Pacific Biosciences of California, Inc. Patent applications |
Patent application number | Title | Published |
20160069806 | 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. | 03-10-2016 |
20150376694 | 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. | 12-31-2015 |
20150344950 | Functionalized Cyanine Dyes (PEG) - The invention provides a novel class of cyanine dyes that are functionalized with a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates. | 12-03-2015 |
20150330987 | LABELED NUCLEOTIDE ANALOGS HAVING PROTEIN SHIELDS - Compositions, methods, and systems are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The nucleotide analogs have two avidin proteins connected by a central dye component, and each avidin protein is further connected to a nucleotide component. The protein can prevent the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties. | 11-19-2015 |
20150197794 | Phospholinked Dye Analogs with an Amino Acid Linker - In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an amino acid or peptide linker. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an amino acid or peptide linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including multiple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention. | 07-16-2015 |
20150159196 | 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. | 06-11-2015 |
20150125854 | METHODS AND COMPOSITIONS FOR PERFORMING ANALYTICAL OPERATIONS - Methods for performing analytical reactions and compositions for use in such methods, where the methods have reduced signal levels deriving from non-specific adsorption of detected reagents to other components of the analytical method, e.g., other reagents, solid phase components, vessels, etc. | 05-07-2015 |
20150105273 | 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. | 04-16-2015 |
20150072894 | CYANINE DYES - The invention provides a novel class of cyanine dyes that are functionalized with sulfonic acid groups and a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates. | 03-12-2015 |
20150065353 | REAL-TIME ELECTRONIC SEQUENCING - Real time electronic sequencing methods, devices, and systems are described. Arrays of nanoscale electronic elements comprising capacitive devices with one or two electrodes, or arrays of nanoFET devices are used to provide sequence information about a template nucleic acid in a polymerase-template complex bound proximate to the nanoscale electronic elements or to the substrate proximate to the nanoscale electronic element. A sequencing reaction mixture comprising nucleotide analogs having impedance labels, capacitive labels, or conductivity labels is introduced to the array of nanoscale electronic elements comprising capacitive devices or nanoFETs under conditions of polymerase mediated nucleic acid synthesis. The time sequence of incorporation of nucleotide analogs is determined by identifying the types of labels of the nucleotide analogs that are incorporated into the growing strand using measured impedance, conductivity, or capacitance. | 03-05-2015 |
20150024968 | ANALYTICAL DEVICES HAVING COMPACT LENS TRAIN ARRAYS - Apparatus, systems and methods for use in analyzing discrete reactions are provided. The analytical devices of the invention use an array of nanoscale regions (a chip) that has discrete patches of nanoscale regions. The chip mates with a collection device comprising an array of compact lens trains (CLTs) where each of the CLTs corresponds to a single patch of nanoscale regions. Each CLT collects the emitted light from a patch on the chip, collimates the light, performs color separation on the collimated emitted light, and focuses the separated light onto a portion of pixels on the detector below the CLT. Such systems are useful for monitoring many analytical reactions at one time including single molecule sequencing reactions. | 01-22-2015 |
20150018252 | METHODS FOR PROVIDING AND DELIVERING AN ENVIRONMENTALLY SEALED CHIP - The invention provides methods relating methods for environmentally 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 are extracted using a piercing tool and an extraction tool. | 01-15-2015 |
20150011433 | BIS-BIOTINYLATION TAGS - Multi-biotinylated reactants are provided which can be used in divalent complexes for various applications such as colocalization, labeling, immobilization, and purification. Methods for constructing, purifying, and using the bis-biotinylated reactants are also provided. In certain embodiments, two bis-biotinylated reactants are bound to a single streptavidin tetramer to provide a complex having a 1:1 stoichiometry with respect to the bis-biotinylated reactants. | 01-08-2015 |
20140364324 | NANOPORE SEQUENCING USING CHARGE BLOCKADE LABELS - The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid. | 12-11-2014 |
20140309144 | NANOPORE SEQUENCING USING CHARGE BLOCKADE LABELS - The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid. | 10-16-2014 |
20140303016 | 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. | 10-09-2014 |
20140295498 | Targeted Rolling Circle Amplification - Methods for amplifying a desired target region of a nucleic acid through rolling circle amplification with a strand-displacing polymerase are provided. Concatameric hairpin products are resolved with endonuclease digestion, and the resulting amplified product hairpins or fragments can be circularized and employed as templates in a subsequent round of amplification. The methods are effective for targeted amplification of even highly repetitive sequences. Compositions, kits, and systems related to or useful in the methods are also described. | 10-02-2014 |
20140287964 | INTEGRATED ILLUMINATION OF OPTICAL ANALYTICAL DEVICES - Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include integrated illumination elements and optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput. | 09-25-2014 |
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 |
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 |
20140199016 | Illumination of Optical Analytical Devices - Optical analytical devices and their methods of use are provided. The devices are useful in the analysis of highly multiplexed optical reactions in large numbers at high densities, including biochemical reactions, such as nucleic acid sequencing reactions. The devices include optical waveguides for illumination of the optical reactions. The devices further provide for the efficient coupling of optical excitation energy from the waveguides to the optical reactions. Optical signals emitted from the reactions can thus be measured with high sensitivity and discrimination using features such as spectra, amplitude, and time resolution, or combinations thereof. The devices of the invention are well suited for miniaturization and high throughput. | 07-17-2014 |
20140193315 | APPARATUS FOR LOADING MOLECULES ONTO SUBSTRATES - Disclosed are compositions, devices, and methods for loading molecules of interest onto a substrate by contacting beads having molecules of interest attached to them with the substrate, for example by providing a field that brings the beads into proximity or contact with the substrate and moves the beads with respect to the substrate. Such molecules of interest can be deposited onto substrates for single-molecule analysis. | 07-10-2014 |
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 |
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 |
20140178863 | 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. | 06-26-2014 |
20140175052 | METHOD FOR PREPARING ZERO-MODE WAVEGUIDE ARRAYS WITH COATED WALLS - The application relates to methods of manufacture of improved optical containment structures. The invention relates to arrays of zero-mode waveguide structures comprising nanoscale apertures having non-reflective coatings on their walls. The methods provide for selectively coating the walls of the zero mode waveguides, allowing for selective functionalization of the bases. | 06-26-2014 |
20140171331 | 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. | 06-19-2014 |
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 |
20140134629 | 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. | 05-15-2014 |
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 |
20140127680 | 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. | 05-08-2014 |
20140094375 | Recombinant Polymerases for Incorporation of Protein Shield Nucleotide Analogs - 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 or nucleic acid amplification. Such properties include enhanced performance with large nucleotide analogs, increased stability, increased readlength, and improved detection of modified bases, and can also include resistance to photodamage, 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 accuracy, altered speed, increased cosolvent resistance, 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. | 04-03-2014 |
20140094374 | Recombinant Polymerases with Increased Readlength and Stability for 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 or nucleic acid amplification. Such properties include increased stability, increased readlength, enhanced performance with large nucleotide analogs, and improved detection of modified bases, and can also include resistance to photodamage, 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 accuracy, altered speed, increased cosolvent resistance, 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. | 04-03-2014 |
20140093935 | CHARGED TRIPLET-STATE QUENCHERS FOR MITIGATION OF PHOTO-INDUCED DAMAGE - Mitigation of photo-induced damage in excitation illuminated reactions and analyses utilizing such reactions results in an enhanced performance for the reactions and the analyses. There is provided a novel class of triplet-state quenchers for mitigating photo-induced damage which are both simple in structure and effective at preventing and/or reducing photo-induced damage to reaction components of excitation illuminated reaction mixtures. Also provided are methods of using the compounds of the invention, devices and kits incorporating the compounds of the invention. | 04-03-2014 |
20140080127 | HETEROARYLCYANINE DYES - The present invention provides heteroaryl functionalized cyanine dyes including a reactive functional moiety, or which are conjugated to a carrier molecule. | 03-20-2014 |
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 |
20140061048 | NANOPORE SEQUENCING USING N-MERS - The invention relates to devices and methods for nanopore sequencing. The invention provides for using the signals from n-mers to provide sequence information, for example where the system has less than single base resolution. 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. | 03-06-2014 |
20140038178 | 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. | 02-06-2014 |
20140017690 | 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. | 01-16-2014 |
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 |
20140017674 | Methods and Compositions for Performing Analytical Operations - Methods for performing analytical reactions and compositions for use in such methods, where the methods have reduced signal levels deriving from non-specific adsorption of detected reagents to other components of the analytical method, e.g., other reagents, solid phase components, vessels, etc. | 01-16-2014 |
20140005404 | Heteroarylcyanine Dyes | 01-02-2014 |
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 |
20130338010 | FILTER ARCHITECTURE FOR ANALYTICAL DEVICES - An approach to the design of the set of filters which allows for the collection of a larger portion of the optical signal while still distinguishing the presence of the various fluorophores is described. In some embodiments, the filter sets of the invention each block a smaller portion of the spectrum, allowing for a larger portion of the emitted light to be detected. The combined information from the light passing through two or more of the filters is then used to determine the presence of a given fluorophore. The filter sets of the invention can be particularly useful in integrated devices in which the light from a single molecule reaction in a small reaction region is directed to a detector or to a specific portion of a detector. | 12-19-2013 |
20130330817 | 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. | 12-12-2013 |
20130330731 | 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. | 12-12-2013 |
20130330722 | Methods and Compositions for Isolating Template Nucleic Acids - The present invention is directed to methods and compositions for isolating template nucleic acids containing target sequences of interest, wherein those isolated template nucleic acids can be further assessed for information related to sequence and nucleic acid modifications. | 12-12-2013 |
20130316912 | POLYMERASE ENZYME SUBSTRATES WITH PROTEIN SHIELD - Compositions and methods are provided for nucleotide analogs comprising protein shields for improving enzyme photostability in single molecule real time sequencing. Nucleotide analogs of the invention have a protein shield between the dye moieties and nucleotide moieties of the analog. The protein prevents the direct interaction of the dye moiety with the enzyme carrying out nucleotide synthesis preventing photodamage to the enzyme. The nucleotide analogs of the invention can have multiple dyes and multiple nucleotide moieties. | 11-28-2013 |
20130309678 | 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. | 11-21-2013 |
20130251592 | 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. | 09-26-2013 |
20130240359 | NANOPORE SEQUENCING USING CHARGE BLOCKADE LABELS - The invention relates to devices and methods for nanopore sequencing. The invention includes compositions and methods of nucleic acid sequencing using a single polymerase enzyme complex comprising a polymerase enzyme and a template nucleic acid attached proximal to a nanopore, and nucleotide analogs in solution comprising charge blockade label that are attached to the polyphosphate portion of the nucleotide analog such that the charge blockade labels are cleaved when the nucleotide analog is incorporated into a growing nucleic acid and the charge blockade label is detected by the nanopore to determine the presence and identity of the incorporated nucleotide and thereby determine the sequence of a template nucleic acid. | 09-19-2013 |
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 |
20130217007 | Recombinant Polymerases With Increased Phototolerance - 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 include increased resistance to photodamage, and can also 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. | 08-22-2013 |
20130217006 | 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. | 08-22-2013 |
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 |
20130143206 | 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. | 06-06-2013 |
20130138358 | 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. | 05-30-2013 |
20130130363 | 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. | 05-23-2013 |
20130130323 | PREVENTION AND ALLEVIATION OF STERIC HINDRANCE DURING SINGLE MOLECULE SYNTHESIS - The present invention provides compositions and methods for reducing steric hindrance in the product of nucleic acid polymerase reaction. Methods and compositions of the invention encompass application of exonucleases, endonucleases, and uracil-DNA glycosylases to a nucleic acid polymerase reaction such that newly formed nucleic acid strands are modified (e.g., cleaved) while the polymerase reaction continues to proceed. | 05-23-2013 |
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 |
20130109577 | REAL-TIME REDOX SEQUENCING | 05-02-2013 |
20130071849 | 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. | 03-21-2013 |
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 |
20130023039 | HIGH MULTIPLEX ARRAYS AND SYSTEMS - 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. | 01-24-2013 |
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 |
20120330566 | 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. | 12-27-2012 |
20120322692 | LOADING MOLECULES ONTO SUBSTRATES - Disclosed are compositions, devices, and methods for loading molecules of interest onto a substrate by contacting beads having molecules of interest attached to them with the substrate, for example by providing a field that brings the beads into proximity or contact with the substrate and moves the beads with respect to the substrate. Such molecules of interest can be deposited onto substrates for single-molecule analysis. | 12-20-2012 |
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 |
20120309650 | 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. | 12-06-2012 |
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 |
20120289408 | 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. | 11-15-2012 |
20120196279 | METHODS AND COMPOSITIONS FOR NUCLEIC ACID SAMPLE PREPARATION - Provided are methods and compositions for the production of double-stranded nucleic acids, which can optionally be used as templates in high-throughput sequencing systems. In certain embodiments, these templates do not require exogenous primers to facilitate initiation of polymerase-dependent nascent strand synthesis. In certain embodiments, these templates comprise a single-stranded or gapped region that serves as a polymerase priming site. | 08-02-2012 |
20120164631 | APPARATUS AND METHOD FOR PERFORMING NUCLEIC ACID ANALYSIS - The present invention relates to optical confinements, methods of preparing and methods of using them for analyzing molecules and/or monitoring chemical reactions. The apparatus and methods embodied in the present invention are particularly useful for high-throughput and low-cost single-molecular analysis. | 06-28-2012 |
20120115736 | NUCLEIC ACID SEQUENCE ANALYSIS - Provided are methods for sequencing a 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. In certain embodiments, a template is fixed to a surface through a template localizing moiety. 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 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. Also provided are methods for using data from analytical reactions wherein two different enzymes are employed, e.g., at a same or different reaction regions. | 05-10-2012 |
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 |
20120077190 | 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. | 03-29-2012 |
20120077189 | SCAFFOLD-BASED POLYMERASE ENZYME SUBSTRATES - The invention provides a novel class of scaffold-based labeled polymerase enzyme substrates. The polymerase enzyme substrates have a multivalent core or scaffold to which is attached fluorescent dye moieties and nucleoside phosphate moities. The polymerase enzyme substrates have multiple fluorescent dye moities and/or multiple nucleoside phosphate moieties. Preferred multivalent cores comprise trifunctional six membered aromatic moities. The invention also provides for sequencing methods and kits with scaffold-based labeled polymerase enzyme substrates. | 03-29-2012 |
20120071359 | PURIFIED EXTENDED POLYMERASE/TEMPLATE COMPLEX FOR SEQUENCING - Methods, Compositions, and Systems are provided for obtaining polymerase-template complex mixtures with improved levels of active polymerase. In some aspects, methods are described in which a polymerase-template complex is exposed to reaction conditions in which a complementary strand to the template is produced. The extended reaction mixture is purified, for example by gel filtration chromatography to produce a mixture of polymerase-template complex having a higher active fraction. This purified mixture can be used for further analyses including single molecule sequencing. | 03-22-2012 |
20120071353 | APPARATUS AND METHOD FOR PERFORMING NUCLEIC ACID ANALYSIS - The present invention relates to optical confinements, methods of preparing and methods of using them for analyzing molecules and/or monitoring chemical reactions. The apparatus and methods embodied in the present invention are particularly useful for high-throughput and low-cost single-molecular analysis. | 03-22-2012 |
20120058482 | FUNCTIONALIZED CYANINE DYES (PEG) - The invention provides a novel class of cyanine dyes that are functionalized with a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates. | 03-08-2012 |
20120058473 | Molecular Adaptors for Dye Conjugates - In various embodiments, the present invention provides fluorescent dyes that are linked to another species through an adaptor moiety. In an exemplary embodiment, the dye is linked to a polyphosphate nucleic acid through an adaptor. An adaptor can be a component of a linker. These conjugates find use in single molecule DNA sequencing and other applications. In various embodiments, the dye moiety is a cyanine dye. Cyanine dyes that are highly charged, such as those including multiple sulfonate, alkylsulfonate, carboxylate and/or alkylcarboxylate moieties are examples of cyanine dyes of use in the compounds of the invention. | 03-08-2012 |
20120058469 | FUNCTIONALIZED CYANINE DYES (PEG) - The invention provides a novel class of cyanine dyes that are functionalized with a linker moiety that facilitates their conjugation to other species and substituent groups which increase the water-solubility, and optimize the optical properties of the dyes. Also provided are conjugates of the dyes, methods of using the dyes and their conjugates and kits including the dyes and their conjugates. | 03-08-2012 |
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 |