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 based on an amplifier RF input signal. An analog-to-digital converter (ADC) can generate a digital representation of the RF signal. A controller circuit can receive the digital representation and adjust an amplitude of the amplifier RF input signal based on differences between an amplitude of a fundamental frequency of the RF signal being different than an expected amplitude.

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 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: 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: 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: 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 based on an amplifier RF input signal. An analog-to-digital converter (ADC) can generate a digital representation of the RF signal. A controller circuit can receive the digital representation and adjust an amplitude of the amplifier RF input signal based on differences between an amplitude of a fundamental frequency of the RF signal being different than an expected amplitude.

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: 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: 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 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 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 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: generating ions; directing the ions through an ion optical component within a first chamber having a first vacuum pressure, the ion optical component maintained at a first electrical potential; transferring the ions through an ion guide within a second chamber having a second vacuum pressure less than the first vacuum pressure, the ion guide maintained at a second electrical potential, wherein a difference between the first and second potentials imparts kinetic energy that causes collision-induced ion fragmentation within the second chamber that removes adduct species; and transferring the ions into another ion guide within a third chamber having a third vacuum pressure less than the second vacuum pressure, the other ion guide maintained at a third electrical potential, wherein a difference between the third and second potentials reduces a portion of the imparted kinetic energy of the ions passing into the third chamber.

Abstract: A method of operating an electrostatic trapping mass analyzer, comprising: introducing a sample of ions into a trapping region of the mass analyzer, wherein a trapping field within the trapping region is such that the ions exhibit radial motion with respect to a central longitudinal axis of the trapping region while undergoing harmonic motion in a dimension defined by the central longitudinal axis, the frequency of harmonic motion of a particular ion being a function of its mass-to-charge ratio; superimposing a modulation field onto the trapping field within the trapping region, the modulation field acting to either increase or reduce the harmonic motion energies of the ions by an amount varying according to the frequency of harmonic motion; and acquiring a mass spectrum of the ions in the trapping region by measuring a signal representative of an image current induced by the harmonic motion of the ions.

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 method of operating an electrostatic trapping mass analyzer, comprising: introducing a sample of ions into a trapping region of the mass analyzer, wherein a trapping field within the trapping region is such that the ions exhibit radial motion with respect to a central longitudinal axis of the trapping region while undergoing harmonic motion in a dimension defined by the central longitudinal axis, the frequency of harmonic motion of a particular ion being a function of its mass-to-charge ratio; superimposing a modulation field onto the trapping field within the trapping region, the modulation field acting to either increase or reduce the harmonic motion energies of the ions by an amount varying according to the frequency of harmonic motion; and acquiring a mass spectrum of the ions in the trapping region by measuring a signal representative of an image current induced by the harmonic motion of the ions.

Abstract: A method of operating an electrostatic trapping mass analyzer, comprising: introducing a sample of ions into a trapping region of the mass analyzer, wherein a trapping field within the trapping region is such that the ions exhibit radial motion with respect to a central longitudinal axis of the trapping region while undergoing harmonic motion in a dimension defined by the central longitudinal axis, the frequency of harmonic motion of a particular ion being a function of its mass-to-charge ratio; superimposing a modulation field onto the trapping field within the trapping region, the modulation field acting to either increase or reduce the harmonic motion energies of the ions by an amount varying according to the frequency of harmonic motion; and acquiring a mass spectrum of the ions in the trapping region by measuring a signal representative of an image current induced by the harmonic motion of the ions.

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 hybrid mass spectrometer design and architecture, and methods of operating mass spectrometers are disclosed. According to one operating method, an analysis time is determined for each one of a plurality of ion species to be analyzed in an ordered sequence, and an injection time is calculated for at least some of the ion species based on an analysis time of a preceding ion species in the ordered list. The method enables more efficient utilization of analyzer time.

Abstract: A method of operating an electrostatic trapping mass analyzer, comprising: introducing a sample of ions into a trapping region of the mass analyzer, wherein a trapping field within the trapping region is such that the ions exhibit radial motion with respect to a central longitudinal axis of the trapping region while undergoing harmonic motion in a dimension defined by the central longitudinal axis, the frequency of harmonic motion of a particular ion being a function of its mass-to-charge ratio; superimposing a modulation field onto the trapping field within the trapping region, the modulation field acting to either increase or reduce the harmonic motion energies of the ions by an amount varying according to the frequency of harmonic motion; and acquiring a mass spectrum of the ions in the trapping region by measuring a signal representative of an image current induced by the harmonic motion of the ions.