Tandem mass spectrometers

Abstract

A method of tandem mass spectrometry comprises performing a first MSMS analysis, where ions having a first m / z detected in a survey mode are fragmented or reacted and mass analysed to obtain first MSMS data. A m / z detected in the first MSMS data is added to an exclusion list. A second MSMS analysis is performed on ions having a second different m / z detected in the survey mode, if the second m / z is not present on the exclusion list. This may prevent fragment or product ions from being selected for subsequent MSMS analyses. Alternatively, ions may be added to the exclusion list based on m / z and ion mobility detected in the survey mode, e.g. if mobility is too high for m / z for it to be a precursor ion. Ions may also be added to the exclusion list if their m / z in the survey mode do not follow a trend when a mass filter or separator is scanned with time. Alternatively, if an ion selected for second MSMS analysis is also detected in the first MSMS data, fragmentation may have occurred in the survey mode and the second MSMS data may be discarded, marked, or combined with the first MSMS data.

Description

CROSS-REFERENCE TO RELATED APPLICATION This application claims priority from and the benefit of United Kingdom patent application No. 2319580.3 filed on 20 December 2023, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION The present invention relates generally to mass spectrometers and in particular to tandem mass spectrometers, e.g. for the discovery, detection and quantitation of molecules such as peptides. BACKGROUND Tandem mass spectrometry, also known as MS / MS, is a ubiquitous tool for discovery, detection and quantitation of molecules such as peptides in complex mixtures. In such techniques a sample is ionised and the mass spectrometer may be operated in a survey mode so as to determine the mass to charge ratios of precursor ion species generated from the ionised sample. The mass spectrometer may then be operated in a mode in which one of the precursor ion species is isolated using a mass filter and fragmented so as to form fragment ions. The fragment ions are then mass analysed so as to determine their mass to charge ratios. As such, the mass spectrometer is able to associate the mass to charge ratio of a precursor ion species with the mass to charge ratios of its fragment ions. This process is repeated, but wherein a different one of the precursor ion species detected in the survey mode is isolated and fragmented each time that the process is repeated. The combination of the mass to charge ratio of a precursor ion species and the mass to charge ratios of its fragment ions is typically highly specific, and so enables the identification or detection of the precursor ion species with high confidence. SUMMARY From a first aspect the present invention provides a method of mass spectrometry comprising: operating a mass spectrometer in a survey mode for a first period in which ions are mass analysed so as to obtain first survey mass spectral data; performing a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain first MSMS mass spectral data; adding a mass to charge ratio detected in the first MSMS mass spectral data to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and performing a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain second MSMS mass spectral data, wherein the method comprises checking that the second mass to charge is not present on the exclusion list prior to performing the second MSMS analysis. The step of checking that the second mass to charge is not present on the exclusion list may comprise checking if the second mass to charge ratio is within a predefined mass to charge ratio tolerance of each mass to charge ratio on the exclusion list. If the second mass to charge ratio is within a pre-defined mass to charge ratio tolerance of a mass to charge ratio on the exclusion list, then the second mass to charge ratio is determined to be present on the exclusion list. In contrast, if the second mass to charge ratio is not within a pre-defined mass to charge ratio tolerance of each mass to charge ratio on the exclusion list, then the second mass to charge ratio is determined not to be present on the exclusion list. The use of such a mass to charge ratio tolerance is useful as different mass to charge ratio measurements for ions of the same species may not exactly match each other, or their theoretical value, owing to ion statistics, background noise and interferences etc. The tolerance may be set or calculated by a user, calculated during the experiment, or may be pre-fixed in the spectrometer. Each MSMS analysis comprises selecting a mass to charge ratio that is present in the survey mass spectral data. When the second MSMS analysis is performed, the mass spectrometer performing the method checks that that second mass to charge ratio is not present on the exclusion list (at the time that the second MSMS analysis is going to be performed) prior to selecting it for fragmentation or reaction. If the second mass to charge ratio was present on the exclusion list (e.g. within the above-mentioned tolerance) then the spectrometer would not select it for fragmentation or reaction, i.e. it would not perform an MSMS analysis on ions of that mass to charge ratio. As the present invention adds one or more mass to charge ratio detected in MSMS spectral data to the exclusion list, it will be appreciated that it prevents at least some fragment or product ions from being selected for a subsequent MSMS analysis. This is desirable, as subjecting fragment or product ions to the MSMS mode typically produces less useful mass spectral data than subjecting precursor ions to the MSMS mode. It is known to subject a peptide precursor ion species detected in a survey mode to MSMS analysis so as to obtain mass to charge ratios for its fragment ions, wherein the mass to charge ratios of the peptide ion and its fragment ions are then used in database searching to identify the peptide and / or the protein that it is derived from. It is also known to use the identified protein to look up the theoretical mass to charge ratios of other peptide ions of this protein and add these to the exclusion list. However, this does not avoid the problems described above with fragment or other product ions being selected for MSMS analysis. It will be appreciated that it is known to use the mass to charge ratios of a peptide ion and its fragment ions in database searching to identify the peptide species. It has been recognised that the identified peptide could then, in theory, be used to look up the mass to charge ratios of its theoretical fragment ions and that these mass to charge ratios could be added to the exclusion list. However, the inventor of the present invention has recognised that substantially all ion species found in MSMS spectral data are likely to yield at least partially redundant information if they are themselves selected for MS / MS analysis. This is true irrespective of whether the selected precursor species that produced the MSMS spectral data can be identified, or whether the ions detected in the MSMS spectral data can be assigned to be one of the main expected ion series of an identified precursor ion species (e.g. y- or b- ions for peptides). The inventor has therefore recognised that any ion detected in the MSMS spectral data can be added to the exclusion list and that there is no need to perform a time-consuming and complicated database or algorithm search when selecting ions to add to the exclusion list. Furthermore, it is often the case that not all of the ions detected in MSMS spectral data can be assigned to a precursor ion via database searching. This is for a multitude of reasons, including the fragment ions being produced due to unusual fragmentation mechanisms or different precursor ion species being simultaneously co-isolated for the MSMS analysis. As these fragment ions cannot be assigned to a precursor, they are very unlikely to yield useful information by being subjected to MSMS analysis and so it is desired to add them to the exclusion list. Accordingly, in the method of the present invention described above, said step of adding the mass to charge ratio detected in the first MSMS mass spectral data to the exclusion list may comprise determining that the mass to charge ratio is to be added to the exclusion list without this step of determining that the mass to charge ratio is to be added to the exclusion list using a database search or algorithm to assign the mass to charge ratio to a known or inferred compound, such as to a particular ion species. Alternatively, or additionally, said step of adding the mass to charge ratio detected in the first MSMS mass spectral data to the exclusion list may comprise determining that the mass to charge ratio is to be added to the exclusion list without this step of determining that the mass to charge ratio is to be added to the exclusion list using the mass to charge ratio to identify a precursor ion. The method may comprise performing one or more additional MSMS analysis on one or more additional mass to charge ratio detected in the survey mode, respectively. Each time an MSMS analysis is performed on a mass to charge ratio selected from those detected in the survey mode, the mass spectrometer performing the method checks that that mass to charge ratio is not present on the exclusion list (at the time that MSMS analysis is performed). Each MSMS analysis may comprise isolating ions having one of the mass to charge ratio detected in the survey mode, fragmenting or reacting the isolated ions, and mass analysing the resulting fragment or product ions so as to obtain MSMS mass spectral data. Accordingly, the first MSMS analysis may comprise isolating ions having said first mass to charge ratio detected in the survey mode, fragmenting or reacting the isolated ions and mass analysing the resulting ions so as to obtain the first MSMS mass spectral data. Similarly, the second MSMS analysis may comprise isolating ions having said second mass to charge ratio detected in the survey mode, fragmenting or reacting the isolated ions and mass analysing the resulting ions so as to obtain the second MSMS mass spectral data. In contrast, ions may not be isolated in the survey mode prior to mass analysis. The method may be performed on a mass spectrometer comprising an ion source, a fragmentation or reaction device, and a mass analyser. In the survey mode, ions generated by the ion source may substantially not be fragmented or reacted in the fragmentation or reaction device, or may be fragmented or reacted in the fragmentation or reaction device at a relatively low rate, prior to being mass analysed; and in each of the MSMS analyses, ions generated by the ion source may be fragmented or reacted in the fragmentation or reaction device at a higher rate than in the survey mode and the resulting fragment or product ions are mass analysed. Each time that a mass to charge ratio is selected to be subjected to an MSMS analysis, that mass to charge ratio may then be added to the exclusion list so as to prevent it from being subjected to a subsequent MSMS analysis, e.g. for a predetermined duration or at least part of the same experimental run. Accordingly, ions having said first mass to charge ratio detected in the survey mode may also be added to the exclusion list so as to prevent ions having that mass to charge ratio from being subjected to an MSMS analysis that is subsequent to the first MSMS analysis. Alternatively, or additionally, ions having said second mass to charge ratio detected in the survey mode may be added to the exclusion list so as to prevent ions having that mass to charge ratio from being subjected to an MSMS analysis that is subsequent to the second MSMS analysis. The method may comprise adding a mass to charge ratio detected in the second MSMS mass spectral data to the exclusion list so as to prevent ions having that mass to charge ratio from being subjected to at least one subsequent MSMS analysis. Although two MSMS analyses have been described as being performed on mass to charge ratios discovered in the survey mode, it is contemplated that one or more additional MSMS analyses may be performed on mass to charge ratios discovered in the survey mode, where the one or more additional analyses are performed on mass to charge ratios that are not on the exclusion list at the time that they are performed. Accordingly, the method may comprise performing a third MSMS analysis in which ions having a third, different mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to third obtain MSMS mass spectral data; wherein the method comprises checking that the third mass to charge is not present on the exclusion list prior to performing the third MSMS analysis. At least one, or each, mass to charge ratio that is added to the exclusion list may only prevented from being subjected to MSMS analyses that are performed within a predetermined time of the mass to charge ratio having been added to the exclusion list. The method is performed during an experimental run and the predetermined time is preferably a duration that is shorter than the duration of the experimental run. For the avoidance of doubt, the duration of the experimental run may be considered to be the duration which a given sample is being mass analysed, e.g. the time during which a sample is substantially continually supplied to the ion source and / or continually ionised. The mass to charge ratio may be removed from the exclusion list at the end of the predetermined time from having been added. The method may be performed on a sample that is being separated by a sample separator such that different analytes in the sample elute from the sample separator during different elution peaks and are then ionised; and the predetermined time may be substantially the same as the duration of an analyte peak eluting from the sample separator. The sample separator may be a liquid or gas chromatography separator. The mass to charge ratio(s) may be removed from the exclusion list at the end of the predetermined time. This technique is useful because fragment or product ions that are detected whilst a first analyte peak elutes from the sample separator may have substantially the same mass to charge ratio as a precursor ion species generated whilst a subsequent analyte peak elutes from the sample separator. As the mass to charge ratios of the fragment ions are removed from the exclusion list before the subsequent analyte peak has started to elute, or at least before it has finished eluting, this enables the precursor ions generated from the subsequent analyte peak to be analysed in an MSMS analysis. At least one, or each, mass to charge ratio that is added to the exclusion list may be prevented from being subjected to all subsequent MSMS analyses performed during the same experimental run. For the avoidance of doubt, an experimental run may be considered to be the duration which a given sample is being mass analysed, e.g. the time during which a sample is substantially continually supplied to the ion source and / or continually ionised. MSMS spectral data can contain many ion species and so it may be desirable to select only one, or only some, of the ion species to add to the exclusion list. This helps to avoid mass to charge ratios being added to the exclusion list that correspond to the mass to charge ratios of precursors ion species. For example, a fragment ion species detected in the MSMS analysis may have substantially the same mass to charge ratio as a precursor ion species. Accordingly, each mass to charge ratio added to the exclusion list may only be added if it has corresponding MSMS mass spectral data that meets one or more criteria. A mass to charge ratio may only be added to the exclusion list if its corresponding MSMS mass spectral data has an intensity that is higher than a preselected threshold value; and / or it may be that only mass to charge ratios corresponding to those of the N most intense mass peaks in the mass spectral data from an MSMS analysis are added to the exclusion list, where N is an integer <10, <9, <8, <7, <6, <5, <4, <3, <2 or 1. This helps to ensure that only relatively high intensity ion species in the MSMS mass spectral data, which are likely to be fragment ions, are added to the exclusion list. Although the value of N has been described as preferably being <10, it is contemplated that N could be higher, e.g. to account for complex spectral data. For example, the value of N may be an integer that is <100, <80, <60, <40, or <20. A mass to charge ratio may only be added to the exclusion list if ions that provide its corresponding MSMS mass spectral data have been determined to correspond to the detection of multiply charged ions. Alternatively, or additionally, a mass to charge ratio may be selected to be added to the exclusion list based on its mass to charge ratio. For instance, a mass to charge ratio may only be added to the exclusion list if its corresponding mass spectral data has a mass to charge ratio in a certain range, such as below a threshold vale. As described herein, the present invention seeks to prevent fragment or product ions that have been inadvertently generated and detected in the survey mode from being selected for analysis in the MSMS mode. Such fragment or product ions would be expected to be detected with a relatively low intensity in the survey mode and a higher intensity in the MSMS mode. Accordingly, said step of adding a mass to charge ratio to the exclusion list may comprise determining a mass to charge ratio that is detected in both the survey mode and the first MSMS analysis, where the mass spectral data for that mass to charge ratio indicates that the ions having this mass to charge ratio are more abundant in the first MSMS analysis than in the survey mode, and adding that mass to charge ratio to the exclusion list. Accordingly, the method may comprise: operating the mass spectrometer in the survey mode for the first period in which ions are mass analysed so as to obtain first survey mass spectral data; performing the first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain first MSMS mass spectral data; determining if ions having the same mass to charge ratio have been detected in both the first survey mass spectral data and the first MSMS mass spectral data; adding said same mass to charge ratio to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and performing the second MSMS analysis in which ions having the second, different mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain second MSMS mass spectral data, wherein the method comprises checking that the second mass to charge is not present on the exclusion list prior to performing the second MSMS analysis. The mass to charge ratio that is detected in both the first survey mass spectral data and the first MSMS mass spectral data may be considered to correspond to a fragment or product ion that generated in the survey mode and which is therefore not desired to be selected for analysis in the MSMS mode. It is expected that such ions would be detected to be more abundant in the MSMS mode than in the MS mode. Accordingly, said same mass to charge ratio may only be added to the exclusion list if the mass spectral data for that mass to charge ratio indicates that the ions having this mass to charge ratio are more abundant in the first MSMS than in said first survey mass spectral data, i.e. said same mass to charge ratio may not be added to the exclusion list if it is detected with an abundance in said first MSMS mass spectral data that is equal to and / or lower than in said first survey mass spectral data. The mass to charge ratio may only be added to the exclusion list if the first MSMS analysis is performed within a predetermined time of the survey mode. For example, if the spectrometer comprises a sample separator, such as a liquid or gas chromatography separator, the mass to charge ratio may only be added to the exclusion list if it has been detected in both the survey mode and the MSMS mode within a duration corresponding to the duration of an analyte peak that would elute from the sample separator. It is contemplated that a mass to charge ratio corresponding to a modified version of each mass to charge ratio that has been added to the exclusion list may also be added to the exclusion list. Accordingly, when a mass to charge ratio detected in an MSMS analysis is added to the exclusion list, the method may comprise: determining or estimating the charge state of the ions in corresponding MSMS mass spectral data that have that mass to charge ratio; determining one or more modified mass to charge ratio corresponding to one or more mass to charge ratio that the ions would have if they had a different charge state; and then adding said one or more modified mass to charge ratio to the exclusion list. When a mass to charge ratio detected in an MSMS analysis is added to the exclusion list, the method may comprise: calculating a modified version of this mass to charge ratio by adding or subtracting a pre-selected mass to charge ratio; and then adding said modified mass to charge ratio to the exclusion list. The pre-selected mass to charge ratio may be, for example, the mass to charge ratio that would be caused by an adduct that is likely to join to a fragment or product ion, a loss that is likely to be lost from a fragment or product ion, or a post-translational variant that may occur in a fragment or product ion. Alternatively, the pre-selected mass to charge ratio may be the increased or decreased mass to charge ratio of an isotopic variant of the fragment or product ion, such that mass to charge ratios corresponding to these isotopic variants may be added to the exclusion list. Although embodiments have been described in which ions may be excluded from MSMS analysis only on the basis of their mass to charge ratio, i.e. the only physicochemical property on the exclusion list may be mass to charge ratio, it is contemplated that ions may be required to also have a certain value of another physicochemical property in order to be excluded from selection for a subsequent MSMS analysis. For example, ions having a certain combination of mass to charge ratio and ion mobility may be added to the exclusion list so that ions having such a combination of properties are not subjected to a subsequent MSMS analysis. Such embodiments prevent precursor ions from being unnecessarily excluded from an MSMS analysis simply because they happen to have substantially the same mass to charge ratio as the fragment ion of a different precursor ion species. Accordingly, in the survey mode the ions may be separated by ion mobility prior to being mass analysed, and the mass to charge ratio detected for any given ion may be associated with a value that is related to its ion mobility. In the first MSMS analysis, ions resulting from the fragmentation or reaction may be separated by ion mobility prior to being mass analysed, and the mass to charge ratio detected for any given ion maybe associated with a value that is related to its ion mobility. The step of adding the mass to charge ratio detected in the first MSMS mass spectral data to the exclusion list may comprise adding a combination of a mass to charge ratio detected in the first MSMS analysis and its associated value related to its ion mobility. The step of checking that the second mass to charge ratio detected in the survey mode is not present on the exclusion list prior to performing the second MSMS analysis may comprise: checking that ions having a combination of said second mass to charge ratio and its associated value related to its ion mobility are not present on the exclusion list. Embodiments are contemplated in which a sample being analysed in an experimental run is analysed in the survey mode during multiple time periods that are interspersed with the MSMS analyses. As described above, the survey mode is performed for said first period and is then followed by multiple MSMS analyses for precursor ion species detected in the survey mode. This may then be followed operating the spectrometer in the survey mode for a second period, which is then followed by an MSMS analysis for each of one or more of the precursor ion species detected in the second period. This enables the precursor ions from different species that arrive at the ion source at different respective times to be detected in the different survey mode periods and then analysed in subsequent MSMS analyses. For example, if the sample is separated by a sample separator, such as a liquid or gas chromatography device, prior to being ionised by the ion source then different analytes may arrive at the ion source over different time periods. If the survey mode was performed over only a single period then only some of the precursor ions from the sample would be detected as being present, whereas by performing the survey mode during multiple spaced apart periods the embodiments are able to detect precursor ions that elute from the sample separator at different times, such as in different chromatographic peaks. Accordingly, the method may be performed on a sample that is being separated by a sample separator such that different analytes in the sample elute from the sample separator during different elution peaks and are then ionised; wherein said survey mode is performed during the first period whilst a first analyte peak elutes from the separator; and the method comprises performing the survey mode during a second period, whilst a second analyte peak subsequently elutes from the separator, in which ions are mass analysed so as to obtain second survey mass spectral data. The second period in which the survey mode is performed may have corresponding features to that of the first period of the survey mode. The method may comprise performing an additional MSMS analysis in which ions having a mass to charge ratio detected in the second period of the survey mode are fragmented or reacted and then mass analysed so as to obtain MSMS mass spectral data; adding a mass to charge ratio detected in this additional MSMS mass spectral data to an exclusion list so as to prevent ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and then performing a further MSMS analysis in which ions having a different mass to charge ratio detected in the second period of the survey mode are fragmented or reacted and then mass analysed so as to obtain further MSMS mass spectral data, wherein the method comprises checking that the different mass to charge is not present on the exclusion list prior to performing the further MSMS analysis. The sample separator device may be a liquid or gas chromatography device. The first period of the survey mode, said first MSMS analysis and said second MSMS analysis may be performed as a first chromatographic peak elutes from the liquid or gas chromatography device; and the second period of the survey mode, said additional MSMS analysis, and said further MSMS analysis may be performed as a second chromatographic peak subsequently elutes from the liquid or gas chromatography device. The method may be a method of tandem mass spectrometry. In such a method the mass to charge ratio that is selected for each MSMS analysis may be associated with the mass to charge ratios of the fragment or product ions that are detected in that MSMS analysis. This combination of mass to charge ratios may then be used to identify the ion having the mass to charge ratio that is selected for the MSMS analysis. All of the method steps herein may be performed within a single experimental run. The present invention also provides a mass spectrometer that is arranged and configured to perform the methods described herein. Accordingly, the present invention provides a mass spectrometer comprising: an ion source; fragmentation or reaction device; a mass analyser; and control circuitry configured to control the mass spectrometer to: (i) operate the mass spectrometer in a survey mode in which ions are mass analysed in the mass analyser so as to obtain first survey mass spectral data; (ii) perform a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain first MSMS mass spectral data; (iii) add a mass to charge ratio detected in the first MSMS mass spectral data to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and (iv) perform a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain second MSMS mass spectral data, wherein the spectrometer checks that the second mass to charge is not present on the exclusion list prior to performing the second MSMS mode. The exclusion list may be stored in a memory of the mass spectrometer or on an electronic device in communication with the spectrometer. The spectrometer may be configured to perform, e.g. automatically, any of the methods described herein. Embodiments have been described in which fragment or product ions are prevented from being selected for MSMS analysis by adding a mass to charge ratio detected in the first MSMS mass spectral data to an exclusion list. However, it is alternatively contemplated that fragment or product ions may be prevented from being selected for MSMS analysis by determining that ions in the survey mode mass spectral data are fragment or product ions and then adding these ions to the exclusion list. Accordingly, from a second aspect the present invention provides a method of mass spectrometry comprising: operating a mass spectrometer in a survey mode for a first period in which the mass to charge ratio and mobility of ions are analysed so as to obtain first survey mass spectral data; determining that a first ion detected in the first survey mode mass spectral data is not desired to be selected for MSMS analysis based on the combination of mass to charge ratio and mobility detected for that ion in the first survey mass spectral data; adding the mass to charge ratio of the first ion to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and then performing an MSMS analysis in which ions having a mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain MSMS mass spectral data, wherein the method comprises checking that the mass to charge ratio of the ions is not present on the exclusion list prior to performing the MSMS analysis. This method may make the determination that said first ion is a fragment or product ion, from said combination of mass to charge ratio and mobility, and that it is not desired to subject ions of this mass to charge ratio to MSMS analysis. For example, the first ion may be detected as having a mobility that is too high for its detected mass to charge ratio for it to be a precursor ion. Accordingly, the step of determining that the first ion is not desired to be selected for MSMS analysis may comprise: comparing said combination of mass to charge ratio and mobility to data that is indicative of combinations of mass to charge ratio and mobility that are desired to be selected for MSMS analysis; determining from said data that the combination of mass to charge ratio and mobility for the first ion is not a combination that is desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis; or comparing said combination of mass to charge ratio and mobility to data that is indicative of combinations of mass to charge ratio and mobility that are not desired to be selected for MSMS analysis; determining from said data that the combination of mass to charge ratio and mobility for the first ion is a combination that is not desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis. The mass (as opposed to mass to charge ratio) of the first ion may be determined and this may then be used to determine if the first ion is likely to be a precursor or fragment ion based on its detected mobility. Accordingly, the step of determining that the first ion is not desired to be selected for MSMS analysis may comprise: detecting the charge state of the first ion; determining the mass of the first ion from its detected charge state and its mass to charge ratio; and either a) comparing the combination of mass and mobility for the first ion to data that is indicative of combinations of mass and mobility that are desired to be selected for MSMS analysis; determining from said data that the combination of mass and mobility for the first ion is not a combination that is desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis; or b) comparing the combination of mass and mobility for the first ion to data that is indicative of combinations of mass and mobility that are not desired to be selected for MSMS analysis; determining from said data that the combination of mass and mobility for the first ion is a combination that is not desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis. The method according to the second aspect of the invention may have any of the features described above in relation to the first aspect of the invention, except that the mass to charge ratio that is added to the exclusion list is determined from the first survey mass spectral data rather than from the MSMS mass spectral data (and that the resulting exclusion list may then be used for the first MSMS analysis instead of or in addition to the second first MSMS analysis). The second aspect the present invention also provides a mass spectrometer comprising: an ion source; a fragmentation or reaction device; an ion mobility analyser; a mass analyser; and control circuitry configured to control the mass spectrometer to: (i) perform a survey mode in which the mass to charge ratio and mobility of ions are analysed by the ion mobility analyser and mass analyser so as to obtain first survey mass spectral data; (ii) determine that a first ion detected in the first survey mode mass spectral data is not desired to be selected for MSMS analysis based on the combination of mass to charge ratio and mobility detected for that ion in the first survey mass spectral data; (iii) add the mass to charge ratio of the first ion to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and (iv) perform an MSMS analysis in which ions having a mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain MSMS mass spectral data, wherein the spectrometer checks that the mass to charge ratio of the ions is not present on the exclusion list prior to performing the MSMS analysis. The exclusion list may be stored in a memory of the mass spectrometer or on an electronic device in communication with the spectrometer. The spectrometer may be configured to perform, e.g. automatically, the methods described in relation to the second aspect of the invention. It is contemplated that fragment or product ions may be prevented from being selected for MSMS analysis by determining that ions in the survey mode mass spectral data do not follow a trend and then adding these ions to the exclusion list. Accordingly, from a third aspect the present invention provides a method of mass spectrometry comprising: operating a mass spectrometer in a survey mode for a first period that comprises: passing ions to a mass filter or mass to charge ratio separator that is operated such that it transmits ions towards a mass analyser with either progressively increasing or progressively decreasing mass to charge ratios as time progresses; mass analysing ions using the mass analyser so as to obtain first survey mass spectral data that follows a trend in which the mass to charge ratios of the ions detected by the mass analyser either progressively increases or progressively decreases with time, respectively; determining a first mass to charge ratio in the first survey mass spectral data that does not follow said trend; adding the first mass to charge ratio to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and then performing an MSMS analysis in which ions having a mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain MSMS mass spectral data, wherein the method comprises checking that the mass to charge ratio of the ions is not present on the exclusion list prior to performing the MSMS analysis. As the mass filter or mass to charge ratio separator transmits ions having progressively increasing or decreasing mass to charge ratios, it would be expected that when these ions are detected at the mass analyser the mass to charge ratios of the ions detected by the mass analyser would either progressively increase or decrease, respectively. However, if any of the ions transmitted by the mass filter or mass to charge ratio separator fragment or react to form fragment or product ions, then the resulting ions would be detected by the mass analyser as having a mass to charge ratio that does not follow the trend. As such, the mass spectrometer is able to identify these mass to charge ratios as ones that should be added to the exclusion list. The mass to charge ratio separator may be located upstream of the mass filter that is used to select ions for MSMS analysis in the MSMS mode of operation. The mass to charge ratio separator may be used in the MSMS analysis to enhance the duty cycle of the spectrometer by scanning the mass filter that is used to select ions for MSMS analysis in a manner that is synchronised with the elution of ions from the mass to charge ratio separator. In such a technique fewer ions will be discarded by the mass filter at any given time during the MSMS analysis, as mass to charge ratios that are not capable of being transmitted by the mass filter at that time will not yet have emerged from the downstream end of the mass to charge ratio separator. In the embodiments in which the survey scan uses the mass filter to transmit ions towards the mass analyser with progressively increasing or decreasing mass to charge ratios, this mass filter may be the same mass filter that is used to select ions for MSMS analysis in the MSMS mode of operation. The method may determine that the first mass to charge ratio in the first survey mass spectral data does not follow said trend by determining that the first mass to charge ratio is either above or below the mass to charge ratio that is expected to be detected, according to the trend, at the time that the first mass to charge ratio is detected. The first mass to charge ratio may be determined not to follow the trend by determining that the first mass to charge ratio is a more than a pre-selected amount above or below the mass to charge ratio that is expected to be detected. The method according to the third aspect of the invention may have any of the features described above in relation to the first aspect of the invention, except that the mass to charge ratio that is added to the exclusion list is determined from the trend in the first survey mass spectral data rather than from the MSMS mass spectral data (and that the resulting exclusion list may then be used for the first MSMS analysis instead of or in addition to the second first MSMS analysis). The third aspect the present invention also provides a mass spectrometer comprising: an ion source; a fragmentation or reaction device; a mass filter or mass to charge ratio separator; a mass analyser; and control circuitry configured to control the mass spectrometer to: (i) operate the mass spectrometer in a survey mode in which: the mass filter or mass to charge ratio separator is operated such that it transmits ions towards the mass analyser with either progressively increasing or progressively decreasing mass to charge ratios as time progresses; and the mass analyser mass analyses ions so as to obtain first survey mass spectral data that follows a trend in which the mass to charge ratios of the ions detected by the mass analyser either progressively increases or progressively decreases with time, respectively; (ii) determine a first mass to charge ratio in the first survey mass spectral data that does not follow said trend; (iii) add the first mass to charge ratio to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and (iv) perform an MSMS analysis in which ions having a mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain MSMS mass spectral data, wherein the spectrometer checks that the mass to charge ratio of the ions is not present on the exclusion list prior to performing the MSMS analysis. The exclusion list may be stored on the spectrometer or on an electronic device in communication with the spectrometer. The spectrometer may be configured to perform, e.g. automatically, the methods described in relation to the third aspect of the invention. The present invention also extends to recognising, after the event, that a fragment or product ion has been selected for MSMS analysis and that it may be desired to discard, or process in some other way, the resulting MSMS mass spectral data based on this determination. This technique is useful, for example, in circumstances where a fragment ion that has been detected in the survey mode may be selected for MSMS analysis before it has had an opportunity to be added to an exclusion list. For example, if a fragment ion in the survey data is selected for MSMS analysis before its parent ion has been selected for MSMS analysis, then the technique according to the first aspect of the present invention would not have been able to prevent this fragment ion from being selected for MSMS analysis. Accordingly, from a fourth aspect the present invention provides a method of mass spectrometry comprising: operating a mass spectrometer in a survey mode in which ions are mass analysed so as to obtain survey mass spectral data; performing a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain first MSMS mass spectral data; performing a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain second MSMS mass spectral data; determining that ions having the second mass to charge ratio are detected in the first MSMS mass spectral data; and in response thereto performing one of: i) discarding the second MSMS mass spectral data; ii) combining the second MSMS mass spectral data with the first MSMS mass spectral data; iii) marking the second MSMS mass spectral data as being mass spectral data from the MSMS analysis of a fragment or product ion species; or iv) determining that ion fragmentation has occurred in the survey mode. As it is determined that the ions having the second mass to charge ratio are detected in the first MSMS mass spectral data, these ions are determined to be likely to be fragment or product ions derived from the ions having the first mass to charge ratio. As such, it may be desired to discard the second MSMS mass spectral data, as per feature i) above, since it is generally undesirable to subject fragment or product ions to MSMS analysis. Alternatively, as the ions having the second mass to charge ratio are determined to be likely to be fragment or product ions derived from the ions having the first mass to charge ratio, it may be desired to combine the second MSMS mass spectral data with the first MSMS mass spectral data, as per feature ii) above. Alternatively, it may be desired to process the second MSMS mass spectral data in some other way and, as such, the data may be marked as being mass spectral data from the MSMS analysis of a fragment or product ion species, as per feature iii) above. The step of discarding the second MSMS mass spectral data may comprise not using this data to generate a mass spectrum, not combining this data with other mass spectral data, or deleting this data. The step of combining the second MSMS mass spectral data with the first MSMS mass spectral data may comprise combining the data so as to form a composite mass spectrum that includes the combined data. If it is determined that ion fragmentation has occurred in the survey mode, as per feature iv), then the method may, in response thereto, adjust a setting of the spectrometer that influences the degree of fragmentation in the spectrometer in a future instance of the survey mode. For example, this may comprise adjusting the operation of the ion source, e.g. so as to reduce in-source fragmentation of ions. For example, one or more voltage applied to the ion source may be varied, such as by being reduced. By way of example only, if the ion source is an electrospray ionisation source then the electrospray voltage may be adjusted. Additionally, or alternatively, to adjusting the ion source, a voltage or setting applied to another ion-optical component used in the survey mode may be adjusted so as to reduce the fragmentation in the survey mode. This could include travelling wave parameters (e.g. velocity or amplitude) in a travelling-wave based ion mobility or mass-to-charge separator. Additionally, or alternatively, the pressure in an ion-optical component used in the survey mode may be adjusted so as to reduce the fragmentation in the survey mode. For example, if the ions are transmitted through an ion mobility separator in the survey mode then the pressure in the ion mobility separator may be reduced in order to reduce fragmentation. The step or performing either i), ii), iii) or iv) may only be conducted if mass spectral data for the second mass to charge ratio indicates that ions having this mass to charge ratio are more abundant in the first MSMS analysis than in the survey mass spectral data, e.g. after correcting for relative dwell time or scan time between survey and MSMS data. This indicates that the ions having the second mass to charge ratio are relatively likely to be fragment or product ions. If the mass spectral data for the second mass to charge ratio indicates that ions having this mass to charge ratio are less abundant in the first MSMS analysis than in the survey mass spectral data, and / or have the same abundance, then the step or performing either i), ii), iii) or iv) may not be conducted. The step of determining that ions having the second mass to charge ratio are detected in the first MSMS mass spectral data may only be performed for first and second MSMS analyses that have occurred within a pre-selected duration of each other. For example, the method may comprise separating a sample using a liquid or gas chromatography device and ionising analytes as they elute from the device so as to form said ions. The first MSMS analysis and the second MSMS analysis may be performed one after the other, and at substantially the same time. The method may comprise performing one or mode additional MSMS analysis on one or mode additional mass to charge ratio detected in the survey mode, respectively. The mass spectrometer may determine if the mass to charge ratio of the selected ion in the one or more additional MSMS analysis is present in the MSMS mass spectral data from another of the MSMS analyses. If it is then the MSMS mass spectral data from said one or more additional MSMS analysis may be discarded, or may be combined with the MSMS mass spectral data from said another of the MSMS analyses, or may be marked as being mass spectral data from the MSMS analysis of a fragment or product ion species, or may be used to determine that ion fragmentation has occurred in the survey mode. Each MSMS analysis may comprise selecting and isolating ions having one of the mass to charge ratio detected in the survey mode, fragmenting or reacting the isolated ions, and mass analysing the resulting fragment or product ions so as to obtain MSMS mass spectral data. Accordingly, the first MSMS analysis may comprise isolating ions having said first mass to charge ratio detected in the survey mode, fragmenting or reacting the isolated ions and mass analysing the resulting ions so as to obtain the first MSMS mass spectral data. Similarly, the second MSMS analysis may comprise isolating ions having said second mass to charge ratio detected in the survey mode, fragmenting or reacting the isolated ions and mass analysing the resulting ions so as to obtain the second MSMS mass spectral data. In contrast, ions may not be isolated in the survey mode prior to mass analysis. The method is performed on a mass spectrometer comprising an ion source, a fragmentation or reaction device, and a mass analyser. Desirably, in the survey mode, ions generated by the ion source are substantially not fragmented or reacted in the fragmentation or reaction device, or are fragmented or reacted in the ion source or fragmentation or reaction device at a relatively low rate, prior to being mass analysed. In each of the MSMS analyses, ions generated by the ion source are fragmented or reacted in the fragmentation or reaction device at a higher rate than in the survey mode and the resulting fragment or product ions are mass analysed. The method may be performed in real-time as the MSMS data is acquired, or it may be performed in a post-processing step after all of the MSMS data has been acquired. The fourth aspect the present invention also provides a mass spectrometer comprising: an ion source; a fragmentation or reaction device; a mass analyser; and control circuitry configured to control the mass spectrometer to: (a) operate the mass spectrometer in a survey mode in which ions are mass analysed by the mass analyser so as to obtain survey mass spectral data; (b) perform a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain first MSMS mass spectral data; (c) perform a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain second MSMS mass spectral data; (d) determine that ions having the second mass to charge ratio are detected in the first MSMS mass spectral data; and in response thereto perform one of: i) discard the second MSMS mass spectral data; ii) combine the second MSMS mass spectral data with the first MSMS mass spectral data; iii) mark the second MSMS mass spectral data as being mass spectral data from the MSMS analysis of a fragment or product ion species; or iv) determine that ion fragmentation has occurred in the survey mode. The spectrometer may be configured to perform, e.g. automatically, the methods described in relation to the fourth aspect of the invention. 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 a mass spectrometer according to an embodiment of the present invention; and Fig. 2 shows a mass spectrometer according to another embodiment of the present invention. DETAILED DESCRIPTION Fig. 1 shows a block diagram of a mass spectrometer according to an embodiment of the present invention that comprises a sample separator 2, an ion source 4, a quadrupole mass filter 6, a fragmentation or reaction cell 8 and an orthogonal acceleration time of flight mass analyser 10. In order to analyse a sample, a sample is transmitted from the sample separator 2 to the ion source 4 and ionised so as to form precursor ions of analyte species that are present in the sample. The sample separator may be, for example, a liquid chromatography separator. The spectrometer may be operated in a data dependent acquisition (DDA) mode of operation that comprises a survey (MS) mode for determining the mass to charge ratios of the precursor ions, and an MSMS mode that sequentially isolates the precursor ion species for further analysis of each of them. In the survey (MS) mode the precursor ions are transmitted to the time of flight mass analyser 10 and are mass analysed. In this mode the quadrupole mass filter 6 may be operated as an ion guide by applying voltages to its electrodes such that it is capable of transmitting ions having a relatively wide range of mass to charge ratios, i.e. substantially all precursor ions of interest. The fragmentation or reaction cell 8 may be deactivated in this mode such that the precursor ions travel through it to the mass analyser 10 substantially without being fragmented or reacted to form fragment or product ions. Once the spectrometer has determined the mass to charge ratios of the precursor ions in the survey mode, it switches to an MSMS mode of operation. In the MSMS mode the spectrometer selects a first of the precursor ion species that were detected in the survey mode to analyse further and then controls the voltages that are applied to the mass filter 6 such that only ions having a mass to charge ratio corresponding to that of the first precursor ion species are transmitted by the mass filter. Ions having all other mass to charge ratios are filtered out and not transmitted by the mass filter. The ions that are transmitted by the mass filter are then conveyed into the fragmentation or reaction device 8, which is activated such that the ions are fragmented or reacted to form first fragment ions, or reacted with other ions or molecules so as to form first product ions. The first fragment or product ions are then conveyed to the mass analyser 10 and are mass analysed so as to determine their mass to charge ratios. The spectrometer may then associate this MSMS mass spectral data for the first fragment or product ions with the first precursor ion species (i.e. with a precursor ion species having the mass to charge ratio of the first precursor ion species). The spectrometer may then select a second of the precursor ion species that were detected in the survey mode to analyse further. The spectrometer then controls the voltages that are applied to the mass filter 6 such that only ions having a mass to charge ratio corresponding to that of the second precursor ion species are transmitted by the mass filter into the fragmentation or reaction device 8, which is activated such that the ions are fragmented or reacted to form second fragment or product ions. The second fragment or product ions are then conveyed to the mass analyser 10 and are mass analysed so as to determine their mass to charge ratios. The spectrometer may then associate this MSMS mass spectral data for the second fragment or product ions with the second precursor ion species (i.e. with a precursor ion species having the mass to charge ratio of the second precursor ion species). This process of isolating a precursor ion species, fragmenting or reacting those ions, and mass analysing the resulting fragment or product ions may be repeated one or more times, wherein each time it is repeated the ions that are isolated are ions of a different one of the precursor ions species detected in the survey mode. It will be appreciated that the mass spectral data obtained according to such an experiment may then be used by the spectrometer to identify the precursor ion species and one or more analyte in the sample. The spectrometer may be configured so as not to perform the MSMS analysis on all of the precursor ion species that are detected in the survey mode (i.e. not to isolate and fragment / react all of the precursor ions species detected in the survey mode), but to perform the MSMS analysis on only some of the precursor ion species detected in the survey mode. For example, the spectrometer may be configured to only perform the MSMS analysis on precursor ion species that have mass to charge ratios in one or more range of mass to charge ratios. For instance, precursor ions having mass to charge ratios in one or more range of mass to charge ratios may be considered to be of interest by a user. The spectrometer may have a user interface configured to allow the user to input the one or more range of mass to charge ratios of interest. The spectrometer may be configured to operate, in response to such an input, to perform MSMS analysis on each of the precursor ion species that is detected in the survey mode and that has a mass to charge ratio within said one or more range of interest. The spectrometer may be configured to exclude some of the precursor ions detected in the survey mode from being subjected to an MSMS analysis. The spectrometer may have a user interface configured to allow the user to input one or more range of mass to charge ratios of precursor ions to be excluded from being subjected to MSMS analysis. The spectrometer may be configured to operate, in response to such an input, so as not to perform an MSMS analysis on each of the precursor ion species that is detected in the survey mode and that has a mass to charge ratio within the one or more range to be excluded. Embodiments are contemplated in which a sample being supplied substantially continually to the ion source 4 is analysed in the survey mode during multiple separate time periods. For example, the spectrometer may be operated in the survey mode for a first period, followed by a period in an MSMS mode for each of a plurality of the precursor ion species detected during the first period (i.e. during the survey mode). This may then be followed by a second period in the survey mode, which is then followed by a period in the MSMS mode for each of one or more of the precursor ion species detected in the second period (i.e. during the survey mode). This enables the precursor ions from different species that arrive at the ion source 4 at different respective times to be detected in the different survey mode periods and then analysed in subsequent MSMS mode periods. For example, if the sample is separated by a separator device 2, such as a liquid or gas chromatography device, prior to being ionised by the ion source 4 then different analytes may arrive at the ion source over different time periods. If the survey mode was performed during only a single period then only some of the precursor ions from the sample would be detected as being present, whereas by performing the survey mode in multiple spaced apart periods the embodiments are able to detect precursor ions that elute from the sample separator 2 at different times, such as in different chromatographic peaks. In embodiments where the survey mode is performed during multiple periods on the same sample, the spectrometer may be configured to exclude precursor ion species that have been detected in a given survey mode period from being further analysed (e.g. isolated and fragmented or reacted) if they have already been detected in a previous survey mode period and further analysed (e.g. if they have already been isolated, fragmented or reacted and the resulting fragment or product ions mass analysed). The precursor ion species may only be excluded if MSMS data for those precursor ion species that is sufficient to meet one or more criterion has already been acquired. For example, a precursor ion species may be excluded if the related MSMS mass spectral data that was obtained previously is sufficient to identify the precursor ion species, and / or if the MSMS mass spectral data has a minimum threshold intensity and / or mass resolution. If the MSMS mass spectral data already acquired for the precursor ion species is insufficient to meet said one or more criterion then it may not be excluded and hence that precursor ion species may be subjected to the MSMS mode of analysis if it is detected in a later survey mode period. These embodiments that exclude precursor ion species from MSMS analysis if sufficient mass spectral data has already been obtained enable more time to be available for the MSMS analysis of precursor ion species that are newly detected in a survey mode period or for which sufficient data has not yet been acquired. It has been recognised that the mass spectral data obtained in the survey mode may not be only due to the mass analysis of precursor ion species, but that a significant number of fragment or product ions (e.g. peptide fragment ions) may have inadvertently been generated between the ion source and mass analyser that are then mass analysed, even though the fragmentation or reaction device is deactivated or bypassed. If these fragment or product ions are detected in the survey mode then the spectrometer may then select them as target ions to be subjected to an MSMS analysis, which may be undesirable. For example, if these fragment or product ions are subjected to MSMS analysis then the resulting mass spectral data often provides less information than that of their respective intact precursor ion species. This is because the fragment or product ions have lower masses, and often have lower charge states, than their precursor ion species, and software designed to interpret MSMS mass spectral data usually searches preferentially for intact precursor ion species. This problem can be mitigated by determining the charge state of the ions that are detected in the survey mode and preventing mass to charge ratios corresponding to those of singly charged ions from being analysed in the MSMS mode. This can reduce the number of fragment or product ions that are selected for MSMS. However, real-time charge state detection tends to be error-prone due to the limited time available to process the mass spectral data. Also, such techniques are ineffective to exclude fragment or product ions that are multiply charged. The present invention recognises that the mass to charge ratios of fragment or product ions will be known from the mass spectral data that is obtained in the MSMS mode of operation, and that at least some of such fragment or product ions can therefore be excluded from subsequently being selected for being subjected to the MSMS mode of operation by adding the mass to charge ratios of at least some of the detected fragment or product ions to an exclusion list. Accordingly, as described above, the spectrometer may operate in a survey mode for a first period so as to determine the mass to charge ratios of the ions that are transmitted to the mass analyser 10 when the fragmentation or reaction cell 8 is deactivated, or bypassed by the ions. The detected ions will primarily be precursor ions generated from the sample at the ion source 4, but as described above some of these ions may have fragmented or reacted and their fragment or product ions will be detected in the mass spectral data of the survey mode. The spectrometer then switches to an MSMS mode of operation in which it selects a mass to charge ratio corresponding to that of a first one of the ion species that was detected in the first period (i.e. during the survey mode) and analyses such ions further. As described above, the spectrometer does this by controlling the voltages that are applied to the mass filter 6 such that only ions having a mass to charge ratio corresponding to that of the first ion species are transmitted by the mass filter. Ions having all other mass to charge ratios may be filtered out and not transmitted by the mass filter. The ions that are transmitted by the mass filter are then conveyed into the fragmentation or reaction device 8, which is activated such that the ions are fragmented or reacted to form first fragment ions, or reacted with other ions or molecules so as to form first product ions. The first fragment or product ions are then conveyed to the mass analyser 10 and are mass analysed so as to determine their mass to charge ratios. The spectrometer may then associate this mass spectral data for the first fragment or product ions with the first precursor ion species. Additionally, the spectrometer may add at least one, or at least some, of the mass to charge ratios of the detected first fragment or product ions to an exclusion list such that the spectrometer does not subsequently select ions having such mass to charge ratios for MSMS analysis. The spectrometer may be configured to maintain such mass to charge ratios on the exclusion list for the entire time that the sample is being analysed (e.g. for the whole of the experimental run that the sample is being substantially continually supplied to the ion source), or for only a portion of the time that the sample is being analysed. For example, if the spectrometer comprises a sample separator 2, such as a liquid or gas chromatography separator, then the mass to charge ratios may be added to and maintained on the exclusion list only for a time period that is substantially the same as the duration of an analyte peak that would elute from the sample separator. The mass to charge ratios may be removed from the exclusion list at the end of this time period. This technique is useful because fragment or product ions that are detected whilst a first analyte peak elutes from the sample separator 2 may have substantially the same mass to charge ratios as precursor ion species that are generated as a subsequent analyte peak elutes from the sample separator. As the mass to charge ratios of the fragment or product ions are removed from the exclusion list before the subsequent analyte peak has started to elute, or at least before it has finished eluting, this enables the precursor ions generated from the subsequent analyte peak to be subjected to MSMS analysis. It will therefore be appreciated that the spectrometer is unable to select a fragment or product ion of one of the precursor ions for MSMS analysis whilst that fragment or product ion remains on the exclusion list. The spectrometer may then select a second mass to charge ratio corresponding to that of a second one of the ion species that was detected during the first period (i.e. in the survey mode), and that is not on the exclusion list. The spectrometer then proceeds to perform an MSMS analysis to analyse such ions further. The spectrometer does this by controlling the voltages that are applied to the mass filter 6 such that only ions having a mass to charge ratio corresponding to that of the second ion species are transmitted by the mass filter. Ions having all other mass to charge ratios may be filtered out and not transmitted by the mass filter. The ions that are transmitted by the mass filter are then conveyed into the fragmentation or reaction device 8, which is activated such that the ions are fragmented or reacted to form second fragment ions, or reacted with other ions or molecules so as to form second product ions. The second fragment or product ions are then conveyed to the mass analyser 10 and are mass analysed so as to determine their mass to charge ratios. The spectrometer may then associate this mass spectral data for the second fragment or product ions with the second precursor ion species. Additionally, the spectrometer may add at least one, or at least some, of the mass to charge ratios of the detected second fragment or product ions to an exclusion list such that the spectrometer does not subsequently select ions having such mass to charge ratios for MSMS analysis. The spectrometer may be configured to maintain such mass to charge ratios on the exclusion list for the entire time that the sample is being analysed (e.g. for the whole of the experimental run that the sample is being substantially continually supplied to the ion source 2), or for only a portion of the time that the sample is being analysed. For example, if the spectrometer comprises a sample separator 2, such as a liquid or gas chromatography separator, then the mass to charge ratios may be added to and maintained on the exclusion list for a time period that is substantially the same as the duration of an analyte peak that would elute from the sample separator. The mass to charge ratios may then be removed from the exclusion list at the end of this time period. The above-described process of isolating ion species, fragmenting or reacting those ions, mass analysing the resulting fragment or product ions, and then adding at least one or at least some of the mass to charge ratios of the detected fragment or product ions to an exclusion list may be repeated one or more times, wherein each time it is repeated the ions that are isolated are ions having a different one of the mass to charge ratios detected in the first period, i.e. in the survey mode, and that are not on the exclusion list at the time the isolation step is performed. The above process of operating the spectrometer in the survey mode and then in the MSMS mode may be repeated one or more times during the experimental run. For example, after analysing the ions in the MSMS mode as described above, the spectrometer may perform the survey mode for a second period. After this the spectrometer may then again switch to the MSMS mode of operation in which it sequentially selects mass to charge ratios corresponding to ion species detected in the second period (i.e. during the survey mode) and analyses such ions further. The mass spectral data obtained according to the experiment may be used by the spectrometer to identify the precursor ion species and one or more analyte in the sample. Embodiments have been described in which mass to charge ratios corresponding to those of fragment or product ions detected in the MSMS mode have been added to the exclusion list. It is contemplated that mass to charge ratios corresponding to modified versions of these ions may also be added to the exclusion list. For example, the charge state of a detected fragment or product ion may be detected or estimated and then the mass to charge ratio detected for that ion may be modified to one or more different mass to charge ratios that the ion would have if it had one or more different charge states. These one or more different mass to charge ratios may then be added to the exclusion list, at least for a portion of the experiment as described above. Additionally, or alternatively, the mass to charge ratio for a detected fragment or product ion may be modified in other manners. For example, a pre-selected mass to charge ratio may be added to, or subtracted from, the mass to charge ratio of the detected fragment or product ion so as to obtain a mass to charge ratio that is added to the exclusion list, at least for a portion of the experiment as described above. The pre-selected mass to charge ratio may be, for example, the mass to charge ratio that would be caused by an adduct that is likely to join to the fragment or product ion, a loss that is likely to be lost from the fragment or product ion, or a post-translational variant that may occur in the fragment or product ion. Alternatively, or additionally, the pre-selected mass to charge ratio may include the additional or reduced mass to charge ratio that an isotopic variant of the detected fragment or product ion could have. The spectrometer may be preprogrammed with the pre-selected mass to charge ratio, and / or it may have a user interface into which a user inputs the pre-selected mass to charge ratio. These modified mass to charge ratios may then be added to the exclusion list, at least for a portion of the experiment as described above. It will be appreciated that the mass spectrometer comprises control circuitry 12 that is configured to control the mass spectrometer so as to perform the methods described herein. As described above, the spectrometer may have additional, or different, ion-optical components to those shown in Fig. 1. For example, the spectrometer may have an ion mobility separator for separating the fragment ions generated in the fragmentation or reaction device before these ions are detected. Fig. 2 shows an embodiment that is the same as that shown in Fig. 1, except that an ion mobility separator (IMS) 14 is provided between the fragmentation or reaction device 8 and the mass analyser 10. In the survey mode the precursor ions are separated in the IMS device 14 such that precursor ions having different mobilities arrive at the mass analyser 10 and are mass analysed at different respective times. The spectrometer correlates the mass to charge ratio detected for any given precursor ion species with the value of a parameter that is related to its ion mobility through the IMS device 14, such as its time of detection. The precursor ions detected in the survey mode may be analysed in the MSMS mode in the manner described herein above. The fragment or product ions that are generated from any given precursor ion species in each MSMS analysis are separated in the IMS device 14 such that fragment or product ions having different mobilities arrive at the mass analyser 10 and are mass analysed at different respective times. The spectrometer correlates the mass to charge ratio detected for any given fragment or product ion with the value of a parameter that is related to its ion mobility through the IMS device 14, such as its time of detection. When one or more of these detected fragment ions is added to the exclusion list, it may be added such that only ions having both the mass to charge ratio and ion mobility of the fragment or product ion will be excluded from subsequently being selected for MSMS analysis. Such embodiments prevent precursor ions from being unnecessarily excluded from an MSMS analysis simply because they happen to have substantially the same mass to charge ratio as the fragment or product ion derived from a different precursor ion species, i.e. these precursor ions are not excluded because they have a different mobility to that of the fragment / product ion. As mentioned above, fragment or product ions may undesirably be generated in the survey mode, i.e. not due to the fragmentation or reaction caused by device 8, and it may be desired to add these ions to the exclusion list so that they are not selected for MSMS analysis. If these undesired fragment or product ions are generated downstream of the IMS device 14, then the spectrometer will not actually determine the mobility of these fragment or product ions, but it will instead determine these ions as having the same mobility as their precursor species since it is their precursor species that pass through the IMS device 14. In this case, the mobility of the undesired fragment / product ions detected in the MS / MS analysis cannot be used to prevent a precursor ion from being unnecessarily excluded from an MSMS analysis simply because the precursor species happens to have substantially the same mass to charge ratio as the undesired fragment or product ion. The spectrometer may however still determine that the undesired fragment or product ion species detected in the survey mode are not precursor ion species. For example, as described further below, the spectrometer may determine that the same mass to charge ratio is present in both the survey mode mass spectral data and MSMS mode mass spectral data, and may then determine that these ions are fragment / product ions due to their relative intensities in the survey mode mass spectral data and MSMS mode mass spectral data. Once this determination has been made by the spectrometer, this mass to charge ratio may be added to the exclusion list so that it is not subsequently subjected to MSMS analysis. The spectrometers described herein may determine that the ions detected in the survey mode mass spectral data are undesired fragment / product ions based on the mass to charge ratio and mobility determined for those ions in the survey mode. For example, if an undesired fragment / product ion is a relatively small fragment / product ion, it may be detected in the survey mode as having a mobility that is too high for an ion of the detected mass to charge ratio to be a precursor ion. The charge state of the ion may also be determined and used, along with the detected mass to charge ratio, to determine the mass of the ion. This enables the spectrometer to more accurately determine the size of the ion, and hence whether or not it is likely to be a precursor ion or an undesired fragment / product ion, based on its determined mobility. If the spectrometer determines that these detected ions are fragment / product ions, then the spectrometer may be configured to add the mass to charge ratio(s) of these ions to the exclusion list such that ions having these mass to charge ratios are not subsequently subjected to MS / MS analysis. Any of the IMS devices that are described herein may be configured to drive ions through a background gas arranged therein such that the ions separate according to mobility. The ions may be driven through the background gas by an electric field in order that they separate according to mobility. For example, the ions may be driven by applying a static DC potential difference along the IMS device and / or by repeatedly travelling a DC potential along the IMS device. The electric field may be arranged so as to urge the ions in a downstream direction, i.e. towards the TOF mass analyser, through the IMS device. In these IMS devices the ions to be separate may be pulsed together into the entrance of the IMS device at substantially the same time. Alternatively, the background gas may be flowed through the IMS device in one direction, such as the downstream direction, and the electric field may be arranged to urge the ions in an opposite direction, such as the upstream direction, against the gas flow so as to cause the ions to separate according to mobility. The ions may be trapped within the IMS device. The gas flow and / or electric field may be varied with time such that ions having different mobilities exit the IMS device in the downstream direction at different times. Alternatively, the IMS device may separate the ions according to their mobility by applying a static DC potential difference along the IMS device such that an electric field urges the ions in a first direction, and repeatedly travelling a DC potential along the IMS device in an opposite, second direction for urging ions in the opposite direction. The first direction may be the downstream direction along the IMS device and the second direction may be the upstream direction, or vice versa. The DC potential difference and / or a parameter of the DC potential (such as speed along the IMS device or amplitude) may be varied with time such that ions having different mobilities exit the IMS device in the downstream direction at different times. Although IMS devices have been described herein as separating and eluting ions according to mobility, it is contemplated that ions may be separated and eluted according to mass to charge ratio, or a mixture of mobility and mass to charge ratio. It is known that in IMS devices in which a DC potential is repeatedly travelled along the device in order to separate ions by mobility, there is a mass to charge ratio dependence in the ion separation, e.g. as described in K. Richardson, D. Langridge, K. Giles, Fundamentals of travelling wave ion mobility revisited: I. Smoothly moving waves, International Journal of Mass Spectrometry, Volume 428, 2018, Pages 71-80. Operational parameters of the separator, such as pressure and / or speed of the travelling DC potentials, may be selected such that it primarily separates ions by mobility, such that it primarily separates ions by mass to charge ratio, or such that it operates in a mode where the ion separation is significantly dependent on both mobility and mass to charge ratio. It will therefore be appreciated that the IMS device described herein, e.g. in relation to Fig. 2, may be replaced with a separator that operates in any one of these modes. It is contemplated that the spectrometers described herein may include a mass to charge ratio separator (not shown) upstream of the mass filter 6 and that is configured to separate ions passing therethrough by mass to charge ratio such that ions having different mass to charge ratios arrive at the mass filter 8 at different, respective times. This may be used to enhance the duty cycle of the spectrometer in the MSMS mode by scanning the mass filter 8 in a manner that is synchronised with the elution of ions from the mass to charge ratio separator. In other words, in such a technique fewer ions will be discarded by the mass filter at any given time, as mass to charge ratios that are not capable of being transmitted by the mass filter at that time will not yet have emerged from the downstream end of the mass to charge ratio separator. In such embodiments, in the survey mode, the precursor ions are separated in the mass to charge ratio separator such that precursor ions having different mass to charge ratios arrive at the mass analyser 10 and are mass analysed at different respective times. The mass spectral data obtained will therefore follow a trend in which the mass to charge ratios of the precursor ions detected either progressively increases or progressively decreases with time, depending on whether the mass to charge ratio separator elutes ions in order of increasing or decreasing mass to charge ratio, respectively. However, if a precursor ion species fragments or reacts downstream of the mass to charge ratio separator, in the survey mode, so as to form the undesired fragment or product ions then such undesired ions will be detected as having mass to charge ratios that do not follow the trend of progressively increasing or progressively decreasing mass to charge ratio. The spectrometer may determine one or more mass to charge ratios that do not follow this trend and add such mass to charge ratio(s) to the exclusion list so as to prevent the mass to charge ratio(s) from being selected for MSMS analysis. As described above, the embodiments of the present invention add one or more mass to charge ratios that are detected in the MSMS mode to the exclusion list, so as to prevent ions having these mass to charge ratios from being subjected to a subsequent MSMS analysis, for at least part of the experiment. However, MSMS mass spectral data can contain many ion species and so it may be desirable to select only one, or only some, of the species to add to the exclusion list. This helps to avoid mass to charge ratios being added to the exclusion list that correspond to the mass to charge ratios of precursors ion species. For example, a fragment or product ion species detected in the MSMS mode may have substantially the same mass to charge ratio as a precursor ion species. Accordingly, one or more mass to charge ratios that are detected in the MSMS mode may be selected to be added to the exclusion list only if the corresponding mass spectral data for those one or more mass to charge ratios meets one or more criteria. For example, a mass to charge ratio may be selected to be added to the exclusion list based on the intensity of its corresponding mass spectral data. For instance a mass to charge ratio may only be added to the exclusion list if its corresponding mass spectral data has a relative or absolute intensity that is higher than a preselected threshold value. This helps to ensure that only relatively high intensity ion species in the MSMS mass spectral data, which are likely to be fragment or product ions, are added to the exclusion list. Alternatively, or additionally, only mass to charge ratios corresponding to those of the N most intense mass peaks in the MSMS mass spectral data may be added to the exclusion list, where N is a preselected integer. The value of N may be, for example, <10, <9, <8, <7, <6, <5, <4, <3, <2 or even 1. Alternatively, or additionally, the mass spectrometer may determine the charge states of the fragment or product ions and select one or more mass to charge ratio to be added to the exclusion list based on the detected charge state of the fragment or product ions. For example, a mass to charge ratio may only be added to the exclusion list if its corresponding mass spectral data has been determined to correspond to the detection of multiply charged ions. Alternatively, or additionally, a mass to charge ratio may be selected to be added to the exclusion list based on its mass to charge ratio. For instance a mass to charge ratio may only be added to the exclusion list if its corresponding mass spectral data has a mass to charge ratio in a certain range, such as below a threshold value. As described herein, the present invention seeks to prevent fragment or product ions that have been inadvertently generated and detected in the survey MS mode from being subsequently selected for analysis in the MSMS mode. Such fragment or product ions would be expected to be detected with a relatively low abundance in the survey mode and a higher abundance in the MSMS mode. As such, the spectrometer may be configured to determine ions having a mass to charge ratio that is detected in both the survey mode and the MSMS mode, where those ions are more abundant in the MSMS mode, and to add that mass to charge ratio to the exclusion list. The spectrometer may be configured to add the mass to charge ratio to the exclusion list if it has been detected in an MSMS analysis that is performed within a predetermined time of the survey mode. For example, if the spectrometer comprises a sample separator, such as a liquid or gas chromatography separator, the mass to charge ratio may only be added to the exclusion list if it has been detected in both the survey mode and the MSMS mode within a duration corresponding to the duration of an analyte peak that would elute from the sample separator. Although the present invention has been described with reference to 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. For example, although a particular instrument has been described, it will be appreciated that the present invention is not limited to a mass spectrometer having the all of the above features, or having only the above features. For instance, additional ion- optical devices may be provided between the ion source and the mass filter and / or between the mass filter and the mass analyser. An ion separator may be provided upstream of the fragmentation or reaction device 8 for separating precursor ions in both the survey mode and the MSMS analyses. The ion separator may separate the precursor ions according to a physicochemical property such an ion mobility or mass to charge ratio. In such embodiments, the precursor ions are separated by the ion separator such that in the survey mode the precursor ions having different values of the physicochemical property arrive at the mass analyser 10 and are mass analysed at different respective times. The spectrometer correlates the mass to charge ratio detected for any given precursor ion species with a time value that is indicative of when it exited the ion separator. The fragment or product ions that are generated from any given precursor ion species in each MSMS analysis will arrive at the mass analyser 10 and be mass analysed at a time that is related to the time that their precursor ion species exited the ion separator. The spectrometer may correlate the mass to charge ratio detected for any given fragment or product ion with a time value that is indicative of when its precursor ion exited the ion separator. The spectrometer may then use the time values to associate the fragment ions with their respective precursor ions. Although a mass filter 6 has been described as being used for isolating each precursor ion species, it is contemplated that another device may be used to do this. For example, a mass selective ion trap may be used to eject the different precursor ion species at different times such that they arrive at the fragmentation or reaction device 8 at different times. In each MSMS analysis the selected precursor ion species may be isolated from all other ion species. However, it is contemplated that multiple precursor ion species may be simultaneously subjected to an MSMS analysis. The mass analyser 10 may be a multi-reflecting time of flight analyser having at least two ion mirrors that the ions are reflected between multiple times as they pass from an ion accelerator to a detector. Alternatively, other types of mass analysers may be employed, such as a quadrupole mass analyser. It is therefore contemplated that the mass spectrometer maybe a tandem quadrupole mass spectrometer. Although embodiments have been described in which fragment or product ions are prevented from being selected for MSMS analysis by adding a mass to charge ratio detected in the first MSMS mass spectral data to an exclusion list, it is alternatively contemplated that the present invention may recognise, after the event, that a fragment or product ion has been selected for MSMS analysis and that it may be desired to discard, or process in some other way, the resulting MSMS mass spectral data based on this determination. Accordingly, the present invention may perform a survey mode, a first MSMS analysis, and a second MSMS analysis as has been described herein above. The spectrometer may examine the MSMS mass spectral data obtained, e.g. in a postprocessing method, to determine if the mass to charge ratio that was selected for the second MSMS analysis was present in the mass spectral data from the first MSMS analysis. If it was then this indicates that the mass to charge ratio that was selected for the second MSMS analysis is reasonably likely to be a fragment or product ion. In such an instance, the spectrometer may discard the MSMS mass spectral data from the second MSMS analysis, or it may combine this MSMS mass spectral data with the MSMS mass 5 spectral data from the first MSMS analysis.

Claims

1. A method of mass spectrometry comprising:operating a mass spectrometer in a survey mode for a first period in which ions are mass analysed so as to obtain first survey mass spectral data;performing a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain first MSMS mass spectral data;adding a mass to charge ratio detected in the first MSMS mass spectral data to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; andperforming a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain second MSMS mass spectral data, wherein the method comprises checking that the second mass to charge is not present on the exclusion list prior to performing the second MSMS analysis.

2. The method of claim 1, wherein said step of adding the mass to charge ratio detected in the first MSMS mass spectral data to the exclusion list comprises:i) determining that the mass to charge ratio is to be added to the exclusion list without this step of determining that the mass to charge ratio is to be added to the exclusion list using the mass to charge ratio to identify a precursor ion; and / orii) determining that the mass to charge ratio is to be added to the exclusion list without this step of determining that the mass to charge ratio is to be added to the exclusion list using a database search or algorithm to assign the mass to charge ratio to a known or inferred compound.

3. The method of claim 1 or 2, wherein the method is performed on a mass spectrometer comprising an ion source, a fragmentation or reaction device, and a mass analyser;wherein, in the survey mode, ions generated by the ion source are substantially not fragmented or reacted in the fragmentation or reaction device, or are fragmented or reacted in the fragmentation or reaction device at a relatively low rate, prior to being mass analysed; andwherein, in each of the MSMS analyses, ions generated by the ion source are fragmented or reacted in the fragmentation or reaction device at a higher rate than in the survey mode and the resulting fragment or product ions are mass analysed.

4. The method of claim 1,2, or 3, comprising adding a mass to charge ratio detected in the second MSMS mass spectral data to the exclusion list so as to prevent ions having that mass to charge ratio from being subjected to at least one subsequent MSMS analysis.

5. The method of any preceding claim, wherein at least one, or each, mass to charge ratio that is added to the exclusion list is only prevented from being subjected to MSMS analyses that are performed within a predetermined time of the mass to charge ratio having been added to the exclusion list.

6. The method of claim 5, wherein the method is performed on a sample that is being separated by a sample separator such that different analytes in the sample elute from the sample separator during different elution peaks and are then ionised; and wherein the predetermined time is substantially the same as the duration of an analyte peak eluting from the sample separator.

7. The method of claim 6, wherein the sample separator is a liquid or gas chromatography separator.

8. The method of any one of claims 1-4, wherein at least one, or each, mass to charge ratio that is added to the exclusion list is prevented from being subjected to all subsequent MSMS analyses performed during the same experimental run.

9. The method of any preceding claim, wherein each mass to charge ratio added to the exclusion list has corresponding MSMS mass spectral data that meets one or more criteria.

10. The method of any preceding claim, wherein a mass to charge ratio is only added to the exclusion list if its corresponding MSMS mass spectral data has an intensity that is higher than a preselected threshold value; and / orwherein only mass to charge ratios corresponding to those of the N most intense mass peaks in the mass spectral data from an MSMS analysis are added to the exclusion list, where N is an integer <10, <9, <8, <7, <6, <5, <4, <3, <2 or 1.

11. The method of any preceding claim, wherein a mass to charge ratio is only added to the exclusion list if ions that provide its corresponding MSMS mass spectral data have been determined to correspond to the detection of multiply charged ions.

12. The method of any preceding claim, wherein said step of adding a mass to charge ratio to the exclusion list comprises determining a mass to charge ratio that is detected in both the survey mode and the first MSMS analysis, where the mass spectral data for that mass to charge ratio indicates that the ions having this mass to charge ratio are moreabundant in the first MSMS analysis than in the survey mode, and adding that mass to charge ratio to the exclusion list.

13. The method of any preceding claim, wherein when a mass to charge ratio detected in an MSMS analysis is added to the exclusion list, the method comprises: determining or estimating the charge state of the ions in corresponding MSMS mass spectral data that have that mass to charge ratio; determining one or more modified mass to charge ratio corresponding to one or more mass to charge ratio that the ions would have if they had a different charge state; and then adding said one or more modified mass to charge ratio to the exclusion list.

14. The method of any preceding claim, wherein when a mass to charge ratio detected in an MSMS analysis is added to the exclusion list, the method comprises: calculating a modified version of this mass to charge ratio by adding or subtracting a pre-selected mass to charge ratio; and then adding said modified mass to charge ratio to the exclusion list.

15. The method of any preceding claim, wherein in the survey mode the ions are separated by ion mobility prior to being mass analysed, and the mass to charge ratio detected for any given ion is associated with a value that is related to its ion mobility;wherein in the first MSMS analysis, ions resulting from the fragmentation or reaction are separated by ion mobility prior to being mass analysed, and the mass to charge ratio detected for any given ion is associated with a value that is related to its ion mobility;wherein the step of adding the mass to charge ratio detected in the first MSMS mass spectral data to the exclusion list comprises adding a combination of a mass to charge ratio detected in the first MSMS analysis and its associated value related to its ion mobility; andwherein said step of checking that the second mass to charge ratio detected in the survey mode is not present on the exclusion list prior to performing the second MSMS analysis comprises: checking that ions having a combination of said second mass to charge ratio and its associated value related to its ion mobility are not present on the exclusion list.

16. The method of any preceding claim, wherein the method is performed on a sample that is being separated by a sample separator such that different analytes in the sample elute from the sample separator during different elution peaks and are then ionised;wherein said survey mode is performed during the first period whilst a first analyte peak elutes from the separator; and the method comprises performing the survey mode during a second period, whilst a second analyte peak subsequently elutes from the separator, in which ions are mass analysed so as to obtain second survey mass spectral data.

17. The method of claim 16, comprising performing an additional MSMS analysis in which ions having a mass to charge ratio detected in the second period of the survey mode are fragmented or reacted and then mass analysed so as to obtain MSMS mass spectral data;adding a mass to charge ratio detected in this additional MSMS mass spectral data to an exclusion list so as to prevent ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and thenperforming a further MSMS analysis in which ions having a different mass to charge ratio detected in the second period of the survey mode are fragmented or reacted and then mass analysed so as to obtain further MSMS mass spectral data, wherein the method comprises checking that the different mass to charge is not present on the exclusion list prior to performing the further MSMS analysis.

18. The method of claim 16 or 17, wherein the sample separator device is a liquid or gas chromatography device; and wherein the first period of the survey mode, said first MSMS analysis and said second MSMS analysis are performed as a first chromatographic peak elutes from the liquid or gas chromatography device; and wherein the second period of the survey mode, said additional MSMS analysis, and said further MSMS analysis are performed as a second chromatographic peak subsequently elutes from the liquid or gas chromatography device.

19. A mass spectrometer comprising:an ion source;fragmentation or reaction device;a mass analyser; andcontrol circuitry configured to control the mass spectrometer to:(i) operate the mass spectrometer in a survey mode in which ions are mass analysed in the mass analyser so as to obtain first survey mass spectral data;(ii) perform a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain first MSMS mass spectral data;(iii) add a mass to charge ratio detected in the first MSMS mass spectral data to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and(iv) perform a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain second MSMS mass spectral data, wherein the spectrometer checks that the second mass to charge is not present on the exclusion list prior to performing the second MSMS mode.

20. A method of mass spectrometry comprising:operating a mass spectrometer in a survey mode for a first period in which the mass to charge ratio and mobility of ions are analysed so as to obtain first survey mass spectral data;determining that a first ion detected in the first survey mode mass spectral data is not desired to be selected for MSMS analysis based on the combination of mass to charge ratio and mobility detected for that ion in the first survey mass spectral data;adding the mass to charge ratio of the first ion to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and thenperforming an MSMS analysis in which ions having a mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain MSMS mass spectral data, wherein the method comprises checking that the mass to charge ratio of the ions is not present on the exclusion list prior to performing the MSMS analysis.

21. The method of claim 20, wherein the step of determining that the first ion is not desired to be selected for MSMS analysis comprises:comparing said combination of mass to charge ratio and mobility to data that is indicative of combinations of mass to charge ratio and mobility that are desired to be selected for MSMS analysis; determining from said data that the combination of mass to charge ratio and mobility for the first ion is not a combination that is desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis; orcomparing said combination of mass to charge ratio and mobility to data that is indicative of combinations of mass to charge ratio and mobility that are not desired to be selected for MSMS analysis; determining from said data that the combination of mass to charge ratio and mobility for the first ion is a combination that is not desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis.

22. The method of claim 20 or 21, wherein the step of determining that the first ion is not desired to be selected for MSMS analysis comprises:detecting the charge state of the first ion;determining the mass of the first ion from its detected charge state and its mass to charge ratio; and eithera) comparing the combination of mass and mobility for the first ion to data that is indicative of combinations of mass and mobility that are desired to be selected for MSMS analysis; determining from said data that the combination of mass and mobility for the first ion is not a combination that is desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis; orb) comparing the combination of mass and mobility for the first ion to data that is indicative of combinations of mass and mobility that are not desired to be selected forMSMS analysis; determining from said data that the combination of mass and mobility for the first ion is a combination that is not desired to be selected for MSMS analysis and, in response to this, determining that the first ion is not desired to be selected for MSMS analysis.

23. A method of mass spectrometry comprising:operating a mass spectrometer in a survey mode for a first period that comprises: passing ions to a mass filter or mass to charge ratio separator that is operated such that it transmits ions towards a mass analyser with either progressively increasing or progressively decreasing mass to charge ratios as time progresses; mass analysing ions using the mass analyser so as to obtain first survey mass spectral data that follows a trend in which the mass to charge ratios of the ions detected by the mass analyser either progressively increases or progressively decreases with time, respectively;determining a first mass to charge ratio in the first survey mass spectral data that does not follow said trend;adding the first mass to charge ratio to an exclusion list for preventing ions having that mass to charge ratio from being subjected to a subsequent MSMS analysis; and thenperforming an MSMS analysis in which ions having a mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain MSMS mass spectral data, wherein the method comprises checking that the mass to charge ratio of the ions is not present on the exclusion list prior to performing the MSMS analysis.

24. A method of mass spectrometry comprising:operating a mass spectrometer in a survey mode in which ions are mass analysed so as to obtain survey mass spectral data;performing a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain first MSMS mass spectral data;performing a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted and then mass analysed so as to obtain second MSMS mass spectral data;determining that ions having the second mass to charge ratio are detected in the first MSMS mass spectral data; and in response thereto performing one of:i) discarding the second MSMS mass spectral data;ii) combining the second MSMS mass spectral data with the first MSMS mass spectral data;iii) marking the second MSMS mass spectral data as being mass spectral data from the MSMS analysis of a fragment or product ion species; oriv) determining that ion fragmentation has occurred in the survey mode.

25. The method of claim 24, wherein the step or performing i), ii), iii) or iv) is only conducted if mass spectral data for the second mass to charge ratio indicates that ions having this mass to charge ratio are more abundant in the first MSMS analysis than in the survey mass spectral data.

26. A mass spectrometer comprising:an ion source;a fragmentation or reaction device;a mass analyser; andcontrol circuitry configured to control the mass spectrometer to:(a) operate the mass spectrometer in a survey mode in which ions are mass analysed by the mass analyser so as to obtain survey mass spectral data;(b) perform a first MSMS analysis in which ions having a first mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain first MSMS mass spectral data;(c) perform a second MSMS analysis in which ions having a second, different mass to charge ratio detected in the survey mode are fragmented or reacted in the fragmentation or reaction device and then mass analysed in the mass analyser so as to obtain second MSMS mass spectral data;(d) determine that ions having the second mass to charge ratio are detected in the first MSMS mass spectral data; and in response thereto perform one of:i) discard the second MSMS mass spectral data;ii) combine the second MSMS mass spectral data with the first MSMS mass spectral data;iii) mark the second MSMS mass spectral data as being mass spectral data from the MSMS analysis of a fragment or product ion species; oriv) determine that ion fragmentation has occurred in the survey mode.36

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