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 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 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: 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 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: 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 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.

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: 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: 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 method for mass spectrometry comprises: receiving or generating a respective value of an optimal collision energy for generating each one of a plurality of n product-ion species of interest from at least one precursor-ion species, each optimal collision energy corresponding to a respective maximum fragmentation efficiency; determining a number, m, wherein m<n, of precursor-ion collision energy values required to fragment all of the at least one precursor-ion species such that a fragmentation efficiency of each product-ion species of interest generated by the fragmentation is equal to the respective maximum fragmentation efficiency, within a pre-determined tolerance; and performing a mass spectrometric analysis that includes fragmenting the one or more precursor-ion species in a collision cell by imparting, in sequence, each of and only the m precursor-ion collision energy values to ions received from an ion source.

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 comprises: obtaining a precursor mass-to-charge value, (m/z)p, of a target precursor ion having formula [M+2A]2+, M being a peptide molecule and A being one or more adducts; generating ions from a sample by an ion source; purifying and fragmenting ions comprising the (m/z)p, thereby generating a plurality of MS-2 species; co-purifying and co-fragmenting a selected subset of the MS-2 species, thereby generating a plurality MS-3 species, wherein each selected MS-2 species is a y-type ion species comprising a respective (m/z)f that is greater than (m/z)p; mass analyzing the MS-3 species and selecting a subset thereof, each selected MS-3 species comprising a respective (m/z)g that satisfies a mass-to-charge selection criterion; and determining a quantity of the peptide from a summation of mass spectral intensities corresponding to the selected MS-3 species.

Abstract: A method comprises: obtaining a precursor mass-to-charge value, (m/z)p, of a target precursor ion having formula [M+2A]2+, M being a peptide molecule and A being one or more adducts; generating ions from a sample by an ion source; purifying and fragmenting ions comprising the (m/z)p, thereby generating a plurality of MS-2 species; co-purifying and co-fragmenting a selected subset of the MS-2 species, thereby generating a plurality MS-3 species, wherein each selected MS-2 species is a y-type ion species comprising a respective (m/z)f that is greater than (m/z)p; mass analyzing the MS-3 species and selecting a subset thereof, each selected MS-3 species comprising a respective (m/z)g that satisfies a mass-to-charge selection criterion; and determining a quantity of the peptide from a summation of mass spectral intensities corresponding to the selected MS-3 species.

Abstract: A method for mass spectrometry comprises: receiving or generating a respective value of an optimal collision energy for generating each one of a plurality of n product-ion species of interest from at least one precursor-ion species, each optimal collision energy corresponding to a respective maximum fragmentation efficiency; determining a number, m, wherein m<n , of precursor-ion collision energy values required to fragment all of the at least one precursor-ion species such that a fragmentation efficiency of each product-ion species of interest generated by the fragmentation is equal to the respective maximum fragmentation efficiency, within a pre-determined tolerance; and performing a mass spectrometric analysis that includes fragmenting the one or more precursor-ion species in a collision cell by imparting, in sequence, each of and only the m precursor-ion collision energy values to ions received from an ion source.

Abstract: A method for analyzing a sample includes identifying a plurality of precursors for analysis and grouping the precursors into two or more groups. The precursors are grouped such that for the precursors within a group the masses of ions of the precursors in the group are within a first mass range, and the number of precursors within the group is below a maximum allowable number of precursors. The method further includes generating ions from the sample; isolating precursor ions of a group; determining the mass-to-charge ratio of the precursor ions or fragments thereof; and repeating the isolating and determining steps for each group. The method also includes identifying or quantifying the presence of one or more precursors within the sample based on the presence of fragmented ions having a mass-to-charge ratio corresponding to the product ions for the one or more precursors.

Abstract: A method for determining optimal values of a mass spectral operating parameter for mass spectral analysis of each of a plurality of compounds comprises: acquiring a plurality of mass spectral measurements of each of at least one characteristic ion species of each respective compound during its introduction into a mass spectrometer while a quantity of each introduced compound varies with time wherein, for each characteristic ion species, the operational parameter is caused to vary between successive mass spectral measurements of the said species; calculating, for each characteristic ion species, a corrected intensity of at least a portion of the plurality of mass spectral measurements of said each species, based on a best-fit synthetic model curve that relates to the time variation of the respective corresponding compound; and determining the optimal values of the operating parameter from analyses of variation of the corrected intensities with respect to the operational parameter variation.

Abstract: This disclosure describes a method of adjusting the amplitude of broadband waveforms for isolation, especially during injection to a multipole trapping device. Isolation during injection to a trapping device is known to be an effective way of accumulating a desired population of ions while rejecting unwanted species. The waveform amplitude required to eject unwanted species varies as a function of isolation time, but using automated gain control, the time required to accumulate a given population of ions may vary over several orders of magnitude. Thus, when the injection times are very long, precursor ions of interest are resonated for a long time and may be inadvertently ejected from the trap, using conventional methods. By setting the waveform amplitude lower for longer accumulation times, good isolation efficiency can be maintained for the precursor, while still rejecting unwanted ions.

Abstract: A method for identifying components of a sample includes providing a sample to an ion source and generating a plurality of ions from constituent components of the sample, applying a first RF waveform at a first RF amplitude to an ion trap with field resonances while directing the plurality of ions into the ion trap, and applying a second RF waveform at a second RF amplitude to the ion trap while focusing the plurality of ions towards the center of the ion trap along the longitudinal axis. The method further includes ejecting the plurality of ions from the ion trap into a mass analyzer, and using the mass analyzer to determine the mass-to-charge ratio of the ions.

Abstract: This disclosure describes a method of adjusting the amplitude of broadband waveforms for isolation, especially during injection to a multipole trapping device. Isolation during injection to a trapping device is known to be an effective way of accumulating a desired population of ions while rejecting unwanted species. The waveform amplitude required to eject unwanted species varies as a function of isolation time, but using automated gain control, the time required to accumulate a given population of ions may vary over several orders of magnitude. Thus, when the injection times are very long, precursor ions of interest are resonated for a long time and may be inadvertently ejected from the trap, using conventional methods. By setting the waveform amplitude lower for longer accumulation times, good isolation efficiency can be maintained for the precursor, while still rejecting unwanted ions.