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Assignees
Member
CepheidCepheid is a global leader in molecular diagnostics, dedicated to improving healthcare by developing, manufacturing, and marketing automated, easy-to-use molecular systems and tests. Their mission is to provide rapid, accurate, and actionable genetic testing for a wide range of infectious diseases, oncology, and human genetics. Cepheid's flagship GeneXpert System delivers scalable, sample-to-answer PCR testing for institutions of any size, supporting both centralized and decentralized care. The company is committed to expanding access to high-quality diagnostics worldwide, supporting public health initiatives, driving innovation in molecular testing, and advancing sustainability and responsible business practices.
Cepheid is a global leader in molecular diagnostics, dedicated to improving healthcare by developing, manufacturing, and marketing automated, easy-to-use molecular systems and tests. Their mission is to provide rapid, accurate, and actionable genetic testing for a wide range of infectious diseases, oncology, and human genetics. Cepheid's flagship GeneXpert System delivers scalable, sample-to-answer PCR testing for institutions of any size, supporting both centralized and decentralized care. The company is committed to expanding access to high-quality diagnostics worldwide, supporting public health initiatives, driving innovation in molecular testing, and advancing sustainability and responsible business practices.
Publication Number
US-12196460-B2
Publication Date
2025-01-14
Expiration Date
Abstract
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.
Core Innovation
The invention provides thermal control devices adapted to provide improved control and efficiency in temperature cycling. Such thermal control devices 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.
The patent addresses deficiencies of known heating/cooling devices used in biological testing systems, including fan-based cooling systems that occupy large physical space, require significant power, and suffer start-up lag and shutdown overlap; and systems that use large thermal masses that limit heating and cooling rates leading to long thermal cycling times and unwanted side reactions. There is an unmet need for thermal control devices with greater heating and cooling rates that are not dependent on the ambient environment and can be produced at low cost and minimal size for inclusion in diagnostic devices, and for devices that better control temperature cycling within a reaction chamber within required speed, accuracy, and precision.
Claims Coverage
Independent claim identified: claim 1. The independent claim recites multiple inventive features involving paired thermoelectric coolers thermally coupled through a thermal interposer and coordinated control to improve thermal cycling efficiency.
First thermoelectric cooler
A first thermoelectric cooler having an active face and a reference face, wherein the active face is configured to thermally engage a reaction vessel.
Second thermoelectric cooler
A second thermoelectric cooler having an active face and a reference face arranged to interact thermally with the first thermoelectric cooler through a thermal interposer.
Thermal interposer between thermoelectric coolers
A thermal interposer disposed between the first and second thermoelectric coolers such that the reference face of the first thermoelectric cooler is thermally coupled with the active face of the second thermoelectric cooler.
Controller coordinated operation
A controller operatively coupled to each of the first and second thermoelectric coolers, the controller configured to operate the second thermoelectric cooler concurrent with the first thermoelectric cooler so as to increase efficiency of the first thermoelectric cooler as a temperature of the active face of the first thermoelectric cooler changes from an initial temperature to a desired target temperature.
Thermal interposer acting as thermal capacitor
The thermal interposer acts as a thermal capacitor to facilitate controlled storage and release of thermal energy thereby improving speed and efficiency of the thermal cycling.
Thermal engagement with reaction vessel
The active face of the first thermoelectric cooler thermally engages the reaction vessel so that operation of the first thermoelectric cooler changes a temperature of the reaction vessel [procedural detail omitted for safety].
Temperature sensors coupled to controller
A first temperature sensor adapted to sense the temperature of the active face of the first thermoelectric cooler and a second temperature sensor adapted to sense a temperature of the thermal capacitor, wherein the sensors are coupled with the controller such that operation of the thermoelectric coolers is based, at least in part, on inputs from the sensors.
Primary and secondary control loops
A controller configuration comprising a primary control loop receiving input from the first temperature sensor and a secondary control loop receiving input from the second temperature sensor, where the bandwidth response of the primary control loop can be timed faster than the secondary control loop and both loops are closed-loop in certain embodiments.
Heat sink to prevent thermal runaway
A heat sink coupled with the reference face of the second thermoelectric cooler to prevent thermal runaway during cycling, incorporated within a generally planar device configuration.
Planar configuration enabling optical detection
A generally planar configuration dimensioned to correspond to a planar portion of a reaction vessel, wherein the device can be adapted to engage the reaction vessel on a single side to allow optical detection from an opposing side and wherein two devices can be used on opposing sides to allow simultaneous heating and optical interrogation through minor walls.
The independent claim centers on a dual-thermoelectric cooler architecture thermally coupled by a thermal interposer that acts as a thermal capacitor, with coordinated controller operation and temperature sensing via primary and secondary control loops to improve speed and efficiency of thermal cycling in thermal engagement with a reaction vessel, and further includes heat-sink and planar configuration features to support reliable operation and optical detection.
Stated Advantages
Improved control, rapidity and efficiency in thermal cycling.
Increased heating and cooling speed and efficiency relative to conventional systems.
Reduced dependence on ambient environment allowing operation in higher ambient temperatures and portable/field testing contexts.
Compact, planar construction suitable for use with reduced-size sample analysis devices and enabling single-sided heating to allow optical detection from an opposing side.
Enhanced thermal efficiency and robustness through coordinated operation of multiple thermal elements and use of a thermal capacitor.
Enables use of thermal modeling (including real-time modeling with Kalman filtering) to predict in situ reaction chamber temperatures and improve control and assay development.
Documented Applications
Thermal cycling for polymerase chain reaction (PCR) and related nucleic acid amplification processes.
Nucleic acid amplification methods including rapid-PCR, ligase chain reaction (LCR), self-sustained sequence replication, enzyme kinetic studies, homogeneous ligand binding assays, and complex biochemical mechanistic studies that require complex temperature changes.
Use with a removable thermal control module interfacing with a disposable assay cartridge and a reaction vessel within a sample analysis device for detection of target nucleic acid analytes.
Point-of-care and field testing systems for rapid detection of viral/bacterial outbreaks where portability and reduced size are important.
One-sided heating configurations that permit optical excitation and detection through opposing faces or minor walls of a reaction vessel during thermal cycling.
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