Abstract: Control of an amplitude of a signal applied to rods of a quadrupole is described. In one aspect, a mass spectrometer includes an amplifier circuit that causes a radio frequency (RF) signal to be applied to the rods of the quadrupole. A controller circuit can determine that the actual amplitude of the RF signal differs than the expected amplitude and, in response, identify current and past environmental and performance parameters to adjust the amplitude.

Abstract: An ion guide includes a first arrangement of electrodes on a first surface, a second arrangement of electrodes on a second surface, and an ion containment space in a gap therebetween. The first arrangement includes first electrodes and second electrodes. Each first electrode includes a first main portion and a first edge portion. The first edge portion is wider than the first main portion. The second arrangement includes third electrodes and fourth electrodes. Each fourth electrode includes a fourth main portion and a fourth edge portion. The fourth edge portion is wider than the fourth main portion. The first edge portions are positioned opposite the fourth edge portions. The first electrodes and the third electrodes are configured to receive first RF voltages and the second electrodes and the fourth electrodes are configured to receive second RF voltages that are phase-shifted with respect to the first RF voltages.

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 mass spectrometry method comprises: introducing a first packet of ions into an electrostatic trap mass analyzer through a set of electrostatic lenses, wherein, during the introducing of the first packet, either the lenses are operated in a first mode of operation or an injection voltage of a first pre-determined magnitude is applied to an electrode of the mass analyzer; mass analyzing the first ion packet using the mass analyzer; introducing a second packet of ions into the mass analyzer through the set of lenses, wherein, during the introducing of the second packet, either the lenses are operated in a second mode of operation or an injection voltage of a second pre-determined magnitude is applied to the electrode of the mass analyzer; and mass analyzing the second packet of ions using the electrostatic trap mass analyzer.

Abstract: Isobaric mass spectrometry tags (e.g., TMT) are susceptible to ratio compression, which arises from the co-isolation and co-fragmentation of interfering species that also contribute to the final reporter ion ratios. Additional stages of ion activation/transformation (e.g., MSn and PTR) have been shown to decrease ratio compression. Embodiments of the present invention include a mass spectrometry cleavable moiety on the isobaric mass tags. The cleavable moiety allows for a predictable mass loss, and results in an improved tag reporter ion purity.

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 spectrometry method comprises: introducing a first packet of ions into an electrostatic trap mass analyzer through a set of electrostatic lenses, wherein, during the introducing of the first packet, either the lenses are operated in a first mode of operation or an injection voltage of a first pre-determined magnitude is applied to an electrode of the mass analyzer; mass analyzing the first ion packet using the mass analyzer; introducing a second packet of ions into the mass analyzer through the set of lenses, wherein, during the introducing of the second packet, either the lenses are operated in a second mode of operation or an injection voltage of a second pre-determined magnitude is applied to the electrode of the mass analyzer; and mass analyzing the second packet of ions using the electrostatic trap mass analyzer.

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 includes applying distinct isobaric tags to each of a plurality of samples; combining the samples; performing a separation of species within the combined samples; isolating and fragmenting labeled parent ions within a m/z range to produce a plurality of reporter ions, each reporter ion corresponding to one of the isobaric tags; determining intensities of the plurality of reporter ions and ions representative of a parent species at a plurality of points along a peak; and fitting the intensity of the ions representative of a parent species and the plurality of reporter ions at the plurality of points to obtain a relative abundance of the parent species in each of the plurality of samples.

Abstract: A mass spectrometry method comprises: storing a first packet of ions within an ion storage apparatus; transferring the first ion packet into an electrostatic trap mass analyzer through a set of electrostatic lenses, wherein, during the transfer, either the lenses are operated in a first mode of operation or an injection voltage of a first pre-determined magnitude is applied to an electrode of the mass analyzer; mass analyzing the first ion packet using the mass analyzer; storing a second packet of ions within the ion storage apparatus; transferring the second ion packet into the mass analyzer through the set of lenses, wherein, during the transfer, either the lenses are operated in a second mode of operation or an injection voltage of a second pre-determined magnitude is applied to the electrode of the mass analyzer; and mass analyzing the second packet of ions using the electrostatic trap mass analyzer.

Abstract: Control of an amplitude of a signal applied to rods of a quadrupole is described. In one aspect, a mass spectrometer includes an amplifier circuit that causes a radio frequency (RF) signal to be applied to the rods of the quadrupole. A controller circuit can determine that the actual amplitude of the RF signal differs than the expected amplitude and, in response, identify current and past environmental and performance parameters to adjust the amplitude.

Abstract: A system comprises: (1) a central location comprising: (a) computer storage media having one or more databases thereon; and (b) one or more computers configured to communicate with the computer storage media: and (2) a plurality of sites, each site comprising: (a) an analytical apparatus; and (b) a site computer system comprising program instructions operable to generate a collection of apparatus signatures, each apparatus signature comprising a collection of data relating to the operation of the analytical apparatus at a time when said signature is generated, wherein the one or more computers at the central location are configured to store each collection of signatures in the one or more databases. In embodiments, each site computer system stores the plurality of apparatus signatures generated at the respective site and transmits the stored apparatus signatures to the one or more computers at the central location.

Abstract: A mass spectrometry method comprises: storing a first packet of ions within an ion storage apparatus; transferring the first ion packet into an electrostatic trap mass analyzer through a set of electrostatic lenses, wherein, during the transfer, either the lenses are operated in a first mode of operation or an injection voltage of a first pre-determined magnitude is applied to an electrode of the mass analyzer; mass analyzing the first ion packet using the mass analyzer; storing a second packet of ions within the ion storage apparatus; transferring the second ion packet into the mass analyzer through the set of lenses, wherein, during the transfer, either the lenses are operated in a second mode of operation or an injection voltage of a second pre-determined magnitude is applied to the electrode of the mass analyzer; and mass analyzing the second packet of ions using the electrostatic trap mass analyzer.

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: Apparatus and methods for performing charge detection mass spectrometry are disclosed. An analyte ion is injected into an electrostatic trap, which has electrodes shaped and arranged to establish a trapping field that causes the analyte ion to undergo harmonic motion along a longitudinal axis. A time-varying signal is generated by a detector representative of the harmonic motion. A data system processes the time-varying signal to derive the frequency of ion motion and the amplitude at the harmonic motion frequency, and determines the mass-to-charge ratio (m/z) of the ion based on the derived frequency and the charge from the derived amplitude. The product of the experimentally determined m/z and charge yields the mass of the analyte ion. The electrodes preferably include an elongated inner electrode surrounded by an outer electrode, forming an orbital or non-orbital electrostatic trap.

Abstract: An electron multiplier includes a series of discrete electron emissive surfaces or a continuous electron emissive resistive surface configured to provide an electron amplification chain; and a housing surrounding the series of electron emissive surfaces or the continuous electron emissive resistive surface and separating the environment inside the housing from the environment outside the housing. The housing includes an electron-transparent, gas-impermeable barrier configured to allow electrons to pass through into the housing to reach a first discrete electron emissive surface of the series of discrete electron emissive surfaces or a first portion of the continuous electron emissive resistive surface.

Abstract: Apparatus and methods for performing charge detection mass spectrometry for measurement of the mass of a single ion of interest are disclosed. The ion of interest is caused to undergo harmonic oscillatory movement in the trapping field of an electrostatic trap, such that an image current detector generates a time-varying signal representative of the ion's oscillatory movement. This time-varying signal (transient) is processed (e.g., via a Fourier transform) to derive the ion's frequency and consequently determine the ion's mass-to-charge ratio (m/z). Ion charge is determined by construction of a Selective Temporal Overview of Resonant Ion (STORI) plot, which tracks the temporal evolution of signals attributable to the ion of interest, and where the slope of the STORI plot is related to the charge. The STORI plot may also be employed to identify ion decay events during transient acquisition and/or the presence of multiple ions of the same mass or non-resolvable ions.

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: An ion separation apparatus comprises: (a) first and second ion carpets, each comprising: a substrate having first and second faces; and a set of electrodes disposed on or beneath the first face, wherein a configuration of a first plurality of the set of electrodes defines at least one group of circle sectors; (b) an ion exit aperture passing through one ion carpet; and (c) one or more power supplies configured to provide radio frequency voltages to a first subset of the electrodes of each ion carpet, to provide electrical potential differences across electrodes of the first subset of electrodes of each ion carpet, and to provide time-varying voltages to the first plurality of electrodes of each ion carpet that migrate through the sectors as a traveling wave, wherein the ion carpets are disposed parallel to one another with a gap therebetween, the first faces facing one another across the gap.