Variable temperature reactor, heater and control circuit for the same
Inventors
Buckland, Justin • Jellicoe, Tom • Stokoe, Alex • ARAYA-WILLIAMS, AMARU
Assignees
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Publication Number
US-11338296-B2
Publication Date
2022-05-24
Expiration Date
Abstract
There is described a variable-temperature reactor for hosting a predetermined reaction therein. The reactor comprises a reaction cell, a heater, and a heat sink. The reaction cell has a reaction volume with thickness Hv and width Wv where Wv>4Hv and is defined by faces with one of the larger area faces of the reaction volume being bounded by an outer wall with thickness Hw. The heater is in contact with the said outer wall. The heater comprises a heat-generating heater element located on the face closer to the reaction volume and a heater support on the opposite face. The heater support is in contact with a heat sink, such that the heater support provides a thermal resistance RT between the heater element and the heat sink. The reactor, when filled with reagents having thermal diffusion coefficient Dv has a diffusion time tv, in the thickness direction, tv=Hv2/Dv. tv is less than the reaction time constant tR. The outer wall has a thermal diffusion coefficient Dw and has a thermal diffusion time tw=Hw2|Dw<tv.
Core Innovation
The invention provides a variable-temperature reactor for hosting a reaction in one or more enclosed flat reaction volumes. The reaction cell includes one or more side walls and a first thin outer wall arranged in contact with a first end of the side walls, and either a cover or a second thin outer wall arranged in contact with a second end of the side walls and arranged substantially in parallel with the first thin outer wall. The side walls and the thin outer walls enclose flat reaction volumes having a width and a thickness.
The flat reaction volume geometry is defined so the width is greater than four times the thickness in each flat reaction volume, and the flat reaction volume thickness is about 100 microns to about 250 microns. The first thin outer wall has a thickness of less than about 76 microns and a thermal diffusion coefficient selected to provide a thin outer wall thermal diffusion time of less than about one second.
A heater is arranged in contact with the first thin outer wall and includes a heater element sized and arranged to extend across a full area of each flat reaction volume, and a heater support arranged in contact with the heater element on a side opposite the first thin outer wall. A heat sink is in contact with the heater support such that the heater support provides a thermal resistance between the heater element and the heat sink.
The disclosed concepts include variable-temperature cycling between a higher temperature and a lower temperature, with design principles aimed at controlling heat flow and compensating for heater edge non-uniformity. The document also describes using the heater as a temperature sensor, and provides options for thin-wall measurement features such as Kelvin contacts. Example applications explicitly include fast PCR thermocycling and label-free calorimetric/DTA/DSC monitoring, including Wheatstone bridge differential detection for thermal measurements.
Claims Coverage
The independent claim includes the core variable-temperature reactor architecture with thin outer walls forming enclosed flat reaction volumes and thermal coupling via a heater support providing a thermal resistance to a heat sink. The independent claim family further covers additional independent configurations and refinements focused on cycling behavior, ramp rate, thermal resistance relationships, heat-sink/heater-support material effusivity, heater measurement structures, and dual-sided heating.
Thin outer wall flat reaction volumes with width-to-thickness constraint and short diffusion time
A reaction cell encloses one or more flat reaction volumes by one or more side walls and a first thin outer wall arranged in contact with a first end and either a cover or a second thin outer wall arranged in contact with a second end substantially parallel to the first thin outer wall, where the flat reaction volume width is greater than four times the flat reaction volume thickness, the flat reaction volume thickness is about 100 microns to about 250 microns, and the first thin outer wall has a thickness of less than about 76 microns with a thermal diffusion coefficient selected to provide a thin outer wall thermal diffusion time of less than about one second.
Full-area heater contacting thin outer wall with heater support thermal resistance to heat sink
A heater includes a heater element arranged in contact with the first thin outer wall and sized and arranged to extend across a full area of each flat reaction volume, and a heater support arranged in contact with the heater element on a side opposite the first thin outer wall, with a heat sink in contact with the heater support such that the heater support provides a thermal resistance between the heater element and the heat sink.
Repeated temperature cycling with thermal resistance and temperature-difference/heater-power relationship
A variable-temperature reactor repeatedly cycles its reactor temperature between a lower and higher temperature, both above a heat sink temperature, using the heater, with an inequality-based relationship constraining thermal resistance and heater power output such that the thermal resistance of the heater support times heater power is between 0.5 and 2 times the summed temperature differences between the higher and heat sink temperatures and between the lower and heat sink temperatures.
Minimum temperature ramp rate
The variable-temperature reactor changes the reactor temperature at a temperature ramp rate of at least 70°C per second using the heater.
Heat-sink and heater-support thermal effusivity ratio
A variable-temperature reactor configured such that the heat sink material has a thermal effusivity more than ten times that of the heater support material, with thermal effusivity defined as the square root of the product of thermal conductivity, density, and specific heat capacity.
Kelvin contacts for electrical resistance measurement in the heater
The variable-temperature reactor further includes Kelvin contacts in its heater for electrical resistance measurements.
Dual-sided thin outer walls with second heater and second heat sink
A variable-temperature reactor having a reaction cell with first and second thin outer walls arranged opposite each other, where a second heater contacts the second thin outer wall and a second heat sink contacts the second heater.
Across the independent claim and its main refinements, the inventive coverage centers on thin outer wall-defined flat reaction volumes with constrained width-to-thickness geometry and short thin-wall thermal diffusion time, combined with a full-area heater thermally coupled to a heat sink through a heater support that provides thermal resistance, with further claim coverage on thermal cycling behavior, minimum ramp rate, heater-support/heat-sink effusivity relationships, dual-sided heating, and Kelvin-contact heater measurement.
Stated Advantages
Provides controlled thermal coupling between the heater element and the heat sink through thermal resistance provided by the heater support.
Enables rapid temperature cycling using thermal diffusion time constraints relative to a reaction time constant.
Implements temperature cycling between a higher temperature and a lower temperature using the heater.
Allows label-free calorimetric/DTA/DSC monitoring, including differential thermal analysis using Wheatstone bridge detection.
Supports fast PCR thermocycling.
Documented Applications
Fast PCR thermocycling, including DNA amplification and a DNA melt curve.
Label-free calorimetric monitoring including differential thermal analysis (DTA) and differential scanning calorimetry (DSC), including Wheatstone bridge differential detection and calorimetric detection of DNA melting.
Digital PCR concept described as wall-free, droplet-free digital PCR using short cycle times, including multiplexed PCR with diffusion restriction channels and preloaded reagents.
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