Method of gain calibration

Patent metadata

Field	Value
Publication number	US-11996277-B2
Application number	US-202217660525-A
Country	US
Kind code	B2
Filing date	Apr 25, 2022
Priority date	May 14, 2021
Publication date	May 28, 2024
Grant date	May 28, 2024

Abstract

A method of gain calibration for an ion detector operating at a detector voltage is described. The method includes steps of: generating single ions; determining a parameter of a first relationship between a detector output of an ion detector and a number of ions for a first detector voltage; detecting an ion peak at the ion detector using the first detector voltage; adjusting the detector voltage; and determining a parameter of a second relationship between the detector output and the number of ions for the second detector voltage. A system including a mass spectrometer arrangement and a controller configured to operate the mass spectrometer arrangement in accordance with this method is also described.

First claim

The invention claimed is:

1. A method of gain calibration for an ion detector operating at a detector voltage, the method comprising steps of:
generating single ions;
determining a parameter of a first relationship between a detector output of an ion detector and a number of ions for a first detector voltage, by detecting single ions at the ion detector;
detecting an ion peak at the ion detector using the first detector voltage, to determine a number of ions in the ion peak, based on the parameter of the first relationship;
adjusting the detector voltage to reduce a ratio between the detector output and a noise level and thereby obtain a second detector voltage at which the detector output for the ion peak remains above the noise level;
determining a parameter of a second relationship between the detector output and the number of ions for the second detector voltage, based on the determined number of ions in the ion peak.

2. The method of claim 1 , further comprising:
monitoring a gain calibration of the ion detector by:
detecting a second ion peak at the ion detector using a third detector voltage;
determining a number of ions in the second ion peak;
determining a second parameter of the second relationship between the detector output of the ion detector and the number of ions for the third detector voltage, based on the determined number of ions in the second ion peak;
comparing the second parameter of the second relationship to an expected value, based on the second relationship; and
determining, based on the comparison, whether a drift in the gain has occurred.

3. The method of claim 2 , further comprising:
based on determining that a drift in the gain has occurred:
calculating an adjustment parameter, to adjust the detector voltage to a level at which the relationship between the detector output and the number of ions corresponds to the expected value of the second parameter of the second relationship, based on the second relationship; and
setting the detector voltage, based on the adjustment parameter.

4. The method of claim 1 , further comprising:
operating the ion detector at the second detector voltage.

5. The method of claim 1 , wherein
the ion detector forms part of a time-of-flight (TOF) mass spectrometer (MS).

6. The method of claim 5 , further comprising:
generating the single ions by setting the TOF MS to operate in a time-defocused mode, in which ions having the same mass-to-charge (m/z) ratio arrive at the ion detector at different times.

7. The method of claim 2 , wherein
the ion detector forms part of a time-of-flight (TOF) mass spectrometer (MS) and detecting the second ion peak comprises setting the TOF MS to operate in the time-defocused mode, such that the second ion peak corresponds to a single ion.

8. The method of claim 1 , further comprising:
step-wise adjusting the detector voltage during the step of adjusting the detector voltage; and
calculating a calibration curve, based on the detector output generated by detecting single ions at the ion detector for each detector voltage step.

9. The method of claim 1 , wherein
the first relationship and the second relationship are the same relationship; and
the parameter of the first relationship and the parameter of the second relationship are different.

10. The method of claim 1 , wherein the ion detector comprises: a first ion detector device; and a second ion detector device; and wherein the steps of determining a parameter of a first relationship and detecting an ion peak at the ion detector are performed with respect to the first ion detector device and the steps of adjusting the detector voltage and determining a parameter of a second relationship are performed with reference to the second ion detector device.

11. The method of claim 10 , wherein the second ion detector device forms part of a time-of-flight mass (TOF) mass spectrometer (MS) or an ion trap.

12. The method of claim 10 , wherein the first ion detector device forms part of a Fourier transform mass spectrometer (FTMS).

13. The method of any of claim 10 , wherein the FTMS is an orbital trapping or Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer.

14. The method of claim 2 , wherein the ion detector comprises: a first ion detector device; and a second ion detector device; and wherein the steps of determining a parameter of a first relationship and detecting an ion peak at the ion detector are performed with respect to the first ion detector device, the steps of adjusting the detector voltage and determining a parameter of a second relationship are performed with reference to the second ion detector device, the step of detecting the second ion peak at the ion detector is performed with respect to the first ion detector device, and the step of determining a parameter of a third relationship is performed with reference to the second ion detector device.

15. The method of claim 10 , wherein the parameter of the first relationship is a signal-to-noise (S/N) ratio.

16. The method of claim 15 , further comprising:
detecting multiply-charged single ions at the first ion detector device;
calculating the S/N ratio of the multiply-charged single ions;
determining the S/N ratio of a singly-charged single ion, based on the calculated S/N ratio of the multiply-charged single ions.

17. The method of claim 10 , wherein
a correction factor is applied to the determined number of ions in the ion peak, to account for transmission of ions to the second ion detector device.

18. The method of claim 17 , wherein the correction factor is between 30% and 50%.

19. The method of claim 1 , further comprising:
generating the single ions by beam attenuation, fragmentation, scattering ions with background gas or using an electrospray ionisation (ESI) source.

20. A system comprising a mass spectrometer arrangement and a controller configured to operate the mass spectrometer arrangement in accordance with the method of claim 1 .

Assignees

• Thermo Fisher Scient Bremen Gmbh

Inventors

• Stewart Hamish
• Petzoldt Johannes
• Hagedorn Bernd
• Grinfeld Dmitry

Classifications

• H01J49/0036 Primary

  Step by step routines describing the handling of the data generated during a measurement · CPC title

• H01J49/025 Primary

  Detectors specially adapted to particle spectrometers (data acquisition H01J49/0036; detectors per se G01T, e.g. G01T1/28, G01T1/29) · CPC title

• H01J49/406

  with multiple reflections · CPC title

• H01J49/0009 Primary

  Calibration of the apparatus · CPC title

• H01J49/0031 Primary

  Step by step routines describing the use of the apparatus (H01J49/0081 takes precedence) · CPC title