| Pacific Biosciences of California, Inc. Patent applications |
| Patent application number | Title | Published |
|---|
| 20120034602 | Recombinant Polymerases For Improved Single Molecule Sequencing - Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions, and/or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include enhanced metal ion coordination, reduced exonuclease activity, reduced reaction rates at one or more steps of the polymerase kinetic cycle, decreased branching fraction, altered cofactor selectivity, increased yield, increased thermostability, increased accuracy, increased speed, increased readlength, and the like. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template. | 02-09-2012 |
| 20120028250 | MITIGATION OF PHOTODAMAGE IN ANALYTICAL REACTIONS - Compositions, devices, systems and methods for reducing and/or preventing photodamage of one or more reactants in illuminated analytical reactions by one or more of incorporating photodamage mitigating agents within the reaction mixture and/or interrogating different observation regions of the reaction mixture for a period that is less than a photodamage threshold period. | 02-02-2012 |
| 20120028248 | ENGINEERED FLUORESCENT DYE LABELED NUCLEOTIDE ANALOGS FOR DNA SEQUENCING - Engineered nucleotide compositions, having polymerase interacting components that improve the interactivity of the polymerase and the nucleotide, particularly for nucleic acid sequencing applications. Compositions include the interactive polymerases along with the nucleotide analogs. Kits, methods and systems are provided for analysis of nucleoc acid synthesis reactions. | 02-02-2012 |
| 20120021525 | OPTICS COLLECTION AND DETECTION SYSTEM AND METHOD - Optics collection and detection systems are provided for measuring optical signals from an array of optical sources over time. Methods of using the optics collection and detection systems are also described. | 01-26-2012 |
| 20120019828 | INTEGRATED ANALYTICAL SYSTEM AND METHOD - An analytical assembly within a unified device structure for integration into an analytical system. The analytical assembly is scalable and includes a plurality of analytical devices, each of which includes a reaction cell, an optical sensor, and at least one optical element positioned in optical communication with both the reaction cell and the sensor and which delivers optical signals from the cell to the sensor. Additional elements are optionally integrated into the analytical assembly. Methods for forming and operating the analytical system are also disclosed. | 01-26-2012 |
| 20120015825 | ANALYTICAL SYSTEMS AND METHODS WITH SOFTWARE MASK - Methods and systems for obtaining and processing optical signal data from analytical reactions, and in processing signal data from arrays of sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof are described. Defining and applying a 2-dimensional software mask allows for obtaining signal data from arrays with higher signal to noise than where the mask is not applied. | 01-19-2012 |
| 20120014837 | ILLUMINATION OF INTEGRATED ANALYTICAL SYSTEMS - An analytical device including an optically opaque cladding, a sequencing layer including a substrate disposed below the cladding, and a waveguide assembly for receiving optical illumination and introducing illumination into the device. The illumination may be received from a top, a side edge, and a bottom of the device. The waveguide assembly may include a nanoscale aperture disposed in the substrate and extending through the cladding. The aperture defines a reaction cell for receiving a set of reactants. In various aspects, the device includes a sensor element and the illumination pathway is through the sensor element. Waveguides and illumination devices, such as plasmonic illumination devices, are also disclosed. Methods for forming and operating the devices are also disclosed. | 01-19-2012 |
| 20120009567 | SEQUENCING REACTIONS WITH ALKALI METAL CATIONS FOR PULSE WIDTH CONTROL - Compositions, kits, methods and systems for single molecule nucleotide sequencing comprising producing polymerase reactions having monovalent cations that control the median pulse width for incorporated nucleotides are disclosed. The levels of alkali metals such as lithium, sodium, potassium, rubidium, and cesium in the polymerization are used to control pulse width while allowing other sequencing parameters to remain within a desirable range. | 01-12-2012 |
| 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 |
| 20110306096 | BIOTINYLATION TAG PEPTIDES - Biotinylation peptides are provided which can be fused with other peptides or proteins of interest using recombinant DNA techniques to provide efficient methods for biotinylating the resulting fusion proteins in vivo or in vitro. | 12-15-2011 |
| 20110291027 | METHODS AND SYSTEMS FOR SIMULTANEOUS REAL-TIME MONITORING OF OPTICAL SIGNALS FROM MULTIPLE SOURCES - Methods and systems for real-time monitoring of optical signals from arrays of signal sources, and particularly optical signal sources that have spectrally different signal components. Systems include signal source arrays in optical communication with optical trains that direct excitation radiation to and emitted signals from such arrays and image the signals onto detector arrays, from which such signals may be subjected to additional processing. | 12-01-2011 |
| 20110287981 | METHODS AND SYSTEMS FOR SIMULTANEOUS REAL-TIME MONITORING OF OPTICAL SIGNALS FROM MULTIPLE SOURCES - Methods and systems for real-time monitoring of optical signals from arrays of signal sources, and particularly optical signal sources that have spectrally different signal components. Systems include signal source arrays in optical communication with optical trains that direct excitation radiation to and emitted signals from such arrays and image the signals onto detector arrays, from which such signals may be subjected to additional processing. | 11-24-2011 |
| 20110281768 | DIAGNOSTIC SEQUENCING WITH SMALL NUCLEIC ACID CIRCLES - Methods, substrates, and systems for diagnostic sequencing are provided. Small circles of nucleic acids from about 10 bases to about 200 bases can be sequenced, for example using template dependent sequencing by synthesis. The use of small circles of nucleic acids allows for repeated sequencing of the same portions of the nucleic acid, providing for higher accuracy sequence determinations. | 11-17-2011 |
| 20110278475 | MULTIPLEX ILLUMINATION SYSTEM AND METHOD - Systems and methods for analyzing highly multiplexed sample arrays using highly multiplexed, high density optical systems to illuminate high density sample arrays and/or provide detection from such high density arrays. Systems and methods comprise substrates having an array of discrete signal sources having a pitch P | 11-17-2011 |
| 20110257889 | SEQUENCE ASSEMBLY AND CONSENSUS SEQUENCE DETERMINATION - Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof. In particularly preferred embodiments, nucleic acid sequences generated by such methods are subjected to de novo assembly and/or consensus sequence determination. | 10-20-2011 |
| 20110257040 | NANOSCALE APERTURES HAVING ISLANDS OF FUNCTIONALITY - Methods, compositions and arrays for non-random loading of single analyte molecules into array structures are provided. Arrays of confined regions are produced wherein each confined region comprises a single island within the confined region. The island can be selectively functionalized with a coupling agent to couple a single molecule of interest within the confined region. | 10-20-2011 |
| 20110256631 | METHODS AND PROCESSES FOR CALLING BASES IN SEQUENCE BY INCORPORATION METHODS - Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof. | 10-20-2011 |
| 20110256618 | Nucleic acid sequencing methods and systems - Sequencing methods that use an exonuclease that comprises template dependent nucleobase binding activity are provided. Related compositions and sequencing systems are also provided. | 10-20-2011 |
| 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 |
| 20110222179 | MICROMIRROR ARRAYS HAVING SELF ALIGNED FEATURES - Methods, arrays, and systems for the optical analysis of multiple chemical, biological, or biochemical reactions are provided. The invention includes methods for producing arrays of micromirrors on transparent substrates, each micromirror comprising a nanostructure or optical confinement on its top. The arrays are produced by a process in which lateral dimensions of both the nanostructures and micromirrors are defined in a single step, allowing for control of the relative placement of the features on the substrate, minimizing the process-related defects, allowing for improved optical performance and consistency. In some aspects, the invention provides methods of selectively etching large features on a substrate while not concurrently etching small features. In some aspects, the invention provides methods of etching large features on a substrate using hard mask materials. | 09-15-2011 |
| 20110217698 | METHOD TO IMPROVE SINGLE MOLECULE ANALYSES - The quality of information from single molecule analyses is improved by employing a method in which a single molecule reaction carried out within an optical confinement is monitored, the single molecule reaction is halted, and data from the optical confinement is obtained while the reaction is not occurring. Characteristic optical behavior observed while the reaction is halted is used to improve the quality of information obtained during the single molecule reaction, for example, by correcting the reaction data, excluding the reaction data, or providing a confidence level to the reaction data. | 09-08-2011 |
| 20110212437 | SINGLE MOLECULE SEQUENCING WITH TWO DISTINCT CHEMISTRY STEPS - Methods, Compositions, and Systems are provided for nucleic acid sequencing where the sequential incorporation of nucleotides uses two distinct chemical steps. A plurality of nucleotide analogs, each having a labeled leaving group at its 3′ hydroxyl can be sequentially added to a growing strand in the presence of a selective cleaving activity that cleaves the 3′ hydroxyl leaving group preferentially after it has been incorporated. The selective cleaving agent can comprise an exonuclease activity, and the exonuclease activity can be a polymerase-associated exonuclease activity. Nucleotide analogs having labels on both a cleavable polyphosphate portion and on a 3′ hydroxyl leaving group can provide signals characteristic of nucleotide analog incorporation. Systems having illumination optics, collection optics, and substrates observe signals from the labels as they are being incorporated into a growing nucleic acid strand, allowing for the sequencing of template nucleic acids. | 09-01-2011 |
| 20110212436 | MOLECULAR REDUNDANT SEQUENCING - Methods, systems and compositions where a target nucleic acid includes a registration sequence disposed therein for identification of the number or relative position of determined sequence from the template sequence. Particularly preferred aspects include a registration sequence in a circular template nucleic acid sequence which is, in turn, used in sequence by incorporation processes that rely upon template dependent, polymerase mediated primer extension in the identification of the sequence of the template. | 09-01-2011 |
| 20110210094 | METHODS FOR PRODUCING ZMWS WITH ISLANDS OF FUNCTIONALITY - The application relates to methods for producing islands of functionality within nanoscale apertures. Islands of functionality can be produced by growing an aperture constriction layer from the walls, functionalizing the exposed base of the aperture, then removing the aperture constriction layer. The aperture constriction layer can be produced, for example, by anodically growing an oxide layer onto a cladding through which the aperture extends. The islands of functionality can be used to bind a single molecule of interest, such as an enzyme within the nanoscale aperture. | 09-01-2011 |
| 20110195406 | INTERMITTENT DETECTION DURING ANALYTICAL REACTIONS - Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period. | 08-11-2011 |
| 20110189659 | Generation of modified polymerases for improved accuracy in single molecule sequencing - Provided are compositions comprising recombinant DNA polymerases that include amino acid substitutions, insertions, deletions and/or heterologous or exogenous features that confer modified properties upon the polymerase for enhanced single molecule sequencing. Such properties can include reduced reaction rates at one or more steps of the polymerase kinetic cycle, increased closed polymerase/DNA complex stability, enhanced metal ion coordination, reduced exonuclease activity, decreased branching fractions, and the like. Polymerases that exhibit branching fractions that are less than the branching fractions of the polymerases from which they were derived, or branching fractions that are less than about 25% for a phosphate-labeled nucleotide analog, are also provided. Also provided are nucleic acids which encode the polymerases with the aforementioned phenotypes, as well as methods of using such polymerases to make a DNA or to sequence a DNA template. | 08-04-2011 |
| 20110183409 | SEALED CHIP PACKAGE - The invention provides environmental packages, instruments, and methods for sealing, protecting, and providing analysis chips for processing and analysis. The analysis chips are bonded directly or indirectly to chip carriers which are held within the chambers of an environmental packaging strip. The chambers are sealed with a sealing film such that the chip carriers can be extracted using a piercing tool and an extraction tool. | 07-28-2011 |
| 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 |
| 20110177496 | FIELD-SWITCH SEQUENCING - The present invention provides novel compositions, methods and apparatus for DNA sequencing that can be performed, e.g., in a two-electrode chamber. The present invention also provides a method for sequencing a nucleic acid comprising immobilizing a plurality of complexes comprising a target nucleic acid, a primer nucleic acid, and a polymerase onto a surface, contacting the surface with a plurality of charged particles comprising a nucleotide phosphate by applying an electric field, reversing the electric field to transport unbound charged particles away from the surface, and detecting the incorporation of a nucleotide phosphate into a single molecule of the primer nucleic acid. | 07-21-2011 |
| 20110160077 | SEQUENCING METHODS USING ENZYME CONFORMATION - Systems and methods are provided for single-molecule sequencing of template nucleic acids in which the signal from a label attached to a polymerase enzyme is used to monitor conformational changes in the polymerase which occur while labeled nucleotides or nucleotide analogs are added to a growing nucleic acid chain which is complementary to the template nucleic acid. The signal indicative of the conformational state of the enzyme is used to determine with higher confidence when true nucleotide or nucleotide analog incorporation events occur, allowing for the improved quality of base calls and sequence determination. | 06-30-2011 |
| 20110117637 | ZERO-MODE WAVEGUIDES WITH NON-REFLECTING WALLS - The application relates to improved optical containment structures, methods of manufacture and use, and systems for employing same. The optical containment structures generally comprise zero-mode waveguide structures having non-reflective walls. The non-reflective walls allow the preparation of optical containment regions in which the optical containment dimensions can be decoupled from the solution containment dimensions. The application also relates to methods for producing islands of functionality within nanoscale apertures. | 05-19-2011 |
| 20110082051 | SUBSTRATES, SYSTEMS AND METHODS FOR ANALYZING MATERIALS - Substrates, systems and methods for analyzing materials that include waveguide arrays disposed upon or within the substrate such that evanescent fields emanating from the waveguides illuminate materials disposed upon or proximal to the surface of the substrate, permitting analysis of such materials. The substrates, systems and methods are used in a variety of analytical operations, including, inter alia, nucleic acid analysis, including hybridization and sequencing analyses, cellular analyses and other molecular analyses. | 04-07-2011 |
| 20110059450 | LABELED NUCLEOTIDE ANALOGS AND USES THEREFOR - Labeled nucleotide analogs used in place of naturally occurring nucleoside 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. | 03-10-2011 |
| 20110039266 | FLOWCELL SYSTEMS FOR SINGLE MOLECULE DETECTION - The present invention provides compounds, methods and systems for sequencing nucleic acid using single molecule detection. Using labeled NPs that exhibit charge-switching behavior, single-molecule DNA sequencing in a microchannel sorting system is realized. In operation, sequencing products are detected enabling real-time sequencing as successive detectable moieties flow through a detection channel. By electrically sorting charged molecules, the cleaved product molecules are detected in isolation without interference from unincorporated NPs and without illuminating the polymerase-DNA complex. | 02-17-2011 |
| 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 |
| 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 |
| 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 |
| 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 |
| 20100261247 | Active surface coupled polymerases - Active surface coupled polymerases, surfaces that include such polymerases, and methods of making and using surface-attached polymerases are provided. | 10-14-2010 |
| 20100260465 | Protein engineering strategies to optimize activity of surface attached proteins - Isolated and/or recombinant enzymes that include surface binding domains, surfaces with active enzymes bound to them and methods of coupling enzymes to surfaces are provided. Enzymes can include large and/or multiple surface coupling domains for surface coupling. | 10-14-2010 |
| 20100255488 | FRET-LABELED COMPOUNDS AND USES THEREFOR - FRET-labeled compounds are provided for use in analytical reactions. In certain embodiments, FRET-labeled nucleotide analogs are used in place of naturally occurring nucleoside triphosphates or other analogs in analytical reactions comprising nucleic acids, for example, template-directed nucleic acid synthesis, DNA sequencing, RNA sequencing, single-base identification, hybridization, binding assays, and other analytical reactions. | 10-07-2010 |
| 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 |
| 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 |
| 20100169026 | Algorithms for sequence determination - The present invention is generally directed to powerful and flexible methods and systems for consensus sequence determination from replicate biomolecule sequence data. It is an object of the present invention to improve the accuracy of consensus biomolecule sequence determination from replicate sequence data by providing methods for assimilating replicate sequence into a final consensus sequence more accurately than any one-pass sequence analysis system. | 07-01-2010 |
| 20100167299 | 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. | 07-01-2010 |
| 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 |
| 20100136592 | Photo-Induced Damage Mitigating Agents and Preparation and Methods of Use Thereof - Compositions, devices, systems and methods for reducing and/or preventing photo-induced damage of one or more reactants in an illuminated analytical reaction by addition of one or more photo-induced damage mitigating agents to the reaction mixture and allowing the reaction to proceed for a period that is less than a photo-induced damage threshold period. | 06-03-2010 |
| 20100112645 | Generation of modified polymerases for improved accuracy in single molecule sequencing - Provided are compositions comprising modified recombinant polymerases that exhibit branching fractions that are less than the branching fractions of the polymerases from which they were derived, or branching fractions that are less than about 25% for a phosphate-labeled nucleotide analog. Also provided are compositions comprising modified recombinant polymerases that exhibit closed polymerase/DNA complexes with increased stability relative to the parental polymerases. Also provided are compositions comprising modified recombinant polymerases that exhibit decreased rate constants relative to the parental polymerases. Provided are methods for generating polymerases with the aforementioned phenotypes. Provided are methods of using such polymerases to make a DNA or to sequence a DNA template. | 05-06-2010 |
| 20100099100 | 'ULTRA-HIGH MULTIPLEX ANALYTICAL SYSTEMS AND METHODS" - Apparatus, systems and methods for use in analyzing discrete reactions at ultra high multiplex with reduced optical noise, and increased system flexibility. Apparatus include substrates having integrated optical components that increase multiplex capability by one or more of increasing density of reaction regions, improving transmission of light to or collection of light from discrete reactions regions. Integrated optical components include reflective optical elements which re-direct illumination light and light emitted from the discrete regions to more efficiently collect emitted light. Particularly preferred applications include single molecule reaction analysis, such as polymerase mediated template dependent nucleic acid synthesis and sequence determination. | 04-22-2010 |
| 20100093555 | Enzymes resistant to photodamage - Provided are compositions comprising modified DNA polymerases that exhibit improved photostability compared to the parental polymerases from which they were derived. Provided are methods for generating enzymes, such as DNA polymerases, with the aforementioned phenotype. Provided are methods of using polymerases with increased resistance to photodamage to make a DNA or to sequence a DNA template. | 04-15-2010 |
| 20100092960 | Helicase-assisted sequencing with molecular beacons - Provided are compositions that include an at least partially single-stranded nucleic acid, at least one first molecular beacon, and an enzyme comprising a helicase activity, which enzyme is capable of removing the first molecular beacon from the single-stranded nucleic acid wherein the first molecular beacon is hybridized to a first complementary subsequence of the nucleic acid. Also provided are methods of determining the sequence of a template nucleic acid that include removing molecular beacons that are hybridized to the template from the template in a sequential manner using an enzyme that exhibits a helicase activity, detecting a sequence of fluorescent signals that is produced by the removal of a molecular beacons, and converting the sequence of fluorescent signals into nucleotide sequence information. Sequencing systems in which compositions and methods of the invention can be used are also provided. | 04-15-2010 |
| 20100081143 | Preparations, Compositions, and Methods for Nucleic Acid Sequencing - Preparations, compositions and methods of sequencing nucleic acids are provided. The preparations, methods and compositions employ multiple priming sites on a target nucleic acid and typically utilize single molecule sequencing processes to identify sequence portions of the target which are then assembled to obtain the sequence of the target. | 04-01-2010 |
| 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 |
| 20100075328 | IMMOBILIZED NUCLEIC ACID COMPLEXES FOR SEQUENCE ANALYSIS - Provided are methods for sequencing a nucleic acid that include fixing a template to a surface through a template localizing moiety and sequencing the nucleic acid with a sequencing enzyme, e.g. a polymerase or exonuclease. The sequencing enzyme can optionally be exchanged with a second sequencing enzyme, which continues the sequencing of the nucleic acid. The template localizing moiety can optionally anneal with the nucleic acid and/or associate with the sequencing enzyme. Also provided are compositions comprising a nucleic acid fixed to a surface via a template localizing moiety, and a first sequencing enzyme, which can sequence the nucleic acid and optionally exchange with a second sequencing enzyme present in the composition. Compositions in which a template localizing moiety is immobilized on a surface are provided. Compositions for sequencing reactions are provided. Also provided are sequencing systems comprising reaction regions in which or near which template localizing moieties are immobilized. | 03-25-2010 |
| 20100075327 | INTERMITTENT DETECTION DURING ANALYTICAL REACTIONS - Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period. | 03-25-2010 |
| 20100075309 | INTERMITTENT DETECTION DURING ANALYTICAL REACTIONS - Methods, devices, and systems for performing intermittent detection during analytical reactions are provided. Such methods facilitate collection of reaction data from disparate reaction times. Further, such methods are useful for reducing photo-induced damage of one or more reactants in an illuminated analytical reaction at a given reaction time. In preferred embodiments, the reaction mixture is subjected to at least one illuminated and non-illuminated period and allowed to proceed such that the time in which the reaction mixture is illuminated is less than a photo-induced damage threshold period. | 03-25-2010 |
| 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 |
| 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 |
| 20100035254 | COMPOSITION AND METHOD FOR NUCLEIC ACID SEQUENCING - The present invention provides compositions and methods for detecting incorporation of a labeled nucleotide triphosphate onto the growing end of a primer nucleic acid molecule. The method is used, for example, to genotype and sequence a nucleic acid. In a preferred embodiment, the method described herein detects individual NTP molecules. | 02-11-2010 |
| 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 |
| 20100003765 | METHODS AND SYSTEMS FOR MITIGATING OXYGEN ENHANCED DAMAGE IN REAL-TIME ANALYTICAL OPERATIONS - Methods and systems for performing analytical reactions under reduced or non-oxygen conditions, where such reactions are potentially subject to damaging effects of oxygen, including particularly fluorescent based detection methods where fluorescent species may be prone to generation of reactive oxygen species. | 01-07-2010 |
| 20090325260 | CIS REACTIVE OXYGEN QUENCHERS INTEGRATED INTO LINKERS - The present invention provides methods and compositions for performing illuminated reactions, particularly sequencing reactions, while mitigating and/or preventing photodamage to reactants that can result from prolonged illumination. In particular, the invention provides methods and compositions for incorporating photoprotective agents into conjugates comprising reporter molecules and nucleoside polyphosphates. | 12-31-2009 |
| 20090325166 | SUBSTRATES FOR PERFORMING ANALYTICAL REACTIONS - Substrates, including zero mode waveguide substrates that have been fabricated to provide additional functional elements and/or components including increased volumes for positioning of active surfaces and/or components for the mitigation of negative electrochemical properties of the underlying substrates. | 12-31-2009 |
| 20090298075 | COMPOSITIONS AND METHODS FOR NUCLEIC ACID SEQUENCING - Compositions and methods for nucleic acid sequencing include template constructs that comprise double stranded portions in a partially or completely contiguous constructs, to provide for redundant sequence determination through one or both of sequencing sense and antisense strands, and iteratively sequencing the entire construct multiple times. Additional sequence components are also optionally included within such template constructs. Methods are also provided for the use and preparation of these constructs as well as sequencing compositions for their application. | 12-03-2009 |
| 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 |
| 20090280538 | Methods and compositions for nucleic acid sample preparation - Provided are methods and compositions for the production of linear single-stranded nucleic acids, which can be used as templates in high-throughput sequencing systems. Also provided are methods and compositions for the production of closed single-stranded nucleic acid loops, which can be used as templates in high-throughput sequencing systems. | 11-12-2009 |
| 20090247426 | FOCUSED LIBRARY GENERATION - The present invention relates generally to in vitro methods for generating mutant nucleic acid and polypeptide libraries. In particular, the present invention provides methods and compositions for mutagenesis and recombination of polynucleotide sequences in amplification methods that utilize primer oligonucleotides, and for expressing the resultant nucleic acid libraries to generate polypeptide libraries. | 10-01-2009 |
| 20090246791 | ENGINEERED FLUORESCENT DYE LABELED NUCLEOTIDE ANALOGS FOR DNA SEQUENCING - Engineered nucleotide compositions, having polymerase interacting components that improve the interactivity of the polymerase and the nucleotide, particularly for nucleic acid sequencing applications. Compositions include the interactive polymerases along with the nucleotide analogs. Kits, methods and systems are provided for analysis of nucleic acid synthesis reactions. | 10-01-2009 |
| 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 |
| 20090208961 | COMPOSITIONS AND METHODS FOR USE IN ANALYTICAL REACTIONS - Compositions, methods, substrates and systems for use in analysis of single molecule reactions and particularly single molecule nucleic acid sequence analysis. Compositions that include non-reactive, distinguishable or undetectable competitive substrates for the reaction system of interest are provided, as well as their use in systems and substrates for such applications, such compounds typically preferably polyphosphate chains or analogous structures. | 08-20-2009 |
| 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 |
| 20090181396 | METHODS AND SYSTEMS FOR ANALYSIS OF FLUORESCENT REACTIONS WITH MODULATED EXCITATION - Methods, systems and their components for monitoring fluorescent signals and particularly transient fluorescent signals from reaction mixtures of interest, which methods and systems employ modulated excitation light sources to reduce impacts of excessive illumination on the reaction components or the data obtained therefrom. | 07-16-2009 |
| 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 |
| 20090118129 | VIRTUAL READS FOR READLENGTH ENHANCEMENT - Methods arrays and systems that facilitate contig assembly during nucleic acid sequencing are provided. Geographical locations of analyte molecules on an array are correlated with subsequence relationships within larger nucleic acids. | 05-07-2009 |
| 20090105094 | Error-free amplification of DNA for clonal sequencing - Methods of preparing nucleic acid templates and providing the nucleic acid templates to low copy number reaction volumes are provided. Related compositions of nucleic acid templates are also provided. | 04-23-2009 |
| 20090061430 | Reactive surfaces, substrates and methods of producing and using same - Reactive surfaces, substrates and methods of producing and using such substrates and surfaces are provided. The substrates and surfaces provide low density reactive groups preferably on an otherwise non-reactive surface for use in different applications including single molecule analyses. | 03-05-2009 |
| 20090061429 | Reactive surfaces, substrates and methods of producing and using same - Reactive surfaces, substrates and methods of producing and using such substrates and surfaces are provided. The substrates and surfaces provide low density reactive groups preferably on an otherwise non-reactive surface for use in different applications including single molecule analyses. | 03-05-2009 |
| 20090029385 | Molecular redundant sequencing - Methods, systems and compositions where a target nucleic acid includes a registration sequence disposed therein for identification of the number or relative position of determined sequence from the template sequence. Particularly preferred aspects include a registration sequence in a circular template nucleic acid sequence which is, in turn, used in sequence by incorporation processes that rely upon template dependent, polymerase mediated primer extension in the identification of the sequence of the template. | 01-29-2009 |
| 20090024331 | METHODS AND PROCESSES FOR CALLING BASES IN SEQUENCE BY INCORPORATION METHODS - Computer implemented methods, and systems performing such methods for processing signal data from analytical operations and systems, and particularly in processing signal data from sequence-by-incorporation processes to identify nucleotide sequences of template nucleic acids and larger nucleic acid molecules, e.g., genomes or fragments thereof. | 01-22-2009 |
| 20090018324 | LABELED NUCLEOTIDE ANALOGS AND USES THEREFOR - Labeled nucleotide analogs used in place of naturally occurring nucleoside 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. | 01-15-2009 |
| 20080283772 | Methods and systems for analyzing fluorescent materials with reduced authofluorescence - Mitigative and remedial approaches to reduction of autofluorescence background noise are applied in analytical systems that rely upon sensitive measurement of fluorescent signals from arrays of fluorescent signal sources. Such systems are for particular use in fluorescence based sequencing by incorporation systems that rely upon small numbers or individual fluorescent molecules in detecting incorporation of nucleotides in primer extension reactions | 11-20-2008 |
| 20080277595 | Highly multiplexed confocal detection systems and methods of using same - Systems and methods for analyzing highly multiplexed sample arrays using highly multiplexed, high density optical systems to illuminate high density sample arrays and/or provide detection and preferably confocal detection off signals emanating from such high density arrays. Systems and methods are applied in a variety of different analytical operations, including analysis of biological and biochemical reactions, including nucleic acid synthesis and derivation of sequence information from such synthesis. | 11-13-2008 |
| 20080241892 | Modified surfaces for immobilization of active molecules - Modified surfaces, substrates, and methods of producing and using such substrates and surfaces are provided. The substrates and surfaces provide either non-reactive surfaces or low density reactive groups, preferably on an otherwise non-reactive surface, for use in different applications including single molecule analyses. | 10-02-2008 |
| 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 |
| 20080234143 | Mechanical methods for producing substrates having selectively immobilized molecules - Methods, systems and substrates for providing molecules of interest in selected regions of substrates for use in analytical operations. Methods employ mechanical methods of applying force for the removal of molecules of interest from other than the desired locations on a substrate. | 09-25-2008 |
| 20080226307 | Methods and systems for monitoring multiple optical signals from a single source - Methods and systems for monitoring a plurality of different optical signals from a single source of such signals, where each such different optical signal is spatially separated from other such signals and directed to different detectors or locations upon a single detector, which direction is generally accomplished through the use of a small number of optical components and/or manipulations. | 09-18-2008 |
| 20080220537 | Substrates and methods for selective immobilization of active molecules - Substrates and methods for providing increased selectivity in the immobilization of active molecules of interest in desired locations of substrates for use in analytical operations and particularly optical analytical operations. | 09-11-2008 |
| 20080212960 | Methods and systems for simultaneous real-time monitoring of optical signals from multiple sources - Methods and systems for real-time monitoring of optical signals from arrays of signal sources, and particularly optical signal sources that have spectrally different signal components. Systems include signal source arrays in optical communication with optical trains that direct excitation radiation to and emitted signals from such arrays and image the signals onto detector arrays, from which such signals may be subjected to additional processing. | 09-04-2008 |
| 20080199932 | Active surface coupled polymerases - Active surface coupled polymerases, surfaces that include such polymerases, and methods of making and using surface-attached polymerases are provided. | 08-21-2008 |
| 20080199874 | CONTROLLABLE STRAND SCISSION OF MINI CIRCLE DNA - The invention provides methods and compositions for the controlled termination of polymerase mediated primer extension reactions. The methods and compositions of the invention are broadly useful, and in a preferred aspect can be used in identifying sequence elements of template nucleic acids. Control of termination not only provides temporal control over termination, but, when used in conjunction with optically confined reaction regions, also spatially controls such termination. | 08-21-2008 |
