Dh Technologies Development Pte. Ltd.

Pavel Ryumin

Takashi Baba

William Morgan Loyd

Nic G Bloomfield

Igor Chemushevich

Methods and systems for identifying or classifying charge states of detected ions. An example method for classifying a charge state of detected ions may include generating a pulse for each ion in a plurality of ions detected by a detector, wherein each pulse has a pulse characteristic; generating a pulse-characteristic distribution of the generated pulses; and based on the pulse-characteristic distribution, generating an identification of the charge state of one or more ions in the plurality of ions.

Charge state determination of a single ion detection event

Method and devices for performing top down analysis of an antibody are described which involve utilizing an ion source to generate a plurality of ions from a sample containing at least one intact antibody. Further, transmitting said plurality of ions through a quadrupole rod set while applying an RF signal thereto and in the absence of a resolving DC voltage so as to preferentially transmit precursor ions having an m/z value greater than a low mass cutoff of about 1500 m/z from the quadrupole rod set to an ECD cell. The method and device can also performing an ECD reaction in the ECD cell on said precursor ions and also detect reaction products from the ECD reaction.

Background reduction in top-down antibody analysis

An ion source ionizes a compound, producing precursor ions with different m/z values. A reagent source supplies charge reducing reagent. An ion guide is positioned between a mass filter and both the ion source and the reagent source. The ion guide applies an AC voltage and DC voltage to its electrodes that creates a pseudopotential to trap the precursor ions in the ion guide below a threshold m/z. This AC voltage, in turn, causes the trapped precursor ions to be charge reduced by the reagent so that m/z values of the trapped precursor ions increase to a single m/z value above the threshold m/z. The ion guide applies the DC voltage to its electrodes relative to a DC voltage applied to electrodes of the mass filter that causes the precursor ions with m/z values increased to the single m/z value to be continuously transmitted to the mass filter.

Precursor accumulation in a single charge state in mass spectrometry

Intensity measurements made by electron multiplier and image-charge detectors are proportional to charge state. These intensities are used to separate detected ions into different data sets and create mass spectra from the different data sets. Ion measurements are separated by charge state using (i) a single electron multiplier detector, (ii) a single image-charge detector, or (iii) multiple electron multiplier ADC detectors. Using (i), the intensity of a peak calculated from each measured pulse is compared to predetermined intensity ranges and each peak is stored in a corresponding data set. Using (ii), each measured transient time-domain signal is converted to frequency-domain peaks, the intensity of each frequency-domain peak is compared to predetermined intensity ranges, and each peak is stored in a corresponding data set. Using (iii), each detector is adapted to measure a predetermined intensity range and store calculated peaks from the measured pulses in corresponding data sets.

Acquisition strategy for top-down analysis with reduced background and peak overlapping

A dissociation device fragments a precursor ion, producing at least two different product ions with overlapping m/z values in the dissociation device. The dissociation device applies an AC voltage and a DC voltage creating a pseudopotential that traps ions below a threshold m/z including the at least two product ions. The dissociation device receives a charge reducing reagent that causes the trapped at least two product ions to be charge reduced until their m/z values increase above the threshold m/z set by the AC voltage. The increase in the m/z values of the at least two product ions decreases their overlap. The at least two product ions with increased m/z values are transmitted to another device for subsequent mass analysis by applying the DC voltage to the dissociation device relative to a DC voltage applied to the other device.

Method for top down proteomics using ExD and PTR

An electron-ion interaction module for use in a mass spectrometer, having a plurality of rod sets arranged relative to one another such that said rod sets share a common longitudinal axis and each of said rod sets is longitudinally separated from an adjacent rod set by a gap, each of said rod sets comprising a plurality of rods arranged around said common longitudinal axis. The module further includes at least one magnet disposed around said rod sets so as to at least partially surround one or more of said plurality of rod sets and configured to generate a static magnetic field along said longitudinal axis. The rod sets are configured to receive electrons from an electron source and ions from an ion source within an interaction volume defined by the rods. One or more RF voltage sources coupled to the plurality of rod sets applies voltages to the rods.

RF-ion guide with improved transmission of electrons

In one aspect, an electron-ion reaction module, e.g., an electron capture dissociation module, for use in a mass spectrometer is disclosed, which comprises a chamber, an electron source for generating electrons and introducing the electrons into the chamber, a gate electrode positioned relative to the electron source and the chamber, and a DC voltage source operatively coupled to the gate electrode for applying control voltages to the gate electrode. The electron-ion interaction module can further include a controller operably coupled to the DC voltage source and configured for adjusting the DC voltage applied to the gate electrode to adjust flow of electrons into the chamber.

Electron beam throttling for electron capture dissociation

A separation device separates an unknown intact mAb or reduced mAb subunits of a known mAb class from a sample. An ion source device ionizes the mAb. A mass spectrometer fragments the ionized mAb using an ECD device and mass analyzes resulting product ions using a mass analyzer, producing one or more product ion spectra. Theoretical product ion peaks are calculated for one or more constant portions of the mAb class. The theoretical product ion peaks are removed from the one or more product ion spectra, producing one or more difference product ion spectra. De novo sequencing is applied to the one or more difference product ion spectra, producing one or more candidate sequences for one or more variable portions of the mAb. A genome database is searched for matches to the one or more candidate sequences, producing one or more matched sequences for the one or more variable portions.

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Toronto, Canada

Pavel Ryumin