Patents Assigned to Fluidigm Corporation
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Patent number: 9364829Abstract: The invention relates to methods, reagents and devices for detection and characterization of nucleic acids, cells, and other biological samples. Assay method are provided in which a sample is partitioned into sub-samples, and analysis of the contents of the sub-samples carried out. The invention also provides microfluidic devices for conducting the assay. The invention also provides an analysis method using a universal primers and probes for amplification and detection.Type: GrantFiled: November 12, 2010Date of Patent: June 14, 2016Assignee: FLUIDIGM CORPORATIONInventors: Christian A. Heid, Antoine Daridon
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Patent number: 9353406Abstract: Reagents and methods are provided for detecting the presence of a target polynucleotide in a sample are disclosed. In one aspect, a method for producing a labeled amplification product by amplifying a target nucleic acid sequence to produce an amplification product comprising the target sequence, a first probe-binding sequence 5? to the target sequence, and a second probe-binding sequence 3? to the target sequence, thereby producing an amplification product; and hybridizing a first detection probe to the amplification product, the first detection probe comprising a first segment that hybridizes to the first probe-binding sequence and a second segment that hybridizes to the second probe-binding sequence, thereby producing a labeled amplification product is disclosed.Type: GrantFiled: October 24, 2011Date of Patent: May 31, 2016Assignee: Fluidigm CorporationInventors: Kenneth J. Livak, Jason A. A. West, Robert C. Jones
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Patent number: 9316331Abstract: Multilevel microfluidic devices include a control line that can simultaneously actuate valves for both sample and reagent lines. Microfluidic devices are configured to contain a first reagent in a first chamber and a second reagent in a second chamber, where either or both of the first and second reagents are contained at a desired or selected pressure. Operation of a microfluidic device includes transmitting second reagent from the second chamber to the first chamber, for mixing or contact with the first reagent. Microfluidic device features such as channels, valves, chambers, can be at least partially contained, embedded, or formed by or within one or more layers or levels of an elastomeric block.Type: GrantFiled: November 27, 2013Date of Patent: April 19, 2016Assignee: Fluidigm CorporationInventors: Geoffrey Facer, Brian Fowler, Emerson Cheung Quan, Marc Unger
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Patent number: 9304065Abstract: Methods, systems, and devices are described for multiple single-cell capturing and processing utilizing microfluidics. Tools and techniques are provided for capturing, partitioning, and/or manipulating individual cells from a larger population of cells along with generating genetic information and/or reactions related to each individual cell. Different capture configurations may be utilized to capture individual cells and then processing each individual cell in a multi-chamber reaction configuration. Some embodiments may provide for specific target amplification, whole genome amplification, whole transcriptome amplification, real-time PCR preparation, copy number variation, preamplification, mRNA sequencing, and/or haplotyping of the multiple individual cells that have been partitioned from the larger population of cells. Some embodiments may provide for other applications. Some embodiments may be configured for imaging the individual cells or associated reaction products as part of the processing.Type: GrantFiled: February 28, 2013Date of Patent: April 5, 2016Assignee: Fluidigm CorporationInventors: Brian Fowler, Jake Kimball, Myo Thu Maung, Andrew May, Michael C. Norris, Dominique G. Toppani, Marc A. Unger, Jing Wang, Jason A. A. West
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Patent number: 9284605Abstract: The invention provides methods and devices for detecting, enumerating or identifying target nucleic acid molecules using immobilized capture probes and single molecule sequencing techniques.Type: GrantFiled: June 27, 2014Date of Patent: March 15, 2016Assignee: Fluidigm CorporationInventor: Stanley N. Lapidus
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Patent number: 9249459Abstract: The present invention provides methods for analysis of genomic DNA and/or RNA from small samples or even single cells. Methods for analyzing genomic DNA can entail whole genome amplification (WGA), followed by preamplification and amplification of selected target nucleic acids. Methods for analyzing RNA can entail reverse transcription of the desired RNA, followed by preamplification and amplification of selected target nucleic acids.Type: GrantFiled: December 10, 2013Date of Patent: February 2, 2016Assignee: Fluidigm CorporationInventors: Amy Hamilton, Min Lin, Alain Mir, Martin Pieprzyk
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Patent number: 9234237Abstract: An apparatus for imaging one or more selected fluorescence indications from a microfluidic device. The apparatus includes an imaging path coupled to least one chamber in at least one microfluidic device. The imaging path provides for transmission of one or more fluorescent emission signals derived from one or more samples in the at least one chamber of the at least one microfluidic device. The chamber has a chamber size, the chamber size being characterized by an actual spatial dimension normal to the imaging path. The apparatus also includes an optical lens system coupled to the imaging path. The optical lens system is adapted to transmit the one or more fluorescent signals associated with the chamber.Type: GrantFiled: November 19, 2014Date of Patent: January 12, 2016Assignee: Fluidigm CorporationInventors: Marc A. Unger, Geoffrey Richard Facer, Barry Clerkson, Christopher G. Cesar, Neil Switz
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Publication number: 20150361486Abstract: The invention provides a method for detecting a target nucleotide sequence by tagging the nucleotide sequence with a nucleotide tag, providing a probe oligonucleotide with a melting temperature Tm1, comprising a regulatory sequence and a nucleotide tag recognition sequence; incorporating the probe oligonucleotide into the tagged polynucleotide in a polynucleotide amplification reaction, providing a regulatory oligonucleotide with a melting temperature Tm2, comprising a sequence segment that complementary to the regulatory sequence and a tail segment that does not hybridize to the probe nucleotide when the sequence segment and the regulatory sequence are annealed, amplifying the tagged target nucleic acid sequence in a PCR amplification reaction using the probe oligonucleotide as a primer, and using a DNA polymerase with high strand displacement activity and low 5?-nuclease activity, and detecting the amplification product; wherein Tm1 and Tm2 are higher than the annealing temperature associated with the polynType: ApplicationFiled: May 15, 2015Publication date: December 17, 2015Applicant: FLUIDIGM CORPORATIONInventors: Kenneth J. Livak, Stacey N. Meyers, Xiaohui Wang, Jun Wang
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Patent number: 9205468Abstract: A method for rendering a microfluidic device suitable for reuse for nucleic acid analysis is provided. The method may include flowing a nucleic acid inactivating solution into a microfluidic channel of the device by pumping; and then flowing a wash solution into the channel by pumping, thereby displacing the nucleic acid inactivating solution from the channel, whereby any residual nucleic acid from a prior use of the device is inactivated.Type: GrantFiled: November 30, 2010Date of Patent: December 8, 2015Assignee: Fluidigm CorporationInventors: Jing Wang, Timothy M. Woudenberg
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Patent number: 9182322Abstract: Microfluidic devices are described that include a rigid base layer, and an elastomeric layer on the base layer. The elastomeric layer may include at least part of a fluid channel for transporting a liquid reagent, and a vent channel that accepts gas diffusing through the elastomeric layer from the flow channel and vents it out of the elastomeric layer. The devices may also include a mixing chamber fluidly connected to the fluid channel, and a control channel overlapping with a deflectable membrane that defines a portion of the flow channel, where the control channel may be operable to change a rate at which the liquid reagent flows through the fluid channel. The devices may further include a rigid plastic layer on the elastomeric layer.Type: GrantFiled: November 27, 2013Date of Patent: November 10, 2015Assignee: Fluidigm CorporationInventors: Tim Woudenberg, Jing Wang, Hou-Pu Chou
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Patent number: 9168531Abstract: A thermal cycler for a microfluidic device includes a controller operable to provide a series of electrical signals, a heat sink, and a heating element in thermal communication with the heat sink and operable to receive the series of electrical signals from the controller. The thermal cycler also includes a thermal chuck in thermal communication with the heating element. The thermal chuck comprises a heating surface operable to make thermal contact with the microfluidic device. The heating surface is characterized by a temperature ramp rate between 2.5 degrees Celsius per second and 5.5 degrees Celsius per second and a temperature difference between a first portion of the heating surface supporting a first portion of the microfluidic device and a second portion of the heating surface supporting a second portion of the microfluidic device is less than 0.25° C.Type: GrantFiled: March 26, 2012Date of Patent: October 27, 2015Assignee: FLUIDIGM CORPORATIONInventors: Jake Kimball, Brandon Ripley, Gang Sun, Dominique Toppani, Myo Thu Maung
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Patent number: 9163053Abstract: The invention generally relates to nucleotide analogs and methods of their use in sequencing-by-synthesis reactions. In certain embodiments, the invention provides a nucleotide analog including a detectable label attached to a nitrogenous base portion of a nucleotide analog by a cleavable linker, in which contact of the analog with at least one activating agent results in cleavage of the label and elimination of the linker, thereby producing a natural nucleotide, a 9-deaza-G, 9-deaza-A, or ?-uridine.Type: GrantFiled: December 4, 2009Date of Patent: October 20, 2015Assignee: Fluidigm CorporationInventors: Suhaib Siddiqi, J. William Efcavitch, Judith Mitchell, Subramanian Marappan, Jayson Bowers, Mirna Jaroza
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Patent number: 9157116Abstract: High throughput methods are used that combine the features of using a matrix-type microfluidic device, labeled nucleic acid probes, and homogenous assays to detect and/or quantify nucleic acid analytes. The high throughput methods are capable of detecting nucleic acid analyes with high PCR and probe specificity, producing a low fluorescence background and therefore, a high signal to noise ratio. Additionally, the high throughput methods are capable of detecting low copy number nucleic acid analyte per cell.Type: GrantFiled: February 9, 2009Date of Patent: October 13, 2015Assignee: Fluidigm CorporationInventors: Kenneth J. Livak, Marc Unger
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Patent number: 9150913Abstract: An M×N matrix microfluidic device for performing a matrix of reactions, the device having a plurality of reaction cells in communication with one of either a sample inlet or a reagent inlet through a via formed within an elastomeric block of the device. Methods provided include a method for forming vias in parallel in an elastomeric layer of an elastomeric block of a microfluidic device, the method comprising using patterned photoresist masks and etching reagents to etch away regions or portions of an elastomeric layer of the elastomeric block.Type: GrantFiled: July 12, 2012Date of Patent: October 6, 2015Assignee: Fluidigm CorporationInventors: Lincoln McBride, Geoffrey Facer, Marc Unger, Michael Lucero, Hany Ramez Nassef
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Publication number: 20150273735Abstract: An integrated fluidic chip includes a substrate defined by a lateral surface area greater than 28 square inches. The integrated fluidic chip also includes a first elastomeric layer having a mold surface and a top surface. The mold surface of the first elastomeric layer is joined to a portion of the substrate. The first elastomeric layer includes a plurality of first channels extending normally from the substrate to a first dimension inside the first elastomeric layer. The integrated fluidic chip further includes a second elastomeric layer having a mold surface and a top surface. The mold surface of the second elastomeric layer is joined to at least a portion of the top surface of the first elastomeric layer.Type: ApplicationFiled: July 23, 2009Publication date: October 1, 2015Applicant: FLUIDIGM CORPORATIONInventor: David S. Cohen
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Patent number: 9103825Abstract: A microfluidic device adapted to perform many simultaneous binding assays including but not limited to immunological experiments, such as ELISA assays, with minimal cross-talk between primary and secondary antibodies.Type: GrantFiled: April 21, 2010Date of Patent: August 11, 2015Assignee: FLUIDIGM CORPORATIONInventors: Hany Ramez Nassef, Hou-Pu Chou, Michael Lucero, Andrew May, Kathy Yokobata
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Patent number: 9103761Abstract: The presence of a detectable entity within a detection volume of a microfabricated elastomeric structure is sensed through a change in the electrical or magnetic environment of the detection volume. In embodiments utilizing electronic detection, an electric field is applied to the detection volume and a change in impedance, current, or combined impedance and current due to the presence of the detectable entity is measured. In embodiments utilizing magnetic detection, the magnetic properties of a magnetized detected entity alter the magnetic field of the detection volume. This changed magnetic field induces a current which can reveal the detectable entity. The change in resistance of a magnetoresistive element may also reveal the passage of a magnetized detectable entity.Type: GrantFiled: April 22, 2013Date of Patent: August 11, 2015Assignee: FLUIDIGM CORPORATIONInventors: Hany Nassef, Geoffrey Facer, Marc Unger
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Patent number: 9090934Abstract: The invention provides an assay method for detection and/or quantification of a plurality of nucleic acid or protein targets in a sample. In the method probes are used to associate a detectable tag sequence with each of the selected targets present in the sample. Probes or primers sufficient to identify at least 25, and preferably at least 500, different targets are used. The method involves segregating aliquots of the sample from each other and detecting the tag sequences in each aliquot.Type: GrantFiled: July 14, 2014Date of Patent: July 28, 2015Assignee: Fluidigm CorporationInventors: Michael Lucero, Marc Unger
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Patent number: 9074204Abstract: Described herein are methods useful for incorporating one or more adaptors and/or nucleotide tag(s) and/or barcode nucleotide sequence(s) one, or typically more, target nucleotide sequences. In particular embodiments, nucleic acid fragments having adaptors, e.g., suitable for use in high-throughput DNA sequencing are generated. In other embodiments, information about a reaction mixture is encoded into a reaction product. Also described herein are methods and kits useful for amplifying one or more target nucleic acids in preparation for applications such as bidirectional nucleic acid sequencing. In particular embodiments, methods of the invention entail additionally carrying out bidirectional DNA sequencing. Also described herein are methods for encoding and detecting and/or quantifying alleles by primer extension.Type: GrantFiled: May 21, 2012Date of Patent: July 7, 2015Assignee: Fluidigm CorporationInventors: Megan Anderson, Peilin Chen, Brian Fowler, Robert C. Jones, Fiona Kaper, Ronald Lebofsky, Andrew May
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Patent number: D732185Type: GrantFiled: March 13, 2013Date of Patent: June 16, 2015Assignee: Fluidigm CorporationInventors: Temujin W. Kuechle, Raphael Hebert, David Moriconi