Abstract: 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.

Abstract: A photodetecting device includes a semiconductor substrate, a plurality of avalanche photodiodes each including a light receiving region disposed at a first principal surface side of the semiconductor substrate, the avalanche photodiodes being arranged two-dimensionally at the semiconductor substrate, and a through-electrode electrically connected to a corresponding light receiving region. The through-electrode is provided in a through-hole penetrating through the semiconductor substrate in an area where the plurality of avalanche photodiodes are arranged two-dimensionally. At the first principal surface side of the semiconductor substrate, a groove surrounding the through-hole is formed between the through-hole and the light receiving region adjacent to the through-hole.

Abstract: A photodetecting device includes a semiconductor substrate, a plurality of avalanche photodiodes each having a light receiving region, the avalanche photodiodes being arranged in a matrix at the semiconductor substrate, and a plurality of through-electrodes electrically connected to corresponding light receiving regions. The plurality of through-electrodes are arranged for each area surrounded by four mutually adjacent avalanche photodiodes of the plurality of avalanche photodiodes. Each of the light receiving regions has, when viewed from a direction perpendicular to a first principal surface of the semiconductor substrate, a polygonal shape including a pair of first sides opposing each other in a row direction and extending in a column direction and four second side opposing four through-electrodes surrounding the light receiving region and extending in directions intersecting with the row direction and the column direction. The length of the first side is shorter than the length of the second side.

Abstract: A photodetecting device includes a semiconductor substrate, a plurality of avalanche photodiodes each including a light receiving region disposed at a first principal surface side of the semiconductor substrate, the avalanche photodiodes being arranged two-dimensionally at the semiconductor substrate, and a through-electrode electrically connected to a corresponding light receiving region. The through-electrode is provided in a through-hole penetrating through the semiconductor substrate in an area where the plurality of avalanche photodiodes are arranged two-dimensionally. At the first principal surface side of the semiconductor substrate, a groove surrounding the through-hole is formed between the through-hole and the light receiving region adjacent to the through-hole.

Abstract: Methods and systems are provided herein for selectively removing product ions resulting from an ECD dissociation event from the interaction region of an ECD reaction cell, while other precursor peptide ions continue to undergo ECD within the interaction region, thereby reducing or preventing the occurrence of multiple electron capture events by the product ions. In some aspects, the preferential extraction of product ions from the interaction region during the ECD reaction can occur without an auxiliary AC field being generated within the interaction region. Additionally, in some aspects, the methods and systems disclosed herein can subject the various product ions to a non-dissociative charge reduction via exposure to reagent ions of the opposite polarity so as to selectively concentrate product ions to a lower charge state.

Abstract: 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.

Abstract: 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.

Abstract: A photodetecting device includes a semiconductor substrate including a one-dimensionally distributed plurality of pixels. The photodetecting device includes, for each pixel, a plurality of avalanche photodiodes arranged to operate in Geiger mode, a plurality of quenching resistors electrically connected in series with the respective avalanche photodiodes, and a signal processing unit arranged to process output signals from the plurality of avalanche photodiodes. Light receiving regions of the plurality of avalanche photodiodes are two-dimensionally distributed for each pixel. Each signal processing unit includes a gate grounded circuit and a current mirror circuit electrically connected to the gate grounded circuit. The gate grounded circuit is electrically connected to the plurality of avalanche photodiodes of the corresponding pixel via the plurality of quenching resistors. The current minor circuit is arranged to output a signal corresponding to output signals from the plurality of avalanche photodiodes.

Abstract: A mass isolation device selects a precursor ion of a sample that has been digested using a protease. A first fragmentation device fragments the precursor ion using collision-induced dissociation (CID), and the resulting product ions are analyzed using a mass analyzer producing a CID spectrum. A list of theoretical candidate glycopeptide sequences is determined from CID spectrum. The mass isolation device again selects the precursor ion of the sample. A second fragmentation device fragments the precursor ion using electron-based dissociation (ExD), and the resulting product ions are analyzed using the mass analyzer producing a CID spectrum. For each sequence of the list, the sequence is computationally fragmented, producing theoretical fragments, mass-to-charge ratio (m/z) values are calculated for the theoretical fragments, and the sequence is scored using c and z fragment matching rules. The highest scoring sequence is identified as a peptide sequence of a glycopeptide of the sample.

Abstract: A calibration apparatus for a mass analyzer includes an ion source device and a dual-purpose electron beam generating unit. The ion source device ionizes an analyte of a sample, producing analyte ions. The dual-purpose electron beam generating unit is positioned between the ion source device and the mass analyzer. In a first mode, the dual-purpose electron beam generating unit is used to create fragments of analyte ions of unknown mass-to-charge ratio. In a second mode, the dual-purpose electron beam generating unit is used to create ions of calibration compounds of known mass-to-charge ratio. All ions are subsequently transferred to the mass analyzer.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: A photodetector device includes an avalanche photodiode array substrate. A circuit substrate includes time measurement circuits and a clock driver. Each of the time measurement circuit includes a delay line unit, and is arranged to acquire, from an operation result of a delay line, time information indicating timing at which a pulse signal is input from a corresponding avalanche photodiode. The delay line unit is arranged to initiate an operation of the delay line in response to input of the pulse signal to the time measurement circuit, and to stop the operation of the delay line in response to input of a clock signal from a clock driver to the time measurement circuit, and is arranged to detect a time interval shorter than a cycle of the clock signal by the operation of the delay line.

Abstract: A photodetecting device includes a semiconductor photodetecting element including a plurality of pixels distributed two-dimensionally and a mount substrate including a plurality of signal processing units arranged to process output signals from the corresponding pixels. The semiconductor photodetecting element includes, for each of the pixels, a plurality of avalanche photodiodes arranged to operate in Geiger mode, a plurality of quenching resistors each electrically connected in series with a respective avalanche photodiodes, and a through-electrode electrically connected to the plurality of quenching resistors. Each of the signal processing units includes a current mirror circuit electrically connected to the plurality of avalanche photodiodes via the corresponding through-electrode and arranged to output a signal corresponding to output signals from the plurality of avalanche photodiodes.

Abstract: A photodetector device includes an avalanche photodiode array substrate formed from compound semiconductor. A plurality of avalanche photodiodes arranged to operate in a Geiger mode are two-dimensionally arranged on the avalanche photodiode array substrate. A circuit substrate includes a plurality of output units which are connected to each other in parallel to form at least one channel. Each of the output units includes a passive quenching element and a capacitative element. The passive quenching element is connected in series to at least one of the plurality of avalanche photodiodes. The capacitative element is connected in series to at least one of the avalanche photodiodes and is connected in parallel to the passive quenching element.

Abstract: 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.

Abstract: A semiconductor substrate has a first main surface and a second main surface that oppose each other and a plurality of cells that are arrayed two-dimensionally in a matrix. Each cell includes at least one avalanche photodiode arranged to operate in a Geiger mode. A trench penetrating through the semiconductor substrate is formed in the semiconductor substrate to surround each cell when viewed in a direction orthogonal to the first main surface. A light-shielding member optically separates mutually adjacent cells of the plurality of cells. The light-shielding member includes a first portion extending in a thickness direction of the semiconductor substrate between an opening end of the trench at the first main surface and an opening end of the trench at the second main surface and a second portion projecting out from the second main surface. The insulating film includes a portion that covers the second portion.

Abstract: A photodetector device includes an avalanche photodiode array substrate formed from compound semiconductor. A plurality of avalanche photodiodes arranged to operate in a Geiger mode are two-dimensionally arranged on the avalanche photodiode array substrate. A circuit substrate includes a plurality of output units which are connected to each other in parallel to form at least one channel. Each of the output units includes a passive quenching element and a capacitative element. The passive quenching element is connected in series to at least one of the plurality of avalanche photodiodes. The capacitative element is connected in series to at least one of the avalanche photodiodes and is connected in parallel to the passive quenching element.

Abstract: 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.