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EP-4078651-B1 - FOURIER TRANSFORM QUADRUPOLE CALIBRATION METHOD

EP4078651B1EP 4078651 B1EP4078651 B1EP 4078651B1EP-4078651-B1

Inventors

  • HAGER, JAMES

Dates

Publication Date
20260506
Application Date
20200929

Claims (15)

  1. A method of calibrating a Fourier Transform (FT) quadrupole mass spectrometer (1000), comprising: measuring a plurality of secular frequencies of a calibrant ion in a quadrupole FT mass analyzer (1002) for a plurality of RF voltages (V RF ) applied to at least one rod of said quadrupole mass analyzer, characterized by calculating Mathieu β and q parameters for each of said measured secular frequencies, determining RF voltage amplitude (V RF ) for each calculated q parameter, for each calculated q parameter, determining an offset RF voltage amplitude (ΔV RF )corresponding to a deviation of said applied V RF and said calculated V RF to generate a ΔV RF v.s. q calibration curve.
  2. The method of claim 1, further comprising measuring a secular frequency of an analyte, calculating Mathieu β and q parameters for said analyte based on said measured secular frequency, using said calibration curve to determine an adjusted q parameter for said analyte, and calculating an m/z ratio of said analyte based on said adjusted q parameter.
  3. The method of claim 1, further comprising measuring a resolving DC voltage applied to at least one of the quadrupole rods (1004a - 1004d).
  4. The method of claim 3, further comprising calculating Mathieu a parameter based on said measured resolving DC voltage.
  5. The method of claim 4, wherein said q parameter is determined based on said calculated β and a parameters.
  6. The method of claim 1, wherein said plurality of RF voltages have a peak-to-peak amplitude in a range of about 50 to about 5000 volts.
  7. The method of claim 1, wherein said plurality of RF voltages have a frequency in a range of about 0.5 to about 3 MHz.
  8. The method of claim 1, wherein said resolving DC voltage is in a range of about 5 to about 250 volts.
  9. The method of claim 2, further comprising a resolving DC voltage applied to at least one rod of said quadrupole FT mass analyzer; optionally wherein said Mathieu q parameter is determined based on said calculated β and a parameters.
  10. The method of claim 1, wherein said step of measuring the secular frequencies comprises introducing the calibrant ion into the FT mass analyzer.
  11. The method of claim 10, further comprising applying a pulsed excitation voltage to at least one rod of said quadrupole mass analyzer so as to excite said calibrant ion at a secular frequency thereof; optionally wherein said pulsed excitation voltage comprises a dipolar excitation.
  12. A mass spectrometer, comprising: a Fourier Transform (FT) mass analyzer (1000) having a plurality of rods arranged in a quadrupole configuration and having an input port for receiving a plurality of ions and an output port through which the ions exit the mass analyzer, a system for measuring a plurality of secular frequencies of a calibrant ion introduced into said quadrupole mass analyzer for a plurality of RF voltages (V RF ) applied to at least one rod of said FT mass analyzer (1002), and characterized by an analysis module receiving said measured secular frequencies and performing the following operations: calculating Mathieu β and q parameters for each of said measured secular frequencies, determining RF voltage amplitude (V RF ) for each calculated q parameter, for each calculated q parameter, determining an offset RF voltage amplitude (ΔV RF ) corresponding to a deviation of said applied V RF and said calculated V RF to generate a ΔV RF v.s. q calibration curve.
  13. The mass spectrometer of claim 12, wherein said system is further configured to measure a resolving DC voltage applied to at least one of the rods of FT mass analyzer.
  14. The mass spectrometer of claim 13, wherein said analysis module is configured to receive said measured resolving DC voltage and calculate a Mathieu parameter based on said measured resolving DC voltage.
  15. The mass spectrometer of claim 14, wherein said analysis module determines the q parameter based on said calculated β and a parameters.

Description

Related Application This application claims priority to U.S. provisional application no. 62/949,342 filed on December 17, 2019, entitled "Fourier Transform Quadrupole Calibration Method". Background The present teachings generally relate to methods and systems for performing mass spectrometry, and more particularly to methods and systems for calibrating a Fourier Transform (FT) mass spectrometer. Mass spectroscopy (MS) is an analytical technique for determining the elemental composition of test substances with both quantitative and qualitative applications. For example, MS can be used to identify unknown compounds, to determine the isotopic composition of elements in a molecule, and to determine the structure of a particular compound by observing its fragmentation, as well as to quantify the amount of a particular compound in the sample. A variety of mass analyzers are known. Some such mass analyzers employ a plurality of rods arranged in a multipole arrangement, e.g., a quadrupole arrangement. The application of radiofrequency (RF) voltages to the rods can provide an electromagnetic field for radial confinement of ions as they pass through the mass analyzer. There is a difficulty in calibrating any RF voltage-based mass spectrometer where the measured quantity in the secular frequency of ions within the mass spectrometer (i.e., the characteristic oscillation frequency of an ion in the RF field). Conventional calibration methods based on secular frequency of ions within a quadrupole field are known, but they are typically complicated. For example, a calibration method for a secular frequency scanning ion trap is known, but it is difficult to implement and depends on knowing mass-dependent delays for ion ejection from the ion trap. The inherent difficulty in such calibration methods arises from non-linear relationship between the measured ion secular frequency and m/z ratios of the ions. Document WO 2018/142265 A1 discloses a known Fourier Transform quadrupole mass spectrometer. Accordingly, there is a need for improved calibration methods and systems for calibrating a Fourier Transform (FT) mass spectrometer. Summary In one aspect, a method of calibrating a Fourier Transform (FT) quadrupole mass spectrometer is disclosed, which comprises measuring a plurality of secular frequencies of a calibrant ion in a quadrupole FT mass analyzer for a plurality of RF voltages (VRF) applied to at least one rod of the quadrupole mass analyzer, calculating Mathieu β and q parameters for each of the measured secular frequencies, and determining RF voltage amplitude (VRF) for each calculated q parameter. For each calculated q parameter, an offset RF voltage amplitude (ΔVRF) corresponding to a deviation of the applied VRF and the calculated VRF is determined so as to generate a ΔVRF v.s. q calibration curve. In some embodiments, the secular frequency of the calibrant ion can be determined by introducing the calibrant ion into the FT mass analyzer and applying a pulsed excitation voltage to at least one rod of the quadrupole mass analyzer so as to excite the calibrant ion at a secular frequency thereof. In some embodiment, the pulsed excitation voltage can be in the form of a dipolar excitation. The calibration curve can then be employed to obtain accurate values of the q parameter for an analyte under study. For example, in some embodiments, a secular frequency of an analyte under study is measured, and the measured secular frequency is employed to calculate Mathieu β and q parameters for that analyte. The above calibration curve can then be employed to adjust the calculated q parameter and the adjusted q parameter can be used to calculate an m/z ratio of the analyte. In some embodiments, a resolving DC voltage can be applied to at least one rod of the quadrupole mass analyzer. In such embodiments, in addition to Mathieu β parameter, Mathieu a parameter can also be calculated based on the measured resolving DC voltage. The q parameter associated with the analyte under study can then be determined based on the calculated Mathieu β and a parameters. In some embodiments, the RF voltage(s) applied to the one or more rods of the FT mass analyzer can be in a range of about 50 volts to about 5000 volts (peak-to-peak). Further, in some such embodiments, the RF voltages can have a frequency in a range of about 0.5 MHz to about 3 MHz. In some embodiments, the resolving DC voltage applied to at least one rod of the quadrupole FT mass analyzer can be, for example, in a range of about 5 to about 250 volts. In a related aspect, a mass spectrometer is disclosed, which comprises a Fourier Transform (FT) mass analyzer having a plurality of rods arranged in a quadrupole configuration and having an input port for receiving a plurality of ions and an output port through which the ions exit the mass analyzer. The mass spectrometer can further include a system for measuring a plurality of secular frequencies of a calibrant ion introduced into the