GB2584336A

GB2584336A - Method of calibrating analytical instrument

Info

Publication number: GB2584336A
Application number: GB1907773.4A
Authority: GB
Inventors: Berney Andrew; Palmer Martin
Original assignee: Micromass UK Ltd
Current assignee: Micromass UK Ltd
Priority date: 2019-05-31
Filing date: 2019-05-31
Publication date: 2020-12-02
Also published as: GB201907773D0

Abstract

Measured spectral mass peak values are initially automatically assigned to reference values 606, and an indication of which measured value has been assigned to which reference value is displayed via a user interface 608. Corrections to the automatic assignment can then be received from a user 610, before a calibration is performed 612, 614.

Description

METHOD OF CALIBRATING ANALYTICAL INSTRUMENT

CROSS REFERENCE TO RELATED APPLICATION None.

FIELD OF THE INVENTION

The present invention provides a method of calibrating an analytical instrument such as a mass and/or ion mobility spectrometer.

BACKGROUND

Analytical instruments such as mass and/or ion mobility spectrometers are typically calibrated using a compound that will produce ions having known values of one or more physico-chemical properties (such as a known mass to charge ratio and/or collision cross section (CCS)). The calibrant compound is ionised, and one or more physico-chemical properties (such as mass to charge ratio and/or drift time) of the resulting ions are measured using the instrument.

The measured physico-chemical property values are compared to reference physico-chemical property values, and differences between the measured values and the reference values are determined and used to calibrate the instrument.

The Applicants believe that there remains scope for improvements to methods of calibrating analytical instruments.

SUMMARY

According to an aspect, there is provided a method of calibrating an analytical instrument comprising: ionising a calibrant so as to produce ions; using the analytical instrument to measure a physico-chemical property of the ions and/or of product or fragment ions derived from said ions; -2 -for each of plural reference values of the physico-chemical property, automatically assigning a measured value of the physico-chemical property to the reference value of the physico-chemical property; displaying via a user interface information indicating which measured value has been assigned to each of the plural reference values; receiving, via the user interface, for one or more of the reference values (i) an indication of a change to the measured value assigned to the reference value; and/or (ii) an indication that the reference value should be omitted when determining a calibration for the analytical instrument; and then for each of plural of the reference values, determining a difference between the reference value and the measured value assigned to that reference value; and determining a calibration for the analytical instrument using the differences. Various embodiments relate to a method of calibrating an analytical instrument in which an automated calibration process may be assisted by a user.

As such, various embodiments are related to a semi-automated (assisted) calibration process.

In accordance with various embodiments, a calibrant compound is ionised so as to produce ions, and the analytical instrument is used to measure a physicochemical property (such as mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section (CCS)) of the ions (and/or of product or fragment ions derived from the ions). For example, the analytical instrument may be used to produce a mass spectrum and/or an ion mobility spectrum of the calibrant ions (and/or of product or fragment ions derived from the calibrant ions).

The calibrant may be selected so as to produce ions having known values of the physico-chemical property (such as one or more known mass to charge ratio or time of flight values and/or one or more known collision cross section (CCS) or (ion mobility) drift time values). These known values may be stored a set of plural reference values of the physico-chemical property.

In accordance with various embodiments, each of plural of the reference values of the physico-chemical property (such as each of plural reference values of mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section (CCS)) may be compared to the measured values of the physico-chemical property of the ions. In particular, the analytical instrument may (attempt to) automatically assign a (single) measured value of the physico-chemical property to each of plural of the reference values of the physico-chemical property. In other -3 -words, for each of plural of the reference values, the analytical instrument may (attempt) to find the (single) measured value that corresponds most closely to the reference value.

For example, the analytical instrument may (attempt to) automatically assign an ion peak in the mass and/or an ion mobility spectrum to each reference value of some or all of the reference values.

In this regard, the Applicants have recognised that (as will be described in more detail below) a problem with this kind of automated calibration process is that it is possible for the analytical instrument to wrongly assign a measured value (ion peak) to a reference value, and that this can be the case regardless of the level of sophistication in the algorithm(s) used to assign measured values to reference values. The effect of such incorrect assignments can be to reduce the accuracy of the calibration, and so degrade the performance of the analytical instrument.

Moreover (and as will be described in more detail below), the Applicants have recognised that a human user will often be capable of recognising instances of a measured value (ion peak) being incorrectly assigned to a reference value, where an algorithm is not. This may be the case, for example, where a user has some knowledge of and/or experience with a particular calibrant that is being used to calibrate the instrument.

Thus, in accordance with various embodiments information indicating which of the measured values has been assigned to each of the plural reference values may be displayed to a user via a user interface. The measured values and/or the reference values may also be displayed to the user via the user interface.

For example, the mass and/or ion mobility spectrum may be displayed via the user interface, and each ion peak within the spectrum that has been assigned to a reference value may be indicated as such, for example by using colour coding or otherwise. Correspondingly, each ion peak within the spectrum that is unassigned to a reference value may be indicated as such, for example by using colour coding or otherwise.

The analytical instrument may then receive, via the user interface (from the user), for one or more of the reference values, (i) an indication of a change to the measured value assigned to the reference value; and/or (ii) an indication that the reference value should be omitted when determining a calibration for the analytical instrument. -4 -

Thus, in accordance with various embodiments, a user is able to examine information indicating which of the measured values has been assigned to each of plural reference values, optionally together with the measured values and/or the reference values. Where a user determines that a particular measured value has been incorrectly assigned to a reference value, the user can indicate this to the analytical instrument via the user interface.

For example, where a measured value (such as an ion peak within the spectrum) has been incorrectly assigned to a particular reference value, the user can indicate via the user interface another measured value (such as another ion peak within the spectrum) that should be assigned to that reference value in place of the incorrectly assigned measured value. The incorrectly assigned measured value may then be disregarded when determining a calibration for the analytical instrument.

Additionally or alternatively, for example where a user considers that it is not possible to reliably determine which measured value should be assigned to a particular reference value, the user can indicate to the instrument that that reference value (and its assigned measured value) should be disregarded (should not be used) when determining a calibration for the analytical instrument.

Once the automated peak assignment has been manually corrected or adjusted by the user in this manner, a calibration for the analytical instrument may be determined. This may involve, for each of some or all of the plural reference values (for example, for each of the reference values that are not to be omitted), determining a difference between the reference value and the measured value that has been (automatically or manually) assigned to that reference value, and then using these differences to determine the calibration for the analytical instrument.

Since as described above, in various embodiments the number of instances of a measured value being incorrectly assigned to a reference value may be reduced, the calibration may accordingly be more accurate.

It will accordingly be appreciated that various embodiments provide an improved method of calibrating an analytical instrument.

According to an aspect, there is provided a computer program comprising computer software code for performing the method described above when the program is run on a data processor.

The method may comprise receiving, via the user interface, an indication of a selection of one or more parameters and/or settings for the calibration. -5 -

The method may comprise controlling the analytical instrument to measure the physico-chemical property of the ions and/or of product or fragment ions derived from the ions in accordance with the selected parameters and/or settings.

The method may comprise displaying, via the user interface, information indicative of a plurality of different combinations of the one or more parameters and/or settings for the calibration.

The method may comprise receiving, via the user interface, an indication of a selection of one or more of the different combinations.

The method may comprise controlling the analytical instrument to measure the physico-chemical property of the ions and/or of product or fragment ions derived from the ions in accordance with each of the selected combinations of parameters and/or settings.

The method may comprise determining a respective calibration for the analytical instrument for each of the selected combinations of parameters and/or settings.

The one or more parameters and/or settings may comprise: (i) a physico chemical property range for the calibration; 00 a polarity for the calibration; (iii) a resolution for the calibration; and/or (iv) a type of calibration.

The method may comprise receiving, via the user interface, an indication of a selection of a calibrant for the calibration.

The method may comprise ionising the selected calibrant so as to produce the ions.

The reference values may comprise known values of the physico-chemical property for the selected calibrant.

The method may comprise displaying, via the user interface, at least some of the measured values and/or at least some of the reference values.

The physico-chemical property may comprise mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section.

The method may comprise ionising an analyte so as to produce analyte ions.

The method may comprise using the analytical instrument to measure the physico-chemical property of the analyte ions and/or of product or fragment ions derived from the analyte ions. -6 -

The method may comprise using the determined calibration to calibrate the measured physico-chemical property of the analyte ions and/or of product or fragment ions derived from the analyte ions.

According to an aspect, there is provided an analytical instrument comprising: an ion source configured to ionise a calibrant so as to produce ions; an analyser configured to measure a physico-chemical property of the ions and/or of product or fragment ions derived from said ions; and a control system; wherein the control system is configured to: for each of plural reference values of the physico-chemical property, automatically assign a measured value of the physico-chemical property to the reference value of the physico-chemical property; display via a user interface information indicating which measured value has been assigned to each of the plural reference values; receive, via the user interface, for one or more of the reference values (i) an indication that the reference value should be omitted when determining a calibration for the analytical instrument, and/or (ii) an indication of a change to the measured value assigned to the reference value; and then for each of plural of the reference values, determine a difference between the reference value and the measured value assigned to that reference value; and determine a calibration for the analytical instrument using the differences.

The control system may be configured to receive, via the user interface, an indication of a selection of one or more parameters and/or settings for the calibration.

The control system may be configured to control the analytical instrument to measure the physico-chemical property of the ions and/or of the product or fragment ions derived from the ions in accordance with the selected parameters and/or settings.

The control system may be configured to display, via the user interface, information indicative of a plurality of different combinations of one or more parameters and/or settings for the calibration.

The control system may be configured to receive, via the user interface, an indication of a selection of one or more of the different combinations. -7 -

The control system may be configured to control the analytical instrument to measure the physico-chemical property of the ions and/or of product or fragment ions derived from the ions in accordance with each of the selected combinations of parameters and/or settings.

The control system may be configured to determine a respective calibration for the analytical instrument for each of the selected combinations of parameters and/or settings.

The one or more parameters and/or settings may comprise: (i) a physico chemical property range for the calibration; (ii) a polarity for the calibration; (iii) a resolution for the calibration; and/or (iv) a type of calibration.

The control system may be configured to receive, via the user interface, a selection of a calibrant.

The ion source may be configured to ionise the selected calibrant so as to produce the ions.

The control system may be configured to display, via the user interface, at least some of the measured values and/or at least some of the reference values. The analyser may comprise a mass analyser and/or an ion mobility analyser configured to measure the mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section of the ions. The analyser may be configured to measure a physico-chemical property of the ions, such as the drift time of the ions, that allows the collision cross section of the ions to be determined.

The ion source may be configured to ionise an analyte so as to produce analyte ions.

The analyser may be configured to measure the physico-chemical property of the analyte ions and/or of product or fragment ions derived from the analyte ions.

The control system may be configured to use the determined calibration to calibrate the measured physico-chemical property of the analyte ions and/or of product or fragment ions derived from the analyte ions.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be described, by way of example only, and with reference to the accompanying drawings in which: Fig. 1 shows schematically an analytical instrument in accordance with various embodiments; -8 -Figs. 2-5 show an overview screen of a user interface for an analytical instrument in accordance with various embodiments; Fig. 6 shows a flow chart illustrating a method of calibrating an analytical instrument in accordance with various embodiments; Fig. 7 show an overview screen of a user interface for an analytical instrument in accordance with various embodiments; Figs. 8-10 show a calibration assessment screen of a user interface for an analytical instrument in accordance with various embodiments; and Figs. 11-12 show an overview screen of a user interface for an analytical instrument in accordance with various embodiments.

DETAILED DESCRIPTION

Fig. 1 shows schematically an analytical instrument such as a mass and/or ion mobility spectrometer in accordance with various embodiments. As shown in Fig. 1, the analytical instrument comprises an ion source 10, one or more functional components 20 that are arranged downstream from the ion source 10, and an analyser 30 that is arranged downstream from the ion source 10 and from the one or more functional components 20.

As illustrated by Fig. 1 the analytical instrument may be configured such that ions can be provided by (sent from) the ion source 10 to the analyser 30 via the one or more functional components 20.

The ion source 10 may be configured to generate ions, for example by ionising a calibrant (or an analyte). The ion source 10 may comprise any suitable ion source such as an ion source selected from the group consisting of: (i) an Electrospray ionisation ("ESI") ion source; (h) an Atmospheric Pressure Photo Ionisation ("APPI") ion source; (iii) an Atmospheric Pressure Chemical Ionisation ("APCI") ion source; (iv) a Matrix Assisted Laser Desorption Ionisation ("MALDI") ion source; (v) a Laser Desorption Ionisation ("LDI") ion source; (vi) an Atmospheric Pressure Ionisation ("API") ion source; (vii) a Desorption Ionisation on Silicon ("DIOS") ion source; (viii) an Electron Impact ("El") ion source; (ix) a Chemical Ionisation ("Cl") ion source; (x) a Field Ionisation ("Fr) ion source; (xi) a Field Desorption ("FD") ion source; (xii) an Inductively Coupled Plasma ("ICP") ion source; (xiii) a Fast Atom Bombardment ("FAB") ion source; (xiv) a Liquid Secondary Ion Mass Spectrometry ("LSIMS") ion source; (xv) a Desorption -9 -Electrospray Ionisation ("DESI") ion source; (xvi) a Nickel-63 radioactive ion source; (xvii) an Atmospheric Pressure Matrix Assisted Laser Desorption Ionisation ion source; (xviii) a Thermospray ion source; (xix) an Atmospheric Sampling Glow Discharge Ionisation ("ASGDI") ion source; (xx) a Glow Discharge ("GD") ion source; (xxi) an Impactor ion source; (xxii) a Direct Analysis in Real Time ("DART") ion source; (xxiii) a Laserspray Ionisation ("LSI") ion source; (xxiv) a Sonicspray Ionisation ("SSI") ion source; (xxv) a Matrix Assisted Inlet Ionisation ("MAII") ion source; (xxvi) a Solvent Assisted Inlet Ionisation ("SAII") ion source; (xxvii) a Desorption Electrospray Ionisation ("DESI") ion source; (xxviii) a Laser Ablation Electrospray Ionisation ("LAESI") ion source; (xxix) a Surface Assisted Laser Desorption Ionisation ("SALDI") ion source; (xxx) a Low Temperature Plasma ("LTP") ion source; and (xxxi) a Helium Plasma Ionisation ("HePI") ion source. In various particular embodiments, the ion source 10 comprises an Electrospray Ionisation ("ESI") ion source.

The analytical instrument may comprise a chromatography or other separation device (not shown in Fig. 1) upstream of (and coupled to) the ion source 10. The chromatography separation device may comprise a liquid chromatography or gas chromatography device. Alternatively, the separation device may comprise: (i) a Capillary Electrophoresis ("CE") separation device; (ii) a Capillary Electrochromatography ("CEC") separation device; (iii) a substantially rigid ceramic-based multilayer microfluidic substrate ("ceramic tile") separation device; or (iv) a supercritical fluid chromatography separation device.

The analyser 30 may be configured to analyse ions, so as to determine (measure) one or more of their physico chemical properties, such as their mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section (CCS).

The analyser 30 may comprise a mass analyser (that is configured to determine the mass to charge ratio or time of flight of ions) and/or an ion mobility analyser (that is configured to determine the ion mobility drift time or collision cross section (CCS) of ions).

Where the analyser 30 comprises a mass analyser, the mass analyser may comprise any suitable mass analyser such as a mass analyser selected from the group consisting of: (i) a quadrupole mass analyser; 00 a 2D or linear quadrupole mass analyser; (iii) a Paul or 3D quadrupole mass analyser; (iv) a Penning trap mass analyser; (v) an ion trap mass analyser; (vi) a magnetic sector mass analyser; (vii) Ion Cyclotron Resonance ("ICR") mass analyser; (viii) a Fourier Transform Ion Cyclotron Resonance ("FTICR") mass analyser; (ix) an electrostatic mass analyser arranged to generate an electrostatic field having a quadro-logarithmic potential distribution; (x) a Fourier Transform electrostatic mass analyser; (xi) a Fourier Transform mass analyser; (xii) a Time of Flight mass analyser; (xiii) an orthogonal acceleration Time of Flight mass analyser; and (xiv) a linear acceleration Time of Flight mass analyser.

In various particular embodiments, the analyser 30 comprises a Time of Flight mass analyser.

The one or more functional components 20 may comprise any suitable such components, devices and functional elements of an analytical instrument (mass and/or ion mobility spectrometer).

For example, in various embodiments, the one or more functional components 20 comprise one or more ion guides, one or more ion traps, and/or one or more mass filters, for example which may be selected from the group consisting of: (i) a quadrupole mass filter; (ii) a 2D or linear quadrupole ion trap; (iii) a Paul or 3D quadrupole ion trap; (iv) a Penning ion trap; (v) an ion trap; (vi) a magnetic sector mass filter; (vii) a Time of Flight mass filter; and (viii) a Wien filter.

The one or more functional components 20 may comprise an activation, collision, fragmentation or reaction device configured to activate, fragment or react ions.

The one or more functional components 20 may comprise an ion mobility separator configured to separate ions according to their ion mobility. The ion mobility separator may comprise a linear ion mobility separator, or a closed loop (cyclic) ion mobility separator.

The analytical instrument may be operated in various modes of operation including a mass spectrometry ("MS") mode of operation; a tandem mass spectrometry ("MS/MS") mode of operation; a mode of operation in which parent or precursor ions are alternatively fragmented or reacted so as to produce fragment or product ions, and not fragmented or reacted or fragmented or reacted to a lesser degree; a Multiple Reaction Monitoring ("MRM") mode of operation; a Data Dependent Analysis ("DDA") mode of operation; a Data Independent Analysis ("DIA") mode of operation a Quantification mode of operation or an Ion Mobility Spectrometry ("IMS") mode of operation.

It should be noted that Fig. 1 is merely schematic, and that the analytical instrument may (and in various embodiments does) include other components, devices and functional elements to those shown in Fig. 1.

As shown in Fig. 1, the analytical instrument may comprise a control system 40, that may be configured to control the operation of the analytical instrument, for example in the manner of the various embodiments described herein. The control system may comprise suitable control circuitry that is configured to cause the instrument to operate in the manner of the various embodiments described herein. The control system may comprise suitable processing circuitry configured to perform any one or more or all of the necessary processing and/or post-processing operations in respect of the various embodiments described herein. In various embodiments, the control system may comprise a suitable computing device, a microprocessor system, a programmable FPGA (field programmable gate array), and the like.

As shown in Fig. 1, the control system 40 may comprise or may be connected to a display 50. The control system 40 may be configured to provide a user interface such as a graphical user interface (GUI) to the display 50. The display 50 may be configured to display the user interface.

The control system 40 may also comprise or may be connected to one or more input devices (not shown in Fig. 1), such as a keyboard, mouse, trackpad, touchscreen, microphone, and the like. The control system 40 and/or the user interface may be configured to receive inputs from a user, such as data and control signals, via the one or more input devices.

Various embodiments are directed to a method of calibrating an analytical instrument such as the analytical instrument of Fig. 1. Various embodiments relate to a method of calibrating an analytical instrument in which an automated calibration process may be assisted by a user. Thus, various embodiments are related to a semi-automated (assisted) calibration technique.

Figs. 2-5 show a set-up screen or window of a user interface of an analytical instrument that may be used by a user to configure a calibration of the analytical instrument. The initial set-up screen or window of Figs. 2-5 may be displayed to the user on the display 50, for example, when the instrument is to be calibrated and/or has not previously been calibrated.

The (set-up screen or window of the) user interface may be configured to allow a user to configure various steps that may be performed by the instrument during set-up and/or calibration of the analytical instrument. The (set-up screen or window of the) user interface may also be configured to display information indicative of the status of the various steps.

Figs. 2-5 show the set-up screen at various stages as a user selects various options for a calibration.

As shown in Figs. 2-5, the set-up screen or window of the user interface may comprise one or more panels (although other arrangements would be possible). Thus, for example, the set-up screen or window may comprise a header panel 100, an ADC and detector setup panel 200, a calibration panel 300, and/or a log panel. Other arrangements would be possible. For example, the set-up screen or window of the user interface may comprise more or less panels than the panels illustrated in Figs. 2-5.

The (set-up screen or window of the) user interface may be configured to allow a user to select one or more parameters and/or settings for the calibration.

Correspondingly, the method may comprise an optional step of a user selecting one or more parameters and/or settings for the calibration. That is, the method may comprise receiving, via the user interface, a selection of one or more parameters and/or settings for the calibration.

Once selected, the calibration may be performed using the one or more parameters and/or settings in the manner described herein. Thus, in various embodiments, the method may comprise controlling the analytical instrument to measure the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) in accordance with the selected parameters and/or settings.

In various embodiments, the (set-up screen or window of the) user interface may be configured to allow a user to select one or more of (and the one or more parameters and/or settings may comprise): (i) a physico chemical property range for the calibration; (ii) a polarity for the calibration; (iii) a resolution for the calibration; and/or (iv) a type of calibration.

In various particular embodiments, the user interface may be configured to allow a user to select a physico-chemical property range for the calibration, such as a mass to charge ratio range for the calibration. In these embodiments, the user interface may be configured, for example, to allow a user to select a range from a set of possible ranges. The set of possible ranges may include, for example, a relatively narrow range, a relatively broad range, and optionally one or more intermediate ranges.

Thus, for example, as shown in Fig. 2, the user interface may be configured such that a user can select one or more of four possible mass to charge ratio ranges for the calibration. In Fig. 2, the selectable ranges comprise (i) 50-1200 Da, (ii) 50-2000 Da, (iii) 50-4000 Da, and (iv) 50-8000 Da. Other ranges and numbers of ranges would be possible.

Thus, according to various embodiments, the method may comprise receiving, via the user interface a selection of a physico-chemical property range for the calibration (optionally from a set of possible ranges), and then controlling the analytical instrument to measure the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) within the selected range.

In various particular embodiments, the user interface may be configured to allow a user to select either positive or negative polarity for the calibration. That is, the user may be able to select, via the user interface, to calibrate the instrument with the instrument operating in positive ion mode, or in negative ion mode. When operating in positive ion mode, the instrument may be configured to ionise the calibrant so as to produce positive ions, and to measure the physico-chemical property of the positive ions. When operating in negative ion mode, the instrument may be configured to ionise the calibrant so as to produce negative ions, and to measure the physico-chemical property of the negative ions.

Thus, according to various embodiments, the method may comprise receiving, via the user interface a selection of a polarity for the calibration, and then controlling the analytical instrument to operate in the corresponding (positive or negative) ion mode when measuring the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions).

In various particular embodiments, the user interface may be configured to allow a user to select a resolution for the calibration, for example from a set of possible resolutions. The set of possible resolutions may include, for example, a relatively high resolution, a relatively low resolution, and optionally one or more intermediate resolutions.

Thus, for example, as shown in Fig. 2, the user interface may be configured to allow a user to select either a relatively low resolution or a relatively high resolution mode. The relatively low resolution mode may comprise, for example a "V" mode, wherein ions pass through the (time of flight) mass analyser while following an approximately V-shaped path, and the relatively high resolution mode may comprise a "W' mode, wherein ions pass through the (time of flight) mass analyser while following an approximately W-shaped path. Other modes and resolutions would be possible.

Thus, according to various embodiments, the method may comprise receiving, via the user interface, a selection of a resolution for the calibration, and then controlling the analytical instrument to measure the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) using the selected resolution.

In various particular embodiments, the user interface may be configured to allow a user to select the type of calibration, for example as being either with or without ion mobility separation. That is, the user may be able to select, via the user interface, to calibrate the instrument when operating the instrument with or without ion mobility separation.

When operating without ion mobility separation, the instrument may be configured to measure the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) without separating the ions (and/or product or fragment ions derived from the ions) according to their ion mobility. When operating with ion mobility separation, the instrument may be configured to separate the ions (and/or product or fragment ions derived from the ions) according to their ion mobility when measuring the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions).

Thus, according to various embodiments, the method may comprise receiving, via the user interface, a selection of a type of calibration, and then controlling the analytical instrument to measure the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) using the selected type of calibration.

According to various embodiments, and as shown in Fig. 2, each of one or more or all of the various possible combinations of the above described parameters or settings (i)-(iv) may be selectable in the user interface. As such, the user interface may display information indicative of a plurality of different combinations of one or more parameters and/or settings for the calibration.

Thus, in various embodiments, the (set-up screen or window of the) user interface may be configured to allow a user to select one or more combinations of the various parameters and/or settings for the calibration. Correspondingly, the method may comprise an optional step of a user selecting one or more combinations of parameters and/or settings for the calibration. That is, the method may comprise receiving, via the user interface, an indication of a selection of one or more combinations of parameters and/or settings for the calibration.

Once selected, a calibration may be performed using each of the selected combinations of parameters and/or settings in the manner described herein. This may comprise controlling the analytical instrument to measure the physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) in accordance with each of the selected combinations of parameters and/or settings.

A respective calibration for the analytical instrument may be determined for each of the selected combinations of parameters and/or settings.

In various particular embodiments, as shown in Fig. 2, the user interface may be configured to allow a user to select a combination of parameters and/or settings for the calibration from a set 310 of possible combinations. Information indicative of the set 310 of possible combinations may be displayed via the user interface, and the user interface may be configured to allow a user to select one or more of the combinations. In these embodiments, each combination of the set 310 of possible combinations may be referred to as a respective "slot'.

As shown in Fig. 2, each combination may be associated with and selectable by a respective check box. For example, referring to Fig. 2, by selecting check box 312, a user may indicate to the analytical instrument that a calibration should be determined using positive ion mode within a mass range of 50-1200 Da using a relatively low resolution mode. Other arrangements would be possible.

In the embodiment depicted in Fig. 2, there are twenty-four possible combinations ("slots") that may be selected by a user. However, it would be possible for there to be more or less possible combinations in the set 310.

In various embodiments, the (set-up screen or window of the) user interface may be configured to allow a user to select any number of combinations from the set 310 of possible combinations, and the instrument may be configured to determine a (different) calibration for each selected combination. Thus, for example, a single combination may be selected (and the instrument may determine a single calibration), or multiple combinations may be selected (and the instrument may determine multiple calibrations).

In this regard, the Applicants have firstly recognised that it can be desirable to configure the instrument to be capable of generating multiple different calibrations, for example one for each of the various possible combinations of parameters and/or settings described above. Each of the different calibrations may then be used to calibrate the instrument when operating the instrument using a combination of parameters and/or settings that corresponds to the combination of parameters and/or settings used to generate the calibration. This can improve the resulting calibration.

However, the Applicants have furthermore recognised that it may not always be necessary to determine all of the possible different calibrations when setting up or configuring the instrument. For example, a user of the instrument may intend to operate the instrument with only one or a small number of particular combinations of parameters and/or settings, such as only a particular physico chemical property range, polarity and/or resolution.

Thus, according to various embodiments, the user interface is configured such that a user can select one or more than one combination of the above described parameters and/or settings. This allows the user to select only those combinations of parameters and/or settings that are intended to be used. This in turn means that the calibration can be performed in a quicker and more efficient manner.

Thus, for example, as shown in Figs. 2 and 3, sixteen of the set 310 of twenty-four possible combinations have been selected. As shown in Figs. 4 and 5, only two of the set 310 of possible combinations have been selected. In this case, the first calibration slot 312, as discussed above, corresponds to a calibration in positive ion mode within a mass range of 50-1200 Da using a relatively low resolution mode ("positive V mode"). The second calibration slot 314 corresponds to a calibration in positive ion mode within a mass range of 50-1200 using a relatively high resolution mode ("positive W mode").

Thus, in various embodiments, the (set up screen or window of the) user interface may be configured such that a user can select one or plural calibration combinations from the set 310 of possible calibration combinations.

Correspondingly, the method may comprises receiving, via the user interface, a selection of one or plural combinations from the set 310 of combinations. A calibration may then be determined for each selected combination, for example by performing the method of various embodiments described herein (and described in more detail below with respect to Fig. 6).

In various particular embodiments, the (set-up screen or window of the) user interface may be configured to allow a user to select a desired calibrant compound. Correspondingly, the method may comprise an optional initial step of a user selecting a calibrant compound for calibrating the analytical instrument. As such, the method may comprise receiving, via the user interface, an indication of a selection of a calibrant compound to be used to calibrate the instrument. Once selected, the calibrant compound may be used to calibrate the analytical instrument in the manner described herein.

The calibrant compound to be used may be selected from a set of plural calibrant compounds. This may comprise, for example, a user selecting a calibrant compound from a list of possible calibrant compounds. Thus, for example, as shown in Figs. 2-4, the user interface may comprise a list 320 of calibrant compounds, and may be configured to allow a user to select a calibrant compound from the list 320.

In various embodiments, the set (list 320) of plural calibrant compounds may comprise one or more pre-defined calibrant compounds. Additionally or alternatively, the set of plural calibrant compounds may be configurable by a user. Thus, for example, a user may be able to add a desired calibrant compound to the set of possible calibrant compounds. This provides additional flexibility to the calibration process, and allows for example, a user to use a particular calibrant compound that may be more suited to a particular experiment.

Any suitable calibrant compound may be selected and used. When ionised using the ion source 10 of the analytical instrument, the or each calibrant compound may produce ions having known values of one or more physico-chemical properties (such as one or more known values of mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section (CCS)). These known values may be stored (for example within a memory of or accessible by the control system 40) as a set of plural reference values of the one or more physico-chemical properties (in respect of each calibrant compound).

Thus, in various embodiments, one or more sets of references values are stored within a memory of or accessible by the control system 40 of the analytical instrument, where each set of references values corresponds to a particular calibrant compound of the set (list 320) of calibrant compounds.

In various embodiments, the calibrant compound may be configured so as to produce (when ionised using the ion source 10 of the analytical instrument) ions across most or all of a physico-chemical property (mass to charge ratio or mobility) range. The calibrant compound may be configured so as to produce (when ionised using the ion source 10 of the analytical instrument) ions that are relatively abundant, and that may be approximately equally spaced apart across most or all of the physico-chemical property (mass to charge ratio or mobility) range. In various embodiments, the calibrant compound may be configured so as to produce (when ionised using the ion source 10 of the analytical instrument) precursor ions, without producing substantial numbers of product (fragment) ions (that is, without substantially fragmenting within the ion source 10).

Suitable calibrant compounds may include, for example, sodium iodide, sodium formate, polyalanine, and the like, and mixtures thereof.

In various embodiments, the user interface (and the instrument) may be configured such that a respective calibrant compound may be selected for each calibration combination (slot). A different calibrant compound may be used in respect of each different calibration combination (each different calibration slot).

This provides additional flexibility to the calibration process, and allows a user to select a calibrant compound that is most suited to each of the calibrations (each of the slots).

Thus, for example, Fig. 2 shows the situation where a default calibration compound (namely sodium iodide) is selected for the first calibration slot 312. As shown in Fig. 3, the calibrant compound to be used for the particular slot can be changed by selecting a desired calibrant compound from the list 320. Fig. 4 shows the situation where a desired calibration compound (namely "Major Mix") has been selected for the first calibration slot 312.

Thus, in various particular embodiments, the (set-up screen or window of the) user interface may be configured to allow a user to select a desired calibrant compound, optionally in respect of each selected combination of parameters and/or settings. As such, the method may comprise receiving, via the user interface, a selection of a calibrant compound to be used to calibrate the instrument, optionally for each of one or more combination of parameters and/or settings (for each of one or more calibrations). Once selected, the selected calibrant compound may be used to calibrate the analytical instrument in the manner described herein.

Once a user has configured the calibration or calibrations using the set-up screen (in the manner described above), the user may then indicate to the instrument that the calibration(s) should be performed. For example, as shown in Figs. 2-5, the user interface may comprise a button 110, which may be selectable by a user in order to indicate to the instrument that the calibration(s) should be performed (other arrangements would, however, be possible). Thus, in various embodiments, the (set-up screen or window of the) user interface may be configured to allow a user to cause the instrument to perform the calibration(s).

Correspondingly, the method may comprise receiving, via the user interface, an indication that the calibration(s) should be performed, and then ionising the calibrant (and so on) in response to receiving the indication.

In various embodiments, the (set-up screen or window of the) user interface may be configured to display information indicative of the status of the calibration(s). For example, as shown in Figs. 2-4, each combination of parameters and/or settings (each calibration slot) may be associated with a respective label 332, 334 in the user interface.

As shown in Figs. 2-4, when a calibration for a particular combination of parameters and/or settings (a particular calibration slot) has not yet been performed, information indicative of this may be displayed (via the user interface). For example, as shown in Figs. 2-4, each calibration slot that has not yet been performed may be labelled as "Not Run" or similar. Other arrangements would be possible.

As shown in Fig. 5, once a calibration has been initiated, information indicative of this may be displayed (via the user interface). For example, as shown in Fig, 5, each calibration slot may be labelled as "Pending" or similar. Other arrangements would be possible. Thus, in various embodiments, once the calibration(s) have been initiated, the analytical instrument may indicate this to the user (via the user interface). This may comprise updating the label 332, 334 associated with each initiated calibration slot.

In various embodiments, during the calibration(s), a status bar 120 may be displayed by the user interface, and/or text may be displayed in the log panel 400, for example that may be indicative of the status of the calibration(s).

As shown in Figs. 2-5, when the desired calibration(s) have been initiated, they may optionally be preceded by one or both of an analogue to digital converter (ADC) setup step and/or a detector setup step. Each of these steps may be performed in either or both of a positive ion mode and/or a negative ion mode. In various embodiments, these steps may be performed only when the instrument has not previously been calibrated, and may be omitted, for example, when the instrument is being recalibrated.

Fig. 6 is a flow diagram illustrating a method of calibrating an analytical instrument in accordance with various embodiments. The method illustrated by Fig. 6 may be performed in respect of one or more or each calibration combination (slot) described above. Thus, for example, in the example illustrated by Fig. 5, where two calibration slots 312, 314 have been selected, the method of Fig. 6 may be performed twice, once for the first calibration slot 312 and once for the second calibration slot 314.

As shown in Fig. 6, in accordance with various embodiments, the selected calibrant compound is ionised so as to produce calibrant ions (step 602 in Fig. 6). This may be done using the ion source 10.

The analytical instrument may then be used to measure a physico-chemical property (such as mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section (CCS)) of the calibrant ions. (Additionally or alternatively, the analytical instrument may be used to measure the physico-chemical property of product or fragment ions derived from the calibrant ions.) This may be done in accordance with the selected parameters and/or settings as described above, for example using the selected physico-chemical property range, polarity, and/or resolution, and/or with or without ion mobility separation.

Using the analytical instrument to measure a physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) may comprise passing the calibrant ions from the ion source 10 through the one or more functional components 20, and into the analyser 30. The ions (and/or product or fragment ions derived from the ions) may then be analysed by the analyser 30, for example so as to produce a mass spectrum and/or an ion mobility spectrum of the calibrant ions (and/or of product or fragment ions derived from the calibrant ions) (step 604 in Fig. 6). Thus, using the analytical instrument to measure a physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) may comprise using the analytical instrument to produce a mass spectrum and/or an ion mobility spectrum of the calibrant ions (and/or of product or fragment ions derived from the calibrant ions).

The spectrum may be subjected to a peak-detecting algorithm in order to determine a set of measured values, for example where each measured value corresponds to (the centre of) an ion peak in the spectrum. Thus, using the -21 -analytical instrument to measure a physico-chemical property of the ions (and/or of product or fragment ions derived from the ions) may comprise determining a set of measured values.

In accordance with various embodiments, each of plural of the reference values of the physico-chemical property (such as each of plural reference values of mass to charge ratio, time of flight, (ion mobility) drift time and/or collision cross section (CCS)) for the selected calibrant may be compared to the measured values of the physico-chemical property of the ions. In particular, the analytical instrument may (attempt to) automatically assign a (single) measured value of the physico-chemical property to each of plural of the reference values of the physico-chemical property. In other words, for each of plural of the reference values, the analytical instrument may (attempt) to find the (single) measured value of the set of measured values that corresponds most closely to the reference value.

Thus for example, the analytical instrument may (attempt to) automatically assign a (single) ion peak in the mass and/or an ion mobility spectrum to each reference value of some or all of the reference values (step 606 in Fig. 6). This may be done, for example by the control system 40, using one or more appropriate algorithms.

In this regard, the Applicants have recognised that a problem with this kind of automated calibration process is that it is possible for the analytical instrument to wrongly assign a measured value (ion peak) to a reference value, and that this can be the case regardless of the level of sophistication in the algorithm(s) used to assign measured values to reference values. For example, the algorithm(s) may be less reliable at high mass to charge ratio values, where ion peaks may be broader than at lower mass to charge ratio values. The algorithm(s) may also be less reliable where a calibrant compound produces fragment ions which may overlap with the desired precursor calibrant ions.

The effect of such incorrect assignments can be to reduce the accuracy of the calibration, and so degrade the performance of the analytical instrument.

Moreover, the Applicants have recognised that a human user will often be capable of recognising instances of a measured value (ion peak) being incorrectly assigned to a reference value, where an algorithm is not. This may be the case, for example, where a user has some knowledge of and/or experience with a particular calibrant that is being used to calibrate the instrument, for example where a user has selected their own calibrant.

Thus, in various embodiments, the automated peak assignment process may be assisted by a user.

Fig. 7 shows set-up screen or window of the user interface after the analytical instrument has performed the automatic peak assignment (after step 606 in Fig. 6). As shown in Fig. 7, the ADC and detector setup steps in positive ion mode have been successfully completed. The automated peak assignment has also been performed for the two selected calibration slots 312, 314.

As shown in Fig. 7, once the analytical instrument has attempted to automatically assign measured values of the physico-chemical property to each reference value, the analytical instrument may indicate to this the user, via the user interface. The user interface may indicate that the automatic assignment has been attempted and that user interaction may be required. For example, as shown in Fig. 7, each calibration slot for which the automated peak assignment has been performed may be labelled as "Awaiting Assistance" or similar. Other arrangements would be possible.

Thus, in various embodiments, once the automated peak assignment has been completed, the analytical instrument may indicate this to the user (via the user interface). This may comprise updating the label 332, 334 associated with each calibration slot. In various embodiments, once the automated peak assignment has been completed, the calibration process may be paused until the further interaction is received from the user.

The (set-up screen or window of the) user interface may be configured such that the user can select a calibration slot, so as to then assess the accuracy of the automatic assignment. For example, the user interface may be configured such that a user may select each label 332, 334 associated with each slot in order to then assess the automatic assignment for that particular calibration slot. Fig. 8 shows a calibration assessment screen or window of the user interface that may be displayed when a particular calibration is selected in the manner described above. The calibration assessment screen or window may comprise a number of panels, such as a header panel 800, a peak picker panel 810, and a summary panel 820. Other arrangements would be possible.

In various embodiments, the measured values and/or the reference values may be displayed via the (calibration assessment screen or window of the) user interface. Thus for example, as shown in Fig. 8, the mass and/or ion mobility spectrum 812 may be displayed via the user interface. A reference mass and/or ion mobility spectrum 814 may also be displayed, for example where the reference mass and/or ion mobility spectrum 814 is a mass and/or ion mobility spectrum 814 comprising an ion peak corresponding to each reference value of the set of reference values.

As shown in Fig. 8, each of the measured and/or reference values may be displayed in the corresponding spectrum as a vertical line. The position of a line in a horizontal direction may indicate the value of the physico-chemical property (for example mass-to-charge ratio, time of flight, (ion mobility) drift time and/or collision cross section), and the length of a line in the vertical direction may indicate, for example, the relative intensity of that particular value of the physico chemical property. As also shown in Fig. 8, some or all of the vertical lines representing a measured and/or reference value may be displayed together with an associated label which may, for example, indicate the numerical value of the respective measured and/or reference value.

In accordance with various embodiments information indicating which of the measured values has been assigned to each of the plural reference values may be displayed to a user via the user interface (step 608 in Fig. 6).

This information may take any suitable form. As shown in Fig. 8, in various embodiments, each ion peak within the spectrum 812 that has been assigned to a reference value may be indicated as such, for example by using colour coding or otherwise. Correspondingly, each ion peak within the spectrum 812 that is unassigned to a reference value may be indicated as such, for example by using colour coding or otherwise.

In various embodiments, the (calibration assessment screen or window of the) user interface may be configured such that a user can resize (for example, zoom in or zoom out) one or both scales of the mass and/or ion mobility spectrum 812 and/or the reference mass and/or ion mobility spectrum 814. This allows the user to examine in detail particular regions of the spectra.

Fig. 9 shows the calibration assessment screen or window, after the horizontal scale of the measured and reference spectra (of Fig. 8) has been resized (zoomed-in) to show mass-to-charge ratio values between around 400 and 600 Da. As can be seen in Fig. 9, in this example, three ion peaks are present in the mass spectrum 812 with mass-to-charge ratio values of around 500 Da. In Fig. 9, the leftmost ion peak is highlighted in bold, indicating that this ion peak has been automatically assigned by the analytical instrument to the corresponding reference value.

However, as discussed above, it may be the case that this automatic assignment is incorrect, and for example, that the ion peak immediately to the right of the leftmost ion peak should instead be assigned to the reference value. By allowing a user to examine the mass spectra 812, 814 in the manner described herein, the user may be able to recognise such instances of a measured value being wrongly assigned to a reference value.

Thus, in accordance with various embodiments, a user is able to examine information indicating which of the measured values has been assigned to each of plural reference values, optionally together with the measured values and/or the reference values. Where a user determines that a particular measured value has been incorrectly assigned to a reference value, the user can indicate this to the analytical instrument via the user interface (step 610 in Fig. 6).

Such an indication may take any suitable form. For example, a user selecting an ion peak in the mass spectrum 812 that is associated with a particular reference value may cause the analytical instrument to deselect that ion peak, so as to remove the association between the ion peak and the corresponding reference value. A user subsequently selecting another ion peak may cause the analytical instrument to associate that ion peak with the corresponding reference value.

Fig. 10 shows the calibration assessment screen or window after the analytical instrument has received an indication from the user that the leftmost ion peak has been wrongly assigned to corresponding reference value, and that instead the ion peak immediately to the right of the leftmost ion peak should be assigned to the corresponding reference value. As shown in Fig. 10, the ion peak immediately to the right of the leftmost ion peak is now highlighted in bold, indicating that this ion peak is now assigned to the corresponding reference value.

As shown in Figs. 8-10, the (percentage) differences (or "residuals") 816 between the measured and references values may be displayed in the (calibration assessment screen or window of the) user interface. The residuals may be displayed with error bars and/or bands indicating a degree of error associated with each difference value.

As can be seen by comparing Figs. 9 and 10, by selecting the ion peak immediately to the right of the leftmost ion peak in the mass spectrum 812, the vertical scale of the residuals 816 has been reduced from ±200ppm to ±100 ppm, indicating that the accuracy of the calibration has increased.

Additionally or alternatively, for example where a user considers that it is not possible to reliably determine which measured value should be assigned to a reference value, the user can indicate to the analytical instrument that that reference value (and its assigned measured value) should be disregarded (should not be used) when determining a calibration for the analytical instrument.

Such an indication may take any suitable form. For example, a user selecting a reference value in the reference spectrum 814 may cause the analytical instrument to disregard that particular reference value (and its assigned measured value).

Thus, in accordance with various embodiments, the analytical instrument may receive, via the user interface (from the user), for one or more of the reference values, (i) an indication of a change to the measured value assigned to the reference value, and/or (ii) an indication that the reference value should be omitted when determining a calibration for the analytical instrument.

Additionally or alternatively, for example where a user considers that a particular calibration is not reliable, the user can indicate to the analytical instrument that the calibration should be repeated or rejected.

Once the automated peak assignment has been corrected or adjusted by the user in the manner described above, a calibration for the analytical instrument may be determined. The user may initiate the determination of the calibration, for example by selecting a button 802 in the user interface. Other arrangements would be possible.

The calibration may be determined by, for each of some or all of the plural reference values, determining a (percentage) difference between the reference value and the measured value that has been (automatically or manually) assigned to that reference value (step 612 in Fig. 6), and then using these difference to determine the calibration for the analytical instrument (step 614 in Fig. 6).

In various embodiments, a (percentage) difference between the reference value and the measured value assigned to that reference value is determined for all of the reference values except those for which an indication that the reference value should be omitted from the calibration is received.

A calibration profile such as a calibration curve for the analytical instrument may then be determined using the differences.

Since, as described above in various embodiments, the number of instances of a measured value being incorrectly assigned to a reference value may be reduced, the calibration may accordingly be more accurate. In addition, various embodiments allow flexibility in the choice of calibrant, and can improve calibration at high mass to charge ratio values.

In various embodiments, a collision cross section (CCS) calibration may be determined by extracting an arrival time distribution (ATD) from the measured data for each reference mass to charge ratio value, and determining a drift time for each reference mass to charge ratio value from the respective ATD. These drift time values may then be plotted against reference collision cross section values, and a curve may be fitted to this data. This curve may then be used to convert a measured analyte drift time value to collision cross section.

Once a calibration has been determined for a particular calibration slot, the user interface of the analytical instrument may return to the overview screen or window. As shown in Fig. 11, each calibration slot may be labelled as "Success" or similar. Other arrangements would be possible. Thus, in various embodiments, once the calibration(s) have been completed, the analytical instrument may indicate this to the user (via the user interface). This may comprise updating the label 332, 334 associated with each completed calibration slot.

The steps described in relation to Fig. 6 may then be repeated for all other selected slots. Fig. 12 shows the user interface when the calibration has been determined for both selected slots.

Once a calibration has been determined for each of the one or more calibration slots, the calibration(s) may be used to calibrate the instrument. This may involve ionising an analyte so as to produce analyte ions, and using the analytical instrument to measure the physico-chemical property of the analyte ions (and/or of product or fragment ions derived from the analyte ions). The calibration(s) may be used to correct the measured physico-chemical property values of the analyte ions (and/or of the product or fragment ions derived from the analyte ions).

Although the present invention has been described with reference to preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made without departing from the scope of the invention as set forth in the accompanying claims.

Claims

Claims 1. A method of calibrating an analytical instrument comprising: ionising a calibrant so as to produce ions; using the analytical instrument to measure a physico-chemical property of the ions and/or of product or fragment ions derived from said ions; for each of plural reference values of the physico-chemical property, automatically assigning a measured value of the physico-chemical property to the reference value of the physico-chemical property; displaying, via a user interface, information indicating which measured value has been assigned to each of the plural reference values; receiving, via the user interface, for one or more of the reference values (i) an indication of a change to the measured value assigned to the reference value and/or (ii) an indication that the reference value should be omitted when determining a calibration for the analytical instrument; and then for each of plural of the reference values, determining a difference between the reference value and the measured value assigned to that reference value; and determining a calibration for the analytical instrument using the differences.
2. The method of claim 1, further comprising: receiving, via the user interface, an indication of a selection of one or more parameters and/or settings for the calibration; and controlling the analytical instrument to measure the physico-chemical property of the ions and/or of the product or fragment ions derived from the ions in accordance with the selected parameters and/or settings.
3. The method of claim 1 or 2, further comprising: displaying, via the user interface, information indicative of a plurality of different combinations of one or more parameters and/or settings for the calibration; receiving, via the user interface, an indication of a selection of one or more of the different combinations; and controlling the analytical instrument to measure the physico-chemical property of the ions and/or of the product or fragment ions derived from the ions in accordance with each of the selected combinations of parameters and/or settings.
4. The method of claim 3, further comprising determining a respective calibration for the analytical instrument for each of the selected combinations of parameters and/or settings.
5. The method of any one of claims 2 to 4, wherein the one or more parameters and/or settings comprise: (i) a physico chemical property range for the calibration; (ii) a polarity for the calibration; (iii) a resolution for the calibration; and/or (iv) a type of calibration.
6. The method of any one of the preceding claims, further comprising: receiving, via the user interface, an indication of a selection of a calibrant for the calibration; and ionising the selected calibrant so as to produce the ions.
7. The method of claim 6, wherein the reference values comprise known values of the physico-chemical property for the selected calibrant.
8. The method of any one of the preceding claims, further comprising displaying, via the user interface, at least some of the measured values and/or at least some of the reference values.
9. The method of any one of the preceding claims, wherein the physico-chemical property comprises mass to charge ratio, time of flight, drift time and/or collision cross section.
10. The method of any one of the preceding claims, further comprising: ionising an analyte so as to produce analyte ions; using the analytical instrument to measure the physico-chemical property of the analyte ions and/or of product or fragment ions derived from the analyte ions; and using the determined calibration to calibrate the measured physico-chemical property of the analyte ions and/or of the product or fragment ions derived from the analyte ions.
11 An analytical instrument comprising: an ion source configured to ionise a calibrant so as to produce ions; an analyser configured to measure a physico-chemical property of the ions and/or of product or fragment ions derived from said ions; and a control system; wherein the control system is configured to: for each of plural reference values of the physico-chemical property, automatically assign a measured value of the physico-chemical property to the reference value of the physico-chemical property; display via a user interface information indicating which measured value has been assigned to each of the plural reference values; receive, via the user interface, for one or more of the reference values (i) an indication of a change to the measured value assigned to the reference value, and/or (ii) an indication that the reference value should be omitted when determining a calibration for the analytical instrument; and then for each of plural of the reference values, determine a difference between the reference value and the measured value assigned to that reference value; and determine a calibration for the analytical instrument using the differences.
12. The analytical instrument of claim 11, wherein the control system is configured: to receive, via the user interface, an indication of a selection of one or more parameters and/or settings for the calibration; and to control the analytical instrument to measure the physico-chemical property of the ions and/or of the product or fragment ions derived from the ions in accordance with the selected parameters and/or settings.
-31 - 13. The analytical instrument of claim 11 or 12, wherein the control system is configured: to display, via the user interface, information indicative of a plurality of different combinations of one or more parameters and/or settings for the calibration; to receive, via the user interface, an indication of a selection of one or more of the different combinations; and to control the analytical instrument to measure the physico-chemical property of the ions and/or of the product or fragment ions derived from the ions in accordance with each of the selected combinations of parameters and/or settings.
14. The analytical instrument of claim 13, wherein the control system is configured to determine a respective calibration for the analytical instrument for each of the selected combinations of parameters and/or settings.
15. The analytical instrument of any one of claims 12 to 14, wherein the one or more parameters and/or settings comprise: (i) a physico chemical property range for the calibration; (ii) a polarity for the calibration; (iii) a resolution for the calibration; and/or (iv) a type of calibration.
16. The analytical instrument of any one of claims 11 to 15, wherein: the control system is configured to receive, via the user interface, a selection of a calibrant; and the ion source is configured to ionise the selected calibrant so as to produce the ions.
17. The analytical instrument of any one of claims 11 to 16, wherein the control system is configured to display, via the user interface, at least some of the measured values and/or at least some of the reference values.
18. The analytical instrument of any one of claims 11 to 17, wherein the analyser comprises a mass analyser and/or an ion mobility analyser configured to measure the mass to charge ratio, time of flight, drift time and/or collision cross section of the ions and/or of the product or fragment ions derived from the ions.
19. The analytical instrument of any one of claims 11 to 18, wherein: the ion source is configured to ionise an analyte so as to produce analyte ions; the analyser is configured to measure the physico-chemical property of the analyte ions and/or of product or fragment ions derived from the analyte ions; and the control system is configured to use the determined calibration to calibrate the measured physico-chemical property of the analyte ions and/or of the product or fragment ions derived from the analyte ions.
20. A computer program comprising computer software code for performing the method of any one of claims 1 to 10 when the program is run on a data processor.