Canon U.S. Life Sciences, Inc.

Canon U.s.a., Inc.

Other

Kenton C Hasson

Gregory A Dale

Johnathan Stuart Coursey

Shulin Zeng

Gregory H Owen

Hiroshi Inoue

Hongye Liang

Sami Kanderian

Brian P Murphy

Takayoshi Hanagata

John Patrick Keady

Eric D Schneider

Ivor T Knight

Scott Corey

Weidong Cao

Brian Bean

Ben Lane

Ying-Xin Wang

Ray Tsao

Bradley Scott Thomas

Deborah John Boles

Conrad Laskowski

Alex K Flamm

Michele R Stone

Scott O Sundberg

Franklin Regan

Jason Schmidt

Dwayne W Warfield

Kunihiro Sakai

George Maltezos

Arvind Virmani

Hanyoup Kim

Harini Shandilya

Renee Howell

Melissa Gosse

Jeremy Savage

Makoto Ogusu

Fernando Weber DeCastro

Chris Felice

Ronald Kurz

Kazuhiko Hasegawa

Ralph McCann

Jason Clemons

Yoichi Murakami

Abhijit Dohale

Sarah Warfield, Legal Representative

Brian Scrivens

Jason Zsak

Christopher Sneeder

Yasuyuki Numajiri

Denis Alias

Fernando DeCastro

The present invention relates to methods and systems that result in high quality, reproducible, thermal melt analysis on a microfluidic platform. The present invention relates to methods and systems using thermal systems including heat spreading devices, including interconnection methods and materials developed to connect heat spreaders to microfluidic devices. The present invention also relates to methods and systems for controlling, measuring, and calibrating the thermal systems of the present invention.

Systems and methods using external heater systems in microfluidic devices

The present invention relates to sample-to-answer systems, devices, cartridges, and method of using the same for detecting the presence of microorganisms in a sample, such as bacteria.

Sample-to-answer system for microorganism detection featuring target enrichment, amplification and detection

An apparatus for performing a thermocyclic process, such as amplifying DNA, includes a microfluidic chip with a channel formed therein and one or more thermal distribution elements disposed over portions of the chip. Each thermal distribution element is configured to distribute thermal energy from an external thermal energy source substantially uniformly over the portion of the chip covered by the thermal distribution element. The portion of the chip covered by the thermal distribution element thereby comprises a discrete temperature zone. Other temperature zones can be defined by other thermal distribution elements or by portions of the chip not covered by a thermal distribution element. The channel is configured so that a fluid flowing through the channel would enter and exit the different temperature zones a plurality of times, thereby alternately exposing the fluid to the temperature of each zone for a period of time required for the fluid to traverse the zone.

Systems and methods for amplifying nucleic acids

Methods, devices, and systems for performing polymerase chain reaction (PCR) amplification and melt data acquisition according to a single slug approach in which a single slug in a microfluidic channel fills an entire thermal zone of the microfluidic channel, and the thermal zone used for both PCR temperature cycling and melt data acquisition. A detector may be configured to detect fluorescence from the thermal zone during the PCR temperature cycling for real-time PCR and/or during temperature ramping in the melt data acquisition. Slug position control may be achieved by detecting leading or trailing edges in a slug build target zone into which a slug passes after passing through the thermal zone. The single slug approach may break coupling between one or more events of the PCR amplification and melt data acquisition and enable events to be independently optimized.

Methods, devices, and systems for processing multiple assays

The present invention relates to the use of one or more amplicons as temperature calibrators. In some embodiments, the calibrators may be used to calibrate the temperature of a microfluidic channel in which amplification and/or melt analysis is performed. In some embodiments, the amplicons may be genomic, ultra conserved elements and/or synthetic. The amplicon(s) may have a known or expected melt temperature(s). The calibrators may be added to primers of study or may follow or lead the primers of study in the channel. The amplicon(s) may be amplified and melted, and the temperature(s) at which the amplicon(s) melted may be determined. The measured temperature(s) may be compared to the known temperature(s) at which the amplicon(s) was expected to melt. The difference(s) between the measured and expected temperatures may be used to calibrate/adjust one or more temperature control elements used to control and/or detect the temperature of the channel.

Thermal calibration

The present invention relates to methods for amplifying nucleic acids in micro-channels. More specifically, the present invention relates to methods for performing a real-time polymerase chain reaction (PCR) in a continuous-flow microfluidic system and to methods for monitoring real-time PCR in such systems.

Real-time PCR in micro-channels

The present invention relates to systems and methods of temperature referencing for melt curve data collection. More specifically, the present invention relates to systems and methods for collecting DNA melt curve data for a DNA sample and a temperature reference material.

System and method for temperature referencing for melt curve data collection

The present invention relates to systems and methods for the real time processing of nucleic acid during polymerase chain reaction (PCR) and thermal melt applications. According to an aspect of the invention, a system for the rapid serial processing of multiple nucleic acid assays is provided. In one embodiment, the system includes, but is not limited to: a microfluidic cartridge having microfluidic (flow-through) channels, a fluorescence imaging system, a temperature measurement and control system; a pressure measurement and control system for applying variable pneumatic pressures to the microfluidic cartridge; a storage device for holding multiple reagents (e.g., a well-plate); a liquid handling system comprising at least one robotic pipettor for aspirating, mixing, and dispensing reagent mixtures to the microfluidic cartridge; systems for data storage, processing, and output; and a system controller to coordinate the various devices and functions.

System and method for serial processing of multiple nucleic acid assays

This invention relates to systems and methods for imaging sample materials within a microfluidic device during an assay reaction process. In accordance with certain aspects of the invention, images are formed with a pixel array and a region of interest ('ROI') is defined within the pixel array. Image values, such as fluorescent intensity, can be computed as averages of individual pixel values within the ROI. Where the ROI is subject to non-uniform conditions, such as non-uniform heating, the ROI can be divided into sub-ROIs which are sufficiently small that the condition is uniform within the sub-ROI.

Optical system for high resolution thermal melt detection

The invention relates to systems and methods including a combination of thermal generating device technologies to achieve more efficiency and accuracy in PCR temperature cycling of nucleic samples undergoing amplification.

Combined thermal devices for thermal cycling

An interface cartridge for a microfluidic chip, with microfluidic process channels and fluidic connection holes at opposed ends of the process channels, provides ancillary fluid structure, including fluid flow channels and input and/or waste wells, which mix and/or convey reaction fluids to the fluidic connection holes and into the process channels of the microfluidic chip.

Fluid interface cartridge for a microfluidic chip

The present invention relates to systems and methods of monitoring velocity or flow in channels, especially in microfluidic channels. In some embodiments, the present invention relates to systems and methods of monitoring velocity or flow rate in systems and methods for performing a real-time polymerase chain reaction (PCR) in a continuous-flow microfluidic system.

Microfluidic flow monitoring

The invention relates to systems and methods for calibrating and using resistance temperature detectors. In one embodiment, the system includes a calibration circuit comprising a resistance temperature detector in a bridge circuit with at least one potentiometer, and a programmable gain amplifier coupled to the bridge circuit. Embodiments of the invention further comprise methods for calibrating the bridge circuit and the programmable gain amplifier for use with the resistance temperature detector and methods for determining the self heating voltage of the bridge circuit.

Systems and methods for auto-calibration of resistive temperature sensors

Systems and methods for air cooling a microfluidic device using confinement channels to isolate cooling air from exposed liquids are disclosed. The systems and methods may also thermally condition the cooling airflow for improved robustness of the microfluidic device. In one embodiment, the air cooling system includes a split-level cooling manifold including an inlet duct that directs cooling air to a microfluidic device and an outlet duct that directs air heated by the microfluidic device away from the microfluidic device. The temperature of cooling air may be measured. The cooling air may be preheated to a temperature that is higher than an expected ambient temperature. The temperature of the cooling air after being heated by a microfluidic device may be measured.

Air cooling systems and methods for microfluidic devices

Systems for processing multiple assays background

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Germantown, MD, United States of America

Kenton C Hasson