Dynamic control of accumulation time for chromatography-mass spectrometry

Abstract

A mass spectrometry procedure comprising: (a) eluting a sample from a chromatography system; (b) calculating a desired maximum duration of mass analysis scans (Dmax) for the sample eluting from the chromatography system based on the duration of a chromatographic peak of the sample while eluting from the chromatography system, a minimum number (M) of mass analysis scans to be performed per chromatographic peak, and a number (N) of target analytes to be identified in the sample eluting from the chromatography system at that time; (c) calculating a maximum accumulation time of sample ions (Amax) based on the desired maximum duration of the mass analysis scans (Dmax); (d) ionizing the sample to generate sample ions using an ion source; (e) guiding the sample ions along an ion pathway from the ion source to a mass analyzer;(f) Performing a first set of mass analysis scans, each of the first set of mass analysis scans comprising: accumulating a fraction of sample ions at a location along the ion trajectory, the fraction of sample ions being accumulated for a duration not exceeding the maximum accumulation time of sample ions (Amax); and mass-analyzing the fraction of sample ions using the mass analyzer (110), wherein the mass analyzer (110) is a Fourier transform mass analyzer or a time-of-flight mass analyzer.

Description

Territory of Revelation The present disclosure relates to mass spectrometry. In particular, the present disclosure relates to methods and systems for mass spectrometry, including a Fourier transform mass spectrometer or a time-of-flight mass spectrometer. General state of the art Some mass analyzers may use image stream detection of ions to analyze an ion sample. In particular, some mass analyzers can use the Fourier transform of the acquired image stream to determine the frequency and / or mass spectrum of the ions. Such mass analyzers are commonly known as Fourier-transform mass analyzers. Fourier-transform mass analyzers generally include an ion capture device to capture an ion bunch as part of the mass analysis. It may be desirable to control the ion population within the ion capture device to limit space charge effects. Some mass analyzers can measure the time of flight of an ion sample to analyze the ions. Such mass analyzers are commonly known as time-of-flight (TOF) mass analyzers. TOF mass analyzers generally include an ion capture device to accumulate an ion bunch for injection into the TOF mass analyzer. It may be desirable to control the ion population within the ion capture device to limit space charge effects. The ion population to be accumulated in an ion-capture device of a mass analyzer can be controlled using an automatic gain control (AGC) system. For example, an AGC system, as described in US 5,107,109 A, can be used to control the ion population in an ion trap. In particular, an AGC system can attempt to control the accumulation of ions in an ion trap so that the number of ions (ion population) does not reach a level at which space charge effects become significant. AGC systems can aim to control the duration per packet over which ions are injected from an ion source and accumulate in the ion trap to ensure that the ion population per packet is generally consistent. Mass analyzers, such as Fourier transform mass analyzers and time-of-flight (TOF) mass analyzers, can be used to analyze samples supplied by a chromatography system. Chromatography systems are particularly useful for analyzing complex samples containing multiple different analyte molecules. When an analyte molecule elutes from a chromatography system, the rate at which it is eluted can vary over the duration of a chromatographic peak. For example, the rate at which a sample analyte elutes from a chromatography system can change significantly over the duration of the chromatographic peak, from a negligible value to a peak flow rate and back again to a negligible value. Varying the rate at which analyte ions are fed to an ion capture device of a Fourier transform mass analyzer or a TOF mass analyzer presents a challenge for AGC systems. If the flow rate of analyte ions to an ion capture device is very low (e.g., negligible), it can take a significant amount of time for the desired number of ions to accumulate in the ion trap. Conversely, at a relatively low rate of ions fed to the ion capture device, the accumulation time for the device to reach a desired ion population can be relatively long. In some known AGC systems, the system may include an upper limit on the time required to accumulate ions in an ion capture device. For example, at the start of a bulk analysis experiment, a user might specify a maximum injection time for the ion capture device. This maximum injection time sets a limit on the duration for which ions are injected into the ion capture device before scanning by the bulk analyzer (i.e., the time spent accumulating an ion packet in the ion capture device). Therefore, if the flow rate of analyte ions (e.g., from a chromatography system) is relatively low or negligible, the AGC system may stop ion accumulation once the maximum injection time is reached.Accordingly, the maximum injection time of an AGC system can ensure that a minimum scan rate for the mass analyzer is effectively specified by a user at the beginning of each trial. US 2018 / 0 224 406 A1 concerns the data-independent analysis of organic and, in particular, biological samples such as proteins, peptides, metabolites, lipids, and the like. WO 2013 / 171 554 A1 concerns a data-independent analysis of samples using the SWATH method. Brief description of the invention According to a first aspect of the disclosure, a mass spectrometry method according to claim 1 is provided. In some embodiments, the mass analyzer can be a Fourier transform mass analyzer, a time-of-flight mass analyzer, or an ion trap mass analyzer. Advantageously, according to the first aspect, the method performs a first set of mass analysis scans (scans) using a mass analyzer (which in some embodiments may be a Fourier transform mass analyzer or a time-of-flight (ToF) mass analyzer). For each of the scans of the first set of scans, a fraction of the sample ions is accumulated at a location along the ion trajectory between the ion source and the mass analyzer. For example, in the case of a ToF, a fraction of ions may be accumulated in an ion capture device, which subsequently injects ion bunches into the ToF. In the case of a Fourier transform mass analyzer such as an orbital trap mass analyzer, the fraction of ions may be accumulated in the orbital trap mass analyzer prior to scanning.As such, the sample ions can be accumulated in an ion capture device that is separate from the mass analyzer, or the sample ions can be accumulated in the mass analyzer. As discussed above, the rate at which the sample (i.e., the sample molecules) elutes from the chromatography system can vary over several orders of magnitude. Consequently, the rate at which sample ions can accumulate varies over the duration of the chromatography period. To characterize a chromatographic peak of a sample as it elutes from a chromatography system, it is desirable to perform a minimum number of scans over the duration of the chromatographic peak. Thus, according to the first aspect of the disclosure, the method determines a desired maximum duration of mass analysis scans (scan duration) for the first set of scans, based on an expected duration of the chromatographic peak and the minimum number of scans to be performed. Based on this determination, the method then sets a maximum accumulation duration based on the desired maximum scan duration.The maximum accumulation time sets an upper limit for the time spent accumulating each fraction of the ions to be analyzed by the mass analyzer, ensuring that the first set of mass analysis scans is performed at a minimum rate sufficient to characterize the chromatographic peak, but not significantly higher than this rate. Thus, according to the first aspect, the method provides a way to control a maximum accumulation time (a maximum injection time) for mass spectrometer control, taking into account variations in the sample flow rate. As noted above, the rate at which the first set of scans is performed is not significantly higher than the rate sufficient to provide the desired minimum number of scans over the duration of the chromatographic peak. Therefore, according to the procedure outlined in the first aspect, the first set of bulk analysis scans can be performed with the longest possible maximum accumulation time in order to try to maximize the number of sample ions accumulated in bulk analysis scans whose duration is limited by the maximum accumulation time. The method described in the first aspect can be particularly useful for analyzing complex samples where a number of target analytes need to be identified. In some embodiments, the method can be configured to identify a target analyte based on the duration of the chromatographic peak. In some embodiments, a multitude of target analytes to be identified can elute over the duration of a trial. In some trials, the multitude of target analytes to be identified can elute at different times (i.e., different chromatographic peaks). Thus, the method of the first aspect can determine a suitable maximum accumulation time for the duration of the trial. In some other trials, a multitude of target analytes can elute during the same chromatographic peak, or a multitude of chromatographic peaks of different target analytes can overlap in time. Therefore, according to the invention, the desired maximum scan time is calculated based on the number of target analytes to be identified in the sample eluting from the chromatography system at that time.Accordingly, the procedure of the first aspect can dynamically update the desired maximum scan duration (and maximum accumulation time) over the duration of a trial to reflect changes in the number of target analytes to be identified at any given time, thereby ensuring that a minimum number of scans are performed over the duration of the chromatographic peak for each of the target analytes. In some embodiments, the mass analyzer can be configured to analyze more than one target analyte per mass analysis scan. As such, the mass analyzer can be capable of multiplexing the analysis of a large number of target analytes. Thus, in some embodiments, variations in the number of target analytes eluting from the chromatography system can be accommodated by multiplexing the analysis of one or more target analytes per mass analysis scan. In some embodiments, performing a mass analysis scan to identify more than one target analyte can increase the time required to perform the mass analysis scan. Therefore, in some embodiments, the method can accommodate variations in the time required to perform the mass analysis scan due to multiplexing by adjusting the maximum accumulation time accordingly.In some embodiments, the maximum accumulation time is also calculated based on the number of target analytes to be identified per bulk analysis scan. Accordingly, the method can attempt to ensure that bulk analysis scans are performed with the desired scan duration, while taking into account changes in the amount of multiplexing over the course of a trial. In some embodiments, the method can take into account the number of target analytes to be identified in the sample currently eluted from the chromatography system and the number of target analytes to be identified per mass analysis scan. The number of target analytes to be identified per mass analysis scan can be determined either by a user setting or by a physical limitation of the mass analyzer. For example, a mass analyzer may be configured to identify no more than three target analytes per mass analysis scan. In experiments where the number of target analytes to be identified in the sample currently eluted from the chromatography system does not exceed the number of target analytes to be identified per mass analysis scan, the desired maximum scan duration is calculated according to the first aspect.If the number of target analytes to be identified in the sample currently eluted from the chromatography system exceeds the number of target analytes to be identified per bulk analysis scan, at least one additional bulk analysis scan must be performed to analyze all target analytes. Thus, the procedure can update the desired maximum scan duration to ensure that the required number of bulk analysis scans are performed over the duration of a chromatographic peak for each target analyte.As such, in some embodiments, the method can calculate a desired maximum scan duration for the sample eluting from the chromatography system based on the following: the duration of a chromatographic peak of the sample while it is eluting from the chromatography system, the number of target analytes to be identified in the sample currently eluting from the chromatography system, the minimum number of scans to be performed per chromatographic peak, and the number of target analytes to be identified per mass analysis scan. In some embodiments, the mass spectrometry method according to the first aspect may further comprise: (g) calculating an average scan duration for the first set of mass analysis scans, wherein, if the average duration of the first set of scans is greater than the desired maximum scan duration, the maximum accumulation duration is reduced to provide a set maximum accumulation duration; and (h) performing a second set of mass analysis scans, wherein each of the second set of mass analysis scans comprises: accumulating a fraction of sample ions at a location along the ionic trajectory, wherein the fraction of ions is accumulated for a duration that does not exceed the set maximum accumulation duration; and mass-analyzing the fraction of sample ions using the mass analyzer. As a person skilled in the art will recognize, the duration of a bulk analysis scan can be affected by the time required to accumulate a fraction of sample ions (a packet of sample ions), time-invariant overheads, and variable overheads. As discussed above, the time required to accumulate a fraction of sample ions can depend on the sample ion flow rate from the sample ion source and the maximum accumulation time. The analyzer's time-invariant overheads include fixed-duration processes that can be performed during each bulk analysis scan. For example, time-invariant overheads include time-bound processes that are performed on every scan, such as a fixed time interval during which the bulk analyzer performs the scan and analyzes the data. Variable overheads include processes with variable time and / or variable frequency (i.e., processes that run at varying intervals).(those that are not performed on every scan). Examples of variable overheads include: pre-scans performed by the mass analyzer, polarity switching processes, switching of external electric field sources, etc. In some embodiments, the possible presence of variable overheads during the execution of a set of mass analysis scans makes it difficult to accurately determine a maximum accumulation time at the beginning of the first set of scans that results in a scan duration not exceeding the desired maximum scan duration. Therefore, the procedure according to step (g) can check whether the maximum accumulation time calculated in step (b) (i.e., an initial prediction) results in the first set of scans being performed within the desired duration. Often, the first set of scans can include one or more scans performed at the beginning of a chromatographic peak, so the criteria for the maximum accumulation time can be met. Thus, it is possible that the average duration of the first set of scans is close to the desired maximum duration.In some cases, the average duration of the first set of scans may exceed the desired maximum scan duration due to the presence of time-varying overheads. As such, the procedure may determine that the first set of scans is not performed at a rate sufficient to provide a minimum number of scans over the duration of the chromatographic peak. To attempt to adjust the rate at which scans are performed, the procedure can calculate a set maximum accumulation time by decreasing the maximum accumulation time. The procedure then performs a second set of mass analysis scans with the set maximum accumulation time. Accordingly, the second set of scans can be performed with an average scan duration that is shorter than the first set of scans, thereby increasing the number of scans performed over the duration of the chromatographic peak. The invention according to the first aspect includes a plurality of steps designated by letters. It is understood that these steps can be carried out simultaneously or in parallel, if possible. According to a second aspect of the invention, a mass spectrometer is provided for mass analysis of a sample according to claim 11. In some embodiments, the mass analyzer can be a Fourier transform mass analyzer, a time-of-flight mass analyzer, or an ion trap mass analyzer. Accordingly, the second aspect of the invention provides a mass spectrometer capable of implementing the methods described in the first aspect of the disclosure. Thus, the second aspect of the invention may include one of the optional features, and all the associated advantages of the first aspect apply equally to the corresponding features of the second aspect. The control system of the second aspect is configured to execute a number of numbered steps. It is understood that these steps can be performed simultaneously or in parallel, if possible. Therefore, the control system of the mass spectrometer according to the second aspect of the invention is also configured to calculate the desired maximum duration of the mass analysis scans, based on the number of target analytes to be analyzed over the duration of the chromatographic peak. Brief description of the drawings The invention can be implemented in practice in many ways, and one specific embodiment is now described by way of example with reference to the figures, wherein: - Fig. 1 shows a schematic arrangement of a mass spectrometer suitable for carrying out methods according to embodiments of the present invention; - Fig. 2 shows a graphical representation of the variation of the maximum accumulation time over the duration of a chromatographic peak according to an embodiment of the invention; - Fig. 3 shows a graphical representation of the variation of the maximum accumulation time for a mass analysis experiment that includes a plurality of chromatographic peaks according to an embodiment of the invention; - Fig. 4 shows how the maximum accumulation time Amax for the mass spectrometer of Fig. 1 can be calculated depending on the type of experiment to be carried out. Detailed description In this document, the term mass can refer to the mass-to-charge ratio m / z. Fig. 1 shows a schematic arrangement of a mass spectrometer 10 suitable for carrying out methods according to embodiments of the present invention. The arrangement in Fig. 1 schematically represents the configuration of the Q-Exactive® mass spectrometer from Thermo Fisher Scientific, Inc. In Fig. 1, a sample to be analyzed (for example, from an autosampler) is fed into a chromatography device, such as a liquid chromatography (LC) column (not shown in Fig. 1). One such example of an LC column is the monolithic ProSwift column from Thermo Fisher Scientific, Inc., which provides high-performance liquid chromatography (HPLC) by passing the sample, carried in a mobile phase, under high pressure through a stationary phase of irregularly shaped or spherical particles. In the HPLC column, sample molecules elute at different rates depending on their degree of interaction with the stationary phase. A chromatograph can be constructed by measuring the amount of sample molecules eluting from the HPLC column over time using a detector (for example, a mass spectrometer). Sample molecules eluting from the HPLC column are detected as peaks above a baseline measurement on the chromatograph. Where different sample molecules exhibit different elution rates, a multitude of peaks can be detected on the chromatograph. Preferably, individual sample peaks are separated from other peaks in the chromatogram in time so that different sample molecules do not interfere with each other. In a chromatograph, the presence of a chromatographic peak corresponds to the time period during which the sample molecules are present at the detector. As such, the width of a chromatographic peak is equivalent to this time period. Preferably, a chromatographic peak has a Gaussian profile, or it can be assumed to have a Gaussian profile. Accordingly, the width of the chromatographic peak can be calculated based on a number of standard deviations calculated from the peak. For example, a peak width can be calculated based on four standard deviations of a chromatographic peak. Alternatively, a peak width can be calculated based on the width at half the maximum peak height. Other methods known in the art for determining the peak width may also be suitable.As such, the MS1 data acquired according to the inventive method thus provide a mass chromatogram of the sample eluted from the column. The sample molecules separated by liquid chromatography are then ionized using an electrospray ionization (ESI) source 20 at atmospheric pressure. Sample ions then enter a vacuum chamber of the mass spectrometer 10 and are guided through a capillary 25 into an RF-only s-lens 30. The ions are focused by the s-lens 30 into an injection flatpole 40, which injects the ions into a curved flatpole 50 with an axial field. The curved flatpole 50 guides (charged) ions along a curved path, while unwanted neutral molecules, such as carried solvent molecules, are not guided along the curved path and are lost. An ion gate (TK lens) 60 is arranged at the distal end of the bent flat pole 50 and controls the passage of ions from the bent flat pole 50 into a quadrupole mass filter 70 arranged downstream of the process. The quadrupole mass filter 70 is typically, but not necessarily, segmented and serves as a bandpass filter, allowing the passage of a selected mass number or a limited mass range while excluding ions with other mass-to-charge ratios (m / z). The ions then pass through an array of quadrupole exit lens / half-lens 80 and into a transfer multipole 90. The transfer multipole 90 guides the mass-filtered ions from the quadrupole mass filter 70 into a curved trap (C-trap) 100. The C-trap 100 has longitudinally oriented, curved electrodes supplied with RF voltages and end caps supplied with DC voltages. The result is a potential well extending along the curved longitudinal axis of the C-trap 100. In a first operating mode, the end cap DC voltages are applied to the C-trap, so that ions arriving from the transfer multipole 90 accumulate in the potential well of the C-trap 100, where they are cooled. Cooled ions are located in a cloud towards the bottom of the potential well and are then ejected orthogonally from the C-trap 100 to the mass analyzer 110. The number of ions accumulated in the C-trap 100 (i.e., the ion population) determines the number of ions subsequently ejected from the C-trap 100 into the mass analyzer 110. The C-trap 90 can eject ions as a packet of ions into the mass analyzer 110. To control the accumulation of ions in the C-trap 100, the controller 130 can include an automatic gain control (AGC) portion configured to control the number of ions in each packet ejected from the C-trap 100 into the mass analyzer 110. Specifically, the AGC portion of the controller can be designed to prevent the number of ions in a packet from exceeding a certain limit to avoid space charge effects. To control the number of ions in a packet, the AGC portion of the controller 130 can also control the duration for which the C-trap 100 accumulates ions. Further information on AGC systems suitable for use with a C-trap 100 and an orbital trap mass analyzer 110 is included in US 2016 / 0233078A1.To ensure that the AGC component of the controller does not accumulate ions over a longer period when the rate of sample ions supplied to the C-trap 100 is relatively low, the controller 130 is also configured to set an upper limit on the duration for which the C-trap 1000 can accumulate sample ions for each packet. This upper limit is the maximum accumulation time for the mass spectrometer of Fig. 1. In some embodiments, the time spent injecting sample ions from the transfer multipole 90 into the C-trap 100 (i.e., an injection time) can also be considered the time spent accumulating ions in the C-trap 100. As such, a setting for the maximum injection time of a mass spectrometer can be viewed as a setting that controls a maximum accumulation time for the ion-capture device (C-trap 100) into which the ions are injected. Accordingly, a controller 130 can control the duration for which ions accumulate in the C-trap 100 in order to control the ion population to be analyzed by the mass analyzer. In some embodiments, the accumulation time of ions in the C-trap 100 can be a rate-limiting step for performing a mass analysis scan. As shown in Fig. 1, the mass analyzer 110 is an orbital trap mass analyzer 110, similar to the Orbitrap® mass analyzer sold by Thermo Fisher Scientific, Inc. The orbital trap mass analyzer 110 has an off-center injection port, and the ions are injected as coherent packets through the off-center injection port into the orbital trap device 110. Ions are then trapped within the orbital trap mass analyzer 110 by a hyperlogarithmic electric field and subjected to back-and-forth motion in a longitudinal direction as they orbit the inner electrode. The axial component (z-component) of the motion of the ion bunches in the orbital trap mass analyzer 110 is (more or less) defined as simple harmonic motion, where the angular frequency in the z-direction is related to the square root of the mass-to-charge ratio of a given ion species. Thus, ions are separated over time according to their mass-to-charge ratio. Ions in the orbital trap mass analyzer 110 are detected using an image detector (not shown in Fig. 1) that generates a transient in the time domain containing information about all ion species as they pass through the image detector. The transient is then subjected to a fast Fourier transform (FFT), which produces a series of peaks in the frequency domain. From these peaks, a mass spectrum can be generated that represents the abundance / ion intensity versus m / z. In the configuration described above, the sample ions (more specifically, a subset of the sample ions within a relevant mass range, selected by the quadrupole mass filter) are analyzed by the orbital trap mass analyzer 110 without fragmentation. The resulting mass spectrum is designated MS1. MS / MS (or more generally MSn) can also be performed by the mass spectrometer 10 of Fig. 1. To achieve this, precursor sample ions are generated and fed to the quadrupole mass filter 70, where a subsidiary mass range is selected. The ions exiting the quadrupole mass filter 70 are cooled again in the C-trap 100, but then ejected axially to a fragmentation chamber or cell 120. The fragmentation chamber 120 in the mass spectrometer 10 of Fig. 1 is a device for higher-energy collisional dissociation (HCD), into which a collision gas is supplied. Precursor ions arriving in fragmentation chamber 120 are bombarded with molecules of high-energy collision gas, leading to the fragmentation of the precursor ions into fragment ions.The fragment ions are then ejected from the fragmentation chamber 120 back to the C-trap 100, where they are recaptured and cooled in the potential well. Finally, the fragment ions captured in the C-trap are ejected at a right angle to the orbital trap device 110 for analysis and detection. The resulting mass spectrum of the fragment ions is designated MS2. Although an HCD fragmentation chamber 120 is shown in Fig. 1, other fragmentation devices can be used instead, employing methods such as collision-induced dissociation (CID), electron capture dissociation (ECD), electron transfer dissociation (ETD), photodissociation, and so on. The “dead end” configuration of the fragmentation chamber 120 in Fig. 1, wherein precursor ions are axially ejected from the C-trap 100 in a first direction towards the fragmentation chamber 120 and the resulting fragment ions are returned to the C-trap 100 in the opposite direction, is described in more detail in WO 2006 / 103 412 A2. The mass spectrometer 10 is controlled by a controller 130, which is configured, for example, to control the timing for the ejection of the capture components, to set the appropriate potentials at the electrodes of the quadrupole, etc., to focus and filter the ions, to capture the mass spectral data from the orbital trap device 110, to control the sequence of the MS1 and MS2 scans, and so on. It is understood that the controller 130 can include a computer that can be operated according to a computer program containing instructions to cause the mass spectrometer to perform the steps of the method according to the present invention. It is understood that the specific arrangement of the components shown in Fig. 1 is not essential for the methods described below. In fact, the methods described in this disclosure can be implemented on any controller for controlling the injection of ions into a Fourier transform mass analyzer, a TOF mass analyzer, or an ion trap mass analyzer. Furthermore, the person skilled in the art will recognize that the mass spectrometer 10 of Fig. 1 is an example of a device in which ions are transported from an ion source (ESI source 20) to a mass analyzer (110) of an ion transport device. As such, in the embodiment of Fig. 1, the capillary 25, the S-lens 30, the injection flat pole 40, the bent flat pole 50, the ion gate 60, the quadrupole mass filter 70, the exit lens / half-lens assembly 80, the transfer multipole 90, and the C-trap 100 are examples of ion transport devices. The ion transport devices are configured to transport sample ions from the ESI ion source 20 to the mass analyzer 110. In other embodiments, other configurations of ion transport device(s) can be used to transport ions from an ion source to a mass analyzer. An exemplary embodiment of the method is now described with reference to Fig. 2 and Fig. 3, in which sample molecules are supplied from a liquid chromatography (LC) column as part of the exemplary apparatus described above (as shown in Fig. 1). According to embodiments of the invention, the controller 130 can calculate a desired maximum scan duration (D) based on input information regarding the experiment to be performed. The input information includes an expected chromatographic peak duration (W), the number of target analytes (N) to be analyzed over the duration of the chromatographic peak, and the minimum number of bulk analysis scans to be performed over the duration of a chromatographic peak (M). Before starting an experiment, a user can specify one or more of the variables W, N, and M. Alternatively, the controller 130 can look up suitable values ​​for one of W, N, and / or M from a library of predefined values ​​based on the type of experiment being performed. For example, a user can provide the controller 130 with information regarding a target analyte to be identified in the sample, and the controller 130 can select appropriate values ​​for W, N, and M accordingly. Based on the input information for W, N, and M, the controller 130 is configured to calculate the desired maximum scan duration Dmax. In some embodiments of the invention, the controller can calculate Dmax using the following equation: Based on the calculated desired maximum scan duration Dmax, the controller 130 can then calculate a maximum accumulation time (Amax) for the accumulation of ions in the C-trap for each mass analysis scan. In some embodiments, the controller 130 can determine Amax based on Dmax and any invariant overheads associated with performing a mass analysis scan. For example, time-invariant overheads may include the time required to inject ions from the C-trap 100 into the mass analyzer 110, or the time required by the mass analyzer to perform the mass analysis scan. In some embodiments, the C-trap 100 may be configured to accumulate a packet of ions for the next mass analysis scan in parallel with the mass analyzer 110 performing a mass analysis scan (parallel acquisition). Accordingly, in some embodiments, the time-invariant overheads may be negligible relative to Dmax. For example, in some embodiments, the controller 130 may determine that Amax is essentially equal to Dmax. In the embodiment of Fig.1. The time-invariant overheads can be approximately 10 ms. As such, the controller can calculate Amax as Amax = Dmax - 0.01 s (i.e., Dmax minus a time-invariant overhead time). In some embodiments, the mass analyzer used to perform the mass analysis scans may have a minimum scan duration. Therefore, while it is possible in some embodiments to reduce the maximum accumulation time below such a minimum scan duration, this may not be desirable because it does not further increase the rate at which mass analysis scans are performed. Thus, in some embodiments, the controller 130 may include a minimum desired scan duration setting (Dmin). In other embodiments, the controller may define a minimum accumulation time setting (Amin) below which the maximum accumulation time Amax must not be reduced. In some embodiments, the relationship between Dmax and Amax is defined such that the limits Dmin and Amin can be used interchangeably.For example, in the embodiment of Fig. 1, where the C-trap 100 can be configured to accumulate an ion packet for the next mass analysis scan in parallel with the mass analyzer 110 performing a mass analysis scan, the parallel acquisition method may require a minimum time interval per scan (i.e., the mass analyzer 110 determines a value for Dmin). Accordingly, the controller 130 can be configured to ensure that the C-trap 100 accumulates ions for the minimum time interval. In some embodiments, Dmin may be at least 10 ms, 20 ms, 50 ms, 100 ms, or 150 ms, although the actual value may depend on the mass analyzer used. In the embodiment of Fig. 1, Dmin may be 128 ms. The controller 130 can calculate Dmax and Amax before the start of the experiment, or the controller 130 can calculate Dmax and Amax during the experiment. According to this disclosure, a mass analysis scan refers to a process in which the mass analyzer 110 is used to analyze an ion packet to obtain a mass spectrum that provides information regarding the mass-to-charge ratios of the ion packet. In some embodiments, an AGC portion of the controller 130 may also be configured to control the mass spectrometer 10 to perform other types of scans that are not mass analysis scans. For example, the AGC may be configured to control the mass spectrometer 10 to perform one or more pre-scans during an experiment to obtain additional information for controlling the mass spectrometer 10. According to the procedure, the controller 130 is configured to cause the ESI ion source 20 to ionize sample molecules received from the LC column in order to generate sample ions. The controller is also configured to control the ion transport devices 25, 30, 40, 50, 60, 70, 80, and 90 to guide the sample ions along the ion pathway from the ion source of the C-trap 100, where the sample ions are accumulated. If the rate of sample ions supplied to the C-trap 100 is relatively high, the AGC component of the controller 130 can control the duration for which ions accumulate in the C-trap 100 to ensure that the ion population of each ion packet supplied to the mass analyzer 110 is relatively consistent. If the rate of sample ions supplied to the C-trap 100 is relatively low, the C-trap 100 can accumulate ions for a duration up to the maximum accumulation time, Amax. Once the maximum accumulation time is reached, the controller 130 is configured to eject the accumulated ion packet into the mass analyzer 110 so that the ion packet can be scanned. The mass analyzer 110 analyzes the ion packet, while the C-trap 100 accumulates the next ion packet for mass analysis. Thus, the controller 130 is configured according to the procedure to control the mass spectrometer 10 to perform an initial set of mass analysis scans. By ensuring that each mass analysis scan is performed with a maximum accumulation time calculated based on the desired scan duration, the procedure can provide a scan frequency suitable for characterizing a chromatographic peak of the sample. In a further embodiment of the invention, the controller 130 can also be configured to account for time-varying overheads that may occur during the experiment. A graphical representation of this further embodiment is shown in Fig. 2. The experiment of Fig. 2 is performed on a mass spectrometer 10, as shown in Fig. 1. The graph in Fig. 2 shows the extracted ion current (XIC), the actual accumulation time, the maximum accumulation time set by the controller 130, and the actual mass analysis scan duration for each mass analysis scan performed during the experiment. The extracted ion current for each mass analysis scan is the extracted ion current measured by the orbital trap mass analyzer 110, which is representative of the order of magnitude of the ion population for each mass analysis scan. For the experiment shown in Fig. 2, a sample with a chromatographic peak width at FWHM (W) of 1 s is to be measured, and a target analyte is to be identified (N = 1). It is desirable that at least 5 mass analysis scans be performed over the duration of the chromatographic peak (M = 5). Accordingly, Dmax can be calculated from the controller 130 based on equation (1) as the desired maximum scan duration of 200 ms. For the experiment to be performed, it can also be specified that the results of the experimental setup have time-invariant overheads of 10 ms (e.g., to account for ion injection and scan time overheads). Thus, a maximum accumulation time Amax for the first set of scans can be determined to be 190 ms. As shown in Fig. 2, the first three scans (a first set of scans) are performed with Amax = 190 ms. In some experiments, the first set of scans, performed at the beginning of the experiment, may have a relatively low sample ion flow rate, resulting in the actual accumulation time for each scan in the first set being approximately equal to the maximum accumulation time, Amaxist. For example, as shown in the experiment of Fig. 2, the XIC for each of the first three scans is relatively low (approximately 0.1 au). Consequently, considering time-invariant and / or variable overheads, the average duration for the first set of scans may exceed the desired duration, Dmax. According to a further embodiment, the controller 130 can be configured to calculate an average scan duration for the first set of mass analysis scans. If the average duration of the first set of scans is greater than the desired maximum scan duration, the controller is configured to reduce the maximum accumulation duration to provide a set maximum accumulation duration (Amax') for the C-trap. The controller 130 is then configured to cause the mass spectrometer 10 to perform a second set of mass analysis scans using the set maximum accumulation duration. According to a further embodiment, the controller 130 can calculate the average scan duration for the first set of mass analysis scans based on the first X mass analysis scans performed during the experiment, where X is at least 3. For example, X can be 3, 4, 5, or 7. The controller 130 can calculate the set accumulation time by reducing Amaxum by a predetermined amount. For example, the controller 130 can reduce Amaxum by at least 1 ms. In some embodiments, the controller 130 can reduce Amaxum by 5 ms, 10 ms, or 20 ms. In some embodiments, the controller 130 can reduce Amaxum by a scaling factor k. As such, Amax' = Amax * k, where k < 1. For example, k can be 0.99, 0.95, 0.9, or 0.8. Thus, as shown in Fig. 2, the controller 130 determines that the maximum accumulation time selected for the first set of scans results in an average scan duration that exceeds the desired scan duration. Accordingly, the controller 130 adjusts the maximum accumulation time to attempt to reduce the average scan duration for the second set of scans. As shown in Fig. 2, the controller calculates Amax' = 190 ms * 0.9 = 171 ms (i.e., k = 0.9), thus providing a set maximum accumulation time. Thus, a second set of bulk analysis scans can be performed using the Amax'. As shown in Fig. 2, the XIC remains at approximately 0.1 for bulk analysis scans 4-6, so that each bulk analysis scan accumulates sample ions up to the Amax'. Accordingly, changing the Amax' reduces the average scan time, thereby increasing the number of scans performed per chromatographic peak. In some embodiments, the controller 130 can continue to monitor the average scan duration throughout the entire experiment and make further adjustments to the maximum injection time as needed to ensure that the desired minimum number of criteria for the mass analysis scan (M) is met. For example, when the second set of scans is performed, the controller 130 can calculate an average scan duration for the previous n mass analysis scans. If the average duration of the previous n mass analysis scans is greater than the desired maximum scan duration, the controller can further reduce the set maximum accumulation duration. For example, the controller can further reduce the set maximum accumulation duration in a manner similar to the settings described above. For example, the controller 130 can reduce the set maximum accumulation duration using the scaling factor k. The average scan duration for the previous n mass analysis scans can be the previous three scans of the second set of mass analysis scans (i.e., n = 3). In some embodiments, n can be an integer that is at least 2, 3, 4, or 6.In some embodiments, n can be calculated based on the number of target analytes to be identified (N). For example, n can be determined by the controller as a multiple of N (i.e., n = jN, where j is at least 2, 3, 4, or 5). In particular, n can be determined by the controller as five times N. In the embodiment shown in Fig. 2, n = 3. Accordingly, after the first three mass analysis scans of the second set of scans (i.e., after mass analysis scan 6), the controller 130 calculates an average scan duration for the first three mass analysis scans of the second set of mass analysis scans (i.e., the fourth to sixth mass analysis scans shown in Fig. 2). As shown in Fig. 2, the average scan duration for mass analysis scans 4 to 6 remains above the desired scan duration. Consequently, the maximum accumulation time for the fourth mass analysis scan of the second set of mass analysis scans (i.e., the seventh scan) is further reduced. Thus, as shown in Fig. 2, the maximum accumulation time can be set until the mass analysis scan time falls below the desired maximum mass analysis scan time (or the average scan time falls below the desired maximum scan time). By continuously adjusting the maximum accumulation time, the controller 130 can ensure that the number of mass analysis scans performed over the duration of a chromatographic peak corresponds to the desired setting M entered by a user. For some experiments, a sample containing a variety of target analyte molecules can be mass-analyzed using the mass spectrometer 10. With such samples, the sample may elute from the chromatography system with a multitude of chromatographic peaks distributed over time, each peak potentially having different widths (i.e., W can vary per target analyte). Furthermore, some target analyte molecules may elute from the chromatography system simultaneously (or overlapping in time), so the number of target analyte molecules to be analyzed at any given time during the experiment may be greater than 1 (i.e., N ≥ 1). Consequently, a single fixed maximum accumulation time (i.e., a fixed maximum injection time) may not be suitable for characterizing all chromatographic peaks present in the experiment. In some embodiments, the controller 130 can be configured to dynamically adjust the maximum accumulation time throughout an entire experiment. As such, a mass spectrometry procedure can be provided essentially as discussed above, wherein the sample eluting from the chromatography system involves providing a multitude of chromatographic peaks of the sample over time. Accordingly, the controller 130 can further be configured to update the desired maximum scan duration (Dmax) and maximum accumulation duration (Amax) over time based on the chromatographic peaks eluting from the chromatography system. Information on each of the target analytes expected in the sample (e.g., the associated chromatographic peak width W, the time at which elution is expected (i.e., the retention time for the chromatography system)) can be provided by a user before the start of an experiment. For example, Fig. 3 shows another embodiment of the invention in which the desired maximum scan duration is initially calculated and subsequently updated (twice) over the duration of a trial in order to analyze a large number of chromatographic peaks. A user can provide the controller with a configuration file containing input information for the mass spectrometry experiment to be performed. This input information can include details that identify the target analytes to be identified during the experiment. For each target analyte to be identified, the input information can specify the target analyte's mass-to-charge ratio and chromatography retention time information. The configuration file can also specify an expected chromatographic peak width (W) for the target analytes to be identified. The peak width can be specified per target analyte, or a global value can be provided for all target analytes (i.e., the same value of W is used for all target analytes). The chromatography retention time information for each target analyte can include information regarding the expected retention time for the target analyte in the chromatography unit connected to mass spectrometer 1. Based on the expected retention time, the controller can determine when each target analyte is expected to be active (i.e., eluted from the chromatography unit) during the experiment. In some embodiments, the chromatography retention time information can define a period over which each target analyte is expected to elute from the chromatography apparatus. This period can be defined by a start time for analyte elution and an end time for analyte elution. It can be specified that some target analytes are active throughout the entire duration of the experiment; in this case, the chromatography retention time for the target analyte may not include a start time for analyte elution and no end time for analyte elution. For example, the chromatography information for three target analytes may include the following: Table 1 Table 1 240,1158799 477,2303108119 314,1158093 Based on the chromatography retention time information for each target analyte, the controller 130 can determine the number of target analytes to be identified in the sample (N) at a given time point in the experiment. As such, the controller can update the value of N based on the number of target analytes expected to be active at any given time point in the experiment, based on the chromatography retention time information. After updating the number of target analytes N, the controller 130 can recalculate the desired maximum mass analysis scan duration DMAX (and subsequently AMAX and AMAX' according to the procedures described above) to reflect the change in the experiment. Thus, the controller 130 can dynamically update the maximum accumulation time for performing mass analysis scans during the course of the experiment. For example, for the three target analytes shown in Table 1 above, the controller 130 can determine at time t = 82 s that one target analyte is currently active (N = 1). At time t = 90, the controller 130 can determine that two target analytes are currently active (N = 2). The controller 130 can then repeat the update process to determine a maximum accumulation time (AMAX or AMAX') according to embodiments of this disclosure. Each time the desired maximum mass analysis scan duration DMAX is recalculated, the controller 130 can be configured to repeat the scaling process to set AMAX'. In some embodiments of the disclosure, the controller 130 can also be configured to update the maximum accumulation duration setting only when a change in the number of active targets (N) exceeds a threshold. For example, the controller 130 can be configured to update the maximum accumulation duration in response to a change in the value of N that is at least 20% of the current value. In other embodiments, the threshold for updating DMAX can be at least 25%, 30%, 35%, 40%, or 50% of the current value of N. For example, Fig. 3 shows a graphical representation of AMAX and AMAX' during a trial in which the number of active targets (N) changes over the duration of the trial. The threshold for updating DMAX is at least 35% of the current value of N. As shown in Fig. 3, N is initially set to 3 at the start of the trial. Over the first 6 scans of the trial, a value for AMAX' is calculated, providing the desired number of mass analysis scans (M) over the duration of a chromatographic peak. For scans from 0 to 100, the number of active targets varies between 2 and 4, but due to the threshold, DMAX (and therefore AMAX) is not updated. Before performing scan 100, controller 130 determines that N has increased to 5, which is above the threshold. Consequently, controller 130 recalculates DMAX and AMAX, and then AMAX', using the new value for N.Thus, the controller can dynamically adjust the maximum accumulation time to adapt to changes in the number of target analytes expected over the course of a trial. It is shown that a further update of N occurs at the number of 200 bulk analysis scans, at which point the controller detects that two target analytes are now active. Fig. 4 provides another diagram showing how the maximum accumulation time Amax for the mass spectrometer of Fig. 1 can be calculated depending on the type of experiment being performed. For the experiments in Fig. 4, targeted single-ion monitoring experiments are carried out on a sample with a chromatographic peak width of 3 s. The mass spectrometer 10 has a minimum accumulation time of 128 ms. In some embodiments, the mass analyzer may be capable of analyzing more than one target analyte per mass analysis scan. As such, the mass analyzer may be configured to multiplex a mass analysis scan so that more than one (i.e., multiple) target analyte(s) are analyzed in a single mass analysis scan. The amount of multiplexing to be performed per mass analysis scan may be the number of target analytes to be identified per scan. For example, the mass analyzer 110 of the mass spectrometer 10 can be capable of analyzing at least two target analytes in a single mass analysis scan. The mass analyzer 110 can also be configured to multiplex at least three, four, five, or seven target analytes in a single mass analysis scan. The controller 130 can determine the number of target analytes to be analyzed in a single mass analysis scan based on a configuration file that provides information regarding the target analytes to be analyzed during the experiment. Performing a multiplex mass analysis scan can increase the time required to perform the mass analysis scan. For example, each additional target analyte to be analyzed per mass analysis scan can increase the time required to perform the mass analysis scan by a fixed amount.Thus, for a given DMAX, an AMAX can be calculated to account for each multiplexing operation performed. For example, some mass analyzers capable of multiplexing mass analysis scans may have a time-varying overhead of a per mass analysis scan. Therefore, the maximum accumulation time can be calculated as: P is the number of target analytes to be analyzed per bulk analysis scan (i.e., the extent of multiplexing that the bulk analyzer is capable of performing). For example, for bulk analyzer 110 of Fig. 1, the time-variable overhead a may be 5 ms. In other embodiments, a may be at least 1 ms, 5 ms, 10 ms, or 20 ms. Fig. 4 shows a graphical representation of 5 different single-ion monitoring (SIM) trials with varying numbers of target analytes to be analyzed simultaneously (i.e., different N values) and different multiplexing levels (P). For all trials, the chromatographic peak width W is 3 s, and each bulk analysis scan has a time-invariant overhead of 4 ms and a time-variable overhead of 5 ms to account for multiplexing (i.e., a = 5 ms). In experiment a), a single target analyte is analyzed in a single bulk analysis scan with M = 3. Consequently, the desired maximum scan duration calculated by the controller is 1000 ms. Taking into account the overheads for performing the bulk analysis scan, AMAX for experiment a) is 991 ms. As further shown in Fig. 4, increasing the number of target analytes (N) in experiments b) and c) without performing multiplexing results in a decrease in DMAX and consequently AMAX. For example, DMAX in experiment c) when M = 3 is 333 ms. In experiments d) and e), multiplexing is performed to allow the analysis of multiple target analytes in a single bulk analysis scan. Therefore, P = 2 for experiment d) and P = 3 for experiment e). Thus, for experiments d) and e), multiple target analytes can be analyzed relative to experiment a) without changing DMAX (i.e., DMAX for experiments d) and e) is 1000 ms when M = 3). Figure 4 also shows the effect of increasing M for each of trials a), b), c), d), and e). As M increases, the controller 130 sets DMAX and consequently AMAX to provide the desired minimum number of mass analysis scans per target analyte. The mass analyzer in Figure 4 has a minimum scan duration of Dmin = 128 ms (i.e., similar to the mass analyzer 110 in Figure 1 discussed above). Therefore, as M increases, the controller does not reduce AMAX below the limit set by Dmin, as this would not further increase the rate at which the scanning is performed. For example, for trial e) with M = 25: W / M = 3000 / 25 = 120 ms, which is below Dmin. Thus, DMAX is set to 128 ms for trial e). AMAX is therefore calculated as DMAX- a*P - 4 ms = 109 ms, taking into account P = 3. In some experiments, the number of target analytes to be identified in the sample currently eluted from the chromatography system (N) may exceed the amount of multiplexing (P) for which the mass analyzer is set (or which it can actually perform). If such functionality is desired, the controller in some embodiments may be configured to take this into account when calculating the desired maximum scan time. For example, the desired maximum scan time in some embodiments may be calculated as: The `Obergr()` function is an upper bound function that returns the smallest integer greater than or equal to N / P. Thus, the controller 130 can be configured to calculate the number of mass analysis scans (`Obergr(N / P)`) required to analyze all current target analytes, taking into account the amount of multiplexing (`P`) the mass analyzer is currently set to perform. Advantageously, the present invention can be used to provide a mass spectrometer and mass spectrometry methods in which the maximum accumulation time during a mass analysis trial is controlled to provide a user with a desired minimum number of mass analysis scans per chromatographic peak and target analyte.

Claims

A mass spectrometry procedure comprising: (a) eluting a sample from a chromatography system; (b) calculating a desired maximum duration of mass analysis scans (Dmax) for the sample eluting from the chromatography system based on the duration of a chromatographic peak of the sample while eluting from the chromatography system, a minimum number (M) of mass analysis scans to be performed per chromatographic peak, and a number (N) of target analytes to be identified in the sample eluting from the chromatography system at that time; (c) calculating a maximum accumulation time of sample ions (Amax) based on the desired maximum duration of the mass analysis scans (Dmax); (d) ionizing the sample to generate sample ions using an ion source; (e) guiding the sample ions along an ion pathway from the ion source to a mass analyzer;(f) Performing a first set of mass analysis scans, each of the first set of mass analysis scans comprising: accumulating a fraction of sample ions at a location along the ion trajectory, the fraction of sample ions being accumulated for a duration not exceeding the maximum accumulation time of sample ions (Amax); and mass-analyzing the fraction of sample ions using the mass analyzer (110), wherein the mass analyzer (110) is a Fourier transform mass analyzer or a time-of-flight mass analyzer. Method according to claim 1, wherein the maximum accumulation time of sample ions (Amax) is also calculated based on a number of target analytes to be identified per mass analysis scan. Method according to claim 2, wherein the desired maximum duration of the mass analysis scans (Dmax) is also calculated based on the number of target analytes to be identified per mass analysis scan. A mass spectrometry method according to any one of claims 1 to 3, further comprising: (g) calculating an average scan duration for the first set of mass analysis scans, wherein, if the average duration of the first set of mass analysis scans is greater than the desired maximum duration of the mass analysis scans (Dmax), the maximum accumulation duration of sample ions (Amax) is reduced to provide a set maximum accumulation duration; and (h) performing a second set of mass analysis scans, wherein each of the second set of mass analysis scans comprises: accumulating a fraction of sample ions at a location along the ion trajectory, wherein the fraction of ions is accumulated for a duration that does not exceed the set maximum accumulation duration; and mass analyzing the fraction of sample ions using the mass analyzer (110). Mass spectrometry method according to claim 4, wherein the maximum accumulation time of sample ions (Amax) is reduced by a scaling factor (k) to provide the set maximum accumulation time. A mass spectrometry method according to claim 4 or claim 5, wherein performing the second set of mass analysis scans further comprises: calculating an average scan duration for the previous n mass analysis scans, wherein, if the average duration of the previous n mass analysis scans is greater than the desired maximum duration of the mass analysis scans (Dmax), the set maximum accumulation duration is further reduced, where n is an integer greater than 2. Method for mass spectrometry according to claim 6, wherein the step of calculating the average scan duration for the previous n mass analysis scans and further reducing the set maximum accumulation duration when the average duration of the previous n mass analysis scans is greater than the desired maximum duration of the mass analysis scans (Dmax) is repeated during the execution of the second set of mass analysis scans. Method for mass spectrometry according to claim 6 or claim 7, wherein n is calculated based on a multiple of the number of target analytes to be identified. A method for mass spectrometry according to one of the preceding claims, wherein the elution of the sample from the chromatography system comprises providing a plurality of chromatographic peaks of the sample over time; and the desired maximum duration of the mass analysis scans (Dmax) and the maximum accumulation time of sample ions (Amax) over time are updated based on the chromatographic peaks eluting from the chromatography system. Method for mass spectrometry according to one of the preceding claims, wherein the mass analyzer (110) is an orbital trap mass analyzer. Mass spectrometer (10) for mass analysis of a sample, comprising: an ion source (20) configured to ionize a sample supplied by a chromatography system; a mass analyzer (110), wherein the mass analyzer (110) is a Fourier transform mass analyzer or a time-of-flight mass analyzer; an ion transport device configured to guide sample ions from the ion source (20) along an ion track to the mass analyzer; a controller (130) configured to: (i) calculate a desired maximum duration of mass analysis scans (Dmax) based on the duration of a chromatographic peak of the sample while it is eluted from the chromatography system, a minimum number (M) of mass analysis scans to be performed per chromatographic peak, and a number (N) of target analytes to be analyzed over the duration of the chromatographic peak;(ii) Calculating a maximum accumulation time of sample ions (Amax) based on the desired maximum scan duration (Dmax); (iii) Causing the ion source (20) to ionize the sample to generate sample ions using an ion source; (iv) Causing the ion optics to guide the sample ions along the ion path from the ion source (20) to a mass analyzer (110); (v) Causing the mass spectrometer (10) to perform a first set of mass analysis scans, each of which comprises: accumulating a fraction of sample ions at a location along the ion path, the fraction of sample ions being accumulated for a duration not exceeding the maximum accumulation time (Amax) of sample ions; and mass analyzing the fraction of sample ions using the mass analyzer (110). Mass spectrometer (10) according to claim 11, wherein the maximum accumulation time of sample ions (Amax) is also calculated based on a number of target analytes to be identified per mass analysis scan. Mass spectrometer (10) according to claim 12, wherein the desired maximum duration of the mass analysis scans (Dmax) is also calculated based on the number of target analytes to be identified per mass analysis scan. Mass spectrometer (10) according to one of claims 11 to 13, including an ion capture device, wherein each fraction of the ions is accumulated in the ion capture device at one point along the ion path. Mass spectrometer (10) according to any one of claims 11 to 14, wherein the controller (130) is further configured to: (vi) calculate an average scan duration for the first set of mass analysis scans, wherein, if the average duration of the first set of mass analysis scans is greater than the desired maximum duration of the mass analysis scans (Dmax), the controller is configured to reduce the maximum accumulation duration of sample ions (Amax) to provide a set maximum accumulation duration; and (vii) cause the mass spectrometer (10) to perform a second set of mass analysis scans, wherein each of the second set of mass analysis scans comprises: accumulating a fraction of sample ions at a location along the ion trajectory, wherein the fraction of ions is accumulated for a duration that does not exceed the set maximum accumulation duration;and mass analysis of the fraction of sample ions using the mass analyzer (110).; Mass spectrometer (10) according to claim 15, wherein the control (130) is configured by a scaling factor (k) to reduce the maximum accumulation time of sample ions (Amax) in order to provide the set maximum accumulation time. Mass spectrometer (10) according to claim 15 or claim 16, wherein the controller (130) is configured to perform the second set of mass analysis scans, further comprising: calculating an average scan duration for the previous n mass analysis scans, wherein, if the average duration of the previous n mass analysis scans is greater than the desired maximum duration of the mass analysis scans (Dmax), the set maximum accumulation duration is further reduced, where n is an integer greater than 2. Mass spectrometer (10) according to claim 17, wherein the controller (130) is configured to repeat the calculation of the average scan duration for the previous n mass analysis scans and to further reduce the set maximum accumulation duration if the average duration of the previous n mass analysis scans during the execution of the second set of mass analysis scans is greater than the desired maximum duration of the mass analysis scans (Dmax). Mass spectrometer (10) according to claim 17 or claim 18, wherein n is calculated based on a multiple of the number of target analytes to be identified. Mass spectrometer (10) according to any one of claims 11 to 19, wherein the ion source (20) is configured to receive a sample from the chromatography system comprising a plurality of chromatographic peaks of the sample over time; and the controller (130) is configured to update the desired maximum duration of mass analysis scans (Dmax) and the maximum accumulation time of sample ions (Amax) over time based on the chromatographic peaks eluting from the chromatography system. Mass spectrometer (10) according to one of claims 11 to 20, wherein the mass analyzer (110) is an orbital trap mass analyzer.

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