The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.
Methods and compositions for generating sequencing reads by partition of origin. One can introduce a unique molecular identifier and bead-specific barcodes to target nucleic acid fragments and the combination of bead-specific barcode, UMI and fragment can be used to identify when multiple bead-specific barcodes originated in the same partition, allowing for improved deconvolution of partition-based sequence analysis.
The present disclosure provides methods and systems for amplifying and analyzing nucleic acid samples. The present disclosure provides methods for preparing cDNA and/or DNA molecules and cDNA and/or DNA libraries using modified reverse transcriptases.
Methods and compositions are provided for improved nucleic acid amplification assays. In some embodiments, the nucleic acid amplification assay is a tagged amplicon primer extension (TAPE) nucleic acid amplification reaction.
C12Q 1/6865 - Amplification à base de promoteurs, p.ex. amplification de séquence d’acide nucléique [NASBA], système de réplication de séquence auto-entretenue [3SR] ou d’amplification à base de transcription [TAS]
C12Q 1/6816 - Tests d’hybridation caractérisés par les moyens de détection
C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
C12Q 1/6848 - Réactions d’amplification d’acides nucléiques caracterisées par les moyens d’empêcher la contamination ou d’augmenter la spécificité ou la sensibilité d’une réaction d’amplification
Methods and compositions comprising primers and probes to detect nucleic acids are provided. The probes comprise a ribonucleotide that can be cleaved by an RNase H2 enzyme when the probe is annealed to a reverse complement of a universal sequence that is introduced to a target nucleic acid, for example via amplification.
The invention provides a method of diagnosing Non-Alcoholic Steatohepatitis (NASH) and/or the hepatic fibrosis status of a subject, especially a subject afflicted with Non-alcoholic fatty liver disease (NAFLD) or NASH, based on the level of only three or more particular biomarkers. The invention further provides a kit suitable for performing said method and the use of said method and methods of treating patients diagnosed in accordance with the disclosed methods.
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
G16B 25/10 - Profilage de l’expression de gènes ou de protéines; Estimation ou normalisation de ratio d’expression
The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.
System, including methods, apparatus, compositions, and kits, for making and using a stabilized emulsion. A method of generating a stabilized emulsion is provided. In the method, an aqueous phase may be provided. The aqueous phase may include an effective concentration of one or more skin-forming proteins. An emulsion may be formed. The emulsion may include droplets of a dispersed phase disposed in a continuous phase, with the aqueous phase being the continuous phase or the dispersed phase. The emulsion may be heated to create an interfacial skin between each droplet and the continuous phase, to transform the droplets into capsules.
C12Q 1/6848 - Réactions d’amplification d’acides nucléiques caracterisées par les moyens d’empêcher la contamination ou d’augmenter la spécificité ou la sensibilité d’une réaction d’amplification
C12Q 1/6816 - Tests d’hybridation caractérisés par les moyens de détection
Methods and systems for thermally controlling a chemical reaction in droplets. In an exemplary method, a first thermal zone and a second thermal zone having different temperatures from one another may be created in a reaction chamber. An emulsion including droplets encapsulated by a carrier fluid may be held in the reaction chamber. The droplets may have a density mismatch with the carrier fluid, and each droplet may include one or more reactants for the chemical reaction. An orientation of the reaction chamber may be changed to move the droplets from the first thermal zone to the second thermal zone, such that a rate of the chemical reaction changes in at least a subset of the droplets.
The digital amplification methods and kits provide the ability to estimate the fetal fraction of cell-free DNA (cfDNA) in a maternal sample, e.g., plasma or serum, by analysis of target sites that are differentially methylated in fetal and maternal cfDNA.
Emulsion compositions are provided herein. Also provided herein are kits containing one or more emulsion compositions or components for making such emulsion compositions. Also provided herein are methods of using such emulsion compositions, such as for amplification of target nucleic acids in emulsion droplets.
C12Q 1/6848 - Réactions d’amplification d’acides nucléiques caracterisées par les moyens d’empêcher la contamination ou d’augmenter la spécificité ou la sensibilité d’une réaction d’amplification
A system and method for SARS-CoV-2 variant classification through mutation detection from qPCR fluorescence signals. The system receives fluorescence signals, wherein a first fluorescence signal indicates quantitative presence of a first genomic region as a control for SARS-CoV-2, and a second fluorescence signal indicates quantitative presence of a second genomic region of a first mutation present in a subset of variants of SARS-CoV-2. The system measures a first Cq for the first fluorescence signal and a second Cq for the second fluorescence signal as the signals cross a threshold RFU. The system calculates a delta Cq as a difference between the two. Further, the system identifies a first peak RFU for the first fluorescence signal and a second peak RFU for the second fluorescence signal, and calculates a RFU ratio of the two. The system detects presence of the first mutation based on the delta Cq and/or the RFU ratio.
C12Q 1/70 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des virus ou des bactériophages
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
15.
SYSTEM AND METHOD FOR TARGET MATERIAL RETRIEVAL FROM MICROWELLS
A system and method for target material retrieval and processing, the system comprising: an adaptor configured to interface with a capture region of a capture substrate for capturing particles in single-particle format within a set of wells, wherein the adaptor comprises a first region configured to interface with the capture region, a second region, and a cavity extending from the first region to the second region; and a support structure coupled to the adaptor and providing a set of operation modes for movement of the adaptor relative to the capture substrate. The system enables methods for magnetic and/or other force-based methods of retrieval of target material (e.g., derived from single cells).
A cell capture system including an array, an inlet manifold, and an outlet manifold. The array includes a plurality of parallel pores, each pore including a chamber and a pore channel, an inlet channel fluidly connected to the chambers of the pores; an outlet channel fluidly connected to the pore channels of the pores. The inlet manifold is fluidly connected to the inlet channel, and the outlet channel is fluidly connected to the outlet channel. A cell removal tool is also disclosed, wherein the cell removal tool is configured to remove a captured cell from a pore chamber.
A clinical diagnostic analyzer for performing an automated crossover study on quality control (QC) material includes a processor, memory, measurement hardware, and an input panel/display. The analyzer prompts a user to load a QC specimen, and to instigate testing and analysis to determine a mean and a standard deviation for the new material. Associated methods for using one or more clinical diagnostic analyzers to calculate a new mean and standard deviation for a new QC material, reduce error in the calculated mean value, and to reduce the total number of days to complete a crossover study are also disclosed.
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet
18.
MODIFICATION OF SURFACE PROPERTIES OF MICROFLUIDIC DEVICES
Compositions, devices, and methods are disclosed for the modification of polymer surfaces with coatings having a dispersion of silicone polymer and hydrophobic silica. The surface coatings provide the polymer surface with high hydrophobicity, as well as increased resistance to biofouling with proteinaceous material. The polymer surfaces can be particularly useful in microfluidic devices and methods that involve the contacting of the covalently modified polymer surfaces with emulsions of aqueous droplets containing biological macromolecules within an oil carrier phase.
C09D 183/00 - Compositions de revêtement à base de composés macromoléculaires obtenus par des réactions créant dans la chaîne principale de la macromolécule une liaison contenant uniquement du silicium, avec ou sans soufre, azote, oxygène ou carbone; Compositions de revêtement à base de dérivés de tels polymères
B81C 1/00 - Fabrication ou traitement de dispositifs ou de systèmes dans ou sur un substrat
19.
METHODS FOR PRODUCING MODIFIED REVERSE TRANSCRIPTASES
The present disclosure provides methods and systems for amplifying and analyzing nucleic acid samples. The present disclosure provides methods for preparing cDNA and/or DNA molecules and cDNA and/or DNA libraries using modified reverse transcriptases.
The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
Systems, including methods and apparatus, for analyzing partitioned samples, such as droplets, using recirculated fluid. The systems may be used to analyze a plurality of partitioned samples, with fluid used with initial samples reused with later samples. This reuse, or recirculation, may reduce the amount of fluid required for performing multiple analyses, with concomitant reductions in costs. Moreover, in some embodiments, it may simplify operation by increasing the number of analyses that may be performed before fluid must be replenished or replaced.
G01N 35/08 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet en utilisant un courant d'échantillons discrets circulant dans une canalisation, p.ex. analyse à injection dans un écoulement
The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.
The subject invention pertains to proteins are purified by a mixed-mode chromatography system formed by attaching a ligand with cation exchange and hydrophobic 1,3-dioxoisoindolin-2-yl group functionalities to a large-pore support matrix, the only linkage between the ligand and the support matrix being a chain having a backbone of one, two, three, four, or five atoms between the hydrophobic group and the support matrix.
B01J 20/285 - Absorbants ou adsorbants poreux à base de polymères
B01J 20/289 - Phases reliées chimiquement à un substrat, p.ex. à de la silice ou à des polymères reliées par l'intermédiaire d'un espaceur
B01J 20/30 - Procédés de préparation, de régénération ou de réactivation
C07K 1/16 - Extraction; Séparation; Purification par chromatographie
B01D 15/38 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction spécifique non couverte par un ou plusieurs des groupes , p.ex. chromatographie d'affinité, chromatographie d'échange par ligand ou chromatographie chirale
B01J 20/28 - Compositions absorbantes ou adsorbantes solides ou compositions facilitant la filtration; Absorbants ou adsorbants pour la chromatographie; Procédés pour leur préparation, régénération ou réactivation caractérisées par leur forme ou leurs propriétés physiques
24.
USE OF HOMOLOGOUS RECOMBINASE TO IMPROVE EFFICIENCY AND SENSITIVITY OF SINGLE CELL ASSAYS
Methods of decreasing bead aggregation and improving specificity of nucleic acid hybridization using non-specific nucleic acid binding proteins is described.
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
C12Q 1/6816 - Tests d’hybridation caractérisés par les moyens de détection
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
The invention generally relates to performing sandwich assays in droplets. In certain embodiments, the invention provides methods for detecting a target analyte that involve forming a compartmentalized portion of fluid including a portion of a sample suspected of containing a target analyte and a sample identifier, a first binding agent having a target identifier, and a second binding agent specific to the target analyte under conditions that produce a complex of the first and second binding agents with the target analyte, separating the complexes, and detecting the complexes, thereby detecting the target analyte.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
B01F 33/3011 - Micromixeurs utilisant des moyens spécifiques pour disposer les écoulements à mélanger, p.ex. des géométries ou des dispositions de canaux utilisant un courant de gainage d'un fluide entourant un courant central d'un autre fluide, p.ex. pour réduire la section transversale du courant central ou pour produire des gouttelettes à partir du courant central
B01F 33/302 - Micromixeurs les matières à mélanger s'écoulant sous forme de gouttelettes
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
C40B 30/04 - Procédés de criblage des bibliothèques en mesurant l'aptitude spécifique à se lier à une molécule cible, p.ex. liaison anticorps-antigène, liaison récepteur-ligand
C40B 40/00 - Bibliothèques en soi, p.ex. matrices, mélanges
C40B 40/04 - Bibliothèques comprenant uniquement des composés organiques
C40B 70/00 - CHIMIE COMBINATOIRE; BIBLIOTHÈQUES, p.ex. CHIMIOTHÈQUES Étiquettes ["tags"] ou marqueurs ["labels"] spécialement adaptés à la chimie combinatoire ou aux chimiothèques, p.ex. "tags" fluorescents ou codes-barres
G01N 33/532 - Production de composés immunochimiques marqués
27.
SYSTEM AND METHOD FOR LEAKAGE CONTROL IN A PARTICLE CAPTURE SYSTEM
A system and method for target material capture, the method comprising: receiving a set of target cells into an array of wells defined at a surface plane of a substrate; receiving a set of particles into the array of wells, thereby co-capturing the set of target cells and the set of particles; achieving a desired state for the array of wells upon receiving a washing fluid into a cavity in communication with the array of wells; receiving a lysis buffer into the cavity; receiving a partitioning fluid into the cavity, thereby displacing the lysis buffer from the cavity and partitioning each of the array of wells from adjacent wells, at the surface plane; and retaining intercellular material of the set of target cells, individually with the set of particles within the array of wells.
Methods of generating a nucleic acid signature for identifying particles associated in a partition are provided. In one aspect, the method comprises: partitioning a sample into a plurality of partitions comprising a particle comprising a solid support surface, the solid support surface having a plurality of oligonucleotide primers conjugated thereon, wherein the oligonucleotide primers comprise a barcode sequence, and wherein the partitions have 0, 1, or more than 1 particles per partition; providing in a partition a substrate comprising a barcode sequence or repeating clonal barcode sequences; and in the partition, associating a first particle conjugated to oligonucleotide primers comprising a first barcode sequence and a second particle conjugated to oligonucleotide primers comprising a second barcode sequence to a barcode sequence from the substrate, thereby generating a nucleic acid signature for the particles in the partition.
Method and system for detecting reverse transcriptase activity of a sample by digital assay. In an exemplary method, a reaction mixture including the sample, an RNA polymer, and reagents for reverse transcription may be prepared. Complementary DNA (cDNA) may be synthesized in the reaction mixture using the RNA polymer as a template. An amount of the cDNA synthesized may be proportional to the reverse transcriptase activity of the sample. Partitions may be formed after synthesizing the cDNA. The partitions may contain copies of the cDNA at partial occupancy. Each partition may include a portion of the reaction mixture. A target representing the cDNA may be amplified in the partitions. Amplification data for the target may be collected from the partitions.
The invention generally relates to methods for quantifying an amount of enzyme molecules. Systems and methods of the invention are provided for measuring an amount of target by forming a plurality of fluid partitions, a subset of which include the target, performing an enzyme-catalyzed reaction in the subset, and detecting the number of partitions in the subset. The amount of target can be determined based on the detected number.
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
C40B 40/04 - Bibliothèques comprenant uniquement des composés organiques
C40B 50/08 - Synthèse en phase liquide, c. à d. dans laquelle tous les blocs servant à créer la bibliothèque sont en phase liquide ou en solution au cours de la création de la bibliothèque; Procédés particuliers de clivage à partir du support liquide
C40B 60/10 - Appareils spécialement adaptés à une utilisation en chimie combinatoire ou avec des bibliothèques pour identifier des éléments des bibliothèques
G01N 33/50 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique
B01F 23/41 - Mélange, p.ex. dispersion ou émulsion, selon les phases à mélanger Émulsion Émulsion
B01F 25/433 - Tubes de mélange dans lesquels la forme du tube influence le mélange, p.ex. tubes de mélange ayant une section transversale variable ou pourvus de profils s'étendant vers l'intérieur
B01F 33/3011 - Micromixeurs utilisant des moyens spécifiques pour disposer les écoulements à mélanger, p.ex. des géométries ou des dispositions de canaux utilisant un courant de gainage d'un fluide entourant un courant central d'un autre fluide, p.ex. pour réduire la section transversale du courant central ou pour produire des gouttelettes à partir du courant central
C12Q 1/25 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des enzymes qui ne peuvent pas être classées dans les groupes
C12Q 1/6804 - Analyse d’acides nucléiques utilisant des immunogènes
C12Q 1/6818 - Tests d’hybridation caractérisés par les moyens de détection impliquant l’interaction de plusieurs marqueurs, p.ex. transfert d’énergie de résonance
C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
G01N 33/542 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec formation d'un complexe immunologique en phase liquide avec inhibition stérique ou modification du signal, p.ex. extinction de fluorescence
G01N 33/573 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet pour enzymes ou isoenzymes
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
32.
METHODS AND HYDROGEL COMPOSITIONS FOR PARTITIONING BIOLOGICAL SAMPLES
Methods of partition-based analysis. In an exemplary method, a device having a port fluidically connected to a chamber may be selected. A sample-containing fluid may be placed into the port. The sample-containing fluid may be moved from the port to the chamber. Partitions of the sample-containing fluid may be formed. A monolayer of the partitions in the chamber may be created. At least a portion of the monolayer may be imaged.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
B01F 23/41 - Mélange, p.ex. dispersion ou émulsion, selon les phases à mélanger Émulsion Émulsion
B01F 33/81 - Combinaisons de mélangeurs similaires, p.ex. avec des dispositifs d'agitation rotatifs dans plusieurs récipients
B01F 33/3011 - Micromixeurs utilisant des moyens spécifiques pour disposer les écoulements à mélanger, p.ex. des géométries ou des dispositions de canaux utilisant un courant de gainage d'un fluide entourant un courant central d'un autre fluide, p.ex. pour réduire la section transversale du courant central ou pour produire des gouttelettes à partir du courant central
B01L 9/00 - Dispositifs de support; Dispositifs de serrage
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
A method comprises providing a microfluidic device including a reservoir; an injection nozzle at the bottom of the reservoir, the injection nozzle being wider at its top than at its bottom; an injection channel below the injection nozzle; and a microfluidic channel below the injection channel. The method further comprises placing fluid in the reservoir, and allowing the fluid to passively flow through the injection nozzle and the injection channel.
Methods, systems, and devices for sampling/isolating material from cells. An exemplary system may comprise a chip including an electrode array of sampling electrodes arranged along a surface of the chip. A cell-receiving area may be located adjacent the surface of the chip. The system also may comprise a tag array of tags supported by the chip and aligned with the electrode array. Each tag of the tag array may include an identifier that is unique to the tag within the tag array. Each tag may be configured to bind nucleic acids, or a capturing agent distinct from the tag may be aligned with each sampling electrode of the electrode array to capture a protein or other analyte of interest. The system further may comprise a control circuit configured to apply an individually controllable voltage to each sampling electrode of the electrode array and measure an electrical property of the sampling electrode.
In one implementation, a microfluidic probe has a non-planar processing surface and an inlet aperture. The shape of the surface may be selected to produce a specific velocity gradient profile across a surface onto which fluid is deposited using the microfluidic probe, for example a constant velocity gradient or a velocity gradient that decreases linearly with distance from the inlet aperture. The microfluidic probe may define and overflow notch in a perimeter edge of the processing surface.
Methods and systems for detecting particles. In an exemplary method, a sample fluid including the particles may be driven from a sample inlet channel, through a confluence region, and into a sample outlet channel defining a longitudinal axis. Focusing fluid may be introduced into the confluence region from at least two focusing channels along respective introduction axes. Introducing may be rotationally asymmetrical about the longitudinal axis. The introduction axes and the longitudinal axis may collectively extend in three dimensions. The particles may be passed through an interrogation zone of the sample outlet channel. The interrogation zone may be irradiated with light. Optical radiation may be detected from the interrogation zone.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
Methods, compositions, and kits for analyzing viral particles. In an exemplary method of analyzing viral particles, capsids of the viral particles may be tagged with a tag. Subsamples of a sample containing the viral particles may be formed. Each subsample of only a subset of the subsamples may include at least one of the viral particles. One or more targets may be amplified from a genome of the viral particles. Tag-related data, and amplification data for the one or more targets, may be collected from the subsamples. In some examples, a capsid occupancy of the viral particles may be determined in a calibration-free approach using the collected data without quantification of the viral particles or capsids thereof.
C12Q 1/70 - Procédés de mesure ou de test faisant intervenir des enzymes, des acides nucléiques ou des micro-organismes; Compositions à cet effet; Procédés pour préparer ces compositions faisant intervenir des virus ou des bactériophages
G01N 33/569 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet pour micro-organismes, p.ex. protozoaires, bactéries, virus
Methods, systems, and computer-readable media for sizing a population of nucleic acid fragments. In an exemplary method of sizing a population of nucleic acid fragments provided by a sample, partitions may be formed, each containing a portion of the sample. Each target of at least two targets may be present in only a fraction of the nucleic acid fragments. Amplification reactions may be performed for each of the at least two targets in the partitions. Amplification data may be collected for the at least two targets from the partitions. Target-defined subsets of the partitions may be enumerated using the amplification data. At least one length characteristic of the population of nucleic acid fragments may be predicted using results of enumerating.
The methods allow for provision of a mixture of a plurality of beads, each bead linked to oligonucleotides, wherein the mixture can be treated as a bulk solution (prior to partitioning) to cleave a covalent bond linking the oligonucleotides to the beads while retaining a non-covalent linkage (via hybridization) between the beads and the oligonucleotides, allowing for distribution of the oligonucleotides and beads to partitions or 2D arrays prior to separation of the oligonucleotides from the beads, which occurs for example in the partitions.
A cell capture system including an array, an inlet manifold, and an outlet manifold. The array includes a plurality of parallel pores, each pore including a chamber and a pore channel, an inlet channel fluidly connected to the chambers of the pores; an outlet channel fluidly connected to the pore channels of the pores. The inlet manifold is fluidly connected to the inlet channel, and the outlet channel is fluidly connected to the outlet channel. A cell removal tool is also disclosed, wherein the cell removal tool is configured to remove a captured cell from a pore chamber.
A cell capture system including an array, an inlet manifold, and an outlet manifold. The array includes a plurality of parallel pores, each pore including a chamber and a pore channel, an inlet channel fluidly connected to the chambers of the pores; an outlet channel fluidly connected to the pore channels of the pores. The inlet manifold is fluidly connected to the inlet channel, and the outlet channel is fluidly connected to the outlet channel. A cell removal tool is also disclosed, wherein the cell removal tool is configured to remove a captured cell from a pore chamber.
G01N 15/00 - Recherche de caractéristiques de particules; Recherche de la perméabilité, du volume des pores ou de l'aire superficielle effective de matériaux poreux
G01N 15/10 - Recherche de particules individuelles
G01N 33/487 - Analyse physique de matériau biologique de matériau biologique liquide
G01N 15/02 - Recherche de la dimension ou de la distribution des dimensions des particules
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet
Method of haplotype analysis. In an exemplary method, an aqueous phase containing nucleic acid may be partitioned into a plurality of discrete volumes. At least one allele sequence may be amplified in the volumes from each of a first polymorphic locus and a second polymorphic locus that exhibit sequence variation in the nucleic acid. At least one measure of co-amplification of allele sequences from both loci in the same volumes may be determined. A haplotype of the first and second loci may be selected based on the at least one measure of co-amplification.
C12Q 1/683 - Tests d’hybridation pour la détection de mutation ou de polymorphisme faisant intervenir des enzymes de restriction, p.ex. polymorphisme de longueur de fragment de resctriction
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
The present invention relates in general to microscopy systems. In particular, the present invention relates to microscopes rendering digital images of samples, with the capability to digitally control the focus of the microscope system, and the software used to control the operation of the digital microscope system. Further, the present invention relates to a microscope structure that allows for compact and multi-functional use of a microscope, providing for light shielding and control with samples that require specific light wavelength characteristics, such as fluorescence, for detection and imaging. The microscope is adjustable, with a structure that can move along range(s) of motion and degree(s) of freedom to allow for ease of access to samples, shielding of samples, and manipulation of a display apparatus.
The invention generally relates to performing sandwich assays in droplets. In certain embodiments, the invention provides methods for detecting a target analyte that involve forming a compartmentalized portion of fluid including a portion of a sample suspected of containing a target analyte and a sample identifier, a first binding agent having a target identifier, and a second binding agent specific to the target analyte under conditions that produce a complex of the first and second binding agents with the target analyte, separating the complexes, and detecting the complexes, thereby detecting the target analyte.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
C40B 40/04 - Bibliothèques comprenant uniquement des composés organiques
C40B 70/00 - CHIMIE COMBINATOIRE; BIBLIOTHÈQUES, p.ex. CHIMIOTHÈQUES Étiquettes ["tags"] ou marqueurs ["labels"] spécialement adaptés à la chimie combinatoire ou aux chimiothèques, p.ex. "tags" fluorescents ou codes-barres
G01N 33/532 - Production de composés immunochimiques marqués
C40B 40/00 - Bibliothèques en soi, p.ex. matrices, mélanges
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
49.
CHROMATOGRAPHY RESIN HAVING AN ANIONIC EXCHANGE-HYDROPHOBIC MIXED MODE LIGAND
B01D 15/36 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction ionique, p.ex. échange d'ions, paire d'ions, suppression d'ions ou exclusion d'ions
The subject application pertains to compositions and methods for enhancing reverse transcriptase (RT) activity and/or reducing the inhibition of RT by inhibitors, such as formalin, tannic acid and/or heparin. In some embodiments, RT inhibition is reduced by the addition of potassium glutamate, histidine hydrochloride monohydrate, poloxamer 188, or any combination thereof to a reaction mixture comprising a polymerase. In other embodiments, RT is enhanced through the addition of a polyvinyl sulfonic acid sodium salt (PVSA) to a reaction mixture. The subject application also provides oligonucleotide primers for use in the reverse transcription of target sequences and its enhancement. These primers have high GC content or low GC content. Methods of using a RT inhibition reducer or a RT enhancer in a composition with an RNA template and RT improves RT yield, RT sensitivity, or RT tolerance to various chemicals are also provided.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/541 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec formation d'un complexe immunologique en phase liquide avec séparation du complexe immunologique de l'antigène ou de l'anticorps non liés faisant intervenir un réactif de précipitation faisant intervenir un double ou un deuxième anticorps
52.
COMPUTER VISION FOR REAL-TIME SEGMENTATION OF FLUORESCENT BIOLOGICAL IMAGES
A segmentation system processes images of a sample that includes fluorescent entities. The segmentation system applies a threshold image that represents background illumination distinct from fluorescence of target entities to pre-process the images. The segmentation system determines numbers of target entities in pre-processed images and determines whether an estimated number of target entities in the sample meets a threshold certainty. The segmentation system continues to analyze one or more images until the threshold certainty is determined. When the threshold certainty is met, the estimated number of target entities may be used to generate a user interface output (e.g., displaying the pre-processed images and visual indicators of the locations of target entities.
Methods and compositions for determining the proximity of two barcoding oligonucleotides (e.g., in a single partition or adjacent on a tissue section) using a determination of the presence of a 9 bp sequence resulting from tagmentation in different nucleic acid fragments linked to different barcoding oligonucleotides is provided.
The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
C12Q 1/6804 - Analyse d’acides nucléiques utilisant des immunogènes
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
C40B 50/08 - Synthèse en phase liquide, c. à d. dans laquelle tous les blocs servant à créer la bibliothèque sont en phase liquide ou en solution au cours de la création de la bibliothèque; Procédés particuliers de clivage à partir du support liquide
The present invention generally relates to droplet libraries and to systems and methods for the formation of libraries of droplets. The present invention also relates to methods utilizing these droplet libraries in various biological, chemical, or diagnostic assays.
B01F 23/41 - Mélange, p.ex. dispersion ou émulsion, selon les phases à mélanger Émulsion Émulsion
C40B 50/08 - Synthèse en phase liquide, c. à d. dans laquelle tous les blocs servant à créer la bibliothèque sont en phase liquide ou en solution au cours de la création de la bibliothèque; Procédés particuliers de clivage à partir du support liquide
G01N 33/50 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique
C40B 40/04 - Bibliothèques comprenant uniquement des composés organiques
B01J 19/00 - Procédés chimiques, physiques ou physico-chimiques en général; Appareils appropriés
B01F 25/433 - Tubes de mélange dans lesquels la forme du tube influence le mélange, p.ex. tubes de mélange ayant une section transversale variable ou pourvus de profils s'étendant vers l'intérieur
G01N 15/14 - Recherche par des moyens électro-optiques
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
B01F 33/3011 - Micromixeurs utilisant des moyens spécifiques pour disposer les écoulements à mélanger, p.ex. des géométries ou des dispositions de canaux utilisant un courant de gainage d'un fluide entourant un courant central d'un autre fluide, p.ex. pour réduire la section transversale du courant central ou pour produire des gouttelettes à partir du courant central
B01L 7/00 - Appareils de chauffage ou de refroidissement; Dispositifs d'isolation thermique
B01F 101/23 - Mélange d'échantillons de laboratoire, p.ex. en vue d'analyser ou de tester les propriétés des matières
G01N 15/10 - Recherche de particules individuelles
Systems and methods for contact imaging of stands with illumination are disclosed herein. A contact imaging system can include a contact imager. The contact imager can include a housing having a base and a lid. The lid can have a closed position against the base and an open position. The contact imager can include a contact area image sensor. The lid can shield the contact area image sensor from ambient light when the lid is in the closed position. The contact imager can include an illuminator that can illuminate at least a portion of a blot on the contact area image sensor when the lid is in the closed position.
H04N 1/10 - Dispositions de balayage employant des supports d'images plans
H04N 1/028 - Balayage, transmission ou reproduction de documents ou similaires, p.ex. transmission de fac-similés; Leurs détails - Détails des têtes de balayage pour la lecture d'images
G06T 5/50 - Amélioration ou restauration d'image en utilisant plusieurs images, p.ex. moyenne, soustraction
Systems and methods for multiplex detection through measurement of localized fluorescence ratios are disclosed herein. This can include creating a plurality of capture structures that each include a detection portion that can couple with a target analyte and a stem that can include a capture structure code uniquely identifying a type of the capture structure. The capture structures can be attached to a sample surface and mixed with a sample containing a plurality of target analytes. A location and the capture structure code of each of the capture structures can be determined. A location at which a target analyte is bound to one of the capture structures can be identified, and the target analyte can be determined based on the capture structure code of the capture structure at the location at which the target analyte is bound to one of the capture structures.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
Inventions covered include methods, systems, and compositions for sample processing, involving morphology-adjustable (e.g., tunable on-demand) functionalized particles. In some embodiments, a method can include distributing a set of functionalized particles, in a first morphological state, across a set of partitions; transitioning the set of functionalized particles, at the set of partitions, from the first morphological state to a second morphological state; transitioning the set of functionalized particles, at the set of partitions, from the second morphological state to a third morphological state, and inducing interactions between the set of functionalized particles and a set of targets, within the set of partitions and according to a set of operations with a set of process fluids.
A system and method for automated single cell capture and processing is described, where the system includes a deck supporting and positioning a set of sample processing elements; a gantry for actuating tools for interactions with the set of sample processing elements supported by the deck; and a base supporting various processing subsystems and a control subsystems in communication with the processing subsystems. The system can automatically execute workflows associated with single cell processing, including mRNA capture, cDNA synthesis, protein-associated assays, and library preparation, for next generation sequencing.
B01L 9/02 - Paillasses ou tables de laboratoire; Leurs garnitures
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet
A circuit for sharing current between parallel LEDs or parallel strings of LEDs, and a method of use of the same, are disclosed herein. The circuit for sharing current between parallel LED pathways can include a first LED pathway, a first transistor coupled to the first set of LEDs and that can control a first current through the first set of LEDs, and a first measurement node having a first sensed voltage. The circuit can include a second LED pathway, a second transistor coupled to the second set of LEDs and that can control a second current through the second set of LEDs, and a second measurement node having a second sensed voltage. The circuit includes a first differential amplifier and a second differential amplifier, each of which can compare sensed voltage and can apply a voltage to a gate of one of the first and second transistors.
H05B 45/46 - Circuits pour faire fonctionner des diodes électroluminescentes [LED] - Détails des circuits de charge à LED avec un contrôle actif à l'intérieur d'une matrice de LED les diodes étant disposées parallèlement
A heat pump that includes a thermoelectric device(s) and a heat sink having a raised portion with a top surface for thermally coupling with a planar face of the thermoelectric device(s). The raised portion of the heat sink includes an outer periphery and a raised central region surrounded by a void region to provide more uniform thermal conductivity when clamped within an assembly. The raised central region is shaped in an any shape corresponding to a shape of uneven thermal conductivity due to clamping pressure applied to the heat sink. The void region can be substantially contiguous and entirely circumscribe the central raised region. The device can optionally include discrete supports formed of a less thermally-conductive material within the void region. The supports can be elastomeric, such as O-rings, and disposed within pockets defined within the void region.
F25B 21/04 - Machines, installations ou systèmes utilisant des effets électriques ou magnétiques utilisant l'effet Nernst-Ettinghausen réversibles
B01L 7/00 - Appareils de chauffage ou de refroidissement; Dispositifs d'isolation thermique
H10N 10/10 - Dispositifs thermoélectriques comportant une jonction de matériaux différents, c. à d. dispositifs présentant l'effet Seebeck ou l'effet Peltier fonctionnant exclusivement par les effets Peltier ou Seebeck
H10N 10/80 - Dispositifs thermoélectriques comportant une jonction de matériaux différents, c. à d. dispositifs présentant l'effet Seebeck ou l'effet Peltier - Détails de structure
63.
METHODS AND COMPOSITIONS FOR GENOTYPING AND PHENOTYPING CELLS
The subject invention pertains to mixed mode chromatography ligands and chromatography matrices suitable for the purification of proteins from biological sources or biological samples. Methods of making chromatography matrices comprising the disclosed ligands and using the disclosed chromatography matrices are also provided.
A fluorescence detection system, including apparatus and methods, suitable for qPCR and other fluorescence-based analyses. The system may comprise various components, including a stage, an illumination module, a detection module, and an optical relay structure. The stage may be configured to support a sample holder. The illumination module may include one or more discrete light sources configured to produce excitation light. The detection module may be configured to detect fluorescence emission light produced, in response to the excitation light, by a fluorescent sample positioned in the sample holder. The optical relay structure may include a beamsplitter assembly configured to direct the excitation light from the illumination module along an illumination path to the sample holder and to direct the fluorescence emission light from the sample holder along a response path to the imaging module. The system may enhance the quality of excitation light hitting samples in the sample holder.
G01N 21/71 - Systèmes dans lesquels le matériau analysé est excité de façon à ce qu'il émette de la lumière ou qu'il produise un changement de la longueur d'onde de la lumière incidente excité thermiquement
This disclosure pertains to a consumable product (microplate) suitable for use in assays utilizing single-molecule recognition through equilibrium Poisson sampling (SiMREPS) and in other assays employing total internal reflection fluorescence (TIRF) or HiLo microscopy. The disclosed microplate is also suitable for use in other high throughput assay systems, such as single-molecule FRET, ligand-receptor binding studies, membrane biology assays, cell-based TIRF and near-TIRF assays. The disclosure further pertains to the use of the microfluidic microplate for the detection of analytes, including nucleic acids, polypeptides, carbohydrates, lipids, post-translational modifications, amino acids, metabolites, and small molecules.
An electronic component assembly having thermal pads with thermal vias coupling an image sensor and a camera board fab is provided for heat dissipation. The electronic component assembly can include: a circuit board having at least one thermal pad disposed on a top surface of the circuit board; and an image sensor disposed on the top surface of the circuit board, having at least one conductive pad disposed at at least one corner of the image sensor. The at least one thermal pad is coupled to the at least one conductive pad of the image sensor and the at least one thermal pad is formed with a plurality of first thermal vias penetrating the thermal pad and the circuit board for transfer of heat of the image sensor.
H04N 5/335 - Transformation d'informations lumineuses ou analogues en informations électriques utilisant des capteurs d'images à l'état solide [capteurs SSIS]
H04N 23/52 - Caméras ou modules de caméras comprenant des capteurs d'images électroniques; Leur commande - Détails de structure Éléments optimisant le fonctionnement du capteur d'images, p. ex. pour la protection contre les interférences électromagnétiques [EMI] ou la commande de la température par des éléments de transfert de chaleur ou de refroidissement
H04N 23/55 - Pièces optiques spécialement adaptées aux capteurs d'images électroniques; Leur montage
H05K 7/20 - Modifications en vue de faciliter la réfrigération, l'aération ou le chauffage
A container assembly for use with a high-pressure liquid chromatography (HPLC) instrument is disclosed, in which the container assembly, when coupled to a source of pressurized gas, provides fluid medium to the HPLC instrument at positive pressure. The container assembly has an external exterior container shell, an internal fluid container for holding fluid medium, an interstitial volume between the external exterior container shell and the internal fluid container, a port for fluidly connecting the volume to a pressurized gas source, and a port for fluidly connecting the internal fluid container to the HPLC instrument. As a pressurized gas in the interstitial volume increases, fluid medium flows out of the port connected to the internal fluid bag and container assembly at a positive pressure. A system incorporating the container assembly, and method of use of the same, are also disclosed.
G01N 30/32 - Contrôle des paramètres physiques du fluide vecteur de la pression ou de la vitesse
B67D 7/02 - Appareils ou dispositifs pour transférer des liquides à partir de récipients ou de réservoirs de stockage en vrac vers des véhicules ou des récipients portables, p.ex. pour la vente au détail pour transférer des liquides autres que des carburants ou des lubrifiants
The invention(s) cover systems and methods for target detection in a multiplexed and rapid manner. Embodiments of the system can include: a base substrate; and an array of sample processing regions defined at a broad surface of the base substrate, wherein each of the array of sample processing regions includes: a set of microwell subarrays arranged in a gradient by volumetric capacity between an upstream end and a downstream end of each respective sample processing region, and a boundary separating each respective sample processing region from adjacent sample processing regions. The system can support methods, with example implementation by an automated platform, for returning preliminary results from a subset of microwells of the samples processing regions, as well as results pertaining to specific and non-specific amplification, for multiple targets of a sample.
Aspects of the present disclosure relate to systems and methods for generating a composite image. This can include a western blot imager with a real time camera. One aspect of the present disclosure relates to an imaging system. The imaging system includes a sample plane that can receive and hold a sample, a photon resolving camera, and a lens attached to the photon resolving camera, the photon resolving camera and the lens positioned to image the sample plane.
G06T 5/50 - Amélioration ou restauration d'image en utilisant plusieurs images, p.ex. moyenne, soustraction
G06V 10/60 - Extraction de caractéristiques d’images ou de vidéos relative aux propriétés luminescentes, p.ex. utilisant un modèle de réflectance ou d’éclairage
G01N 33/68 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des protéines, peptides ou amino-acides
The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, methods of the invention involve forming sample droplets containing, on average, a single target nucleic acid, amplifying the target in the droplets, excluding droplets containing amplicon from the target and amplicon from a variant of the target, and analyzing target amplicons.
Systems and methods for detection of a signal from droplets of an emulsion. An exemplary system may comprise a fluid transporter having a tube with an open end for aspirating droplets, a singulator to arrange the droplets in single file and to space the single-file droplets from one another, and a detection channel in optical communication with a detector configured to detect a signal from droplets. In some embodiments, the singulator may have a channel junction at which a stream of droplets in single file is combined with a stream of spacing fluid, and a tapered spacing channel extending downstream from the channel junction toward the detection channel. In some embodiments, the fluid transporter may suck droplet-containing fluid and spacing fluid through the detection channel from respective sources. In some embodiments, droplets may be subjected to a disaggregation routine before they are passed through the detection channel.
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
G01N 15/14 - Recherche par des moyens électro-optiques
C12Q 1/6848 - Réactions d’amplification d’acides nucléiques caracterisées par les moyens d’empêcher la contamination ou d’augmenter la spécificité ou la sensibilité d’une réaction d’amplification
This invention describes a method for preparation of stable hematology reference materials by producing synthetic hydrogel blood cell surrogates, which mimic human blood components in size, morphology, performance and functionality when analyzed using an automated hematology analyzer employing multiple detection technologies. Different hydrogel particles can be combined and mixed to prepare multi-parameter and multi-level hematology reference materials, which could be used for calibration, linearity verification, proficiency evaluation, and routine performance monitoring of modern automated hematology analyzers. These hydrogel particles can also be combined with processed and stabilized human blood components to prepare the reference materials of this invention.
G01N 33/96 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir un étalon de contrôle du sang ou du sérum
Digital assay system, including methods, apparatus, and compositions, for assay of one or more targets in a set of partitions containing a generic reporter of target amplification.
A system and method for receiving and delivering a fluid, the system comprising: a body configured to interface with an opening of a reservoir and defining: a protrusion defining a set position of the body relative to the reservoir; a wall extending from the protrusion; a receiving surface coupled to the wall and sloping from an apex to a nadir along a first direction, the receiving surface comprising a vent; and an outlet positioned closer to the nadir than the apex of the receiving surface and displaced from the vent, the outlet comprising an extension from the body, the extension configured to contact an interior wall of the reservoir, wherein the body comprises: a bubble-mitigating operation mode in which the receiving surface receives and transmits the fluid along the receiving surface, and a fluid-transmitting operation mode in which the body directs the fluid along the interior wall of the reservoir.
A system and method for target material capture, the method comprising: receiving a set of target cells into an array of wells defined at a surface plane of a substrate; receiving a set of particles into the array of wells, thereby co-capturing the set of target cells and the set of particles; achieving a desired state for the array of wells upon receiving a washing fluid into a cavity in communication with the array of wells; receiving a lysis buffer into the cavity; receiving a partitioning fluid into the cavity, thereby displacing the lysis buffer from the cavity and partitioning each of the array of wells from adjacent wells, at the surface plane; and retaining intercellular material of the set of target cells, individually with the set of particles within the array of wells.
Disclosed is an adjustable mirror mount that is capable of adjusting a mirror in two axes with a high degree of precision and low cross-coupling. Long horizontal and vertical adjustment arms are used to allow the precision adjustment about both a horizontal axis and a vertical axis.
G02B 7/182 - Montures, moyens de réglage ou raccords étanches à la lumière pour éléments optiques pour miroirs pour miroirs
G02B 26/08 - Dispositifs ou dispositions optiques pour la commande de la lumière utilisant des éléments optiques mobiles ou déformables pour commander la direction de la lumière
G02B 27/14 - Systèmes divisant ou combinant des faisceaux fonctionnant uniquement par réflexion
The subject invention pertains to the detection and differentiation of genetic variations by nucleic acid amplification. The invention provides methods of detecting one or more genetic variations in a nucleic acid that are in close proximity simultaneously. The invention further provides primer and probe oligonucleotides and methods of using said primers and probes in assays to detect genetic variants of concern of SARS-CoV-2. The methods of the invention detect genetic variants of other pathogens, including influenza, or genetic variants involved in inheritable diseases or cancer.
C12Q 1/6827 - Tests d’hybridation pour la détection de mutation ou de polymorphisme
C12Q 1/6883 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
80.
System and method for isolating and analyzing cells
A system and method, wherein the system includes: an array of wells defined at a substrate, each well including an open surface and a well cavity and a fluid delivery module including a fluid pathway through which fluid flow is controlled along a fluid path in a direction parallel to the broad face of the substrate; and wherein the method includes: generating a set of genetic complexes within individual wells of the array of wells.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
C12M 1/00 - Appareillage pour l'enzymologie ou la microbiologie
G01N 33/574 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet pour le cancer
C12Q 1/6816 - Tests d’hybridation caractérisés par les moyens de détection
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/569 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet pour micro-organismes, p.ex. protozoaires, bactéries, virus
G01N 15/14 - Recherche par des moyens électro-optiques
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
G01N 15/10 - Recherche de particules individuelles
A reagent sleeve system such as can be used with various analyzers using chemical phenomena, analyzers and methods of using the reagent sleeve system and analyzer are described. The reagent sleeve system can include a reagent sleeve; and a plurality of removable reagent reservoirs located within the reagent sleeve, wherein each of the plurality of removable reagent reservoirs comprises a respective peripheral wall, and first and second end walls, whereby each of the plurality of removable reagent reservoirs contains a reagent located therein, and the first end wall is pierceable by a reagent extractor, and the reagent sleeve comprises a peripheral wall that encompasses the plurality of removable reagent reservoirs and holds the plurality of reagent reservoirs for sequential use.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
G01N 35/10 - Dispositifs pour transférer les échantillons vers, dans ou à partir de l'appareil d'analyse, p.ex. dispositifs d'aspiration, dispositifs d'injection
Systems for protein quantitation using a Fabry-Perot interferometer. In one arrangement, a quantitation device includes an infrared source, a sample holder, and a Fabry-Perot interferometer positioned to receive infrared radiation from the source passing through a sample on the sample holder. A band pass optical filter sets the working range of the interferometer, and radiation exiting the interferometer falls on a detector that produces a signal indicating the intensity of the received radiation. A controller causes the interferometer to be tuned to a number of different resonance wavelengths and receives the intensity signals, for determination of an absorbance spectrum.
G01N 21/31 - Couleur; Propriétés spectrales, c. à d. comparaison de l'effet du matériau sur la lumière pour plusieurs longueurs d'ondes ou plusieurs bandes de longueurs d'ondes différentes en recherchant l'effet relatif du matériau pour les longueurs d'ondes caractéristiques d'éléments ou de molécules spécifiques, p.ex. spectrométrie d'absorption atomique
G01N 21/3577 - Couleur; Propriétés spectrales, c. à d. comparaison de l'effet du matériau sur la lumière pour plusieurs longueurs d'ondes ou plusieurs bandes de longueurs d'ondes différentes en recherchant l'effet relatif du matériau pour les longueurs d'ondes caractéristiques d'éléments ou de molécules spécifiques, p.ex. spectrométrie d'absorption atomique en utilisant la lumière infrarouge pour l'analyse de liquides, p.ex. l'eau polluée
G01N 21/3563 - Couleur; Propriétés spectrales, c. à d. comparaison de l'effet du matériau sur la lumière pour plusieurs longueurs d'ondes ou plusieurs bandes de longueurs d'ondes différentes en recherchant l'effet relatif du matériau pour les longueurs d'ondes caractéristiques d'éléments ou de molécules spécifiques, p.ex. spectrométrie d'absorption atomique en utilisant la lumière infrarouge pour l'analyse de solides; Préparation des échantillons à cet effet
83.
MICROFLUIDIC SYSTEMS AND METHODS FOR REDUCING THE EXCHANGE OF MOLECULES BETWEEN DROPLETS
The present invention generally relates to systems and methods to create stable emulsions with low rates of exchange of molecules between microdroplets.
Comparison of common sequencing reads from sequencing based on partition-based barcoding can be used to improve sequencing results. Increased loading of barcodes per partition can also improve sequencing results.
A system and method for isolating and analyzing single cells, including: a substrate having a broad surface; a set of wells defined at the broad surface of the substrate, and a set of channels, defined by the wall, that fluidly couple each well to at least one adjacent well in the set of wells; and fluid delivery module defining an inlet and comprising a plate, removably coupled to the substrate, the plate defining a recessed region fluidly connected to the inlet and facing the broad surface of the substrate, the fluid delivery module comprising a cell capture mode.
G01N 1/28 - Préparation d'échantillons pour l'analyse
C12M 1/00 - Appareillage pour l'enzymologie ou la microbiologie
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
G01N 35/10 - Dispositifs pour transférer les échantillons vers, dans ou à partir de l'appareil d'analyse, p.ex. dispositifs d'aspiration, dispositifs d'injection
G01N 35/00 - Analyse automatique non limitée à des procédés ou à des matériaux spécifiés dans un seul des groupes ; Manipulation de matériaux à cet effet
G06V 10/145 - Caractéristiques optiques de l’appareil qui effectue l’acquisition ou des dispositifs d’éclairage Éclairage spécialement adapté à la reconnaissance de formes, p.ex. utilisant des réseaux
G06V 10/147 - Caractéristiques optiques de l’appareil qui effectue l’acquisition ou des dispositifs d’éclairage - Détails de capteurs, p.ex. lentilles de capteurs
A cell capture system including an array, an inlet manifold, and an outlet manifold. The array includes a plurality of parallel pores, each pore including a chamber and a pore channel, an inlet channel fluidly connected to the chambers of the pores; an outlet channel fluidly connected to the pore channels of the pores. The inlet manifold is fluidly connected to the inlet channel, and the outlet channel is fluidly connected to the outlet channel. A cell removal tool is also disclosed, wherein the cell removal tool is configured to remove a captured cell from a pore chamber.
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
88.
METHODS AND COMPOSITIONS FOR DETECTING GENETIC MATERIAL
The present disclosure provides methods and compositions for detecting polynucleotides in a sample and for quantifying polynucleotide load in a sample. The polynucleotides can be associated with a disease, disorder, or condition. In some applications, methylated DNA is quantified, e.g., in order to determine the load of polynucleotides in a sample. The present disclosure also provides methods and compositions for determining the load of fetal polynucleotides in a biological sample, e.g., the load of fetal polynucleotides (e.g., DNA, RNA) in maternal plasma. The present disclosure provides methods and compositions for detecting cellular processes such as cellular viability, growth rates, and infection rates. This disclosure also provides compositions and methods for detecting differences in copy number of a target polynucleotide. In some embodiments, the methods and compositions provided herein are useful for diagnosis of fetal genetic abnormalities, when the starting sample is maternal tissue (e.g., blood, plasma). The methods and materials described apply techniques for allowing detection of small, but statistically significant, differences in polynucleotide copy number.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
B01L 9/00 - Dispositifs de support; Dispositifs de serrage
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
B01F 23/41 - Mélange, p.ex. dispersion ou émulsion, selon les phases à mélanger Émulsion Émulsion
B01F 33/81 - Combinaisons de mélangeurs similaires, p.ex. avec des dispositifs d'agitation rotatifs dans plusieurs récipients
B01F 33/3011 - Micromixeurs utilisant des moyens spécifiques pour disposer les écoulements à mélanger, p.ex. des géométries ou des dispositions de canaux utilisant un courant de gainage d'un fluide entourant un courant central d'un autre fluide, p.ex. pour réduire la section transversale du courant central ou pour produire des gouttelettes à partir du courant central
89.
METHODS AND COMPOSITIONS FOR DETECTING GENETIC MATERIAL
This invention provides compositions and methods for detecting differences in copy number of a target polynucleotide. In some cases, the methods and compositions provided herein are useful for diagnosis of fetal genetic abnormalities, when the starting sample is maternal tissue (e.g., blood, plasma). The methods and materials described apply techniques for allowing detection of small, but statistically significant, differences in polynucleotide copy number.
B01L 3/00 - Récipients ou ustensiles pour laboratoires, p.ex. verrerie de laboratoire; Compte-gouttes
B01L 9/00 - Dispositifs de support; Dispositifs de serrage
C12Q 1/686 - Réaction en chaine par polymérase [PCR]
B01F 23/41 - Mélange, p.ex. dispersion ou émulsion, selon les phases à mélanger Émulsion Émulsion
B01F 33/81 - Combinaisons de mélangeurs similaires, p.ex. avec des dispositifs d'agitation rotatifs dans plusieurs récipients
B01F 33/3011 - Micromixeurs utilisant des moyens spécifiques pour disposer les écoulements à mélanger, p.ex. des géométries ou des dispositions de canaux utilisant un courant de gainage d'un fluide entourant un courant central d'un autre fluide, p.ex. pour réduire la section transversale du courant central ou pour produire des gouttelettes à partir du courant central
The present disclosure relates to the development of novel immunoassays for the detection of SARS-CoV-2 or secreted spike protein (or fragments thereof) in saliva, nasal mucosal sample, throat samples, or nasopharyngeal samples.
G01N 33/569 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet pour micro-organismes, p.ex. protozoaires, bactéries, virus
G01N 33/573 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet pour enzymes ou isoenzymes
G01N 33/62 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir l'urée
G01N 33/533 - Production de composés immunochimiques marqués avec un marqueur fluorescent
The subject invention pertains to proteins are purified by a mixed-mode chromatography system formed by attaching a ligand with cation exchange and hydrophobic 1,3-dioxoisoindolin-2-yl group functionalities to a large-pore support matrix, the only linkage between the ligand and the support matrix being a chain having a backbone of one, two, three, four, or five atoms between the hydrophobic group and the support matrix.
B01J 20/28 - Compositions absorbantes ou adsorbantes solides ou compositions facilitant la filtration; Absorbants ou adsorbants pour la chromatographie; Procédés pour leur préparation, régénération ou réactivation caractérisées par leur forme ou leurs propriétés physiques
B01D 15/38 - Adsorption sélective, p.ex. chromatographie caractérisée par le mécanisme de séparation impliquant une interaction spécifique non couverte par un ou plusieurs des groupes , p.ex. chromatographie d'affinité, chromatographie d'échange par ligand ou chromatographie chirale
B01J 20/30 - Procédés de préparation, de régénération ou de réactivation
C07K 1/16 - Extraction; Séparation; Purification par chromatographie
B01J 20/285 - Absorbants ou adsorbants poreux à base de polymères
B01J 20/289 - Phases reliées chimiquement à un substrat, p.ex. à de la silice ou à des polymères reliées par l'intermédiaire d'un espaceur
The invention generally relates to droplet based digital PCR and methods for analyzing a target nucleic acid using the same. In certain embodiments, a method for determining the nucleic acid make-up of a sample is provided.
A thermal management system that include an electronic circuit boards having at least two circuit boards with a space in between and further includes one or more air tubes or conduits. The electronic circuit board and air tubes are configured for drawing air into the space to facilitate cooling of the electronic circuit board concurrent with cooling of a heat sink of a heat pump connected with the electronic circuit board. The system can further include a partition to isolate airflow from the heat sink from airflow through the electronics circuit board, and can further include one or more interface components for maintaining isolation and control of air flow, improving air intake and/or supporting auxiliary components.
A dynamic axial compression column is disclosed herein. This dynamic axial column utilized external compression to prevent the creation of end plate space in the column. The dynamic axial column can include a tube defining a first opening, a second opening, and a lumen extending there between. The dynamic axial column can include a first end plate assembly sealing the first opening and movably extending at least partially into the lumen via the first opening, a second end plate assembly sealing the second opening, a plurality of rods extending along the outside of the tube and connecting the first end plate assembly and the second end plate assembly, and a first plurality of compression devices external to the tube and engaging one of the plurality of rods to bias the first end plate assembly towards the second end plate assembly.
B01D 15/22 - Adsorption sélective, p.ex. chromatographie caractérisée par des caractéristiques de structure ou de fonctionnement relatives à la structure de la colonne
A system for imaging captured cells comprising: an illumination module configured to illuminate a target object; a platform configured to position the target object in relation to the illumination module; a filter module configured to filter light transmitted to the target object and/or to filter light received from the target object, an optical sensor configured to receive light from the target object and to generate image data; and a focusing and optics module configured to manipulate light transmitted to the optical sensor. The system can further comprise one or more of: a control system configured to control at least one of the illumination module, the platform, the focusing and optics module, the filter module, and the optical sensor; a tag identifying system configured to identify and communicate tag information from system elements; a thermal control module configured to adjust temperature parameters of the system; and an image stabilization module.
G01N 21/25 - Couleur; Propriétés spectrales, c. à d. comparaison de l'effet du matériau sur la lumière pour plusieurs longueurs d'ondes ou plusieurs bandes de longueurs d'ondes différentes
A system and method for capturing and analyzing a set of cells, comprising: an array including a set of parallel pores, each pore including a chamber including a chamber inlet and a chamber outlet, and configured to hold a single cell, and a pore channel fluidly connected to the chamber outlet; an inlet channel fluidly connected to each chamber inlet of the set of parallel pores; an outlet channel fluidly connected to each pore channel of the set of parallel pores; a set of electrophoresis channels fluidly coupled to the outlet channel, configured to receive a sieving matrix for electrophoretic separation; and a set of electrodes including a first electrode and a second electrode, wherein the set of electrodes is configured to provide an electric field that facilitates electrophoretic analysis of the set of cells.
Methods and compositions for characterizing a biological sample (e.g., comprising an infectious agent) from a subject are provided. Methods can include detecting linkage of nucleic acids that are linked in a viable cell or organism but that become degraded and thus unlinked in inviable cells or organisms and then characterizing the subject based on the quantity of linked and unlinked sequences.
C12Q 1/6888 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour la détection ou l’identification d’organismes
98.
SYSTEM AND METHOD FOR ISOLATING AND ANALYZING CELLS
A system and method for isolating cells, comprising: a substrate having a broad surface; an array comprising a set of wells defined at the broad surface of the substrate, each well including: a base surface, an open surface directly opposing the base surface, defined at the broad surface of the substrate, and configured to receive one of a single cell and a single cluster of cells from a direction perpendicular to the broad surface of the substrate, and a set of channels that fluidly couple each well to at least one adjacent well; wherein the set of wells includes an interior subset and an exterior subset fluidly coupled to and surrounding the interior subset by way of the set of channels; and a fluid delivery module surrounding the array and fluidly coupled to each well in the set of wells.
C12Q 1/6886 - Produits d’acides nucléiques utilisés dans l’analyse d’acides nucléiques, p.ex. amorces ou sondes pour les maladies provoquées par des altérations du matériel génétique pour le cancer
A system and method for isolating and analyzing single cells, comprising: a substrate having a broad surface; a set of wells defined at the broad surface of the substrate, and a set of channels, defined by the wall, that fluidly couple each well to at least one adjacent well in the set of wells; and fluid delivery module defining an inlet and comprising a plate, removably coupled to the substrate, the plate defining a recessed region fluidly connected to the inlet and facing the broad surface of the substrate, the fluid delivery module comprising a cell capture mode.
The invention provides barcode libraries and methods of making and using them including obtaining a plurality of nucleic acid constructs in which each construct comprises a unique N-mer and a functional N-mer and segregating the constructs into a fluid compartments such that each compartment contains one or more copies of a unique construct. The invention further provides methods for digital PCR and for use of barcode libraries in digital PCR.
C12Q 1/6806 - Préparation d’acides nucléiques pour analyse, p.ex. pour test de réaction en chaîne par polymérase [PCR]
C40B 50/08 - Synthèse en phase liquide, c. à d. dans laquelle tous les blocs servant à créer la bibliothèque sont en phase liquide ou en solution au cours de la création de la bibliothèque; Procédés particuliers de clivage à partir du support liquide
C12Q 1/6874 - Méthodes de séquençage faisant intervenir des réseaux d’acides nucléiques, p.ex. séquençage par hybridation [SBH]
G01N 33/543 - Tests immunologiques; Tests faisant intervenir la formation de liaisons biospécifiques; Matériaux à cet effet avec un support insoluble pour l'immobilisation de composés immunochimiques
G01N 33/58 - Analyse chimique de matériau biologique, p.ex. de sang ou d'urine; Test par des méthodes faisant intervenir la formation de liaisons biospécifiques par ligands; Test immunologique faisant intervenir des substances marquées
C12Q 1/6804 - Analyse d’acides nucléiques utilisant des immunogènes
C12N 15/10 - Procédés pour l'isolement, la préparation ou la purification d'ADN ou d'ARN
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