Patents by Inventor Mehmet Toner

Mehmet Toner 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: 10435751
    Abstract: The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g. fetal cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject, e.g. a fetus by analyzing a cellular sample from the subject.
    Type: Grant
    Filed: July 26, 2018
    Date of Patent: October 8, 2019
    Assignees: Verinata Health, Inc., GPB Scientific, LLC, The General Hospital Corporation
    Inventors: Ravi Kapur, Mehmet Toner, Zihua Wang, Martin Fuchs
  • Publication number: 20190276814
    Abstract: Microfluidic devices and methods for the encapsulation of particles within liquid droplets are disclosed. The new methods and devices form 1-100 picoliter-size monodisperse droplets containing the particles, such as single cells, encapsulated in individual liquid droplets. The particles can be encapsulated in droplets of a fluid by passing a fluid containing the particles through a high aspect-ratio microchannel to order the particles in the fluid, followed by forming the fluid into droplets. The resulting fraction of the liquid droplets with a single particle (e.g., a cell) is higher than the corresponding fraction of single-particle liquid droplets predicted by Poisson statistics.
    Type: Application
    Filed: January 4, 2019
    Publication date: September 12, 2019
    Inventors: Jon F. Edd, Mehmet Toner, Dino DiCarlo, Daniel Irimia
  • Publication number: 20190264166
    Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.
    Type: Application
    Filed: January 24, 2019
    Publication date: August 29, 2019
    Inventors: Philipp S. Spuhler, Kyle C. Smith, Fabio Fachin, Thomas Alan Barber, Ravi Kapur, Mehmet Toner, Vincent Pai, Murat N. Karabacak
  • Patent number: 10391491
    Abstract: Methods and systems for isolating platelet-associated nucleated target cells, e.g., such as circulating epithelial cells, circulating tumor cells (CTCs), circulating endothelial cells (CECs), circulating stem cells (CSCs), neutrophils, and macrophages, from sample fluids, e.g., biological fluids, such as blood, bone marrow, plural effusions, and ascites fluid, are described. The methods include obtaining a cell capture chamber including a plurality of binding moieties bound to one or more walls of the chamber, wherein the binding moieties specifically bind to platelets; flowing the sample fluid through the cell capture chamber under conditions that allow the binding moieties to bind to any platelet-associated nucleated target cells in the sample to form complexes; and separating and collecting platelet-associated nucleated target cells from the complexes.
    Type: Grant
    Filed: August 7, 2015
    Date of Patent: August 27, 2019
    Assignee: The General Hospital Corporation
    Inventors: Mehmet Toner, Shannon Stott, Eduardo Reategui, Xiaocheng Jiang
  • Publication number: 20190176150
    Abstract: A microfluidic device includes: a first microfluidic channel; a second microfluidic channel extending along the first microfluidic channel; and a first array of islands separating the first microfluidic channel from the second microfluidic channel, in which each island is separated from an adjacent island in the array by an opening that fluidly couples the first microfluidic channel to the second microfluidic channel, in which the first microfluidic channel, the second microfluidic channel, and the islands are arranged so that a fluidic resistance of the first microfluidic channel increases relative to a fluidic resistance of the second microfluidic channel along a longitudinal direction of the first microfluidic channel such that, during use of the microfluidic device, a portion of a fluid sample flowing through the first microfluidic channel passes through one or more of the openings between adjacent islands into the second microfluidic channel.
    Type: Application
    Filed: December 6, 2018
    Publication date: June 13, 2019
    Inventors: Ravi Kapur, Kyle C. Smith, Mehmet Toner
  • Patent number: 10307760
    Abstract: One example of systems and methods for inertio-elastic focusing of particles in microchannels includes a substrate including a channel having an inlet and an outlet. A viscoelastic fluid, i.e., a fluid having a dynamic viscosity that varies with shear rate, and that carries suspended particles is driven through the channel. The volumetric flow rate at which the fluid is driven results in the formation of a localized pathline in the fluid at or near a center of the channel. The localized pathline defines a width that is equal to or slightly greater than a hydraulic diameter of the particle. The particles in the fluid are focused into the localized pathline.
    Type: Grant
    Filed: January 30, 2015
    Date of Patent: June 4, 2019
    Assignees: The General Hospital Corporation, Massachusetts Institute of Technology
    Inventors: Mehmet Toner, Gareth McKinley, Eugene Lim, Thomas Ober
  • Publication number: 20190160465
    Abstract: Various systems, methods, and devices are provided for focusing particles suspended within a moving fluid into one or more localized stream lines. The system can include a substrate and at least one channel provided on the substrate having an inlet and an outlet. The system can further include a fluid moving along the channel in a laminar flow having suspended particles and a pumping element driving the laminar flow of the fluid. The fluid, the channel, and the pumping element can be configured to cause inertial forces to act on the particles and to focus the particles into one or more stream lines.
    Type: Application
    Filed: July 30, 2018
    Publication date: May 30, 2019
    Inventors: Mehmet Toner, Dino DiCarlo, Jon F. Edd, Daniel Irimia
  • Publication number: 20190111431
    Abstract: Methods and devices for evaluating coagulation are described, including methods and devices for detecting an anticoagulant agent or a coagulation abnormality. In various embodiments, the methods and devices of the invention measure coagulation of a sample in response to a gradient of one or more coagulation factors. These responses can be evaluated to accurately profile coagulation impairments of the sample, including the presence of anticoagulant medication. In various embodiments, the invention provides point-of-care or bedside testing with a convenient, microfluidic device that can be used by minimally trained personnel.
    Type: Application
    Filed: July 26, 2018
    Publication date: April 18, 2019
    Inventors: Galit H. Frydman, Mehmet Toner, Ronald G. Tompkins, Pavan Bendapudi
  • Publication number: 20190072465
    Abstract: Methods and systems capturing particles suspended in a fluid flowed through a micro-channel, can include flowing the fluid including the particles to be captured through a micro-channel and past a groove defined in a surface of a wall of the micro-channel such that flowing the fluid past the groove forms microvortices in the fluid; contacting at least some of the particles against an adherent disposed on one or more of walls of the microchannel after the microvortices form in the fluid; and capturing at least some of the particles contacting the adherent.
    Type: Application
    Filed: November 5, 2018
    Publication date: March 7, 2019
    Inventors: Mehmet Toner, Shannon Stott, Chia-Hsien Hsu
  • Patent number: 10202577
    Abstract: Microfluidic devices are described that include a microfluidic channel, a first array of one or more magnets above the microfluidic channel, each magnet in the first array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the first array, and a second array of one or more magnets beneath the microfluidic channel, each magnet in the second array having a magnetic pole orientation opposite to a magnetic pole orientation of an adjacent magnet in the second array. The first array is aligned with respect to the second array such that magnetic fields emitted by the first array and second array generate a magnetic flux gradient profile extending through the channel. An absolute value of the profile includes a first maximum and a second maximum that bound a local minimum. The local minimum is located within the microfluidic channel or less than 5 mm away from a wall of the microfluidic channel. Methods of using the new devices are also described.
    Type: Grant
    Filed: October 20, 2014
    Date of Patent: February 12, 2019
    Assignee: The General Hospital Corporation
    Inventors: Philipp S. Spuhler, Kyle C. Smith, Fabio Fachin, Thomas Alan Barber, Ravi Kapur, Mehmet Toner, Vincent Pai, Murat N. Karabacak
  • Publication number: 20190030535
    Abstract: This disclosure describes microfluidic devices that include one or more magnets, each magnet being operable to emit a magnetic field; and a magnetizable layer adjacent to the one or more magnets, in which the magnetizable layer is configured to induce a gradient in the magnetic field of at least one of the magnets. For example, the gradient can be at least 103 T/m at a position that is at least 20 ?m away from a surface of the magnetizable layer. The magnetizable layer includes a first high magnetic permeability material and a low magnetic permeability material arranged adjacent to the high magnetic permeability material. The devices also include a microfluidic channel arranged on a surface of the magnetizable layer, wherein a central longitudinal axis of the microfluidic channel is arranged at an angle to or laterally offset from an interface between the high magnetic permeability material and the low magnetic permeability material.
    Type: Application
    Filed: January 23, 2018
    Publication date: January 31, 2019
    Inventors: Kyle C. Smith, Ramin Haghgooie, Thomas Alan Barber, Ismail Emre Ozkumur, Ravi Kapur, Mehmet Toner
  • Publication number: 20190022653
    Abstract: The invention features methods for separating cells from a sample (e.g., separating fetal red blood cells from maternal blood). The method begins with the introduction of a sample including cells into one or more microfluidic channels. In one embodiment, the device includes at least two processing steps. For example, a mixture of cells is introduced into a microfluidic channel that selectively allows the passage of a desired type of cell, and the population of cells enriched in the desired type is then introduced into a second microfluidic channel that allows the passage of the desired cell to produce a population of cells further enriched in the desired type. The selection of cells is based on a property of the cells in the mixture, for example, size, shape, deformability, surface characteristics (e.g., cell surface receptors or antigens and membrane permeability), or intracellular properties (e.g., expression of a particular enzyme).
    Type: Application
    Filed: September 21, 2018
    Publication date: January 24, 2019
    Inventors: Mehmet Toner, George Truskey, Ravi Kapur
  • Patent number: 10174305
    Abstract: Microfluidic devices and methods for the encapsulation of particles within liquid droplets are disclosed. The new methods and devices form 1-100 picoliter-size monodisperse droplets containing the particles, such as single cells, encapsulated in individual liquid droplets. The particles can be encapsulated in droplets of a fluid by passing a fluid containing the particles through a high aspect-ratio microchannel to order the particles in the fluid, followed by forming the fluid into droplets. The resulting fraction of the liquid droplets with a single particle (e.g., a cell) is higher than the corresponding fraction of single-particle liquid droplets predicted by Poisson statistics.
    Type: Grant
    Filed: June 12, 2017
    Date of Patent: January 8, 2019
    Assignee: The General Hospital Corporation
    Inventors: Jon F. Edd, Mehmet Toner, Dino DiCarlo, Daniel Irimia
  • Publication number: 20190001344
    Abstract: The invention features devices and methods for the deterministic separation of particles. Exemplary methods include the enrichment of a sample in a desired particle or the alteration of a desired particle in the device. The devices and methods are advantageously employed to enrich for rare cells, e.g., fetal cells, present in a sample, e.g., maternal blood and rare cell components, e.g., fetal cell nuclei. The invention further provides a method for preferentially lysing cells of interest in a sample, e.g., to extract clinical information from a cellular component, e.g., a nucleus, of the cells of interest. In general, the method employs differential lysis between the cells of interest and other cells (e.g., other nucleated cells) in the sample.
    Type: Application
    Filed: April 27, 2018
    Publication date: January 3, 2019
    Inventors: Lotien Richard Huang, Thomas A. Barber, Bruce L. Carvalho, Ravi Kapur, Paul Vernucci, Mehmet Toner, Zihua Wang
  • Publication number: 20180364186
    Abstract: This disclosure relates to methods and devices to count particles of interest, such as cells. The methods include obtaining a fluid sample that may contain particles of interest; counting all types of particles in a portion of the sample using a first electrical differential counter to generate a first total; removing any particles of interest from the portion of the fluid sample; counting any particles remaining in the portion of the fluid sample using a second electrical differential counter after the particles of interest are removed to generate a second total; and calculating a number of particles of interest originally in the fluid sample by subtracting the second total from the first total, wherein the difference is the number of particles of interest in the sample. These methods and related devices can be used, for example, to produce a robust, inexpensive diagnostic kit for CD4+ T cell counting in whole blood samples.
    Type: Application
    Filed: May 21, 2018
    Publication date: December 20, 2018
    Inventors: Nicholas Watkins, Rashid Bashir, William Rodriguez, Xuanhong Cheng, Mehmet Toner, Grace Chen, Aaron Oppenheimer
  • Publication number: 20180361383
    Abstract: A microfluidic device includes a particle sorting region having a first, second and third microfluidic channels, a first array of islands separating the first microfluidic channel from the second microfluidic channel, and a second array of islands separating the first microfluidic channel from the third microfluidic channel, in which the island arrays and the microfluidic channels are arranged so that a first fluid is extracted from the first microfluidic channel into the second microfluidic channel and a second fluid is extracted from the third microfluidic channel into the first microfluidic channel, and so that particles are transferred from the first fluid sample into the second fluid sample within the first microfluidic channel.
    Type: Application
    Filed: August 24, 2018
    Publication date: December 20, 2018
    Inventors: Ravi Kapur, Kyle C. Smith, Mehmet Toner
  • Publication number: 20180361384
    Abstract: A microfluidic device includes a particle sorting region having a first, second and third microfluidic channels, a first array of islands separating the first microfluidic channel from the second microfluidic channel, and a second array of islands separating the first microfluidic channel from the third microfluidic channel, in which the island arrays and the microfluidic channels are arranged so that a first fluid is extracted from the first microfluidic channel into the second microfluidic channel and a second fluid is extracted from the third microfluidic channel into the first microfluidic channel, and so that particles are transferred from the first fluid sample into the second fluid sample within the first microfluidic channel.
    Type: Application
    Filed: August 24, 2018
    Publication date: December 20, 2018
    Inventors: Ravi Kapur, Kyle C. Smith, Mehmet Toner
  • Patent number: 10155984
    Abstract: The present invention provides systems, apparatuses, and methods to detect the presence of fetal cells when mixed with a population of maternal cells in a sample and to test fetal abnormalities, e.g. aneuploidy. The present invention involves labeling regions of genomic DNA in each cell in said mixed sample with different labels wherein each label is specific to each cell and quantifying the labeled regions of genomic DNA from each cell in the mixed sample. More particularly the invention involves quantifying labeled DNA polymorphisms from each cell in the mixed sample.
    Type: Grant
    Filed: April 27, 2015
    Date of Patent: December 18, 2018
    Assignees: The General Hospital Corporation, GPB Scientific, LLC, Verinata Health, Inc.
    Inventors: Daniel Shoemaker, Mehmet Toner, Ravi Kapur, Roland B. Stoughton, Ronald W. Davis
  • Patent number: 10150116
    Abstract: A microfluidic device includes: a first microfluidic channel; a second microfluidic channel extending along the first microfluidic channel; and a first array of islands separating the first microfluidic channel from the second microfluidic channel, in which each island is separated from an adjacent island in the array by an opening that fluidly couples the first microfluidic channel to the second microfluidic channel, in which the first microfluidic channel, the second microfluidic channel, and the islands are arranged so that a fluidic resistance of the first microfluidic channel increases relative to a fluidic resistance of the second microfluidic channel along a longitudinal direction of the first microfluidic channel such that, during use of the microfluidic device, a portion of a fluid sample flowing through the first microfluidic channel passes through one or more of the openings between adjacent islands into the second microfluidic channel.
    Type: Grant
    Filed: November 3, 2015
    Date of Patent: December 11, 2018
    Assignee: The General Hospital Corporation
    Inventors: Ravi Kapur, Kyle C. Smith, Mehmet Toner
  • Publication number: 20180327847
    Abstract: The present invention relates to methods for detecting, enriching, and analyzing rare cells that are present in the blood, e.g. fetal cells. The invention further features methods of analyzing rare cell(s) to determine the presence of an abnormality, disease or condition in a subject, e.g. a fetus by analyzing a cellular sample from the subject.
    Type: Application
    Filed: July 26, 2018
    Publication date: November 15, 2018
    Inventors: Ravi Kapur, Mehmet Toner, Zihua Wang, Martin Fuchs