Patent application number | Description | Published |
20080241866 | Systems and methods for enhancing fluorescent signals - Composition, systems, apparatus and methods of enhancing fluorescent signals in biochemical are described. Metal particle proximity to enzymes that produce fluorescent products provide enhanced fluorescence of the product and plasmon resonance of the metal particle. Multi-labeled nucleotides enhance signal production. Reflectance of illumination light and emitted fluorescence increase signal strength for a given illumination light. | 10-02-2008 |
20090176233 | Screening assays for polymerase enhancement - Methods of screening for and selecting for improved polymerases suitable for single molecule sequencing are provided. | 07-09-2009 |
20090208957 | Alternate labeling strategies for single molecule sequencing - Systems and methods of enhancing fluorescent labeling strategies as well as systems and methods of using non-fluorescent and/or non-optic labeling strategies, e.g., as with single molecule sequencing using ZMWs, are described. | 08-20-2009 |
20090233302 | LABELED REACTANTS AND THEIR USES - Labeled reactant compositions, and particularly labeled nucleic acid reaction compositions, that include structural components that maintain potentially damaging labeling components sufficiently distal from the reactant portion of the molecule such that damaging effects of the label group on other reaction components, such as enzymes, are reduced, minimized and/or eliminated. | 09-17-2009 |
20090286245 | TWO SLOW-STEP POLYMERASE ENZYME SYSTEMS AND METHODS - Compositions, kits, methods and systems for nucleotide sequencing comprising producing polymerase reactions that exhibit two kinetically observable steps within an observable phase of the polymerase reaction. Two slow step systems can be produced, for example, by selecting the appropriate polymerase enzyme, polymerase reaction conditions including cofactors, and polymerase reaction substrates including the primed template and nucleotides. | 11-19-2009 |
20100009872 | Single molecule loading methods and compositions - Methods, compositions and arrays for non-random loading of single analyte molecules into array structures are provided. | 01-14-2010 |
20100047802 | NUCLEIC ACID SYNTHESIS COMPOSITIONS AND METHODS AND SYSTEMS FOR USING SAME - The Application relates to compositions, kits, methods, and systems for nucleotide sequencing comprising producing polymerase reactions that comprise both catalytic and non-catalytic divalent metal ions. Effective ratios and amounts of catalytic and non-catalytic divalent metal ions are described. | 02-25-2010 |
20100065726 | SUBSTRATES AND OPTICAL SYSTEMS AND METHODS OF USE THEREOF - This invention provides substrates for use in various applications, including single-molecule analytical reactions. Methods for propagating optical energy within a substrate are provided. Devices comprising waveguide substrates and dielectric omnidirectional reflectors are provided. Waveguide substrates with improved uniformity of optical energy intensity across one or more waveguides and enhanced waveguide illumination efficiency within an analytic detection region of the arrays are provided. | 03-18-2010 |
20100075332 | Engineering polymerases and reaction conditions for modified incorporation properties - Provided are methods for enhanced sequencing of nucleic acid templates. Also provided are reaction conditions that increase branching fractions during polymerization reactions. Also provided are compositions comprising modified recombinant polymerases that exhibit branching fractions that are higher than the branching fractions of the polymerases from which they were derived. Provided are compositions comprising modified recombinant polymerases that exhibit delayed translocation relative to the polymerases from which they were derived. Also provided are compositions comprising modified recombinant polymerases that exhibit increased nucleotide or nucleotide analog residence time at an active site of the polymerase. Provided are methods for generating polymerases with the aforementioned phenotypes and methods of using such polymerases to sequence a DNA template or make a DNA. Also provided are methods and nucleic acid sequencing systems for determining which labeled nucleotide is incorporated at a site during a template-dependent polymerization reaction. | 03-25-2010 |
20100152424 | Modular Nucleotide Compositions and Uses Therefor - Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses. | 06-17-2010 |
20100221716 | Classification of Nucleic Acid Templates - Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid. | 09-02-2010 |
20100240045 | NUCLEOTIDE COMPOSITIONS AND USES THEREOF - The present invention relates to preparation of nucleotide compositions and uses thereof for conducting nucleic acid analyses. The compositions and methods embodied in the present invention are particularly useful for nucleic acid analyses that require high-resolution detection of labeled nucleotides or labeled nucleic acid targets. | 09-23-2010 |
20100311061 | REAL-TIME SEQUENCING METHODS AND SYSTEMS - The present invention is generally directed to compositions, methods, and systems for performing single-molecule, real-time analysis of a variety of different biological reactions. The ability to analyze such reactions provides an opportunity to study those reactions as well as to potentially identify factors and/or approaches for impacting such reactions, e.g., to either enhance or inhibit such reactions. In certain preferred embodiments, RNA templates are used in single-molecule real-time sequencing reactions. | 12-09-2010 |
20100317116 | SINGLE-MOLECULE REAL-TIME ANALYSIS OF PROTEIN SYNTHESIS - The present invention is generally directed to compositions, methods, and systems for performing single-molecule, real-time analysis of analytical reactions in which protein synthesis is occurring. The ability to analyze such reactions provides an opportunity to study those reactions as well as to potentially identify factors and/or approaches for impacting such reactions, e.g., to either enhance, inhibit, or otherwise affect such reactions including, but not limited to, affecting the reaction rate, processivity, fidelity, duration, and the like. | 12-16-2010 |
20100323912 | REAL-TIME ANALYTICAL METHODS AND SYSTEMS - The present invention is generally directed to compositions, methods, and systems for performing single-molecule, real-time analysis of a variety of different biological reactions, and for determining various characteristics of the different biological reactions. The ability to analyze such reactions provides an opportunity to study those reactions as well as to potentially identify factors and/or approaches for impacting such reactions, e.g., to stimulate, enhance, or inhibit such reactions. | 12-23-2010 |
20100331194 | NANOPORE SEQUENCING DEVICES AND METHODS - The invention relates to devices and methods for nanopore sequencing. The invention includes arrays of nanopores having incorporated electronic circuits, for example, in CMOS. In some cases, the arrays of nanopores comprise resistive openings for isolating the electronic signals for improved sequencing. Methods for controlling translocation of through the nanopore are disclosed. | 12-30-2010 |
20110183320 | CLASSIFICATION OF NUCLEIC ACID TEMPLATES - Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid. | 07-28-2011 |
20110244447 | COGNATE SAMPLING KINETICS - Provided are methods and compositions for measuring the transient binding of nucleotides and nucleotide analogs under conditions where the nucleotides or nucleotide analogs are unincorporable. The transient binding can be determined under single molecule observation conditions providing information about the kinetics of nucleotide analog sampling of the active site of the enzyme. The methods can be used for polymerase enzyme development, mechanistic understanding, and drug discovery. | 10-06-2011 |
20110311964 | LABELED REACTANTS AND THEIR USES - Labeled reactant compositions, and particularly labeled nucleic acid reaction compositions, that include structural components that maintain potentially damaging labeling components sufficiently distal from the reactant portion of the molecule such that damaging effects of the label group on other reaction components, such as enzymes, are reduced, minimized and/or eliminated. | 12-22-2011 |
20120085894 | SUBSTRATES AND OPTICAL SYSTEMS AND METHODS OF USE THEREOF - This invention provides substrates for use in various applications, including single-molecule analytical reactions. Methods for propagating optical energy within a substrate are provided. Devices comprising waveguide substrates and dielectric omnidirectional reflectors are provided. Waveguide substrates with improved uniformity of optical energy intensity across one or more waveguides and enhanced waveguide illumination efficiency within an analytic detection region of the arrays are provided. | 04-12-2012 |
20120302459 | Articles Having Localized Molecules Disposed Thereon and Methods of Producing Same - Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate. | 11-29-2012 |
20120322666 | ISOLATION OF POLYMERASE-NUCLEIC ACID COMPLEXES - Compositions, methods and systems are provided for the isolation of polymerase-nucleic acid complexes. Complexes can be separated from free enzyme by using hook molecules to target single stranded regions on the nucleic acid. Active complexes can be isolated from mixtures having both active and inactive complexes by initiating nucleic acid synthesis so as to open up a portion of a double stranded region rendering that region single stranded. Hook molecules are targeted to bind the sequences that are thus exposed. The hook molecules bound to active polymerase-nucleic acid complex are isolated, and the active polymerase-nucleic acid complexes released. | 12-20-2012 |
20130022968 | MODULAR NUCLEOTIDE COMPOSITIONS AND USES THEREFOR - Nucleic acid compositions, methods of making and using such compositions that comprise modular functional groups that can be configured to provide desired functionality to different nucleotide types, through a swappable and preferably non-covalent linkage component. Such compositions are useful in a variety of applications including nucleic acid analyses. | 01-24-2013 |
20130029853 | CLASSIFICATION OF NUCLEIC ACID TEMPLATES - Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid. | 01-31-2013 |
20130109577 | REAL-TIME REDOX SEQUENCING | 05-02-2013 |
20130122490 | PHOSPHOLINK NUCLEOTIDES FOR SEQUENCING APPLICATIONS - The present invention provides labeled phospholink nucleotides that can be used in place of naturally occurring nucleotide triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays, and others. | 05-16-2013 |
20130183663 | LABELED REACTANTS AND THEIR USES - Labeled reactant compositions, and particularly labeled nucleic acid reaction compositions, that include structural components that maintain potentially damaging labeling components sufficiently distal from the reactant portion of the molecule such that damaging effects of the label group on other reaction components, such as enzymes, are reduced, minimized and/or eliminated. | 07-18-2013 |
20130240356 | NANOPORES IN ZERO MODE WAVEGUIDES - Methods, devices, substrates, and systems are disclosed involving arrays of zero-mode waveguides having nanopores extending through the bases that form the bottoms of the zero-mode-waveguides. Electric fields across the nanopores are used to attach single biomolecules such as polymerase enzymes within each zero-mode-waveguide. Electric fields across the nanopores can also be used for the active loading of nucleic acid templates into enzymes attached within the zero mode waveguides. | 09-19-2013 |
20130303385 | METHODS AND COMPOSITIONS FOR SEQUENCING MODIFIED NUCLEIC ACIDS - Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid. | 11-14-2013 |
20130316916 | CLASSIFICATION OF NUCLEIC ACID TEMPLATES - Methods, compositions, and systems are provided for characterization of modified nucleic acids. In certain preferred embodiments, single molecule sequencing methods are provided for identification of modified nucleotides within nucleic acid sequences. Modifications detectable by the methods provided herein include chemically modified bases, enzymatically modified bases, abasic sites, non-natural bases, secondary structures, and agents bound to a template nucleic acid. | 11-28-2013 |
20130327644 | MODIFIED BASE DETECTION WITH NANOPORE SEQUENCING - Methods, compositions, and systems are provided for characterization of modified nucleic acids. Nanopore sequencing is performed using a processive enzyme to control the rate of translation of a single strand of a nucleic acid through a nanopore. The presence and identity of a modified base can be determined by monitoring the kinetics of translation through the pore even though the events that lead to the kinetic changes are separated in time and space from the translation of the modified base or it's compliment through the nanopore. The invention also comprises the use of hemi-genomic DNA in nanopore sequencing. | 12-12-2013 |
20130338013 | SUBSTRATES AND OPTICAL SYSTEMS AND METHODS OF USE THEREOF - This invention provides substrates for use in various applications, including single-molecule analytical reactions. Methods for propagating optical energy within a substrate are provided. Devices comprising waveguide substrates and dielectric omnidirectional reflectors are provided. Waveguide substrates with improved uniformity of optical energy intensity across one or more waveguides and enhanced waveguide illumination efficiency within an analytic detection region of the arrays are provided. | 12-19-2013 |
20140004511 | IDENTIFICATION OF 5-METHYL-C IN NUCLEIC ACID TEMPLATES | 01-02-2014 |
20140017680 | Real-Time Sequencing Methods and Systems - The present invention is generally directed to compositions, methods, and systems for performing single-molecule, real-time analysis of a variety of different biological reactions. The ability to analyze such reactions provides an opportunity to study those reactions as well as to potentially identify factors and/or approaches for impacting such reactions, e.g., to either enhance or inhibit such reactions. In certain preferred embodiments, RNA templates are used in single-molecule real-time sequencing reactions. | 01-16-2014 |
20140065607 | PHOSPHOLINK NUCLEOTIDES FOR SEQUENCING APPLICATIONS - The present invention provides labeled phospholink, nucleotides that can be used in place of naturally occurring nucleotide triphosphates or other analogs in template directed nucleic acid synthesis reactions and other nucleic acid reactions and various analyses based thereon, including DNA sequencing, single base identification, hybridization assays, and others. | 03-06-2014 |
20140134610 | COMPOSITIONS AND METHODS FOR SELECTION OF NUCLEIC ACIDS - Methods are provided for reducing the complexity of a population of nucleic acids prior to performing an analysis of the nucleic acids, e.g., sequence analysis. The methods result in a subset of the initial population enriched for a target region, which is typically located within one or more target fragments. The methods are particularly useful for analyzing populations having a high degree of complexity, e.g., chromosomal-derived DNA, whole genomic DNA, or mRNA populations. | 05-15-2014 |
20140155276 | ISOLATION OF POLYMERASE-NUCLEIC ACID COMPLEXES - Compositions, methods and systems are provided for the isolation of polymerase-nucleic acid complexes. Complexes can be separated from free enzyme by using hook molecules to target single stranded regions on the nucleic acid. Hook oligonucleotides are used to capture polymerase nucleic acid complexes where the nucleic acids comprise circular nucleic acids having a double stranded central region with hairpin regions on each end. Methods for loading such complexes onto substrates and for single molecule sequencing of such complexes are also provided. | 06-05-2014 |
20140179564 | COMPOSITIONS AND METHODS FOR SELECTION OF NUCLEIC ACIDS CONTAINING MODIFIED BASES - Methods are provided for reducing the complexity of a population of nucleic acids prior to performing an analysis of the nucleic acids, e.g., sequence analysis. The methods result in a subset of the initial population enriched for a desired property, or lacking nucleic acids having an undesired property. The methods are particularly useful for analyzing populations having a high degree of complexity, e.g., chromosomal-derived DNA, whole genomic DNA, or mRNA populations. In addition, such methods allow for analysis of pooled samples. | 06-26-2014 |
20140186825 | LABELED NUCLEOTIDE ANALOGS - Labeled reactant compositions, and particularly labeled nucleic acid reaction compositions that include structural components including double-stranded nucleic acids. In some embodiments, the structural components maintain potentially damaging labeling components sufficiently distal from the reactant portion of the molecule such that damaging effects of the label group on other reaction components, such as enzymes, are reduced, minimized and/or eliminated. | 07-03-2014 |
20140206550 | STEP-WISE NUCLEIC ACID SEQUENCING WITH CATALYTIC AND NON-CATALYTIC METALS - The application relates to methods, and systems for nucleotide sequencing comprising producing polymerase reactions that comprise both catalytic and non-catalytic divalent metal ions. Polymerase/template/primer complexes are immobilized on a substrate. The complexes are exposed to a solution comprising a non-catalytic metal and nucleotides labeled with a detectable label on a portion of the nucleotide that is released upon incorporation. The cognate nucleotide is sequestered in the active site of the polymerase, unable to proceed to incorporation. After observing the sequestered cognate nucleotide, the complex is exposed to a catalytic metal, resulting in the incorporation of the bound cognate nucleotide and consequent release of the label resulting in a single-base extended primer. | 07-24-2014 |
20140274732 | METHODS AND COMPOSITIONS FOR NUCLEIC ACID SEQUENCING USING ELECTRONIC SENSING ELEMENTS - The present invention is directed to methods, devices, compositions and systems for obtaining sequence data from nucleic acid templates by utilizing electronic sensing elements. | 09-18-2014 |
20140315756 | Articles Having Localized Molecules Disposed Thereon and Methods of Producing Same - Methods of producing substrates having selected active chemical regions by employing elements of the substrates in assisting the localization of active chemical groups in desired regions of the substrate. The methods may include optical, chemical and/or mechanical processes for the deposition, removal, activation and/or deactivation of chemical groups in selected regions of the substrate to provide selective active regions of the substrate. | 10-23-2014 |