRTOFMS) is known as one of the time-of-flight mass spectrometrys (Non-Patent Document 1 and Patent Document 1). In multiple reflection type flight time measurement type mass spectrometry, sample ions are launched into the flight tube, and the sample ions are reciprocated multiple times between the ion mirrors at both ends of the flight tube. After an appropriate time, the flight tube outlet is opened and the sample ions are launched. Measure the flight time to detection. Since the flight time is proportional to the 1/2 power of the mass of the sample ion, the mass of the sample ion can be measured by comparing the mass with the flight time of a known reference ion.

In the flight time measurement type mass spectrometry, it is necessary to measure the flight time of the reference ion whose mass is known and can be measured constantly as described above. In the flight time measurement method, it is necessary to measure two types of reference ions due to the indefiniteness of the ion launch time. However, as shown in Non-Patent Document 2, the multiple reflection type flight time measurement type mass spectrometry requires measurement. The mass of sample ions can be determined using only one type of reference ion.

In the multi-time type flight time measurement type mass spectrometry, as in Non-Patent Document 2, it was common to measure sample ions and reference ions separately and alternately. By performing the measurements alternately in this way, the drift of the measuring device can be compensated from the flight time of the reference ion. In rare cases where sample ions and reference ions coexist and can be measured at the same time, it is possible to compensate for the drift of the measuring device by using the flight time of the reference ions, but this is not common.

JP-A-57-44953

H. Wollnik et al, Int. J. Mass Spectrometry and Ion Processes, 96 (1990) 267. Y. Ito et al, Phys, Rev. C 88 (2013) 011306 (R). Y. Ito et al., Nuclear Instruments and Methods in Physics Research B 317 (2013) 544.

The conventional alternating measurement method has the following problems. First, when measuring reference ions, sample ions (measurement target ions) cannot be measured, and the measurement efficiency is reduced accordingly. For example, when the cycle of measuring the sample ion for 20 minutes and measuring the reference ion for 5 minutes is repeated, the sample ion cannot be measured for at least 20% of the measurement period.

Second, measuring device drift generally has various causes and different time constants. Therefore, it is not possible to ensure the same measurement conditions when measuring sample ions and when measuring reference ions, and it is difficult to completely compensate for the effects of drift.

In consideration of such a problem, an object of the present invention is to provide a method for performing flight time measurement type mass spectrometry, which has higher measurement efficiency than the conventional one and enables highly accurate and highly accurate measurement. To do.

In the first aspect of the present invention, the mass of the ion is measured by accelerating the ion accumulated in the first ion trap in a pulsed manner and introducing the ion into the flight tube to measure the flight time. It is an analyzer and is characterized by having the following configurations.

That is, the flight time measurement type mass measuring device according to this aspect accumulates the measurement target ions supplied from the source of the measurement target ions, and can introduce the measurement target ions into the first ion trap. It is provided with an ion trap and a third ion trap capable of accumulating reference ions supplied from a source of reference ions and introducing the reference ions into the first ion trap. In this embodiment, the first ion trap is configured so that the ion to be measured can be introduced from the second ion trap and the reference ion can be introduced from the third ion trap.

As described above, since ions can be introduced from the second and third ion traps into the first ion trap, the flight time measurement type mass measuring device of this embodiment can be introduced by the control means (1). Introduction of the measurement target ion from the second ion trap to the first ion trap, measurement of the flight time of the measurement target ion, and (2) from the third ion trap to the first ion trap. The introduction of the reference ion and the measurement of the flight time of the reference ion can be configured to be alternately performed in a predetermined pattern. Here, the predetermined pattern may be any pattern, but it is preferable that the predetermined pattern is a pattern in which the above operations (1) and (2) are alternately performed once.

In the prior art, measurements are performed alternately in a macro time structure of several minutes to several hours, but in this embodiment, measurements are performed alternately in a time structure on the order of 10 milliseconds, which is one launch and measurement of flight time. Since a second ion trap and a third ion trap are prepared for accumulating the measurement target ion and the reference ion, respectively, one of the sample ion and the reference ion is measured during the flight time measurement of the other ion. Can be accumulated in the ion trap. Specifically, during the period from the launch of the reference ion to the measurement of the flight time, the measurement target ion can be supplied from the source to the second ion trap to continue the accumulation. Similarly, during the period from the launch of the ion to be measured to the measurement of the flight time, the reference ion can be supplied from the source to the third ion trap to continue the accumulation. Therefore, the measurement target ion and the reference ion can be measured at the same time without impairing the measurement efficiency.

The flight time measurement type mass measuring device of this embodiment provides a correction means for correcting the flight time of the measurement target ion based on the measurement result of the flight time of the reference ion within a predetermined period including the time of measuring the flight time. It is also preferable to prepare further. Since the frequency of reference ions is adjustable, the reference ions can be measured every time. Therefore, even if the flight time of the reference ion is short, a sufficiently statistically meaningful measurement (acquisition of the flight time distribution) can be performed. By using this, it is possible to track the drift of the device using the flight time of the reference ion in a short time width, and it is possible to maintain the accuracy and accuracy of the measurement even if the measurement takes a very long time. is there.

The present invention can also be regarded as a flight time measurement type mass measurement method including the above steps. That is, the second aspect of the present invention is a flight time measurement in which the mass of the ions is measured by accelerating the ions accumulated in the first ion trap in a pulsed manner and introducing them into the flight tube to measure the flight time. It is a flight time measurement type mass measurement method using an expression mass measuring device.
The step of accumulating the measurement target ion supplied from the measurement target ion source in the second ion trap, and
The step of accumulating the reference ion supplied from the reference ion source in the third ion trap, and
(1) Introduction of the measurement target ion from the second ion trap to the first ion trap, measurement of the flight time of the measurement target ion, and (2) the first ion from the third ion trap. A step of alternately introducing the reference ion into the trap and measuring the flight time of the reference ion in a predetermined pattern, and
It is characterized by including.

According to the present invention, in the flight time measurement type mass spectrometry, the measurement efficiency is higher than the conventional one, and the measurement can be performed with high accuracy.

The figure which shows the structure of the multiple reflection type flight time measurement type mass measuring apparatus (MRTOF mass measuring apparatus) which concerns on embodiment. The figure explaining the potential control in a flight tube in a flight time measurement. The figure which shows the structure of the ion trap in an embodiment. The figure which shows the structure of the high voltage switch. The figure which shows the control sequence of the flight time measurement in an embodiment. The figure explaining the potential in the ion trap for storage and the ion trap for injection in each period. The flowchart explaining the mass determination process (drift correction process) in Embodiment. The figure which shows the experimental example using the MRTOF mass measuring apparatus which concerns on embodiment. The figure which shows the experimental example using the MRTOF mass measuring apparatus which concerns on embodiment.

[Measurement principle]
Hereinafter, the multiple reflection type flight time measurement type mass measuring device (hereinafter, also referred to as MRTOF mass measuring device) according to the embodiment of the present invention will be described. Since the MRTOF mass measuring device according to the present embodiment measures using a single reference ion as in Non-Patent Document 2, the mass of the sample ion (measurement target ion) can be measured only by the single reference ion. I will briefly explain that.

ここで、ＴｏＦが飛行時間、ｍが質量、Ｌが飛行長、Ｋが運動エネルギーである。The flight time of an ion is proportional to the 1/2 power of the mass of the ion as shown in the following equation.

Here, ToF is the flight time, m is the mass, L is the flight length, and K is the kinetic energy.

ここで、ｔ_０は飛行時間の時間原点と実際のイオンの射出時刻との差である。一般に、イオン射出時刻を厳密に決定することはできないので、試料イオンの質量決定のためには２種類の試料イオンの飛行時間を測定する必要がある。Accordingly, the mass m _x sample ion can be determined using its flight time t _x, mass mass m _r and time of flight t _r of known reference ion.

Here, t ₀ is the difference between the time origin of the flight time and the actual ion injection time. In general, since the ion injection time cannot be determined exactly, it is necessary to measure the flight times of two types of sample ions in order to determine the mass of the sample ions.

However, long flight length L in MRTOF mass measuring unit, also since the mass of the reference ions and the sample ions are substantially _equal, the _{t x} ~t r >> t ₀ is satisfied. Therefore, the following approximation holds with sufficiently high accuracy, and the mass of the sample ion can be determined using only a single reference ion.

[Device configuration]
FIG. 1 is a diagram showing a configuration of the MRTOF mass measuring device 10 according to the present embodiment. The MRTOF mass measuring device 10 includes a flight tube 11, a detector 12, an ion trap 13 for injection into the flight tube 11, an ion trap 14 for storing sample ions, an ion trap 15 for storing reference ions, a logic sequencer 16, and an analog multiplexer. 17. A high-voltage switch 18, a high-voltage regulated power supply 19, and an analyzer 20 are provided.

The flight tube 11 includes an ion mirror 11a on the incident side and an ion mirror 11b on the injection side. The ion mirror 11a is provided with an incident port 11c for introducing ions from the injection ion trap 13 into the flight tube 11, and the ion mirror 11b is provided with an injection port 11d for injecting ions from the flight tube 11 into the detector 12. The control of the potential distribution in the ion mirrors 11a and 11b is performed by the high voltage switch 18 controlling the voltage from the high voltage regulated power supply 19 according to the instruction from the logic sequencer 16.

The control of the potential distribution in the ion mirrors 11a and 11b will be described with reference to FIGS. 2 (A) to 2 (C). 2 (A) to 2 (C) are diagrams schematically showing the potential distribution in the flight tube 11.

When the ions are drawn from the injection ion trap 13 and introduced into the flight tube 11, the potential of the ion mirror 11a on the incident side is lowered to open the ion mirror, as shown in FIG. 2 (A). In FIG. 2A, the potential of the ion mirror 11a at the time of incident is indicated by reference numeral 111. This potential 111 is lower than the potential 112 when the ion mirror 11a is closed, and is large enough for the introduced ions to pass through. The ion mirror 11b is closed and has a potential of 113.

Then, as shown in FIG. 2B, the potential of the ion mirror 11a is increased and the ion mirror is closed before the incident ions return to the ion mirror 11a on the incident side. The potential 112 of the ion mirror 11a is large enough that ions cannot be overcome. As a result, the ions in the flight tube 11 reciprocate between the ion mirror 11a and the ion mirror 11b.

As shown in FIG. 2C, the potential of the ion mirror 11b is lowered and the ion mirror is opened at the timing when the ions reciprocate a predetermined number of times (for example, about 100 times). In FIG. 2C, the potential of the ion mirror 11b at the time of emission is indicated by reference numeral 114. This potential 114 is lower than the potential 113 when the ion mirror 11b is closed, and is large enough for ions to pass through. As a result, the ions jump out of the flight tube 11 and are detected by the detector 12.

The kinetic energy of the ions introduced into the flight tube 11 is not always constant. Therefore, it is preferable to set the potential for the ions to fly at different distances according to the kinetic energy so that the flight time required for the round trip between the ion mirrors depends only on the mass of the ions.

The detector 12 detects ions ejected from the flight tube 11. As the detector 12, existing parts such as a microchannel plate, a continuous dynode secondary electron multiplier tube, and a discontinuous dynode secondary electron multiplier tube can be adopted. The time when the ion is detected by the detector 12 is sent to the analyzer 20.

3 (A) and 3 (B) are diagrams showing the configurations of an injection ion trap 13, a sample ion storage ion trap 14, and a reference ion storage ion trap 15. As the sample ion storage ion trap 14 and the reference ion storage ion trap 15, a linear high-frequency quadrupole ion trap can generally be used. The continuously incident ion beam is decelerated and cooled by an ion trap filled with a small amount of gas, and accumulated at the bottom of the DC potential generated in the axial direction. The axial DC potential is supplied by the analog multiplexer 17, and its timing is controlled by the logic sequencer 16. The accumulated ions can be transported to the adjacent injection ion trap 13 at a predetermined timing.

The injection ion trap 13 is a device that cools the ions transported from the storage ion traps 14 and 15 and then ejects them in a pulsed manner in the orthogonal direction at a predetermined timing. Various structures can be taken, but in the embodiment, from the stripe 21 that gives a high frequency potential to the parallel plate type electrode and the central stripe 22 that gives a DC potential divided in the axial direction as shown in FIG. 3 (B). A linear high-frequency ion trap having a structure similar to that of the above was used. An injection port 23 is provided at the center of the central electrode of the central stripe 22, and ions can be injected from the injection ion trap 13 in a direction orthogonal to the parallel flat plate. By controlling the potential applied to the central striped electrode, it is possible to perform incident from above, incident from below, and pulse emission in the direction perpendicular to the center at predetermined timings (see Non-Patent Document 3). ..

The ion beam generated at the sample ion supply source is decelerated and cooled before being introduced into the sample ion storage ion trap 14 (second ion trap). Sample ions are accumulated and cooled in the ion trap 14. The analog multiplexer 17 controls the potential between the ion trap 13 and the ion trap 14 according to the instruction from the logic sequencer 16, so that the sample ions accumulated in the ion trap 14 are moved to the ion trap 13.

The configuration of the reference ion storage ion trap 15 (third ion trap) is the same as that of the sample ion ion trap 14. Reference ions are accumulated in the storage ion trap 15. For the reference ion, select an ion that has almost the same mass as the sample ion and is constantly available. The frequency of supply from the reference ion supply source to the storage ion trap 15 is preferably adjusted so that one ion is supplied for each ion injection cycle described later.

The injection ion trap 13 (first ion trap) can supply sample ions from the storage ion trap 14, and can supply reference ions from the storage ion trap 15. Further, the injection ion trap 13 can cool the accumulated ions and pulse-accelerate the accumulated ions at the timing instructed by the logic sequencer 16 to inject them into the flight tube 11. In the present embodiment, the injection ion trap 13 has a flat plate shape, receives sample ions and reference ions from two in-plane directions facing each other, and ejects ions in the vertical direction. The injection of ions from the injection ion trap 13 into the flight tube 11 is performed by the high voltage switch 18 controlling according to the instruction from the logic sequencer 16.

The high voltage switch 18 performs ion injection from the injection ion trap 13 to the flight tube 11, potential control of the ion mirror 11a, and potential control of the ion mirror 11b. The high voltage switch 18 can be configured by using an existing high voltage FET (field effect transistor). However, if the potentials of the ion mirrors 11a and 11b fluctuate, the flight time of the ions varies. Therefore, high stability is required for the potential control of the ion mirrors 11a and 11b. Therefore, in the present embodiment, a high-voltage switch for controlling the ion mirrors 11a and 11b is configured by using a photodiode switch.

FIG. 4 is a circuit diagram of a high voltage switch 181 that controls the ion mirrors 11a and 11b. One ion mirror can be controlled by the circuit shown in the figure, and one high voltage switch 181 is used for each of the ion mirrors 11a and 11b. The high-voltage switch 181 turns on the high-voltage photodiode switch element 136 on the positive side and outputs a high voltage on the high-potential side according to the input signal from the logic sequencer 16, or the high-voltage photodiode switch element on the negative side. Turn on 146 to switch whether to output a positive voltage on the low potential side.

A control signal for controlling the potential of the ion mirror 11 is input to the input terminal 121 from the logic sequencer 16. Here, the potential of the ion mirror is controlled to take a high potential (potential 112 or 113 in FIG. 2) when the control signal is on, and to take a low potential (potential 111 or 114 in FIG. 2) when the control signal is off. It shall be.

The shock absorber 122 separates the input control signal into a non-inverting signal and an inverting signal. The non-inverting signal is input to the one-shot multivibrator 131. The one-shot multivibrator 131 is a circuit that outputs a short pulse signal at the rising edge of an input signal. After being amplified, this pulse signal is input to the drive circuit 132 for driving the light emitting diode 133. Further, the non-inverting signal output from the shock absorber 122 is input to the drive circuit 134 for driving the light emitting diode 135.

When there is a signal input, the drive circuits 132 and 134 supply electric power to the light emitting diodes 133 and 135 to control the light emission of the light emitting diodes 133 and 135. The photodiode switch element 136 is arranged so as to be able to receive the light emitted by the light emitting diodes 133 and 135, and when receiving the light from the light emitting diodes 133 or 135, the high voltage on the high potential side is output to the output terminal 148. Is output to the ion mirror 11.

The light emitting diode 133 is used for a short period of time when the control signal rises, that is, to enhance the brightness at the beginning of the light emitting diode. The emission brightness of the light emitting diode 133 and the light emitting diode 135 may be the same or different. In order to increase the emission brightness of either one of the light emitting diodes, the supply current may be increased or the number of light emitting diodes may be increased.

With such a configuration, when a control signal for controlling the potential of the ion mirror 11 to a high potential is input, when the control signal rises, the photodiode switch element 136 is emitted by high-intensity light that is a combination of the light emitting diode 133 and the light emitting diode 135. Is driven, and in the steady state, the photodiode switch element 136 is driven by the light from the light emitting diode 135. As a result, the potential of the ion mirror 11 rises sufficiently steeply when the control signal rises, and a stable high-voltage potential is maintained at steady state.

Further, the configuration on the low potential side, that is, the one-shot multivibrator 141, the drive circuit 142, the light emitting diode 143, the drive circuit 144, the light emitting diode 145, and the photodiode switch element 146 are the same as the configuration on the high potential side. The difference is that the inverting signal is supplied from the shock absorber 122 and the photodiode switch element 146 outputs a high voltage on the low potential side.

With such a configuration, when a control signal for controlling the potential of the ion mirror 11 to a low potential is input, when the control signal falls, the photodiode switch element is generated by high-intensity light that combines the light emitting diode 143 and the light emitting diode 145. The 146 is driven, and the photodiode switch element 146 is driven by the light from the light emitting diode 145 in the steady state. As a result, the potential of the ion mirror 11 drops sufficiently steeply when the control signal falls, and a stable high-potential on the low potential side is maintained during steady state.

The control signal input from the logic sequencer 16 to the high voltage switch 181 will be briefly described. In the present embodiment, the potential of the ion mirror 11 becomes high when the control signal is on, and the potential of the ion mirror 11 becomes low when the control signal is off. Therefore, an on signal is normally supplied to the high voltage switch 181. As shown in FIG. 2A, in order to lower the potential of the ion mirror 11a, an off signal is supplied to the high voltage switch 181 that controls the ion mirror 11a. Similarly, as shown in FIG. 2C, an off signal is supplied to the high voltage switch 181 that controls the ion mirror 11b during the period of lowering the potential of the ion mirror 11b.

The analysis device 20 includes a computer (information processing device) including a computing device such as a CPU, a main storage device, an auxiliary storage device, an input device, an output device, and the like, and a TDC (time digital converter) for measuring flight time. By executing the program, the flight time data of the sample ion and the reference ion measured by the detector 12 is stored in the storage device, and the mass of the sample ion is determined from the value.

[Measurement sequence]
Next, control regarding ion accumulation and injection in the present embodiment will be described. In the present embodiment, the ions injected into the flight tube 11 are reciprocated about 100 times and then detected by the detector 12. The time required for the above round trip is about 2 to 8 milliseconds, but if the time required before and after that is taken into consideration, it takes about 10 milliseconds for one injection. In the prior art, the flight time measurement of the sample ion is repeated for, for example, 20 minutes, the flight time of the reference ion is repeated for 5 minutes, and the measurement cycle consisting of these 25 minutes is repeatedly executed. On the other hand, in the present embodiment, the sample ion and the reference ion are measured alternately in a micro measurement cycle on the order of 10 milliseconds.

FIG. 5 is a diagram showing a sequence related to control such as accumulation of sample ions and reference ions in an ion trap, injection into a flight tube 11, and measurement of flight time by the logic sequencer 16. The uppermost part of the figure shows the timing of ion accumulation in the sample ion storage ion trap 14 and the supply of sample ions to the injection ion trap 13. The second stage represents the accumulation of ions in the injection ion trap 13 and the timing of injection of the flight tube 11. The third stage represents the timing of flight time measurement in which ions are flown into the flight tube 11 and the ions are detected by the detector 12. The bottom row represents the timing of ion accumulation in the reference ion storage ion trap 15 and the supply of the reference ion to the injection ion trap 13.

FIG. 5 shows a sequence of one measurement cycle consisting of the flight time measurement of the sample ion and the flight time measurement of the reference ion. In the period 201, the analog multiplexer 17 controls the potential between the ion traps 13 and 14 based on the control command from the logic sequencer 16 to introduce the sample ions accumulated in the ion trap 14 into the injection ion trap 13. The movement of ions between ion traps takes place in a short time (<1 ms). Immediately after the movement of the accumulated sample ions is completed, the accumulation of the sample ions supplied from the supply source starts in the ion trap 14 (period 206).

During period 202, the sample ions are accumulated in the injection ion trap 13 and cooled. FIG. 6A is a diagram showing the potential distribution in the ion traps 13 to 15 and the ions accumulated in each ion trap when the sample ions are cooled in the injection ion trap 13. As shown in FIG. 6A, a potential barrier is provided between the ion traps 13 and 14 and between the ion traps 13 and 15, and no ion movement occurs between the ion traps. Further, at this time, the ions accumulated in the injection ion trap 13 are sample ions, the sample ions are introduced into the ion trap 14 from the supply source, and the reference ions are introduced into the ion trap 15 from the supply source. Has been done.

When the cooling period 202 of the injection ion trap 13 is completed, a voltage is applied in the vertical direction of the ion trap 13 based on a control command from the logic sequencer 16 to pulse sample ions toward the flight tube 11. At the same time, the logic sequencer 16 lowers the potential of the ion mirror 11a on the incident side so that the sample ion can be incident from the incident port 11c.

The period 203 is a flight time measurement period in which the sample ions are detected by the detector 12 after the sample ions are flown in the flight tube 11. After introducing the sample ions into the flight tube 11, the potential of the ion mirror 11a on the incident side is increased and the ion mirror is closed. As a result, the sample ions in the flight tube 11 reciprocate between the ion mirror 11a and the ion mirror 11b. The injection-side ion mirror 11b is opened at the timing when the ions reciprocate a predetermined number of times, and the sample ions jump out of the flight tube 11 and are detected by the detector 12.

Before the flight time measurement period 203 of the sample ions is completed, the reference ions accumulated in the ion trap 15 are introduced into the injection ion trap 13 in the period 203. The specific operation is the same as in the case of the period 201. Further, after the movement of the reference ion from the ion trap 15 to the injection ion trap 13 is completed, the accumulation of the reference ion from the supply source starts in the ion trap 15.

FIG. 6B is a diagram showing the potential distribution in the ion traps 13 to 15 and the ions accumulated in each ion trap when the reference ion is moved from the reference ion storage ion trap 15 to the injection ion trap 13. Is. As shown in the figure, the potential barrier between the ion traps 13 and 15 is removed, and the reference ions accumulated in the ion trap 15 move to the lower potential injection ion trap 13.

During period 204, the reference ions are accumulated in the injection ion trap 13 and cooled. FIG. 6C is a diagram showing the potential distribution in the ion traps 13 to 15 and the ions accumulated in each ion trap when the reference ions are cooled in the injection ion trap 13. The potential distribution is the same as in the case of FIG. 6A, except that the ions accumulated and cooled in the injection ion trap 13 are reference ions. As shown in FIG. 6A, a potential barrier is provided between the ion traps 13 and 14 and between the ion traps 13 and 15, and no ion movement occurs between the ion traps. At this point, the ions accumulated in the injection ion trap 13 are reference ions, sample ions are introduced into the ion trap 14 from the supply source, and reference ions are introduced from the supply source into the ion trap 15. Has been done. During this cooling period 204, the sample ion measurement period 203 is terminated, and the measurement of the next flight time can be started.

When the cooling period 204 of the reference ion in the injection ion trap 13 is completed, the reference ion is injected from the injection ion trap 13 into the flight tube 11 based on the control command from the logic sequencer 16 to start the flight time measurement. The specific operation is the same as the measurement of sample ions (period 203).

With the above, one cycle is completed, and the above processing is repeated after the period 207.

According to this method, since the measurement of the sample ion and the reference ion is switched for each flight, the same measurement conditions can be guaranteed. In addition, storage ion traps are prepared for each of the sample ion and the reference ion so that the sample ion and the reference ion can be stored and cooled independently. As a result, the reference ions can be accumulated in the storage ion trap 14 during the flight time measurement (period 205, etc.), and the reference ions can be accumulated during the flight time measurement of the sample ions (period 203, etc.). Accumulation in the ion trap 15 is possible. In this way, the accumulation of the other ion can be continued during the flight time of the other ion, so that the two measurements can proceed simultaneously without loss.

[Mass determination process]
The mass determination process in the analyzer 20 will be described. In the MRTOF mass measuring device, the mass of the sample ion is determined by obtaining the flight time and statistical error based on the distribution of the flight time of the sample ion and the reference ion (flight time spectrum). Here, if the measuring device drifts (fluctuation of high-voltage power supply, mechanical expansion and contraction of the device, etc.) during the measurement period, the distribution expands or moves, so both statistical error and systematic error become large and the measurement accuracy is improved. The accuracy deteriorates.

However, in the measurement method of the present embodiment, the flight times of the sample ions and the reference ions are measured at about the same time, so that the influence of the drift of the measuring device affects the flight time distribution of the sample ions and the flight time distribution of the reference ions. Equally affected, systematic errors are equally affected. Therefore, even if a large drift occurs during the measurement period, the accuracy of the measurement is only deteriorated, and the accuracy of the measurement can be kept high.

As described above, highly accurate measurement is possible without performing correction processing in consideration of the influence of drift. In the present embodiment, by correcting the influence of drift, it is possible to perform measurement while maintaining accuracy as well as accuracy. Specifically, since the reference ion can be adjusted so that the ion enters almost every flight, a sufficiently statistically significant flight time distribution can be obtained even in a short time. This makes it possible to evaluate and correct the effects of drift using the flight time of the reference ion every short time. Hereinafter, a detailed procedure will be described with reference to FIG. 7.

FIG. 7 is a flowchart illustrating the mass determination process in the present embodiment. In step S401, the analysis device 20 selects the measurement time t. The time between the measurement start time and the measurement end time may be selected for each appropriate time step.

In step S402, the analyzer 20 evaluates the effect of drift from the flight time distribution of the reference ions from time t−α / 2 to time t + α / 2. Here, the time α is the time from which the number of events for which a statistically significant flight time can be obtained can be obtained from the measurement result of the flight time of the reference ion within that period. For example, α = 10 seconds can be set. The effect of drift on the flight time can be determined from the difference between the flight time of the reference ion and the preset flight time of the reference ion by obtaining the flight time of the reference ion based on the flight time distribution within the period.

In step S403, the analyzer 20 corrects the effect of the drift obtained in step S402 on the flight time of the sample ion and the flight time of the reference ion at time t. When the time step in step S401 is Δt, the flight time measured between the time t−Δt / 2 and t + Δt / 2 may be corrected in the same manner.

In step S404, it is determined whether or not the above processing has been performed for all the measurement periods, and if not completed, the process returns to step S401 and the same processing is repeated for the next time step. When the processing for the entire period is completed, the processing proceeds to step S405.

In step S405, the analyzer 20 determines the mass of the sample ions based on the flight time distribution consisting of the flight times of the sample ions and the reference ions corrected as described above.

By determining the mass of sample ions in this way, the effect of drift at each time can be corrected, so even if the measurement takes a very long time (for example, several days), the accuracy and accuracy will be high. It is possible to measure while keeping both high.

[Experimental example]
Hereinafter, the measurement performed using the MRTOF mass measuring device according to the present embodiment will be described. Here, for convenience, a mass measurement test of ¹³⁸ Ba ^{+ was carried out using 138} Ba ⁺ as a sample ion and ¹³³ Cs ⁺ as a reference ion. In order to symbolically observe the drift phenomenon, the vacuum chamber of the MRT OFMS device was heated with a heater and slowly changed by about 10 ° C for measurement.

FIG. 8 (A-1) shows the flight time measurement result ^{of the reference ion 133} Cs ^{+ for each measurement time.} The horizontal axis represents the measurement time, and the vertical axis represents the flight time. The vertical axis is in nanoseconds with 7,924,706.5 nanoseconds as the origin. As can be read from the figure, it can be seen that a flight time drift of 57 ppm occurs in the measurement for 1080 seconds. FIG. 8 (A-2) ^{also shows the time change of the flight time of the sample ion 138} Ba ⁺ , and it can be seen that it has the same time dependence.

FIG. 8 (B-1, B-2) shows the number of detected ^{reference ions 133} Cs ⁺ and sample ions ¹³⁸ Ba ^{+ for each measurement time.} The horizontal axis represents the measurement time, and the vertical axis represents the number of detections per 20,000 cycles (= 400 seconds). The change in the number of detections is caused by the change in the ion beam intensity, and it can be seen from the figure that the ion beam intensity changes during the measurement period.

FIG. 8 (C-1, C-2, D-1, D-2) shows the flight time distribution of each ion. FIG. 8 (C-1, D-1) shows ^{the flight time distribution of reference ion 133} Cs ⁺ (without and with correction processing), and FIG. 8 (C-2, D-2) shows the flight time ^{of sample ion 138} Ba ^+. Distribution (without and with correction) The horizontal axis shows the flight time in nanoseconds based on the reference time (7,925,260 nanoseconds and 8,072,953 nanoseconds, respectively), and the vertical axis shows the ion unit time (3.2 nanoseconds here). ) Indicates the number of detections.

Since the drift as shown in FIG. 8 (A-1, A-2) occurs during the measurement period, the data without the correction process in FIG. 8 (C-1, C-2) greatly spreads. It has an asymmetric flight time distribution. However, since both the reference ion and the sample ion are drifting in the same way, the calculated flight time ratio 1.0186368 (± 3 ppm) is the true value 1.018635944 (± 0.001 ppm) (both ¹³⁸ Ba and ¹³³ Cs are stable isotopes, so they are precise. The mass is known) and the range of statistical error is in good agreement. It shows that highly accurate measurement is possible even if such a large drift occurs.

Further, FIG. 8 (D-1, D-2) also shows the flight time distribution after drift correction by the method shown in FIG. 7. As a result, the spread of flight time is narrowed by almost half, and the flight time measurement accuracy is improved. As a result, the flight time ratio is 1.0186357 (± 0.5ppm), and it can be seen that the accuracy of flight time measurement (that is, mass measurement accuracy) is improved.

9 (A) to 9 (E) are the results of performing the same measurement as above with the high-voltage power supply stabilizing mechanism and the temperature stabilizing mechanism turned off, although the conditions are different. FIG. 9A shows the flight time measurement result ^{of the reference ion 133} Cs ^{+ for each measurement time.} Since the stabilization mechanism was turned off immediately after the start of the measurement, a jump occurred in the measurement result of the flight time, and a large fluctuation occurred thereafter. Specifically, a flight time drift of 25 ppm occurs in the one-hour measurement.

9 (B) and 9 (C) show the flight time distributions of ^{the sample ion 138} Ba ⁺ and the reference ion ¹³³ Cs ^{+ before the correction treatment, respectively.} As can be seen from the figure, the distribution is very wide and two peaks can be seen.

9 (D) and 9 (E) show the flight time distributions of ^{the sample ion 138} Ba ⁺ and the reference ion ¹³³ Cs ^{+ after the correction treatment, respectively.} The correction process corrects the effect of drift and obtains a flight time distribution with a relatively steep peak. As described above, according to the measurement method according to the present embodiment, by adding the correction process, highly accurate measurement becomes possible even when a large drift occurs.

[Advantageous effect of this embodiment]
The flight time measurement type mass spectrometer according to the present embodiment enables the introduction of ions from two ion traps, one for sample ions and the other for reference ions, into the ion trap for injection. This makes it possible to alternately fly the sample ion and the reference ion once. In addition, during one flight time measurement, the other ion can be accumulated. Therefore, the efficiency of measurement is improved.

In the conventional flight time measurement type mass spectrometer, only one storage ion trap can introduce ions into the injection ion trap. Therefore, in order to switch the measurement between the sample ion and the reference ion, the storage is performed. It was necessary to switch the beamline connected to the ion trap. Therefore, unlike the present embodiment, it has not been possible to efficiently perform the measurement in a manner in which the flight time measurement of the sample and the reference ion and the ion accumulation are overlapped.

Further, in the present embodiment, the effect of drift is evaluated using the flight time distribution of reference ions obtained in a relatively short period of time, and the effect of drift is corrected. This also improves the accuracy of the measurement.

Further, in the present embodiment, since the high voltage switch 181 is configured by using the photodiode switch, noise generated during switching can be suppressed, and the voltage waveform of the ion mirror after the switch can be kept stable. it can. The stability of the voltage waveform enables highly accurate mass measurement. When a high-voltage switch is configured by using a high-voltage FET, a high-speed switch (about 0.1 microsecond) is possible, but the voltage waveform after the switch is not stable due to ringing. When a photodiode switch is used, the switch speed is about several microseconds, but the time required for an ion to make one round trip in the flight tube 11 is about 20 to 80 microseconds under typical conditions. Therefore, the high voltage switch 181 of the present embodiment is sufficiently high in speed and excellent in stability.

Further, in the high voltage switch 181 of the present embodiment, the logic circuit to the light emitting diode can be arranged at the ground potential, and the high voltage photodiode switch can be arranged electrostatically completely independently. Therefore, the circuit is not destroyed even if an event such as short-time discharge occurs, and the high voltage switch can be used stably for a long period of time. When a high-voltage FET is used, the element frequently fails when a surge occurs and needs to be replaced. However, by using the high-voltage switch of the present embodiment, such a failure can be avoided.

[Modification example]
The above-described embodiment is merely an example for realizing the present invention, and the present invention is not limited to the disclosed contents. The present invention can be carried out by appropriately adding modifications that can be made by those skilled in the art within the scope of the technical idea.

For example, in the above explanation, the sample ion and the reference ion are alternately injected once to measure the flight time, but while the flight time of one ion is being measured, the other ion is accumulated. If cooling is possible, there are cases where the result of improvement in measurement accuracy and measurement efficiency can be obtained without necessarily alternately injecting ions. For example, consider the case where the sample ions are very rare but have a sufficiently long life. This corresponds to the measurement of long-lived unstable nuclei and environmental trace materials. In this case, it is preferable to fly the reference ion about 50 times while storing the sample ion in the storage ion trap for a long period of about several seconds and flying it once. By doing so, the reference ion can be measured in a short time so that the statistical error is sufficiently reduced without reducing the efficiency of the sample ion measurement. This allows for drift correction with a shorter time frequency and thus allows for more accurate measurements under wider conditions. As a reverse example, consider the measurement of rare unstable nuclei with extremely short life (several milliseconds). In this case, since there is no effect even if the sample ions are stored in the sample storage ion trap for a long time, it is more efficient to repeat the flight of the sample ions as frequently as possible. On the other hand, since it is also necessary to measure the reference ion, for example, a method of maintaining efficiency, accuracy, and accuracy by adopting a special time structure in which the next flight after detecting the target rare nucleus is assigned to the flight of the reference ion is effective.

Further, in the above description, in the mass measurement method of the multiple reflection (cycle) type flight time measurement method, a method using a single reference ion is described as an example, but both multiple reflection and single reference ion are indispensable. It is not a simple configuration. The present invention can also be applied when a plurality of reference ions are used. In this case, it is preferable to configure the ion trap for injection to supply sample ions and two (or more) types of reference ions, and alternately inject these ions to measure the flight time. Further, the present invention is not limited to the closed-circuit multiple reflection type, as long as it is a flight time measurement method, and can be used for any of the open-path multiple-reflection type, linear type, reflector (single-reflection) type, open-path and closed-road track type, and the like. Applicable.

However, the embodiment described above is a preferred embodiment in terms of measuring the mass of rare particles. Since rare particles are generated infrequently, there is a demand for measurement without reducing efficiency as much as possible. In the above embodiment, the flight time can be measured without wasting the generation of rare particles. In addition, since the target rare particles are not ejected in most of the rare particles, long-term measurement is required, and it is unavoidable that the measurement is affected by the drift. Therefore, the above-described embodiment, which enables highly accurate measurement and further accurate measurement by drift correction processing, is useful for mass measurement of rare particles. Further, in the above embodiment, since the flight time can be measured in about several milliseconds, it is possible to measure short-lived nuclei having a lifetime of 0.1 seconds or less and very heavy nuclei, and such rare particles can be measured. Since it can be measured with high efficiency, it is particularly useful for measuring the mass of such particles.

Of course, the present invention is not limited to the measurement of short-lived particles, and can be applied to the measurement of arbitrary charged particles. For example, it can be preferably applied to molecular composition analysis and trace substance analysis. High accuracy and high accuracy can be maintained even when it is difficult to maintain the stability of the device or high-voltage power supply in the harsh measurement environment assumed in such an application.

11: Flight tube 12: Detector 13: Ion trap for injection 14: Ion trap for sample ion storage 15: Reference Ion trap for ion storage

Claims (8)

A flight time measurement type mass measuring device that measures the mass of the ions by accelerating the ions accumulated in the first ion trap and introducing them into the flight tube to measure the flight time.
A second ion trap capable of accumulating the measurement target ions supplied from the measurement target ion source and introducing the measurement target ions into the first ion trap, and
A third ion trap capable of accumulating reference ions supplied from a source of reference ions and introducing the reference ions into the first ion trap, and a third ion trap.
A high-voltage switch for switching the potential of the ion mirror provided in the flight tube between the first potential and the second potential,
With
The high voltage switch
An input unit that inputs a control signal that indicates the potential of the ion mirror, and
A first light emitting element that emits light when the control signal rises,
A second light emitting element that emits light while the control signal is on, and
A first photodiode switch element that controls to apply a first potential to the ion mirror when light emission from the first or second light emitting element is detected.
A third light emitting element that emits light when the control signal falls, and
A fourth light emitting element that emits light while the control signal is off, and
A second photodiode switch element that controls to apply a second potential to the ion mirror when light emission from the third or fourth light emitting element is detected.
Have,
Flight time measurement type mass measuring device. (1) Introduction of the measurement target ion from the second ion trap to the first ion trap, measurement of the flight time of the measurement target ion, and (2) the first ion from the third ion trap. Further provided is a control means for alternately introducing the reference ion into the trap and measuring the flight time of the reference ion in a predetermined pattern.
The flight time measuring type mass measuring device according to claim 1. The control means: (1) introduction of the measurement target ion from the second ion trap to the first ion trap, measurement of the flight time of the measurement target ion, and (2) from the third ion trap. The introduction of the reference ion into the first ion trap and the measurement of the flight time of the reference ion are alternately performed once.
The flight time measuring type mass measuring device according to claim 2. The second ion trap receives the supply of the measurement target ion from the measurement target ion source even during the flight time measurement of the reference ion.
The flight time measuring type mass measuring device according to any one of claims 1 to 3. The direction of introduction of ions from the second ion trap to the first ion trap and the direction of introduction of ions from the third ion trap to the first ion trap are the flight from the first ion trap. It is perpendicular to the direction of ion introduction into the tube,
The flight time measuring type mass measuring device according to any one of claims 1 to 4. A correction means for correcting the flight time of the measurement target ion based on the measurement result of the flight time of the reference ion within a predetermined period including the time of measuring the flight time is further provided.
The flight time measuring type mass measuring device according to any one of claims 1 to 5. The light emission of the first light emitting element is controlled by the control signal via the one-shot multivibrator.
The light emission of the second light emitting element is controlled by the control signal.
The light emission of the third light emitting element is controlled by the inversion signal of the control signal via the one-shot multivibrator.
Light emission of the fourth light emitting element is controlled by an inverted signal of the control signal.
The flight time measuring type mass measuring device according to any one of claims 1 to 6. Flight time measurement type mass measurement using a flight time measurement type mass measuring device that measures the mass of the ions by accelerating the ions accumulated in the first ion trap and introducing them into the flight tube to measure the flight time. It's a method
The step of accumulating the measurement target ion supplied from the measurement target ion source in the second ion trap, and
The step of accumulating the reference ion supplied from the reference ion source in the third ion trap, and
(1) Introduction of the measurement target ion from the second ion trap to the first ion trap, measurement of the flight time of the measurement target ion, and (2) the first ion from the third ion trap. A step of alternately introducing the reference ion into the trap and measuring the flight time of the reference ion in a predetermined pattern, and
A step of inputting a control signal indicating the potential of the ion mirror provided in the flight tube, and
The first potential is set when light emission from at least one of a first light emitting element that emits light at the rising edge of the control signal and a second light emitting element that emits light while the control signal is on is detected. Using a first photodiode switch element that controls to be applied to the ion mirror, a first potential is applied to the ion mirror at the rising edge of the control signal and while the control signal is on, and When the light emission from at least one of the third light emitting element that emits light when the control signal falls and the fourth light emitting element that emits light while the control signal is off is detected, the second potential is set. A step of applying a second potential to the ion mirror when the control signal falls and while the control signal is off, using a second photodiode switch element that is controlled to be applied to the ion mirror. When,
Flight time measurement type mass measurement method including.

Images