Collision cross section measurement in time-of-flight mass analyser

A method of operating a time-of-flight (ToF) mass analyser that is configured to determine a mass to charge ratio (m/z) of ions by determining flight times of ions along an ion path, the method comprising:

• operating the time-of-flight (ToF) mass analyser in a first mode of operation, and analysing ions by determining flight times of the ions along the ion path so as to obtain a first set of data, wherein in the first mode of operation (i) the ion path has a first path length, and (ii) the ion path is maintained at a first pressure;
• operating the time-of-flight (ToF) mass analyser in a second mode of operation, and analysing ions by determining flight times of the ions along the ion path so as to obtain a second set of data, wherein in the second mode of operation (i) the ion path has a second path length, and (ii) the ion path is maintained at a second pressure, wherein the second path length is different to the first path length and/or the second pressure is different to the first pressure;
• comparing an intensity of an ion peak in the first set of data to an intensity of a corresponding ion peak in the second set of data;
• determining, based on the comparison, a collision cross section (CCS) of ions associated with the corresponding ion peaks;
• and
• operating the time-of-flight (ToF) mass analyser in a mass analysis mode of operation, wherein in the mass analysis mode of operation the ion path is maintained at a third pressure, wherein the third pressure is less than the first and second pressures.

A method of determining a calibration for a time-of-flight (ToF) mass analyser that is configured to determine a mass to charge ratio (m/z) of ions by determining flight times of ions along an ion path, the method comprising:

• operating the time-of-flight (ToF) mass analyser in a first mode of operation, and analysing calibrant ions by determining flight times of the calibrant ions along the ion path so as to obtain a first set of data, wherein in the first mode of operation (i) the ion path has a first path length, and (ii) the ion path is maintained at a first pressure;
• operating the time-of-flight (ToF) mass analyser in a second mode of operation, and analysing calibrant ions by determining flight times of the calibrant ions along the ion path so as to obtain a second set of data, wherein in the second mode of operation (i) the ion path has a second path length, and (ii) the ion path is maintained at a second pressure, wherein the second path length is different to the first path length and/or the second pressure is different to the first pressure;
• determining a plurality of ratios, wherein each ratio is a ratio of an intensity of an ion peak in the first set of data to an intensity of a corresponding ion peak in the second set of data;
• and
• using each ratio together with a known collision cross section (CCS) value for calibrant ions associated with that ratio to determine a calibration for the time-of-flight (ToF) mass analyser.

An analytical instrument comprising:

• a time-of-flight (ToF) mass analyser configured to determine the a mass to charge ratio (m/z) of ions by determining flight times of ions along an ion path;
• and
• a control system configured to:
• operate the time-of-flight (ToF) mass analyser in a first mode of operation, and analyse ions by determining flight times of the ions along the ion path so as to obtain a first set of data, wherein in the first mode of operation (i) the ion path has a first path length, and (ii) the ion path is maintained at a first pressure;
• operate the time-of-flight (ToF) mass analyser in a second mode of operation, and analyse ions by determining flight times of the ions along the ion path so as to obtain a second set of data, wherein in the second mode of operation (i) the ion path has a second path length, and (ii) the ion path is maintained at a second pressure, wherein the second path length is different to the first path length and/or the second pressure is different to the first pressure;
• compare an intensity of an ion peak in the first set of data to an intensity of a corresponding ion peak in the second set of data;
• and
• determine, based on the comparison and using a calibration for the time-of-flight (ToF) mass analyser, a collision cross section (CCS) of the ions associated with the corresponding ion peaks.

An analytical instrument comprising:

• a mass analyser configured to determine a mass to charge ratio (m/z) of ions by determining flight times of ions along an ion path;
• and
• a control system configured to:
• operate the mass analyser in a first mode of operation, and analyse ions by determining flight times of the ions along the ion path so as to obtain a first set of data, wherein in the first mode of operation (i) the ion path has a first path length, and (ii) the ion path is maintained at a first pressure;
• operate the mass analyser in a second mode of operation, and analyse ions by determining flight times of the ions along the ion path so as to obtain a second set of data, wherein in the second mode of operation (i) the ion path has a second path length, and (ii) the ion path is maintained at a second pressure, wherein the second path length is different to the first path length and/or the second pressure is different to the first pressure;
• compare an intensity of an ion peak in the first set of data to an intensity of a corresponding ion peak in the second set of data;
• and
• determine, based on the comparison, a collision cross section (CCS) of the ions associated with the corresponding ion peaks,
• wherein the control system is further configured to:
• operate the mass analyser in a mass analysis mode of operation, wherein in the mass analysis mode of operation the ion path is maintained at a third pressure, wherein the third pressure is less than the first and second pressures.