Microfluidic system for amplifying and detecting polynucleotides in parallel
Inventors
Handique, Kalyan • Brahmasandra, Sundaresh N. • Ganesan, Karthik • Williams, Jeff
Assignees
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Publication Number
US-11085069-B2
Publication Date
2021-08-10
Expiration Date
Abstract
The present technology provides for an apparatus for detecting polynucleotides in samples, particularly from biological samples. The technology more particularly relates to microfluidic systems that carry out PCR on nucleotides of interest within microfluidic channels, and detect those nucleotides. The apparatus includes a microfluidic cartridge that is configured to accept a plurality of samples, and which can carry out PCR on each sample individually, or a group of, or all of the plurality of samples simultaneously.
Core Innovation
The invention provides a fully automated, continuous random-access molecular diagnostic test system that performs nucleic-acid amplification and fluorescence detection using multi-sample microfluidic cartridge consumables. Each microfluidic cartridge includes separate sample inlets and a plurality of microfluidic networks, where each microfluidic network includes an amplification region. When nucleic-acid containing samples are received in the microfluidic cartridge, amplification is carried out in the amplification regions associated with the received samples.
The system integrates consumables, accessories, and an instrument that supports cartridge receiving, robotic sample transfer, thermal cycling, and optical fluorescence scanning. An instrument includes a receiving bay configured to receive a microfluidic cartridge, a liquid-handling robot with dispensing heads configured to transfer nucleic-acid containing samples to the separate sample inlets, and separately controllable heat sources at the receiving bay. The heat sources thermal cycle nucleic-acid containing samples in the amplification regions while maintaining the amplification region at a substantially uniform temperature at least once in each thermal cycle, under processor control.
Real-time molecular readout is provided by an optical scanner configured to measure fluorescence emitted from each amplification region when the microfluidic cartridge is received in the receiving bay. The optical scanner is further configured to provide real-time detection of an amplified target nucleic acid sequence in the respective amplification region. Based at least in part on the level of fluorescence measured, the touchscreen computer displays a test result for a nucleic-acid containing sample amplified in the microfluidic cartridge.
The documented system further supports pre-detection quality control, including a fill check prior to real-time detection to confirm that an amplification region is filled with a nucleic-acid-containing sample when the cartridge is received and the sample is transferred into the cartridge. The system also supports multiplexed fluorescence detection by measuring fluorescence at multiple wavelengths.
Claims Coverage
The partial claim set provided includes one independent claim. The independent claim covers the full automated continuous random-access system architecture: multi-sample microfluidic cartridges with amplification regions, robotic sample dispensing, separately controllable heat sources maintaining uniform amplification-region temperature, and optical fluorescence scanning providing real-time detection and touchscreen result display.
Fully automated continuous random-access molecular diagnostic system
A fully automated, continuous random-access molecular diagnostic test system comprising multi-sample microfluidic cartridges, accessories, and an instrument with touchscreen computer for receiving cartridges, transferring samples, thermal cycling, fluorescence measurement, and displaying test results based at least in part on fluorescence.
Multi-sample microfluidic cartridge with amplification region in microfluidic networks
Each microfluidic cartridge comprises a plurality of separate sample inlets, each associated with a microfluidic network having an amplification region within which nucleic acid amplification is carried out when the nucleic-acid containing sample is received in the microfluidic cartridge.
Robotic sample transfer into separate sample inlets at the receiving bay
A liquid-handling robot comprising a plurality of dispensing heads configured to transfer nucleic acid-containing samples to the plurality of separate sample inlets when the microfluidic cartridge is received in the receiving bay.
Separately controllable heat sources for thermal cycling with substantially uniform temperature
A plurality of separately controllable heat sources configured at the receiving bay, each heat source configured to thermal cycle a nucleic acid-containing sample in an amplification region of the microfluidic cartridge, wherein the amplification region is maintained at a substantially uniform temperature at least once in each thermal cycle, under processor control.
Optical fluorescence scanner with real-time amplified target nucleic acid detection
An optical scanner configured to measure a level of fluorescence emitted from each amplification region when the microfluidic cartridge is received in the receiving bay, wherein the optical scanner provides real-time detection of an amplified target nucleic acid sequence in the respective amplification region, and wherein the touchscreen computer is configured to display a test result based at least in part on the level of fluorescence measured.
The independent claim combines multi-sample microfluidic cartridges with amplification regions, robotic sample dispensing to separate sample inlets at a receiving bay, separately controllable heat sources that thermal cycle samples while maintaining substantially uniform amplification-region temperature, and an optical fluorescence scanner that measures fluorescence and enables real-time detection of an amplified target nucleic acid sequence, with touchscreen display of test results based on fluorescence.
Stated Advantages
Real-time detection of an amplified target nucleic acid sequence in the respective amplification region based on measured fluorescence.
Display of a test result for a nucleic-acid containing sample on a touchscreen computer based at least in part on the measured level of fluorescence.
Substantially uniform temperature maintained at least once in each thermal cycle in the amplification region.
Documented Applications
Not explicitly described in patent.
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