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).
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Patent number: 11289319Abstract: 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: GrantFiled: August 6, 2019Date of Patent: March 29, 2022Assignees: Thermo Fisher Scientific (Bremen) GmbH, California Institute of TechnologyInventors: Alexander Makarov, Maria Reinhardt-Szyba, Michael Roukes
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Publication number: 20220084806Abstract: A coupling for connecting together vacuum-based analytical systems requiring to be vibrationally isolated, comprising: a tubular connector having a longitudinal axis, the connector comprising a first end for connection to a first analytical system and a flexible portion reducing transmission of vibrations and permitting displacement of the first analytical system in a direction transverse to the longitudinal axis of the connector; and a seal longitudinally separated from the flexible portion, for vacuum sealing between the connector and a second analytical system; wherein the connector contains ion optics for transmitting ions between the first and second analytical systems.Type: ApplicationFiled: September 7, 2021Publication date: March 17, 2022Inventors: Alexander Makarov, Wilko Balschun, Kyle Fort, Kun Liu
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Patent number: 11217425Abstract: 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: GrantFiled: June 29, 2020Date of Patent: January 4, 2022Assignee: FEI CompanyInventors: Marcus Straw, Alexander Makarov, Josh Gilbert, Aaron Torok, Joseph Christian, Alan Bahm, Kun Liu, Tom Nichols, Jeff Kosmoski, Dmitry Grinfeld
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Publication number: 20210407783Abstract: 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: ApplicationFiled: September 14, 2021Publication date: December 30, 2021Inventors: Alexander A. MAKAROV, Stevan R. HORNING
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Publication number: 20210398791Abstract: A method of reducing fragmentation of ions generated from a sample during transport of the ions through an ion transport apparatus that comprises an ion funnel portion, comprises: applying a selected DC potential difference between an outlet end of the ion transport apparatus and an exit ion lens that is disposed adjacent to the outlet end, wherein a sign of the selected DC potential difference is chosen so as to accelerate the ions from the outlet end of the ion transport apparatus towards and through the exit ion lens.Type: ApplicationFiled: September 3, 2021Publication date: December 23, 2021Inventors: Joshua A. SILVEIRA, Eloy R. WOUTERS, Alexander A. MAKAROV, Mikhail G. SKOBLIN, Viacheslav I. KOZLOVSKIY, Christopher MULLEN, Brian D. ADAMSON
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Publication number: 20210375611Abstract: A mass spectrometer system comprises: (a) an ion source; (b) a mass filter or a time-of-flight (TOF) ion separator configured to receive a stream of first-generation ions from the ion source; (c) an ion storage device having an ion inlet configured to receive a stream of filtered ions comprising a plurality of ion species from the mass filter or TOF separator and to accumulate the plurality of ion species therein; (d) an ion mobility cell having an ion inlet configured to receive an accumulated batch of ion species from the ion storage device and an ion outlet configured to release, one at a time, the individual ion species therefrom; and (e) a mass analyzer configured to receive and mass analyze each first-generation ion species or each fragment ion species generated by fragmentation or other reaction of the various first-generation ion species.Type: ApplicationFiled: May 21, 2021Publication date: December 2, 2021Inventors: Philip M. REMES, Jae C. SCHWARTZ, Alexander A. MAKAROV
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Patent number: 11189473Abstract: 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: GrantFiled: April 17, 2020Date of Patent: November 30, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Lothar Rottmann, Alexander Makarov, Hans-Juergen Schlueter, Christoph Wehe
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Patent number: 11133162Abstract: 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: GrantFiled: July 1, 2020Date of Patent: September 28, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Alexander A. Makarov, Stevan R. Horning
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Patent number: 11133160Abstract: 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: GrantFiled: June 2, 2017Date of Patent: September 28, 2021Assignees: BOARD OF REGENTS, UNIVERSITY OF TEXAS SYSTEM, THERMO FISHER SCIENTIFIC (BREMEN) GMBH, THERMO FINNIGAN LLCInventors: Dustin D. Holden, Jens Griep-Raming, Alexander A. Makarov, Jennifer S. Brodbelt, Yevgeniy Zhuk, Jae C. Schwartz
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Patent number: 11114290Abstract: 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: GrantFiled: May 7, 2020Date of Patent: September 7, 2021Assignees: THERMO FINNIGAN LLC, Thermo Fisher Scientific (Bremen) GmbHInventors: Joshua A. Silveira, Eloy R. Wouters, Alexander A. Makarov, Mikhail G. Skoblin, Viacheslav I. Kozlovskiy
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Publication number: 20210270773Abstract: 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: ApplicationFiled: June 7, 2019Publication date: September 2, 2021Applicant: Thermo Fisher Scientific (Bremen) GmbHInventors: Alexander A. MAKAROV, Anatoly VERENCHIKOV
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Publication number: 20210272790Abstract: 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: ApplicationFiled: March 2, 2021Publication date: September 2, 2021Inventors: Hamish Stewart, Dmitry E. Grinfeld, Alexander A. Makarov
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Patent number: 11087969Abstract: 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: GrantFiled: May 1, 2020Date of Patent: August 10, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Amelia Corinne Peterson, Jan-Peter Hauschild, Alexander Kholomeev, Alexander A. Makarov
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Patent number: 11062895Abstract: 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 iType: GrantFiled: April 8, 2020Date of Patent: July 13, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Amelia Corinne Peterson, Jan-Peter Hauschild, Oliver Lange, Alexander A. Makarov
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Patent number: 11043366Abstract: 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: GrantFiled: January 15, 2020Date of Patent: June 22, 2021Assignees: Thermo Fisher Scientific (Bremen) GmbH, ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)Inventors: Alexander Makarov, Oleg Boyarkine, Vladimir Kopysov
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Patent number: 11031232Abstract: 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: GrantFiled: July 9, 2020Date of Patent: June 8, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Hamish Stewart, Alexander A. Makarov, Christian Albrecht Hock
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Patent number: 11024491Abstract: 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: GrantFiled: June 26, 2020Date of Patent: June 1, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Anastassios Giannakopulos, Alexander Makarov, Christian Albrecht Hock, Nicolaie Eugen Damoc, Hamish Stewart
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Patent number: 10964520Abstract: 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: GrantFiled: November 27, 2019Date of Patent: March 30, 2021Assignee: Thermo Fisher Scientific (Bremen) GmbHInventors: Hamish Stewart, Dmitry E. Grinfeld, Alexander A. Makarov
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Publication number: 20210043435Abstract: 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: ApplicationFiled: August 6, 2019Publication date: February 11, 2021Inventors: Alexander Makarov, Maria Reinhardt-Szyba, Michael Roukes
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Publication number: 20200411282Abstract: 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: ApplicationFiled: June 29, 2020Publication date: December 31, 2020Applicant: FEI CompanyInventors: Marcus Straw, Alexander Makarov, Josh Gilbert, Aaron Torok, Joseph Christian, Alan Bahm, Kun Liu, Tom Nichols, Jeff Kosmoski, Dmitry Grinfeld