Mass spectrometer and control method thereof

Abstract

To reduce the performance variation of a mass spectrometer when measuring positive ions and when measuring negative ions. [Solution] The mass spectrometer comprises a mass spectrometer (20) equipped with a multipole electrode and a power supply circuit that applies voltage to the multipole electrode, and a control unit (25). The control unit predetermines the polarity of the DC voltage to be applied to each of the first electrode group and the second electrode group when the mass spectrometer measures positive ions and when it measures negative ions, and the power supply circuit is configured to be able to switch the polarity of the DC voltage to be applied to the first electrode group and the second electrode group in response to instructions from the control unit.

Description

[Technical Field]

[0001] The present invention relates to a mass spectrometer and a control method thereof. [Background technology]

[0002] Patent Document 1 discloses the results of simulations of the number of ions passing through a quadrupole mass filter and peak shape under different voltage application conditions, in order to use a quadrupole electric field having hexapole components as a quadrupole mass filter. The simulations include a case where a positive DC voltage and a negative DC voltage are applied to the opposing X rods and Y rods of the quadrupole mass filter, respectively, and a case where a negative DC voltage and a positive DC voltage are applied to the opposing X rods and Y rods, respectively. [Prior art documents] [Patent documents]

[0003] [Patent Document 1] Special Publication No. 2007-507064 Summary of the Invention [Problem to be solved by the invention]

[0004] Quadrupole electrodes are well known as an ion mass separation mechanism in mass spectrometers. During quadrupole electrode operation, a positive DC voltage is applied to one of two opposing electrode pairs, and a negative DC voltage is applied to the other, with a high-frequency AC voltage superimposed on each. Typically, the DC voltages applied to the two opposing electrode pairs are fixed in polarity. Patent Document 1 also merely seeks optimal voltage application conditions for obtaining resolution while maintaining signal strength, but does not suggest switching the DC voltages applied to the opposing X and Y rods of a quadrupole mass filter.

[0005] For a quadrupole electrode to perform as designed, the four electrodes that make up the quadrupole electrode must be positioned correctly, and even a misalignment of a few micrometers can lead to performance degradation such as reduced resolution and sensitivity, peak splitting, etc. For this reason, it has been extremely difficult to eliminate the effects of misalignment simply by improving the machining and assembly accuracy of the parts. [Means for solving the problem]

[0006] A mass spectrometer according to one embodiment of the present invention comprises a mass spectrometer including a multipole electrode and a power supply circuit that applies voltages to the multipole electrode, and a control unit. The multipole electrode comprises a plurality of electrodes consisting of a first electrode group and a second electrode group. The first electrode group and the second electrode group are positioned so as to overlap with the second electrode group when the first electrode group is rotated a predetermined angle around the ion optical axis. The power supply circuit applies DC voltages of different polarities superimposed with a high-frequency AC voltage to each of the first electrode group and the second electrode group. The control unit predetermines the polarities of the DC voltages to be applied to each of the first electrode group and the second electrode group when the mass spectrometer measures positive ions and when it measures negative ions. The power supply circuit is configured to be able to switch the polarities of the DC voltages to be applied to the first electrode group and the second electrode group in response to instructions from the control unit. [Effects of the Invention]

[0007] The present invention reduces the performance variation of a mass spectrometer when measuring positive ions and when measuring negative ions. Other objects and novel features will become apparent from the description of this specification and the accompanying drawings. [Brief explanation of the drawings]

[0008] [Figure 1] 1 is a configuration example of a mass spectrometer. [Figure 2] This is an example of a configuration in which quadrupole electrodes are used as the mass separator. [Figure 3] FIG. 1 is a diagram for explaining a problem to be solved by the present invention. [Figure 4] FIG. 1 is a diagram for explaining a problem to be solved by the present invention. [Figure 5] 3A and 3B are diagrams showing patterns of voltages applied to quadrupole electrodes in the present embodiment. [Figure 6] 10 is a flowchart for determining the polarity of a DC voltage to be applied to a quadrupole electrode. [Figure 7A] 1 is a diagram illustrating an example of the configuration of a power supply circuit that applies a voltage to quadrupole electrodes. [Figure 7B] 1 is a diagram illustrating an example of the configuration of a power supply circuit that applies a voltage to quadrupole electrodes. [Figure 8] This is an example of a configuration in which a hexapole electrode and a quadrupole electrode are used in a mass spectrometer. [Figure 9] FIG. 10 is a diagram showing a voltage pattern applied to a hexapole electrode. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

[0010] A mass spectrometer ionizes chemical substances and separates and measures the resulting ions based on their mass. Figure 1 shows an example of the configuration of a mass spectrometer. The mass spectrometer includes a sample injection unit 11, a separation unit 12, a mass spectrometer 20, and a control unit 25. The sample injection unit 11 is, for example, an autosampler, which allows for automated, continuous analysis of many samples. The separation unit 12 is, for example, a gas chromatograph or liquid chromatograph, and separates the components contained in the sample. In the separation unit 12, the sample is transported by a mobile phase (gas or liquid) and separated into individual components based on the strength of interaction with the stationary phase. The sample components separated by the separation unit 12 are detected by a mass spectrometer 20. The ionization unit 21 ionizes the sample components from the separation unit 12. The mass separation unit 22 separates the ions based on their mass-to-charge ratio (m / z) in a vacuum, and a detector 23 detects the ions separated by their mass-to-charge ratio (m / z). The control unit 25 is an information processing device such as a PC (Personal Computer) that controls the mass spectrometer, and is equipped with a data processing unit 26. The data processing unit 26 receives ion detection signals from the detector 23 and performs data processing such as calculating the relative ion intensity for each mass-to-charge ratio (m / z). The mass spectrometer 20 is maintained at a high vacuum by a vacuum pump 24 during measurement, and the sample components ionized by the ionization unit 21 are detected without being scattered or fragmented due to interactions with other gas molecules, enabling highly sensitive detection.

[0011] Several types of mass separator 22 for a mass spectrometer 20 are known, but FIG. 2 shows an example configuration using quadrupole electrodes as the mass separator 22. The four cylindrical electrodes 31 to 34 that make up the quadrupole electrode are arranged equidistant from the central axis (ion optical axis) with their longitudinal directions parallel to each other. FIG. 2 shows an example in which the first electrode 31 and the third electrode 33 form an electrode pair facing each other in the y-axis direction, and the second electrode 32 and the fourth electrode 34 form an electrode pair facing each other in the x-axis direction. To operate the quadrupole electrode as a mass separator, a DC voltage U and a high-frequency AC voltage Vcosωt (ω: frequency, t: time) are superimposed and applied. Furthermore, DC voltages of the same polarity (first polarity) are applied to opposing electrodes, and DC voltages of opposite polarity (second polarity) are applied to adjacent electrodes.

[0012] By applying such voltages to the quadrupole electrodes, an electric field is formed inside the quadrupole electrodes, and this electric field causes ions introduced into the quadrupole electrodes from the ionization unit 21 to oscillate in the x- and y-axis directions. In this example, a negative DC voltage (-U) is applied to the first electrode 31 and the third electrode 33 (the electrode pair in the y-axis direction), and a positive DC voltage (+U) is applied to the second electrode 32 and the fourth electrode 34 (the electrode pair in the x-axis direction). In this case, when measuring positive ions, the target ions (positive ions) oscillate in the y-axis direction while moving in the z-direction, while in measuring negative ions, the target ions (negative ions) oscillate in the x-axis direction while moving in the z-direction. Ions with a mass-to-charge ratio within a specific range determined by the applied voltages (U, V, ω) enter a stable oscillation state and pass through the quadrupole electrodes to reach the detector 23. On the other hand, ions with mass-to-charge ratios other than these oscillate unstably and collide with the electrodes or escape from the system, thereby not reaching the detector 23.

[0013] As long as the four electrodes constituting the quadrupole electrode are positioned equidistant from the ion optical axis (z-axis in Figure 2), the same detection results can be obtained even if the polarity of the applied DC voltage is reversed, i.e., a positive DC voltage is applied to the electrode pair in the y-axis direction and a negative DC voltage is applied to the electrode pair in the x-axis direction. Only the vibration direction of the ions changes.

[0014] However, if the four electrodes are not ideally positioned, variations occur in the trajectories of ions traveling in the z direction. Figure 3 shows a case where the fourth electrode 34 is displaced from its original position in the x direction by ε, where ε is a magnitude of approximately several μm. Figure 4 shows the results of a simulation of the mass spectrum obtained with the quadrupole electrodes when the electrode positions are displaced as shown in Figure 3. The horizontal axis represents the mass-to-charge ratio (m / z), and the vertical axis represents the number of ions detected by the detector 23. The simulation calculated how many ions would reach the detector 23 if 100 ions of a given mass-to-charge ratio were introduced into the quadrupole electrodes from the ionization unit 21. Mass spectrum 41 is the mass spectrum of positive ions, and mass spectrum 42 is the mass spectrum of negative ions. In mass spectrum 41 of positive ions, the electrode pair in the y-axis direction to which a negative DC voltage is applied is positioned at an ideal position, whereas in mass spectrum 42 of negative ions, the electrode pair in the x-axis direction to which a positive DC voltage is applied is misaligned, resulting in a difference in the peak shapes of the two spectra. That is, peak splitting occurs in mass spectrum 42, and the peak apex is gentler than in mass spectrum 41.

[0015] This deterioration of the mass spectrum profile can be resolved by repeating the measurement and averaging the data, but this requires a longer measurement time. The more ideal the profile obtained in a single measurement, the shorter the time required for analysis.

[0016] Therefore, the mass spectrometer of this embodiment is configured to switch the DC voltage applied to the quadrupole electrodes. As shown in FIG. 5 , a first voltage pattern applies a negative DC voltage and a positive DC voltage to the y-axis electrode pair and the x-axis electrode pair, respectively, and a second voltage pattern applies a positive DC voltage and a negative DC voltage to the y-axis electrode pair and the x-axis electrode pair, respectively. Different voltage patterns are used for measuring positive ions and negative ions. If only the x-axis electrode pair is misaligned, as explained with reference to FIGS. 3 and 4 , the first voltage pattern will degrade the mass spectrum profile when measuring negative ions. Therefore, the first voltage pattern is used for measuring positive ions, and the second voltage pattern is used for measuring negative ions. This allows for a good profile equivalent to mass spectrum 41 to be obtained even when measuring negative ions.

[0017] FIG. 6 shows a flowchart for determining the polarity of the DC voltage applied to the quadrupole electrodes in the mass spectrometer of this embodiment. This flow is executed by the control unit 25, for example, during installation of the instrument. First, the control unit 25 sets the polarity of the DC voltage applied to the electrode pairs of the quadrupole electrodes to a first applied voltage pattern (see FIG. 5) (S01). After performing mass axis correction and resolution adjustment (S02), an evaluation sample is introduced into the instrument and a mass spectrum is acquired (S03). The evaluation sample may be any sample within the detection mass range of the mass spectrometer, and the ions generated by the ionization unit 21 may be either positive or negative ions. The polarity of the DC voltage applied to the electrode pairs of the quadrupole electrodes is then set to a second applied voltage pattern (see FIG. 5) (S04). The same evaluation sample as in step S03 is introduced into the instrument and a mass spectrum is acquired (S05). The spectral shape of the mass spectrum acquired in steps S03 and S05 is then determined (S06). The criteria for the determination can be, for example, signal intensity (determined by the peak height of the mass spectrum) or resolution (determined by the peak half-width of the mass spectrum). Based on the determination of the spectrum shape in step S06, the polarity of the DC voltage to be applied to the electrode pair is determined (S07).

[0018] For example, if the ions generated by the evaluation sample are positive ions and it is determined in step S06 that the spectral shape obtained with the first applied voltage pattern is superior to the spectral shape obtained with the second applied voltage pattern, the control unit 25 stores as measurement conditions the first applied voltage pattern for positive ion measurement and the second applied voltage pattern for negative ion measurement. By switching the polarity of the DC voltage applied to the quadrupole electrodes between positive ion measurement and negative ion measurement, it becomes possible to obtain a mass spectrum that is less affected by misalignment, even if the electrodes constituting the quadrupole electrodes are misaligned.

[0019] The applied voltage patterns set in steps S01 and S04 may be reversed. Although evaluation samples of the same polarity are used for selection in the flow of Fig. 6, evaluation may be performed using both an evaluation sample that generates positive ions and an evaluation sample that generates negative ions, and applied voltage patterns that can individually obtain good mass spectra may be selected.

[0020] 7A and 7B show an example configuration of a power supply circuit that applies voltage to the quadrupole electrodes. The power supply circuit includes a control circuit 51, a selector switch 52, DC amplifiers 53 and 54, an RF amplifier 55, and a resonant circuit 56. The resonant circuit 56 includes a transformer, and a high-frequency AC voltage is applied to the primary coil of the transformer from the RF amplifier 55. The transformer also includes two secondary coils, one end of which is connected to the electrode pair in the y-axis direction and the other end of which is connected to the electrode pair in the x-axis direction, respectively. The other end of one secondary coil is connected to the DC amplifier 53, and the other end of the other secondary coil is connected to the DC amplifier 54. A positive DC voltage or a negative DC voltage is input from the control circuit 51 to the DC amplifiers 53 and 54. The control circuit 51 can switch the polarity of the DC voltage input to the DC amplifiers 53 and 54 using the selector switch 52. 7A shows a case where positive and negative DC voltages are input to DC amplifiers 53 and 54, respectively, and Fig. 7B shows a case where negative and positive DC voltages are input to DC amplifiers 53 and 54, respectively. Control circuit 51 is instructed by control unit 25 on the magnitude and polarity of the DC voltage to be applied.

[0021] Although the DC voltage polarity determination flow (Figure 6) was explained as being performed when the device was installed, it can also be performed at other times. For example, continued use of the device can cause degradation of characteristics, such as reduced sensitivity due to contamination of the electrode surface or broadening of the spectrum shape. In such cases, performance can be restored by executing the flow in Figure 6 and switching the voltage pattern applied to the quadrupole electrodes. This has the effect of reducing the frequency of quadrupole electrode maintenance and extending the life of the device.

[0022] Although the above embodiments have been described using quadrupole electrodes as mass separators, mass spectrometers also use hexapole electrodes or octapole electrodes with different numbers of electrodes. These are collectively referred to as multipole electrodes. A multipole electrode includes a plurality of electrodes, consisting of a first electrode group and a second electrode group, and the first electrode group and the second electrode group are positioned so that they overlap with the second electrode group when the first electrode group is rotated a predetermined angle around the ion optical axis. The first electrode group and the second electrode group correspond to electrode pairs in a quadrupole electrode and are distinguished by the polarity of the DC voltage applied thereto. In mass spectrometers, hexapole electrodes and octapole electrodes are used as ion guides to focus passing ions in the ion optical axis direction and as filters to perform mass separation. A DC voltage and a high-frequency AC voltage are also applied to the hexapole and octapole electrodes, and the characteristics differ between when positive ions and negative ions pass through depending on the positional misalignment of the electrodes. Therefore, by switching the polarity of the DC voltage applied to the first electrode group and the second electrode group depending on the polarity of the sample, desirable characteristics can be obtained regardless of the polarity of the sample.

[0023] FIG. 8 shows an example in which a hexapole electrode is arranged as an ion guide 81 in front of the quadrupole electrode 22. In the case of the hexapole electrode, as shown in FIG. 9, the polarity of the DC voltage applied to the first electrode group (electrodes 91, 93, 95) and the second electrode group (electrodes 92, 94, 96) is switched between (positive, negative) (as shown) and (negative, positive). The polarity of the DC voltage applied to the hexapole electrodes can also be switched by providing a power supply circuit such as that shown in FIGS. 7A and 7B. The switching pattern is based on the flow shown in FIG. 6, and a preferred applied voltage pattern can be selected by switching the polarity of the DC voltage to the hexapole electrodes and determining the spectral shape of the mass spectrum obtained for each.

[0024] The present invention is not limited to the above-described embodiment, and includes various modifications. For example, the above-described embodiment has been described in detail to clearly explain the present invention, and the present invention is not necessarily limited to those including all of the described configurations. Furthermore, it is possible to add, delete, or replace part of the configuration of the embodiment with other configurations. [Explanation of symbols]

[0025] 11: sample injection unit, 12: separation unit, 20: mass spectrometer, 21: ionization unit, 22: mass separation unit, 23: detector, 24: vacuum pump, 25: control unit, 26: data processing unit, 31: first electrode, 32: second electrode, 33: third electrode, 34: fourth electrode, 41, 42: mass spectrum, 51: control circuit, 52: changeover switch, 53, 54: DC amplifier, 55: RF amplifier, 56: resonant circuit, 81: ion guide, 91, 92, 93, 94, 95, 96: electrodes.

Claims

1. a mass spectrometer including a multipole electrode and a power supply circuit that applies a voltage to the multipole electrode; a control unit; the multipole electrode comprises a plurality of electrodes consisting of a first electrode group and a second electrode group, the first electrode group and the second electrode group being arranged at positions where they overlap with the second electrode group when the first electrode group is rotated by a predetermined angle around the ion optical axis; the power supply circuit applies a high-frequency AC voltage superimposed on a DC voltage having a polarity different from that of the first electrode group and the second electrode group, the control unit determines in advance polarities of DC voltages to be applied to the first electrode group and the second electrode group when the mass spectrometer measures positive ions and when the mass spectrometer measures negative ions; The power supply circuit is configured to be able to switch the polarity of the DC voltage applied to the first electrode group and the second electrode group in response to an instruction from the control unit.

2. In claim 1, When the mass spectrometer measures positive ions, the power supply circuit applies a DC voltage of a first polarity to the first electrode group and a DC voltage of a second polarity to the second electrode group, and when the mass spectrometer measures negative ions, the power supply circuit applies a DC voltage of a second polarity to the first electrode group and a DC voltage of the first polarity to the second electrode group.

3. In claim 1, The multipole electrode is a quadrupole electrode, A mass spectrometer comprising an electrode pair that is the first electrode group and an electrode pair that is the second electrode group.

4. In claim 1, The control unit causes the mass spectrometer to measure at least either positive ions or negative ions for both a first applied voltage pattern in which the power supply circuit applies a DC voltage of a first polarity to the first electrode group and a DC voltage of a second polarity to the second electrode group, and a second applied voltage pattern in which the power supply circuit applies a DC voltage of a second polarity to the first electrode group and a DC voltage of the first polarity to the second electrode group, and determines the polarities of the DC voltages to be applied to the first electrode group and the second electrode group, respectively, when the mass spectrometer measures positive ions and when it measures negative ions, based on an evaluation of the measurement results.

5. In claim 4, the control unit evaluates the measurement results based on the spectral shape of the mass spectrum obtained when the power supply circuit applies the first applied voltage pattern to the multipole electrodes and the spectral shape of the mass spectrum obtained when the power supply circuit applies the second applied voltage pattern to the multipole electrodes.

6. A method for controlling a mass spectrometer having a mass spectrometer including a multipole electrode and a power supply circuit that applies a voltage to the multipole electrode, and a control unit, comprising: the multipole electrode comprises a plurality of electrodes consisting of a first electrode group and a second electrode group, the first electrode group and the second electrode group being arranged at positions where they overlap with the second electrode group when the first electrode group is rotated by a predetermined angle around the ion optical axis; the power supply circuit applies a high-frequency AC voltage superimposed on a DC voltage having a polarity different from that of the first electrode group and the second electrode group, the power supply circuit is configured to be able to switch polarities of DC voltages applied to the first electrode group and the second electrode group, The control unit predetermines the polarity of the DC voltage to be applied to each of the first electrode group and the second electrode group when the mass spectrometer measures positive ions and when the mass spectrometer measures negative ions, and the power supply circuit switches and controls the polarity of the DC voltage to be applied to the first electrode group and the second electrode group.

7. In claim 6, A method for controlling a mass spectrometer, wherein when the mass spectrometer measures positive ions, the power supply circuit applies a DC voltage of a first polarity to the first electrode group and a DC voltage of a second polarity to the second electrode group, and when the mass spectrometer measures negative ions, the power supply circuit applies a DC voltage of a second polarity to the first electrode group and a DC voltage of the first polarity to the second electrode group.

8. In claim 6, The multipole electrode is a quadrupole electrode, A method for controlling a mass spectrometer including an electrode pair that is the first electrode group and an electrode pair that is the second electrode group.

9. In claim 6, The control unit causes the mass spectrometer to measure at least one of positive ions and negative ions for both a first applied voltage pattern in which the power supply circuit applies a DC voltage of a first polarity to the first electrode group and a DC voltage of a second polarity to the second electrode group, and a second applied voltage pattern in which the power supply circuit applies a DC voltage of a second polarity to the first electrode group and a DC voltage of the first polarity to the second electrode group, and determines the polarities of the DC voltages to be applied to the first electrode group and the second electrode group when the mass spectrometer measures positive ions and when the mass spectrometer measures negative ions based on an evaluation of the measurement results.

10. In claim 9, a control unit for controlling a mass spectrometer, the control unit evaluating a measurement result based on a spectral shape of a mass spectrum obtained when the power supply circuit applies a voltage to the multipole electrodes in the first application voltage pattern and a spectral shape of a mass spectrum obtained when the power supply circuit applies a voltage to the multipole electrodes in the second application voltage pattern.

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