This disclosure provides a novel approach to training clinical diagnostic models using synthetic data generated by an artificial intelligence (Al) model. The disclosed models demonstrate several advantages, including: reducing time, cost, and complexity associated with traditional data collection and labeling. Additionally, the disclosed models address privacy and data management issues and allow for the inclusion of rare or novel cases in the training set.
G01N 33/80 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood groups or blood types
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
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 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6816 - Hybridisation assays characterised by the detection means
Methods and compositions are provided for detecting multiple barcodes in a partition for sequencing applications. Bead-specific barcoding oligonucleotides and/or detection oligonucleotides are used to introduce a bead-specific barcode sequence and a universal adapter sequence to target sequences from a single cell or nucleus. Also provided are beads comprising one or more bead-specific barcoding nucleic acids. In addition, the disclosure provides a plurality of partitions that include a single cell or nucleus or nucleic acids from a single cell or nucleus, beads comprising one or more bead-specific barcoding oligonucleotides, and a DNA polymerase.
Disclosed herein are cfDNA-like DNA fragments and broadly applicable methods to prepare cfDNA-like DNA fragments which produce a high yield and/or large quantities of cfDNA-like DNA fragments. The cfDNA-like DNA fragments produced according to the methods of the disclosure accurately capture the size distribution and diagnostic assay performance of natural cfDNA, and may therefore be used for assay methodological validation, internal assay quality control and external assay quality evaluation with high reproducibility and consistency.
Method of analysis. In the method, a microfluidic device defining a flow path extending from an inlet to an outlet may be selected. A sample-containing fluid may be introduced into the flow path via the inlet. Volumes of the sample-containing fluid may be isolated from one another on the flow path. A two-dimensional monolayer of the volumes may be imaged. The two-dimensional monolayer may be formed along the flow path between the inlet and the outlet.
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
G01N 21/3563 - Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solidsPreparation of samples therefor
G01N 21/49 - Scattering, i.e. diffuse reflection within a body or fluid
The present invention provides novel microfluidic substrates and methods that are useful for performing biological, chemical and diagnostic assays. The substrates can include a plurality of electrically addressable, channel bearing fluidic modules integrally arranged such that a continuous channel is provided for flow of immiscible fluids.
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
B01J 19/00 - Chemical, physical or physico-chemical processes in generalTheir relevant apparatus
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B01L 7/00 - Heating or cooling apparatusHeat insulating devices
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/00 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
The present invention relates to an immunoassay for the detection of Borrelia specific IgG, IgM and IgG/IgM antibodies in biological samples suspected of Lyme infection. The immunoassay can be performed via a standard immunoassay format or on an automated platform. In various embodiments, the immunoassay uses one or more Borrelia specific chimeric peptides VlsE-FlaB (designated pFlaB-mV), VlsE-ErpP (designated pErp59-mV), VlsE-P35 (designated pP35-mV) alone or in combination with one or more outer surface protein C (Osp C) types B or I, p58 and DbpA. Other aspects of the invention provide antigen/substrate combinations and compositions comprising combinations of the disclosed peptides and/or proteins for use in the immunoassays described herein.
C07K 14/20 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Spirochaetales (O), e.g. Treponema, Leptospira
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.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/6804 - Nucleic acid analysis using immunogens
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C40B 50/08 - Liquid phase synthesis, i.e. wherein all library building blocks are in liquid phase or in solution during library creationParticular methods of cleavage from the liquid support
G01N 33/532 - Production of labelled immunochemicals
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving labelled substances
B01J 20/289 - Phases chemically bonded to a substrate, e.g. to silica or to polymers bonded via a spacer
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
Disclosed is a system and method for dynamically adjusting analytical precision of a clinical diagnostic process. The system and method employ a clinical diagnostic analyzer that evaluates a sample and determines whether the resultant value, or mean value, is within a predetermined window or within a threshold of a predetermined value of a precision profile. If so, the analyzer automatically and dynamically determines a desired analytical precision and conducts additional testing of replicate samples to achieve a desired precision and reports the results to a user.
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 15/00 - ICT specially adapted for medical reports, e.g. generation or transmission thereof
A wide-spectrum analysis system. The system may comprise various components, including a stage, a detection module, and an optical relay structure. The stage may be configured to support a sample holder—a gel or blot, a PCR plate or microplate, sample chips, or a microfluidic device, among others—at an examination region. The detection module may be configured to detect light originating from one or more samples positioned in the sample holder. The detection module may be configured to detect light having wavelengths between about 200 nm and about 2000 nm, or subsets thereof. The optical relay structure may be configured to direct the output light from the examination region to the detection module. The system may further comprise an illumination module. Embodiments of the analyzer may be suitable for use with one or more of the following interrogation formats, among others: chemiluminescence, fluorescence, colorimetry, and spectrometry.
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.
01 - Chemical and biological materials for industrial, scientific and agricultural use
09 - Scientific and electric apparatus and instruments
Goods & Services
Chemical reagents for scientific and medical research purposes; diagnostic reagents for clinical or medical laboratory use; Polymerase Chain Reaction (PCR) and digital Polymerase Chain Reaction (dPCR) reagents for scientific and medical research purposes; reagents for amplification and detection of nucleic acids for scientific and medical research purposes; Kits comprising chemicals, reagents, enzymes, and buffer solutions for amplifying and labeling nucleic acids for scientific and research use; Reagent kits comprising biological protein, DNA primers, polymerase or buffers for scientific and medical research use; Kits comprising chemicals, reagents, enzymes, and buffer solutions for amplifying and labeling nucleic acids for scientific or research use; Kits consisting primarily of reagents and magnetic, polymeric, or gel beads for scientific research use purposes. Apparatus, namely, medical laboratory research instruments and scientific laboratory research instruments for preparation, handling, amplification, and analysis of samples containing nucleic acids; accessories in the nature of laboratory apparatus, namely, sample preparation containers and kits consisting primarily of sample preparation containers and reagents, and instruction manuals sold as a unit therewith, used to prepare laboratory samples for use in scientific and medical research, all in connection with the preparation, handling, amplification, and analysis of samples containing nucleic acids; scientific apparatus, instruments and equipment for scientific research, non-medical diagnostic analysis, chemical analysis, clinical analysis and industrial use, namely, DNA and RNA testing apparatus; scientific laboratory equipment and apparatus, namely, digital polymerase chain reaction (dPCR) apparatus, electrophoresis apparatus, gel electrophoresis apparatus, and thermal cyclers, for use in amplifying, labeling, and analyzing nucleic acids, and parts and consumable parts therefor, namely, tubes, pipette tips, plates, cartridges, holders, and containers for liquids and gels; Laboratory apparatus and instruments, namely, digital Polymerase Chain Reaction (dPCR) instruments for amplifying DNA using digital Polymerase Chain Reaction (dPCR) for use in scientific research; Scientific apparatus and instruments, namely, droplet generators for sample preparation of nucleic acids and droplet reader for amplifying and analyzing samples containing nucleic acids; Laboratory equipment and supplies, namely, polymerase chain reaction (PCR) systems comprised of computer hardware, downloaded and recorded computer software for operating polymerase chain reaction (PCR) instruments and analyzing and tabulating test results, thermocycler apparatus, polymerase chain reaction (PCR) kits comprising DNA microarrays, DNA probes and DNA assays.
Systems and methods for automating hands-free workflow of laboratory procedures. The system includes a wearable device with a display and a workflow controller in communication with the wearable device. The workflow controller can be configured to extract a workflow for a specified laboratory procedure from a workflow repository. The workflow can include a plurality of instructions arranged in a specified sequence. One or more instructions of the plurality of instructions can be sequential delivered to the wearable device for an operator to follow. The one or more instructions can include a visual indicator configured to be displayed within the display of the wearable device. The wearable device can be configured to receive voice commands and the workflow controller can be configured to navigate the workflow based on the voice commands. The wearable device can be used to scan codes and display additional information during workflow implementation.
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
17.
OPTICAL BLACK PIXEL REFERENCE TO REMOVE IMAGE BIAS NOISE FOR WESTERN BLOT IMAGING
An imaging system dynamically computes an offset for an image based on an active region and a reference region of an image sensor used to generate the image. The imaging system applies the offset to pixels of the image. The imaging system further processes the image by performing flat-fielding, binning, or both.
H04N 25/633 - Noise processing, e.g. detecting, correcting, reducing or removing noise applied to dark current by using optical black pixels
H04N 25/46 - Extracting pixel data from image sensors by controlling scanning circuits, e.g. by modifying the number of pixels sampled or to be sampled by combining or binning pixels
18.
OPTICAL BLACK PIXEL REFERENCE TO REMOVE IMAGE BIAS NOISE FOR WESTERN BLOT IMAGING
An imaging system dynamically computes an offset for an image based on an active region and a reference region of an image sensor used to generate the image. The imaging system applies the offset to pixels of the image. The imaging system further processes the image by performing flat-fielding, binning, or both.
H04N 25/633 - Noise processing, e.g. detecting, correcting, reducing or removing noise applied to dark current by using optical black pixels
H04N 25/59 - Control of the dynamic range by controlling the amount of charge storable in the pixel, e.g. modification of the charge conversion ratio of the floating node capacitance
H04N 25/76 - Addressed sensors, e.g. MOS or CMOS sensors
19.
CHROMATOGRAPHY RESIN HAVING AN ANIONIC EXCHANGE-HYDROPHOBIC MIXED MODE LIGAND
B01D 15/32 - Bonded phase chromatography, e.g. with normal bonded phase, reversed phase or hydrophobic interaction
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
B01J 20/289 - Phases chemically bonded to a substrate, e.g. to silica or to polymers bonded via a spacer
01 - Chemical and biological materials for industrial, scientific and agricultural use
Goods & Services
Chemical reagents for scientific and medical research purposes; diagnostic reagents for clinical or medical laboratory use; reagents for amplification and detection of nucleic acids for scientific and medical research purposes; Assays and reagents for use in genetic research; diagnostic preparations for scientific or research use; diagnostic preparations for clinical or medical laboratory use; kits comprising chemicals, reagents, enzymes, and buffer solutions for amplifying and labeling nucleic acids for scientific and research use; Reagent kits comprising biological protein, DNA primers, polymerase or buffers for scientific and medical research use; Chemical, biochemical and biotechnological products for industrial and scientific purposes, namely, diagnostic preparations except for human or veterinary medical purposes, non-medical reagents, enzymes, oligonucleotides, and buffer solutions for scientific or research use for amplifying, labeling, and analyzing biopolymers and nucleic acids; Kits comprising chemicals, reagents, enzymes, and buffer solutions for amplifying and labeling nucleic acids for scientific or research use; Kits comprising chemicals for sample preparation, modification and manipulation of cells and for marking, separating, isolating, purifying, duplicating, sequencing and for the analysis of biopolymers, in particular nucleic acids, proteins, macromolecules and biologically active substances, in particular nucleic acids or biological or biochemical sample material, in particular chemicals for reagents, enzymes and buffer solutions for nucleic acid purification, enrichment, amplification, sequencing and analysis
01 - Chemical and biological materials for industrial, scientific and agricultural use
Goods & Services
Reagents, and kits consisting primarily of reagents or of reagents and sample preparation containers, for use in scientific and medical research; reagents for scientific and research use for preparation, handling, amplification, and analysis of samples containing nucleic acids for use in the industries of agriculture, biodefense, food science, forensics, horticulture, medicine, pharmaceuticals, and toxicology, all in connection with the preparation, handling amplification, and analysis of samples containing nucleic acids.
23.
METHODS AND COMPOSITIONS FOR DECONVOLUTING PARTITION BARCODES
Methods and compositions for method of generating a population of captured target nucleic acids are provided. Exemplary methods can include contacting the plurality of oligonucleotides individually linked to a solid support with a sample comprising target nucleic acids having 3' ends and 5' ends, wherein target nucleic acids anneal to some of the free 3' ends of the oligonucleotides, and wherein there is an excess of oligonucleotides such that at least some oligonucleotides remain with free 3' ends; and then extending the target nucleic acid 3' end with a polymerase using the oligonucleotide as a template to form double-stranded portions that comprise a restriction enzyme recognition sequence; and then cleaving the restriction enzyme recognition sequence with a restriction enzyme to form released target nucleic acids having a single-stranded 5' end and a double-stranded 3' end and leaving oligonucleotides remain with free 3' ends uncleaved from the solid support; and optionally then separating the solid support and uncleaved oligonucleotides from the released target nucleic acids to form a solution of target nucleic acids.
Apparatus, namely, nucleic acid, including DNA and RNA, testing apparatus for medical diagnostic analysis and determination of medical conditions; Medical diagnostic apparatus and instruments, namely, Polymerase Chain Reaction (PCR) instrument to perform amplification and analyzation of nucleic acids; Medical apparatus and instruments, namely, droplet generators for sample preparation of nucleic acids and droplet readers analyzing samples containing nucleic acids; Medical devices and instruments, namely, a digital Polymerase Chain Reaction (dPCR) platform for use in measuring and quantifying DNA for medical diagnostic purposes; Medical diagnostic apparatus for the analysis of bodily fluids, tissues, biomolecules, DNA, antibodies, proteins, molecular material or cellular material; well plates for use as medical apparatus; cartridges for use as medical apparatus; Medical diagnostic kits consisting primarily of probes, buffers and reagents for use in analyzing samples containing nucleic acids.
Apparatus, namely, nucleic acid, including DNA and RNA, testing apparatus for medical diagnostic analysis and determination of medical conditions; Medical diagnostic apparatus and instruments, namely, Polymerase Chain Reaction (PCR) instrument to perform amplification and analyzation of nucleic acids; Medical apparatus and instruments, namely, droplet generators for sample preparation of nucleic acids and droplet readers analyzing samples containing nucleic acids; Medical devices and instruments, namely, a digital Polymerase Chain Reaction (dPCR) platform for use in measuring and quantifying DNA for medical diagnostic purposes; Medical diagnostic apparatus for the analysis of bodily fluids, tissues, biomolecules, DNA, antibodies, proteins, molecular material or cellular material; well plates for use as medical apparatus; cartridges for use as medical apparatus; Medical diagnostic kits consisting primarily of probes, buffers and reagents for use in analyzing samples containing nucleic acids
A system, including method and apparatus, for generating droplets suitable for droplet-based assays. The disclosed systems may include either one-piece or multi-piece droplet generation components configured to form sample-containing droplets by merging aqueous, sample-containing fluid with a background emulsion fluid such as oil, to form an emulsion of sample-containing droplets suspended in the background fluid. In some cases, the disclosed systems may include channels or other suitable mechanisms configured to transport the sample-containing droplets to an outlet region, so that subsequent assay steps may be performed.
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
B01L 7/00 - Heating or cooling apparatusHeat insulating devices
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
Hybrid reverse transcriptases are provided that comprise a non-retroviral retrotransposon, or a fragment of the non-retroviral retrotransposon having reverse transcriptase activity, joined to a nucleic acid binding protein. Also provided are methods of using the hybrid reverse transcriptases to prepare a cDNA molecule library.
This disclosure provides methods of synthesizing fluorosurfactants and fluorosurfactants produced by the disclosed methods. These fluorosurfactants can be used in various protocols, such as PCR protocols.
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.
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
B01F 33/302 - Micromixers the materials to be mixed flowing in the form of droplets
B01F 33/81 - Combinations of similar mixers, e.g. with rotary stirring devices in two or more receptacles
G01N 35/08 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
Methods and compositions are provided for preparing RNAs, from a single cell, for sequencing applications. Bead-specific barcoding oligonucleotides are used to introduce a beadspecific barcode sequence, a universal adapter sequence, and optionally one or more tail sequences to cDNA from the single cell. Also provided are plurality of partitions that include a single cell or nucleus or nucleic acids from a single cell or nucleus, beads comprising beadspecific barcoding oligonucleotides, a detection oligonucleotide, a reverse transcriptase, and a DNA polymerase.
A system, method, and platform for target detection, the system including: a base substrate; a set of sample processing regions defined at a broad surface of the substrate, wherein each of the set of sample processing regions includes: a set of microwell subarrays arranged in a gradient 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; and a cover substrate configured to mate with the base substrate in a coupled mode, the cover substrate comprising a network of venting channels aligned with the set of sample processing regions upon mating the base substrate with the cover substrate in the coupled mode, the network of venting channels providing gas exchange between the base substrate and an environment surrounding the microwell assembly. The invention(s) can be used for MPN assays.
The invention provides methods for the detection of molecular targets by digital PCR (dPCR) with a blocker for non-target molecules. Each target is provided with a unique mixture of probes. The blocker binds to a non-target molecule and blocks it from contributing to fluorescence from partitions. Two or more colors of fluorescence intensity are read, and two colors of fluorescence intensity are plotted as a 2D plot. In the plot, different targets contribute well-resolved clusters. Each cluster in the plot essentially lies a long its own radius allowing for radial multiplexing. The use of a blocker selects against the detection of non-target molecules and improves the resolution of radial multiplexing, allowing multiple targets to be detected.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
The invention provides methods for the detection of molecular targets by digital PCR (dPCR) with a blocker for non-target molecules. Each target is provided with a unique mixture of probes. The blocker binds to a non-target molecule and blocks it from contributing to fluorescence from partitions. Two or more colors of fluorescence intensity are read, and two colors of fluorescence intensity are plotted as a 2D plot. In the plot, different targets contribute well-resolved clusters. Each cluster in the plot essentially lies a long its own radius allowing for radial multiplexing. The use of a blocker selects against the detection of non-target molecules and improves the resolution of radial multiplexing, allowing multiple targets to be detected.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
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.
The subject invention pertains to the detection of modifications to a polynucleotide by binding an affinity binding element to the nucleotide sequence. The affinity binding element can comprise a compound that binds to the modified nucleotide base and a nucleotide sequence that is complementary to the target nucleotide sequence, an oligonucleotide primer that is complementary to the target nucleotide sequence, or a nucleotide sequence complementary to a connector oligonucleotide. The invention provides methods of detecting one or more modifications to a nucleotide sequence. The invention further provides affinity binding elements and, optionally, primer oligonucleotides and/or probe oligonucleotides, and methods of using said affinity binding elements in assays to a detect modified base. The methods of the invention detect a modified nucleotide that are implicated in cancer, psychiatric disorders, or metabolic diseases.
Sample racks and removable partitions removably coupled to the body of the sample rack are provided to stably support sample containers received for sample analysis while maintaining proper alignment of each sample container. A partition can comprise at least two stackable segments, each having gripping flexures disposed to hold a sample container in the desired orientation during use. The sample rack can further include a retaining cap disposed over the partitions to hold them in place during use.
Systems including thermocyclers with dual vapor champers and methods of use of the same are described. The system can be used in performing automated Polymerase Chain Reaction (PCR). The system can include a thermocycler that can thermocycle samples in a PCR cartridge. The thermocycler can include a thermal element, and a first vapor chamber thermally coupled to the thermal element. The first vapor chamber can thermally couple to the PCR cartridge during thermocycling of the PCR cartridge. The system can include an imager and a processor communicatively coupled with each of the thermocycler and the imager. The processor can control the operation of each of the thermocycler and the imager to perform digital PCR. The processor can thermocycle the sample in the PCR cartridge with the thermocycler, and image the sample in the PCR cartridge with the imager.
Methods and compositions for deconvoluting partitions comprising multiple bead-specific barcodes are provided. The methods can involve for example in vitro transcription of detection oligonucleotides within partitions, which can be linked to bead-specific barcodes and sequenced.
Provided herein are methods of detecting fragmentation of an RNA transcript in a sample where the method includes using a first primer pair to amplify a first RNA sequence of the RNA transcript that is at most partially fragmented and a second primer pair to amplify a second RNA sequence of the RNA transcript where all or a portion of the second RNA sequence is fragmented into at least a first RNA fragment and a optionally second RNA fragment.
C12Q 1/683 - Hybridisation assays for detection of mutation or polymorphism involving restriction enzymes, e.g. restriction fragment length polymorphism [RFLP]
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 15/01 - Investigating characteristics of particlesInvestigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
A method of analysis for alleles of a target includes forming plural fluid volumes. Each of those volumes includes first and second primer pairs to amplify corresponding first and second alleles of a target. Each of those volumes also includes first and second reporters with corresponding first and second photoluminophores and providing corresponding primers of the corresponding first and second primer pairs. Each of the first and second reporters may include an oligomer that has a quencher and is configured to base-pair with the primer of the corresponding first and second primer pair. The first and second alleles may be amplified using the corresponding first and second primer pairs. The method detects photoluminescence and determines a level of each allele.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
This disclosure 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 are also disclosed. Similarly, methods of purifying proteins from a biological sample, source solution, or source liquid using the disclosed chromatography matrices are also provided.
B01J 41/08 - Use of material as anion exchangersTreatment of material for improving the anion exchange properties
B01J 45/00 - Ion-exchange in which a complex or a chelate is formedUse of material as complex or chelate forming ion-exchangersTreatment of material for improving the complex or chelate forming ion-exchange properties
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 subject invention pertains to multimodal chromatography resins comprising anionic and cationic ligands on each resin particle and methods of synthesizing the multimodal chromatography resin by contacting a base with quaternary amines and/or tertiary amines on the surface of a substrate. The multimodal resins can be tuned by changing the ratios of cation to anions. The multimodal chromatography resins can be used for purifying proteins.
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01J 20/286 - Phases chemically bonded to a substrate, e.g. to silica or to polymers
Provided herein is a chromatography media composed of a particulate substrate (such as beads or other particulate substrates) that is coated with hydroxyapatite (HA) and in which the particulate substrate used as the base upon which calcium phosphate (CaP) is formed is treated with heat to remove the substrate, convert the CaP to HA, and form the desired HA microstructure so as to form a templated porous HA substrate (TPHA substrate). Also provided is a chromatography media (optionally contained within a column) comprising a TPHA substrate (e.g., a plurality of TPHA particles). The TPHA particles are porous or macroporous and uses thereof.
B01J 20/04 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising compounds of alkali metals, alkaline earth metals or magnesium
Provided herein is a chromatography media composed of a porous solid substrate (such as a membrane, metal, or metallic alloy) that is coated with hydroxyapatite (IA). Also provided is a chromatography media comprising a HA-coated substrate and uses thereof. Thus this disclosure provides a chromatography media composed of a porous solid substrate (such as a membrane, metal, or metallic alloy) that is coated with I-IA. Also provided is a chromatography media comprising a HA-coated substrate and uses thereof. Methods of preparing the HA-coated substrate are also provided.
B01J 20/04 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising compounds of alkali metals, alkaline earth metals or magnesium
B01D 15/08 - Selective adsorption, e.g. chromatography
B01J 20/28 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof characterised by their form or physical properties
The subject invention pertains to multimodal chromatography resins comprising anionic and cationic ligands on each resin particle and methods of synthesizing the multimodal chromatography resin by contacting a base with quaternary amines and/or tertiary amines on the surface of a substrate. The multimodal resins can be tuned by changing the ratios of cation to anions. The multimodal chromatography resins can be used for purifying proteins.
B01J 43/00 - Amphoteric ion-exchange, i.e. using ion-exchangers having cationic and anionic groupsUse of material as amphoteric ion-exchangersTreatment of material for improving their amphoteric ion-exchange properties
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
Provided herein is a chromatography media composed of a particulate substrate (such as beads or other particulate substrates) that is coated with hydroxypatite (HA) and in which the particulate substrate used as the base upon which calcium phosphate (CaP) is formed is treated with heat to remove the substrate, convert the CaP to HA, and form the desired HA microstructure so as to form a templated porous HA substrate (TPHA substrate). Also provided is a choromatography media (optionally contained within a column) comprising a TPHA substrate (e.g., a plurality of TPHA particles). The TPHA particles are porous or macroporous and uses thereof..
B01D 53/02 - Separation of gases or vapoursRecovering vapours of volatile solvents from gasesChemical or biological purification of waste gases, e.g. engine exhaust gases, smoke, fumes, flue gases or aerosols by adsorption, e.g. preparative gas chromatography
B01J 20/04 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising compounds of alkali metals, alkaline earth metals or magnesium
B01J 20/06 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising oxides or hydroxides of metals not provided for in group
This disclosure relates to particulate hydroxyapatite (HA)-coated substrates, methods of making particulate HA-coated substrates, and methods of using particulate HA-coated substrates. Thus, the disclosure provides chromatography media composed of a particulate substrate (such as polymer beads or other particulate substrates) that is coated with HA. Also provided is a chromatography media (optionally contained within a column) comprising a HA-coated substrate (e.g., a plurality of beads or another particulate substrate that is coated with HA). The beads or particulate substrate can be a porous or non-porous substrate.
B01J 20/04 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising compounds of alkali metals, alkaline earth metals or magnesium
B01D 15/20 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the sorbent material
B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
This disclosure relates to particulate hydroxyapatite (HA)-coated substrates, methods of making particulate HA-coated substrates, and methods of using particulate HA-coated substrates. Thus, the disclosure provides chromatography media composed of a particulate substrate (such as polymer beads or other particulate substrates) that is coated with HA. Also provided is a chromatography media, (optionally contained within a column) comprising a HA-coated substrate (e.g., a plurality of beads or another particulate substrate that is coated with HA). The beads or particulate substrate can be a porous or non-porous substrate.
B01J 20/04 - Solid sorbent compositions or filter aid compositionsSorbents for chromatographyProcesses for preparing, regenerating or reactivating thereof comprising inorganic material comprising compounds of alkali metals, alkaline earth metals or magnesium
A61L 27/32 - Phosphorus-containing materials, e.g. apatite
C01B 25/32 - Phosphates of magnesium, calcium, strontium, or barium
C04B 28/34 - Compositions of mortars, concrete or artificial stone, containing inorganic binders or the reaction product of an inorganic and an organic binder, e.g. polycarboxylate cements containing cold phosphate binders
Provided herein is a chromatography media composed of a porous solid substrate (such as a membrane, metal, or metallic alloy) that is coated with hydroxyapatite ( HA ) Also provided is a chromatography media comprising a HA-coated substrate and uses thereof. Thus this disclosure provides a chromatography media composed of a porous solid substrate (such as a membrane, metal, or metallic alloy) that is coated with HA. Also provided is a chromatography media comprising a HA-coated substrate and uses thereof. Methods of preparing the HA-coated substrate are also provided.
Compositions and methods for fixing cells or nuclei or extracellular vesicles with dithiobismaleimidoethane (DTME) and subsequent reverse transcription in the cells or nuclei or extracellular vesicles are provided.
C40B 40/02 - Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cellsLibraries contained in or displayed by vectors, e.g. plasmidsLibraries containing only microorganisms or vectors
C40B 50/06 - Biochemical methods, e.g. using enzymes or whole viable microorganisms
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
Compositions and methods for fixing cells or nuclei or extracellular vesicles with dithiobismaleimidoethane (DTME) and subsequent reverse transcription in the cells or nuclei or extracellular vesicles are provided.
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 - Transforming light or analogous information into electric information using solid-state image sensors [SSIS]
H04N 23/52 - Elements optimising image sensor operation, e.g. for electromagnetic interference [EMI] protection or temperature control by heat transfer or cooling elements
H04N 23/55 - Optical parts specially adapted for electronic image sensorsMounting thereof
H05K 7/20 - Modifications to facilitate cooling, ventilating, or heating
Methods and compositions for nucleotide sequencing are provided. In some embodiments, click chemistry is used to link barcoding oligonucleotides to DNA fragments comprising adapters introduced by a transposase.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/26 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
C12Q 1/48 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving transferase
C12Q 1/6804 - Nucleic acid analysis using immunogens
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6834 - Enzymatic or biochemical coupling of nucleic acids to a solid phase
A system for isolating cells in at least one of single-cell format and single-cluster format, comprising a reservoir, including a reservoir inlet and a reservoir outlet, configured to receive a biological sample and to receive at least one fluid, a manifold configured to receive and deliver the biological sample and the at least one fluid from the reservoir into a biological sample substrate, the manifold comprising a broad surface comprising a central region configured to receive the biological sample substrate, a set of openings configured to enable fluid flow transmission across the biological sample substrate, a manifold inlet configured to transmit flow from the reservoir the first subset of openings, a manifold outlet configured at a downstream end of the broad surface and coupled to the second subset of openings, the manifold outlet configured to transmit waste fluid from the manifold.
A probe cleaning system and method including multiple pressurized sources and a valve that are configured for cleaning a probe. The valve includes multiple inlet channels, an outlet channel, and a selector. Each inlet channel can be connected to a specified pressurized cleaning source of the multiple pressurized cleaning sources. The plurality of inlet channels are isolated from each other to avoid cross-contamination. The selector can be configured to open a specified inlet channel to pass one specified pressurized cleaning source to the outlet channel at a specified time. The probe can be coupled to the outlet channel of the valve to receive the specified pressurized cleaning source when the specified inlet channel of the valve is opened during a cleaning cycle.
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups Handling materials therefor
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
A61B 1/00 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor
A61B 1/12 - Instruments for performing medical examinations of the interior of cavities or tubes of the body by visual or photographical inspection, e.g. endoscopesIlluminating arrangements therefor with cooling or rinsing arrangements
A61B 90/70 - Cleaning devices specially adapted for surgical instruments
A61L 2/00 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lensesAccessories therefor
A61L 2/16 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lensesAccessories therefor using chemical substances
Methods and compositions for nucleotide sequencing are provided. In some embodiments, click chemistry is used to link barcoding oligonucleotides to DNA fragments comprising adapters introduced by a transposase.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
The present relates to chromatic focusing via filter thickness tuning. Chromatic focusing can be achieved via an imaging system that includes a sample holding plane, a light source that illuminates the sample on the plane, and an imager that captures an image of the sample on the plane. The imager includes a sensor, a lens, and a filter wheel defining a plurality of filter apertures including a first aperture containing a first filter passing light of a first color and having a first focal point shift, and a second aperture containing a second filter passing light of a second color and having a second focal point shift. The focal point shifts cause both light of the first color passing through the first filter and through the lens and light of the second color passing through the second filter and through the lens to focus on the sensor.
Systems, methods, and devices for imaging of stain-free fluorescence on western blot membranes with excitation by epi illumination with UV LEDs are disclosed herein. A method can include collecting and preparing a sample, separating the sample via gel electrophoresis in a gel block, transferring the separated sample from the gel block to an analysis block, generating an image of the sample with an imager, and evaluating the image of the sample. The imager can include a plane to receive and hold a block containing a sample and including a first side and a second side, a camera to image a sample on the plane and positioned above the first side of the plane, and an LED light source positioned above the first side of the plane. The LED light source can illuminate the sample on the plane via epi-illumination, and emits light having a wavelength in a range from approximately 325 nm to approximately 400 nm.
The present relates to chromatic focusing via filter thickness tuning. Chromatic focusing can be achieved via an imaging system that includes a sample holding plane, a light source that illuminates the sample on the plane, and an imager that captures an image of the sample on the plane. The imager includes a sensor, a lens, and a filter wheel defining a plurality of filter apertures including a first aperture containing a first filter passing light of a first color and having a first focal point shift, and a second aperture containing a second filter passing light of a second color and having a second focal point shift. The focal point shifts cause both light of the first color passing through the first filter and through the lens and light of the second color passing through the second filter and through the lens to focus on the sensor.
Systems, methods, and devices for imaging of stain-free fluorescence on western blot membranes with excitation by epi illumination with UV LEDs are disclosed herein. A method can include collecting and preparing a sample, separating the sample via gel electrophoresis in a gel block, transferring the separated sample from the gel block to an analysis block, generating an image of the sample with an imager, and evaluating the image of the sample. The imager can include a plane to receive and hold a block containing a sample and including a first side and a second side, a camera to image a sample on the plane and positioned above the first side of the plane, and an LED light source positioned above the first side of the plane. The LED light source can illuminate the sample on the plane via epi-illumination, and emits light having a wavelength in a range from approximately 325 nm to approximately 400 nm.
01 - Chemical and biological materials for industrial, scientific and agricultural use
Goods & Services
Kits comprised primarily of assays for non-medical purposes in scientific labs, chemical reagents for non-medical purposes in scientific labs, cell growth media for growing cells for non-medical purposes in scientific labs, microbes being cells for non-medical purposes in scientific labs, and also containing laboratory equipment in the nature of plastic consumables being petri dishes, inoculation loops, microtubes and culture tubes for scientific laboratory use; chemical reagents for scientific laboratory purposes; biochemical reagents for scientific laboratory purposes; microbial preparations for scientific laboratory use, namely microbial strains being cells for scientific and research use, namely, for generating signals for scientific educational purposes; microbial preparations for scientific laboratory use, namely microbial strains being cells for non-medical purposes in scientific labs, namely, for generating signals for scientific educational purposes
Disclosed herein are a system and method for determining a liquid level in a container based on data extracted from a digital image of the container. An image capture apparatus captures an image of a container used to store liquid reagents used by analytical instruments to test patient samples. A controller receives the captured image and extracts an analysis region based on a container type and applies a gradient filter to the analysis region. A location of a minimum gradient value (i.e., a row index) is determined based on the air-to-liquid boundary of the liquid in the extracted analysis region. A volume module calculates the liquid level in the analysis region by dividing the row index by a length of a gradient column vector and compares the determined liquid level to a threshold analysis region fraction for the container type to determine whether to output an alert.
G06T 7/62 - Analysis of geometric attributes of area, perimeter, diameter or volume
G06T 7/73 - Determining position or orientation of objects or cameras using feature-based methods
G16H 10/40 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
G16H 40/40 - ICT specially adapted for the management or administration of healthcare resources or facilitiesICT specially adapted for the management or operation of medical equipment or devices for the management of medical equipment or devices, e.g. scheduling maintenance or upgrades
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.
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 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
B01F 33/302 - Micromixers the materials to be mixed flowing in the form of droplets
C12Q 1/6874 - Methods for sequencing involving nucleic acid arrays, e.g. sequencing by hybridisation [SBH]
C40B 30/04 - Methods of screening libraries by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
C40B 40/00 - Libraries per se, e.g. arrays, mixtures
C40B 40/04 - Libraries containing only organic compounds
C40B 70/00 - Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or barcodes
G01N 33/532 - Production of labelled immunochemicals
71.
METHODS AND COMPOSITIONS FOR NUCLEIC ACID ANALYSIS
Provided herein are methods, compositions, and kits for assays, many of which involve amplification reactions such as digital PCR or droplet digital PCR. The assays may be used for such applications as sequencing, copy number variation analysis, and others. In some cases, the assays involve subdividing a sample into multiple partitions (e.g., droplets) and merging the partitions with other partitions that comprise adaptors with barcodes.
B01J 41/14 - Macromolecular compounds obtained by reactions only involving unsaturated carbon-to-carbon bonds
B01J 41/07 - Processes using organic exchangers in the weakly basic form
B01J 47/014 - Ion-exchange processes in generalApparatus therefor in which the adsorbent properties of the ion-exchanger are involved, e.g. recovery of proteins or other high-molecular compounds
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 15/01 - Investigating characteristics of particlesInvestigating permeability, pore-volume or surface-area of porous materials specially adapted for biological cells, e.g. blood cells
A system and method, wherein the method includes: (a) receiving a fluid comprising a process reagent for an assay and nucleic acid material from a sample into a fluid pathway coupled to an array of wells, wherein the array of wells is defined within a substrate and each well in the array of wells extends vertically into a planar surface of the substrate; (b) distributing the fluid along the fluid pathway and into wells of the array of wells; and (c) distributing a liquid immiscible with the fluid comprising the process reagent and nucleic acid material along the fluid pathway upon positive pressure generation by a pump of a flow control system in communication with an inlet to the fluid pathway, thereby displacing said fluid along the fluid pathway and into wells of the array of wells and preventing contents of each well from transferring to adjacent wells.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
C12M 1/00 - Apparatus for enzymology or microbiology
C12Q 1/6816 - Hybridisation assays characterised by the detection means
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
Provided herein are multiplex assays for detecting antibodies indicative of presence and stage of syphilis infection in an individual. Individuals infected with syphilis produce antibodies directed to syphilis components and the lipid cellular debris associated with the infection. The present disclosure represents the first combination of these diverse antibody targets in a single assay.
G01N 33/571 - ImmunoassayBiospecific binding assayMaterials therefor for microorganisms, e.g. protozoa, bacteria, viruses for venereal disease, e.g. syphilis, gonorrhoea, herpes
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/92 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving lipids, e.g. cholesterol
77.
SYNTHESIZING BARCODING SEQUENCES UTILIZING PHASE-SHIFT BLOCKS AND USES THEREOF
Provided herein are compositions and methods for generating phase-shift barcode oligonucleotides for library construction for next-generation sequencing. In some cases, barcode oligonucleotides are attached to particles or beads. Also provided are methods and kits for using the phase-shift barcode oligonucleotides in sequencing assays.
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.
Provided is a heterohybridoma-based method of generating recombinant rabbit monoclonal antibodies, recombinant anti-IL-6 receptor-alpha (IL-6Rα) antibodies generated using such methods, and immune assay methods kits employing such antibodies.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
In certain aspects, methods of the invention involve performing modification state specific enzymatic reaction of nucleic acid in a sample, determining a value associated with efficiency of the modification state specific enzymatic reaction based on a control, determining an amount of target nucleic acid in the sample, and normalizing the amount of target nucleic acid based on the efficiency value. Based on the normalized amount of target nucleic acid, the method further includes determining whether the normalized amount of target nucleic acid is indicative of a condition.
Methods and kits for purifying protein-nanoparticle conjugates are provided. In some embodiments, a multimodal medium having a size exclusion mode and a capture mode is used to purify the protein-nanoparticle conjugates.
A61K 47/69 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
B01D 15/34 - Size-selective separation, e.g. size-exclusion chromatographyGel filtrationPermeation
B01D 15/38 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving specific interaction not covered by one or more of groups , e.g. affinity, ligand exchange or chiral chromatography
C07K 1/16 - ExtractionSeparationPurification by chromatography
C07K 16/00 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies
The methods and reagents are provided for barcoding and analysis of DNA samples using partition (e.g., droplet) technology while avoiding performing amplification in droplets.
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
The invention generally relates to methods and systems for manipulating droplet size. In certain aspects, the invention provides methods for manipulating droplet size that include forming droplets of aqueous fluid surrounded by an immiscible carrier fluid, and manipulating droplet size during the forming step by adjusting pressure exerted on the aqueous fluid or the carrier fluid.
B01F 33/3011 - Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
B01F 35/221 - Control or regulation of operational parameters, e.g. level of material in the mixer, temperature or pressure
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glasswareDroppers
B05B 1/02 - Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops
B05B 1/08 - Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means designed to produce a jet, spray, or other discharge of particular shape or nature, e.g. in single drops of pulsating nature, e.g. delivering liquid in successive separate quantities
B05B 1/26 - Nozzles, spray heads or other outlets, with or without auxiliary devices such as valves, heating means with means for mechanically breaking-up or deflecting the jet after discharge, e.g. with fixed deflectorsBreaking-up the discharged liquid or other fluent material by impinging jets
B05B 7/00 - Spraying apparatus for discharge of liquids or other fluent materials from two or more sources, e.g. of liquid and air, of powder and gas
86.
Dynamic axial compression for preparative columns using external compression
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 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the construction of the column
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.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
88.
METHODS AND COMPOSITIONS FOR TRACKING BARCODES IN PARTITIONS
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.
B01J 8/08 - Chemical or physical processes in general, conducted in the presence of fluids and solid particlesApparatus for such processes with moving particles
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
C40B 40/08 - Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
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 - Promoter-based amplification, e.g. nucleic acid sequence-based amplification [NASBA], self-sustained sequence replication [3SR] or transcription-based amplification system [TAS]
C12Q 1/6816 - Hybridisation assays characterised by the detection means
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
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.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6853 - Nucleic acid amplification reactions using modified primers or templates
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C12Q 1/6816 - Hybridisation assays characterised by the detection means
92.
UNIVERSAL FLUORESCENT PROBES ACTIVATED WITH RNaseH2
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.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
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.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
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 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
C12Q 1/6816 - Hybridisation assays characterised by the detection means
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.
