Processing ion peak areas in mass spectrometry

1 . A method of analysing a signal generated by a mass analyser, the method comprising:

receiving a signal generated by the mass analyser, the signal including one or more ion peaks;

determining the area of a first ion peak of the one or more ion peaks; and

estimating the number of ions that contributed to the first ion peak by: (i) determining a correction to be applied to the area of the first ion peak from a correction function, wherein the correction function describes a relationship between average single ion area and ion mass (m), mass-to-charge ratio (m/ ) and/or charge ( ) for the mass analyser; and (ii) applying the correction to the area of the first ion peak.

2 . The method of claim 1 , wherein the correction function describes the relationship between average single ion area and ion mass or m/z for the analyser across a m/z range, wherein the m/z range is from about 25, 50, 75 or 100, to about 6000, 8000, 10,000, or 15,000.

3 . The method of claim 2 , wherein a mass or m/z dependence of the correction function is continuous across the m/z range.

4 . The method of claim 1 , wherein:

a mass or m/z dependence of the correction function has a maximum at a transition mass, increases with increasing mass at masses below the transition mass, and decreases with increasing mass at masses above the transition mass.

5 . The method of claim 4 , wherein the analyser includes an ion detector comprising at least a dynode, and wherein the transition mass depends on one or more properties of the dynode.

6 . The method of claim 1 , wherein a mass or m/z dependence of the correction function has the form (√{square root over (2T)}) b am −b/2 exp(−(2T) 1/2 m −1/2 /v 0 ) or av b exp(−v/v 0 ), where T is the kinetic energy of an ion, m is its mass, v is its velocity, and a, b and v 0 are best fit parameters.

7 . The method of claim 1 , wherein the correction function describes a relationship between average single ion area and charge for the analyser across a charge range from 1 elementary charge to 10 or more elementary charges.

8 . The method of claim 7 , wherein a charge dependence of the correction function varies linearly with charge.

9 . The method of claim 1 , where the correction function for the analyser is obtained by scaling a global correction function.

10 . The method of claim 1 , further comprising:

determining the area of one or more further ion peaks of the one or more ion peaks; and

estimating the number of ions that contributed to each of the one or more further ion peaks by, for each of the one or more further ion peaks: (i) determining a correction to be applied to the area of the ion peak from the correction function; and (ii) applying the correction to the area of the ion peak.

11 . The method of claim 1 , wherein the correction function or a global correction function is determined by fitting a model to measured single ion area (SIA) data.

12 . The method of claim 11 , wherein the single ion area (SIA) data is corrected SIA data derived from raw SIA data by correcting the raw SIA data for detector efficiency.

13 . A method of operating an analytical instrument that comprises an ion source and a mass analyser, the method comprising:

generating ions in the ion source;

analysing the ions with the mass analyser so as to generate a signal; and

analysing the signal using the method of claim 1 .

14 . The method of claim 1 , wherein the mass analyser is a time-of-flight (ToF) mass analyser.

15 . The method of claim 14 , wherein the time-of-flight mass analyser includes an ion trap, and wherein the method comprises:

accumulating a first packet of ions in the ion trap;

analysing the first packet of ions so as to generate a first signal;

analysing the first signal so as to estimate the total number of ions in the first packet of ions; and

accumulating a second packet of ions in the ion trap;

wherein the estimated total number of ions in the first packet of ions is used to control the total number of ions in the second packet of ions.

16 . A non-transitory computer readable storage medium storing computer software code which when executed on a processor performs the method of claim 1 .

17 . A control system for an analytical instrument, the control system configured to cause the analytical instrument to perform the method of claim 1 .

18 . An analytical instrument comprising an ion analyser and the control system of claim 17 .

19 . A method of determining a correction function for a mass analyser, the method comprising:

using a mass analyser to analyse a plurality of single ions, wherein the plurality of single ions includes ions having mass, m/z, and/or charge spread across most or all of mass, m/z, and/or charge range(s) of interest for the analyser;

generating single ion area (SIA) data by determining the area of each ion peak of a plurality of ion peaks generated by the analyser in response to analysing the plurality of single ions; and

determining a correction function by fitting a model to the SIA data.

20 . An analytical instrument comprising:

a mass analyser; and

a control system configured to:

receive a signal generated by the mass analyser, the signal including one or more ion peaks;

determine the area of a first ion peak of the one or more ion peaks; and

estimate the number of ions that contributed to the first ion peak by: (i) determining a correction to be applied to the area of the first ion peak from a correction function, wherein the correction function describes a relationship between average single ion area and ion mass, mass-to-charge ratio, and/or charge for the mass analyser; and (ii) applying the correction to the area of the first ion peak.

21 . The analytical instrument of claim 20 , wherein the mass analyser is a time-of-flight mass analyser comprising an ion trap, and the instrument is configured to:

accumulate a first packet of ions in the ion trap;

analyse the first packet of ions so as to generate a first signal;

estimate the total number of ions in the first packet of ions; and

use the estimated total number of ions in the first packet of ions to control the number of ions in a second packet of ions accumulated in the ion trap.