WO2018138838A1

WO2018138838A1 - Mass spectrometry method and mass spectrometry device

Info

Publication number: WO2018138838A1
Application number: PCT/JP2017/002774
Authority: WO
Inventors: 真二宮内; 浩子上田; 良弘上野
Original assignee: 株式会社島津製作所
Priority date: 2017-01-26
Filing date: 2017-01-26
Publication date: 2018-08-02
Also published as: JPWO2018138838A1

Abstract

In this invention, during analysis, a control unit (7) controls a gas introducing unit (11) in such a manner that an appropriate amount of inert gas is introduced into the internal space of a quadrupole mass filter (4). An ion generated at an ion source (2) and passing through the internal space of the quadrupole mass filter (4) is cooled by contacting the gas that has been introduced. Caused by an offset in the positioning of a rod electrode from the quadrupole mass filter (4), or the like, a multipolar component overlaps with the quadrupole electric field formed in the filter (4), thereby generating a non-linear resonance. By cooling the ion passing through the quadrupole mass filter (4), the increase of undesirable energy caused by the non-linear resonance is suppressed, thereby attenuating the distortion of a peak in a mass spectrum.

Description

Mass spectrometry method and mass spectrometer

The present invention relates to a mass spectrometer using a quadrupole mass filter that selects ions having a specific mass-to-charge ratio m / z, and a mass spectrometry method in the mass spectrometer. The mass spectrometer referred to here is not only a general single quadrupole mass spectrometer using a quadrupole mass filter as the only mass separator, but also a two-stage quadrupole for performing MS / MS analysis. Q detected by dissociating ions selected by a triple quadrupole mass spectrometer equipped with a quadrupole mass filter or a quadrupole mass filter and then separating them according to the mass-to-charge ratio using a time-of-flight mass separator -It shall include a TOF mass spectrometer.

In a general quadrupole mass spectrometer, various ions generated from a sample are introduced into a quadrupole mass filter to selectively pass only ions having a specific mass-to-charge ratio m / z. Ions are detected by a detector to obtain an intensity signal corresponding to the amount of ions.

A quadrupole mass filter is generally composed of four rod electrodes arranged in parallel to each other so as to surround a linear ion optical axis, and a voltage obtained by adding a DC voltage and a high-frequency voltage to each of the four rod electrodes. Applied. Due to the applied voltage, a quadrupole electric field is formed in the internal space of the quadrupole mass filter, and only ions having a certain mass-to-charge ratio or included in the mass-to-charge ratio range vibrate appropriately while the quadrupole is vibrating. The other ions pass through the internal space of the mass filter and diverge on the way. The conditions under which ions can stably pass through a quadrupole mass filter have been theoretically studied for a long time.

As disclosed in Non-Patent Document 1, etc., the behavior of ions in an ideal quadrupole electric field is well known, but an ideal quadrupole electric field is formed in an actual quadrupole mass filter. It is very difficult. For example, an ideal rod electrode has a hyperbolic shape in cross section facing the ion optical axis, but in many cases, a rod electrode having a circular cross section is used as a rod electrode in order to avoid complicated manufacturing. In addition, the configuration of the quadrupole mass filter deviates from the ideal state due to limitations in processing accuracy of each rod electrode and assembly accuracy of a plurality of rod electrodes. Therefore, higher-order multipole field components are superimposed on the quadrupole field formed by the quadrupole mass filter, and the behavior of ions passing through such an electric field is the ideal quadrupole field. It is different from the case of passing. As a result, when an ion having a predetermined mass-to-charge ratio is observed while performing mass scanning over a predetermined mass-to-charge ratio range, the shape of the peak corresponding to the target ion in the obtained mass spectrum is somewhat distorted. .

Specifically, when there is a deviation from an ideal quadrupole electric field in a quadrupole mass filter, a nonlinear resonance phenomenon occurs, and a peak that should originally have a shape as shown in FIG. As shown in FIG. 4 (b), it is known that the top portion has a cracked shape (see Non-Patent Documents 3 and 4).

Conventionally, for example, in Non-Patent Document 2, for example, high-order multiplexing is performed by adjusting the ratio of the radius of each rod electrode to the inscribed circle radius of the plurality of rod electrodes, that is, the position of the rod electrodes. Attempts have been made to improve the distortion of peaks on the mass spectrum by reducing the polar electric field components.
However, since the assembly error of the rod electrode varies from device to device, the magnitude of the high-order multipole electric field component also varies from device to device. It is difficult to reduce enough. Such work is very time consuming and not very practical.

JP 2000-36283 A (paragraph [0006])

The present invention has been made to solve the above-mentioned problems, and the main object of the present invention is on the mass spectrum resulting from the fact that the quadrupole electric field formed by the quadrupole mass filter is not ideal. An object of the present invention is to provide a mass spectrometer and a mass spectrometry method that can easily reduce peak distortion.

In mass spectrometers as well as quadrupole mass spectrometers, a mass separator that separates ions according to a mass-to-charge ratio is usually placed in a chamber that is maintained at a vacuum level as high as possible. This is because, for example, in a quadrupole mass spectrometer, when ions, which can pass through the quadrupole mass filter, come into contact with the residual gas, the trajectory may change and cannot pass through. . That is, if the mass separator is placed under a relatively low degree of vacuum, the ion transmittance is reduced, leading to a reduction in detection sensitivity. On the other hand, the inventor repeated simulation calculations and examinations under various conditions, and in the region where ions pass through the quadrupole mass filter, there are many opportunities for contact between the ions and neutral gas particles. It was found that the peak distortion on the mass spectrum is reduced on the contrary, although the transmittance of ions decreases. This is presumed to be the effect that the energy of ions increased by nonlinear resonance due to higher-order multipole electric field components is cooled by contact with neutral gas particles. The present invention has been made based on these findings.

The mass spectrometric method according to the present invention, which has been made to solve the above-mentioned problems, is a method of vacuuming a quadrupole mass filter that selectively passes ions having a predetermined mass-to-charge ratio or included in a predetermined mass-to-charge ratio range. A mass spectrometry method using a mass spectrometer provided in a chamber,
At the time of analysis, at least the gas pressure in the space through which ions are to pass through the quadrupole mass filter is higher than the gas pressure when the vacuum pump that evacuates the vacuum chamber is operated at the maximum exhaust speed. By adjusting the pumping speed of the vacuum pump or the amount of gas introduced into the vacuum chamber from the outside, the ions are cooled by contact between the ions and the gas in the space in the quadrupole mass filter. It is characterized by that.

In addition, a first aspect of the mass spectrometer according to the present invention, which has been made to solve the above-mentioned problems, is configured to selectively pass ions having a predetermined mass-to-charge ratio or included in a predetermined mass-to-charge ratio range. A mass spectrometer comprising a multipole mass filter inside a vacuum chamber,
a) a gas introduction part for introducing a cooling gas into a space in which ions are to pass in the quadrupole mass filter;
b) a control unit for controlling the amount of gas introduced by the gas introduction unit;
It is characterized by having.

In addition, a second aspect of the mass spectrometer according to the present invention, which has been made to solve the above-described problems, is configured to selectively pass ions having a predetermined mass-to-charge ratio or included in a predetermined mass-to-charge ratio range. A mass spectrometer comprising a multipole mass filter inside a vacuum chamber,
a) a vacuum pump for evacuating the vacuum chamber;
b) The pumping speed of the vacuum pump is set so that the gas pressure in the vacuum chamber at the time of analysis becomes a predetermined gas pressure higher than the gas pressure in the vacuum chamber when the vacuum pump is operated at the maximum pumping speed. A control unit to control;
It is characterized by having.

That is, in the conventional general mass spectrometer, the vacuum pump is operated at the maximum exhaust speed so that the gas pressure in the vacuum chamber in which the quadrupole mass filter is arranged is as low as possible. On the other hand, in the mass spectrometry method and the mass spectrometer according to the present invention, a predetermined gas (usually inactive) is activated by operating the vacuum pump at a lower capacity than the maximum exhaust speed during analysis, or by a gas introduction unit. Gas) is intentionally introduced into the space surrounded by the rod electrodes of the quadrupole mass filter, so that more neutral particles are present in the space. As a result, when ions suitable for the passage condition corresponding to the voltage applied to the quadrupole mass filter try to pass through the interior space of the quadrupole mass filter, the ions are more likely to come into contact with neutral particles and cooling. Is promoted. As a result, the electric field formed by the quadrupole mass filter has many higher-order multipole components, and even when nonlinear resonance occurs, the undesired increase in energy is suppressed, and the peak on the mass spectrum is suppressed. Distortion will be reduced.

However, if the chance of contact between ions for analysis and neutral particles increases in the internal space of the quadrupole mass filter, the trajectory of some ions that would otherwise pass through the quadrupole mass filter It will change and the transmission efficiency of ion will fall. That is, when the gas pressure in the internal space of the quadrupole mass filter is increased, the distortion of the peak on the mass spectrum is reduced, so that the accuracy of the mass spectrum is improved, but the signal intensity itself is lowered and the sensitivity may be lowered. There is. Therefore, when the amount of ions originally intended for analysis is small, sufficient signal intensity may not be observed if ion cooling is promoted in the internal space of the quadrupole mass filter.

Therefore, in the first aspect of the mass spectrometer according to the present invention, the high-accuracy measurement mode in which the gas introduction amount is relatively large under the control of the control unit, and the gas introduction amount is relatively small. The high sensitivity measurement mode may be configured to be selectable by the user.

On the other hand, in the second aspect of the mass spectrometer according to the present invention, the high-precision measurement mode in which the target value of the gas pressure under the control of the control unit is relatively high, and the target value of the gas pressure is It may be configured to have a relatively low high sensitivity measurement mode that can be selected by the user.

According to these configurations, in the high-accuracy measurement mode, ion cooling is promoted in the internal space of the quadrupole mass filter, so that peak distortion on the mass spectrum is reduced as described above, and a peak having a good shape is obtained. Can be acquired. On the other hand, in the high-sensitivity measurement mode, ion cooling is relatively less likely to occur in the internal space of the quadrupole mass filter, so that peak distortion on the mass spectrum is conspicuous but the ion transmission efficiency is high, so the peak of high signal intensity is high. Can be obtained. Thereby, the user can freely select the measurement giving priority to the accuracy and the measurement giving priority to the sensitivity according to the purpose of the analysis and the amount of the component which is the analysis purpose.

According to the mass spectrometer and the mass spectrometry method according to the present invention, even when the quadrupole electric field formed by the quadrupole mass filter is not ideal and the multipole component is superimposed, The peak distortion can be easily reduced. In particular, according to the mass spectrometer and the mass spectrometry method according to the present invention, it is not necessary to change mechanical elements such as the shape and arrangement of the rod electrode in order to reduce the distortion of the peak, and the peak can be obtained only by electrical control. Therefore, even if it is necessary to make adjustments for each device, it is easy and automatic adjustment is easy.

The schematic block diagram of one Example of the quadrupole-type mass spectrometer which concerns on this invention. The figure which shows the simulation result of the peak waveform on the mass spectrum with the case where it accelerates | stimulates in the case where cooling is not promoted in a quadrupole mass filter. The schematic block diagram of the other Example of the quadrupole-type mass spectrometer which concerns on this invention. Explanatory drawing of the distortion of the peak on a mass spectrum by the influence of the multipole component in the electric field formed by a quadrupole mass filter.

An embodiment of a quadrupole mass spectrometer according to the present invention will be described with reference to the accompanying drawings.
FIG. 1 is a schematic configuration diagram of a quadrupole mass spectrometer according to the present embodiment.

The quadrupole mass spectrometer according to the present embodiment includes an ion source 2, an ion lens 3, a quadrupole mass filter 4, and a vacuum chamber 1 having a substantially sealed structure that is evacuated by a vacuum pump 9. And a detector 5. The detection signal obtained by the detector 5 is input to the data processing unit 6. The degree of vacuum (gas pressure) in the vacuum chamber 1 is detected by a vacuum gauge 10 such as an ion gauge, and the control unit 7 operates the vacuum pump 9 and the inside of the quadrupole mass filter 4 according to the detected degree of vacuum. The operation of the gas introduction unit 11 for introducing a predetermined gas into the space is controlled. An input unit 8 operated by a user is connected to the control unit 7.

The ion source 2 ionizes components (compounds) in the sample gas introduced from the outside by, for example, electron ionization (EI). Ions generated by the ion source 2 and drawn rightward as indicated by white arrows in FIG. 1 are converged by the action of an electric field by the ion lens 3 and introduced into the quadrupole mass filter 4. The quadrupole mass filter 4 is composed of four rod electrodes arranged in parallel around the ion optical axis C, and a high-frequency voltage is superimposed on a DC voltage on each of the four rod electrodes from a power source (not shown). Applied voltage.

Of the ions introduced into the space in the long axis direction of the quadrupole mass filter 4 along the ion optical axis C, the ions are formed by a DC voltage and a high-frequency voltage applied to the rod electrode of the quadrupole mass filter 4. Due to the action of the electric field, only ions having a specific mass-to-charge ratio (or included in the mass-to-charge ratio range) pass through the vicinity of the ion optical axis C while oscillating other ions. Ions that have passed through the quadrupole mass filter 4 reach the detector 5, and the detector 5 generates a detection signal corresponding to the amount of ions that arrived and sends it to the data processing unit 6. When the DC voltage applied to the rod electrode of the quadrupole mass filter 4 and the high-frequency voltage are changed while maintaining a predetermined relationship, the mass-to-charge ratio of ions that can pass through the quadrupole mass filter 4 changes. Therefore, by scanning the DC voltage and the high-frequency voltage within a predetermined range, the mass-to-charge ratio of ions that can reach the detector 5 can be changed within the predetermined range. The data processing unit 6 can create a mass spectrum indicating the relationship between the mass-to-charge ratio and the signal intensity based on the detection signal obtained thereby.

In order to maintain the inside of the vacuum chamber 1 at a high degree of vacuum, the vacuum pump 9 is usually a combination of a turbo molecular pump and a rotary pump. In the conventional mass spectrometer, the vacuum pump 9 is operated at a maximum exhaust speed or a speed close thereto at the time of performing analysis, and the vacuum chamber 1 is maintained at a high degree of vacuum. Characteristic control is performed as described in (1).

FIG. 2 is a diagram showing simulation results of peak waveforms on the mass spectrum in the internal space of the quadrupole mass filter, with and without considering cooling by Ar gas. In the simulation, the mean free path of ions is limited to 25 cm in consideration of contact between ions and Ar gas in the case of cooling, while the mean free path is not limited in the case of no cooling, and the mass to charge ratio is The relative ion permeation amount for ions near m / z 500 was calculated. As shown in FIG. 2, when the cooling is not performed, the relative permeation amount is about 2.5 times higher than when the cooling is performed, but a large crack occurs at the peak. This is a phenomenon caused by the above-described nonlinear resonance. On the contrary, in the case of cooling, although the relative permeation amount decreases, the crack at the peak top is almost eliminated. From this, it can be understood that the peak distortion due to nonlinear resonance can be reduced by cooling the ions passing through the internal space of the quadrupole mass filter.

In order to cool ions in the internal space of the quadrupole mass filter 4, the density of neutral gas particles in the space may be increased. This is the opposite of the conventional operation in which the degree of vacuum in the vacuum chamber 1 is made as high as possible so that ions do not come into contact with the residual gas or the like. In the mass spectrometer of the present embodiment, either of two methods can be adopted to increase the density of neutral gas particles in the internal space of the quadrupole mass filter 4.

[1] Operation Control of Vacuum Pump 9 One of the above methods is to intentionally lower the degree of vacuum in the vacuum chamber 1 by suppressing the exhaust speed of the vacuum pump 9, that is, the exhaust performance. In this case, the gas introduction part 11 is not used.
The control unit 7 is set in advance (before the analysis is performed) with a vacuum degree target value so that the peak waveform shape can be improved by cooling. This vacuum degree target value may be experimentally obtained by the manufacturer of the apparatus and stored in the memory, or a user who uses the apparatus may experimentally investigate and store it in the memory. . In any case, in the analysis, the control unit 7 controls the exhaust speed of the vacuum pump 9 so that the degree of vacuum detected by the vacuum gauge 10 becomes the target degree of vacuum. The pumping speed at this time is smaller than the maximum pumping speed of the vacuum pump 9, and an inert gas occupying most of the sample gas continuously supplied in the vacuum chamber 1 (for example, used in a gas chromatograph connected to the preceding stage) The carrier gas of He, N ₂ , Ar, etc.) remains moderately. Ions generated by the ion source 2 and trying to pass through the internal space of the quadrupole mass filter 4 come into contact with such residual gas and are cooled. Accordingly, an increase in undesired energy due to nonlinear resonance can be suppressed, and distortion such as peak cracking on the mass spectrum can be reduced.

[2] Introduction of gas from outside Another method is to continuously or intermittently introduce an inert gas from the gas introduction part 11 into the internal space of the quadrupole mass filter 4. Parameters such as the supply amount of inert gas and the supply time may be determined in advance so that the peak waveform shape can be improved by cooling. Ions generated by the ion source 2 and trying to pass through the internal space of the quadrupole mass filter 4 come into contact with the inert gas supplied to the space from the gas introduction unit 11 and are cooled. Accordingly, an increase in undesired energy due to nonlinear resonance can be suppressed, and distortion such as peak cracking on the mass spectrum can be reduced.

Note that the degree of vacuum and the amount of gas supply appropriate for obtaining the effects described above also differ depending on the mass-to-charge ratio of the ions to be analyzed. Therefore, when the mass-to-charge ratio of ions to be analyzed is determined as in, for example, selected ion monitoring (SIM) measurement, the vacuum pump 9 is adjusted so that the degree of vacuum and the amount of gas supply correspond to the mass-to-charge ratio. Alternatively, the gas introduction unit 11 may be controlled.

FIG. 3 is a schematic configuration diagram of a quadrupole mass spectrometer according to another embodiment of the present invention. The same components as those in the apparatus of the embodiment shown in FIG.
As can be seen from FIG. 2, when cooling is performed in the internal space of the quadrupole mass filter, the peak distortion is improved, but the relative permeation amount of ions is reduced, and the sensitivity is lowered accordingly. For this reason, if the amount of ions to be analyzed is originally small, such as microanalysis, the target ions may not be observed with sufficient signal intensity when cooling is performed. Therefore, the mass spectrometer shown in FIG. 3 has a high-accuracy measurement mode that prioritizes the reduction of peak distortion and a high-sensitivity measurement mode that prioritizes the amount of ions to be detected, and switches between these two measurement modes. Is possible.

The input unit 8 includes a mode selection unit 81, and the control unit 8 includes a target vacuum degree switching unit 71. Prior to execution of analysis, the user selects one of the high-precision measurement mode and the high-sensitivity measurement mode by the mode selection unit 81 according to the purpose of analysis, the type of sample, and the like. When this selection instruction is received, the target vacuum degree switching unit 71 in the control unit 7 sets the vacuum degree target value to P1 in the high accuracy measurement mode and P2 higher than P1 (the gas pressure is low) in the high sensitivity measurement mode. In the high sensitivity measurement mode, the vacuum pump 9 may be continuously operated at the maximum exhaust speed without setting the target vacuum value. Moreover, you may make it switch the gas supply amount from the gas introduction part 11 according to each measurement mode instead of control of the vacuum pump 9. FIG. In any case, when the high-sensitivity measurement mode is selected, the gas pressure in the internal space of the quadrupole mass filter 4 is lower than when the high-precision measurement mode is selected, and the ions contact the gas. The possibility of doing is low. Thereby, since the cooling effect is not substantially obtained and the peak distortion is not reduced, the transmittance of ions is increased, which is advantageous in terms of detection sensitivity.

1 and 3, the present invention is applied to a single quadrupole mass spectrometer. However, the present invention is not limited to various mass spectrometers using other quadrupole mass filters. Specifically, it can be clearly applied to a triple quadrupole mass spectrometer or a Q-TOF mass spectrometer. These mass spectrometers have a collision cell for collision-induced dissociation of ions, and an inert gas such as Ar is introduced into the collision cell as a collision gas. It can also be used for cooling in the interior space.

Further, the above-described embodiment is merely an example of the present invention, and is not limited to the above-described modification example, and changes, modifications, and additions are appropriately included in the scope of the claims of the present application even within the scope of the present invention. It is natural.

DESCRIPTION OF SYMBOLS 1 ... Vacuum chamber 2 ... Ion source 3 ... Ion lens 4 ... Quadrupole mass filter 5 ... Detector 6 ... Data processing part 7 ... Control part 71 ... Target vacuum degree switching part 8 ... Input part 81 ... Mode selection part 9 ... Vacuum pump 10 ... Vacuum gauge 11 ... Gas introduction part C ... Ion optical axis

Claims

A mass spectrometry method using a mass spectrometer having a quadrupole mass filter having a predetermined mass-to-charge ratio or selectively passing ions included in a predetermined mass-to-charge ratio range inside a vacuum chamber,
At the time of analysis, at least the gas pressure in the space through which ions are to pass through the quadrupole mass filter is higher than the gas pressure when the vacuum pump that evacuates the vacuum chamber is operated at the maximum exhaust speed. By adjusting the pumping speed of the vacuum pump or the amount of gas introduced into the vacuum chamber from the outside, the ions are cooled by contact between the ions and the gas in the space in the quadrupole mass filter. A mass spectrometric method characterized by that.
A mass spectrometer comprising a quadrupole mass filter in a vacuum chamber for selectively passing ions having a predetermined mass-to-charge ratio or included in a predetermined mass-to-charge ratio range,
a) a gas introduction part for introducing a cooling gas into a space in which ions are to pass in the quadrupole mass filter;
b) a control unit for controlling the amount of gas introduced by the gas introduction unit;
A mass spectrometer comprising:
A mass spectrometer comprising a quadrupole mass filter in a vacuum chamber for selectively passing ions having a predetermined mass-to-charge ratio or included in a predetermined mass-to-charge ratio range,
a) a vacuum pump for evacuating the vacuum chamber;
b) The pumping speed of the vacuum pump is set so that the gas pressure in the vacuum chamber at the time of analysis becomes a predetermined gas pressure higher than the gas pressure in the vacuum chamber when the vacuum pump is operated at the maximum pumping speed. A control unit to control;
A mass spectrometer comprising:
The mass spectrometer according to claim 2,
A high-accuracy measurement mode with a relatively large amount of gas introduction under the control of the control unit and a high-sensitivity measurement mode with a relatively small amount of gas introduction are selectable by the user. Mass spectrometer.
The mass spectrometer according to claim 3,
A high-accuracy measurement mode with a relatively high gas pressure target value under the control of the control unit and a high-sensitivity measurement mode with a relatively low gas pressure target value are selectable by the user. A mass spectrometer characterized by the above.