Thermal control device and methods utilizing temperature distribution modeling
Inventors
Lee, Marissa • Koay, Jessica • Rohrs, Charles • Solis, Earl • Piccini, Matthew • Casler, Jr., Richard J.
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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-12321183-B2
Publication Date
2025-06-03
Expiration Date
Abstract
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.
Core Innovation
The present invention relates to a thermal control device that performs temperature control, particularly thermal cycling of a biological reaction-vessel with improved control, rapidity and efficiency. Such thermal control device and methods can include one or more active elements, such as 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. Methods of calibration of such systems utilizing a thermal calibrator as a proxy for the reaction-vessel are also provided herein. [procedural detail omitted for safety]
Conventional thermal cycling systems commonly use cooling devices that occupy substantial space and require significant power and exhibit start-up lag time and shutdown overlap, which negatively affect precision and portability. Such fan-based cooling systems can perform poorly in higher ambient temperature environments and limit heating and cooling rates, which in turn can lead to inefficient or ineffective biochemical reactions and undesired 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.
The invention is cast within a control-theoretic framework emphasizing observability and controllability, employing a state-estimator to infer reaction-vessel temperature distribution from noisy measurements and a controller that regulates the distribution to follow a temperature distribution command trajectory. The controller determines an estimated reaction-vessel temperature distribution using at least one of a state of the power electronics and temperature outputs from one or more sensors, and can employ a pole-zero filter model and modes including common-mode, differential-mode, and superposition to regulate average sample temperature and sample temperature gradients. The system is configured to achieve a regulated output of the temperature distribution that is substantially independent of the ambient temperature.
Claims Coverage
This patent includes two independent claims and nine main inventive features extracted from those claims.
Active element positioned to direct a heat-flux
at least one active element that generates a heat-flux, wherein the at least one active element is positioned to direct the heat-flux into at least one face of the reaction-vessel when placed adjacent thereto;
Electronics module with power electronics
an electronics module having power electronics that power the at least one active element;
Temperature sensors for ambient and active element measurement
one or more temperature sensors that are positioned and configured to measure: an ambient temperature indicative of the thermal operating environment around the reaction-vessel; and/or the temperature of a portion of the at least one active element;
Control unit determining estimated thermal model using power electronics state
a control unit having a processor, the control unit being communicatively coupled with the one or more temperature sensors and operably coupled with the electronics module, wherein the processor is configured to: determine an estimated thermal model of a reaction-vessel temperature distribution across the reaction-vessel using at least a state of the power electronics of the electronics module as an input;
Control unit regulating temperature distribution independent of ambient
determine or obtain a temperature command or a function representing a desired temperature distribution profile for the reaction-vessel; and regulate a reaction-vessel temperature distribution in accordance with the temperature command or the function and the estimated thermal model of the reaction-vessel temperature-distribution so as to achieve a regulated output of the reaction-vessel temperature distribution that is substantially independent of the ambient temperature.
Obtaining temperature outputs from sensors
obtaining, with a control unit of the thermal control device, a temperature output from one or more temperature sensors of a temperature control system, the temperature output corresponding to a temperature of a portion of the at least one active element and/or an ambient temperature indicative of the thermal operating environment around the reaction-vessel;
Determining estimated thermal model using power electronics state (method)
determining an estimated thermal model of a reaction-vessel temperature distribution across the reaction-vessel using at least a state of a power electronics as an input;
Determining or obtaining a temperature command or function
determining or obtaining a temperature command or a function representing a desired temperature distribution profile for the reaction-vessel;
Operating active element to regulate distribution independent of ambient
operating the at least one active element so as to regulate a reaction-vessel temperature distribution in accordance with the temperature command or the function and the estimated thermal model of the reaction-vessel temperature distribution so as to achieve a regulated output of the distribution that is substantially independent of the ambient temperature.
The independent claims recite a thermal control system and a corresponding method that combine one or more active elements, power electronics, temperature sensors, and a processor-determined estimated thermal model to regulate a reaction-vessel temperature distribution according to a temperature command so as to achieve a regulated output substantially independent of ambient temperature.
Stated Advantages
Improved control, speed and efficiency in temperature cycling.
Ability to achieve a regulated output of the reaction-vessel temperature distribution that is substantially independent of the ambient temperature.
Greater heating and cooling rates not dependent on the ambient environment and suitable for reduced size, low cost inclusion in diagnostic devices.
Improved accuracy and precision of temperature control for thermal cycling without direct measurement of the reaction-vessel temperature distribution.
Adaptability to engage a reaction-vessel on a single side to allow optical detection from an opposing side during thermal cycling.
Documented Applications
Polymerase chain reaction (PCR) for DNA amplification.
Rapid-PCR.
Ligase chain reaction (LCR).
Self-sustained sequence replication.
Enzyme kinetic studies.
Homogeneous ligand binding assays.
Complex biochemical mechanistic studies that require complex temperature changes.
Nucleic acid amplification processes involving thermal cycling of a fluid sample.
Use with a removable thermal control module coupled to a disposable assay cartridge for nucleic acid amplification tests (NAAT) such as PCR and RT-PCR.
Point-of-care and field testing systems for rapid detection of viral or bacterial outbreaks.
Isothermal amplification methods and other applications requiring precise temperature control without cycling.
Calibration of thermal control systems using a thermal calibrator as a proxy for reaction-vessel temperature distribution measurement.
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