WO2020166111A1

WO2020166111A1 - Mass spectrometer

Info

Publication number: WO2020166111A1
Application number: PCT/JP2019/030136
Authority: WO
Inventors: 一狭間
Original assignee: 株式会社島津製作所
Priority date: 2019-02-14
Filing date: 2019-08-01
Publication date: 2020-08-20
Also published as: JPWO2020166111A1; JP7074214B2

Abstract

This mass spectrometer has an ion trap (2), uses resonant excitation discharge to perform a mass scan, and is provided with: voltage generation units (4, 5) which generate a high-voltage square wave and a low-voltage square wave; a voltage amplitude adjustment information acquisition unit (72) which, on the basis of the results of performing, for multiple calibration samples of which the precise m/z value is known, a mass scan in which, while adjusting the voltage amplitude of the high-voltage square wave, the frequency of the high-voltage square wave and the low-voltage square wave is synchronously scanned so as to scan m/z of target ions, acquires voltage amplitude adjustment information for which mass error in m/z corresponding to each of the multiple calibration samples falls within a permissible range; and a control unit (76) which, during implementation of mass spectrometry across a prescribed m/z range for a target sample, on the basis of the voltage amplitude adjustment information, controls the voltage generation unit so as to change the voltage amplitude accompanying scanning of the high-voltage square wave frequency. By this means, it is possible to improve mass accuracy in the mass spectrum in the case of performing mass scanning using resonant excitation discharge.

Description

Mass spectrometer

The present invention relates to a mass spectrometer equipped with an ion trap that captures ions by the action of a high-frequency electric field.

In a mass spectrometer, an ion trap captures and confine ions by the action of a high-frequency electric field, selects ions having a specific mass-to-charge ratio m/z, and further dissociates the selected ions. Used for. As the ion trap, one ring electrode whose inner surface has a rotating one-lobed hyperboloid shape and a pair of end cap electrodes whose inner surfaces are opposed to each other with the ring electrode sandwiched therebetween have a rotating two-lobed hyperboloid shape The three-dimensional quadrupole type ion trap and the linear type ion trap composed of four substantially cylindrical rod electrodes arranged in parallel with each other are well known. In this specification, for convenience, the ion trap will be described by taking a “three-dimensional quadrupole ion trap” as an example.

In a general ion trap, a sinusoidal high-frequency voltage is usually applied to the ring electrode to form a high-frequency electric field for trapping ions in the space surrounded by the ring electrode and the end cap electrode, and the high-frequency electric field generates ions. Confine while vibrating. On the other hand, an ion trap that traps ions by applying a rectangular wave voltage to the ring electrode instead of the sinusoidal high frequency voltage has been developed (see Patent Document 1, Non-Patent Document 1, etc.). This type of ion trap is called a digital ion trap (DIT=Digital Ion Trap) because a square wave voltage having a voltage level corresponding to two logical values of “H” and “L” is usually used. ..

In the digital ion trap, as described in Non-Patent Document 1, a rectangular wave voltage having a predetermined frequency according to the mass-to-charge ratio range of ions to be trapped is applied to a ring electrode as a trapping high-frequency voltage. To confine ions in the mass-to-charge ratio range. When the ions thus trapped are sequentially ejected from the ion emission port according to the mass-to-charge ratio and detected by a detector provided outside the ion emission port, the resonance excitation phenomenon of the ions is used. That is, a rectangular wave low voltage (usually, the voltage amplitude is several times), which is obtained by dividing a rectangular wave high voltage (usually, the voltage amplitude is several hundreds V or more) applied to the ring electrode by a predetermined division ratio (for example, 1/4 division). V, which is significantly smaller than the above-mentioned rectangular wave high voltage, is referred to as “low voltage”) and is applied to the end cap electrodes, and the rectangular wave high voltage and the rectangular wave low voltage are maintained while the voltage amplitude of the rectangular wave voltage is kept constant. Scan frequencies synchronously. As a result, the ions trapped in the ion trap are resonantly excited in the order of mass-to-charge ratio and vibrate greatly, and are ejected to the outside of the ion trap through the ion emission port. By detecting the ejected ions with a detector, it is possible to create a mass spectrum over a predetermined mass-charge ratio range.

As described in Non-Patent Document 1, although the relationship between the frequency of the rectangular wave high voltage in resonant excitation and ejection and the mass-to-charge ratio of ejected (resonance excited) ions is theoretically determined, it is actually Due to various factors such as the shape of the electrodes that make up the ion trap, the limit of assembly accuracy, etc., there is a difference between the mass-to-charge ratio of ions that should be theoretically ejected and the mass-to-charge ratio of ions that are actually ejected. Occurs. Therefore, generally, the difference between the theoretical mass-to-charge ratio value and the measured mass-to-charge ratio value is obtained for a plurality of species (usually two species) of which the precise mass-to-charge ratio is known, and based on the plurality of difference values. A calibration formula is calculated by using the calibration formula, and mass calibration (calibration) is performed to calibrate a measured mass-to-charge ratio using the calibration formula (see Patent Document 1 and the like). Usually, the calibration formula is a linear formula based on the difference value between two kinds of ions.

JP, 2011-96542, A

However, according to the experiments by the present inventor, even if the above-described mass calibration is performed, the mass error may not be sufficiently reduced partially in the mass-to-charge ratio range. May be low.

The present invention has been made to solve the above-mentioned problems, and in a mass spectrometer that uses a digital ion trap and selectively ejects ions from the ion trap by resonance excitation ejection to detect, the target mass charge Its main purpose is to improve the mass accuracy of the mass spectrum over the entire ratio range.

One embodiment of the present invention made to solve the above problem has an ion trap for trapping ions in a space surrounded by three or more electrodes, and at least one electrode is provided with a rectangular wave voltage for trapping ions. By applying a rectangular wave voltage for resonance excitation to a pair of electrodes arranged opposite to each other while being applied, ions having a specific mass-to-charge ratio are selectively ejected from the ion trap by resonance excitation. In the mass spectrometer to detect by
A voltage generation unit that generates a rectangular wave voltage for ion trapping and a rectangular wave voltage for resonance excitation,
Targeting a plurality of calibration samples whose precise mass-to-charge ratio values are known, while adjusting the voltage amplitude of the rectangular wave high voltage for ion trapping, the ion trapping is performed so as to scan the mass-to-charge ratio of the ions to be detected. And based on the result of the mass analysis in which the frequency of the rectangular wave voltage for resonance excitation is synchronously scanned, the voltage amplitude adjustment in which the mass error in the mass-to-charge ratio corresponding to each of the plurality of calibration samples falls within the allowable range. A voltage amplitude adjustment information acquisition unit that acquires information,
At the time of performing mass analysis over a predetermined mass-to-charge ratio range for the target sample, based on the voltage amplitude adjustment information, a rectangular wave high voltage for ion trapping accompanying the frequency scanning of the rectangular wave voltage for ion trapping and resonance excitation. A control unit that controls the voltage generation unit to change the voltage amplitude of
It is equipped with.

For example, in a three-dimensional quadrupole type digital ion trap, when the frequency of a rectangular wave voltage for trapping ions applied to a ring electrode is changed, the mass-charge ratio of ions excited by resonance excitation changes. Even if the voltage amplitude of the voltage is changed, the mass-to-charge ratio of the ions excited by resonance excitation changes. In the mass spectrometer according to the present invention, when the frequency of the rectangular wave high voltage is scanned, the voltage amplitude of the rectangular wave high voltage is not maintained constant, but the voltage amplitude is positively changed during mass scanning. The mass error in each mass-to-charge ratio of is reduced.

According to the mass spectrometer of the present invention, when the frequency of the rectangular wave voltage is scanned for the mass scanning over the predetermined mass-to-charge ratio range, the mass error is reduced as the frequency changes. The amplitude of the rectangular wave voltage is adjusted appropriately. As a result, compared with the case where the voltage amplitude of the rectangular wave voltage is controlled to be constant, the mass error within the target mass-to-charge ratio range, especially the mass error that partially increases within the mass-to-charge ratio range, is reduced. It is possible to obtain a mass spectrum with high mass accuracy as a whole.

The schematic block diagram of the digital ion trap mass spectrometer (DIT-MS) which is one embodiment of the present invention. 9 is a flowchart of a characteristic processing operation in the DIT-MS of the present embodiment. The schematic diagram which shows an example of the change of the voltage amplitude with the frequency change of the rectangular wave high voltage at the time of mass scanning in DIT-MS of this embodiment. FIG. 6 is a timing chart showing an example of a rectangular wave voltage waveform at the time of resonance excitation discharge in DIT-MS.

The ion trap used in the mass spectrometer according to the present invention is usually a three-dimensional quadrupole ion trap or a linear ion trap. In the case of a three-dimensional quadrupole type ion trap, the ion trap is usually composed of an annular ring electrode and a pair of end cap electrodes that are arranged to face each other with the ring electrode interposed therebetween. A rectangular wave voltage and a rectangular wave voltage for resonance excitation are applied to the pair of end cap electrodes. On the other hand, in the case of a linear type ion trap, the ion trap is usually composed of four rod electrodes arranged in parallel with each other so as to surround the central axis, and the two rod electrodes facing each other with the central axis interposed therebetween are as described above. It replaces the ring electrode, and another two rod electrodes replace the pair of end cap electrodes.

A digital ion trap mass spectrometer (DIT-MS) that is an embodiment of a mass spectrometer according to the present invention will be described with reference to the accompanying drawings. This DIT-MS uses a three-dimensional quadrupole ion trap, but it is obvious to those skilled in the art that it can be replaced with a linear ion trap.
FIG. 1 is a configuration diagram of a main part of a DIT-MS according to this embodiment.

[Overall configuration of this device]
The DIT-MS includes an ionization unit 1 that ionizes a target sample, a three-dimensional quadrupole ion trap 2 that separates ions according to a mass-to-charge ratio, and a detection unit 3 that detects ions.

The ionization unit 1 uses a matrix-assisted laser desorption/ionization (MALDI) method, and includes a laser irradiation unit 11 that emits a pulsed laser beam, a sample plate 12 to which a sample 13 containing a sample component is attached, and a laser beam. And an ion electrode 15 that guides the extracted ions. Of course, the type of ionization method in the ionization unit 1 is not limited to the MALDI method, and other laser ionization methods or ionization methods that do not use laser light may be used.

The ion trap 2 includes one ring-shaped ring electrode 21 and an inlet-side end cap electrode 22 and an outlet-side end cap electrode 24, which are arranged to face each other so as to sandwich the ring-shaped ring electrode 21. A part of the space surrounded by the

electrodes

21, 22, and 24 serves as an ion trapping region. An ion entrance port 23 is formed in the center of the entrance-side end cap electrode 22, and the ions emitted from the ionization section 1 pass through the ion entrance port 23 and are introduced into the ion trap 2. On the other hand, an ion emission port 25 is formed substantially at the center of the outlet side end cap electrode 24, and the ions ejected from the ion trap 2 through the ion emission port 25 reach the detection unit 3 and are detected.

The detection unit 3 includes a conversion dynode 31 that converts ions into electrons, and a secondary electron multiplier 32 that multiplies and detects electrons coming from the conversion dynode 31, and detects according to the amount of incident ions. A signal is generated and sent to the data processing unit 8. The data processing unit 8 has a function of creating a mass spectrum based on a detection signal obtained by the detection unit 3 with respect to ions that are sequentially ejected while being mass-separated in the ion trap 2. The data processing unit 8 creates a calibration formula based on the difference between the theoretical value of the mass-to-charge ratio of the calibrant (calibration sample) and the actual measurement value of the mass-to-charge ratio, and the mass calibration unit 81 that performs mass calibration using this calibration formula. Is included as a functional block.

The main power supply unit 4 applies a rectangular wave high voltage to the ring electrode 21 of the ion trap 2, and generates a first voltage source 41 that generates a positive first voltage V _H and a negative second voltage V _L. A second voltage source 42, and a first switching element 43 and a second switching element 44 connected in series between the output terminal of the first voltage source 41 and the output terminal of the second voltage source 42. On the other hand, the auxiliary power supply unit 5 applies different rectangular wave low voltages to the

end cap electrodes

22 and 24 of the ion trap 2.

The timing signal generator 6 is a hardware logic circuit, and under the control of the controller 7, the first switching element 43 and the second switching element 44 are turned on alternately (however, they are not turned on at the same time. As described above, a drive pulse having a predetermined frequency is generated and supplied to each of the switching

elements

43 and 44. The first voltage V _H is output when the first switching element 43 is turned on, and the second voltage V _L is output when the second switching element 44 is turned on. Therefore, ideally, as shown in FIG. 4A, the output voltage V _OUT of the main power supply unit 4 is a rectangular wave of a predetermined frequency f (cycle t) in which the high level is V _H and the low level is V _L. It becomes a voltage. Here, V _H and V _L are high voltages whose absolute values are almost the same and their polarities are opposite to each other. For example, their absolute values are several hundreds V to 1 kV. The frequency f is usually in the range of several tens kHz to several MHz. However, V _H and V _L may have the same polarity depending on the reference potential of the system.

Further, the timing signal generator 6 gives a pulse signal obtained by dividing the drive pulse supplied to the main power source 4 at an appropriate ratio (for example, 1/4) to the auxiliary power source 5. The auxiliary power supply unit 5 generates a rectangular wave low voltage as shown in FIG. 4B, which has a frequency of f/4 and an amplitude value of, for example, about several V, based on the signal obtained from the timing signal generation unit 6. To do.

The control unit 7 controls each unit in order to perform the analysis operation, and as the functional blocks characteristic of this embodiment, the voltage-m/z shift amount information storage unit 71, the mass scanning voltage information acquisition control unit, and the like. 72, a mass error calculation unit 73, a mass error determination unit 74, an adjusted voltage information storage unit 75, a mass scanning voltage control unit 76, and the like. The control unit 7 can be configured by a hardware circuit, but normally, at least a part of the control unit 7 is mainly configured by a personal computer, and by executing a dedicated control/processing program installed in the personal computer. , Its function may be achieved.

[Explanation of basic mass spectrometry operation of this device]
A mass spectrometric operation in the DIT-MS of this embodiment will be schematically described.
In the ionization unit 1, when laser light is emitted from the laser irradiation unit 11 to the sample 13 for a short time under the control of the control unit 7, the sample component in the sample 13 is ionized. The generated ions are converged by the ion lens 15 and introduced into the space in the ion trap 2 via the ion entrance 23 to be captured.

The mass-charge ratio range of the ions that are stably trapped in the ion trap 2 depends on the frequency of the rectangular wave high voltage applied to the ring electrode 21. Therefore, when the ions are confined in the ion trap 2 as described above, the timing signal generator 6 supplies a drive pulse having a predetermined frequency to the

switching elements

43 and 44 according to the instruction from the controller 7, and responds to this. A rectangular wave high voltage having a frequency is generated by the main power supply unit 4 and applied to the ring electrode 21. At this time, the voltage applied to the

end cap electrodes

22 and 24 is maintained at the ground potential. It should be noted that when trapping ions in a predetermined, somewhat wide mass-to-charge ratio range, the frequency of the rectangular wave high voltage is appropriately selected according to the mass-to-charge ratio range.

As described above, when trapping ions having various mass-to-charge ratios and then obtaining a mass spectrum of the ions, a resonance excitation phenomenon is used to allow the ions to be trapped through the ion emission port 25 in order of mass-to-charge ratio. It is discharged from 2, and detected by the detection unit 3. At this time, the rectangular wave high voltage for ion trapping is applied from the main power source section 4 to the ring electrode 21, while the frequency of the ion trapping rectangular wave high voltage is divided from the auxiliary power source section 5 to the

end cap electrodes

22 and 24, respectively. A rectangular wave voltage (rectangular wave low voltage) for resonance excitation is applied. Then, the frequency of the rectangular wave high voltage for ion trapping and the frequency of the rectangular wave low voltage for resonance excitation are synchronously scanned. As a result, ions having a specific mass-to-charge ratio are resonantly excited and greatly vibrate, and are sequentially ejected from the ion trap 2.

[Explanation of control and processing operations characteristic of this apparatus]
Generally, during the above-described resonance excitation discharge, the voltage amplitude of the rectangular wave high voltage, that is, the voltage values of the first voltage V _H and the second voltage V _L are controlled to be constant. However, when the frequency of the drive pulse for turning on/off the switching

elements

43 and 44 is continuously changed, the pulse width is changed, the influence of the transient state of the voltage change is changed, and the

voltage sources

41 and 42 are changed. The load also changes. Therefore, as the frequency of the rectangular wave high voltage changes, the voltage amplitude of the rectangular wave high voltage changes and the voltage waveform shape also changes. Such variations in voltage amplitude and waveform shape are presumed to be a major factor in mass errors during mass scanning and their fluctuations.

On the other hand, in the DIT-MS of the present embodiment, when the frequency of the rectangular wave high voltage is scanned, the voltage amplitude of the rectangular wave high voltage is changed without being kept constant, so that the entire mass scanning is performed. The mass error is reduced.

The control and processing therefor will be described with reference to FIGS. 2 and 3. FIG. 2 is a flow chart of a characteristic processing operation in this DIT-MS, and FIG. 3 is a schematic diagram showing an example of a change in voltage amplitude with a frequency change of a rectangular wave high voltage during mass scanning in this DIT-MS. Here, as an example, it is assumed that five kinds of calibrants whose precise mass-to-charge ratio values (theoretical values) are known are used. The number of calibrants may be two or more.

The relationship between the amount of change in the voltage amplitude of the square wave high voltage and the amount of change in the mass-to-charge ratio was experimentally investigated in advance for each mass-to-charge ratio value corresponding to the calibrant used, and the voltage-m/z shift amount information was obtained. It is stored in the storage unit 71. Specifically, for example, the change value of the mass-to-charge ratio when the voltage amplitude of the rectangular wave high voltage is reduced by 0.1 V from the specified voltage amplitude value may be obtained.

During the mass calibration using the calibrant, the voltage information acquisition control unit 72 for mass scanning of the control unit 7 outputs the outputs of the first voltage source 41 and the second voltage source 42 in order to make the voltage amplitude of the rectangular wave high voltage constant. The voltages are set to be fixed at predetermined values (step S1). Under such a voltage condition, mass spectrometry is performed on five kinds of calibrants, and mass spectrum data over a predetermined mass-charge ratio range is acquired (step S2). Here, the five kinds of calibrants are Cal.a, Cal.b, Cal.c, Cal.d, and Cal.e as shown in FIG. 3, and the mass-to-charge ratio of Cal.a is the smallest. , Cal.a, Cal.b, Cal.c, Cal.d, Cal.e, in that order.

In the data processing unit 8, the mass calibration unit 81 calculates the mass-to-charge ratio actual measurement value from the mass spectrum data of the two calibrants Cal.a and Cal.e whose mass-to-charge ratio is minimum and maximum, and calculates the calibrants. A linear calibration formula is obtained based on the difference between the measured value and the theoretical value of the mass-to-charge ratio of. Then, using this calibration formula, mass calibration is performed for all calibrants Cal.a, Cal.b, Cal.c, Cal.d, Cal.e, and the mass-to-charge ratio value after this mass calibration is measured. The value is sent to the control unit 7 (step S3).

In the control unit 7, the mass error calculation unit 73 first selects the calibrant Cal.a having the smallest mass-to-charge ratio, and obtains the mass error of the mass-to-charge ratio corresponding to the calibrant (step S4). The mass error determination unit 74 determines whether the mass error is within a predetermined allowable range (step S5). If the mass error is within the allowable range, the process proceeds from step S5 to step S8 described later.

On the other hand, if the mass error deviates from the allowable range, the mass scanning voltage information acquisition control unit 72 determines that the information stored in the voltage-m/z shift amount information storage unit 71, that is, the corresponding calibrant. By referring to the relationship between the amount of change in the voltage amplitude of the corresponding rectangular wave high voltage and the amount of change in the mass-to-charge ratio, the amount of change in the voltage amplitude at which the mass error becomes zero is calculated. Then, in a predetermined frequency range near the frequency of the rectangular wave high voltage at which ions having a mass-to-charge ratio corresponding to the calibrant are resonantly excited and ejected, the frequency is scanned so as to change the voltage amplitude according to the calculation result. As a result, mass spectrometry of the corresponding calibrant is performed again (step S6).

In the data processing unit 8, the mass calibration unit 81 calibrates the mass-to-charge ratio value of the calibrant to be measured, which is obtained from the obtained mass spectrum data, using the above calibration formula, and obtains the measured mass-to-charge ratio value. Then, the mass error calculator 73 calculates the mass error of the mass-to-charge ratio corresponding to the calibrant (step S7). After that, the process returns from step S7 to S5, and the mass error determination unit 74 determines whether or not the mass error is within the allowable range. Then, if the mass error is not within the allowable range, the processes of steps S5 to S6 are repeated. Thereby, in the vicinity of the frequency of the rectangular wave high voltage corresponding to the ions derived from the calibrant, it is possible to determine the amount of change in the voltage amplitude such that the mass error falls within the allowable range. When it is determined to be Yes in step S5, the determined amount of change in voltage amplitude is stored in the adjusted voltage information storage unit 75 corresponding to the frequency of the rectangular wave high voltage (step S8).

After that, the mass scanning voltage information acquisition control unit 72 determines whether or not there remains a calibrant for which the amount of change in voltage amplitude has not been determined (step S9). If the calibrant still remains, the calibrant having the next largest mass-to-charge ratio is selected, and the mass error calculation unit 73 obtains the mass error of the mass-to-charge ratio corresponding to the calibrant (step S10) and returns to step S5. , Executes the processing described above. Therefore, by repeating steps S10→S5 to S7→S8→S9, after mass calibration is performed for all five kinds of calibrants Cal.a, Cal.b, Cal.c, Cal.d, and Cal.e. The amount of change in the voltage amplitude is determined so that the mass error is within the allowable range, and the information is stored in the adjusted voltage information storage unit 75.

Now, assuming that the initial mass errors of the five kinds of calibrants Cal.a, Cal.b, Cal.c, Cal.d, and Cal.e are in the state shown by ● in FIG. 3(a). Since the initial mass errors of the three kinds of calibrants Cal.b, Cal.c, and Cal.d are out of the allowable range, the voltage amplitude of the rectangular wave high voltage is adjusted.

In an ion trap that performs resonant excitation and ejection by applying a rectangular wave voltage as shown in FIG. 4, the regulation observed on the mass spectrum when the positive electrode side high voltage (first voltage V _H ) of the rectangular wave high voltage is lowered. The ion peak of the mass-to-charge ratio of is shifted to the lower mass side. On the other hand, when the high voltage (second voltage V _L ) on the negative side of the rectangular wave high voltage is lowered, the ion peak of the specified mass-to-charge ratio observed on the mass spectrum shifts to the high mass side. Therefore, in the DIT-MS of the present embodiment, when the mass error is a negative value, the voltage amplitude is changed so as to lower the negative electrode side high voltage (second voltage V _L ). On the other hand, when the mass error is a positive value, the voltage amplitude is changed so as to lower the high voltage on the positive electrode side (first voltage V _H ).

Therefore, when the mass error in each calibrant is as shown in FIG. 3A, the voltage adjustment amount at the frequency corresponding to each calibrant tends to be as shown in FIG. 3B. However, in FIG. 3B, the negative voltage adjustment amount means to reduce the voltage. That is, in FIG. 3B, the plot indicated by ◯ is the adjustment amount of the first voltage V _H having the positive polarity, and the plot indicated by □ is the adjustment amount of the second voltage V _{L having} the negative polarity. For the calibrants Cal.b and Cal.c, the voltage amplitude of the rectangular wave high voltage is adjusted by adjusting the first voltage V _H in the decreasing direction. Further, for the calibrant Cal.d, the voltage amplitude of the rectangular wave high voltage is adjusted by adjusting the second voltage V _L in the decreasing direction.

In FIG. 3B, a straight line connects the voltage adjustment amount at the frequency corresponding to the calibrant with one mass-to-charge ratio and the voltage adjustment amount at the frequency corresponding to the calibrant with the mass-to-charge ratio adjacent thereto. However, this is not necessarily a straight line and may be connected by an appropriate curve.

When performing mass spectrometry on a sample containing a target sample component to obtain a mass spectrum over a predetermined mass-to-charge ratio range, the mass scanning time voltage control unit 76 sets a rectangular wave height corresponding to the mass-to-charge ratio range. Determine the frequency scan range of voltage. Then, based on the information of the voltage adjustment amount corresponding to the frequency stored in the adjusted voltage information storage unit 75, the first voltage V _H and the second voltage generated by the first voltage source 41 in accordance with the frequency scanning. The value of the second voltage V _L generated by the source 42 is changed. As a result, the voltage amplitude of the rectangular wave high voltage generated by switching is adjusted according to the frequency change, and the mass error is reduced over the entire mass-charge ratio range. As a result, the mass accuracy of the obtained mass spectrum can be improved.

In the above embodiment, the number of calibrants is 5, but this may be 2 or more. Generally, the larger the number of calibrants, the more accurately the voltage adjustment amount can be obtained, which is advantageous for improving the mass accuracy of the mass spectrum. On the other hand, the time and labor required to prepare the calibrant increase, and the time required for the above-described process for obtaining the voltage adjustment amount also increases. Therefore, a suitable number of calibrants is usually about several.

Also, in the above embodiment, the three-dimensional quadrupole ion trap was used as the ion trap, but it is natural that it can be replaced with a linear ion trap. Further, the configuration of the main power supply unit 4 shown in FIG. 1 is merely an example, and it is needless to say that the configuration is not limited to the exemplified one as long as it is a configuration capable of generating the waveform of the voltage amplitude and the frequency required as the rectangular wave high voltage. is there.

Furthermore, the above-described embodiments and modified examples are merely examples of the present invention, and it is needless to say that any appropriate modification, addition, or modification made within the scope of the present invention is also included in the scope of the claims of the present application. ..

[Various aspects]
Those skilled in the art will appreciate that the exemplary embodiments described above are specific examples of the following aspects.

(Claim 1) An aspect of the mass spectrometer according to the present invention has an ion trap that traps ions in a space surrounded by three or more electrodes, and applies a rectangular wave voltage for trapping ions to at least one electrode. While a rectangular wave voltage for resonance excitation is applied to each of a pair of electrodes arranged opposite to each other, the ions having a specific mass-to-charge ratio are selectively ejected from the ion trap by resonance excitation. In the mass spectrometer that detects
A voltage generation unit that generates a rectangular wave voltage for ion trapping and a rectangular wave voltage for resonance excitation,
Targeting a plurality of calibration samples whose precise mass-to-charge ratio values are known, while adjusting the voltage amplitude of the rectangular wave high voltage for ion trapping, the ion trapping is performed so as to scan the mass-to-charge ratio of the ions to be detected. And based on the result of the mass analysis in which the frequency of the rectangular wave voltage for resonance excitation is synchronously scanned, the voltage amplitude adjustment in which the mass error in the mass-to-charge ratio corresponding to each of the plurality of calibration samples falls within the allowable range. A voltage amplitude adjustment information acquisition unit that acquires information,
At the time of performing mass analysis over a predetermined mass-to-charge ratio range for the target sample, based on the voltage amplitude adjustment information, a rectangular wave high voltage for ion trapping accompanying the frequency scanning of the rectangular wave voltage for ion trapping and resonance excitation. A control unit that controls the voltage generation unit to change the voltage amplitude of
Equipped with.

According to the mass spectrometer described in the first paragraph, when the frequency of the rectangular wave voltage for ion trapping is scanned during resonance excitation and ejection, the voltage amplitude is also appropriately changed with the scanning of the frequency. Thereby, a mass error in the course of scanning the mass-to-charge ratio of the ion to be detected can be reduced, and the mass accuracy of the mass spectrum can be improved.

(Item 2) In the mass spectrometer according to item 1,
The voltage amplitude adjustment information acquisition unit is a pre-information storage unit in which information indicating the relationship between the adjustment amount of the voltage amplitude of the rectangular wave high voltage for ion trapping and the change amount of the mass-to-charge ratio of the calibration sample is stored in advance. Have,
The voltage amplitude of the square wave high voltage for ion trapping may be adjusted based on the information stored in the advance information storage unit when the mass spectrometry is performed on the calibration sample.

According to the mass spectrometer described in the second paragraph, the voltage at the time of mass analysis for the calibration sample is utilized by using the information indicating the relationship between the adjustment amount of the voltage amplitude and the change amount of the mass-to-charge ratio which is obtained in advance. The amplitude can be determined. Thereby, the voltage amplitude at the time of mass spectrometry for the calibration sample can be determined more quickly and accurately.

(3rd and 4th items) The mass spectrometer according to the 1st or 2nd item makes the voltage amplitude of the rectangular wave high voltage for ion trapping constant for at least two of the plurality of calibration samples. Further, based on the result of performing the mass analysis while maintaining, mass calibration information calculation unit that calculates calibration information for correcting the mass error over a predetermined mass-to-charge ratio range, further comprising:
The voltage amplitude adjustment information acquisition unit may obtain the mass error after performing the mass calibration using the calibration information.

According to the mass spectrometers described in

Sections

3 and 4, the mass error that remains after the mass calibration is performed (that is, cannot be completely calibrated) may be reduced by adjusting the voltage amplitude. Therefore, in many cases, the adjustment amount of the voltage amplitude is small, and the adjustment of the voltage amplitude according to the change of the frequency becomes easy.

DESCRIPTION OF SYMBOLS 1... Ionization part 11... Laser irradiation part 12... Sample plate 13... Sample 14... Aperture electrode 15... Ion lens 2... Ion trap 21... Ring electrode 22... Entrance side end cap electrode 23... Ion entrance port 24... Exit side end cap Electrode 25... Ion emission port 3... Detection part 31... Conversion dynode 32... Secondary electron multiplier 4... Main power supply part 41... First voltage source 42... Second voltage source 43... First switching element 44... Second switching Element 5... Auxiliary power supply unit 6... Timing signal generating unit 7... Control unit 71... m/z shift amount information storage unit 72... Mass scanning voltage information acquisition control unit 73... Mass error calculation unit 74... Mass error determination unit 75... Voltage information storage unit 76... Mass scanning voltage control unit 8... Data processing unit 81... Mass calibration unit

Claims

An ion trap that traps ions in a space surrounded by three or more electrodes is provided, and a rectangular wave voltage for ion trapping is applied to at least one electrode while resonating with a pair of electrodes that are arranged opposite to each other. By applying a rectangular wave voltage for excitation, in a mass spectrometer for selectively ejecting and detecting ions having a specific mass-to-charge ratio from the ion trap by resonance excitation,
A voltage generation unit that generates a rectangular wave voltage for ion trapping and a rectangular wave voltage for resonance excitation,
Targeting a plurality of calibration samples whose precise mass-to-charge ratio values are known, while adjusting the voltage amplitude of the rectangular wave high voltage for ion trapping, the ion trapping is performed so as to scan the mass-to-charge ratio of the ions to be detected. And based on the result of the mass analysis in which the frequency of the rectangular wave voltage for resonance excitation is synchronously scanned, the voltage amplitude adjustment in which the mass error in the mass-to-charge ratio corresponding to each of the plurality of calibration samples falls within the allowable range. A voltage amplitude adjustment information acquisition unit that acquires information,
At the time of performing mass analysis over a predetermined mass-to-charge ratio range for the target sample, based on the voltage amplitude adjustment information, a rectangular wave high voltage for ion trapping accompanying the frequency scanning of the rectangular wave voltage for ion trapping and resonance excitation. A control unit that controls the voltage generation unit to change the voltage amplitude of
A mass spectrometer equipped with.
The voltage amplitude adjustment information acquisition unit is a pre-information storage unit in which information indicating the relationship between the adjustment amount of the voltage amplitude of the rectangular wave high voltage for ion trapping and the change amount of the mass-to-charge ratio of the calibration sample is stored in advance. Have,
The mass spectrometer according to claim 1, wherein the voltage amplitude of the rectangular wave high voltage for ion trapping is adjusted based on the information stored in the advance information storage unit when the mass spectrometry is performed on the calibration sample.
For at least two of the plurality of calibration samples, based on the results of performing mass analysis while keeping the voltage amplitude of the square wave high voltage for ion trapping constant, a mass error over a predetermined mass-to-charge ratio range. Further comprising a mass calibration information calculation unit for calculating calibration information to be corrected,
The mass spectrometer according to claim 1, wherein the voltage amplitude adjustment information acquisition unit obtains a mass error after performing mass calibration using the calibration information.
For at least two of the plurality of calibration samples, based on the results of performing mass analysis while keeping the voltage amplitude of the square wave high voltage for ion trapping constant, a mass error over a predetermined mass-to-charge ratio range. Further comprising a mass calibration information calculation unit for calculating calibration information to be corrected,
The mass spectrometer according to claim 2, wherein the voltage amplitude adjustment information acquisition unit obtains a mass error after performing mass calibration using the calibration information.