Abstract: A mass spectrometer is described that includes a multipole configured to pass an ion stream, the ion stream comprising an abundance of one or more ion species within stability boundaries defined by (a, q) values. A detector formed by a plurality of dynodes is configured to detect the spatial and temporal properties of the abundance of ions, where each dynode arranged such that it is struck by ions in a known spatial relationship with the ion stream. The detector also includes a plurality of charged particle detectors, each associated with one or more of the plurality of dynodes. A processing system is configured to record and store a pattern of detection of ions in the abundance of ions by the dynodes in the detector.

Abstract: A multipole assembly configured to be disposed in a mass spectrometer includes a plurality of elongate electrodes arranged about an axis extending along a longitudinal trajectory of the plurality of elongate electrodes and configured to confine ions radially about the axis, and a piezoelectric actuator configured to adjust a position of a first electrode included in the plurality of elongate electrodes.

Abstract: A method for analyzing and quantifying a panel of drugs in a clinical sample comprises: trapping a first portion of drug parent compounds and their metabolites on a first chromatographic column; trapping a second portion of the drug parent compounds and their metabolites on a second chromatographic column; separately eluting the first and second portions of the drug parent compounds and their metabolites from the first and second chromatographic columns; detecting concentrations of each of the drug parent compounds and metabolites eluted from each of the first and second chromatographic columns with a detector; and summing the detected concentration of each drug parent compound together with the detected concentrations of all of its respective analytes so as to derive a respective total concentration of each drug in the sample.

Abstract: A system comprises an electrostatic trapping mass analyzer and an information processor configured to receive a transient signal from the electrostatic trapping mass analyzer at a maximum resolution, the information processor comprising instructions operable to: partition the transient signal into segments and, while a quality metric is either less than a pre-determined minimum threshold or greater than a pre-determined maximum threshold value, to perform the steps of: (i) defining a test transient as being equal to either a first one of the segments or a previously defined transient with an appended signal segment; (ii) generating a spectrum of component frequencies by calculating a mathematical transform of the test transient; and (iii) determining the quality metric from the spectrum of component frequencies; and set an instrumental resolution to be employed for subsequent mass spectral data acquisitions in accordance with a length of the most-recently-defined test transient.

Abstract: A method is disclosed for analyzing ions by mass spectrometry by repeatedly executing a data acquisition cycle to acquire product ion data across a precursor mass range of interest. The data acquisition cycle comprises performing, for each of a plurality of isolation windows having different mass ranges, steps of (i) isolating precursor ions within the mass range of the isolation window, (ii) fragmenting the isolated precursor ions to generate product ions, and (iii) mass analyzing the product ions. The step of mass analyzing the product ions includes concurrently mass analyzing product ions corresponding to N isolation windows, N being an integer greater than or equal to one, wherein N is changed at least once across the data acquisition cycle.

Abstract: A system for analyzing a sample includes a chromatographic device, an electrospray source, and a mass resolving device. The chromatographic device is configured to separate components of the sample as a function of retention time within a chromatographic column. The electrospray source is configured to direct a first portion of a flow from the chromatographic device via a waste outlet to a pressurized waste reservoir, direct a second portion of the flow to an electrospray ionization outlet to form a spray, and charge and desolvate the spray to form ions of the components of the sample. A flow rate of the second portion of the liquid flow is substantially determined by a pressure of the pressurized waste reservoir. The mass resolving device configured to receive the ions and characterize the mass-to-charge ratio of the ions.

Abstract: A method of operating a quadrupole mass filter is disclosed. A first set of RF and resolving DC voltages are applied to electrodes of a quadrupole mass filter to selectively transmit first ions having a first mass-to-charge ratio (m/z). A second set of RF and resolving DC voltages are applied to electrodes of the quadrupole mass filter to selectively transmit second ions having a second m/z. Detection of the second ions is initiated after completion of a settling time. The settling time is determined in accordance with the relationship: Eq. 1, where ts is the settling time, (m/z)1 is the first mass-to-charge ratio, (m/z)2 is the second mass-to-charge ratio and A, B and C are empirically derived coefficients.

Abstract: An ion detector includes a first stage dynode configured to receive an ion beam and generate electrons, a photon source arranged to provide photons to the first stage dynode, the photons of sufficient energy to cause the first stage dynode to emit photoelectrons, an electron multiplier configured to receive the electrons or the photoelectrons from the first stage dynode and generate an output proportional to the number of electrons or photoelectrons, and a controller. The controller is configured to receive the output generated in response to the photoelectrons; calculate a gain curve of the detector based on the output; and set a voltage of the electron multiplier or the first stage dynode to achieve a target gain for the ion beam.

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 system for analyzing a sample includes a source; a mobility separator configured to separate ions based on a mobility in a gas; a plurality of ion channels; and a mass analyzer. The mobility separator includes a two-dimensional grid of electrodes spanning a passage between first and second walls. The first and second walls include an inlet aperture and a plurality of exit apertures, respectively. The two-dimensional grid of electrodes configured to generate an electric field within the passage. The plurality of ion channels arranged adjacent to the plurality of exit apertures. Movement of ions between the inlet aperture and the plurality of exit apertures are governed by the electric field and a gas flow through the passage between to the first and second walls such that the ions are sorted and directed to different channels based on their respective mobility.

Abstract: A method for parallel accumulation and serial fragmentation of ions, wherein ions are injected into a device capable of serial ejection using a pseudopotential barrier created by an RF voltage. In all instances, the ions may be filtered prior to accumulation in the device capable of serial ejection. In some cases this filtering may take the form of discrete isolation windows using isolation waveforms with multiple notches. In some cases these waveforms may be applied to a quadrupole mass filter. Following accumulation of the precursor ions, the initial population may be serially ejected using a pseudopotential barrier created by an RF voltage. Following serial ejection, the individual precursor ion populations are analyzed. In some cases, this analysis might involve additional rounds of ion isolation and manipulation (e.g., MSn, CID, ETD, etc.).

Abstract: A system for analyzing a sample includes a source configured to generate ions from constituent components of the sample; a mobility separator configured to separate ions received from the source based on the mobility in a gas; a plurality of ion channels arranged adjacent to the plurality of exit apertures of the mobility separator such that ions from the mobility separator are directed to different channels according to their respective mobility; a mass analyzer configured to determine the mass-to-charge ratio of the ions; and a controller. The controller is configured to identify retention time windows with minimum overlap of ions with similar mobility and sets of ions within the retention time windows; adjust mobility separation parameters for specific sets of ions to optimize separation of compounds; and quantify a plurality of target analytes.

Abstract: An ion separation device comprising a plurality of electrodes arranged in a two-dimensional grid, a gas supply configured to provide a gas flow along the first direction, and an ion inlet arranged to receive ions. The plurality of electrodes is configured to create one or more pseudopotential barriers of increasing magnitude along a first direction. A drag force is applied to the ions by the gas flow is opposed by a pseudopotential gradient of the plurality of electrodes.

Abstract: A capillary column includes a fused silica tubing and a polyimide coating over the fusing silica tubing. Additionally, the capillary column further includes a first plurality of integrated ferrules positioned along at least a first portion of the fused silica tubing and spaced apart from one another by a first fixed interval.

Abstract: A system includes a database server and a plurality of processing nodes. The plurality of processing nodes are configured to receive mass spectrometry data from a plurality of samples; align the mass spectrometry data to correct for changes in retention time to generate a reference alignment; cluster compounds across the plurality of samples; store the reference alignment and clustered compound data to the database server; receive additional mass spectrometry data from additional samples; align the additional mass spectrometry data to a reference alignment within the database; correlate the compounds from the additional samples with the clustered compound data; classify the compounds; perform statistical analysis on the classified compounds to identify compounds meeting threshold criteria; and provide an indication of compounds meeting the threshold criteria.

Abstract: A method for monitoring a fluidic system of a liquid chromatography system is characterized by: (a) drawing a fluid into a syringe pump; (b) configuring a valve so as to fluidically couple the pump to either a fluidic pathway through the fluidic system or to a plug that prevents fluid flow; (c) causing the syringe pump to progressively compress the fluid therein or expel the fluid to the fluidic pathway, while measuring a pressure of the fluid; (d) determining a profile of the variation of the measured pressure; (e) comparing the determined profile to an expected profile that depends upon the fluid; and (f) providing a notification of a sub-optimal operating condition or malfunction if the determined profile varies from the expected profile by greater than a predetermined tolerance.

Abstract: A mass spectrometer includes a collision cell and a system controller. The collision cell includes a plurality of rod pairs configured to generate pseudopotential well through the application of radio frequency potentials to the rod pairs. The collision cell configured to generate a target fragment from a parent ion by colliding the parent ion with one or more gas molecules. The system controller is configured to set a radio frequency amplitude of the radio frequency potentials to a default amplitude; monitor the production of a target fragment ion while adjusting the collision energy; set the collision energy to optimize the production of the target fragment ion; apply a linear full range ramp to the radio frequency amplitude to determine an optimal radio frequency amplitude; and set the radio frequency amplitude to the optimal radio frequency amplitude for the parent ion, target fragment ion pair.

Abstract: A method of operating an electrostatic trapping mass analyzer, comprises: (a) operating the electrostatic trapping mass analyzer at a maximum resolution so as to acquire a transient signal; (b) partitioning the transient signal into signal segments; (c) while a quality metric is either less than a pre-determined minimum threshold or greater than a pre-determined maximum threshold value, performing the steps of: (i) defining a test transient as being equal to either a first one of the segments or a previously defined transient with an appended signal segment; (ii) calculating a mathematical transform of the test transient and thereby generating a spectrum of component frequencies; and (iii) determining the quality metric from the spectrum of component frequencies; and (d) setting an instrumental resolution to be employed for subsequent mass spectral data acquisitions in accordance with a length of the most-recently-defined test transient.

Abstract: A calibration device and a method of calibrating a mass spectrometer are described where two or more immiscible mass spectrometry calibration compounds in close proximity to each other share a common headspace volume above their liquid surfaces. This arrangement allows each calibrant to evaporate at differing rates while allowing the headspace concentrations to remain relatively unchanged over time (forming a quasi-equilibrium calibrant mixture). The mixture is either delivered to an ion source of a mass spectrometer or to a vacuum pump via a flow restrictor from a calibration vial. The calibrant gas mixture in the headspace volume may be used to calibrate a mass spectrometer.

Abstract: A method of assessing the linearity and dynamic range of a mass spectrometer is described comprising analyzing two or more test standards containing positional isomers, for example, using a series of N isomeric analytes with or without an internal standard where N is an integer from 2 to 6 inclusive. The concentrations of the N isomeric analytes may or may not be interleaved between two or more standards. The method allows for repeated instrument characterization without having many of the problems associated with using only a single standard such as octafluoronaphthalene (OFN), for example, persistence, and it may lessen sample carryover issues between adjacent samples. Methods are described using positional isomers of dibromodifluorobenzene in various configurations that show an improved means for qualitative and quantitative analysis of one or more analytes by GC-MS.