Film seal assemblies that seal one or more reagents within a sample cartridge, which allow for single lid cartridge designs. Such film seal assemblies can include one or more layers, a bottom-most layer that permanently seals with a sample cartridge having multiple chambers for one or more reagents, and top-most layer that releasably seals vent opening(s) in the film seal assembly and is removable by the end user. This configuration allows use of a single lid, which can be integrally formed with cartridge body or a separate component attached atop the cartridge body. The film seal assembly can include peelable liner(s) or can releasably attached to an underside of the single lid. Such film assemblies can include multiple layers that include a polypropylene layer for permanently sealing to a rigid propylene cartridge body and polyester top layers for releasably and hermetically sealing with a liner or the lid.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B65D 17/50 - Non-integral frangible members applied to, or inserted in, preformed openings, e.g. tearable strips or plastic plugs
B65D 51/16 - Closures not otherwise provided for with means for venting air or gas
B65D 51/22 - Caps, lids, or covers co-operating with an inner closure arranged to be opened by piercing, cutting, or tearing having means for piercing, cutting, or tearing the inner closure
B65D 53/08 - Flexible adhesive strips adapted to seal filling or discharging apertures
G01N 35/04 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations - Details of the conveyor system
Methods and systems for detecting defect in sample cartridges in real-time during manufacturing. Such systems utilize one or more external sensors that detect characteristics or parameters of the sample cartridge and/or the manufacturing process from one or more data sets. The external sensor(s) include any of: an RGB camera, IR camera, high-resolution optical camera, and ultrasonic microphone or combination thereof. An automated system obtains data sets from external sensor(s) and compares the data sets to a baseline of the sample cartridge and/or manufacturing process such that defects can be determined based on a variance from the baseline. Such methods can utilize feature extraction and spectrum analysis to identify features or characteristics for comparison with the baseline. A machine learning model can be used to determine an algorithm based on data sets of acceptable sample cartridges and data sets from the external sensor(s) that are associated with the cartridge defect.
G05B 19/418 - Total factory control, i.e. centrally controlling a plurality of machines, e.g. direct or distributed numerical control (DNC), flexible manufacturing systems (FMS), integrated manufacturing systems (IMS), computer integrated manufacturing (CIM)
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B29C 65/08 - Joining of preformed parts; Apparatus therefor by heating, with or without pressure using ultrasonic vibrations
Methods and system for identifying faulty sample cartridges in real-time during manufacturing are provided herein. Such systems use monitored operational parameters associated with operation of manufacturing equipment that manufactures the sample cartridges. One or more data sets of operational parameters are obtained from existing equipment controls and/or additional sensors and compared to corresponding operational parameters associated with acceptable cartridges. A faulty detection unit can be configured to compare the operational parameters and can optionally include algorithms and/or models, such as a machine learning model, by which faulty cartridges can be identified. The comparison can include determining whether the monitored operational parameters are within a pre-defined range of acceptable values and/or deviate from a characteristic profile of the operational parameter in a manner indicative of faulty cartridges. The faulty cartridge detection can be integrated within automation controls so that faulty cartridges can be detected in real-time and automatically discarded during manufacturing.
G05B 19/418 - Total factory control, i.e. centrally controlling a plurality of machines, e.g. direct or distributed numerical control (DNC), flexible manufacturing systems (FMS), integrated manufacturing systems (IMS), computer integrated manufacturing (CIM)
4.
TRANSFER LEARNING METHODS AND MODELS FACILITATING DEFECT DETECTION
Methods and systems for training a model for automated defect detection of a product during manufacturing are provided herein. Such methods utilize a combination of supervised transfer learning through auxiliary tasks and a combination of supervised and unsupervised learning. The methods can utilize supervised transfer learning with expert labels on a generalized auxiliary task, such as product classification, which is transferred to more specific auxiliary tasks, such as identification of specific product features and/or anomaly detection, where additional expert labels are then applied to the anomalies, and another iteration of supervised learning further improves the model. The anomalies can correspond to features associated with defects, which can be induced experimentally to improve efficiency of the training procedure. The product can be a sample cartridge such that the model allows detection of faulty cartridges based on sample cartridge and/or manufacturing process data.
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
6.
NUCLEIC ACID EXTRACTION AND ISOLATION WITH HEAT LABILE SILANES AND CHEMICALLY MODIFIED SOLID SUPPORTS
Compositions and methods for isolating and detecting nucleic acid in a biological sample are provided. The compositions and methods utilize a modified solid support comprising an amine or amide group.
Improved sample cartridges, valve assemblies and methods of manufacture and assembly are provided herein. Such systems can include a sample processing cartridge having a unitary cartridge body with integral syringe tube and valve interface. Such systems can further includes valve assemblies with an overmolded gasket and gaskets with a protruding conical valve sealing surface. Various additional features can include thin film sealing for cartridge as well as valve assemblies for chemical lysis. Thin film sealing for cartridge lids can include various multi-layered designs to facilitate injection and sealing of reagents within the cartridge. Magnetic separation features are also included. Such features can be included in various design iterations as needed for compatibility with existing technologies and to accommodate needs for manufacturing workflows.
Described herein are methods and compositions that provide highly efficient nucleic acid amplification. The method employs pairs of primers that differ significantly in Tm and a novel temperature/time course characterized by a temperature pulse during denaturation that enables a high-Tm primer (but not a low-Tm primer) to anneal and prime the synthesis of an additional nucleic acid strand beyond the two strands synthesized in a cycle of classical PCR. In some embodiments, this allows a 3-fold or greater increase of amplification product for each amplification cycle and therefore increased sensitivity and speed over conventional PCR.
Compositions and methods for detecting mycobacterium tuberculosis (MTB) infection in a patient suspected of being infected with MTB and for distinguishing active tuberculosis (ATB), incipient tuberculosis (ITB) or subclinical tuberculosis (STB) from latent tuberculosis and other pulmonary and infectious diseases are provided. The methods may also be used to monitor treatment responses of MTB infected patients. Changes in the expression level of genes are used to aid in the diagnosis, prognosis, and treatment of tuberculosis.
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
10.
ECHO AMPLIFICATION: A COMPREHENSIVE SYSTEM OF CHEMISTRY AND METHODS FOR AMPLIFICATION AND DETECTION OF SPECIFIC NUCLEIC ACID SEQUENCES
Described herein is a comprehensive novel amplification system that can employ novel nucleic acid constructs as blocked primers, such constructs including a target-specific region, wherein the target-specific region comprises a target-specific cleavage domain, and a universal adapter sequence located 5' of the target-specific region, wherein the universal adapter sequence comprises a non-natural nucleotide base. Also described is a fusion protein between a polymerase and an endonuclease, which is useful in this system, as well as related methods and kits.
Systems and methods for monitoring, characterizing and controlling operation of LEDs are provided herein. Methods include measuring a voltage (V) across a LED (1), and correlating the voltage (V) to a junction temperature of the LED (1). This correlation can be used to improve operation of the LED (1) by increasing the signal to noise ratio of the LED signal (5), characterize the LED (1) by comparing to an l-V curve, control LED operation to compensate for LED degradation and avoid crosstalk, and/or to generally improve performance and life expectancy of the LED (1). Improved performance of the LED (1) can include stabilizing the photon output (5) during performance of an assay to provide a desired dye reporter signal required for the assay and/or reducing an intra-shot during of the LED output (5) during the assay. System and device with control units (2) configured to perform these methods are also described herein.
Reaction vessels, cartridges, devices and methods for facilitating high-level multiplexing are described herein. Such reaction vessels can include a planar frame defining a fluidic path between a first planar substrate and a second planar substrate, a fluidic interface is located at one end of the planar frame with a pair of fluidic ports, a well chamber and a pre-amplification chamber. Devices for spotting reagents in wells of high-level multiplexing reaction vessels and improved reagent solutions are also described herein.
Sample cartridge, valve assembly and processing methods for providing mechanical lysis, chemical lysis or both for a given fluid sample are provided herein. Such systems can include a sample processing cartridge having a valve assembly configured for transport of the processing of fluid sample within the sample cartridge. The valve assembly can include a valve body and cap that secure a filter therebetween and facilitate inflow of mechanical or chemical lysing agents as needed for a fluid sample. Assay workflows for performing both mechanical and chemical lysis of a fluid sample within the same workflow of a single universal sample cartridge are also provided.
The present disclosure is directed to methods and kits for discriminating between a bacterial infection and viral infection in a human subject. More specifically, the methods can comprise detecting the expression level of a combination of ABL1, IRF9, ITGAM, LY6E, PSTPIP2 and RUNX1 in biological samples from the human subject and determining whether the human subject has a bacterial or viral infection based on those expression levels.
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
15.
THERMAL CONTROL DEVICE AND METHODS UTILIZING TEMPERATURE DISTRIBUTION MODELING
Thermal control devices and methods to provide improved control, speed and efficiency in temperature cycling are provided herein. Such thermal control device and methods can include one or more active elements, such a thermoelectric cooler device, that is controlled by an algorithm that regulates a temperature distribution of an adjacent reaction-vessel according to a temperature distribution command trajectory and estimated reaction-vessel temperature distribution. Some embodiments include two active elements that are bilaterally applied to opposing sides of the reaction-vessel. In some embodiments, the estimated reaction-vessel temperature is determined based on a state of power electronics of the element and a temperature output of one or more sensors of a portion of the element and/or an ambient environment of the reaction-vessel. Methods of calibration of such systems utilizing a thermal calibrator as a proxy for the reaction-vessel are also provided herein.
Methods and systems for estimating force and motor torque in a mechatronic system are provided herein. Such methods and system are suited for improved control of small-scale mechatronic system, particularly a syringe, valve, and cartridge loader or door opening/closing mechanism of a diagnostic assay system. The methods can compensate for friction and account for various second-order effects, thereby allowing for more accurate pressure estimation, thereby allowing improved syringe operation. The methods can further allow for improved estimation of force or motor torque to allow for improved control of an actuatable valve interfacing the sample cartridge and cartridge loader or door opening/closing system. Methods of calibrating such systems are also provided.
An n phase encoder for use in a mechatronic system, including a movable element (104, 304) that applies a magnetic field with period S representing a total displacement, and a stationary support (201, 310) with n magnetic field sensors (202a-c, 312) mounted thereon and positioned on the stationary support (201, 310) so as to measure the magnetic field imparted by the movable element (104, 304), wherein n is greater than 1, the encoder being configured to obtain signals from the n magnetic field sensors (202a-c, 312) corresponding to the measurements of the magnetic field imparted by the movable element (104, 304), and to process n signals from the n magnetic field sensors (202a-c, 312) by utilizing a transformation matrix to determine a displacement of the movable element (104, 304), as well as associated signal processing and calibration methods.
G01D 5/244 - Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means generating pulses or pulse trains
G01D 5/14 - Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means influencing the magnitude of a current or voltage
G01D 5/245 - Mechanical means for transferring the output of a sensing member; Means for converting the output of a sensing member to another variable where the form or nature of the sensing member does not constrain the means for converting; Transducers not specially adapted for a specific variable using electric or magnetic means generating pulses or pulse trains using a variable number of pulses in a train
18.
DIAGNOSTIC ASSAY SYSTEM WITH REPLACEABLE PROCESSING MODULES AND REMOTE MONITORING
A biological sample processing apparatus having an enclosure and a plurality of sample processing modules held within an enclosure with a tiltable graphical user interface screen. In one aspect, the individual modules that are readily removable for repair, replacement or upgrade. Each module is configured to be independently operable and readily inserted into the enclosure for connection with a processing unit of the enclosure. Each module can include quick-release mechanisms so that the module can be readily removed and replaced manually or with minimal tools through the front of the enclosure without requiring substantial or total disassembly of the module or entire enclosure. In another aspect, the user interface screen can display identifying information, such as a barcode, that can be scanned by a user's portable device so as to monitor the progress of an assay remotely.
Compositions and methods for detecting mycobacterium tuberculosis (MTB) infection in a patient suspected of being infected with mycobacterium tuberculosis and for distinguishing between active and latent tuberculosis infection are provided. The methods may also be used to monitor progression of MTB infection or to monitor treatment of MTB infected patients. Changes in the expression level of genes are used to aid in the diagnosis, prognosis and treatment of tuberculosis.
Automated oligonucleotide synthesis-compatible fluorescent dye phosphoramidite compounds, solid supports, and labeled polynucleotides incorporating the compounds are provided. The compounds allow universal incorporation of the fluorescent label into any position of the polynucleotide.
C07D 491/02 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains two hetero rings
C09B 57/00 - Other synthetic dyes of known constitution
G01N 33/542 - Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
G01N 33/58 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
22.
METHODS OF DETECTING SARS-COV-2, INFLUENZA, AND RSV
Compositions and methods for detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), influenza A, influenza B, and respiratory syncytial virus (RSV) are provided.
Described herein are methods and compositions that provide highly efficient nucleic acid amplification and signal detection using a cycling probe. In some embodiments, this allows a 3-fold or greater increase of amplification product for each amplification cycle and therefore increased sensitivity and speed over conventional PCR. Modified bases can be employed in primers to provide this base-3 or greater amplification with satisfactory PCR cycle times, which are improved, as compared to those observed in the absence of modified bases.
Described herein are methods and compositions that make use of pseudo-complementary bases to reduce unwanted hybridization in assays to detect and/or quantify particular nucleotide sequences, as well as in nucleic acid sequencing protocols.
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or 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
25.
MOTOR HAVING INTEGRATED ACTUATOR WITH ABSOLUTE ENCODER AND METHODS OF USE
A DC electric motor having a stator mounted to a substrate, the stator having a coil assembly having a magnetic core, a rotor mounted to the stator with a first set of permanent magnets distributed radially about the rotor to facilitate rotation of the rotor and a second set of permanent magnets on the rotor to facilitate determination of an absolute position of the rotor. The motor further includes first and second set of sensors for detection of the magnets of the inner and outer rings. During operation of the motor passage of the permanent magnets over the sensors produces a substantially sinusoidal signal of varying voltage substantially without noise and/or saturation, allowing an absolute position of the rotor relative the substrate to be determined from the sinusoidal signals without requiring use of an encoder or position sensors and without requiring noise-reduction or filtering of the signal.
H02K 29/08 - Motors or generators having non-mechanical commutating devices, e.g. discharge tubes or semiconductor devices with position sensing devices using magnetic effect devices, e.g. Hall-plates or magneto-resistors
A lid apparatus for a multi-chambered container. The lid apparatus has a top-lid that is hingedly attached to a bottom-cap. The top-lid includes one or more openings for fluid filling multiple passages that extend from the bottom-cap. A lower bottom-cap includes welding features for welding to the multi-chambered container. The bottom-cap further includes one or more auxiliary ports for injecting a reagent when the lid apparatus is in a closed configuration sealingly attached to the multi-chambered sample container.
Diagnostic detection chip device designs that reduce cost of fabrication and assembly are described herein. Such chip device designs include features that facilitate use of the chip within a chip carrier device with integrated fluid flow control features and compatibility with conventional sample cartridges and sample processing systems. Associated methods of manufacture and assembly of the chip devices are also provided herein.
Methods and primer set compositions that provide highly efficient nucleic acid amplification. In some embodiments, this allows a 3-fold or greater increase of amplification product for each amplification cycle and therefore increased sensitivity and speed over conventional PCR. The method is based on the use of a set of nested primers an outer primer which comprises modified bases, e.g. 2-amino-adenine or 2-thio-thymine, and an inner primer which comprises a single-stranded target-binding region and a double stranded region comprising a flap sequence which is not complementary to target and a region which is complementary to the outer primer. The modified bases improve PCR cycle times, as compared to those observed in the absence of modified bases by allowing the outer primer to bind the target. The method and composition may also employ and contain, respectively, a third intermediate primer which has a structure as the inner primer.
Systems for processing a fluid sample to facilitate analysis with a semiconductor detection chip are provided herein. Such systems can include a sample processing cartridge (100) coupleable with a chip carrier device (200) configured for transport of the processed fluid sample from the sample cartridge. The chip carrier device can include one or more fluid channels extending between fluid-tight couplings attachable to transfer ports of the sample processing cartridge. The chip carrier device can include multiple portions or adapters, including a fluid sample portion, a flowcell portion and a chip carrier. Also provided are methods of preparing and transporting a fluid sample from a sample cartridge into a chip carrier device for analysis with a semiconductor detection chip carried within the chip carrier device.
Methods and cleaning compositions for reduction of nucleic acid contamination on surfaces, in air, and in solutions using modified pectin are provided.
A61L 2/16 - Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
Solid supports modified with pectins derivatives are provided. The solid supports are useful in nucleic acid isolation, separation, and detection methods.
Automated oligonucleotide synthesis-compatible sulforhodamine dye phosphoramidite compounds and labeled polynucleotides incorporating these dyes are provided.
C09B 57/00 - Other synthetic dyes of known constitution
C07H 19/073 - Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
G01N 33/483 - Physical analysis of biological material
34.
INTEGRATED IMMUNO-PCR AND NUCLEIC ACID ANALYSIS IN AN AUTOMATED REACTION CARTRIDGE
In various embodiments methods detecting and/or quantifying a target analyte using immuno-PCR and optionally nucleic acid amplification are provided. In certain embodiments the methods utilize a cartridge for performing immuno-PCR to detect and/or quantify one or more target analytes, and optionally detecting and/or quantifying a nucleic acid, where the cartridge comprises a sample receiving chamber; a chamber comprising a matrix material that acts as a filter and/or a DNA binding agent; a temperature controlled channel or chamber; and a plurality of chambers containing reagents and/or buffers for performing immuno-PCR, where the plurality of chambers comprises a chamber containing a capture antibody that binds the analyte that is to be detected; the plurality of chambers comprises a chamber containing a detection antibody where said detection antibody is optionally attached directly or indirectly to a signal DNA; the plurality of chambers comprises a chamber containing a PCR master mix; the plurality of chambers comprises a chamber containing primers for amplifying all or a region of said signal DNA; and the plurality of chambers comprises a chamber containing a probe for detecting all or a region of said signal DNA.
INTEGRATED PURIFICATION AND MEASUREMENT OF DNA METHYLATION AND CO-MEASUREMENT OF MUTATIONS AND/OR MRNA EXPRESSION LEVELS IN AN AUTOMATED REACTION CARTRIDGE
Methods of determining methylation of DNA are provided. In one illustrative, but non-limiting embodiment the method comprises i) contacting a biological sample comprising a nucleic acid to a first matrix material comprising a first column or filter where said matrix material binds and/or filters nucleic acids in said sample and thereby purifies the DNA; ii) eluting the bound DNA from the first matrix material and denaturing the DNA to produce eluted denatured DNA; iii) heating the eluted DNA in the presence of bi sulfite ions to produce a deaminated nucleic acid; iv) contacting said deaminated nucleic acid to a second matrix material comprising a second column to bind said deaminated nucleic acid to said second matrix material; v) desulphonating the bound deaminated nucleic acid and/or simultaneously eluting and desulphonating the nucleic acid by contacting the deaminated nucleic acid with an alkaline solution to produce a bi sulfite converted nucleic acid; vi) eluting said bi sulfite converted nucleic acid from said second matrix material; and vii) performing methylation specific PCR and/or nucleic acid sequencing, and/or high resolution melting analysis (HRM) on said bisulfite-converted nucleic acid to determine the methylation of said nucleic acid, wherein at least steps iv) through vi) are performed in a single reaction cartridge.
A handling system for high throughput processing of a large volume of biological samples is provided herein. Such systems can include an array support assembly that supports multiple diagnostic assay modules in an array having at least two dimensions, a loader that loads multiple diagnostic assay cartridges within the multiple diagnostic assay modules. The array support assembly can be movable relative the loader to facilitate loading and unloading so as to provide more efficient processing.
The present disclosure relates to aptamers for temperature-dependent reversible inhibition of thermostable polymerase activity in order to improve sensitivity and specificity of various reactions and assays involving hot start polynucleotide synthesis. Methods for use of the aptamers and related compositions and kits are also provided.
Methods and reagents are provided for the rapid extraction of nucleic acids from a cell or tissue sample. In certain embodiments the sample comprises a formalin fixed paraffin embedded sample (e.g., a FFPET sample), or a fine needle aspirate and/or a cell/tissue smear. In some embodiments, the methods comprise incubating one or more sections of said tissue sample in a lysis solution comprising a buffer sufficient to maintain the pH of said solution at a pH ranging from about pH 4 to about pH 9; a chaotropic agent; a chelating agent; and a detergent; where the incubating is at a temperature ranging from about 50°C to about 100°C; and recovering the nucleic acid from said lysis solution.
Improved sub-assemblies and methods of control for use in a diagnostic assay system adapted to receive an assay cartridge are provided herein. Such sub-assemblies include: a brushless DC motor, a door opening/closing mechanism and cartridge loading mechanism, a syringe and valve drive mechanism assembly, a sonication horn, a thermal control device and optical detection/excitation device. Such systems can further include a communications unit configured to wirelessly communicate with a mobile device of a user so as to receive a user input relating to functionality of the system with respect to an assay cartridge received therein and relaying a diagnostic result relating to the assay cartridge to the mobile device.
Thermal control devices adapted to provide improved control and efficiency in temperature cycling are provided herein. Such thermal control device can include a thermoelectric cooler controlled in coordination with another thermal manipulation device to control an opposing face of the thermoelectric cooler and/or a microenvironment. Some such thermal control devices include a first and second thermoelectric cooler separated by a thermal capacitor. The thermal control devices can be configured in a planar configuration with a means for thermally coupling with a planar reaction vessel of a sample analyzer for use in thermal cycling in a polymerase chain reaction of the fluid sample in the reaction vessel. Methods of thermal cycling using such a thermal control devices are also provided.
A DC electric motor having a stator mounted to a substrate, the stator having a coil assembly having a magnetic core, a rotor mounted to the stator with permanent magnets distributed radially about the rotor, the permanent magnets extending beyond the magnetic core, and sensors mounted to the substrate adjacent the permanent magnets. During operation of the motor passage of the permanent magnets over the sensors produces a substantially sinusoidal signal of varying voltage substantially without noise and/or saturation, allowing an angular position of the rotor relative the substrate to be determined from linear portions of the sinusoidal signal without requiring use of an encoder or position sensors and without requiring noise-reduction or filtering of the signal.
H02K 29/08 - Motors or generators having non-mechanical commutating devices, e.g. discharge tubes or semiconductor devices with position sensing devices using magnetic effect devices, e.g. Hall-plates or magneto-resistors
H02K 11/215 - Magnetic effect devices, e.g. Hall-effect or magneto-resistive elements
H02K 11/33 - Drive circuits, e.g. power electronics
H02K 21/22 - Synchronous motors having permanent magnets; Synchronous generators having permanent magnets with stationary armatures and rotating magnets with magnets rotating around the armatures, e.g. flywheel magnetos
42.
INTEGRATED PURIFICATION AND MEASUREMENT OF DNA METHYLATION AND CO-MEASUREMENT OF MUTATIONS AND/OR MRNA EXPRESSION LEVELS IN AN AUTOMATED REACTION CARTRIDGE
In various embodiments methods of determining methylation of DNA are provided. In one illustrative, but non-limiting embodiment the method comprises i) contacting a biological sample comprising a nucleic acid to a first matrix material comprising a first column or filter where said matrix material binds and/or filters nucleic acids in said sample and thereby purifies the DNA; ii) eluting the bound DNA from the first matrix material and denaturing the DNA to produce eluted denatured DNA; iii) heating the eluted DNA in the presence of bisulfite ions to produce a deaminated nucleic acid; iv) contacting said deaminated nucleic acid to a second matrix material comprising a second column to bind said deaminated nucleic acid to said second matrix material; v) desulfonating the bound deaminated nucleic acid and/or simultaneously eluting and desulfonating the nucleic acid by contacting the deaminated nucleic acid with an alkaline solution to produce a bisulfite converted nucleic acid; vi) eluting said bisulfite converted nucleic acid from said second matrix material; and vii) performing methylation specific PCR and/or nucleic acid sequencing, and/or high resolution melting analysis (HRM) on said bisulfite-converted nucleic acid to determine the methylation of said nucleic acid, wherein at least steps iv) through vi) are performed in a single reaction cartridge.
A fluidic bridge device for transport of a fluid sample between a first sample processing device and a second sample processing device. The fluidic bridge may include one or more fluid channels extending between fluid-tight couplings attachable to transfer ports of the first and second sample processing device. In one aspect the first device is a sample preparation device and the second device is an assay device. The fluidic bridge can include at least two fluid conduits, at least one for transport of the prepared sample, and at least one other to facilitate displacement of air to allow flow of the prepared sample through the other fluid conduit. The fluid channels can include one or more of an amplification chamber, a processing chamber, a gas-permeable vent, a bubble trap, a filter, and an external port. Methods of preparing and transporting a fluid sample between devices are provided herein.
Described herein are methods and compositions that provide highly efficient nucleic acid amplification. In some embodiments, this allows a greater than 2-fold increase of amplification product for each amplification cycle and therefore increased sensitivity and speed over conventional PCR.
The present invention provides systems and methods for rapid screening of individuals who may have been exposed to and carrying biological agents potentially contagious or otherwise harmful to the general public.
Compositions and methods for detecting Ebola are provided. The methods relate to detecting the presence or absence of Ebola virus in a sample from a subject comprising detecting the presence or absence of at least one Ebola gene selected from glycoprotein (GP) and nucleocapsid protein (NP) in the sample, in particular by quantitative PCR. The compositions comprise primers and probes for said quantitative PCR.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
Disclosed are modified thymine bases that provide enhanced base-pairing affinity for adenine or 2,6-diaminopurine bases in polynucleotide hybridization complexes. Also disclosed are polynucleotide oligomers, polynucleotide hybridization complexes that comprise such modified thymine bases. Also disclosed are various methods of use. For example, in some embodiments, modified polynucleotide oligomers disclosed herein can be used as primers and probes for nucleic acid amplification and/or detection.
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
50.
MODIFIED CYTOSINE POLYNUCLEOTIDE OLIGOMERS AND METHODS
Disclosed are modified cytosine bases that provide enhanced base-pairing affinity for guanine bases in polynucleotide hybridization complexes. Also disclosed are polynucleotide oligomers, polynucleotide hybridization complexes that comprise such modified cytosine bases. Also disclosed are various methods of use. For example, in some embodiments, modified polynucleotide oligomers disclosed herein can be used as primers and probes for nucleic acid amplification and/or detection.
Compositions and methods for detecting Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are provided. The present invention also provides methods and compositions for screening for infection/inflammation based on genomic copy number. Described herein is a method that entails assaying a sample obtained from the urogenital tract of the mammal for an indicator of genomic copy number, wherein a genomic copy number level that is higher than a control genomic copy number level is indicative of the presence of infection or inflammation of the urogenital tract. Also described in a kit of the invention that includes a primer and/or probe for detecting or sequencing an indicator of genomic copy number, wherein the indicator of genomic copy number comprises a nucleic acid sequence that is expected to be present in the genome of the mammal in one or two copies; and a primer and/or probe for detecting or sequencing a nucleic acid sequence that is indicative of a pathogen that infects the urogenital tract or a miRNA correlated with inflammation.
Methods of detecting cancer are provided. Methods of detecting changes in the levels of one or more small RNAs associated with cancer are also provided. Compositions and kits are also provided.
Methods of detecting lung cancer, such as non-small cell lung cancer, including squamous cell carcinoma and adenocarcinoma, are provided. Methods of detecting changes in the levels of one or more small RNAs associated with lung cancer are also provided. Compositions and kits are also provided.
A lid apparatus for a multi-chambered container. The lid apparatus has a top-lid that is hingedly attached to a bottom-cap. The top-lid includes one or more openings for fluid filling multiple passages that extend from the bottom-cap. A lower bottom-cap includes welding features for welding to the multi-chambered container.
Compositions and methods for detecting bladder cancer are provided. In some embodiments, methods of detecting low grade bladder cancer are provided. In some embodiments, methods of monitoring recurrence of bladder cancer are provided. The methods comprise detecting androgen receptor (AR) and/or uroplakin 1B (UPK1B). Methods for monitoring therapy with androgen receptor antagonists by determining the expression of AR and/or UPK1B are also provided. In some embodiments the expression is determined in urine samples.
The present invention provides method for amplifying a specific RNA molecule in a sample, the method comprising: (a) adding a poly(ribonucleotide) sequence to RNA molecules in the sample; (b) reverse transcribing the poly-adenylated RNA molecules using a reverse primer comprising a sequence that anneals to said poly(ribonucleotide) sequence; and (c) amplifying and detecting the cDNA molecule(s) using the same reverse primer and using a forward primer specific for the RNA molecule to be detected; wherein at least one of the forward and reverse primers comprises a hairpin primer. The invention also provides kits useful for practicing this method.
Methods and reagents are provided for the rapid extraction of nucleic acids from a fixed paraffin embedded sample (e.g., a FFPET sample). In some embodiments, the methods comprise incubating one or more sections of said tissue sample in a lysis solution comprising a buffer sufficient to maintain the pH of said solution at a pH ranging from about pH 4 to about pH 9; a chaotropic agent; a chelating agent; and a detergent; where the incubating is at a temperature ranging from about 50C to about 100C; and recovering the nucleic acid from said lysis solution.
A honeycomb tube with a planar frame defining a fluidic path between a first planar surface and a second planar surface. A fluidic interface is located at one end of the planar frame. The fluidic interface has a fluidic inlet and fluidic outlet. The fluidic path further includes a well chamber having an well-substrate with a plurality of wells. The well chamber is arranged in the planar frame between the first or second surface and the well-substrate.
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 33/487 - Physical analysis of biological material of liquid biological material
An analytic system for carrying out a chemical assay, the system having a bay with an opening on one side, the bay of a size and shape to enclose a cartridge carrying sample material to be analyzed, one or more mechanisms within the bay through which the cartridge and or material within the cartridge is influenced, a door of a size to cover the opening, a securing mechanism associated with the bay and the door, by which the door is secured when closed.
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
G01N 37/00 - INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES - Details not covered by any other group of this subclass
G01V 8/10 - Detecting, e.g. by using light barriers
A remote monitoring system for medical data collection can include a data-flagging process embeds authorization and settings information into a file containing the test results. Such data flagging can occur at a medical device or testing site, and may be based in policy settings received from a remote system. A file containing the test results can also include data category information that can be used to protect sensitive information by preventing such information from being communicated to the wrong server.
Compositions and methods for detecting Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are provided. The present invention also provides methods and compositions for screening for infection/inflammation based on genomic copy number. Described herein is a method that entails assaying a sample obtained from the urogenital tract of the mammal for an indicator of genomic copy number, wherein a genomic copy number level that is higher than a control genomic copy number level is indicative of the presence of infection or inflammation of the urogenital tract. Also described in a kit of the invention that includes a primer and/or probe for detecting or sequencing an indicator of genomic copy number, wherein the indicator of genomic copy number comprises a nucleic acid sequence that is expected to be present in the genome of the mammal in one or two copies; and a primer and/or probe for detecting or sequencing a nucleic acid sequence that is indicative of a pathogen that infects the urogenital tract or a miRNA correlated with inflammation.
A thermal cycling apparatus having a sample interfacing wall extending from a mounting wall. The sample interfacing wall can accept and apply thermal cycles to samples. An air source can direct an air stream to cool the sample. Another source can direct heated air away from the sample.
A biological sample processing apparatus having an enclosure. A plurality of sample processing modules are held by the enclosure. Each sample processing module is configured to hold a removable sample cartridge and to only perform sample processing on a sample within the corresponding removable sample cartridge. Each sample processing module is configured to perform at least one of a plurality of testing processes on the sample within the removable sample cartridge. At least one module in the apparatus is configured to perform nucleic acid amplification and detection.
Compositions and methods for detecting bladder cancer are provided. In some embodiments, methods of monitoring recurrence of bladder cancer are provided. In some embodiments, the methods comprise detecting a set of markers consisting of CRH, IGF2, KRT20, and ANXA10.
Methods of detecting sepsis in a sample from a patient are provided. Methods of detecting changes in expression of one or more RNAs associated with sepsis are also provided. Compositions and kits are also provided.
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 40/08 - Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries
Methods of detecting lung cancer, such as non-small cell lung cancer, including squamous cell carcinoma and adenocarcinoma, are provided. Methods of detecting changes in the levels of one or more small RNAs associated with lung cancer are also provided. Compositions and kits are also provided.
Methods of diagnosing lung cancer in a sample from a patient by detecting changes in expression of one or more target RNAs associated with lung cancer are provided.
Methods of sepsis in a sample from a patient are provided. Methods of detecting changes in expression of one or more microRNAs associated with sepsis are also provided. Compositions and kits are also provided.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Methods of detecting cervical dysplasia, such as cervical dysplasia likely to progress to carcinoma in a sample of human cervical cells, are provided. Methods of detecting changes in expression of one or more microRNAs or mRNAs associated with cervical dysplasia or cervical cancer are also provided. Compositions and kits are also provided.
The present invention provides methods and kits for conducting multiplex nucleic acid amplification reactions by controlling target sequence replication times. In one aspect, such control is exerted by selecting different lengths of target polynucleotides for amplification. In another aspect, control is exerted by providing sequence-specific polymerase inhibitors, such as specific blocking oligonucleotides. In accordance with the invention, multiple target polynucleotides can be sequentially amplified in an amplification reaction conducted in different stages, wherein amplification of sequences with longer replication times is permitted in one stage but precluded in other stages by modifying polymerase extension times in the course of the reaction.
The invention provides methods and apparatus for carrying out multiple amplification reactions in a single reaction chamber by successive cycles of loading reaction mixture, amplifying, and removing spent reaction mixture in a fluidly closed reaction system. In particular, the present invention allows amplification of a plurality of target polynucleotides from a single sample by carrying out under closed-loop control successive amplifications of different target polynucleotides from different portions of the sample.
C12P 19/34 - Polynucleotides, e.g. nucleic acids, oligoribonucleotides
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C07H 19/00 - Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro derivatives thereof
The present invention concerns a method for identifying the functionality of each member of a family of nucleic acids based on the functionality of a second family of nucleic acids that can interact with the first family. Nucleic acids from the first family are put into functionally related clusters that share biological information obtained from the second family. The invention also relates to the refinement and accurate prediction of interactions between the first family and the second family of nucleic acids. The invention also applies to the use of such functional information to identify targets and mechanisms for therapeutic applications.
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
G06F 19/24 - for machine learning, data mining or biostatistics, e.g. pattern finding, knowledge discovery, rule extraction, correlation, clustering or classification
74.
METHODS FOR THE IDENTIFICATION OF MICRORNA AND THEIR APPLICATIONS IN RESEARCH AND HUMAN HEALTH
The present invention concerns a method for prediction and identification of microRNA precursors (pre-microRNA) and microRNA molecules using data processing programs and databases. The invention also pertains to the isolated form of these pre- microRNAs, microRNA molecules and derived nucleic acids there of. The invention also relates to recombinant vector, host cell, support, pharmaceutical composition or kit comprising such microRNA molecules or there of derivated molecules. The invention also applies to the use of such microRNA molecules and/or their identified targets in research, prognostic, diagnostic tools/methods as well as for therapeutic applications.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12N 15/63 - Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
G06F 19/18 - for functional genomics or proteomics, e.g. genotype-phenotype associations, linkage disequilibrium, population genetics, binding site identification, mutagenesis, genotyping or genome annotation, protein-protein interactions or protein-nucleic acid interactions
G06F 19/22 - for sequence comparison involving nucleotides or amino acids, e.g. homology search, motif or Single-Nucleotide Polymorphism [SNP] discovery or sequence alignment
75.
METHOD AND APPARATUS FOR STORING AND DISPENSING REAGENT BEADS
Embodiments of the invention provide an efficient and effective technique for storing and dispensing reagent beads. In one embodiment, an apparatus is provided for dispensing reagent beads contained in a bead storage device which includes a bead carrier having a plurality of wells; a plurality of reagent beads disposed in the wells; and a cover tape releasably attached to the bead carrier to cover the wells and retain the reagent beads in the wells. The apparatus comprises a channel in which to place the bead storage device with the bead carrier facing a support wall of the channel and the cover tape facing a stripping wall of the channel. The stripping wall includes a stripping gap disposed between a stripping edge and an opposite edge, and a dispense opening provided adjacent the opposite edge on a side of the stripping wall opposite from the stripping edge. The cover tape is insertable through the stripping gap to be pulled against the stripping edge to peel the cover tape from the bead carrier to move the wells of the bead carrier inside the channel toward the dispense opening and expose the wells individually to dispense the reagent beads.
The present invention relates to novel polar fluorescent and quenchers dyes, and minor groove binder with enhanced polarity. The present invention further relates to methods of preparing oligonucleotide probes labeled with polar arsonate dyes under the condition of automated synthesis and method of using such probes.
Embodiments of the invention provide a cap for a vessel for performing a multi-stage process for analyzing a sample, such as nested PCT or RT-PCR. In one embodiment, the cap comprises a body configured to be mated to the vessel to enclose a vessel interior, a cap cavity for holding reagents, and a cap cavity control portion that is adjustable with respect to the body between a first-stage position in which the cap cavity is enclosed and fluidicly isolated from the vessel interior and a second-stage position in which the cap cavity is fluidicly coupled with the vessel interior.
The invention is directed to systems, methods and apparatus for carrying out multi-stage amplification reactions, especially under fluidly closed conditions. In one aspect, methods of the invention are carried out in a fluidly closed reaction system that permits the isolation of a portion of a first (or prior) reaction mixture and its use a s a sample or specimen in a second (or subsequent) reaction mixture, thereby substantially avoiding interfering effects that first reaction components may have in the second reaction if both reaction mixture were simply combined together. In the aspect, systems, methods, and apparatus of the invention may be used with any amplification reaction that permits multiple stages of amplification based on the use of nested primers.
The present invention relates to methods and compositions providing optimized reaction conditions for nucleic acid amplification reactions and for methods and compositions that reduce contamination of amplification reactions during set up.
The invention provides a multi-bead assay system for a protein based assay comprising at least two different beads. The first bead comprises protein and a protein stabilization matrix. The first bead forms a first solution when dissolved in liquid, and the first solution permts a first activity level for the assay. The second bead comprises a potentiation bead matrix that when dissolved in the first solution forms a second solution that potentiates the protein based assay to achieve a second actitivy level that is higher than the first activity level.
Described are methods, kits and systems for multiplexed detection of biological agents in a sample, e.g., multiplexed detection of e.g., bacteria, viruses, and biological toxins. The method utilizes two markers for each agent; the presence or absence in a sample of each f the two markers per agent is determined in separate reactions; however each reaction is used to detect a single marker for multiple agents. Also disclosed is the multiplexed detection method using real time PCR. The invention provides an efficient, cost-effective, and specific method for multiplexed detection of biological agents.
A method for preparing a sample suspected to contain a target nucleic acid sequence for a nucleic acid amplification reaction and for verifying the effectiveness of the sample preparation comprises the step of mixing the sample with sample preparation controls. The sample preparation controls are cells, spores, microorganisms, or viruses that contain a marker nucleic acid sequence. The sample mixed with the sample preparation controls is subjected to a lysis treatment, and nucleic acid released by the lysis treatment is subjected to nucleic acid amplification conditions. The presence or absence of the target nucleic acid sequence and of the marker nucleic acid sequence is then determined. Positive detection of the marker nucleic acid sequence indicates that the sample preparation process was satisfactory, while the inability to detect the marker nucleic acid sequence indicates inadequate sample preparation.
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