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-12551897-B2
Publication Date
2026-02-17
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>4 HV 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 relates to performing nucleic acid amplification with rapid polymerase chain reaction (PCR) thermocycling in a reaction cell that encloses a flat reaction volume. A liquid sample comprising nucleic acid and a polymerase enzyme is heated and cooled within the flat reaction volume, while the heating is carried out by a heater element and cooling is carried out by a heat sink. The heater element is arranged so that one side contacts the reaction cell and the opposite side contacts a heater support arranged between the heater element and the heat sink.
The heater support provides a thermal resistance R_T between the heater element and the heat sink, and the thermal resistance is between about 20 Kelvin/watt and about 5 Kelvin/watt. The system is configured so that the thermal diffusion time constraints associated with a thin reaction volume and a thin outer wall enable fast, uniform temperature cycling without large thermal inertia. PCR thermocycling is performed with a cycle time of about 5 seconds or less, with each cycle including raising the temperature from a low temperature to a high temperature and back down to the low temperature.
Thermocycling is performed as one continuous body of liquid within the flat reaction volume, and all thermocycling occurs within the reaction cell without moving the sample between two different temperature zones that are spatially separated. The amplified DNA is detected after PCR thermocycling within the flat reaction volume. The described reactor configuration supports rapid PCR and related multi-step thermal processes, and enables label-free calorimetric and related detection using resistive heating concepts such as Kelvin contacts and optional Wheatstone-bridge sample/reference detection.
Claims Coverage
The independent claim covers rapid PCR thermocycling in a flat, thin reaction volume with continuous heating and cooling of an unpartitioned liquid body, including a heater-support thermal resistance range, a short cycle-time requirement, and detection of amplified DNA. No other independent claims are provided in the partial content.
Flat reaction volume PCR thermocycling with heater and heat sink
A method of performing nucleic acid amplification with rapid polymerase chain reaction (PCR) thermocycling, the method comprising obtaining a liquid sample comprising nucleic acid; introducing the sample and a polymerase enzyme into a reaction cell enclosing a flat reaction volume; heating the sample within the flat reaction volume with a heater element and cooling within the flat reaction volume with a heat sink; conducting an initial hot-start of the sample in the flat reaction volume to activate the polymerase enzyme; performing PCR thermocycling with a cycle time of about 5 seconds or less; and detecting the amplified DNA.
Heater support thermal resistance between heater element and heat sink
Where one side of the heater element contacts the reaction cell, and an opposite side of the heater element contacts a heater support arranged between the heater element and the heat sink; where the heater support provides a thermal resistance R_T; and where the thermal resistance of the heater support between the heater element and the heat sink is between about 20 Kelvin/watt and about 5 Kelvin/watt.
Continuous-body thermocycling without separated temperature zones
Where the sample is heated and cooled as one continuous body of liquid within the flat reaction volume, and where all thermocycling of the sample occurs in the flat reaction volume within the reaction cell without moving the sample between two different temperature zones that are spatially separated.
Short PCR cycle including heating and cooling within one flat reaction volume
Performing PCR thermocycling with a cycle time of about 5 seconds or less, where a cycle includes at least raising a temperature of the sample in the flat reaction volume from a low temperature to a high temperature and back down to the low temperature.
Across the provided independent claim, the core coverage centers on rapid PCR thermocycling in a flat reaction volume with continuous liquid heating and cooling inside a single reaction zone, using a heater/support/heat-sink thermal-resistance arrangement with a specified R_T range, and detection of amplified DNA after executing short PCR cycles including high-to-low temperature transitions.
Stated Advantages
Enables rapid PCR thermocycling with a cycle time of about 5 seconds or less.
Allows fast, uniform temperature cycling without large thermal inertia, based on thermal diffusion time constraints.
Performs thermocycling without moving the sample between two different temperature zones that are spatially separated.
Documented Applications
Rapid polymerase chain reaction (PCR) thermocycling for nucleic acid amplification, including detection of amplified DNA.
Related multi-step thermal processes supported by the described variable-temperature reactor configuration.
Label-free calorimetric and related detection using resistive heaters, including calorimetry/DTA/DSC and AC calorimetry concepts and optional sample/reference detection.
PCR thermocycling for DNA melting and fluorescence monitoring contexts as described in the partial content.
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