Isotachophoresis (i.e., Displacement Electrophoresis) Or Measurement Of Ion Or Particle Mobility Patents (Class 204/549)
  • Patent number: 10519439
    Abstract: The disclosure generally relates to compositions and methods for the production of nucleic acid molecules. In some aspects, the invention allows for the microscale generation of nucleic acid molecules, optionally followed by assembly of these nucleic acid molecules into larger molecules. In some aspects, the invention allows for efficient production of nucleic acid molecules (e.g., large nucleic acid molecules such as genomes).
    Type: Grant
    Filed: March 20, 2017
    Date of Patent: December 31, 2019
    Assignees: LIFE TECHNOLOGIES CORPORATION, THERMO FISHER SCIENTIFIC GENEART GMBH
    Inventors: Todd Peterson, Axel Trefzer, Thomas Poehmerer
  • Patent number: 10488419
    Abstract: The present invention provides devices and methods for identification and/or quantitation of particles through detection of fluorescence labeled particles in an apparatus for differential charged particle mobility analysis and fluorescence detection.
    Type: Grant
    Filed: September 24, 2018
    Date of Patent: November 26, 2019
    Assignee: QUEST DIAGNOSTICS INVESTMENTS INCORPORATED
    Inventor: Michael P. Caulfield
  • Patent number: 10422768
    Abstract: When measuring electrophoretic mobility it is customary to apply an electric field and determine the electrophoretic velocity while minimizing all other contributions to the particle movement. A method and apparatus for the measurement of mobility while the sample is flowing is disclosed. Combined with a fractionation system, this approach further enables the direct measurement of individual species' mobility within a multi-modal sample. Other advantages of this new mobility measurement approach include the ability to easily pressurize the sample to suppress electrolysis, mitigation of oxidation-reduction effects and efficient heat dissipation.
    Type: Grant
    Filed: November 6, 2015
    Date of Patent: September 24, 2019
    Assignee: WYATT TECHNOLOGY CORPORATION
    Inventors: Hung-Te Hsieh, Steven P. Trainoff
  • Patent number: 10279427
    Abstract: A rectilinear beam distributor capable of maintaining visibility of visible light emitted from a guide laser is provided. In a beam distributor, a beam direction changing unit has a dichroic property that the beam direction changing unit reflects an incident beam and transmits a visible light. A guide laser is disposed so as to move with movement of the beam direction changing unit in an optical axis direction of the incident beam when oscillating the visible light so that the visible light passes through the beam direction changing unit and the optical axis thereof is identical to a reflection beam.
    Type: Grant
    Filed: October 18, 2017
    Date of Patent: May 7, 2019
    Assignee: FANUC CORPORATION
    Inventor: Munekazu Matsuda
  • Patent number: 10131137
    Abstract: A sheet-fed printing press includes a printing cylinder and a high-precision sensor system for monitoring a sheet run in the area of the printing cylinder. At least one gage, which is mounted on the printing cylinder, can be detected by the sensor system. It is particularly advantageous if the sensor system is configured to be self-calibrating. A method for calibrating a sensor system and a method for aligning a sensor system are also provided.
    Type: Grant
    Filed: March 1, 2017
    Date of Patent: November 20, 2018
    Assignee: Heidelberger Druckmaschinen AG
    Inventors: Andreas Henn, Thomas Schmidt, Wolfgang Kabus, Stefan Knauf, Juergen Ritz, Olaf Lorenz, Christian Bull, Stefan Muench, Thomas Goebel
  • Patent number: 10018552
    Abstract: A particle analysis apparatus includes: an acquisition unit that acquires a plurality of images each captured at a different time in each of which a particle moving in a predetermined direction in a medium is imaged; and a determination unit that determines, based on a movement amount of a particle due to Brownian motion in the medium, whether or not an image of a first particle included in an image captured at a first time of the plurality of images acquired by the acquisition unit and an image of a second particle included in an image captured at a second time which is different from the first time of the plurality of images acquired by the acquisition unit are images indicating the same particle.
    Type: Grant
    Filed: July 14, 2016
    Date of Patent: July 10, 2018
    Assignee: Nikon Corporation
    Inventors: Daishi Tanaka, Hisao Osawa, Kuno Suzuki
  • Patent number: 9885688
    Abstract: The present invention provides a system including: a protein having a domain that binds a membranal component; an inlet for sample flow, an Isotachophoresis (ITP) system and a flow generating means connected or coupled to the aqueous parts of the ITP. The invention also provides a method for detecting and or sorting cells with this system.
    Type: Grant
    Filed: November 28, 2014
    Date of Patent: February 6, 2018
    Assignee: Technion Research and Development Foundation Limited
    Inventors: Moran Bercovici, Ortal Schwartz
  • Patent number: 9700891
    Abstract: A technique relates to an integrated nanofluidic device. A loading layer includes an inlet channel reservoir, a diverted fraction reservoir, and a passed fraction reservoir. A sorting layer is attached to the loading layer such that fluid is permitted to communicate between the loading and sorting layers, where the sorting layer includes a bank of sorting elements. The sorting layer has inlet channels and outlet channels connected to the sorting elements, and the inlet channel reservoir is connected to the inlet channels by an inlet feed hole. The diverted fraction reservoir is connected to the outlet channels by a diverted fraction outlet feed hole, and the passed fraction reservoir is connected to the sorting elements by passed fraction feed holes. The passed fraction feed holes are respectively connected to the sorting elements.
    Type: Grant
    Filed: November 13, 2015
    Date of Patent: July 11, 2017
    Assignee: INTERNATIONAL BUSINESS MACHINES CORPORATION
    Inventors: Joshua T. Smith, Benjamin H. Wunsch, Cornelia T. Yang
  • Patent number: 9502225
    Abstract: Methods, systems and devices that generate differential axial transport in a fluidic device having at least one fluidic sample separation flow channel and at least one ESI emitter in communication with the at least one sample separation flow channel. In response to the generated differential axial transport, the at least one target analyte contained in a sample reservoir in communication with the sample separation channel is selectively transported to the at least one ESI emitter while inhibiting transport of contaminant materials contained in the sample reservoir toward the at least one ESI emitter thereby preferentially directing analyte molecules out of the at least one ESI emitter. The methods, systems and devices are particularly suitable for use with a mass spectrometer.
    Type: Grant
    Filed: June 5, 2013
    Date of Patent: November 22, 2016
    Assignee: The University of North Carolina at Chapel Hill
    Inventors: John Scott Mellors, John Michael Ramsey, Nicholas George Batz
  • Patent number: 9247766
    Abstract: The invention provides methods for enriching a milk extract for angiogenin, such methods involving separation by size, charge or immunoaffinity. The invention also provides the angiogenin enriched extract produced by the methods and provides them in pharmaceutical and neutraceutical compositions and foods for treating a variety of diseases or disorders that can be treated by angiogenin.
    Type: Grant
    Filed: May 14, 2009
    Date of Patent: February 2, 2016
    Assignees: Murray Goulburn Co-Operative Co., Limited, Agriculture Victoria Services Pty Ltd.
    Inventors: Matthew McDonagh, Benjamin Cocks, Angus Tester, Peter Hobman, Andrew Brown
  • Patent number: 9081012
    Abstract: The present invention relates to an apparatus for the isolation of extracellular vesicles from human fluid, and more particularly, to an apparatus comprising a channel formed on a microchip and a porous polymer monolith filter connected to the channel. The apparatus can be used to the diagnosis of disease including cancer from vesicular nucleic acid in a non-invasive manner. Capable of isolating and purifying a large quantity of vesicles from a small amount of a body fluid sample within a short time, the apparatus is expected to be advantageously and widely applied in the medical research and clinical diagnosis of disease including cancer.
    Type: Grant
    Filed: March 14, 2013
    Date of Patent: July 14, 2015
    Assignee: POSTECH ACADEMY-INDUSTRY FOUNDATION
    Inventors: Jae Sung Park, Jun Ho Kim, Ryan Thomas Davies
  • Patent number: 8999131
    Abstract: An electrophoretic mobility measurement cell includes a container having a rectangular parallelepiped internal space for introducing a sample solution, two electrodes for applying an electric field to the internal space, tubular sample injection and extraction portions in communication with the internal space, first and second caps for covering the sample injection and extraction portions and sealing the internal space, the first cap has a first side surface contacting an inner side surface of the tubular sample injection portion, the inner side surface formed so that the cross-sectional area of the tube increases with distance from the internal space, and the area of the cross section of the first side surface decreases in the direction of insertion of the first cap. The cell and electrode portions are formed integrally, the electrode portions are made disposable together with the cell, and bubbles are unlikely to remain during injection of the sample solution.
    Type: Grant
    Filed: October 3, 2013
    Date of Patent: April 7, 2015
    Assignee: Otsuka Electronics Co., Ltd.
    Inventors: Mayumi Ikegami, Katsuhiro Morisawa, Tamotsu Hamao, Hidehiro Atagi
  • Patent number: 8986530
    Abstract: Embodiments of analysis systems, electrophoresis devices, and associated methods of analysis are described herein. In one embodiment, a method of analyzing a sample containing an electrolyte includes sequentially introducing a leading electrolyte, a sample electrolyte, and a trailing electrolyte into a extraction channel carried by a substrate. The extraction channel has a constriction in cross-sectional area. The method also includes applying an electrical field to separate components of the sample electrolyte into stacks and to concentrate the separated components by forcing the sample electrolyte to migrate through the constriction in the extraction channel. Thereafter, the applied electrical field is removed and the separated and concentrated components of the sample are detected in a detection channel carried by the substrate.
    Type: Grant
    Filed: April 12, 2012
    Date of Patent: March 24, 2015
    Assignee: Washington State University
    Inventors: Cornelius F. Ivory, Dan M. Leatzow
  • Patent number: 8986529
    Abstract: Improved electrophoretic analysis is provided by interaction of anionic and cationic isotachophoresis (ITP) shock waves that propagate toward each other, and analysis of the resulting interaction zones. These shock wave interactions can provide qualitatively different capabilities from conventional ITP methods. Shock wave interaction can enable a single assay to identify analyte and quantify its concentration via isotachophoretic focusing followed by separation of the concentrated analytes via electrophoresis, without any mid-assay alteration of the externally imposed experimental conditions (i.e., no switching, valve operation, etc. during the measurement). As another example, shock wave interaction can enable a single assay to provide coupled ITP processes with different electrolyte concentrations (as in cascade-ITP) in a single simple system (again, without any mid-assay alteration of the externally imposed experimental conditions).
    Type: Grant
    Filed: September 12, 2011
    Date of Patent: March 24, 2015
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Juan G. Santiago, Robert D. Chambers, Supreet Singh Bahga
  • Publication number: 20150068904
    Abstract: The invention relates to mutant forms of lysenin. The invention also relates to analyte characterisation using lysenin.
    Type: Application
    Filed: March 15, 2013
    Publication date: March 12, 2015
    Applicant: OXFORD NANOPORE TECHNOLOGIES LIMITED
    Inventors: Mark Bruce, James Clarke, Andrew Heron, Lakmal Jayasinghe, Jayne Wallace
  • Publication number: 20150047982
    Abstract: The present invention provides a system including: a peptide nucleic acid (PNA) molecule; a DNA molecule, an RNA molecule, or a combination thereof; and an Isotachophoresis (ITP) system. Furthermore, the invention provides a method for sequence-specifically separating and/or identifying a nucleic acid molecule of interest by utilizing the system of the invention to separate and possibly label and/or detect a nucleic acid molecule of interest.
    Type: Application
    Filed: August 18, 2014
    Publication date: February 19, 2015
    Inventors: Moran Bercovici, Nadya Ostromohov, Ortal Schwartz
  • Publication number: 20140360879
    Abstract: Isotachophoresis (ITP) is exploited to control various aspects of chemical reactions. In a first aspect, at least one of the reactants of a chemical reaction is confined to an ITP zone, but the resulting product of the chemical reaction is separated from this ITP zone by the ITP process. In a second aspect, one or more reactants of a chemical reaction are confined to an ITP zone, and one or more other reactants of the chemical reaction are not confined to this ITP zone. In a third aspect, ITP is employed to confine at least one reactant of a chemical reaction to an ITP zone, and at least one reactant of the chemical reaction is delivered to the ITP zone in two or more discrete doses. These aspects are especially relevant to performing polymerase chain reactions using chemical denaturants as opposed to thermal cycling.
    Type: Application
    Filed: August 21, 2014
    Publication date: December 11, 2014
    Inventors: Juan G. Santiago, Alexandre Persat
  • Patent number: 8864967
    Abstract: A device for displacing a small volume of liquid under the effect of an electric control, including a first substrate with a hydrophobic surface provided with a first electrical conductor, a second electrical conductor positioned facing the first conductor, and a third conductor, forming with the second conductor, a mechanism for analyzing or heating a volume of liquid.
    Type: Grant
    Filed: June 30, 2005
    Date of Patent: October 21, 2014
    Assignee: Commissariat a l'Energie Atomique
    Inventors: Gilles Marchand, Yves Fouillet, Philippe Clementz
  • Patent number: 8821704
    Abstract: Isotachophoresis (ITP) is exploited to control various aspects of chemical reactions. In a first aspect, at least one of the reactants of a chemical reaction is confined to an ITP zone, but the resulting product of the chemical reaction is separated from this ITP zone by the ITP process. In a second aspect, one or more reactants of a chemical reaction are confined to an ITP zone, and one or more other reactants of the chemical reaction are not confined to this ITP zone. In a third aspect, ITP is employed to confine at least one reactant of a chemical reaction to an ITP zone, and at least one reactant of the chemical reaction is delivered to the ITP zone in two or more discrete doses. These aspects are especially relevant to performing polymerase chain reactions using chemical denaturants as opposed to thermal cycling.
    Type: Grant
    Filed: February 11, 2013
    Date of Patent: September 2, 2014
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Juan G. Santiago, Alexandre Persat
  • Patent number: 8795499
    Abstract: Methods are provided for forming a complex comprising an analyte (or an analyte analog) from a blood-derived sample and labeling substances, and separating the complex from excess labeling substances and coexisting substances from the blood-derived sample, in a rapid, simple, convenient, and highly precise isotachophoresis (ITP) process by adding 2-(N-morpholino)ethane sulfonate (MES) salt and/or glutamate salt to the ITP sample. Methods are also provided for measuring the analyte in blood-derived samples with high precision and high sensitivity, based on the amount of the complex separated or the amount of uncomplexed labeling substance-containing molecules.
    Type: Grant
    Filed: October 31, 2013
    Date of Patent: August 5, 2014
    Assignee: Wako Pure Chemical Industries, Ltd.
    Inventors: Tatsuo Kurosawa, Mitsuo Watanabe, Takuma Ohtsubo
  • Publication number: 20140209464
    Abstract: Among other things, for use in directional motion of chiral objects in a mixture, a field is applied across the chamber and is rotating relative to the chamber to cause rotation of the chiral objects. The rotation of the objects causes them to move directionally based on their chirality. The method applies to sugars, proteins, and peptides, among other things, and can be used in a wide variety of applications.
    Type: Application
    Filed: March 28, 2014
    Publication date: July 31, 2014
    Applicant: Dynamic Connections, LLC
    Inventors: Osman Kibar, Mirianas Chachisvilis, Eugene Tu, Thomas H. Marsilje
  • Publication number: 20140166486
    Abstract: The present invention provides methods, devices, and kits for separating and selecting top sperm from a sperm sample of a subject. In one aspect, for example, such a method can include removing a portion of negatively charged protein from sperm in the sperm sample, immobilizing the sperm, electrophoretically separating the sperm, and selecting mature sperm based on electromotility properties.
    Type: Application
    Filed: August 23, 2013
    Publication date: June 19, 2014
    Inventors: Douglas T. Carrell, Luke Simon
  • Publication number: 20140144780
    Abstract: An apparatus for measuring information indicative of electromobility in a sample includes a light source for generating coherent light, a modulator that modulates the optical path length, particularly a reciprocatable modulator arranged for modulating a first part of the generated light, a sample cell for accommodating the measured sample for applying an electric field to the sample and for receiving a second part of the generated light for interaction with the sample in the electric field, a modulator monitor for monitoring the modulator by detecting interference between a first part of the light coming from the modulator and an unmodulated third part of the generated light, and a light detector arranged separately from the modulator monitor for detecting interference between a second part of light coming from the modulator and light received from the sample cell. The detected signal includes the information indicative of electromobility in the sample.
    Type: Application
    Filed: November 27, 2013
    Publication date: May 29, 2014
    Applicant: Anton Paar GmbH
    Inventors: Harald Noack, Christian Moitzi
  • Patent number: 8721858
    Abstract: A novel method for visualizing electrokinetic process zones (e.g., for isotachophoresis (ITP)) is provided. We introduce negligibly small concentrations of a fluorophore that is not focused by isotachophoresis. This non-focusing tracer (NFT) migrates through multiple isotachophoresis zones. As it enters each zone, the NFT concentration adapts to the local electric field in each zone. ITP zones can then be visualized with a point detector or camera. The method can be used to detect, identify, and quantify unknown analyte zones, and can visualize complex and even transient electrophoresis processes. This visualization technique is particularly suited to microfluidic and lab-on-a-chip applications, as typical fluorescence microscopes and CCD cameras can provide high-resolution spatiotemporal data.
    Type: Grant
    Filed: March 14, 2011
    Date of Patent: May 13, 2014
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Robert D. Chambers, Juan G. Santiago, Moran Bercovici
  • Publication number: 20140124372
    Abstract: A molecule trapping method includes forming a fluid bridge between a first reservoir and a second reservoir, translocating a molecule from the first reservoir to the second reservoir through the fluid bridge, detecting when a segment of the molecule is in the fluid bridge, breaking the fluid bridge and forming an a gap between the first and the second reservoirs, thereby trapping a segment of the molecule in the gap and making measurements on the segment of the molecule.
    Type: Application
    Filed: January 13, 2014
    Publication date: May 8, 2014
    Applicant: International Business Machines Corporation
    Inventors: Venkat S.K. Balagurusamy, Stanislav Polonsky
  • Publication number: 20140110260
    Abstract: Methods are provided for forming a complex comprising an analyte (or an analyte analogue) from a blood-derived sample and labeling substances, and separating the complex from excess labeling substances and coexisting substances from the blood-derived sample, in a rapid, simple, convenient, and highly precise isotachophoresis (ITP) process by adding 2-(N-morpholino)ethane sulfonate (MES) salt and/or glutamate salt to the ITP sample. Methods are also provided for measuring the analyte in blood-derived samples with high precision and high sensitivity, based on the amount of the complex separated or the amount of uncomplexed labeling substance-containing molecules.
    Type: Application
    Filed: October 31, 2013
    Publication date: April 24, 2014
    Applicant: Wako Pure Chemical Industries, Ltd.
    Inventors: Tatsuo Kurosawa, Mitsuo Watanabe, Takuma Ohtsubo
  • Publication number: 20140027286
    Abstract: An electrophoretic mobility measurement cell includes a container having a rectangular parallelepiped internal space for introducing a sample solution, two electrodes for applying an electric field to the internal space, tubular sample injection and extraction portions in communication with the internal space, first and second caps for covering the sample injection and extraction portions and sealing the internal space, the first cap has a first side surface contacting an inner side surface of the tubular sample injection portion, the inner side surface formed so that the cross-sectional area of the tube increases with distance from the internal space, and the area of the cross section of the first side surface decreases in the direction of insertion of the first cap. The cell and electrode portions are formed integrally, the electrode portions are made disposable together with the cell, and bubbles are unlikely to remain during injection of the sample solution.
    Type: Application
    Filed: October 3, 2013
    Publication date: January 30, 2014
    Inventors: Mayumi Ikegami, Katsuhiro Morisawa, Tamotsu Hamao, Hidehiro Atagi
  • Publication number: 20140014515
    Abstract: Techniques for enhanced isotachophoresis assays using additives with spatial gradients include forming a concentration gradient of an additive along a channel from an input port to an output port. The channel is used for isotachophoresis with ions of a leading electrolyte having a first mobility greater than a mobility of an analyte, and ions of a trailing electrolyte having a second mobility less than the mobility of the analyte. The additive is different from both the leading electrolyte and the trailing electrolyte; and the additive has a third mobility that assures the analyte will encounter the additive. The method further comprises introducing a mixture of the trailing electrolyte and a sample including the analyte. The method further comprises applying an electric field to the channel; and, measuring the analyte.
    Type: Application
    Filed: October 3, 2011
    Publication date: January 16, 2014
    Applicant: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Juan G. Santiago, Alexandre Persat, Giancarlo Garcia, Charbel Eid
  • Patent number: 8598863
    Abstract: The present invention is an apparatus and method for detecting the motion characteristics of particles in a flow channel. The apparatus includes first and second electrode groups, each having a pair of electrodes, which are arranged to be spaced apart from each other in a flow channel. The pair of electrodes function as both a drive electrode and a sensing electrode for directly applying voltage and measuring impedance between the electrodes. An operation control unit measures variation in electrical pulses generated in the first and second electrode groups, thus detecting motion characteristics of the particles. The present invention is advantageous in that it does not require complicated optical measuring instruments or analyzing instruments, and in that it can be used to easily detect the motion characteristics of particles in a flow channel merely by analyzing variation in electrical pulses without requiring preliminary information.
    Type: Grant
    Filed: July 16, 2007
    Date of Patent: December 3, 2013
    Assignee: Korea Advanced Institute of Science and Technology (KAIST)
    Inventors: Young-Ho Cho, Tae Yoon Kim, Dong Woo Lee
  • Patent number: 8585883
    Abstract: An isotachophoresis method for preconcentrating and isolating a plurality n of charged analytes (Ai, with i=1 to n) contained in a sample is disclosed, wherein each one of the analytes Ai has an effective electrophoretic mobility ?Ai obeying the fully ordered relationship ?A1>?A2>etc.>?An, comprising the step of preparing a mixture of said sample and a number n?1 of spacer compounds (Sk, with k=1 to n?1) wherein each one of said spacer compounds (Sk) has an effective electrophoretic mobility ?Sk obeying the fully ordered relationship ?Ak>?Sk>?Ak+1. An axial electric field is applied along the longitudinal axis of a separation channel, thereby causing a preconcentration and separation of the analytes and spacers forming respective focused spacer zones and focused analyte zones that flow along the longitudinal axis.
    Type: Grant
    Filed: June 23, 2011
    Date of Patent: November 19, 2013
    Assignee: Swissfluidics AG
    Inventor: Reto Schoch
  • Patent number: 8580097
    Abstract: Methods are provided for forming a complex comprising an analyte (or an analyte analogue) from a blood-derived sample and labeling substances, and separating the complex from excess labeling substances and coexisting substances from the blood-derived sample, in a rapid, simple, convenient, and highly precise isotachophoresis (ITP) process by adding 2-(N-morpholino)ethane sulfonate (MES) salt and/or glutamate salt to the ITP sample. Methods are also provided for measuring the analyte in blood-derived samples with high precision and high sensitivity, based on the amount of the complex separated or the amount of uncomplexed labeling substance-containing molecules.
    Type: Grant
    Filed: February 19, 2010
    Date of Patent: November 12, 2013
    Assignee: Wako Pure Chemical Industries, Ltd.
    Inventors: Tatsuo Kurosawa, Mitsuo Watanabe, Takuma Ohtsubo
  • Patent number: 8562804
    Abstract: Indirect detection and/or identification of analytes by ITP can be enhanced by adding a mixture of labeled carrier ampholytes (CAs) to the sample to provide a continuous range of mobility markers. Each analyte can be detected and quantified by corresponding gaps in the CA signal. This approach does not require a priori choice of fluorophores and can be readily applied (without extensive and specific design) to a wide range of analytes. Analyte identification can be expedited by computing a normalized signal integral (NSI) from the CA signals. Empirical calibrations can relate the NSI to effective mobility. Effective mobility results under two or more different pH conditions can be used to determine analyte pKa and fully ionized mobility, which are analyte properties that can facilitate analyte identification.
    Type: Grant
    Filed: May 31, 2011
    Date of Patent: October 22, 2013
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Juan G. Santiago, Moran Bercovici, Govind V. Kaigala, Robert D. Chambers
  • Patent number: 8535512
    Abstract: Methods and devices for sequencing nucleic acids are disclosed herein. Devices are also provided herein for measuring DNA with nano-pores sized to allow DNA to pass through the nano-pore. The capacitance can be measured for the DNA molecule passing through the nano-pore. The capacitance measurements can be correlated to determine the sequence of base pairs passing through the nano-pore to sequence the DNA.
    Type: Grant
    Filed: September 29, 2011
    Date of Patent: September 17, 2013
    Assignee: California Institute of Technology
    Inventors: Sameer Walavalkar, Axel Scherer, Thomas A. Tombrello, Aditya Rajagopal, Andrew P. Homyk, Erika Garcia
  • Patent number: 8524061
    Abstract: Isotachophoresis (ITP) can be employed to simultaneously focus the target and ligand of an assay into the same ITP focus zone. The target and ligand can bind to each other in the ITP focus zone, and then the resulting bound complex can be detected (e.g., by fluorescence). The sensitivity of this approach can be greatly increased by the enhanced concentration of both target and ligand that ITP provides in the focus zone. Since ITP can be performed quickly, the resulting assay is both rapid and sensitive. Markers of bacterial urinary tract infections have been experimentally detected at clinically relevant concentrations with this approach. MicroRNA sequences have also been profiled with this approach, which is clinically relevant because MicroRNA is expected to provide useful markers for disease. In one experiment, miR-122 in human kidney and liver was detected and quantified.
    Type: Grant
    Filed: November 29, 2011
    Date of Patent: September 3, 2013
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Paul J. Utz, Juan G. Santiago, Michael G. Kattah, Alexandre Persat
  • Publication number: 20130180856
    Abstract: The invention provides apparatus for separation of particles and methods for using the apparatus. In an embodiment, the apparatus includes three arms extending radially from a central reservoir, each arm being associated with a separation electrode. At least one on the arms includes a separation medium. Using a sequence of driving and mobility-changing voltages, target particles can be separated from closely related particles within a sample. For example, single point mutations can be resolved from a sample containing predominantly wild type nucleic acids.
    Type: Application
    Filed: January 11, 2013
    Publication date: July 18, 2013
    Inventors: Andrea Marziali, Joel Pel
  • Publication number: 20130168250
    Abstract: The present invention is directed to droplet actuator systems, devices, and methods. In one embodiment, a microfluidic article of manufacture is provided. The microfluidic article of manufacture includes a first substrate; a second substrate separated from the first substrate to form a droplet operations gap; gap height setting spacers associated with the first and/or second substrate or situated between the first and second substrates; a spring forcing the second substrate against the gap height setting spacers, thereby establishing a substantially uniform gap height between the first and second substrates; and electrodes associated with the first and/or second substrate and configured to conduct droplet operations in the droplet operations gap.
    Type: Application
    Filed: September 15, 2011
    Publication date: July 4, 2013
    Applicant: ADVANCED LIQUID LOGIC INC
    Inventors: Michael Fogleman, Ryan A. Sturmer, Gregory F. Smith
  • Publication number: 20130146462
    Abstract: Isotachophoresis (ITP) is exploited to control various aspects of chemical reactions. In a first aspect, at least one of the reactants of a chemical reaction is confined to an ITP zone, but the resulting product of the chemical reaction is separated from this ITP zone by the ITP process. In a second aspect, one or more reactants of a chemical reaction are confined to an ITP zone, and one or more other reactants of the chemical reaction are not confined to this ITP zone. In a third aspect, ITP is employed to confine at least one reactant of a chemical reaction to an ITP zone, and at least one reactant of the chemical reaction is delivered to the ITP zone in two or more discrete doses. These aspects are especially relevant to performing polymerase chain reactions using chemical denaturants as opposed to thermal cycling.
    Type: Application
    Filed: February 11, 2013
    Publication date: June 13, 2013
    Inventor: The Board of Trustees of the Leland Stanford
  • Patent number: 8460530
    Abstract: A method of modifying the concentration of reactants and carrying out a chemical reaction on a microfluidic device in which first and second reactants are delivered into a reaction channel combined, the second reactant different from the first reactant and capable of reacting with the first reactant. The first reactant is subjected to a stacking process, thereby producing a first stacked reactant. The second reactant is subjected to the stacking process, thereby producing a second stacked reactant. The first stacked reactant is exposed to the second stacked reactant so that the first stacked reactant and the second stacked reactant undergo a chemical reaction.
    Type: Grant
    Filed: September 16, 2011
    Date of Patent: June 11, 2013
    Assignee: Caliper Life Sciences, Inc.
    Inventors: Charles Park, Irina Kazakova
  • Patent number: 8444837
    Abstract: A device for producing at least one of fluid flows and particles flows includes a substrate having a substrate surface. The substrate surface includes a matrix including a plurality of regions having at least one of a different magnitude of a surface charge, a different sign of the surface charge, and a different height above the substrate. A fluid including at least partially electrically charged particles is disposed at the substrate surface. A first control element is configured to supply a plurality of electrical voltages to a plurality of electrode pairs. The electric field exerts a first force on a component of the fluid within an electrical double layer. The component is disposed adjacent to the substrate surface. The electric field exerts a second force within the double layer and outside the double layer, the second force is exerted on the at least partially electrically charged particles.
    Type: Grant
    Filed: January 27, 2007
    Date of Patent: May 21, 2013
    Assignee: Forschungszentrum Karlsruhe GmbH
    Inventors: Andreas Class, Dominik Barz
  • Patent number: 8414754
    Abstract: Analysis of samples is facilitated. According to an example embodiment, an electrophoresis approach involves electrophoretically stacking and/or separating a sample or samples. An electrolyte and a mixture of one or more samples with another electrolyte are added to a microchannel or capillary. An electric field is applied to stack (and, in some applications, further separate) the one or more samples. Generally, the electric field and electrolyte are used to facilitate isotachophoretic (ITP) stacking. In some embodiments, a further electric field is applied and used with the electrolyte to facilitate subsequent capillary electrophoresis (CE).
    Type: Grant
    Filed: May 30, 2007
    Date of Patent: April 9, 2013
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Juan G. Santiago, Byoungsok Jung, Rajiv Bharadwaj, Tarun Kumar Khurana
  • Patent number: 8394251
    Abstract: Isotachophoresis (ITP) is exploited to control various aspects of chemical reactions. In a first aspect, at least one of the reactants of a chemical reaction is confined to an ITP zone, but the resulting product of the chemical reaction is separated from this ITP zone by the ITP process. In a second aspect, one or more reactants of a chemical reaction are confined to an ITP zone, and one or more other reactants of the chemical reaction are not confined to this ITP zone. In a third aspect, ITP is employed to confine at least one reactant of a chemical reaction to an ITP zone, and at least one reactant of the chemical reaction is delivered to the ITP zone in two or more discrete doses. These aspects are especially relevant to performing polymerase chain reactions using chemical denaturants as opposed to thermal cycling.
    Type: Grant
    Filed: October 7, 2009
    Date of Patent: March 12, 2013
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Juan G. Santiago, Alexandre Persat
  • Publication number: 20130048499
    Abstract: Improved resolution and detection of nanoparticles are achieved when a nanopore connecting liquid compartments in a device running on the Coulter principle is provided with fluid lipid walls. The fluid lipid walls are made of a lipid bilayer, and preferably include lipid anchored mobile ligands as part of the lipid bilayer. By varying the nature and concentration of the mobile ligand in the lipid bilayer, multifunctional coatings of lipids are provided.
    Type: Application
    Filed: February 20, 2012
    Publication date: February 28, 2013
    Applicant: The Regents of the University of Michigan
    Inventors: Michael Mayer, Erik Yusko, Jerry Yang
  • Publication number: 20120285831
    Abstract: The invention provides apparatus and methods of preparation of lipoproteins from a biological sample, including HDL, LDL, Lp(a), IDL, and VLDL, for diagnostic purposes utilizing differential charged-particle mobility analysis methods. Further provided are methods for analyzing the size distribution of lipoproteins by differential charged-particle mobility, which lipoproteins are prepared by methods of the invention. Further provided are methods for assessing lipid-related health risk, cardiovascular condition, risk of cardiovascular disease, and responsiveness to a therapeutic intervention, which methods utilize lipoprotein size distributions determined by methods of the invention.
    Type: Application
    Filed: December 29, 2011
    Publication date: November 15, 2012
    Inventors: Michael P. Caulfield, Jackie Liu, Dawn Shalhout, Zhihong Chen
  • Patent number: 8246799
    Abstract: Devices and methods for detecting the length of analytes and/or sequencing analytes are provided in which two or more electrical signals are obtained as an analyte traverses a nanopore or fluidic channel. Detection of the relative position of probes hybridized to a biomolecule and/or the length of the analyte (e.g., a biomolecule) rely on detection events to determine a distance associated with the biomolecule. Multiple signals may be obtained (e.g., as functions of time) corresponding to a plurality of detector volumes at known locations along a fluidic channel through which the biomolecule passes, and the distances may be determined from the multiple signals.
    Type: Grant
    Filed: May 28, 2010
    Date of Patent: August 21, 2012
    Assignee: Nabsys, Inc.
    Inventors: John S. Oliver, Petre Ianakiev
  • Publication number: 20120181176
    Abstract: Methods for the detection of biologically relevant molecules that comprise concentrating such molecules into microscopic holes in a sheet of chemically inert material, restricting the openings, and measuring the electric current through the holes or the fluorescence near the hole openings. The electric current or fluorescence will change as the molecules diffuse out of the holes, providing a measure of the diffusion rate and thereby detecting the presence and characteristics of the molecules. For molecules that interact, the diffusion rate will be slower than for molecules that do not interact, yielding a determination of the molecular interaction. Capping the population of holes and inserting into a mass spectrometer allows identification of the molecules.
    Type: Application
    Filed: February 15, 2011
    Publication date: July 19, 2012
    Inventor: Christopher Gordon Atwood
  • Publication number: 20120175258
    Abstract: An isotachophoresis system for separating a sample containing particles into discrete packets including a flow channel, the flow channel having a large diameter section and a small diameter section; a negative electrode operably connected to the flow channel; a positive electrode operably connected to the flow channel; a leading carrier fluid in the flow channel; a trailing carrier fluid in the flow channel; and a control for separating the particles in the sample into discrete packets using the leading carrier fluid, the trailing carrier fluid, the large diameter section, and the small diameter section.
    Type: Application
    Filed: May 12, 2011
    Publication date: July 12, 2012
    Applicant: Lawrence Livermore National Security, LLC
    Inventor: Raymond P. Mariella, JR.
  • Publication number: 20120160689
    Abstract: Isotachophoresis (ITP) can be employed to simultaneously focus the target and ligand of an assay into the same ITP focus zone. The target and ligand can bind to each other in the ITP focus zone, and then the resulting bound complex can be detected (e.g., by fluorescence). The sensitivity of this approach can be greatly increased by the enhanced concentration of both target and ligand that ITP provides in the focus zone. Since ITP can be performed quickly, the resulting assay is both rapid and sensitive. Markers of bacterial urinary tract infections have been experimentally detected at clinically relevant concentrations with this approach. MicroRNA sequences have also been profiled with this approach, which is clinically relevant because MicroRNA is expected to provide useful markers for disease. In one experiment, miR-122 in human kidney and liver was detected and quantified.
    Type: Application
    Filed: November 29, 2011
    Publication date: June 28, 2012
    Inventors: Paul J. Utz, Juan G. Santiago, Michael G. Kattah, Alexandre Persat
  • Publication number: 20120152746
    Abstract: Indirect detection and/or identification of analytes by ITP can be enhanced by adding a mixture of labeled carrier ampholytes (CAs) to the sample to provide a continuous range of mobility markers. Each analyte can be detected and quantified by corresponding gaps in the CA signal. This approach does not require a priori choice of fluorophores and can be readily applied (without extensive and specific design) to a wide range of analytes. Analyte identification can be expedited by computing a normalized signal integral (NSI) from the CA signals. Empirical calibrations can relate the NSI to effective mobility. Effective mobility results under two or more different pH conditions can be used to determine analyte pKa and fully ionized mobility, which are analyte properties that can facilitate analyte identification.
    Type: Application
    Filed: May 31, 2011
    Publication date: June 21, 2012
    Inventors: Juan G. Santiago, Moran Bercovici, Govind V. Kaigala, Robert D. Chambers
  • Publication number: 20120091001
    Abstract: The invention pertains to a method and apparatus to separate and quantify particles using time-variable force fields. The force fields can be for dielectrophoresis (positive or negative), electrophoresis or electrohydrodinamic. In a first aspect of the method, the fields are translated and/or modified in space at a speed substantially comparable to the speed of translation of the fastest particles in the sample so that only these follow by changing position, while the slowest particles are not affected. According to the invention the translation and/or modification of the force field can also occur with varying speed, which is especially useful when this happens with periodic law on a field with spatial periodicity.
    Type: Application
    Filed: January 8, 2007
    Publication date: April 19, 2012
    Inventors: Nicolò Manaresi, Gianni Medoro
  • Publication number: 20120073972
    Abstract: A high-throughput optical suspension characterization instrument is disclosed, which can include hydraulically separate and at least partially transparent sample containers. A selection mechanism is operative to selectively direct light from a light source (12) through different ones of the sample containers along an optical axis, and an off-axis scattering detector (38,24) is responsive to scattered light from the light source after it has interacted with a sample. Phase analysis light scattering is used to determine the electrophoretic mobility and zeta potential of samples. A second instrument is disclosed, wherein all sample containers are illuminated simultaneously. Transmitted light is collected by a camera. The electrophoretic mobility and hydrodynamic size of the samples may be determined.
    Type: Application
    Filed: October 9, 2009
    Publication date: March 29, 2012
    Inventor: Fraser McNeil Watson