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.
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.
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 a 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. The well chamber is in fluidic communication between the pre-amplification chamber and the fluidic outlet.
Automated oligonucleotide synthesis-compatible sulforhodamine dye phosphoramidite compounds and labeled polynucleotides incorporating these dyes are provided.
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.
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 coupleable with a chip carrier device 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.
Test cartridges for performing multi-target assay panels, in particular multiplex vaginal panels (MVP) and methods of use and manufacture. Such cartridges can include a cartridge body having multiple chambers and rotatable valve assembly to facilitate controlled fluid flow, and various reagents and buffers to chemically lyse nucleic acids from multiple targets in MVP. Specialized valve assemblies have been utilized to resist alkaline lysing buffers required to chemically lyse multiple targets, including various protozoa, yeasts and bacteria, including Atopobium spp. (Atopobium vaginae, Atopobium novel species CCUG 55226); Bacterial Vaginosis-Associated Bacterium 2 (BVAB2); and Megasphaera-1. Methods include detecting levels of each respective target in a single sample from a single multi-target assay cartridge and identifying the subject as having bacterial vaginosis, vulvovaginal candidiasis (or the presence of Candida spp.), or trichomoniasis (or presence of Trichomonas vaginalis) based on detected levels of each of: Atopobium spp., BVAB2, Megasphaera-1, Candida spp., and Trichomonas vaginalis.
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
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
C12Q 1/6893 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for protozoa
C12Q 1/6895 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for plants, fungi or algae
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
8.
ENCODERLESS MOTOR WITH IMPROVED GRANULARITY 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 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.
H02P 6/16 - Circuit arrangements for detecting position
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 11/00 - Structural association of dynamo-electric machines with electric components or with devices for shielding, monitoring or protection
H02K 15/02 - Methods or apparatus specially adapted for manufacturing, assembling, maintaining or repairing of dynamo-electric machines of stator or rotor bodies
9.
DIAGNOSTIC DETECTION CHIP DEVICES AND METHODS OF MANUFACTURE AND ASSEMBLY
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.
RFID-based operations management systems and methods are provided herein, particularly RFID based Kanban systems. Such system can realize increased efficiencies, improved visibility of inventory throughout the workflow and improved response to variations in demand. RFID based solutions can automatically transact consumption of Kanban inventory in real-time and trigger replenishment signals to warehouses automatically, resulting in increased Kanban inventory accuracy and lower manual efforts for replenishment and consumption posting. This approach can interface with existing operational management software (e.g. ERP systems, such as SAP) seamlessly integrating with product manufacturing workflows. Such systems are uniquely applicable to manufacture of biological testing kits, where demands fluctuate considerably in response to crises, disasters, epidemics and pandemics.
G06Q 10/087 - Inventory or stock management, e.g. order filling, procurement or balancing against orders
G06K 19/07 - Record carriers with conductive marks, printed circuits or semiconductor circuit elements, e.g. credit or identity cards with integrated circuit chips
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.
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
H04L 67/12 - Protocols specially adapted for proprietary or special-purpose networking environments, e.g. medical networks, sensor networks, networks in vehicles or remote metering networks
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.
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
H02P 27/06 - Arrangements or methods for the control of AC motors characterised by the kind of supply voltage using variable-frequency supply voltage, e.g. inverter or converter supply voltage using dc to ac converters or inverters
H02P 6/182 - Circuit arrangements for detecting position without separate position detecting elements using back-emf in windings
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
13.
PSEUDO-COMPLEMENTARY BASES IN GENOTYPING AND NUCLEIC ACID SEQUENCING
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.
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.
Described herein are methods and 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. 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.
Systems and methods for monitoring, characterizing and controlling operation of LEDs are provided herein. Methods includes measuring a voltage across the LED, and correlating the voltage to a junction temperature of the LED. This correlation can be used to improve operation of the LED by increasing the signal to noise ratio of the LED signal, characterize the LED by comparing to an I-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. Improved performance of the LED can include stabilizing the photon output 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 during the assay. System and device with control units 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 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.
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.
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
C12Q 1/6893 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for protozoa
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.
G05D 23/19 - Control of temperature characterised by the use of electric means
F25B 21/02 - Machines, plants or systems, using electric or magnetic effects using Nernst-Ettinghausen effect
G01K 1/02 - Means for indicating or recording specially adapted for thermometers
G01K 13/024 - Thermometers specially adapted for specific purposes for measuring temperature of moving fluids or granular materials capable of flow of moving gases
G01N 1/42 - Low-temperature sample treatment, e.g. cryofixation
G01N 1/44 - Sample treatment involving radiation, e.g. heat
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
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.
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising modifying the aptamer by uracil-DNA glycosylase enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamers are circular and comprise one or more deoxyuridine nucleotides providing for aptamer-specific recognition and modification of the circular aptamer by the uracil-DNA glycosylase enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing uracil-DNA glycosylase enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one uracil-DNA glycosylase enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific modification of the aptamer by the uracil-DNA glycosylase enzymatic activity.
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. The oligonucleotide aptamers of the present invention are circular and comprise one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the circular aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.
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 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) 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 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.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
32.
ENCODERLESS MOTOR WITH IMPROVED QUANTIZATION AND METHODS OF USE AND CALIBRATION
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 to be determined from the sinusoidal signals by utilizing a transformation matrix or piece-wise algorithm applied in substantially linear portions of the sinusoidal signals without requiring use of additional hardware encoder or position sensors and without requiring noise-reduction or filtering of the signal.
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.
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamer comprises one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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.
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
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.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
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 491/052 - Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-membered
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 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.
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.
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 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.
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 11/00 - Structural association of dynamo-electric machines with electric components or with devices for shielding, monitoring or protection
H02K 15/02 - Methods or apparatus specially adapted for manufacturing, assembling, maintaining or repairing of dynamo-electric machines of stator or rotor bodies
H02P 6/16 - Circuit arrangements for detecting position
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 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
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.
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 33/543 - Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
C12Q 1/6804 - Nucleic acid analysis using immunogens
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.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
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
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.
H02P 7/025 - Arrangements for regulating or controlling the speed or torque of electric DC motors the DC motors being of the linear type the DC motors being of the moving coil type, e.g. voice coil motors
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.
G06F 15/173 - Interprocessor communication using an interconnection network, e.g. matrix, shuffle, pyramid, star or snowflake
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
H04L 67/12 - Protocols specially adapted for proprietary or special-purpose networking environments, e.g. medical networks, sensor networks, networks in vehicles or remote metering networks
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
G16H 40/40 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT 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
Solid supports modified with pectins derivatives are provided. The solid supports are useful in nucleic acid isolation, separation, and detection methods.
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.
Methods and cleaning compositions for reduction of nucleic acid contamination on surfaces, in air, and in solutions using modified pectin are provided.
C11D 11/00 - Special methods for preparing compositions containing mixtures of detergents
C11D 17/04 - Detergent materials or soaps characterised by their shape or physical properties combined with or containing other objects
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
A61L 101/50 - Polysaccharides or derivatives thereof
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. The well chamber is in fluidic communication between the pre-amplification chamber and the fluidic outlet.
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.
G01N 35/02 - 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
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
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
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising modifying the aptamer by uracil-DNA glycosylase enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamers are circular and comprise one or more deoxyuridine nucleotides providing for aptamer-specific recognition and modification of the circular aptamer by the uracil-DNA glycosylase enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing uracil-DNA glycosylase enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one uracil-DNA glycosylase enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific modification of the aptamer by the uracil-DNA glycosylase enzymatic activity.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamer comprises one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. The oligonucleotide aptamers of the present invention are circular and comprise one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the circular aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
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.
Described herein are methods and 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. 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.
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising modifying the aptamer by uracil-DNA glycosylase enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamers are circular and comprise one or more deoxyuridine nucleotides providing for aptamer-specific recognition and modification of the circular aptamer by the uracil-DNA glycosylase enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing uracil-DNA glycosylase enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one uracil-DNA glycosylase enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific modification of the aptamer by the uracil-DNA glycosylase enzymatic activity.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. In some aspects, the oligonucleotide aptamer comprises one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
Provided are methods and compositions for activating oligonucleotide aptamer-deactivated DNA polymerases, comprising cleaving the aptamer by endonuclease V enzymatic activity to reduce or eliminate binding of the oligonucleotide aptamer to the DNA polymerase, thereby activating DNA synthesis activity of the DNA polymerase in a reaction mixture. Mixtures for use in methods of the invention are also provided. The oligonucleotide aptamers of the present invention are circular and comprise one or more deoxyinosine nucleotides providing for aptamer-specific recognition and cleavage of the circular aptamer by the endonuclease V enzymatic activity. Exemplary oligonucleotide aptamers, mixtures and methods employing endonuclease V enzymatic activity are provided. The methods can be practiced using kits comprising a DNA polymerase-binding oligonucleotide aptamer and at least one endonuclease V enzymatic activity having oligonucleotide aptamer-specific recognition to provide for specific cleavage of the aptamer by the endonuclease V enzymatic activity.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C07H 21/02 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
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.
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
H02P 6/182 - Circuit arrangements for detecting position without separate position detecting elements using back-emf in windings
H02P 27/06 - Arrangements or methods for the control of AC motors characterised by the kind of supply voltage using variable-frequency supply voltage, e.g. inverter or converter supply voltage using dc to ac converters or inverters
G01N 35/10 - Devices for transferring samples to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
G01N 33/487 - Physical analysis of biological material of liquid biological material
68.
System, device and methods of sample processing using semiconductor detection chips
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 coupleable with a chip carrier device 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.
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.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
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.
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. In some embodiments, the methods comprise detecting androgen receptor (AR) and/or uroplakin 1B (UPK1B).
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
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.
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
74.
Encoderless motor with improved granularity 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 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.
H02P 6/16 - Circuit arrangements for detecting position
H02K 11/00 - Structural association of dynamo-electric machines with electric components or with devices for shielding, monitoring or protection
H02K 15/02 - Methods or apparatus specially adapted for manufacturing, assembling, maintaining or repairing of dynamo-electric machines of stator or rotor bodies
H02K 11/215 - Magnetic effect devices, e.g. Hall-effect or magneto-resistive elements
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 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
75.
Thermostable polymerase inhibitor compositions and methods
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.
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.
C12Q 1/6893 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for protozoa
78.
Methods for DNA and RNA extraction from fixed paraffin-embedded tissue samples
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 50° C. to about 100° C.; and recovering the nucleic acid from said lysis solution.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
G16B 25/00 - ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
G16B 25/10 - Gene or protein expression profiling; Expression-ratio estimation or normalisation
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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
G01N 1/06 - Devices for withdrawing samples in the solid state, e.g. by cutting providing a thin slice, e.g. microtome
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.
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.
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.
G06F 15/173 - Interprocessor communication using an interconnection network, e.g. matrix, shuffle, pyramid, star or snowflake
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
H04L 29/08 - Transmission control procedure, e.g. data link level control procedure
H04L 29/06 - Communication control; Communication processing characterised by a protocol
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
G16H 40/40 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT 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
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. The well chamber is in fluidic communication between the pre-amplification chamber and the fluidic outlet.
C12Q 1/6876 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
83.
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 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) 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 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.
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.
C12Q 1/6848 - Nucleic acid amplification reactions characterised by the means for preventing contamination or increasing the specificity or sensitivity of an amplification reaction
B01L 3/00 - Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
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
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 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.
G01N 35/02 - 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
G01N 35/00 - Automatic analysis not limited to methods or materials provided for in any single one of groups ; Handling materials therefor
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
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.
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.
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 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving 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
C12Q 1/6893 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for protozoa
93.
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.
C12Q 1/6806 - Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
C12Q 1/6827 - Hybridisation assays for detection of mutation or polymorphism
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
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
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.
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.
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.
H02P 6/16 - Circuit arrangements for detecting position
H02K 15/02 - Methods or apparatus specially adapted for manufacturing, assembling, maintaining or repairing of dynamo-electric machines of stator or rotor bodies
H02K 11/00 - Structural association of dynamo-electric machines with electric components or with devices for shielding, monitoring or protection
H02K 11/215 - Magnetic effect devices, e.g. Hall-effect or magneto-resistive elements
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 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
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.
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.
B01L 7/00 - Heating or cooling apparatus; Heat insulating devices
H02P 27/06 - Arrangements or methods for the control of AC motors characterised by the kind of supply voltage using variable-frequency supply voltage, e.g. inverter or converter supply voltage using dc to ac converters or inverters
H02P 6/182 - Circuit arrangements for detecting position without separate position detecting elements using back-emf in windings
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.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
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
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
C12Q 1/6895 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for plants, fungi or algae