Patents Assigned to DH Technologies Development Pte. Ltd.
  • Mass filtering of ions using a rotating field
    Patent number: 10096459
    Abstract: Systems and methods for filtering a continuous beam of ions are provided. An acceleration electric field is applied to a continuous beam of ions using an accelerator to produce an accelerated beam of ions. A field is applied to the accelerated beam to separate ions in time and space using a deflector producing a separated beam of ions. The field applied by the deflector is a rotating field or a circulant rastering field. The rotating field can be a rotating magnetic or electric field. Only accept those ions from the separated beam whose m/z values lie within a range centered around a target m/z value using an aperture. The aperture can include a pinhole aperture in a rotating disk or an annular aperture in a first stationary disk, a second deflector, and a pinhole aperture in the center of a second stationary disk.
    Type: Grant
    Filed: September 21, 2015
    Date of Patent: October 9, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Robert Alois Grothe, Jr.
  • Specific analysis of ketone and aldehyde analytes using reagent compounds, labeling strategies, and mass spectrometry workflow
    Patent number: 10094809
    Abstract: Labeling reagents, sets of labeling reagents, and labeling techniques are provided for the relative quantitation, absolute quantitation, or both, of ketone or aldehyde compounds including, but not limited to, analytes comprising steroids or ketosteroids and includes testosterone. The analytes can be medical or pharmaceutical compounds in biological samples. Methods for labeling, analyzing, and quantifying ketone or aldehyde compounds are also disclosed as are methods that also use mass spectrometry.
    Type: Grant
    Filed: October 31, 2016
    Date of Patent: October 9, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Subhakar Dey, Sasi Pillai, Brian L. Williamson, Subhasish Purkayastha, Michal Weinstock
  • Analysis of a panel of cerebrotendinous xanthomatosis biomarkers using site specific derivation and LC/MS/MS workflow
    Patent number: 10078091
    Abstract: A method, a labeling reagent, sets of labeling reagents, and labeling techniques are provided for the analysis of ketosterol biomarkers such as bile acid precursors from human plasma, serum or whole blood. This method is used for new born screening for Cerebrotendinous Xanthomatosis (CTX). Methods for labeling, analyzing, and quantifying ketosterol biomarkers are also disclosed as are methods that also use mass spectrometry.
    Type: Grant
    Filed: May 17, 2013
    Date of Patent: September 18, 2018
    Assignees: DH Technologies Development Pte. Ltd., Oregon Health and Science University
    Inventors: Andrea DeBarber, Subhasish Purkayastha, Robert D. Steiner, Michal Weinstock
  • Rapid scanning of wide quadrupole RF windows while toggling fragmentation energy
    Patent number: 10079137
    Abstract: A sample is ionized using an ion source and the ion beam is received using a tandem mass spectrometer. An m/z range is divided into two or more precursor ion isolation windows. Two or more values for a fragmentation parameter are selected. A first value of the two or more values for the fragmentation parameter has a level that fragments a minimal amount of ions of the ion beam. The one or more additional values have increasingly aggressive levels that produce increasingly more fragmentation of the ions of the ion beam. For each precursor ion isolation window, the tandem mass spectrometer is instructed to perform a selection and fragmentation of the ion beam using the precursor ion isolation window and the first value and is instructed to perform one or more additional selections and fragmentations of the ion beam using the precursor ion isolation window and using the one or more additional values.
    Type: Grant
    Filed: January 29, 2016
    Date of Patent: September 18, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Nic G. Bloomfield
  • Flow through MSfor improved selectivity
    Patent number: 10074525
    Abstract: Systems and methods are provided for selecting and fragmenting a first precursor ion in an MS3 experiment. One or more first excitation parameters are calculated that define a first dipole excitation using a processor. The first dipole excitation is used to select a first precursor ion and fragment the first precursor ion to produce a second precursor ion. The first dipole excitation is applied to the continuous beam of ions by sending a first set of data including the first excitation parameters to a mass spectrometer. The first set of data is sent so that a first quadrupole applies the first dipole excitation to a continuous beam of ions. The mass spectrometer includes an ion source that provides the continuous beam of ions and the first quadrupole that receives the continuous beam of ions and is adapted to apply dipole excitation to the continuous beam of ions.
    Type: Grant
    Filed: October 7, 2014
    Date of Patent: September 11, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Bruce Andrew Collings, Bruce A. Thomson
  • Systems and methods for rapidly screening samples by mass spectrometry
    Patent number: 10074526
    Abstract: Systems and methods are used to rapidly screening samples. A fast sample introduction device that is non-chromatographic is instructed to supply each sample of a plurality samples to a tandem mass spectrometer using a processor. The fast sample introduction device can include a flow injection analysis device, an ion mobility analysis device, or a rapid sample cleanup device. The tandem mass spectrometer is instructed to perform fragmentation scans at two or more mass selection windows across a mass range of each sample of the plurality of samples using the processor. The two or more mass selection windows across the mass range can have fixed or variable window widths. The tandem mass spectrometer can be instructed to obtain a mass spectrum of the mass range before instructing the tandem mass spectrometer to perform the fragmentation scans.
    Type: Grant
    Filed: December 2, 2016
    Date of Patent: September 11, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Ronald F. Bonner, Stephen A. Tate
  • Device for improved detection of ions in mass spectrometry
    Patent number: 10074529
    Abstract: An electron multiplier is positioned relative to at least one dynode to direct a beam of secondary particles from the at least one dynode to a collector area of the electron multiplier and not to a channel area of the electron multiplier for a range of electron multiplier voltages applied by one or more voltage sources to the electron multiplier and for a dynode voltage applied by the one or more voltage sources to the at least one dynode. The electron multiplier includes an aperture with an entrance cone and walls of the entrance cone comprise the collector area and an apex of the entrance cone comprises the channel area. An electron multiplier voltage of the range of electron multiplier voltages is applied to the electron multiplier and the dynode voltage is applied to the at least one dynode using the one or more voltage sources.
    Type: Grant
    Filed: January 29, 2016
    Date of Patent: September 11, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Bruce Andrew Collings, Pascal Martin, Stephen Bruce Locke
  • Systems and methods for using variable mass selection window widths in tandem mass spectrometry
    Patent number: 10074527
    Abstract: Systems and methods are used to analyze a sample using variable mass selection window widths. A tandem mass spectrometer is instructed to perform at least two fragmentation scans of a sample with different mass selection window widths using a processor. The tandem mass spectrometer includes a mass analyzer that allows variable mass selection window widths. The selection of the different mass selection window widths can be based on one or more properties of sample compounds. The properties may include a sample compound molecular weight distribution that is calculated from a molecular weight distribution of expected compounds or is determined from a list of molecular weights for one or more known compounds. The tandem mass spectrometer can also be instructed to perform an analysis of the sample before instructing the tandem mass spectrometer to perform the at least two fragmentation scans of the sample.
    Type: Grant
    Filed: November 7, 2017
    Date of Patent: September 11, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Ronald F. Bonner, Stephen A. Tate
  • Multiplexed precursor isolation for mass spectrometry
    Patent number: 10068752
    Abstract: Systems and methods for multiplexed precursor ion selection are provided. A mass isolator includes a selection region of rods, a transmission region of rods, and a barrier electrode lens separating the selection and transmission regions. Two or more different precursor ions are selected by applying two or more different AC voltage frequencies to rods of a selection region in order to resonate the two or more different precursor ions from a continuous beam of ions. The two or more different precursor ions are transmitted by applying a DC voltage to the barrier electrode lens, creating an electric field potential barrier over which only the resonating ions are transmitted. Precursor ions of product ions from combined product ion spectra produced by multiplexed precursor ion selection are identified by grouping the target precursor ions.
    Type: Grant
    Filed: October 7, 2014
    Date of Patent: September 4, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Takashi Baba
  • Systems and methods for identifying precursor ions from product ions using arbitrary transmission windowing
    Patent number: 10068753
    Abstract: A transmission window that has a constant rate of precursor ion transmission for each precursor ion is stepped across a mass range, producing a series of overlapping transmission windows across the mass range. The precursor ions produced at each step are fragmented. Resulting product ions are analyzed, producing a product ion spectrum for each step of the transmission window and a plurality of product ion spectra for the mass range. For at least one product ion of the plurality of product ion spectra, a function that describes how an intensity of the at least one product ion from the plurality of product ion spectra varies with precursor ion mass as the transmission window is stepped across the mass range is calculated. A precursor ion of the at least one product ion is identified from the function. An elution profile can also be determined from the function.
    Type: Grant
    Filed: October 7, 2014
    Date of Patent: September 4, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Nic G. Bloomfield, Frank Londry
  • Electron induced dissociation devices and methods
    Patent number: 10062556
    Abstract: A method and apparatus for conducting reactions between precursor ions and reagent ions, for example, a reaction between a precursor cation and an electron, such as ECD, are disclosed. The apparatus comprises first, second, and third pathways, each of which extends at least partially along a central axis, and wherein the second central axis is orthogonal to the first and third central axes. Charged species can be introduced into the second pathway as the ions are transmitted therethrough, thereby increasing precursor ion and charged species interaction without simultaneous trapping of the species.
    Type: Grant
    Filed: December 21, 2015
    Date of Patent: August 28, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Takashi Baba
  • Method for Removing Trapped Ions from a Multipole Device
    Publication number: 20180218895
    Abstract: A method and apparatus for clearing ions from a multipole ion transmission device which includes introducing a DC or RF clear out pulse to one or more of the rods of the multipole device. The DC pulse is selected so as to supply sufficient kinetic energy to the ions to overcome a pseudo-potential trapping well generated by the RF potentials of the ion transmission device. For an RF pulse, the auxiliary RF signal uses frequencies that correspond to the ejected ion's frequencies of motion. In select embodiments, the multipole device can be a quadrupole or the apparatus can be part of a tandem mass spectrometer.
    Type: Application
    Filed: November 28, 2014
    Publication date: August 2, 2018
    Applicant: DH Technologies Development PTE Ltd.
    Inventors: Bruce Andrew Collings, John Vandermey
  • Methods for analysis of lipids using mass spectrometry
    Patent number: 10032614
    Abstract: A method and apparatus for analyzing samples using mass spectrometry are disclosed. The apparatus includes a reaction device configured to dissociate sample ions into fragments by reacting the sample ions with a charged species (e.g., electrons) such as through ECD, EID, or EIEIO. The kinetic energy of the charged species is such that the fragments may be detected and produce spectra that allow for the determination of isomeric species in the sample and the location of double bonds of sample molecules. The fragments may include radical fragments and non-radical fragments. The apparatus may also include an oxygen gas source configured to react with the radical fragments to produce oxygen-radical fragments. Spectra resulting from analysis of the fragments may allow for the determination of the oxygen-radical fragments resulting from the dissociation of the sample molecules.
    Type: Grant
    Filed: June 4, 2015
    Date of Patent: July 24, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Takashi Baba, John Lawrence Campbell
  • Inline ion reaction device cell and method of operation
    Patent number: 10014166
    Abstract: A method and apparatus for conducting ion to charged species reactions, more particularly reactions wherein the charged species is an electron, such as ECD. The apparatus comprises first and second pathways which are orthogonal to one another. The first pathway through which ions are introduced comprises multiple multipoles with a gap situated there between. The second pathway introduces the charged species through the gap orthogonally to the first pathway. In this way, a cross-type reaction device allows ion-charged species interactions to occur.
    Type: Grant
    Filed: May 29, 2014
    Date of Patent: July 3, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Takashi Baba
  • Methods and systems for selecting ions for ion fragmentation
    Patent number: 10008376
    Abstract: The present teachings are directed to methods and systems for the selection of ions for subsequent ion fragmentation in the analysis of a sample. Rather than select the most intense subset of precursor ions for further analysis in an attempt to maximize the number of high quality, identifiable MS/MS spectra, in some settings, systems and methods for analyzing and 5 identifying precursor ions for further processing can benefit from a discovery approach in which precursor ions are selected randomly/stochastically.
    Type: Grant
    Filed: October 27, 2015
    Date of Patent: June 26, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Nic Bloomfield, Stephen A. Tate
  • Methods for detection in differential mobility spectrometer using a peptide metal complex
    Patent number: 10001456
    Abstract: Methods and systems for separating and/or quantifying peptides using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicant's teachings, the methods and systems can provide for the separation of one or more peptides, for example, peptides that may be difficult to separate with conventional techniques, such as mass spectrometry (MS), by complexing the peptides with a metal cation (e.g., Ca2+) prior to DMS. In some aspects, the present teachings can prevent proton stripping from ionized peptides that can occur in DMS to prevent unintended and/or undesirable alterations to the peptide's charge state distribution.
    Type: Grant
    Filed: August 28, 2015
    Date of Patent: June 19, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: John L Campbell, Yves LeBlanc, Chang Liu
  • RF-only detection scheme and simultaneous detection of multiple ions
    Patent number: 9997340
    Abstract: A mass spectrometer apparatus and method for conducting simultaneous MS/MS analysis including: a device to select a precursor ion having a specified m/z; a gas-filled collision cell; an RF-only multipole mass spectrometer, the mass spectrometer having a generator attached thereto for generating at least two auxiliary AC fields in the RF-only multipole mass spectrometer; a gate for providing a repulsive DC or AC barrier downstream to an exit of the RF-only multipole mass spectrometer; an ion detection system situated downstream from the DC or AC barrier for measuring an ion current derived from ions that overcome the repulsive barrier. The mass spectrometer may also be configured so that each of the auxiliary AC fields are generated by the introduction of individual auxiliary AC frequencies and each frequency is amplitude modulated at a unique frequency.
    Type: Grant
    Filed: September 12, 2014
    Date of Patent: June 12, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: James Hager, Christopher M Lock
  • High dynamic range detector correction algorithm
    Patent number: 9991104
    Abstract: Systems and methods are provided to perform dead time correction. An observed ion count rate is obtained using a non-paralyzable detection system of a mass spectrometer. The detection system includes an ion detector, a comparator/discriminator, a mono-stable circuit and a counter. The non-paralyzable detection system exhibits dead time extension at high count rates. The extension of the dead time occurs because the mono-stable circuit requires a rising edge to trigger and can only be triggered again after the output pulse from the comparator/discriminator has gone low. This allows a second comparator/discriminator pulse arriving just before the end of the dead time started by a first comparator/discriminator pulse to extend the dead time to the trailing edge of the second comparator/discriminator pulse. A true ion count rate is calculated by performing dead time correction of the observed ion count rate.
    Type: Grant
    Filed: April 19, 2013
    Date of Patent: June 5, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventors: Bruce Andrew Collings, Martian Dima, Gordana Ivosev
  • Grouping amplitudes of TOF extractions to detect convolution due to resolution saturation
    Patent number: 9978575
    Abstract: Sample molecules are ionized producing a beam of ions using an ion source. A plurality of ion extractions are performed on the beam of ions using a TOF mass spectrometer. Electrical detections from each extraction are measured using an ADC, producing a mass sub-spectrum for each extraction. An ion m/z from the plurality of mass sub-spectra is selected. For each mass sub-spectrum, the amplitude and m/z of an ion within a m/z tolerance of the ion m/z is assigned to the corresponding amplitude band of a plurality of predetermined amplitude bands, producing a plurality of amplitude and m/z values for the each amplitude band. For each amplitude band of the plurality of predetermined amplitude bands, the plurality of amplitude and m/z values are combined into a peak, resulting in a plurality of peaks corresponding to the plurality of predetermined amplitude bands.
    Type: Grant
    Filed: September 21, 2015
    Date of Patent: May 22, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Nic G. Bloomfield
  • Time-of-flight analysis of a continuous beam of ions by a detector array
    Patent number: 9978576
    Abstract: Systems and methods are provided for time-of-flight analysis of a continuous beam of ions by a detector array. A sample is ionized using an ion source to produce a continuous beam of ions. An electric field is applied to the continuous beam of ions using an accelerator to produce an accelerated beam of ions. A rotating magnetic and/or electric field is applied to the accelerated beam to separate ions with different mass-to-charge ratios over an area of a two-dimensional detector using a deflector located between the accelerator and the two-dimensional detector. An arrival time and a two-dimensional arrival position of each ion of the accelerated beam are recorded using the two-dimensional detector. Alternatively, an electric field that is periodic with time is applied in order to sweep the accelerated beam over a periodically repeating path on the two-dimensional rectangular detector.
    Type: Grant
    Filed: September 22, 2017
    Date of Patent: May 22, 2018
    Assignee: DH Technologies Development Pte. Ltd.
    Inventor: Robert Alois Grothe, Jr.