Patents Assigned to DH Technologies Development Pte. Ltd.
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Patent number: 11133163Abstract: A system and method are provided for loading a sample into an analytical instrument using acoustic droplet ejection (“ADE”) in combination with a continuous flow sampling probe. An acoustic droplet ejector is used to eject small droplets of a fluid sample containing an analyte into the sampling tip of a continuous flow sampling probe, where the acoustically ejected droplet combines with a continuous, circulating flow stream of solvent within the flow probe. Fluid circulation within the probe transports the sample through a sample transport capillary to an outlet that directs the analyte away from the probe to an analytical instrument, e.g., a device that detects the presence, concentration quantity, and/or identity of the analyte. When the analytical instrument is a mass spectrometer or other type of device requiring the analyte to be in ionized form, the exiting droplets pass through an ionization region, e.g.Type: GrantFiled: August 4, 2020Date of Patent: September 28, 2021Assignees: LABCYTE, INC., DH TECHNOLOGIES DEVELOPMENT PTE. LTDInventors: Sammy Datwani, Don W. Arnold, Lucien P. Ghislain, Chang Liu, Thomas Covey
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Patent number: 11133167Abstract: In one aspect, a curtain and orifice plate assembly for use in a mass spectrometry system is disclosed, which comprises a curtain plate including a first printed circuit board (PCB) having an aperture configured for receiving ions generated by an ion source of the mass spectrometry system and at least one gas-flow channel, where said first PCB has at least one metal coating disposed on at least a portion thereof. The assembly further includes an orifice plate coupled to the curtain plate, which includes a PCB providing an orifice that is substantially aligned with the aperture of the curtain plate so that the ions entering the assembly via said aperture of the curtain plate can exit the assembly via said orifice of the orifice plate, where the second PCB has at least one metal coating disposed on at least a portion thereof.Type: GrantFiled: March 1, 2019Date of Patent: September 28, 2021Assignee: DH Technologies Development Pte. Ltd.Inventor: Robert Haufler
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Patent number: 11107666Abstract: 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: GrantFiled: November 2, 2020Date of Patent: August 31, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Ronald F. Bonner, Stephen A. Tate
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Patent number: 11085925Abstract: Methods and systems for separating and/or quantifying compounds, using differential mobility spectrometry (DMS) are provided herein. In accordance with various aspects of the applicants' teachings, the methods and systems can provide for the quantification of one or more compounds, for example, using isomeric labels that can be less costly to produce relative to conventional tags that incorporate stable-isotope labels. The present teachings can quantify the relative amount of a compound based on the effect of using an easily charged functional group as well as a functional group positioned at a resonant or non-resonant position through a DMS. In some aspects, methods and systems in accordance with various aspects of the present teachings provide for the detection and/or quantification of the analytes labeled with isomeric tags that can be differentiated via a DMS upstream of a first stage mass analyzer and/or prior to fragmentation of the labeled analyte, for example.Type: GrantFiled: November 29, 2016Date of Patent: August 10, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: John L. Campbell, Yves LeBlanc, Chang Liu
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Patent number: 11069516Abstract: One or more ions are received along a central axis through a first set of reflectron plates of an ELIT. Voltages are applied to the first set of plates and to a second set of reflectron plates in order to trap and oscillate the one or more ions. A first induced current is measured from a cylindrical pickup electrode between the first set of reflectron plates and the second set of reflectron plates. A second induced current is measured from one or more plates of the first set of reflectron plates. A third induced current is measured from one or more plates of the second set of reflectron plates. The first measured induced current, second measured induced current and third measured induced current are combined to reduce higher order frequency harmonics of the induced current.Type: GrantFiled: September 13, 2018Date of Patent: July 20, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Takashi Baba, Eric Thomas Dziekonski
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Patent number: 11067538Abstract: An apparatus includes a first electrode and a second electrode. The second electrode is placed in parallel with the first electrode to provide constant gap distance. The gap between the first electrode and the second electrode is at atmospheric pressure. Ions are introduced into the center of the gap and travel through the apparatus in a direction parallel to the first electrode and the second electrode. The apparatus is configured as a high-field symmetric-waveform apparatus for filtering high mobility ions or for fragmenting ions. The apparatus is also configured for three modes of operation: as a conventional DMS; as a filter high mobility ions; and as fragmentation device. A symmetric electric field is produced in the gap with a maximum density normalized field strength greater than 10 Td to filter high mobility ions and with a maximum density normalized field strength greater than 100 Td to fragment ions.Type: GrantFiled: March 21, 2017Date of Patent: July 20, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Bradley B. Schneider, Erkinjon Nazarov, Thomas R. Covey
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Patent number: 11069517Abstract: A system is disclosed for identifying precursor ions originating from an ion source device. A mass filter filters an ion beam by using a series of overlapping precursor ion mass selection windows across the precursor ion mass range. A mass analyzer analyzes the precursor ions of each precursor ion mass selection window of the series, producing a plurality of precursor ion spectra for the precursor ion mass range. A precursor ion is selected from the spectra. The intensities for the selected precursor ion are retrieved from the spectra and a trace is produced that describes how the intensity of the selected precursor ion varies with the location of the precursor ion mass selection window. The selected precursor ion is identified as a precursor ion originating from the ion source device if the trace includes a nonzero intensity for the m/z value of the selected precursor ion.Type: GrantFiled: February 1, 2018Date of Patent: July 20, 2021Assignee: DH Technologies Development Pte. Ltd.Inventor: Stephen Alexander Tate
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Patent number: 11031219Abstract: Systems and methods are disclosed for determining if the dynamic range of quantitation in mass spectrometry can be extended. A DIA method is performed on a sample for a compound of interest at each acquisition time of a plurality of acquisition times. A plurality of product ion spectra are produced for each window of two or more precursor ion mass selection windows. A known product ion of the compound of interest is selected. Two or more XICs are calculated from two or more different precursor ion windows for the known product ion. A ratio of one XIC of the two or more XICs to at least one other XIC of the two or more XICs is calculated. If the ratio is above a threshold, the XIC is used in the quantitation. If not, two or more XICs can be combined into a single XIC that is used for the quantitation.Type: GrantFiled: June 9, 2017Date of Patent: June 8, 2021Assignees: DH Technologies Development Pte. Ltd.Inventors: Ronald Francis Bonner, Lyle Lorrence Burton, Gérard Hopfgartner, Gordana Ivosev
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Patent number: 11031225Abstract: Because most ion optics of mass spectrometry systems are subject to ion deposition and may exhibit significantly different behavior following substantial contamination (e.g., loss of sensitivity), fouled surfaces must be regularly cleaned to maintain sensitivity. While the surfaces of front-end components (e.g., curtain plates, orifice plates, Qjet, Q0, IQ0) may be relatively easy to clean, the fouling of components contained within the downstream high-vacuum chambers (e.g., Q1, IQ1) can incur substantial delays and expense as the high-vacuum chambers must be vented and substantially disassembled prior to cleaning. Methods and systems for controlling contamination of components of mass spectrometer systems are provided herein. By reducing the transmission of contaminating ions during non-data acquisition periods, the present teachings can increase throughput, improve robustness, and/or decrease the downtime typically required to vent/disassemble/clean the fouled components.Type: GrantFiled: September 13, 2017Date of Patent: June 8, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Thomas R. Covey, Yves LeBlanc, Bradley B. Schneider
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Patent number: 11024494Abstract: An interference in a first MRM transition measurement for a compound of interest is determined by using a second MRM transition that includes an isotope of the precursor ion in the first MRM transition. Both transitions include the same product ion. A first intensity is measured for the first MRM transition and a second intensity is measured for the second MRM transition. A ratio of the first intensity to the second intensity is calculated. A theoretical ratio of the quantity of first precursor ion to the second precursor ion is calculated according to their isotopic relationship. A difference between the ratio and the theoretical ratio is calculated and compared to a threshold value. If the difference is less than the threshold value, the first intensity of the first MRM transition is identified as including an interference for the compound of interest.Type: GrantFiled: September 25, 2018Date of Patent: June 1, 2021Assignee: DH Technologies Development Pte. Ltd.Inventor: Yves Le Blanc
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Patent number: 11004669Abstract: 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 and/or the orientation of those double bonds within the sample molecules. The fragments may include radical fragments and non-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 as confirmation of the presence of those radical fragments.Type: GrantFiled: December 15, 2016Date of Patent: May 11, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Takashi Baba, Paul Baker, John Lawrence Campbell, Yves Le Blanc
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Patent number: 11002744Abstract: A system and method is described for characterizing glycopeptides which includes a first quadrupole mass filter, a multipole rod set of an ion guide, a lens electrode, an ExD device and a mass analyzer. The multipole rod set is adapted to receive a radial radio frequency (RF) trapping voltage and a radial dipole direct current (DC) voltage The lens electrode is adapted to receive an axial trapping alternating current (AC) voltage and a DC voltage. The ExD device performs electron capture dissociation or electron transfer dissociation, the ExD device being positioned so that an entrance of the ExD device is disposed on the other side of the lens electrode opposite the multipole rod set. The mass analyzer is positioned at an exit of the ExD device for receiving ions from the ExD device.Type: GrantFiled: June 28, 2018Date of Patent: May 11, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Takashi Baba, Yves Le Blanc
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Patent number: 10998179Abstract: Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which the flow of desorption solvent within a sampling probe fluidly coupled to an ion source can be selectively controlled such that one or more analyte species can be desorbed from a sample substrate inserted within the sampling probe within a decreased volume of desorption solvent for subsequently delivery to the ion source. In various aspects, sensitivity can be increased due to higher desorption efficiency (e.g., due to increased desorption time) and/or decreased dilution of the desorbed analytes.Type: GrantFiled: October 12, 2017Date of Patent: May 4, 2021Assignee: DH Technologies Development Pte. Ltd.Inventors: Don W. Arnold, Thomas R. Covey, Chang Liu
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Patent number: 10954931Abstract: In a linear displacement pump, liquid is discharged by driving a piston along at least part of a stroke length. While discharging the liquid, a linear position of the piston is sensed at a plurality of positions along the stroke length, and a plurality of output signals is produced. Based on one or more of the output signals, an operational state of the pump is determined.Type: GrantFiled: December 12, 2014Date of Patent: March 23, 2021Assignee: DH TECHNOLOGIES DEVELOPMENT PTE. LTD.Inventors: Phillip H. Paul, Kenneth R. Hencken
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Patent number: 10957526Abstract: In one aspect, an ion trap is disclosed, which includes a curved linear ion trap having a plurality of electrodes arranged around a central curved axis so as to provide a volume for trapping ions, said plurality of electrodes comprising at least one inner electrode and at least one outer electrode radially separated from said inner electrode. The ion trap further includes a pair of inner and outer ion guide electrodes providing a volume therebetween for receiving ions ejected from said curved ion trap and guiding the ejected ions to one or more spatial locations along a focal line, said inner and outer ion guide electrodes being positioned external to said ion trapping volume and in proximity of said at least inner and outer electrodes of the curved ion trap, respectively, wherein a DC voltage is applied between said ion guide electrodes to provide an electric filed therebetween for guiding the ejected ions to said spatial locations.Type: GrantFiled: November 2, 2017Date of Patent: March 23, 2021Assignee: DH Technologies Development Pte. Ltd.Inventor: Takashi Baba
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Patent number: 10825669Abstract: A metabolized product ion spectrum is produced for a metabolized version of a known compound using tandem mass spectrometry. Metabolized structures are inferred from the metabolized product ion spectrum. An unmetabolized product ion spectrum is received for an unmetabolized version of the known compound and unmetabolized structures are inferred from the unmetabolized product ion spectrum. Each of the metabolized structures is compared to the unmetabolized structures, producing matched and unmatched structures. For each unmatched structure, a biotransformation repository is searched for modifications and each unmatched structure and the modifications found are again compared to the unmetabolized structures, producing modified matched structures. For each atomic index of the known compound, an unmodified specificity is calculated from the matched structures, a modified intensity specificity is calculated from the modified matched structures, and a score is calculated from the specificities.Type: GrantFiled: December 22, 2017Date of Patent: November 3, 2020Assignee: DH Technologies Development Pte. Ltd.Inventors: Eva Duchoslav, Pui Yee Iris Shek, Alina Dindyal-Popescu
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Patent number: 10825668Abstract: One or more known compounds of a sample are ionized using an ion source, producing an ion beam of precursor ions. A tandem mass spectrometer receives the ion beam from the ion source, selects one or more precursor ions from the ion beam using a precursor ion mass selection window, fragments precursor ions within the precursor ion mass selection window, and mass analyzes the resulting product ions, producing an unknown product ion mass spectrum. A library product ion mass spectrum for a known compound is retrieved from a memory. Each peak of the unknown spectrum is analyzed for a potential non-halogen isotopic peak using a processor, and if a potential non-halogen isotopic peak is found, it is removed if it does not have a corresponding peak in the library spectrum.Type: GrantFiled: August 9, 2016Date of Patent: November 3, 2020Assignee: DH Technologies Development Pte. Ltd.Inventors: Lyle Lorrence Burton, David Michael Cox
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Patent number: 10825667Abstract: 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: GrantFiled: August 13, 2018Date of Patent: November 3, 2020Assignee: DH Technologies Development Pte. Ltd.Inventors: Ronald F. Bonner, Stephen A. Tate
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Patent number: 10818486Abstract: Methods and systems are provided for reducing the occurrence of unwanted electrical discharge when operating an electrospray ion source to generate ions for mass spectrometric analysis. In accordance with various aspects of the applicant's teachings, the methods and systems described herein can provide for controlling the ion emission current so as to limit the onset of avalanche of electrical discharge between the electrospray electrode and the counter electrode under ionization conditions that typically tend to increase the likelihood of such discharge (arcing), while nonetheless providing for maximal ionization efficiency.Type: GrantFiled: December 8, 2016Date of Patent: October 27, 2020Assignee: DH Technologies Development Pte. Ltd.Inventors: John J. Corr, Thomas R. Covey, Peter Kovarik
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Patent number: 10784098Abstract: Two-channel electrical and photo-electrical TOF ion detection systems are provided. These systems maintain the resolution and dynamic range advantages of four-channel systems but at a lower cost. Electrodes or light pipes are configured to direct electrons or photons produced by ion impacts into two separate channels. The first channel receives electrons or photons resulting from the inner or central part of the rectangular pattern of each ion impact. The second channel receives electrons or photons resulting from the two outer ends of the rectangular pattern of each ion impact. In a two-channel digitizer, the first channel and the second channel are independently calibrated to align the first digital value and the second digital value in time and account for the convex shape of the ion impacts of each ion packet and/or the curvature of a microchannel plate.Type: GrantFiled: March 1, 2018Date of Patent: September 22, 2020Assignee: DH Technologies Development Pte. Ltd.Inventors: Igor Chernushevich, Nic G. Bloomfield