Patents by Inventor Alexander A. Makarov

Alexander A. Makarov has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).

  • Publication number: 20200328073
    Abstract: A method of operating a mass spectrometer, comprising: generating ions from a sample; mass filtering the ions using a quadrupole mass filter having a set of selection parameters to transmit ions within at least one selected range of mass-to-charge ratios narrower than an initial range, wherein the quadrupole comprises four parallel elongate electrodes arranged in opposing pairs to which are applied RF and DC, wherein an attractive DC voltage is applied to one pair of opposing electrodes and a repulsive DC voltage is applied to the other pair; mass analysing or detecting the ions transmitted by the quadrupole mass filter; repeating the steps of generating ions, mass filtering and mass analysing or detecting multiple times; switching a configuration of the pairs of opposing electrodes to which the attractive DC voltage and the repulsive DC voltage are applied multiple times over the course of repeating the steps so that over long term operation the build-up of contamination on each pair of opposing electrodes i
    Type: Application
    Filed: April 8, 2020
    Publication date: October 15, 2020
    Inventors: Amelia Corinne Peterson, Jan-Peter Hauschild, Oliver Lange, Alexander A. Makarov
  • Publication number: 20200294784
    Abstract: Trapping ions in an ion trapping assembly is described. In one aspect, this is implemented by introducing ions into the ion trapping assembly, applying a first RF trapping amplitude to the ion trapping assembly so as to trap introduced ions which have m/z ratios within a first range of m/z ratios, and cooling the trapped ions. In some aspects, also performed is reducing the RF trapping amplitude from the first RF trapping amplitude to a second, lower, RF trapping amplitude so as to reduce the low mass cut-off of the ion trapping assembly and trapping, at the second, lower RF trapping amplitude, introduced ions having m/z ratios within a second range of m/z ratios. A lower mass limit of the second range of m/z ratios is below the low mass cut-off of the ion trapping assembly when the first RF trapping amplitude is applied.
    Type: Application
    Filed: March 11, 2020
    Publication date: September 17, 2020
    Inventors: Dirk Nolting, Alexander A. Makarov, Amelia Corinne Petersen
  • Patent number: 10755907
    Abstract: A method of producing a mass spectrum from a time-varying transient signal detected in a mass spectrometer, the method comprising: performing a Fourier transform of the transient signal to produce a first set of complex amplitudes wherein each of the complex amplitudes corresponds to a respective frequency of a first set of frequencies; generating a second set of complex amplitudes, wherein each of the complex amplitudes corresponds to a respective frequency of a second set of frequencies with a minimum spacing less than the inverse of the duration of the transient signal; optimizing the second set of complex amplitudes to produce an improved second set; generating a mass spectrum from at least some of the improved second set of complex amplitudes; wherein optimizing the second set of complex amplitudes to produce an improved second set of complex amplitudes is based on an objective function subject to some phase constraints.
    Type: Grant
    Filed: April 18, 2016
    Date of Patent: August 25, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Konstantin Aizikov, Dmitry Grinfeld, Alexander Makarov
  • Patent number: 10755908
    Abstract: A system and method of mass spectrometry is provided. Ions from an ion source are stored in a first ion storage device and in a second ion storage device. Ions are ejected from the first ion storage device to a first mass analysis device during a first ejection time period, for analysis during a first analysis time period. Ions are ejected from the second ion storage device to a second mass analysis device during a second ejection time period. The ion storage devices are connected in series such that an ion transport aperture of the first ion storage device is in communication with an ion transport aperture of the second ion storage device. The first analysis time period and the second ejection time period at least partly overlap.
    Type: Grant
    Filed: March 26, 2019
    Date of Patent: August 25, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Alexander A. Makarov, Stevan R. Horning
  • Patent number: 10748755
    Abstract: An electrostatic trap such as an orbitrap is disclosed, with an electrode structure. An electrostatic trapping field of the form U?(r, ?, z) is generated to trap ions within the trap so that they undergo isochronous oscillations. The trapping field U?(r, ?, z) is the result of a perturbation W to an ideal field U(r, ?, z) which, for example, is hyperlogarithmic in the case of an orbitrap. The perturbation W may be introduced in various ways, such as by distorting the geometry of the trap so that it no longer follows an equipotential of the ideal field U(r, ?, z), or by adding a distortion field (either electric or magnetic). The magnitude of the perturbation is such that at least some of the trapped ions have an absolute phase spread of more than zero but less than 2? radians over an ion detection period Tm.
    Type: Grant
    Filed: January 30, 2019
    Date of Patent: August 18, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Alexander A. Makarov, Eduard V. Denisov, Gerhard Jung, Wilko Balschun, Stevan R. Horning
  • Publication number: 20200251317
    Abstract: An elemental mass spectrometer uses a mass filter to select ions from ions received from an ion source and transmit the selected ions. A reaction or collision cell receives the transmitted ions and reacts or collides these with a gas to provide product ions thereby. A mass analyzer receives the product ions, analyzes them and provides at least one output based on detection of the analyzed ions. The elemental mass spectrometer is operated to provide a first output from the mass analyzer measuring ions within a first analysis range of mass-to-charge to provide a second output from the mass analyzer measuring ions within a second analysis range of mass-to-charge ratios and to correct the first output for interference on the basis of the second output.
    Type: Application
    Filed: April 17, 2020
    Publication date: August 6, 2020
    Inventors: Lothar Rottman, Alexander Makarov, Hans-Juergen Schlueter, Christoph Wehe
  • Publication number: 20200243322
    Abstract: A multi-reflection mass spectrometer comprising two ion mirrors spaced apart and opposing each other in a direction X, each mirror elongated generally along a drift direction Y, the drift direction Y being orthogonal to the direction X, a pulsed ion injector for injecting pulses of ions into the space between the ion mirrors, the ions entering the space at a non-zero inclination angle to the X direction, the ions thereby forming an ion beam that follows a zigzag ion path having N reflections between the ion mirrors in the direction X whilst drifting along the drift direction Y, a detector for detecting ions after completing the same number N of reflections between the ion mirrors, and an ion focusing arrangement at least partly located between the opposing ion mirrors and configured to provide focusing of the ion beam in the drift direction Y, such that a spatial spread of the ion beam in the drift direction Y passes through a single minimum at or immediately after a reflection having a number between 0.
    Type: Application
    Filed: November 27, 2019
    Publication date: July 30, 2020
    Inventors: Hamish Stewart, Dmitry E. Grinfeld, Alexander A. Makarov
  • Patent number: 10727039
    Abstract: A mass spectrometer comprising: a pulsed ion source for generating pulses of ions having a range of masses; a time-of-flight mass analyzer for receiving and mass analyzing the pulses of ions from the ion source; and an energy controlling electrode assembly located between the pulsed ion source and the time-of-flight mass analyzer configured to receive the pulses of ions from the pulsed ion source and apply a time-dependent potential to the ions thereby to control the energy of the ions depending on their m/z before they reach the time-of-flight mass analyzer. Mass dependent differences in average energy of ions can be reduced for injection into a time-of-flight mass analyzer, which can improve ion transmission and/or instrument resolving power.
    Type: Grant
    Filed: June 18, 2018
    Date of Patent: July 28, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Stewart Hamish, Dmitry Grinfeld, Alexander Makarov
  • Publication number: 20200232995
    Abstract: Provided herein are methods for measuring a molecular flux rate proteins and polypeptides based on analysis of isotopologue abundances of immonium ion fragments within a mass isotopomer using a high resolution mass spectrometric measurement. Such methods may be used, inter alia, to calculate a fraction of newly synthesized protein or polypeptide molecules of interest, a replacement rate of target molecules of interest, and/or a rate of breakdown or degradation of target molecules of interest, e.g., based on isotopologue relative abundances.
    Type: Application
    Filed: September 7, 2016
    Publication date: July 23, 2020
    Applicant: KineMed, Inc.
    Inventors: Marc K. HELLERSTEIN, Thomas E. ANGEL, Alexander A. MAKAROV
  • Patent number: 10714322
    Abstract: A sample introduction system for a spectrometer comprises a desolvation region that receives or generates sample ions from a solvent matrix and removes at least some of the solvent matrix from the sample ions. A separation chamber downstream of the desolvation region has a separation chamber inlet communicating with the desolvation region, for receiving the desolvated sample ions along with non-ionised solvent and solvent ion vapours. The separation chamber has electrodes for generating an electric field within the separation chamber, defining a first flow path for sample ions between the separation chamber inlet and a separation chamber outlet. Unwanted solvent ions and non-ionised solvent vapours are directed away from the separation chamber outlet. The sample introduction system has a reaction chamber with an inlet communicating with the separation chamber outlet, for receiving the sample ions from the separation chamber and for decomposing the received ions into smaller products.
    Type: Grant
    Filed: September 18, 2019
    Date of Patent: July 14, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Alexander A. Makarov, Stevan R. Horning
  • Patent number: 10699888
    Abstract: A data independent acquisition method of mass spectrometry for analyzing a sample within a mass range of interest as it elutes from a chromatography system. The method comprises selecting precursor ions within a mass range of interest to be analyzed, performing at least one MS1 scan of the precursor ions using a Fourier Transform mass analyser and performing a set of MS2 scans by segmenting the precursor ions into a plurality of precursor mass segments, each precursor mass segment having a mass range of no greater than 5 amu, and for each precursor mass segment fragmenting the precursor ions within that precursor mass segment and performing an MS2 scan of the fragmented ions.
    Type: Grant
    Filed: May 30, 2018
    Date of Patent: June 30, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Anastassios Giannakopulos, Alexander Makarov, Christian Albrecht Hock, Nicolaie Eugen Damoc, Hamish Stewart
  • Patent number: 10665438
    Abstract: An elemental mass spectrometer uses a mass filter to select ions from ions received from an ion source and transmit the selected ions. A reaction or collision cell receives the transmitted ions and reacts or collides these with a gas to provide product ions thereby. A mass analyzer receives the product ions, analyzes them and provides at least one output based on detection of the analyzed ions. The elemental mass spectrometer is operated to provide a first output from the mass analyzer measuring ions within a first analysis range of mass-to-charge ratios including a desired mass-to-charge ratio, M, to provide a second output from the mass analyzer measuring ions within a second analysis range of mass-to-charge ratios including a mass-to-charge ratio at least 0.95 atomic mass units lower than the desired mass-to-charge ratio, (M?i), i?0.95 and to correct the first output on the basis of the second output.
    Type: Grant
    Filed: September 9, 2016
    Date of Patent: May 26, 2020
    Assignee: Thermo Fisher Scientific (Bremen) GMBH
    Inventors: Lothar Rottmann, Alexander Makarov, Hans-Juergen Schlueter, Christoph Wehe
  • Publication number: 20200152435
    Abstract: A method of analyzing molecules, comprising: generating ions from a sample of molecules; cooling the generated ions below ambient temperature; fragmenting at least some of the cooled ions by irradiating the ions with light at a plurality of different wavelengths (?) within one or more predetermined spectral intervals; recording a fragment mass spectrum of the fragmented ions comprising a detected signal (I) versus m/z over a predetermined range of m/z values for each of the plurality of different wavelengths (?), thereby recording a two-dimensional dependency of the detected signal (I) on m/z and irradiation wavelength (?); and determining from the recorded two-dimensional dependency an identity of at least one of the generated ions and/or relative abundances of different generated ions and thereby determining an identity of at least of one of the molecules and/or relative abundances of different molecules in the sample.
    Type: Application
    Filed: January 15, 2020
    Publication date: May 14, 2020
    Inventors: Alexander MAKAROV, Oleg BOYARKINE, Vladimir KOPYSOV
  • Patent number: 10615016
    Abstract: The present inventive concepts relate to determining an isotope ratio using mass spectrometry. Mass spectra of ions are obtained by generating ions, guiding the ions through a device having a mass transfer function that varies with ion current, providing at least some of the ions to a mass analyser and obtaining a mass spectrum of the ions and determining the ion current of the ions provided to the mass analyser. An isotope ratio of the ions is determined for each mass spectrum. Using the determined isotope ratio and determined ion current for each mass spectrum, a calibration relationship is determined that characterises the variation of the determined isotope ratios and the measured ion currents across the mass spectra. Then, a measured isotope ratio obtained at a determined ion current is adjusted using the calibration relationship to adjust the measured isotope ratio to an adjusted isotope ratio corresponding to a selected ion current.
    Type: Grant
    Filed: September 6, 2018
    Date of Patent: April 7, 2020
    Assignees: Thermo Fisher Scientific (Bremen) GMBH, California Institute of Technology
    Inventors: John Eiler, Alexander Makarov, Johannes Schwieters, Dieter Juchelka, Jens Griep-Raming
  • Patent number: 10546737
    Abstract: A method of analyzing molecules, comprising: generating ions from a sample of molecules; cooling the generated ions below ambient temperature; fragmenting at least some of the cooled ions by irradiating the ions with light at a plurality of different wavelengths (?) within one or more predetermined spectral intervals; recording a fragment mass spectrum of the fragmented ions comprising a detected signal (I) versus m/z over a predetermined range of m/z values for each of the plurality of different wavelengths (?), thereby recording a two-dimensional dependency of the detected signal (I) on m/z and irradiation wavelength (?); and determining from the recorded two-dimensional dependency an identity of at least one of the generated ions and/or relative abundances of different generated ions and thereby determining an identity of at least of one of the molecules and/or relative abundances of different molecules in the sample.
    Type: Grant
    Filed: April 16, 2019
    Date of Patent: January 28, 2020
    Assignees: Thermo Fisher Scientific (Bremen) GmbH, Ecole Polytechnique Federale de Lausanne (EPFL)
    Inventors: Alexander Makarov, Oleg Boyarkine, Vladimir Kopysov
  • Publication number: 20200013604
    Abstract: A sample introduction system for a spectrometer comprises a desolvation region that receives or generates sample ions from a solvent matrix and removes at least some of the solvent matrix from the sample ions. A separation chamber downstream of the desolvation region has a separation chamber inlet communicating with the desolvation region, for receiving the desolvated sample ions along with non-ionised solvent and solvent ion vapours. The separation chamber has electrodes for generating an electric field within the separation chamber, defining a first flow path for sample ions between the separation chamber inlet and a separation chamber outlet. Unwanted solvent ions and non-ionised solvent vapours are directed away from the separation chamber outlet. The sample introduction system has a reaction chamber with an inlet communicating with the separation chamber outlet, for receiving the sample ions from the separation chamber and for decomposing the received ions into smaller products.
    Type: Application
    Filed: September 18, 2019
    Publication date: January 9, 2020
    Inventors: Alexander A. MAKAROV, Stevan R. HORNING
  • Publication number: 20200006045
    Abstract: An ion guide may comprise a set of plate electrodes, each plate electrode having a plurality of apertures formed therethrough. The set of plate electrodes are spatially arranged such that a relative positioning of each plurality of apertures of a respective plate electrode of the set of plate electrodes and respective adjacent plate electrodes of the set of plate electrodes defines a continuous ion flight path through the respective plurality of apertures of each plate electrode of the set of plate electrodes. The continuous ion flight path has a helical-based and/or spiral-based shape.
    Type: Application
    Filed: May 15, 2019
    Publication date: January 2, 2020
    Inventors: Hamish STEWART, Alexander WAGNER, Alexander A. MAKAROV
  • Publication number: 20190383294
    Abstract: A vacuum pump system for evacuating at least five volumes comprising a turbomolecular pump and a forevacuum pump arranged to pump an output of the turbomolecular pump arrangement to atmosphere. The turbomolecular pump has at least five pumping stages separated by rotor blades. Not more than three pumping stages have pumping speeds in excess of ? of the highest pumping speed when under vacuum and/or a pumping port cross section in excess of ? of the highest pumping port cross section, and at least two pumping stages have pumping speeds less than ¼ of the highest pumping speed when under vacuum and/or a pumping port cross section of less than ¼ of the biggest pumping port cross section. The ratio of pressures between the pumping stage with the highest pressure and the pumping stage with the lowest pressure is at least 100000:1 when under vacuum.
    Type: Application
    Filed: August 27, 2019
    Publication date: December 19, 2019
    Inventors: Alexander A. MAKAROV, Wilko BALSCHUN
  • Patent number: 10510525
    Abstract: An apparatus for separating ions includes an electrode arrangement having a length extending between first and second ends. The first end is configured to introduce a beam of ions into an ion transmission space of the arrangement. An electronic controller applies an RF potential and a DC potential to an electrode of the electrode arrangement, for generating a ponderomotive RF electric field and a mass-independent DC electric field. The application of the potentials is controlled such that a ratio of the strength of the ponderomotive RF electric field to the strength of the mass-independent DC electric field varies along the length of the electrode arrangement. The generated electric field supports extraction of ions having different m/z values at respective different positions along the length of the electrode arrangement. Ions are extracted in one of increasing and decreasing sequential order of m/z ratio with increasing distance from the first end.
    Type: Grant
    Filed: January 10, 2019
    Date of Patent: December 17, 2019
    Assignees: Thermo Fisher Scientific (Bremen) GmbH, Thermo Finnigan LLC
    Inventors: Dmitry E. Grinfeld, Mikhail V. Ugarov, Viatcheslav V. Kovtoun, Alexander A. Makarov
  • Patent number: 10488529
    Abstract: A method of imaging analyte elements in an organic sample includes providing the sample as a layer on a substrate and reacting the sample on the substrate to produce one or more volatile products that leave the sample while the one or more elements remain in the sample. A majority of the sample layer by weight is removed from the substrate by the reaction and the remaining sample layer is enriched in the one or more elements which are not spatially disturbed by the reaction. The method including subsequently detecting the one or more elements in the concentrated sample layer using an imaging elemental analyzer.
    Type: Grant
    Filed: December 12, 2018
    Date of Patent: November 26, 2019
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Alexander A. Makarov, Johannes Schwieters