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JP-7855924-B2 - Time-of-flight mass spectrometer and method for adjusting the same

JP7855924B2JP 7855924 B2JP7855924 B2JP 7855924B2JP-7855924-B2

Inventors

  • 内山 皓介
  • 大城 朝是

Assignees

  • 株式会社島津製作所

Dates

Publication Date
20260511
Application Date
20220530

Claims (9)

  1. A time-of-flight mass spectrometer comprising a measuring unit including a flight electric field forming unit that forms an electric field in the flight space for ions to fly, and an ion acceleration unit that accelerates the ions to be measured and sends them into the flight space, An analysis processing unit, which creates a spectrum showing the relationship between time of flight or mass-to-charge ratio and ionic intensity based on the data obtained by the measurement unit, An index value calculation unit calculates, as an index value, the difference between the time of flight or mass-to-charge ratio between the midpoint of the first peak width at an intensity obtained by multiplying the peak's top intensity by a first ratio and the midpoint of the second peak width at an intensity obtained by multiplying the peak's top intensity by a second ratio smaller than the first ratio, for the peaks observed in the spectrum. An evaluation result storage unit that evaluates and stores the left-right symmetry of the peak from the aforementioned index value, A time-of-flight mass spectrometer equipped with the following features.
  2. The time-of-flight mass spectrometer according to claim 1, wherein the first ratio is 40% or more and 60% or less .
  3. The time-of-flight mass spectrometer according to claim 1, wherein the second ratio is 5% or more and 30% or less .
  4. The time-of-flight mass spectrometer according to claim 1, further comprising a display processing unit for displaying the evaluation results from the evaluation result storage unit.
  5. The time-of-flight mass spectrometer according to claim 1, further comprising an adjustment unit that adjusts the voltage applied to at least one electrode in the measurement unit using the evaluation results from the evaluation result storage unit.
  6. The measurement unit further comprises an adjustment unit that performs a measurement in the measurement unit while changing the voltage applied to at least one electrode in the measurement unit, and adjusts the voltage using one or more of the mass resolution, sensitivity, and mass peak waveform shape based on the measurement results, The time-of-flight mass spectrometer according to claim 1, wherein the index value calculation unit calculates an index value based on the measurement result each time the voltage is changed in the adjustment unit and a measurement is performed.
  7. The time-of-flight mass spectrometer according to claim 6, further comprising an ion introduction unit for introducing ions into the ion acceleration unit, the ion acceleration unit accelerating the introduced ions in a direction perpendicular to them, the flight electric field forming unit including a flight tube that forms a space for ions to fly freely, and a reflectron that forms an electric field that reflects ions, and the adjustment unit adjusting the voltage applied to at least one electrode included in the ion acceleration unit, the flight tube, or the reflectron.
  8. The ion acceleration unit includes a first accelerating electrode to which a pulse voltage for accelerating ions is applied, and a second accelerating electrode to which a voltage for further accelerating the ions accelerated by the first accelerating electrode is applied, and the adjustment unit adjusts the voltage applied to either the first or the second accelerating electrode, as described in claim 7.
  9. A method for adjusting a time-of-flight mass spectrometer comprising a measuring unit including a flight electric field forming unit that forms an electric field in the flight space for ions to fly, and an ion acceleration unit that accelerates the ions to be measured and sends them into the flight space, Based on the data obtained by the measurement unit, an analysis processing step is performed to create a spectrum showing the relationship between time of flight or mass-to-charge ratio and ionic intensity. An index value calculation step in which, for the peak observed in the spectrum, the difference between the time of flight or the mass-to-charge ratio between the midpoint of the first peak width at an intensity obtained by multiplying the peak's top intensity by a first ratio and the midpoint of the second peak width at an intensity obtained by multiplying the peak's top intensity by a second ratio smaller than the first ratio is calculated as an index value, An adjustment step of adjusting the voltage applied to the electrodes included in the measuring unit using at least the index value or another numerical value obtained from the index value, A method for adjusting a time-of-flight mass spectrometer having the following characteristics.

Description

This invention relates to a time-of-flight mass spectrometer (TOFMS) and a method for adjusting the same. Mass spectrometers have become widely used in recent years for the identification and quantification of compounds in samples. In TOFMS, a type of mass spectrometer, ions derived from the sample are accelerated by imparting a certain kinetic energy to them and introduced into a flight space. The flight time of the ions after they have traveled a predetermined distance within this space is then measured. Since this flight time depends on the ion's mass-to-charge ratio (m/z), a mass spectrum showing the relationship between the m/z value and ionic intensity (ion quantity) can be created by converting the flight time to an m/z value. Generally, TOFMS is often used when high mass resolution and accuracy are required, such as when estimating the structure of unknown compounds from precise mass measurement results. Therefore, TOFMS needs to improve not only its sensitivity but also its mass resolution and accuracy. Typically, mass spectrometers are equipped with an auto-tuning function that automatically adjusts the voltage applied to the electrodes of each part of the instrument that affects the behavior of ions (see Patent Document 1, etc.). Generally, in such auto-tuning, parameter values such as the voltage applied to each part are adjusted so that the top intensity of the mass peak (hereinafter simply referred to as "peak") corresponding to a specific compound obtained when measuring a standard sample is maximized, or so that the mass resolution calculated from the peak is maximized. Japanese Patent Publication No. 2018-120804Japanese Patent Publication No. 2020-85602 "2.00 General Principles of Chromatography," Pharmaceuticals and Medical Devices Agency (PMDA), [Online], [Accessed May 10, 2022], Internet <URL: https://www.pmda.go.jp/files/000242610.pdf> A diagram showing the main components of a quadrupole-time-of-flight mass spectrometer, which is one embodiment of the present invention.A flowchart illustrating the auto-tuning operation in the quadrupole-time-of-flight mass spectrometer of this embodiment.A conceptual diagram illustrating the method for calculating the evaluation value of peak symmetry in this embodiment.A conceptual diagram illustrating a comparison between a conventional asymmetry coefficient and an evaluation value of peak symmetry according to one aspect of the present invention, when the number of measurement points constituting a single peak is small.A flowchart illustrating the flow of the auto-tuning operation in one modified example. A quadrupole-time-of-flight mass spectrometer (hereinafter sometimes referred to as "Q-TOFMS"), which is one embodiment of the TOFMS according to the present invention, will be described with reference to the attached drawings. This Q-TOFMS is a tandem mass spectrometer that combines a quadrupole mass filter and an orthogonal accelerated TOFMS, allowing for selective performance of both general mass spectrometry without ion dissociation and MS/MS analysis with specific ions dissociated. Figure 1 is a diagram showing the main components of the Q-TOFMS according to this embodiment. As shown in Figure 1, this Q-TOFMS comprises a measurement unit 1, a voltage source 2, a control/processing unit 3, an input unit 4, and a display unit 5. The measurement unit 1 performs measurements on a sample (liquid sample) and comprises a vacuum chamber 10 and an ionization chamber 11 connected to the front of the vacuum chamber 10. The interior of the vacuum chamber 10 is roughly divided into four chambers: a first intermediate vacuum chamber 12, a second intermediate vacuum chamber 13, a first analysis chamber 14, and a second analysis chamber 15. The ionization chamber 11 maintains a near-atmospheric pressure atmosphere, and the system is configured as a multi-stage differential pumping system, with the vacuum level increasing progressively from the ionization chamber 11 through the first intermediate vacuum chamber 12, the second intermediate vacuum chamber 13, the first analysis chamber 14, and the second analysis chamber 15. Although Figure 1 omits the details of the vacuum pumps used to evacuate each chamber, generally, the first intermediate vacuum chamber 12, which follows the ionization chamber 11, is evacuated by a rotary pump, and each subsequent chamber is evacuated by a turbomolecular pump using a rotary pump as a roughing pump. An electrospray ion (ESI) source 111 is located in the ionization chamber 11, and the ionization chamber 11 and the first intermediate vacuum chamber 12 are connected through a small-diameter desolvation tube 112. A multipole ion guide 121 is located in the first intermediate vacuum chamber 12, and the first intermediate vacuum chamber 12 and the second intermediate vacuum chamber 13 are separated by a skimmer 122 having an opening at its top. A multipole ion guide 131 is also located in the second intermediate vacuum chamber 13.