Mass spectrometer and control method thereof

Abstract

In order to provide a mass spectrometer with which it is possible to shorten the time required to obtain a mass spectrum over a wide mass-to-charge ratio range, this mass spectrometer comprises an ionization unit that generates ions from a sample, a mass filter that separates the ions according to the mass-to-charge ratio, and a detection unit that detects the ions separated by the mass filter, and is characterized by further comprising: an ion guide that transports the ions to the mass filter; and a control unit that generates a mass spectrum and a mass chromatogram using a detection signal obtained while executing sweep control for increasing over time high-frequency voltage to be applied to the ion guide and step control for keeping the high-frequency voltage constant.

Description

Technical Field

[0001] The present invention relates to a mass spectrometer including an ion guide unit, and particularly relates to control of a voltage applied to the ion guide unit.

Background Art

[0002] A mass spectrometer is an apparatus for analyzing a sample using a mass spectrum obtained by separating and detecting ions generated from the sample according to the mass-to-charge ratio m / z, which is the ratio of mass m to charge z. Many mass spectrometers are provided with an ion guide that utilizes the ion focusing action by a high-frequency electric field in order to efficiently transport the generated ions to a mass filter that separates ions according to the mass-to-charge ratio.

[0003] Since ions are transported while vibrating by the high-frequency electric field of the ion guide, the range of the mass-to-charge ratio of ions that can pass through the ion guide is limited by the magnitude of the high-frequency voltage applied to the ion guide. Therefore, in order to obtain a mass spectrum over a wide range of mass-to-charge ratios, a method is used in which multiple measurements are performed while changing the magnitude of the high-frequency voltage, and the mass spectra corresponding to different mass-to-charge ratio ranges obtained by each measurement are integrated. However, when the mass-to-charge ratio range is wide compared to the case where the mass-to-charge ratio range is narrow, the peak intensity relatively decreases in the region where the mass-to-charge ratio is low.

[0004] Patent Document 1 discloses a mass spectrometer that reduces the decrease in peak intensity in the region where the mass-to-charge ratio is low. Specifically, it is disclosed that the high-frequency voltage applied to the ion guide is set so that the ratio of measurements at a high-frequency voltage in a state where the passage efficiency of ions in the region where the mass-to-charge ratio is low is relatively high is about the same even when the mass-to-charge ratio ranges are different.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

SUMMARY OF THE INVENTION

PROBLEMS TO BE SOLVED BY THE INVENTION

[0006] However, in Patent Document 1, since a plurality of measurements are performed while changing the magnitude of the high-frequency voltage applied to the ion guide, it takes a long time to obtain a mass spectrum over a wide mass-to-charge ratio range.

[0007] Therefore, an object of the present invention is to provide a mass spectrometer and a control method thereof that can shorten the time required to obtain a mass spectrum over a wide mass-to-charge ratio range.

MEANS FOR SOLVING THE PROBLEMS

[0008] To achieve the above object, the present invention provides a mass spectrometer including an ionization unit that generates ions from a sample, a mass filter that separates the ions according to the mass-to-charge ratio, and a detection unit that detects the ions separated by the mass filter, further comprising an ion guide that transports the ions to the mass filter, and a control unit that generates a mass spectrum or a mass chromatogram using a detection signal obtained while performing sweep control for increasing the high-frequency voltage applied to the ion guide over time and step control for keeping the high-frequency voltage constant.

[0009] The present invention also provides a control method for a mass spectrometer including an ionization unit that generates ions from a sample, a mass filter that separates the ions according to the mass-to-charge ratio, and a detection unit that detects the intensity of each separated ion, characterized in that a mass spectrum or a mass chromatogram is generated using a detection signal obtained while performing sweep control for increasing the high-frequency voltage applied to an ion guide that transports the ions to the mass filter over time and step control for keeping the high-frequency voltage constant.

EFFECTS OF THE INVENTION

[0010] According to the present invention, it is possible to provide a mass spectrometer and a control method thereof that can shorten the time required to obtain a mass spectrum over a wide mass-to-charge ratio range.

Brief Description of the Drawings

[0011]

Figure 1

Figure 2

Figure 3

Figure 4A

Figure 4B

Figure 5

Figure 6A

Figure 6B

Figure 6C

Figure 7

Embodiments for Carrying Out the Invention

[0012] Hereinafter, preferred embodiments of the mass spectrometer and its control method according to the present invention will be described with reference to the accompanying drawings. The mass spectrometer is an apparatus for analyzing a sample using a mass spectrum obtained by separating and detecting ions generated from the sample according to the mass-to-charge ratio m / z, which is the ratio of mass m to charge z.

Examples

[0013] Using FIG. 1, an example of the overall configuration of the mass spectrometer of Example 1 will be described. The mass spectrometer includes an ionization unit 101, a counter plate 102, a shaft displacement unit 104, an ion guide 105, a mass filter 107, a detector 109, and a control unit 110. Each unit will be described below.

[0014] The ionization unit 101 is a device that generates ions from a sample. For example, a solution containing the sample is flowed through a capillary to which a high voltage is applied, charged droplets are generated by spraying the solution from the tip of the capillary, and the charged droplets are heated and vaporized to generate ions of the sample.

[0015] The counter plate 102 has holes into which ions are taken in and forms an electric field for taking in ions. Also, in order to suppress the intake of neutral particles and the like other than ions, gas is flowed in a direction opposite to the direction in which ions are taken in. The ions taken into the counter plate 102 are guided to the shaft displacement unit 104 through the first pore 103.

[0016] The shaft displacement unit 104 removes neutral particles and the like other than ions by flowing the ions downstream while deflecting them by an electric field. The ions deflected by the shaft displacement unit 104 are guided to the ion guide 105.

[0017] The ion guide 105 is a device that transports ions to the subsequent mass filter 107. The ions that have passed through the ion guide 105 are guided to the mass filter 107 through the second pore 106. The ion guide 105 is configured, for example, by arranging four or more even-numbered lot electrodes in parallel along the traveling direction of the ions, and applying high-frequency voltages with the same intensity and different polarities to adjacent lot electrodes. By applying the high-frequency voltage, the high-frequency electric field formed in the ion guide 105 vibrates the ions, and the magnitude of the vibration of the ions depends on the mass-to-charge ratio of the ions and the magnitude of the high-frequency voltage. That is, the ion transmission rate, which is the ratio of ions that can pass through the ion guide 105, changes depending on the mass-to-charge ratio of the ions and the magnitude of the high-frequency voltage.

[0018] FIG. 2 shows an example of the ion transmission rate that varies depending on the ion mass and the high-frequency voltage. The vertical axis in FIG. 2 represents the ion transmission rate, and the horizontal axis represents the high-frequency voltage. As shown in FIG. 2, the magnitude of the high-frequency voltage at which a high ion transmission rate is achieved varies depending on the ion mass. Lighter ions have a high ion transmission rate at a small high-frequency voltage, and heavier ions have a high ion transmission rate at a large high-frequency voltage. The relationship illustrated in FIG. 2 may be pre-stored and read out as needed.

[0019] The mass filter 107 is a device that separates ions according to the mass-to-charge ratio m / z, which is the ratio of the ion mass m to the charge z. The ions that have passed through the mass filter 107 are guided to the detector 109 through the third pore 108. The mass filter 107 is configured, for example, by arranging four rod electrodes in parallel along the direction of ion travel, and high-frequency voltages and DC voltages with the same intensity but different polarities are applied to adjacent rod electrodes. The range of the mass-to-charge ratio of the ions that can pass through the mass filter 107 is limited by the magnitudes of the high-frequency voltage and the DC voltage.

[0020] FIG. 3 shows the stable region where the vibration of ions converges and the unstable region where the vibration diverges in the mass filter 107 in a coordinate system with the high-frequency voltage V and the DC voltage U as axes. Since the stable region varies depending on the ion mass, it is necessary to set the high-frequency voltage V and the DC voltage U according to the mass of the observed ions. By continuously changing the two voltages while keeping the ratio of the high-frequency voltage V to the DC voltage U constant, that is, along the scanning line in the figure, a mass spectrum can be obtained.

[0021] The detector 109 is a device that detects ions separated according to the mass-to-charge ratio, and is composed of a conversion dynode, a scintillator, a photomultiplier tube, etc. The detection signal output by the detector 109 is transmitted to the control unit 110.

[0022] The control unit 110 is a device that controls each unit and is constituted by, for example, a computer. Further, based on the detection signal transmitted from the detector 109, the control unit 110 generates a mass spectrum in which ion intensities are plotted for each mass-to-charge ratio, or a mass chromatogram in which the ion intensity of a specific mass-to-charge ratio is recorded over time. The generated mass spectrum and mass chromatogram are displayed on a monitor and used for analyzing a sample. Furthermore, the control unit 110 controls the high-frequency voltage applied to the ion guide 105 so that measurement for obtaining a mass spectrum over a wide mass-to-charge ratio range can be completed in one time.

[0023] An example of a control pattern of the high-frequency voltage applied to the ion guide 105 will be described with reference to FIGS. 4A and 4B. The control unit 110 executes sweep control for increasing the high-frequency voltage applied to the ion guide 105 over time and step control for keeping the high-frequency voltage constant. There is no limit to the number of times of executing the sweep control and the step control, and it may be three times of sweep control and two times of step control as shown in FIG. 4A, or one time of sweep control and step control each as shown in FIG. 4B.

[0024] While the sweep control and the step control are being executed for the ion guide 105, the high-frequency voltage V and the DC voltage U applied to the mass filter 107 are controlled to continuously change along the scanning straight line illustrated in FIG. 3, whereby a mass spectrum is generated. Further, while the sweep control and the step control are being executed for the ion guide 105, if the high-frequency voltage V and the DC voltage U of the mass filter 107 are kept constant, only ions of a specific mass-to-charge ratio are detected, so that a mass chromatogram is generated.

[0025] When the ion guide 105 is under sweep control, ions in a wide mass-to-charge ratio range can reach the mass filter 107, so that measurement for obtaining a mass spectrum can be completed in one time, and the time required for the measurement can be shortened.

[0026] Moreover, by executing step control at an appropriate timing, the measurement accuracy can be improved. For example, the sweep control is switched to step control at the timing when the high-frequency voltage that increases over time by sweep control reaches a range where the change in ion transmission rate is small. By switching to step control, ions can be stably transported to the mass filter 107, and the measurement accuracy can be improved. The range of the high-frequency voltage with a small change in ion transmission rate may be obtained from the data showing the relationship between the ion transmission rate and the high-frequency voltage illustrated in FIG. 2.

[0027] Using FIG. 5, another example of the control pattern of the high-frequency voltage applied to the ion guide 105 will be described. In FIG. 5, the entire scan range is divided into three scan ranges, and sweep control and step control are executed any number of times in each scan range. For example, when measuring the range of mass-to-charge ratio 5 to 1000 in the entire scan range, 5 to 100 is measured in the first scan range, 100 to 500 is measured in the second scan range, and 500 to 1000 is measured in the third scan range. As illustrated in FIG. 2, since the high-frequency voltage showing a high ion transmission rate changes according to the ion mass, it is preferable that the high-frequency voltage of the ion guide 105 is set according to the mass-to-charge ratio to be measured. That is, a relatively small high-frequency voltage is set in the first scan range for measuring the range of mass-to-charge ratio 5 to 100, and a relatively large high-frequency voltage is set in the third scan range for measuring the range of mass-to-charge ratio 500 to 1000. It should be noted that each scan range is preferably set wider than the mass-to-charge ratio range of the measurement target.

[0028] Using FIGS. 6A to 6C, the mass-to-charge ratio range of the measurement target and each scan range will be described. FIG. 6A shows a mass spectrum measured by setting the first scan range from 5 to 130 for the mass-to-charge ratio range from 5 to 100 of the measurement target. That is, the first scan range is 30 wider than the mass-to-charge ratio range of the measurement target. Further, FIG. 6B shows the result of measurement by setting the second scan range from 70 to 530 for the mass-to-charge ratio range from 100 to 500. That is, the second scan range is 60 wider than the mass-to-charge ratio range of the measurement target. Furthermore, FIG. 6C shows the result of measurement by setting the third scan range from 470 to 1000 for the mass-to-charge ratio range from 500 to 1000. That is, the third scan range is 30 wider than the mass-to-charge ratio range of the measurement target. By setting the scan range wider than the mass-to-charge ratio range of the measurement target, the detection omission of ions can be reduced.

[0029] FIG. 7 shows an example of a mass spectrum in the mass-to-charge ratio range from 5 to 1000 generated by integrating the measurement results illustrated in FIGS. 6A to 6C. In the region where each scan range overlaps, the data with the higher ion intensity is adopted.

[0030] As described above, by performing sweep control and step control on the ion guide 105, the time required to obtain a mass spectrum over a wide mass-to-charge ratio range can be shortened. Also, the measurement accuracy can be improved by switching from sweep control to step control at an appropriate timing.

[0031] The embodiments of the present invention have been described above. The present invention is not limited to the above embodiments, and components may be modified without departing from the gist of the invention. Also, a plurality of components disclosed in the above embodiments may be appropriately combined. Further, some components may be deleted from all the components shown in the above embodiments.

Description of Reference Numerals

[0032] 101: Ionization section, 102: Counter plate, 103: First pore, 104: Axial displacement section, 105: Ion guide, 106: Second pore, 107: Mass filter, 108: Third pore, 109: Detector, 110: Control section

Claims

1. An ionization unit that generates ions from a sample, a mass filter that separates the ions according to their mass-to-charge ratio, a mass spectrometer comprising a detection unit that detects the ions separated by the mass filter, an ion guide that transports the ions to the mass filter, further comprising a control unit that generates a mass spectrum or a mass chromatogram using a detection signal obtained while executing a sweep control that increases a high-frequency voltage applied to the ion guide over time and a step control that keeps the high-frequency voltage constant, wherein the control unit switches from the sweep control to the step control at a timing when the high-frequency voltage that increases over time by the sweep control reaches a range where the change in ion transmission rate is small. The mass spectrometer is characterized by this.

2. A control method for a mass spectrometer comprising an ionization unit that generates ions from a sample, a mass filter that separates the ions according to their mass-to-charge ratio, and a detection unit that detects the intensity of each separated ion, generating a mass spectrum or a mass chromatogram using a detection signal obtained while executing a sweep control that increases a high-frequency voltage applied to an ion guide that transports the ions to the mass filter over time and a step control that keeps the high-frequency voltage constant, and switching from the sweep control to the step control at a timing when the high-frequency voltage that increases over time by the sweep control reaches a range where the change in ion transmission rate is small. The control method is characterized by this.

Images