Fluidigm Corporation Patent applications |
Patent application number | Title | Published |
20150361486 | NUCLEIC ACID DETECTION USING PROBES - 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 polynucleotide amplification reaction. | 12-17-2015 |
20150273735 | METHOD AND SYSTEM FOR MANUFACTURING INTEGRATED FLUIDIC CHIPS - 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. | 10-01-2015 |
20140378352 | MICROFLUIDIC PARTICLE-ANALYSIS SYSTEMS - The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or detection of particles, such as cells and/or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or analysis of particles, such as cells, viruses, organelles, beads, and/or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement/positioning, retention/localization, treatment, measurement, release, and/or output of particles. Furthermore, these mechanisms may be combined in any suitable order and/or employed for any suitable number of times within a system. Accordingly, these combinations may allow particles to be sorted, cultured, mixed, treated, and/or assayed, among others, as single particles, mixed groups of particles, arrays of particles, heterogeneous particle sets, and/or homogeneous particle sets, among others, in series and/or in parallel. In addition, these combinations may enable microfluidic systems to be reused. Furthermore, these combinations may allow the response of particles to treatment to be measured on a shorter time scale than was previously possible. Therefore, systems of the invention may allow a broad range of cell and particle assays, such as drug screens, cell characterizations, research studies, and/or clinical analyses, among others, to be scaled down to microfluidic size. Such scaled-down assays may use less sample and reagent, may be less labor intensive, and/or may be more informative than comparable macrofluidic assays. | 12-25-2014 |
20140318633 | Multilevel Microfluidic Systems and Methods - 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. | 10-30-2014 |
20140308178 | Microfluidic Mixing and Reaction Systems for High Efficiency Screening - 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. | 10-16-2014 |
20140296090 | ASSAY METHODS FOR INCREASED THROUGHPUT OF SAMPLES AND/OR TARGETS - The present invention provides assay methods that increase the number of samples and/or target nucleic acids that can be analyzed in a single assay. | 10-02-2014 |
20140272952 | MULTI-PRIMER AMPLIFICATION METHOD FOR BARCODING OF TARGET NUCLEIC ACIDS - In certain embodiments, the present invention provides amplification methods in which nucleotide tag(s) and, optionally, a barcode nucleotide sequence are added to target nucleotide sequences. In other embodiments, the present invention provides a microfluidic device that includes a plurality of first input lines and a plurality of second input lines. The microfluidic device also includes a plurality of sets of first chambers and a plurality of sets of second chambers. Each set of first chambers is in fluid communication with one of the plurality of first input lines. Each set of second chambers is in fluid communication with one of the plurality of second input lines. The microfluidic device further includes a plurality of first pump elements in fluid communication with a first portion of the plurality of second input lines and a plurality of second pump elements in fluid communication with a second portion of the plurality of second input lines. | 09-18-2014 |
20140256561 | SURFACE CHEMISTRY AND DEPOSITION TECHNIQUES - Surface chemistries for the visualization of labeled single molecules (analytes) with improved signal-to-noise properties are provided. To be observed, analyte molecules are bound to surface attachment features that are spaced apart on the surface such that when the analytes are labeled adjacent analytes are optically resolvable from each other. One way to express this concept is that binding elements should be spaced apart such that the Guassian point spread functions of adjacent labels do not overlap. Another way of expressing this concept is that the surface binding elements should be spaced apart by a distance equal to at least the diffraction limit for an optical label attached to the bound analytes. | 09-11-2014 |
20140193896 | High Efficiency and High Precision Microfluidic Devices and Methods - New high density microfluidic devices and methods provide precise metering of fluid volumes and efficient mixing of the metered volumes. A first solution is introduced into a segment of a flow channel in fluidic communication with a reaction chamber. A second solution is flowed through the segment so that the first solution is displaced into the reaction chamber, and a volume of the second solution enters the chamber. The chamber can then be isolated and reactions within the chamber can be initiated and/or detected. High throughput methods of genetic analysis can be carried out with greater accuracy than previously available. | 07-10-2014 |
20140193812 | SINGLE-CELL NUCLEIC ACID ANALYSIS - 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. | 07-10-2014 |
20140154679 | DETERMINATION OF COPY NUMBER DIFFERENCES BY AMPLIFICATION - The present invention provides for determining relative copy number difference for one or more target nucleic acid sequences between a test sample and a reference sample or reference value derived therefrom. The methods facilitate the detection of copy number differences less than 1.5-fold. | 06-05-2014 |
20140133732 | METHODS AND SYSTEMS FOR IMAGE PROCESSING OF MICROFLUIDIC DEVICES - A method of processing data associated with fluorescent emissions from a microfluidic device. The method includes performing an auto-focus process associated with a first image of the microfluidic device and performing an auto-exposure process associated with the first image of the microfluidic device. The method also includes capturing a plurality of images of the microfluidic device. The plurality of images are associated with a plurality of thermal cycles. The method further includes performing image analysis of the plurality of captured images to determine a series of optical intensities and performing data analysis of the series of optical intensities to provide a series of change in threshold values. | 05-15-2014 |
20140130920 | MICROFABRICATED FLUIDIC CIRCUIT ELEMENTS AND APPLICATIONS - A microfabricated fluidic unidirectional valve includes a microfabricated elastomer material having a flow through channel. The microfabricated fluidic unidirectional valve also includes an elastomer flap attached to the elastomer material in the flow through channel. The elastomer flap forms a seal in the flow through channel to prevent fluid from flowing in a first direction through the flow through channel and to allow fluid flow in a second direction through the flow through channel. | 05-15-2014 |
20140087973 | INTEGRATED CARRIER FOR MICROFLUIDIC DEVICE - An injection molding method of fabricating a carrier for holding a microfluidic device can form all of the desired features of such a carrier, including wells, channels and ports having smaller dimensions and greater density than previously achieved, while reducing or avoiding fracturing and the need for drilling the substrate to form certain features, in particular the ports. The carrier includes a substrate with a plurality of wells, each well defining a volume of between 0.1 μl and 100 μl; a plurality of channels within the substrate wherein each well is in fluid communication with at least one of the plurality of channels; a plurality of ports within the carrier substrate wherein each port is for coupling with regions in the carrier substrate adapted to receive fluids or pressure; and a receiving portion for receiving a microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells. The carrier has a polymeric composition and/or an array of structural features achieved via the injection molding fabrication technique that enhance its performance and compatibility with existing instrumentation. | 03-27-2014 |
20140045729 | MICROFLUIDIC REACTION APPARATUS FOR HIGH THROUGHPUT SCREENING - An SBS-formatted microfluidic device where the geometry of the plate defines an array of interrogation areas, and where each interrogation area encompasses at least one reaction site. | 02-13-2014 |
20140045184 | Microfluidic Devices and Methods - Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices. | 02-13-2014 |
20140024559 | Optical Lens System and Method for Microfluidic Devices - 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. | 01-23-2014 |
20130337457 | Multilevel Microfluidic Systems and Methods - 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. | 12-19-2013 |
20130323732 | SINGLE-PARTICLE ANALYSIS OF PARTICLE POPULATIONS - In certain embodiments, the invention provides methods and devices for assaying single particles in a population of particles, wherein at least two parameters are measured for each particle. One or more parameters can be measured while the particles are in the separate reaction volumes. Alternatively or in addition, one or more parameters can be measured in a later analytic step, e.g., where reactions are carried out in the separate reaction volumes and the reaction products are recovered and analyzed. In particular embodiments, one or more parameter measurements are carried out “in parallel,” i.e., essentially simultaneously in the separate reaction volumes. | 12-05-2013 |
20130260381 | COPY NUMBER VARIATION DETERMINATION, METHODS AND SYSTEMS - The present invention methods and systems for determining copy number variation of a target polynucleotide in a genome of a subject including amplification based techniques. Methods can include pre-amplification of the sample followed by distribution of sample and a plurality of reaction volumes, quantitative detection of a target polynucleotide and a reference polynucleotide, and analysis so as to determine the relative copy number of the target polynucleotide sequence in the genome of the subject. | 10-03-2013 |
20130252234 | METHODS AND DEVICES FOR ELECTRONIC SENSING - 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. | 09-26-2013 |
20130186433 | MICROFLUIDIC DEVICE REGENERATION - 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. | 07-25-2013 |
20130171633 | THERMAL REACTION DEVICE AND METHOD FOR USING THE SAME - 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. | 07-04-2013 |
20130089874 | RECIRCULATING FLUIDIC NETWORK AND METHODS FOR USING THE SAME - The present invention provides a variety of microfluidic devices and methods for conducting assays and syntheses. The devices include a solid substrate layer having a surface that is capable of attaching ligand and or anti-ligand, and an elastomeric layer attached to said surface. Preferred embodiments have deflectable membrane valves and pumps, for example, rotary pumps associated therewith. | 04-11-2013 |
20130078610 | METHOD AND SYSTEM FOR THERMAL CYCLING OF MICROFLUIDIC SAMPLES - 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. | 03-28-2013 |
20130065773 | Microfluidic Device and Methods of Using Same - A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses. | 03-14-2013 |
20130045881 | Probe Based Nucleic Acid Detection - 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 Tm | 02-21-2013 |
20130005585 | NUCLEIC ACID ENCODING REACTIONS - 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. | 01-03-2013 |
20130000765 | MICROFABRICATED FLUIDIC CIRCUIT ELEMENTS AND APPLICATIONS - A microfabricated fluidic unidirectional valve includes a microfabricated elastomer material having a flow through channel. The microfabricated fluidic unidirectional valve also includes an elastomer flap attached to the elastomer material in the flow through channel. The elastomer flap forms a seal in the flow through channel to prevent fluid from flowing in a first direction through the flow through channel and to allow fluid flow in a second direction through the flow through channel. | 01-03-2013 |
20120305087 | High Efficiency and High Precision Microfluidic Devices and Methods - New high density microfluidic devices and methods provide precise metering of fluid volumes and efficient mixing of the metered volumes. A first solution is introduced into a segment of a flow channel in fluidic communication with a reaction chamber. A second solution is flowed through the segment so that the first solution is displaced into the reaction chamber, and a volume of the second solution enters the chamber. The chamber can then be isolated and reactions within the chamber can be initiated and/or detected. High throughput methods of genetic analysis can be carried out with greater accuracy than previously available. | 12-06-2012 |
20120288857 | MULTIFUNCTIONAL PROBE-PRIMERS - Methods and reagents for detection and analysis of nucleic acids are provided. Certain methods involves an encoding amplification in which a target sequence is associated with probe-binding sequences and optionally with indexing sequences, (2) an optional distribution step in which the product of the encoding amplification is split into multiple aliquots, and (3) a decoding and detection step in which the presence, absence, quantity, or relative amount of the target sequence in the aliquots is determined. The detection step makes use of a multifunctional “self-digesting” molecular probe comprising a primer polynucleotide and a probe oligonucleotide, linked in a 5′-5′ orientation. | 11-15-2012 |
20120282604 | Copy Number Variation Determination, Methods and Systems - The present invention methods and systems for determining copy number variation of a target polynucleotide in a genome of a subject including amplification based techniques. Methods can include pre-amplification of the sample followed by distribution of sample and a plurality of reaction volumes, quantitative detection of a target polynucleotide and a reference polynucleotide, and analysis so as to determine the relative copy number of the target polynucleotide sequence in the genome of the subject. | 11-08-2012 |
20120261007 | MICROFLUIDIC DEVICES AND METHODS - Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices. | 10-18-2012 |
20120245888 | METHODS AND SYSTEMS FOR IMAGE PROCESSING OF MICROFLUIDIC DEVICES - A method of processing data associated with fluorescent emissions from a microfluidic device. The method includes performing an auto-focus process associated with a first image of the microfluidic device and performing an auto-exposure process associated with the first image of the microfluidic device. The method also includes capturing a plurality of images of the microfluidic device. The plurality of images are associated with a plurality of thermal cycles. The method further includes performing image analysis of the plurality of captured images to determine a series of optical intensities and performing data analysis of the series of optical intensities to provide a series of change in threshold values. | 09-27-2012 |
20120242825 | METHOD AND SYSTEM FOR MICROFLUIDIC DEVICE AND IMAGING THEREOF - A method for producing an image of an object within a chamber of a microfluidic device includes providing the microfluidic device having x, y, and z dimensions and a chamber depth center point located along the z dimension. The chamber depth center point is located a known z dimension distance from a fiducial marking embedded within the microfluidic device. The method also includes placing the microfluidic device within an imaging system that includes an optical device capable of detecting the fiducial marking. The optical device defines an optical path axially aligned with the z dimension and has a focal plane perpendicular to the optical path. When the focal plane is moved along the optical path, the fiducial marking is maximally detected when the focal plane is at the z depth in comparison to when the focal plane is not substantially in-plane with the z depth. | 09-27-2012 |
20120195810 | MICROFLUIDIC DEVICES WITH REMOVABLE COVER AND METHODS OF FABRICATION AND APPLICATION - The present invention includes microfluidic systems having a microfabricated cavity that may be covered with a removable cover, where the removable cover allows at least part of the opening of the microfabricated cavity to be exposed or directly accessed by an operator. The microfluidic systems comprise chambers, flow and control channels formed in elastomeric layers that may comprise PDMS. The removable cover comprises a thermoplastic base film bonded to an elastomer layer by an adhesive layer. When the removable cover is peeled off, the chamber is at least partially open to allow sample extraction from the chamber. The chamber may have macromolecular crystals formed inside or resulting contents from a PCR reaction. The invention also includes a method for making vias in elastomeric layers by using the removable cover. The invention further includes methods and devices for peeling the peelable cover or a removable component such as Integrated Heater Spreader. | 08-02-2012 |
20120115143 | Universal Probe Assay Methods - 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, said 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. | 05-10-2012 |
20120045087 | ANALYSIS ENGINE AND DATABASE FOR MANIPULATING PARAMETERS FOR FLUIDIC SYSTEMS ON A CHIP - Systems for managing workflows to perform chemical or biological reactions using microfluidic devices. | 02-23-2012 |
20120035080 | OPTICAL LENS SYSTEM AND METHOD FOR MICROFLUIDIC DEVICES - 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. | 02-09-2012 |
20120021523 | METHOD AND SYSTEM FOR CRYSTALLIZATION AND X-RAY DIFFRACTION SCREENING - An integrated fluidic circuit includes a substrate layer and a first structure coupled to the substrate layer and including a plurality of channels. The first structure is configured to provide for flow of one or more materials through the plurality of channels. The integrated fluidic circuit also includes a second structure coupled to the substrate layer. The second structure includes a plurality of control channels configured to receive an actuation pressure. The integrated fluidic circuit is characterized by a thickness of less than 1.5 mm. | 01-26-2012 |
20110265304 | INTEGRATED CHIP CARRIERS WITH THERMOCYCLER INTERFACES AND METHODS OF USING THE SAME - Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source. | 11-03-2011 |
20110206576 | MICROFLUIDIC MIXING AND REACTION SYSTEMS FOR HIGH EFFICIENCY SCREENING - 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. | 08-25-2011 |
20110189678 | Microfluidic Device and Methods of Using Same - A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses. | 08-04-2011 |
20110166044 | MICROFLUIDIC REACTION APPARATUS FOR HIGH THROUGHPUT SCREENING - An SBS-formatted microfluidic device where the geometry of the plate defines an array of interrogation areas, and where each interrogation area encompasses at least one reaction site. | 07-07-2011 |
20110143949 | ANALYSIS USING MICROFLUIDIC PARTITIONING DEVICES - 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. | 06-16-2011 |
20110129841 | ANALYSIS USING MICROFLUIDIC PARTITIONING DEVICES - 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. | 06-02-2011 |
20110126910 | Microfluidic devices and methods for binary mixing - The invention provides microfluidic devices and methods for carrying out sequential binary reactions. | 06-02-2011 |
20110053806 | INTEGRATED CARRIER FOR MICROFLUIDIC DEVICE - A carrier for holding a microfluidic device includes a substrate with a plurality of wells, each well defining a volume of between 0.1 μl and 100 μl; a plurality of channels within the substrate wherein each well is in fluid communication with at least one of the plurality of channels; and a receiving portion for receiving a microfluidic device and placing the microfluidic device in fluid communication with the plurality of wells. The carrier has a polymeric composition and/or an array of structural features that enhance its performance and compatibility with existing instrumentation. | 03-03-2011 |
20110053784 | Microfluidic Device and Methods of Using Same - A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses. | 03-03-2011 |
20110020918 | Microfluidic Assay Devices And Methods - 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. | 01-27-2011 |
20100320364 | OPTICAL LENS SYSTEM AND METHOD FOR MICROFLUIDIC DEVICES - 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. | 12-23-2010 |
20100311060 | Integrated Chip Carriers With Thermocycler Interfaces And Methods Of Using The Same - Methods and systems are provided for conducting a reaction at a selected temperature or range of temperatures over time. An array device is provided. The array device contains separate reaction chambers and is formed as an elastomeric block from multiple layers. At least one layer has at least one recess that recess has at least one deflectable membrane integral to the layer with the recess. The array device has a thermal transfer device proximal to at least one of the reaction chambers. The thermal transfer device is formed to contact a thermal control source. Reagents for carrying out a desired reaction are introduced into the array device. The array device is contacted with a thermal control device such that the thermal control device is in thermal communication with the thermal control source so that a temperature of the reaction in at least one of the reaction chamber is changed as a result of a change in temperature of the thermal control source. | 12-09-2010 |
20100285537 | SELECTIVE TAGGING OF SHORT NUCLEIC ACID FRAGMENTS AND SELECTIVE PROTECTION OF TARGET SEQUENCES FROM DEGRADATION - Methods are provided for selective tagging of short nucleic acids comprising a short target nucleotide sequence over longer nucleic acids comprising the same target nucleotide sequence. The methods can involve performing one or two cycles of amplification of a sample comprising long nucleic acids and short nucleic acids, each comprising the same target nucleotide sequence with at least two target-specific primers or primer pairs under suitable annealing conditions, wherein the primer pairs comprise: an inner primer or primer pair that can amplify the target nucleotide sequence on long and short nucleic acids (wherein each inner primer comprises a 5′ nucleotide tag; and an outer primer or primer pair that amplifies the target nucleotide sequence on long nucleic acids, but not on short nucleic acids); whereby the amplification after a second cycle produces at least one tagged target nucleotide sequence that comprises two nucleotide tags, one from each inner primer, with the target nucleotide sequence located between the nucleotide tags. | 11-11-2010 |
20100273219 | MULTI-PRIMER AMPLIFICATION METHOD FOR BARCODING OF TARGET NUCLEIC ACIDS - In certain embodiments, the present invention provides amplification methods in which nucleotide tag(s) and, optionally, a barcode nucleotide sequence are added to target nucleotide sequences. In other embodiments, the present invention provides a microfluidic device that includes a plurality of first input lines and a plurality of second input lines. The microfluidic device also includes a plurality of sets of first chambers and a plurality of sets of second chambers. Each set of first chambers is in fluid communication with one of the plurality of first input lines. Each set of second chambers is in fluid communication with one of the plurality of second input lines. The microfluidic device further includes a plurality of first pump elements in fluid communication with a first portion of the plurality of second input lines and a plurality of second pump elements in fluid communication with a second portion of the plurality of second input lines. | 10-28-2010 |
20100263757 | Microfabricated Fluidic Circuit Elements and Applications - A microfabricated fluidic unidirectional valve includes a microfabricated elastomer material having a flow through channel. The microfabricated fluidic unidirectional valve also includes an elastomer flap attached to the elastomer material in the flow through channel. The elastomer flap forms a seal in the flow through channel to prevent fluid from flowing in a first direction through the flow through channel and to allow fluid flow in a second direction through the flow through channel. | 10-21-2010 |
20100230613 | MICROFLUIDIC DEVICES AND METHODS - Embodiments of the present invention provide improved microfluidic devices and related apparatus, systems, and methods. Methods are provided for reducing mixing times during use of microfluidic devices. Microfluidic devices and related methods of manufacturing are provided with increased manufacturing yield rates. Improved apparatus and related systems are provided for supplying controlled pressure to microfluidic devices. Methods and related microfluidic devices are provided for reducing dehydration of microfluidic devices during use. Microfluidic devices and related methods are provided with improved sample to reagent mixture ratio control. Microfluidic devices and systems are provided with improved resistance to compression fixture pressure induced failures. Methods and systems for conducting temperature controlled reactions using microfluidic devices are provided that reduce condensation levels within the microfluidic device. Methods and systems are provided for improved fluorescent imaging of microfluidic devices. | 09-16-2010 |
20100203538 | DETERMINATION OF COPY NUMBER DIFFERENCES BY AMPLIFICATION - The present invention provides for determining relative copy number difference for one or more target nucleic acid sequences between a test sample and a reference sample or reference value derived therefrom. The methods facilitate the detection of copy number differences less than 1.5-fold. | 08-12-2010 |
20100184202 | Thermal Reaction Device and Method for Using the Same - 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. | 07-22-2010 |
20100183481 | Devices And Methods For Holding Microfluidic Devices - Carriers or holders for holding microfluidic devices are provided. Some of the carriers that are provided include a hydration control device and/or a source of controlled fluid pressure to facilitate use of the carrier in conducting various types of analyses. | 07-22-2010 |
20100178655 | SINGLE-CELL NUCLEIC ACID ANALYSIS - 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. | 07-15-2010 |
20100166608 | METHOD AND SYSTEM FOR MICROFLUIDIC DEVICE AND IMAGING THEREOF - A biological substrate, e.g., microfluidic chip. The substrate includes a rigid substrate material, which has a surface region capable of acting as a handle substrate. The substrate also has a deformable fluid layer coupled to the surface region. One or more well regions are formed in a first portion of the deformable fluid layer and are capable of holding a fluid therein. The one or more channel regions are formed in a second portion of the deformable fluid layer and are coupled to one or more of the well regions. An active region is formed in the deformable fluid layer. At least three fiducial markings are formed within the non-active region and disposed in a spatial manner associated with at least one of the well regions. A control layer is coupled to the fluid layer. | 07-01-2010 |
20100120077 | MICROFLUIDIC PARTICLE-ANALYSIS SYSTEMS - The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or detection of particles, such as cells and/or beads. The invention provides systems, including apparatus, methods, and kits, for the microfluidic manipulation and/or analysis of particles, such as cells, viruses, organelles, beads, and/or vesicles. The invention also provides microfluidic mechanisms for carrying out these manipulations and analyses. These mechanisms may enable controlled input, movement/positioning, retention/localization, treatment, measurement, release, and/or output of particles. Furthermore, these mechanisms may be combined in any suitable order and/or employed for any suitable number of times within a system. Accordingly, these combinations may allow particles to be sorted, cultured, mixed, treated, and/or assayed, among others, as single particles, mixed groups of particles, arrays of particles, heterogeneous particle sets, and/or homogeneous particle sets, among others, in series and/or in parallel. In addition, these combinations may enable microfluidic systems to be reused. Furthermore, these combinations may allow the response of particles to treatment to be measured on a shorter time scale than was previously possible. Therefore, systems of the invention may allow a broad range of cell and particle assays, such as drug screens, cell characterizations, research studies, and/or clinical analyses, among others, to be scaled down to microfluidic size. Such scaled-down assays may use less sample and reagent, may be less labor intensive, and/or may be more informative than comparable macrofluidic assays. | 05-13-2010 |
20100119154 | IMAGE PROCESSING METHOD AND SYSTEM FOR MICROFLUIDIC DEVICES - A method for processing an image of a microfluidic device. The method includes receiving a first image of a microfluidic device. The first image corresponds to a first state. Additionally, the method includes receiving a second image of the microfluidic device. The second image corresponds to a second state. Moreover, the method includes transforming the first image and the second image into a third coordinate space. Also, the method includes obtaining a third image based on at least information associated with the transformed first image and the transformed second image, and processing the third image to obtain information associated with the first state and the second state. | 05-13-2010 |
20090299545 | METHOD AND SYSTEM FOR MICROFLUIDIC DEVICE AND IMAGING THEREOF - A biological substrate, e.g., microfluidic chip. The substrate includes a rigid substrate material, which has a surface region capable of acting as a handle substrate. The substrate also has a deformable fluid layer coupled to the surface region. One or more well regions are formed in a first portion of the deformable fluid layer and are capable of holding a fluid therein. The one or more channel regions are formed in a second portion of the deformable fluid layer and are coupled to one or more of the well regions. An active region is formed in the deformable fluid layer. At least three fiducial markings are formed within the non-active region and disposed in a spatial manner associated with at least one of the well regions. A control layer is coupled to the fluid layer. | 12-03-2009 |
20090294703 | OPTICAL LENS SYSTEM AND METHOD FOR MICROFLUIDIC DEVICES - 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. | 12-03-2009 |
20090257920 | MULTILEVEL MICROFLUIDIC SYSTEMS AND METHODS - 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. | 10-15-2009 |
20090239308 | METHOD AND APPARATUS FOR DETERMINING COPY NUMBER VARIATION USING DIGITAL PCR - A method of estimating a concentration of DNA molecules in a biological sample includes storing a number of a plurality of reaction sites in a memory and distributing the biological sample among the plurality of reaction sites. The method also includes determining a number of the plurality of reaction sites characterized by a presence of one or more of the DNA molecules and computing a portion of the plurality of reaction sites characterized by the presence of the one or more of the DNA molecules. The method further includes estimating the concentration of the DNA molecules as a function of the portion of the plurality of reaction sites and computing a confidence interval for the estimated concentration of DNA molecules. | 09-24-2009 |
20090187009 | SCALE-UP METHODS AND SYSTEMS FOR PERFORMING THE SAME - The present invention provides methods of and systems for translating conditions from a small-volume experiment to a larger-volume experiment. | 07-23-2009 |
20090176230 | Microfluidic device and methods of using same - A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses. | 07-09-2009 |
20090147918 | METHOD AND SYSTEM FOR CRYSTALLIZATION AND X-RAY DIFFRACTION SCREENING - An integrated fluidic circuit includes a substrate layer and a first structure coupled to the substrate layer and including a plurality of channels. The first structure is configured to provide for flow of one or more materials through the plurality of channels. The integrated fluidic circuit also includes a second structure coupled to the substrate layer. The second structure includes a plurality of control channels configured to receive an actuation pressure. The integrated fluidic circuit is characterized by a thickness of less than 1.5 mm. | 06-11-2009 |
20090142236 | Microfluidic Devices and Methods of Using Same - An M.times.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. | 06-04-2009 |
20090069194 | COPY NUMBER VARIATION DETERMINATION, METHODS AND SYSTEMS - The present invention methods and systems for determining copy number variation of a target polynucleotide in a genome of a subject including amplification based techniques. Methods can include pre-amplification of the sample followed by distribution of sample and a plurality of reaction volumes, quantitative detection of a target polynucleotide and a reference polynucleotide, and analysis so as to determine the relative copy number of the target polynucleotide sequence in the genome of the subject. | 03-12-2009 |
20090061428 | Thermal Reaction Device and Method for Using the Same - An M times.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. | 03-05-2009 |
20080281090 | Microfluidic Chemical Reaction Circuits - New microfluidic devices, useful for carrying out chemical reactions, are provided. The devices are adapted for on-chip solvent exchange, chemical processes requiring multiple chemical reactions, and rapid concentration of reagents. | 11-13-2008 |
20080257437 | MICROFABRICATED FLUIDIC CIRCUIT ELEMENTS AND APPLICATIONS - Microfabricated fluidic devices of the present invention include switches that can be opened and closed to allow or block the flow of fluid through a channel in response to the pressure level in a gate of the switch. The microfabricated fluidic switches may be coupled together to perform logic functions and Boolean algebra, such as inverters, AND gates, NAND, gates, NOR gates, and OR gates. The logic gates may be coupled together to form flip-flops that latch signals. The present invention also includes microfabricated fluidic pressure multipliers that increase the pressure in a second chamber relative to a first chamber. Microfabricated fluidic devices of the present invention also include high or low pressure sources. A pressure source of the present includes a pump coupled to a reservoir through unidirectional valves. Microfabricated fluidic devices of the present invention may also include devices that perform analog functions such as switching regulator. | 10-23-2008 |
20080230387 | Microfluidic Devices and Methods of Using Same - A variety of elastomeric-based microfluidic devices and methods for using and manufacturing such devices are provided. Certain of the devices have arrays of reaction sites to facilitate high throughput analyses. Some devices also include reaction sites located at the end of blind channels at which reagents have been previously deposited during manufacture. The reagents become suspended once sample is introduced into the reaction site. The devices can be utilized with a variety of heating devices and thus can be used in a variety of analyses requiring temperature control, including thermocycling applications such as nucleic acid amplification reactions, genotyping and gene expression analyses. | 09-25-2008 |
20080223721 | High Efficiency and High Precision Microfluidic Devices and Methods - New high density microfluidic devices and methods provide precise metering of fluid volumes and efficient mixing of the metered volumes. A first solution is introduced into a segment of a flow channel in fluidic communication with a reaction chamber. A second solution is flowed through the segment so that the first solution is displaced into the reaction chamber, and a volume of the second solution enters the chamber. The chamber can then be isolated and reactions within the chamber can be initiated and/or detected. High throughput methods of genetic analysis can be carried out with greater accuracy than previously available. | 09-18-2008 |