DNA-SEQUENZIERUNG MIT HOHER AUFLÖSUNG MITTELS EINEM MEDIUM GERINGER VISKOSITÄT

VORRICHTUNG UND VERFAHREN FÜR DEN TRANSPORT VON TITIERPLATTEN

NUKLEINSÄURESAMMLUNG

1,2-Dioxetane mit verbesserter Chemolumineszenz

ZUSAMMENSETZUNGEN UND VERFAHREN ZUR EXTRAKTION EINER NUKLEINSÄURE

NUKLEINSÄURESAMMLUNG

NACHWEIS VON AMPLIFIZIERTEN NUKLEINSÄURESEQUENZEN DURCH BIFUNKTIONELLE HAPTENISIERUNG UND FARBIGE MIKROPARTIKEL

Dendritische chemilumineszierende Substrate

KONFOKALE FLÜSSIGKEITSSTANDMESSUNG

CHEMILUMINESZENTE SUBSTRATE FÜR DIE NEURAMINIDASE, TESTS ZUR DETEKTION DER NEURAMINIDASE UND "KIT" ZUR AUSFÜHRUNG DIESER TESTS

MULTIPLES REPORTER-GEN-TESTVERFAHREN

Thermocyclervorrichtung mit Linsenvorrichtung für biologische Tests

Kapillar-Arrayvorrichtung

IN BIOLOGISCHEN PROBEN

Automatisierte Polymerasekettenreaktion

Vorrichtung und Gefässe zur Durchführung einer Polymerasekettenreaktion

1,2-Dioxetane mit verbesserter Chemolumineszenz

KONZENTRATION UND REINIGUNG VON ANALYTEN MIT ELEKTRISCHEN FELDERN

Durchführung einer Polymerasekettenreaktion

Erhöhung von Chemilumineszenz in Assays

Methode zur Bestimmung des Stromflusses in einem Trennungskanal und Zusmmensetzung dafür

ELEKTROPHORETISCHES NUKLEINSÄURE-AUFREINIGUNGSVERFAHREN

Mikroplattenanordnung

ANALYSE VON MASSENSPEKTRALDATEN IN DEN RUHIGEN GEBIETEN

Erhöhung von Chemilumineszenz in Assays

ENERGIESTRAHLFÜHRUNG FÜR EIN ELEKTROPHORESESYSTEM

MALDI-PLATTE MIT ENTFERNBAREM EINSATZ

KUGELABGABESYSTEM

Energieübertragungsfarbstoffe mit verbesserter Fluoreszenz

UNABHÄNGIGES GERÄT ZUR EXTRAKTION, AMPLIFIKATION UND NACHWEIS VON NUKLEINSÄUREN

SYSTEME UND VERFAHREN ZUM NACHWEIS DER FUNKTION NUKLEÄRER REZEPTOREN UNTER VERWENDUNG VON REPORTERENZYMMUTANTEN KOMPLEMENTIERUNGEN

SYSTEME UND VERFAHREN ZUM NACHWEIS DER FUNKTION NUKLEÄRER REZEPTOREN UNTER VERWENDUNG VON REPORTERENZYMMUTANTEN KOMPLEMENTIERUNGEN

PROBENKAMMERARRAY UND VERFAHREN ZUR VERARBEITUNG EINER BIOLOGISCHEN PROBE

Optisches Detektionssystem für einen Thermocycler

SYSTEM UND VERFAHREN ZUR ERWEITERUNG DES DYNAMIKUMFANGS DURCH VERWENDUNG VON ABTASTUNG MIT INTEGRATIONSZEIT VARIABLER LÄNGE

Festphasengebundene PNA-Dimere und deren Synthese

Einschliessen von Matrizen zur Sequenzierung von Nukleinsäuren in Probenmischungen bei verflochtenen Polymernetzwerken

QUANTIFIZIERUNG VON RNA-TRANSKRIPTEN MITTELS GENOMISCHER DNA ALS INTERNEN STANDARD DER AMPLIFIZIERUNGSREAKTION

BINÄRSONDE, KLAMMERZUSAMMENSETZUNG UND VERFAHREN ZUM ZIELHYBRIDISIERUNGSNACHWEIS

VERFAHREN ZUR REDUZIERUNG UNSPEZIFISCHER AMPLIFIKATION BEI PCR

Vorrichtung zur Handhabung von Kügelchen

VORRICHTUNG UND VERFAHREN FÜR HOCHDICHTE ELEKTROPHORESE

AUF DIE ÄHNLICHKEIT DER AUSRICHTUNG BASIERTES ZÄHLVERFAHREN ZUM QUANTIFIZIEREN DER UNTERSCHIEDE ZWISCHEN VERWANDTEN BIOPOLYMERSEQUENZEN

1,2-Dioxetane mit verbesserter Chemolumineszenz

VORRICHTUNG UND VERFAHREN FÜR HOCHDICHTE ELEKTROPHORESE

MULTIENZYM-NACHWEISVERFAHREN

ENERGIESTRAHLFÜHRUNG FÜR EIN ELEKTROPHORESESYSTEM

AUF DIE ÄHNLICHKEIT DER AUSRICHTUNG BASIERTES ZÄHLVERFAHREN ZUM QUANTIFIZIEREN DER UNTERSCHIEDE ZWISCHEN VERWANDTEN BIOPOLYMERSEQUENZEN

BESTIMMUNG DER ANZAHL VON NUKLEINSÄUREWIEDERHOLUNGSEQUENZEINHEITEN DURCH SCHRITTWEISE PRIMERVERLÄNGERUNG

Einschliessen von Matrizen zur Sequenzierung von Nukleinsäuren in Probenmischungen bei verflochtenen Polymernetzwerken

VERFAHREN ZUM ENTSCHÜTZEN VON OLIGONUKLEOTIDEN

GERÄT ZUR ÜBERWACHUNG DER POLYMERASE-KETTEN REAKTION VON DNA

FASERMATRIX ZUM ZUSAMMENBRINGEN VON CHEMISCHEN STOFFEN, SOWIE VERFAHREN ZUR HERSTELLUNG UND ANWENDUNG DAVON

BESTIMMUNG VON ANALYTCHARAKTERISTIKA AUF DER GRUNDLAGE VON BINDUNGSEIGENSCHAFTEN

Methode zur Bestimmung des Stromflusses in einem Trennungskanal und Zusmmensetzung dafür

FLUORESZIERENDE NUKLEOBASEKONJUGATE MIT ANIONISCHE LINKER

Automatisierte Polymerasekettenreaktion

BINÄRSONDE, KLAMMERZUSAMMENSETZUNG UND VERFAHREN ZUM ZIELHYBRIDISIERUNGSNACHWEIS

VERBESSERTE SYSTEME FÜR DEN EMPFINDLICHEN NACHWEIS DER FUNKTION VON G-PROTEIN GEKOPPELTEN REZEPTOREN UND "ORPHAN"-REZEPTOREN MITTELS KOMPLEMENTIERUNG VON MUTANTEN DES REPORTER-ENZYMS

KONZENTRATION UND REINIGUNG VON ANALYTEN MIT ELEKTRISCHEN FELDERN

1,2-Dioxetane mit verbesserter Chemolumineszenz

ÜBERZUGABDECKUNG FÜR BEHEIZTE PLATTENANORDNUNG

Vorrichtung zur Handhabung von Kügelchen

SPEKTRALE EICHUNG VON VERSCHIEDENEN FLUORESZIERENDEN FARBSTOFFEN ZUR VERWENDUNG IN EINER VORRICHTUNG ZUR TRENNUNG VON FLUORESZIERENDEN POLYNUCLEOTIDEN

LUZIFERASE ASSAY, ZUSAMMENSETZUNGEN UND TESTSÄTZE ZU DAMIT IN ZUSAMMENHANG STEHENDEN VERWENDUNGEN

FÜR DEN CHEMILUMINESZENZNACHWEIS OPTIMIERTE FESTPHASEN

Kapillar-Arrayvorrichtung

Energieübertragungsfarbstoffe mit verbesserter Fluoreszenz

VERFAHREN ZUR CHARAKTERISIERUNG VON BIOMOLEKÜLEN MITTELS RESULTAT-GESTEUERTER STRATEGIE

ZUSAMMENSETZUNGEN UND VERFAHREN ZUR EXTRAKTION EINER NUKLEINSÄURE

POLYNUKLEOTID-SEQUENZASSAY

HEIZMODUL FÜR PROBENTRÄGER

VORRICHTUNG UND VERFAHREN FÜR DEN TRANSPORT VON TITRIERPLATTEN

FASERMATRIX ZUM ZUSAMMENBRINGEN VON CHEMISCHEN STOFFEN, SOWIE VERFAHREN ZUR HERSTELLUNG UND ANWENDUNG DAVON

VERFAHREN ZUR REDUZIERUNG UNSPEZIFISCHER AMPLIFIKATION BEI PCR

UNABHÄNGIGES GERÄT ZUR EXTRAKTION, AMPLIFIKATION UND NACHWEIS VON NUKLEINSÄUREN

CODIERUNGS- UND DECODIERUNGSREAKTIONEN ZUR BESTIMMUNG VON TARGET-POLYNUKLEOTIDEN

Dendritische chemilumineszierende Substrate

ANALYSE VON MASSENSPEKTRALDATEN IN DEN RUHIGEN GEBIETEN

BESTIMMUNG DER ANZAHL VON NUKLEINSÄUREWIEDERHOLUNGSEQUENZEINHEITEN DURCH SCHRITTWEISE PRIMERVERLÄNGERUNG

BESTIMMUNG VON ANALYTCHARAKTERISTIKA AUF DER GRUNDLAGE VON BINDUNGSEIGENSCHAFTEN

Optisches Gerät insbesondere zur Überwachung von DNS-Polymerasekettenreaktionen

VORRICHTUNG ZUR HANDHABUNG VON KÜGELCHEN

ABTASTVORRICHTUNG UND VERFAHREN ZUM ABTASTEN VON MEHREREN PROBEN

POLYNUKLEOTID-SEQUENZASSAY

QUANTIFIZIERUNG VON RNA-TRANSKRIPTEN MITTELS GENOMISCHER DNA ALS INTERNEN STANDARD DER AMPLIFIZIERUNGSREAKTION

Methods and apparatus for conducting amplification reactions on high density hydrophilic patterned microplates

A microplate for use in performing PCR on a target. The microplate having a substrate with a hydrophobic surface and a plurality of hydrophilic reaction spots on the hydrophobic surface of the substrate. Each of the reaction spots having a capacity to retain less than 5 nanoliters of an aqueous solution. Each of the plurality of hydrophilic reaction spots having a primer and a detection probe anchored.

Fluorescent nucleobase conjugates having anionic linkers

Provided are nucleotide-dye conjugates and related compounds in which a dye is linked to a nucleobase directly or indirectly by an anionic linker. The anionic character of the linker is provided by one or more anionic moieties which are present in the linker, such as phosphate, phosphonate, sulfonate, and carboxylate groups. When the dye is a provided as a donor/acceptor dye pair, the anionic linker can be located between the donor and the acceptor, or between the nucleobase and either the donor or acceptor, or both. In one embodiment, conjugates of the invention provide enhanced electrophoretic mobility characteristics to sequencing fragments, e.g., for dideoxy sequencing using labeled terminators.

Auto-analysis framework for sequence evaluation

An automated system for evaluating biological samples which includes a centralized registry that contains protocols and configuration information for both instruments and analysis applications. The registry provides for improved automation of biological process runs using an autoanalysis applications manager component or daemon, which accesses and transmits the appropriate protocol and configuration information to selected instruments and/or applications. This information is used to instruct data capture by the biological instruments and direct the analysis of the data by the analysis applications.

Heteroconfigurational polynucleotides and methods of use

Methods, compositions and kits are disclosed that utilize heteroconfigurational polynucleotide comprising a D-form polynucleotide sequence portion and an L-form polynucleotide sequence portion that is covalently linked to the D-form polynucleotide sequence portion.

Method of separating biomolecule-containing samples with a microdevice with integrated memory

The present invention provides microdevices, such as those used in the pharmaceutical and biotechnological fields, including an integrated memory. According to various embodiments, the integrated memory is readable, writable, and rewritable. The present invention further provides processing stations, e.g., for carrying out electrophoresis, pcr, genetic analysis, sample preparation, and/or sample cleanup, etc., that are capable of reading from and/or writing/rewriting to such memory.

Devices, Systems, and Methods for Preparing Emulsions

A vortex mixer and method for forming an emulsion wherein the mixer is adapted to form an emulsion with a desired droplet size and having a desired volume. The vortex mixer provides improved uniformity in emulsion preparation and may be used to create multiple emulsions simultaneously.

Probe/mobility modifier complexes for multiplex nucleic acid detection

Compositions and methods for the analysis of multiple nucleic acid target sequences are disclosed. The compositions comprise a probe comprising a target-specific portion for sequence-specific hybridization to a target nucleic acid sequence, and a tag; and a mobility-modifier comprising a tail and a tag complement for binding to the tag. The associated methods generally comprise the steps of providing a sample potentially containing one or more target nucleic acid sequences; providing one or more probes, each probe comprising a target-specific portion and a tag; providing one or more mobility modifiers, each mobility modifier comprising a tag complement and a tail; contacting the probe(s) and the target nucleic acid sequence(s) under conditions effective for sequence-dependent hybridization of the probe(s) and the target nucleic acid sequence(s); contacting the probe(s) and the mobility-modifier(s) under conditions suitable for selectively binding the probe(s) to the mobility modifier(s), thereby forming one or more a probe/mobility modifier complex(s); and analyzing the probe/mobility modifier complex(s) using a mobility-dependent analysis technique.

Amine-containing compound analysis methods

The present teachings provide methods for analyzing one or more amine-containing compounds in one or more samples using isobaric labels and parent-daughter ion transition monitoring (PDITM). In various embodiments, the methods comprise the steps of: (a) labeling one or more amine-containing compounds with different isobaric tags from a set of isobaric tags, each isobaric tag comprising a reporter ion portion; (b) combining at least a portion of each of the isobarically labeled amine-containing compounds to produce a combined sample; (c) subjecting at least a portion of the combined sample to PDITM; (d) measuring the ion signal of one or more of the transmitted reporter ions; and (e) determining the concentration of one or more of the isobarically labeled amine-containing compounds based at least on a comparison of the measured ion signal of the corresponding reporter ion to one or more measured ion signals of a standard compound.

Fluorescence polarization assay

The present invention relates to methods for detecting the presence of one or more analytes of interest in a sample by measuring changes in fluorescence anisotropy as a result of binding of the analytes to specific aptamers. The aptamers are immobilized on a solid support and may be in the form of an array.

Valve assembly for microfluidic devices, and method for opening and closing the same

A normally open fluid manipulation valve assembly and system and a method for closing, re-opening and re-closing same. The normally open valve assembly can include a substrate including a first surface, with first and second recesses formed in the first surface. A recessed channel can be formed in the first surface. The recessed channel can extend from the first recess to the second recess and can be at least partially defined by a first deformable material having a first modulus of elasticity. The valve assembly can also include an elastically deformable cover. The elastically deformable cover can include a layer of an elastically deformable material having a modulus of elasticity that is greater than the modulus of elasticity of the first deformable material, and an adhesive layer that contacts the first surface of the substrate.

Methods for the enrichment of low-abundance polynucleotides

The invention relates to methods for the selective enrichment of low-abundance polynucleotides in a sample. These methods use enzymatically non-extendable nucleobase oligomers to selectively block polymerase activity on high abundance species, thereby resulting in an enrichment of less abundant species in the sample. The invention also relates to the pools of enriched polynucleotides produced by the methods. The resulting pools of enriched polynucleotides find a variety of uses, including the analysis of gene expression and the creation of cDNA libraries.

Ligand-containing micelles and uses thereof

Ligand-containing micelles and various compositions, kits and methods for their preparation and use are provided.

Microarray controls

The teachings relate to microarray controls.

Peptide conjugates and fluorescence detection methods for intracellular caspase assay

Polypeptides labelled with a donor and acceptor pair of dyes selected from a dibenzorhodamine dye and a diamino-benzophenoxazine dye are peptide conjugates which are useful for intracellular and bead-based assays with fluorescence detection. Peptide conjugates with a caspase-recognition site undergo cleavage into peptide fragments which may be detected, located, and quantitated by the changes in fluorescence. Intracellular cleavage of peptide conjugates is correlated with apoptosis.

3'modified oligonucleotides containing pseudoisocytosine nucleobase derivatives and applications thereof as primers or probes

文中披露了在其3’末端区域含有某些修饰核碱基的引物及其各种用法，所述引物能减少扩增反应期间形成的引物－二聚体。

Methods and compositions for nucleotide analysis

The invention relates generally to the field of nucleic acid sequence analysis. In certain embodiments, the analysis is genotyping. In certain embodiments, the analysis involves detecting single nucleotide polymorphisms (SNPs). The invention also relates to methods, kits, and computer software for nucleic acid analysis.

Methods for normalizing and for identifying small nucleic acids

The present teachings are generally directed to methods for normalizing at least one species of small nucleic acid that is present in a population of small nucleic acid species, wherein the relative concentration of at least one small nucleic acid species is substantially greater than the relative concentration of at least one other small nucleic acid species in the population. At least one small nucleic acid species is normalized using a multiplicity of primers comprising degenerate sequences. In some embodiments, a small nucleic acid species is identified by inserting at least part of an extension product from a normalized population into a vector and subsequently sequencing the insert. In some embodiments, a small nucleic acid species is identified by determining the sequence of at least part of an extension product.

Asynchronous primed PCR

An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30° C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point. The asynchronous PCR thermal cycling protocol can generate a preponderance of the PCR amplicon in single-stranded form by repetition at the end of the protocol of annealing and extension of the higher melting primer.

Asynchronous primed pcr

Asynchronous primed PCR

An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30° C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point. The asynchronous PCR thermal cycling protocol can generate a preponderance of the PCR amplicon in single-stranded form by repetition at the end of the protocol of annealing and extension of the higher melting primer.

Multiplexed amplification of short nucleic acids

The present teachings provide methods, compositions, and kits for reverse transcribing and amplifying small nucleic acids such as micro RNAs. High levels of multiplexing are provided by the use of a zip-coded stem-loop reverse transcription primer, along with a PCR-based pre-amplification reaction that comprises a zip-coded forward primer. Detector probes in downstream decoding PCRs can take advantage of the zip-code introduced by the stem-loop reverse transcription primer. In some embodiments, further amplification is achieved by cycling the reverse transcription reaction. The present teachings also provide compositions and kits useful for performing the reverse transcription and amplification reactions described herein.

Methods and compositions for detecting nucleotides

The present teachings generally relate to methods and materials for the detection of target nucleotides and/or the methylation state of target nucleotides.

Asynchronous primed pcr

An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30 °C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point. The asynchronous PCR thermal cycling protocol can generate a preponderance of the PCR amplicon in single-stranded form by repetition at the end of the protocol of annealing and extension of the higher melting primer.

Asynchronous primed pcr

An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30 °C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point. The asynchronous PCR thermal cycling protocol can generate a preponderance of the PCR amplicon in single-stranded form by repetition at the end of the protocol of annealing and extension of the higher melting primer.

Asynchronous primed pcr

An asynchronous thermal cycling protocol for nucleic acid amplification uses two primers with thermal melting temperatures different by about 10 to 30 °C. After the higher melting primer has annealed and polymerase mediated extension, the uncopied, single-stranded target sequence may be hybridized and detected by a probe. DNA probes may be cleaved by the exonuclease activity of a polymerase. The probe may be a non-cleaving analog such as PNA. When a probe is labelled with a reporter dye and a quencher selected to undergo energy transfer, e.g. FRET, fluorescence from the reporter dye may be effectively quenched when the probe is unbound. Upon hybridization of the probe to complementary target or upon cleavage while bound to target, the reporter dye is no longer quenched, resulting in a detectable amount of fluorescence. The second, lower-melting primer may be annealed and extended to generate a double-stranded nucleic acid. Amplification may be monitored in real time, including each cycle, or at the end point. The asynchronous PCR thermal cycling protocol can generate a preponderance of the PCR amplicon in single-stranded form by repetition at the end of the protocol of annealing and extension of the higher melting primer.

Ligation assembly and detection of polynucleotides on solid-support

Template-dependent ligation with PNA-DNA chimeric probes

Methods and compositions for detecting targets

The present invention relates to methods and kits for detecting the presence or absence of (or quantitating) target nucleic acid sequences using ligation and amplification. The invention also relates to methods, reagents, and kits that employ addressable portions and labeled probes.

Modified oligonucleotides and applications thereof

Disclosed, among other things, are primers containing certain modified nucleobases in the 3′ terminal region of the primers that provide reduced formation of primer-dimers during amplification reactions, and various methods of use thereof.

Multiplex amplification of polynucleotides

Compositions and methods for clonal amplification and analysis of polynucleotides

Compositions and methods of use are disclosed for clonally amplifying and analyzing one or more polynucleotides.

Fluid processing device and method

A fluid processing device and methods are provided that can process one or many different fluid samples, detection for each of which can be multiplexed to detect the presence or absence of each of a panel of target sequences, for example 20 different target sequences. The device can comprise a substrate and one or more fluid processing pathways at least partially defined by the substrate. Each fluid processing pathway can comprise a pre-amplification region and two or more amplification regions disposed downstream from and in fluid communication with the pre-amplification region. A burstable valve can be disposed along each fluid processing pathway and the downstream regions can contain pre-loaded ammonia gas to draw an amplified sample downstream.

Microarray Microcard

A fluid processing device is provided that comprises a substrate including a surface and a fluid processing pathway at least partially formed in or on the surface. The fluid processing pathway can comprise a channel, a reaction region in fluid communication with the channel, a microarray in fluid communication with the channel, and optionally a deformable valve. The microarray can comprise binding and/or detection sites, and each site can comprise a binding moiety. A method and a system using the fluid processing device, are also provided.

Methods and devices for multiplexing amplification reactions

The present invention provides a two-step multiplex amplification reaction wherein the first step truncates the standard initial multiplex amplification round to “boost” the sample copy number by only a 100–1000 fold increase in the target. Following the first step the product is divided into optimized secondary single amplification reactions, each containing one of the primer sets that were used previously in the first or multiplexed booster step. The booster step can occur using an aqueous target nucleic acid or using a solid phase archived nucleic acid. In particular, nucleic acid sequences that uniquely identify E. Coli were identified using the multiplex amplification method.

Novel method for isolating single stranded product

The present teachings relate to methods of purifying, isolating, separating, and identifying target nucleic acids. In some embodiments of the present teachings, an affinity moiety can be incorporated into one of the flanking primers of a nucleic acid amplification reaction primer pair. The reaction mixture can be contacted with a binding moiety specific for the affinity moiety, thereby allowing immobilization of the double stranded amplification product, separation of reaction components lacking the affinity moiety, and isolation of the target nucleic acid strand. Further, one of the flanking primers of the nucleic acid amplification reaction can comprise a label and a mobility modifier, thereby facilitating identification of the target nucleic acids. In some embodiments, the amplification reaction is multiplexed and comprises polymorphic microsatellites useful in human identification. and the manufacturing of molecular size standards. Some embodiments of the present teachings provide for improved methods of performing electrokinetic injection.

Device and method for microfluidic control of a first fluid in contact with a second fluid, wherein the first and second fluids are immiscible

Various embodiments described in the application relate to an apparatus, system, and method for fluidically controlling, within a conduit, discrete volumes of one or more fluids that are immiscible with a second fluid. The discrete volumes can be used for biochemical or molecular biology procedures involving small volumes, for example, microliter-sized volumes, nanoliter-sized volumes, or smaller. The system can comprise combinations of detectors, controllers, valves, and fluid supply units to control the spatial size, location and/or fluidic composition of discrete volumes separated from one another by a fluid that is immiscible with the fluid(s) of the discrete volumes, for example, aqueous immiscible-fluid-discrete volumes separated by an oil.

Multiplex amplification of polynucleotides

The present invention provides methods, reagents and kits for carrying out a variety of assays suitable for analyzing polynucleotides or samples that include an amplification step performed in a multiplex fashion. Also provided are methods for analyzing and improving the efficiency of amplification and for carrying out gene expression analysis.

Microarray microcard

A fluid processing device is provided that comprises a substrate including a surface and a fluid processing pathway at least partially formed in or on the surface. The fluid processing pathway can comprise a channel, a reaction region in fluid communication with the channel, a microarray in fluid communication with the channel, and optionally a deformable valve. The microarray can comprise binding and/or detection sites, and each site can comprise a binding moiety. A method and a system using the fluid processing device, are also provided.

Multiplex amplification of polynucleotides

Multiplex amplification of polynucleotides

The present invention provides methods, reagents and kits for carrying out a variety of assays suitable for analyzing polynucleotides or samples that include an amplification step performed in a multiplex fashion. Also provided are methods for analyzing and improving the efficiency of amplification and for carrying out gene expression analysis.

Multiplex amplification of polynucleotides

The present invention provides methods, reagents and kits for carrying out a variety of assays suitable for analyzing polynucleotides or samples that include an amplification step performed in a multiplex fashion. Also provided are methods for analyzing and improving the efficiency of amplification and for carrying out gene expression analysis.

Multiplex amplification of polynucleotides

The present invention provides methods, reagents and kits for carrying out a variety of assays suitable for analyzing polynucleotides or samples that include an amplification step performed in a multiplex fashion. Also provided are methods for analyzing and improving the efficiency of amplification and for carrying out gene expression analysis.

Multiplex amplification of polynucleotides

The present invention provides methods, reagents and kits for carrying out a variety of assays suitable for analyzing polynucleotides or samples that include an amplification step performed in a multiplex fashion. Also provided are methods for analyzing and improving the efficiency of amplification and for carrying out gene expression analysis.

Matrix storage and dispensing system

The present invention provides a system and process providing variable access to, as well as quick and accurate dispensing of, numerous selected reagents from a mass storage arrangement. According to one embodiment, an array of reagent dispensers is supported over a movable platform assembly. The platform assembly aligns a designated receiving receptacle under a selected dispenser of the array so that a respective reagent can be dispensed therein. Advantageously, the apparatus and process can be carried out under the control of a programmed computer.

Matrix storage and dispensing system

The present invention provides a system and process providing variable access to, as well as quick and accurate dispensing of, numerous selected reagents from a mass storage arrangement. According to one embodiment, an array of reagent dispensers is supported over a movable platform assembly. The platform assembly aligns a designated receiving receptacle under a selected dispenser of the array so that a respective reagent can be dispensed therein. Advantageously, the apparatus and process can be carried out under the control of a programmed computer.

Minimizing the meniscus effect

The present application relates to apparatuses and methods for wet-detection of hybridization assays.

Fluid processing device with captured reagent beads

A fluid processing device, method and system are provided. The fluid processing device can comprise: a substrate; a plurality of reaction regions disposed in or on the substrate; at least one channel interconnecting the plurality of reaction regions, the at least one channel having a cross-sectional area that includes a maximum dimension; and a plurality of reagent-releasing beads. Each reagent-releasing bead can be positioned in a respective one of the reaction regions. Each bead can comprise one or more reaction components for an assay. Each of the reagent-releasing beads can have a minimum dimension that is greater than the maximum dimension of the channel cross-section.

Fluid processing device comprising sample transfer feature

Devices for fluid processing, systems that comprise such devices, and methods that use such devices and/or systems are provided. Such fluid processing devices, systems that include such devices and methods that use such devices and/or systems can be used in any application that involves controlled sample transfer including PCR or other DNA-based procedures as well as other types of molecular biology procedures.

Nucleic acid analysis device

The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. The device includes a substrate which defines a sample-distribution network having (i) a sample inlet, (ii) one or more detection chambers, and (iii) channel means providing a dead-end fluid connection between each of the chambers and the inlet. Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Device and method for multiple analyte detection

The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. The device includes a substrate which defines a sample-distribution network having (i) a sample inlet, (ii) one or more detection chambers, and (iii) channel means providing a dead-end fluid connection between each of the chambers and the inlet. Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Device and method for multiple analyte detection

The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more of a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Microfluidic systems including porous polymer electrodes

Microfluidic devices that incorporate a porous polymer electrode assemblies, including microfluidic device useful for detection of nucleic acids, as well as methods of using the microfluidic devices.

Polynucleotide sequence assay

Polynucleotide sequence detection assays

Portable preparation, analysis, and detection apparatus for nucleic acid processing

本发明教导内容包括一种用于裂解和/或提纯生物样品的装置和方法。所述装置可以包括柱筒，所述柱筒具有包括了生物样品接收区域的腔室、多个电极、和一个或多个筛分基体。电极可以配置成通过产生脉冲电场来裂解生物样品。电极也可以配置成热裂解生物样品。电极还可以配置成电泳式移动生物样品穿过一个或多个筛分基体。一部分样品可以隔离在隔膜上。隔离在隔膜上的这部分样品可以被扩增并被检测到。一部分样品可以隔离在存在于柱筒内的收集区域内。隔离在收集区域内的这部分样品可以从柱筒移除。

Method of making polymer monolith composite substrate and resulting substrate as well as beads and bead array

The present teachings provide for composite substrates for the covalent attachment of biomolecules and method of making the same. The present teachings provide for composite substrates comprising a porous copolymer-monolith covalently attached to a surface of a substrate, wherein the porous copolymer-monolith has been formed by an inverse phase photo-copolymerization process comprising photo-copolymerizing at least one ethylenically unsaturated monomer with polymerizable surface functionalities that are covalently attached to a surface of a derivitized substrate such that, after photo-copolymerization, the porous copolymer-monolith is covalently attached to the surface of the substrate, and wherein the photo-copolymerizing is carried out in the presence of at least one porogenic solvent.

Water-soluble rhodamine dye peptide conjugates

The present invention provides novel, water-soluble, red-emitting fluorescent rhodamine dyes and red-emitting fluorescent energy-transfer dye pairs, as well as labeled conjugates comprising the same and methods for their use. The dyes, energy-transfer dye pairs and labeled conjugates are useful in a variety of aqueous-based applications, particularly in assays involving staining of cells, protein binding, and/or analysis of nucleic acids, such as hybridization assays and nucleic acid sequencing.

Thermus scotoductus nucleic acid polymerases

The invention provides nucleic acids and polypeptides for a nucleic acid polymerase from a thermophilic organism, Thermus scotoductus. The invention also provides methods for using these nucleic acids and polypeptides.

Improved invasion assay

The invention relates to improved methods of detecting and characterizing polynucleotide sequences and variations in polynucleotide sequences. The invention further relates to a device that can be used to detect and characterize polynucleotide sequences and variations in polynucleotide sequences. The invention is directed to an improved invasion assay to methods of analyzing invasion assay data. The invention is based, in part, on a discovery that signals due to the cleavage of a probe annealed to a template polynucleotide (e.g. DNA or RNA) can exhibit behavior over time that is different from the behavior over time of signals produced by background reactions (e.g. reactions that are not dependent on the presence of target polynuclotide). For example, the positive signal produced by many invasion assays (i.e., the signal that indicates an cleavage of a probe oligonucleotide annealed to a target polynucleotide) can be fit to a polynomial that is higher in order than the polynimial required to characterize the background signal. It is thus possible to determine the results of an invasion assay in real time or at the conclusion of the assay by determining whether the behavior of the signal it produced over time is different from that of a typical, estimated theoretical or actually measured background signal.

Invasion assay

The invention relates to improved methods of detecting and characterizing polynucleotide sequences and variations in polynucleotide sequences. The invention further relates to a device that can be used to detect and characterize polynucleotide sequences and variations in polynucleotide sequences.

Thermus scotoductus nucleic acid polymerases

Hybridization assay using self-quenching fluorescence probe

A hybridization assay is provided which uses an oligonucleotide probe which includes a fluorescent reporter molecule and a quencher molecule capable of quenching the fluorescence of the reporter molecule. The oligonucleotide probe is constructed such that the probe exists in at least one single-stranded confirmation when unhybridized where the quencher molecule is near enough to the reporter molecule to quench the fluorescence of the reporter molecule. The oligonucleotide probe also exists in at least one conformation when hybridized to a target polynucleotide where the quencher molecule is not positioned close enough to the reporter molecule to quench the fluorescence of the reporter molecule. By adopting these hybridized and unhybridized conformations, the reporter molecule and quencher molecule on the probe exhibits different fluorescence signal intensities when the probe is hybridized and unhybridized. As a result, it is possible to determine whether the probe is hybridized or unhybridized based on a change in the fluorescence intensity of the reporter molecule, the quencher molecule, or a combination thereof. In addition, because the probe can be designed such that the quencher molecule quenches the reporter molecule when the probe is not hybridized, the probe can be designed such that the reporter molecule exhibits limited fluorescence until the probe is either hybridized or digested.

Oligonucleotides and analogs labeled with energy transfer dyes

Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R 21 Z 1 C(O)R 22 R 28 where R 21 is a C 1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z 1 is either NH, sulfur or oxygen, R 22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R 28 includes a functional group which attaches the linker to the acceptor dye.

Methods and reagents for combined PCR amplification and hybridization probing

An oligonucleotide probe is disclosed, the probe including an oligonucleotide, a fluorescer molecule attached to a first end of the oligonucleotide and a quencher molecule attached to the opposite end of the oligonucleotide. The probe is rendered impervious to digestion by the 5′→3′ exonuclease activity of a polymerase and the 5′→3′ extension of by a polymerase. The invention also includes methods for performing combined PCR amplification and hybridization probing, one such method including the steps of contacting a target nucleic acid sequence with PCR reagents and an oligonucleotide probe as described above, and subjecting these reagents to thermal cycling. One preferred refinement of the above method further includes the addition of a strand displacer to facilitate amplification. Additional similar combined PCR hybridization methods are disclosed, such methods not requiring probes having their 5′ ends protected, wherein (i) the polymerase lacks 5′→3′ exonuclease activity, (ii) a 5′→3′ exonuclease inhibitor is included, and (iii) an exonuclease deactivation step is performed.

Regents labeled with energy transfer dyes

Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R 21 Z 1 C(O)R 22 R 28 where R 21 is a C 1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z 1 is either NH, sulfur or oxygen, R 22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R 28 includes a functional group which attaches the linker to the acceptor dye.

Energy transfer dyes with enhanced fluorescence

Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R 21 Z 1 C(O)R 22 R 28 where R 21 is a C 1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z 1 is either NH, sulfur or oxygen, R 22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R 28 includes a functional group which attaches the linker to the acceptor dye.

Energy transfer dyes with enhanced fluorescence

Novel linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye are provided. These linkers faciliate the efficient transfer of energy between a donor and acceptor dye in an energy transfer dye. One of these linkers for linking a donor dye to an acceptor dye in an energy transfer fluorescent dye has the general structure R 21 Z 1 C(O)R 22 R 28 where R 21 is a C 1-5 alkyl attached to the donor dye, C(O) is a carbonyl group, Z 1 is either NH, sulfur or oxygen, R 22 is a substituent which includes an alkene, diene, alkyne, a five and six membered ring having at least one unsaturated bond or a fused ring structure which is attached to the carbonyl carbon, and R 28 includes a functional group which attaches the linker to the acceptor dye.

UV excitable energy transfer reagents

Novel energy transfer dyes which can be used with shorter wavelength light sources are provided. These dyes include a donor dye with an absorption maxima at a wavelength between about 250 to 450 nm and an acceptor dye which is capable of absorbing energy emitted from the donor dye. One of the energy transfer dyes has a donor dye which is a member of a class of dyes having a coumarin or pyrene ring structure and an acceptor dye which is capable of absorbing energy emitted from the donor dye, wherein the donor dye has an absorption maxima between about 250 and 450 nm and the acceptor dye has an emission maxima at a wavelength greater than about 500 nm.

UV excitable fluorescent energy transfer dyes

Novel energy transfer dyes which can be used with shorter wavelength light sources are provided. These dyes include a donor dye with an absorption maxima at a wavelength between about 250 to 450 nm and an acceptor dye which is capable of absorbing energy emitted from the donor dye. One of the energy transfer dyes has a donor dye which is a member of a class of dyes having a coumarin or pyrene ring structure and an acceptor dye which is capable of absorbing energy emitted from the donor dye, wherein the donor dye has an absorption maxima between about 250 and 450 nm and the acceptor dye has an emission maxima at a wavelength greater than about 500 nm.

UV excitable energy transfer reagents

Novel energy transfer dyes which can be used with shorter wavelength light sources are provided. These dyes include a donor dye with an absorption maxima at a wavelength between about 250 to 450 nm and an acceptor dye which is capable of absorbing energy emitted from the donor dye. One of the energy transfer dyes has a donor dye which is a member of a class of dyes having a coumarin or pyrene ring structure and an acceptor dye which is capable of absorbing energy emitted from the donor dye, wherein the donor dye has an absorption maxima between about 250 and 450 nm and the acceptor dye has an emission maxima at a wavelength greater than about 500 nm.

Methods for the enrichment of low-abundance polynucleotides

The invention relates to methods for the selective enrichment of low-abundance polynucleotides in a sample. These methods use enzymatically non-extendable nucleobase oligomers to selectively block polymerase activity on high abundance species, thereby resulting in an enrichment of less abundant species in the sample. The invention also relates to the pools of enriched polynucleotides produced by the methods. The resulting pools of enriched polynucleotides find a variety of uses, including the analysis of gene expression and the creation of cDNA libraries.

Template-dependent ligation with PNA-DNA chimeric probes

The invention provides methods, kits, and compositions for ligation of PNA-DNA chimeric probes and oligonucleotides when they are hybridized adjacently to template nucleic acids using ligases and ligation reagents. Structural requirements of the chimeras for ligation include 5 to 15 contiguous PNA monomer units, 2 or more contiguous nucleotides, and a 3′ hydroxyl or 5′ hydroxyl terminus. The chimera and/or oligonucleotide may be labelled with fluorescent dyes or other labels. The methods include, for example, oligonucleotide-ligation assays (OLA) and single nucleotide polymorphism detection.

Heteroconfigurational polynucleotide and methods of use

公开了利用含有D型多核苷酸序列部分和与该D型多核苷酸序列部分共价连接的L型多核苷酸序列部分的杂构多核苷酸的方法、组合物和试剂盒。

Isolated human transporter proteins, nucleic acid molecules encoding human transporter proteins, and uses thereof

The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the transporter peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the transporter peptides, and methods of identifying modulators of the transporter peptides.

Instrument for monitoring polymerase chain reaction of dna

An optical instrument monitors PCR replication of DNA in a reaction apparatus having a temperature cycled block with vials of reaction ingredients including dye that fluoresces in presence of double-stranded DNA. A beam splitter passes an excitation beam to the vials to fluoresce the dye. An emission beam from the dye is passed by the beam splitter to a CCD detector from which a processor computes DNA concentration. A reference strip with a plurality of reference emitters emit reference beams of different intensity, from which the processor selects an optimum emitter for compensating for drift. Exposure time is automatically adjusted for keeping within optimum dynamic ranges of the CCD and processor. A module of the beam splitter and associated optical filters is associated with selected dye, and is replaceable for different dyes.

Instrument for monitoring polymerase chain reaction of DNA

An optical instrument monitors PCR replication of DNA in a reaction apparatus having a temperature cycled block with vials of reaction ingredients including dye that fluoresces in presence of double-stranded DNA. A beam splitter passes an excitation beam to the vials to fluoresce the dye. An emission beam from the dye is passed by the beam splitter to a CCD detector from which a processor computes DNA concentration. A reference strip with a plurality of reference emitters emit reference beams of different intensity, from which the processor selects an optimum emitter for compensating for drift. Exposure time is automatically adjusted for keeping within optimum dynamic ranges of the CCD and processor. A module of the beam splitter and associated optical filters is associated with selected dye, and is replaceable for different dyes.

Optical instrument including excitation source

An optical instrument is provided for simultaneously illuminating two or more spaced-apart reaction regions with an excitation beam generated by a light source. A collimating lens can be disposed along a beam path between the light source and the reaction regions to form bundles of collimated excitation beams, wherein each bundle corresponds to a respective reaction region. Methods of analysis using the optical instrument are also provided.

Temperature control for light-emitting diode stabilization

A system is provided that includes a light-emitting diode (LED); a temperature sensor in thermal contact with the LED and capable of measuring an operating temperature and generating an operating temperature signal; and a temperature regulating system capable of receiving the operating temperature signal and regulating the operating temperature based on the operating temperature signal. A method for stabilizing the temperature of an LED is provided. A method is provided that includes providing a system comprising an LED, a reaction region, and a sample in the reaction region; generating excitation beams with the LED; directing excitation beams to the sample; detecting an optical property of the sample to obtain detection data; measuring the operating temperature of the light emitting diode; and adjusting the detection data of an excitation beam characteristic shift related to the operating temperature, when the LED is operated at the operating temperature to generate the excitation beams.

Non-fluorescent quencher compounds and biomolecular assays

Bis-diazo,triaryl and aryldiazo-N-arylphenazonium quencher moieties, substituted with electron-withdrawing and electron-donating substituents which induce polarity in the delocalized aryl/diazo ring systems, are useful as labels when attached to biomolecules such as polynucleotides, nucleosides, nucleotides, and polypeptides. The quencher moieties are non-fluorescent and accept energy from fluorescent reporter labels by any energy-transfer mechanism, such as FRET. Fluorescence quencher compositions are useful in preparing quencher labelled biomolecules for various molecular biology assays based on fluorescence detection.

Method of reducing non-specific amplification in PCR

The invention provides methods for reducing non-specific amplification DNA in a polymerase chain reaction comprising providing a sample comprising a target DNA sequence of interest; contacting the sample with at least one enzyme having nucleic acid polymerase activity; and incubating the sample with said enzyme for a time and under conditions sufficient to amplify the target DNA sequence, forming amplified target sequence; wherein the incubation is performed in the presence of an amount of sorbitol, or sorbitol and DMSO effective to reduce the non-specific amplification relative to the amount of non-specific amplification observed in the absence of sorbitol, or sorbitol and DMSO. The methods are suitable for amplification of ribosomal DNA, particularly from clinical samples. Compositions and kits containing sorbitol, or sorbitol and DMSO for reducing non-specific amplification are also provided.

Methods for selecting protein binding moieties

Methods, compositions, and apparatuses for the identification of binding moieties that bind to targets are provided. Vectors encoding potential binding moieties are also provided. In certain embodiments, methods are provided for the presentation of potential binding moieties by cells, the selection of binding moieties that bind targets, and the amplification of the nucleic acids encoding the binding moieties.

5-methylcytosine detection, compositions and methods therefor

Compositions and methods for detecting 5-methylcytosine in a nucleic acid are disclosed. A 5-methylcytosine discriminator, which is a deoxyribonucleosidetriphosphate comprising a cytosine-pairing moiety such as a guanosine and a moiety which hinders hydrogen bonding between the cytosine-pairing moiety and a 5-methylcytosine is described. The discriminator is able to base pair with a cytosine but not a 5-methylcytosine. A 5-methylcytosine comprised by a target nucleotide can be detected in a reaction using a DNA polymerase and a primer hybridized immediately adjacent to the target nucleotide. In the reaction, pyrophosphate released upon incorporation of a dNTP complementary to a target nucleotide is detected. Lack of incorporation of the discriminator, but incorporation of a dGTP, can indicate that the target nucleotide is a 5-methylcytosine.

High speed, high resolution compositions, methods, and kits for capillary electrophoresis

The invention provides compositions, methods and kits for high speed, high resolution of analytes by capillary electrophoresis starting with uncoated capillaries. The compositions comprise a sieving component, comprising a non-crosslinked acrylamide polymer, and a surface interaction component, comprising at least one uncharged and non-crosslinked water-soluble silica-adsorbing polymer. Methods for employing the novel compositions in capillary electrophoresis are provided. Kits comprising the novel compositions for use in the novel methods are also provided.

Isolated human kinase proteins, nucleic acid molecules encoding human kinase proteins, and uses thereof

The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the kinase peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the kinase peptides, and methods of identifying modulators of the kinase peptides.

Methods and compositions concerning siRNA's as mediators of RNA interference

The present invention concerns an isolated siRNA of from about 5 to about 20 nucleotides that mediates RNA interference. Also disclosed are methods of reducing expression of a target gene in a cell comprising obtaining at least one siRNA of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 basepairs in length; and delivering the siRNA into the cell. The siRNAs can be chemically synthesized RNA or an analog of a naturally occurring RNA.

Isolated human secreted proteins, nucleic acid molecules encoding human secreted proteins, and uses thereof

The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the secreted peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the secreted peptides, and methods of identifying modulators of the secreted peptides.

High density sequence detection methods and apparatus

Methods for amplifying polynucleotides, e.g., by PCR, in a sample comprising polynucleotide targets present at very low concentration, comprising: (a) applying amplification reactants to the surface of a substrate comprising reaction spots, wherein the reactants comprise the sample and an amplification reagent; (b) forming a sealed reaction chamber, having a volume less than about 120 nanoliters, preferably less than about 20 nanoliters, over each of said reaction spots; and (c) thermal cycling the substrate and reactants. In one embodiment, the forming step comprises loading a sealing fluid, e.g., mineral oil, on the surface so as to cover the reaction spots. The present invention also provides microplates, comprising: (a) a substrate having at least about 10,000 reaction spots, each comprising a primer and a droplet of reagent having a volume less than about 120 nanoliters, preferably less then about 20 nanoliters; and (b) a sealing liquid isolating each of the spots.

High density sequence detection methods and apparatus

Methods for amplifying polynucleotides, e.g., by PCR, in a sample comprising polynucleotide targets present at very low concentration, comprising: (a) applying amplification reactants to the surface of a substrate comprising reaction spots, wherein the reactants comprise the sample and an amplification reagent; (b) forming a sealed reaction chamber, having a volume less than about 120 nanoliters, preferably less than about 20 nanoliters, over each of said reaction spots; and (c) thermal cycling the substrate and reactants. In one embodiment, the forming step comprises loading a sealing fluid, e.g., mineral oil, on the surface so as to cover the reaction spots. The present invention also provides microplates, comprising: (a) a substrate having at least about 10,000 reaction spots, each comprising a primer and a droplet of reagent having a volume less than about 120 nanoliters, preferably less then about 20 nanoliters; and (b) a sealing liquid isolating each of the spots.

Scanning system and method for scanning a plurality of samples

A system for detecting fluorescence emitted from a plurality of samples in a sample tray is provided. The system generally includes a plurality of lenses positioned in a linear arrangement, a linear actuator configured to translate the plurality of lenses, an excitation light source for generating an excitation light, an excitation light direction mechanism for directing the excitation light to a single lens of the plurality of lenses at a time so that a single sample holder aligned with the lens is illuminated at a time, and an optical detection system for analyzing light from the sample holders. In certain embodiments, the optical detection system includes a light dispersing element configured to spectrally disperse the light from the sample holder being illuminated, and a lens element configured to receive light from the light dispersing element and direct the light onto a light detection device. A method of scanning a sample tray having a plurality of samples positioned in sample holders to detect fluorescence is also provided.

Scanning system and method for scanning a plurality of samples

A system for detecting fluorescence emitted from a plurality of samples placed in a plurality of sample wells in a detection system. The detection system may include either a single lens which may be used to focus excitation beams on one or a plurality of the sample wells. Alternatively, a plurality of lenses may be placed in a housing and may be used to focus one or a plurality of excitation beams onto one or a plurality of sample wells. In addition, splitters or diffusers may be used to split a single excitation beam into a plurality of excitation beams to excite a plurality of sample wells simultaneously. Therefore, a plurality of sample wells may be excited and detected simultaneously rather than consecutively. The sample wells may generally be arranged in arrays having a plurality of geometries. Specifically, sample wells may be arrayed in rectangular, square, circular, or spiral geometries.

High density sequence detection methods

A method for performing PCR on a liquid sample comprising a plurality of polynucleotide targets, wherein each polynucleotide target is present at very low concentration within the sample. The method comprises applying PCR reactants to the surface of a substrate to produce a plurality of reaction spots on the surface of the substrate; loading the liquid sample and a PCR reagent mixture onto the reaction spots; forming a sealed reaction chamber, having a volume of less than about 20 nanoliters, over each of the reaction spots; and amplifying the sample.

Whole genome expression analysis system

The present invention provides methods for simultaneously determining the genetic expression profile an individual member of a species relative to a standard genome for said species, comprising distributing a sample comprising substantially all the genetic material of said member into an array of reaction chambers on a substrate, wherein each chamber has a volume of less than about 1 microliter, and each chamber comprises (1) a primer for a polynucleotide target within said standard genome, and (2) a probe associated with said primer which emits a concentration dependent signal if the primer binds with said target, and the array comprises at least one chamber comprising a primer for each of the polynucleotide target within said standard genome; performing an amplification reaction on the distributed sample in the array so as to increase the concentration of polynucleotides in each of the chambers in which the polynucleotide binds to a primer; and identifying which of the reaction chambers contains a polynucleotide that has been bound to a primer, by detecting the presence of the probe associated with the primer. In one embodiment, the organism is human, and the array comprises primers for 30,000 genomic polynucleotides. In one embodiment, the amplification is PCR.

Microplates useful for conducting thermocycled nucleotide amplification

An inverted microplate (22’) having a plurality of reaction wells (34’) and a transparent cover (24). The plate (22’) comprising a solution (38) in a well (34’), a surface of the cover (24) in contact with the solution (38) and the head space of the well (34’) a distance from the cover (24). In another embodiment, the reaction plate (22’) is made from a material that has a thermal conductive property. In another embodiment, a well (34’) of a microplate (34’), the well (34’) comprising a closed top and an open bottom, a cover (24), a solution (38) in the well (34’) and the solution (38) touching the surface of the cover (24). Other embodiments include a multi-well microtiter plate (22’) comprising a plurality of reaction wells (34’) and a transparent cover (24), the plate (22’) comprising a solution (38) in a well (34’), the solution (38) held to the surface of the cover (24) by a force.

Labelled oligonucleotides synthesized on solid-supports

Methods and compositions to label oligonucleotides and analogs directly on a solid-support having the structure where S is a solid-support, A is a cleavable linker, X is a moiety with three or more attachment sites, L is a label, Y is a nucleophile, i.e. O, NH, NR or S, and P 1 is an acid cleavable protecting group are provided. The labelled solid-support is reacted in a cyclical fashion to synthesize a labelled oligonucleotide on a solid-support in the 5′ to 3′ direction, having the structure: Labelled oligonucleotides are also synthesized by reacting: (i) a label reagent bearing functionality consisting of carboxylic acid, sulfonic acid, phosphonic acid, or phosphoric acid, (ii) an oligonucleotide on solid support with nucleophilic functionality, and (iii) a coupling reagent, whereby an ester, amide, thioester, sulfonamide, sulfonate, phosphonate, phosphoramidate, phosphorothioate, or phosphate bond is formed. The labelling reaction may be conducted at label sites including the 5′ terminus, the 3′ terminus, a nucleobase, an internucleotide linkage, a sugar, amino, sulfide, hydroxyl, and carboxyl.

Isolated human kinase proteins, nucleic acid molecules encoding human kinase proteins, and uses thereof

The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the kinase peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the kinase peptides, and methods of identifying modulators of the kinase peptides.

Isolated human kinase proteins, nucleic acid molecules encoding human kinase proteins, and uses thereof

The present invention provides amino acid sequences of peptides that are encoded by genes within the human genome, the kinase peptides of the present invention. The present invention specifically provides isolated peptide and nucleic acid molecules, methods of identifying orthologs and paralogs of the kinase peptides, and methods of identifying modulators of the kinase peptides.

Vacuum assist for a microplate

A vacuum assist apparatus can comprise a microplate. The microplate can comprise a first surface and an opposing second surface. A plurality of wells can be formed in the first surface of the microplate. Each of the plurality of wells can be sized to receive an assay therein. A support base can comprise a fluid passage. The microplate can be positioned adjacent and in contact with the support base. A pressure device, in fluid communication with the fluid passage, can exert a vacuum within the fluid passage to actively retain the microplate in the contact with the support base.

Pancreatic cancer secreted targets and uses thereof

The present invention provides a method for diagnosing and detecting diseases associated with pancreas. The present invention provides one or more proteins or fragments thereof, peptides or nucleic acid molecules differentially expressed in pancreatic diseases (PCAST) and antibodies binds to PCAST. The present invention provides that PCAST is used as targets for screening agents that modulates the PCAST activities. Further the present invention provides methods for treating diseases associated with pancreas.

Methods and compositions for analyzing nucleic acids

Methods and compositions for probe amplification to detect, identify, quantitate, and/or analyze a targeted nucleic acid sequence. After hybridization between a probe and the targeted nucleic acid, the probe is modified to distinguish hybridized probe from unhybridized probe. Thereafter, the probe is amplified. Moreover, in specific embodiments, the present invention involves a chimeric probe that is particularly effective when the targeted nucleic acid sequence is short and/or has a relatively low concentration, such as with an miRNA molecule.