Abstract: A method of performing mass spectrometry includes obtaining, based on a series of mass spectra of detected ions derived from components eluting from a chromatography column, a plurality of extracted ion chromatograms (XICs), each XIC comprising a plurality of detection points representing detected intensity for a distinct selected m/z as a function of time; detecting, based on the series of mass spectra, precursor ions of each distinct selected m/z of the plurality of XICs; and determining, for each XIC based on a set of detection points of the XIC, a predicted next detection point to be obtained based on a next mass spectrum to be acquired.

Abstract: A system for performing dynamic DIA directs a mass spectrometer to acquire, based on an acquisition schedule that schedules a plurality of acquisition cycles, MS2 spectra of product ions derived from analytes included in a sample as the analytes elute from a separation system. The acquisition schedule specifies, for each acquisition cycle included in the plurality of acquisition cycles, a dynamic precursor m/z range based on an expected elution time of the analytes. The product ions are produced from precursor ions isolated using an isolation window successively positioned throughout the dynamic precursor m/z range during each acquisition cycle. The system detects an elution time shift in the elution time of the analytes as the analytes elute and adjusts the acquisition schedule based on the detected elution time shift.

Abstract: Methods are described for the automatic determination and correction of retention time shift of a MS data set relative to a control data set, to correct for retention time drifts endemic to targeted LCMS analyses. In an embodiment, a 2D grid of periodic MS spectra versus time is collected for a control experiment, and RT windows are determined with an additional set of unscheduled mass spectral analyses. During successive experiments, spectra from periodic MS scans are used to determine the correspondence between the current time and the time in the control experiment. The active set of MSn scans to be acquired by the instrument is then determined as the scans with adjusted retention time windows that bracket the corrected retention time.

Abstract: A Liquid Chromatography Mass Spectrometry system comprises: a chromatograph; a mass spectrometer configured to ionize separated fractions of a sample received from the chromatograph; and a programmable processor operable to repeatedly execute the steps of: (i) causing the mass spectrometer to perform a data-independent analysis of the precursor ion species using a mass analyzer of the mass spectrometer; (ii) calculating one or more degree-of-matching scores that relate to detection of an internal standard; and (iii) if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a quantitative tandem mass spectrometric analyses of both the internal standard and the analyte; the programmable processor further operable to calculate a quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte and the internal standard.

Abstract: A method of performing mass spectrometry includes accessing a series of mass spectra of detected ions derived from components eluting from a chromatography column; obtaining, based on the series of mass spectra, an elution profile including a plurality of detection points representing intensity of at least a set of the detected ions as a function of time; and determining, based on a set of detection points included in the plurality of detection points, a predicted next detection point of the elution profile to be obtained based on a next mass spectrum to be acquired subsequent to acquisition of the series of mass spectra.

Abstract: A method of operating a mass spectrometer that allows for high-speed operation is disclosed. The method consists in separating the various steps needed to produce a mass spectrum into three or more conceptual stages in a pipeline, such that the instrument is performing steps to process more than two precursor-ion species simultaneously. In general, the number of stages in the pipeline should at least one more and, preferably, at least two more than the number of buffering storage devices in the instrument. The presently-taught methods and apparatus allow for nearly 100% duty cycle of ion accumulation for precursors of interest.

Abstract: A Liquid Chromatography Mass Spectrometry system comprises: a chromatograph; a mass spectrometer configured to ionize separated fractions of a sample received from the chromatograph; and a programmable processor operable to repeatedly execute the steps of: (i) causing the mass spectrometer to perform a data-independent analysis of the precursor ion species using a mass analyzer of the mass spectrometer; (ii) calculating one or more degree-of-matching scores that relate to detection of an internal standard; and (iii) if each of the degree-of-matching scores meets a respective degree-of-matching condition, performing a quantitative tandem mass spectrometric analyses of both the internal standard and the analyte; the programmable processor further operable to calculate a quantity of the analyte in the sample by comparison between intensities of one or more mass spectral signals generated by the quantitative tandem mass spectrometric analyses of the analyte and the internal standard.

Abstract: Methods are described for the automatic determination and correction of retention time shift of a MS data set relative to a control data set, to correct for retention time drifts endemic to targeted LCMS analyses. In an embodiment, a 2D grid of periodic MS spectra versus time is collected for a control experiment, and RT windows are determined with an additional set of unscheduled mass spectral analyses. During successive experiments, spectra from periodic MS scans are used to determine the correspondence between the current time and the time in the control experiment. The active set of MSn scans to be acquired by the instrument is then determined as the scans with adjusted retention time windows that bracket the corrected retention time.

Abstract: A method of performing mass spectrometry includes accessing a series of mass spectra of detected ions derived from components eluting from a chromatography column; obtaining, based on the series of mass spectra, an elution profile including a plurality of detection points representing intensity of at least a set of the detected ions as a function of time; and determining, based on a set of detection points included in the plurality of detection points, a predicted next detection point of the elution profile to be obtained based on a next mass spectrum to be acquired subsequent to acquisition of the series of mass spectra.

Abstract: A method of performing targeted multiplexed mass spectrometry includes performing, at a mass spectrometer, a targeted MS3 analysis of an isobaric tag-labeled target analyte included in a multiplex sample eluting from a column. The targeted MS3 analysis is performed during an acquisition segment scheduled based on an expected retention time of the isobaric tag-labeled target analyte. The method further includes performing, during the acquisition segment, a plurality of MS2 analyses of product ions derived from components included in the multiplex sample and eluting from the column. The method further includes determining, based on MS3 mass spectra acquired by the targeted MS3 analysis and MS2 mass spectra acquired by the plurality of MS2 analyses, a relative quantity of the isobaric tag-labeled target analyte in the multiplex sample.

Abstract: A space-time buffer includes a plurality of discrete trapping regions and a controller. The plurality of discrete trapping regions is configured to trap ions as individual trapping regions or as combinations of trapping regions. The controller is configured to combine at least a portion of the plurality of trapping regions into a larger trap region; fill the larger trap region with a plurality of ions; split the larger trap region into individual trapping regions each containing a portion of the plurality of ions; and eject ions from the trapping regions.

Abstract: Targeted quantification for mass spectrometry is described. In one aspect, a mass spectrometer can generate survey mass spectra and identify the compounds of a sample using the survey mass spectra. Compounds that elute within a same time range and do not form interfering product ions upon fragmentation can be identified, and grouped together for an MS2 scan. A series of MS2 scans can then be generated to acquire MS2 mass spectra.

Abstract: A method of data-independent mass spectrometric analysis of compounds of a compound class of interest comprises: determining or retrieving a distribution, over a mass-to-charge (m/z) ratio range of interest, of a number of primary ion species of members of said compound class having m/z ratios within each respective one of a plurality of m/z sub-ranges of the m/z ratio range of interest; defining m/z positions of a set consisting of a number, nsb, of finite-width bins, within the m/z ratio range of interest, the set of bins excluding m/z sub-ranges within the m/z ratio range of interest that encompass fewer than a threshold number, tsb, of the primary ion species, wherein the defining based on the determined or received distribution; and performing a plurality of tandem mass analyses, each tandem mass analysis pertaining to primary ion species within a respective one of the defined bins.

Abstract: A method comprises: obtaining, from a series of mass spectra including a most recent mass spectrum and a plurality of previously-acquired mass spectra, an elution profile comprising a plurality of detection points each representing intensity of ions accumulated over an accumulation time and detected by a detector as a function of time; classifying, based on a subset of detection points included in the plurality of detection points, a current signal state of the elution profile; and setting, for a next acquisition of a mass spectrum, the accumulation time based on the classified current signal state of the elution profile.

Abstract: A method of performing tandem mass spectrometry includes supplying a sample to a chromatography column, directing components included in the sample and eluting from the chromatography column to a mass spectrometer, acquiring a series of mass spectra including intensity values of ions produced from the components as a function of m/z of the ions, extracting, from the series of mass spectra, a plurality of detection points representing intensity as a function of time for a selected m/z, estimating, based on the plurality of detection points extracted from the series of mass spectra, a relative position of a selected detection point included in the plurality of detection points, and performing, at the mass spectrometer and based on the estimated relative position, a dependent acquisition for the selected m/z. The relative position of the selected detection point represents a position of the selected detection point relative to an expected reference point.

Abstract: A method of performing targeted multiplexed mass spectrometry includes performing, at a mass spectrometer, a targeted MS3 analysis of an isobaric tag-labeled target analyte included in a multiplex sample eluting from a column. The targeted MS3 analysis is performed during an acquisition segment scheduled based on an expected retention time of the isobaric tag-labeled target analyte. The method further includes performing, during the acquisition segment, a plurality of MS2 analyses of product ions derived from components included in the multiplex sample and eluting from the column. The method further includes determining, based on MS3 mass spectra acquired by the targeted MS3 analysis and MS2 mass spectra acquired by the plurality of MS2 analyses, a relative quantity of the isobaric tag-labeled target analyte in the multiplex sample.

Abstract: A mass spectrometer system comprises: (a) an ion source; (b) a mass filter or a time-of-flight (TOF) ion separator configured to receive a stream of first-generation ions from the ion source; (c) an ion storage device having an ion inlet configured to receive a stream of filtered ions comprising a plurality of ion species from the mass filter or TOF separator and to accumulate the plurality of ion species therein; (d) an ion mobility cell having an ion inlet configured to receive an accumulated batch of ion species from the ion storage device and an ion outlet configured to release, one at a time, the individual ion species therefrom; and (e) a mass analyzer configured to receive and mass analyze each first-generation ion species or each fragment ion species generated by fragmentation or other reaction of the various first-generation ion species.

Abstract: A method of performing mass spectrometry includes accumulating, over an accumulation time, ions produced from components eluting from a chromatography column and transferring the accumulated ions to a mass analyzer. During an acquisition, a mass spectrum of detected ions derived from the transferred ions is acquired. An elution profile is obtained from a series of acquired mass spectra including the acquired mass spectrum and a plurality of previously-acquired mass spectra. The elution profile includes a plurality of detection points representing intensity of the detected ions as a function of time. A current signal state of the elution profile is classified based on a subset of detection points included in the plurality of detection points. The accumulation time for a next acquisition of a mass spectrum is set based on the classified current signal state of the elution profile.

Abstract: A method of performing mass spectrometry includes accumulating, over an accumulation time, ions produced from components eluting from a chromatography column and transferring the accumulated ions to a mass analyzer. During an acquisition, a mass spectrum of detected ions derived from the transferred ions is acquired. An elution profile is obtained from a series of acquired mass spectra including the acquired mass spectrum and a plurality of previously-acquired mass spectra. The elution profile includes a plurality of detection points representing intensity of the detected ions as a function of time. A current signal state of the elution profile is classified based on a subset of detection points included in the plurality of detection points. The accumulation time for a next acquisition of a mass spectrum is set based on the classified current signal state of the elution profile.

Abstract: A method for determining a quantity of an analyte in a liquid sample, comprises: adding a known quantity of an internal standard comprising an isotopically labeled version of the analyte to the sample; (b) providing a continuous stream of the sample having the internal standard to an inlet of a Liquid Chromatography Mass Spectrometry (LCMS) system; and repeatedly performing the steps of: performing a data-independent analysis of the precursor ion species using a mass analyzer, whereby mass spectra of a plurality of fragment-ion species are acquired; calculating one or more degree-of-matching scores that relate to either a number of ions of the internal standard that overlap between results of the data-independent analysis and tabulated mass spectral data of the internal standard; and performing quantitative tandem mass spectrometric analyses of the internal standard and the analyte if each of the degree-of-matching scores meets a respective degree-of-matching condition.