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).

  • Patent number: 11133162
    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: July 1, 2020
    Date of Patent: September 28, 2021
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Alexander A. Makarov, Stevan R. Horning
  • Patent number: 11133160
    Abstract: Systems, methods, and devices to dissociate ions using one or more light emitting diodes (LEDs). A mass spectrometer for ion dissociation includes an ion source for providing ions for dissociation, a mass analyzer, and a photodissociation (PD) device. The PD device includes an ion transport device. The ion transport device is configured perform one or more of: transporting the ions through the PD device, and trapping the ions within a region of the PD device. The PD device also includes one or more LEDs positioned to irradiate the ions in the PD device, resulting in fragmentation of the ions.
    Type: Grant
    Filed: June 2, 2017
    Date of Patent: September 28, 2021
    Assignees: BOARD OF REGENTS, UNIVERSITY OF TEXAS SYSTEM, THERMO FISHER SCIENTIFIC (BREMEN) GMBH, THERMO FINNIGAN LLC
    Inventors: Dustin D. Holden, Jens Griep-Raming, Alexander A. Makarov, Jennifer S. Brodbelt, Yevgeniy Zhuk, Jae C. Schwartz
  • Patent number: 11114290
    Abstract: An ion transport system comprises: (I) an ion transfer tube extending between an atmospheric-pressure ionization chamber and a partially evacuated chamber; and (II) an ion funnel within the chamber comprising: (1) an exit electrode that has an exit aperture configured to deliver the gas and charged particles to a high-vacuum chamber; and (2) a funnel portion comprising a plurality of plate electrodes configured as a stack, each electrode comprising a respective aperture, wherein an aperture diameter of each of the plurality of electrodes is greater than or equal to three times an inter-electrode pitch and wherein no DC electrical potential gradient is applied between the exit electrode and an adjacent one of the plurality of plate electrodes.
    Type: Grant
    Filed: May 7, 2020
    Date of Patent: September 7, 2021
    Assignees: THERMO FINNIGAN LLC, Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Joshua A. Silveira, Eloy R. Wouters, Alexander A. Makarov, Mikhail G. Skoblin, Viacheslav I. Kozlovskiy
  • Publication number: 20210270773
    Abstract: An ion mobility spectrometry method is described comprising: providing a sample; generating molecular ions from the sample; separating the molecular ions according to their mobility characteristics; fragmenting at least some of the separated molecular ions to form sub-molecular fragment ions in a fragmentation zone; separating at least some of the fragment ions according to their mobility characteristics; wherein the separation and fragmentation steps are performed at a pressure of at least 50 mbar; detecting at least some of the separated fragment ions; and identifying at least one molecular ion based on its mobility characteristics and/or the mobility characteristics of at least one detected fragment ion.
    Type: Application
    Filed: June 7, 2019
    Publication date: September 2, 2021
    Applicant: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Alexander A. MAKAROV, Anatoly VERENCHIKOV
  • Publication number: 20210272790
    Abstract: A time-of-flight (ToF) mass spectrometer, comprising: a pulsed ion injector for forming an ion beam that travels along an ion path; a detector for detecting ions in the ion beam that arrive at the detector at times according to their m/z values; an ion focusing arrangement located between the ion injector and the detector for focusing the ion beam in at least one direction orthogonal to the ion path; and a variable voltage supply for supplying the ion focusing arrangement with at least one variable voltage that is dependent on a charge state and/or an amount of ions of at least one species of ions in the ion beam. A corresponding method of mass spectrometry is provided. The charge state and/or an amount of ions may be acquired from a pre-scan, or predicted. Tuning of the spectrometer based on a charge state and/or an amount of ions of at least one species of ions in the ion beam may be performed on the fly.
    Type: Application
    Filed: March 2, 2021
    Publication date: September 2, 2021
    Inventors: Hamish Stewart, Dmitry E. Grinfeld, Alexander A. Makarov
  • Patent number: 11087969
    Abstract: A method for controlling the filling of an ion trap with a predetermined quantity of ions. The method comprises generating an ion current by transmitting ions along an ion path to an ion trap, such that ions are accumulated in the ion trap over a transmission time period, wherein the magnitude of the ion current varies in time. The method further comprises detecting at an ion detector at least some ions from the source of ions during a plurality of distinct sampling time intervals interspersed within the transmission time period, and setting the duration of the transmission time period based on the detection of ions at the ion detector. The time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than a timescale for variation of the magnitude of the ion current. A controller for controlling the filling of an ion trap with a predetermined quantity of ions and a mass spectrometer comprising the controller is also described.
    Type: Grant
    Filed: May 1, 2020
    Date of Patent: August 10, 2021
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Amelia Corinne Peterson, Jan-Peter Hauschild, Alexander Kholomeev, Alexander A. Makarov
  • Patent number: 11062895
    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: Grant
    Filed: April 8, 2020
    Date of Patent: July 13, 2021
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Amelia Corinne Peterson, Jan-Peter Hauschild, Oliver Lange, Alexander A. Makarov
  • Patent number: 11043366
    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: January 15, 2020
    Date of Patent: June 22, 2021
    Assignees: Thermo Fisher Scientific (Bremen) GmbH, ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)
    Inventors: Alexander Makarov, Oleg Boyarkine, Vladimir Kopysov
  • Patent number: 11031232
    Abstract: A method of injecting ions into an ion storage device, comprising: providing an RF trapping field in the ion storage device that defines a trapping volume in the ion storage device by applying one or more RF voltages to one or more trapping electrodes; providing a gas in the trapping volume; injecting ions into the trapping volume through an aperture in an end electrode located at a first end of the ion storage device, the end electrode having a DC voltage applied thereto; reflecting the injected ions at a second end of the ion storage device, opposite to the first end, thereby returning the ions to the first end; and ramping the DC voltage applied to the end electrode during the period between injecting the ions through the aperture and the return of the ions to the first end, such that by the time the ions return to the first end for a first time a potential barrier is established by the ramped DC voltage that prevents returning ions from striking the end electrode.
    Type: Grant
    Filed: July 9, 2020
    Date of Patent: June 8, 2021
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Hamish Stewart, Alexander A. Makarov, Christian Albrecht Hock
  • Patent number: 11024491
    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 first, high-resolution mass analyzer 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 using a time of flight mass analyzer.
    Type: Grant
    Filed: June 26, 2020
    Date of Patent: June 1, 2021
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Anastassios Giannakopulos, Alexander Makarov, Christian Albrecht Hock, Nicolaie Eugen Damoc, Hamish Stewart
  • Patent number: 10964520
    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: Grant
    Filed: November 27, 2019
    Date of Patent: March 30, 2021
    Assignee: Thermo Fisher Scientific (Bremen) GmbH
    Inventors: Hamish Stewart, Dmitry E. Grinfeld, Alexander A. Makarov
  • Publication number: 20210043435
    Abstract: The present invention relates to a system for analyzing particles, the system comprising: a NEMS device comprising at least one NEMS sensor for detecting particles impacting the at least one NEMS sensor, each NEMS sensor comprising a NEMS sensor area, a particle lens assembly, the particle lens assembly comprising at least one particle lens for focusing particles onto a NEMS sensor of the at least one NEMS sensor, wherein the particle lens assembly is spaced from the at least one NEMS sensor area by a separation distance, wherein the system is configured to sustain a space defined between the particle lens assembly and the NEMS device at a pressure where a mean free path for a reference particle is greater than the separation distance. The present invention also relates to a corresponding method.
    Type: Application
    Filed: August 6, 2019
    Publication date: February 11, 2021
    Inventors: Alexander Makarov, Maria Reinhardt-Szyba, Michael Roukes
  • Publication number: 20200411282
    Abstract: Systems and method for the preparation and delivery of biological samples for charged particle analysis are disclosed herein. An example system at least includes an ion filter coupled to select a sample ion from an ionized sample supply, the ion filter including a quadrupole filter to select the sample ion from the sample supply, an energy reduction cell coupled to receive the selected sample ion and reduce a kinetic energy of the sample ion, a validation unit coupled to receive the sample ion and determine whether the sample ion is a target sample ion, a substrate coupled to receive the sample, wherein the substrate is electron transparent, an ion transport module coupled to receive the sample ion from the ion filter and transport the sample ion to the substrate, and an imaging system arranged to image, with a low energy charged particle beam, the sample located on the substrate, wherein the substrate is arranged in an analysis location.
    Type: Application
    Filed: June 29, 2020
    Publication date: December 31, 2020
    Applicant: FEI Company
    Inventors: Marcus Straw, Alexander Makarov, Josh Gilbert, Aaron Torok, Joseph Christian, Alan Bahm, Kun Liu, Tom Nichols, Jeff Kosmoski, Dmitry Grinfeld
  • Publication number: 20200388480
    Abstract: The present invention provides a mass spectrometer comprising a first ion trap, a second ion trap, a lens stack for directing ions from the first ion trap to the second ion trap and a housing. The first ion trap is arranged to form a linear or curved potential well and the second ion trap is an electrostatic ion trap, for example, an orbital ion trap, arranged to form an annular potential well. The mass spectrometer further comprises a unitary insert comprising a first cavity which holds the lens stack and a second cavity which holds the second ion trap, wherein the insert is inserted within the housing.
    Type: Application
    Filed: May 20, 2020
    Publication date: December 10, 2020
    Inventors: Alexander A. Makarov, Wilko Balschun, Jan-Peter Hauschild, Aivaras Venckus, Denis Chernyshev, Eduard V. Denisov
  • Publication number: 20200373146
    Abstract: An ion trap 1 comprises one ejection electrode 2 for ion trapping having an opening 4, through which ions in the ion trap 1 can be ejected in an ejection direction E and further electrodes 3 for ion trapping, wherein the ejection electrode 2 and the further electrodes 3 are elongated in a longitudinal direction L. The angle ? between the longitudinal direction L and the ejection direction E is nearly 90°. The ion trap 1 comprises a primary winding 5 connected to an RF power supply 6, a secondary winding 7 coupling with the primary winding 5 for transforming the RF voltage of the RF power supply 6 supplying the transformed RF signals to the ejection electrode 2 and secondary windings 7? coupling with the primary winding 5 for transforming the RF voltage of the RF power supply 6 supplying the transformed RF signals to the further electrodes 3.
    Type: Application
    Filed: May 20, 2020
    Publication date: November 26, 2020
    Inventors: Jan-Peter Hauschild, Alexander A. Makarov, Alexander Kholomeev, Dmitry Grinfeld, Eduard V. Dennisov, Amelia Corinne Peterson
  • Publication number: 20200373138
    Abstract: The present invention provides an electrode arrangement 10, 10? for an ion trap, ion filter, an ion guide, a reaction cell or an ion analyser. The electrode arrangement 10, 10? comprises an RF electrode 12a, 12b, 12a?, 12b? mechanically coupled to a dielectric material 11 . The RF electrode 12a, 12b, 12a?, 12b? is mechanically coupled to the dielectric material 11 by a plurality of separators 13 that are spaced apart and configured to define a gap between the RF electrode 12a, 12b, 12a?, 12b? and the dielectric material 11. Each of the plurality of separators 13 comprises a projecting portion 13b and the dielectric material 11 comprises corresponding receiving portions 11a such that on coupling of the RF electrode 12a, 12b, 12a?, 12b? to the dielectric material 11, the projecting portion 13b of each separator 13 is received within the corresponding receiving portion 11a of the dielectric material 11.
    Type: Application
    Filed: May 18, 2020
    Publication date: November 26, 2020
    Inventors: Alexander A. Makarov, Wilko Balschun, Jan-Peter Hauschild, Denis Chernyshev, Eduard V. Denisov
  • Publication number: 20200357625
    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: Application
    Filed: July 24, 2020
    Publication date: November 12, 2020
    Inventors: Hamish Stewart, Dmitry Grinfeld, Alexander Makarov
  • Publication number: 20200357627
    Abstract: A method for controlling the filling of an ion trap with a predetermined quantity of ions. The method comprises generating an ion current by transmitting ions along an ion path to an ion trap, such that ions are accumulated in the ion trap over a transmission time period, wherein the magnitude of the ion current varies in time. The method further comprises detecting at an ion detector at least some ions from the source of ions during a plurality of distinct sampling time intervals interspersed within the transmission time period, and setting the duration of the transmission time period based on the detection of ions at the ion detector. The time difference between the start of a sampling time interval and the start of an immediately subsequent sampling time interval is less than a timescale for variation of the magnitude of the ion current. A controller for controlling the filling of an ion trap with a predetermined quantity of ions and a mass spectrometer comprising the controller is also described.
    Type: Application
    Filed: May 1, 2020
    Publication date: November 12, 2020
    Inventors: Amelia Corinne Peterson, Jan-Peter Hauschild, Alexander Kholomeev, Alexander A. Makarov
  • Publication number: 20200335317
    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: July 1, 2020
    Publication date: October 22, 2020
    Inventors: Alexander A. MAKAROV, Stevan R. HORNING
  • Publication number: 20200328068
    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 first, high-resolution mass analyzer 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 using a time of flight mass analyzer.
    Type: Application
    Filed: June 26, 2020
    Publication date: October 15, 2020
    Inventors: Anastassios GIANNAKOPULOS, Alexander MAKAROV, Christian Albrecht HOCK, Nicolaie Eugen DAMOC, Hamish STEWART