Variable temperature reactor, heater, and control circuit for the same
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Solution Overview
Problem
Existing PCR thermocycling methods are energy-inefficient, slow, and mechanically complex, with Peltier elements having limited lifetimes due to thermal cycling stresses, and serpentine channels increasing sample volume and reagent costs.
Innovation Solution
A reactor design with a reaction cell, heater, and heat sink, featuring a heater element and support with optimized thermal resistance, allowing rapid temperature changes and uniformity, and incorporating a heater that functions as a temperature sensor, enabling fast thermocycling without mechanical movement or long serpentine channels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Temperature
If a Peltier element is used for heating and cooling in conventional PCR thermocycling, then temperature control is achieved, but the apparatus becomes large, power consumption increases, and thermal cycling time increases due to thermal diffusion through the Peltier element and sample containment parts
Solution Approach 1:
The patent replaces the mechanical Peltier element with a resistive heater and heat sink system. The heater is positioned in direct thermal contact with the reaction cell, eliminating the need for mechanical moving parts and thermal diffusion through Peltier elements. This substitution enables rapid temperature changes by directly heating the reaction cell without the thermal diffusion limitations of Peltier elements.
Solution Approach 2:
The patent extracts the heating function from the Peltier element and separates it into distinct components: a resistive heater and a heat sink. This extraction allows the heater to be optimized for rapid heat generation and the heat sink for efficient heat dissipation, independently optimizing each function to reduce overall thermal cycling time.
2Temperature
If a Peltier element is used for thermal cycling, then temperature adjustment is achieved, but the lifetime of the Peltier element is limited due to mechanical stresses from repeated thermal cycling
Solution Approach 1:
The patent replaces the mechanical Peltier element with a resistive heater system that has no moving parts. The heater is mounted on a support structure that is thermally coupled to a heat sink, creating a static thermal management system that eliminates mechanical stresses from repeated thermal cycling, thereby improving reliability and lifetime.
3Temperature
If a serpentine channel is used to pass the sample through temperature zones, then thermal cycling is achieved, but the sample volume increases and reagent costs increase due to the large surface area of the microfluidic channel
Solution Approach 1:
The patent replaces the serpentine microfluidic channel system with a direct heating approach where the reaction cell is heated directly by the resistive heater. This eliminates the need for long serpentine channels that would require large sample volumes to fill, reducing both sample volume requirements and reagent costs while maintaining effective thermal cycling.
4Temperature
If a remote temperature sensor is used to control the thermocycler, then temperature monitoring is achieved, but there is a lag in the thermal response of the temperature sensor compared with the Peltier, complicating thermal control
Solution Approach 1:
The patent merges the temperature sensing function with the heating function by using the resistive heater itself as the temperature sensor. The heater is positioned in direct thermal contact with the reaction cell, allowing it to simultaneously generate heat and sense temperature changes in real-time, eliminating the time lag associated with remote temperature sensors.
Solution Approach 2:
The resistive heater serves multiple functions: it generates heat for thermal cycling and simultaneously acts as a temperature sensor to monitor reaction cell temperature. This multi-functionality eliminates the need for separate remote sensors, reducing thermal response lag by providing direct, real-time temperature feedback at the heat source.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Achieves rapid temperature ramp rates of 100°C/s, reduces thermal cycling time to <1s, and allows for precise temperature control with minimal mechanical complexity and cost, suitable for PCR and other reactions requiring rapid temperature adjustments.
Implementation Method 1
the heater comprises a heat-generating heater element located on the face closer to the reaction volume
Implementation Method 2
a heat sink, wherein the reaction cell has a reaction volume with thickness HV and width WV
Implementation Method 3
the heater support being in contact with a heat sink, such that the heater support provides a thermal resistance RT between the heater element and the heat sink
Implementation Method 4
the reactor, when filled with reagents having thermal diffusion coefficient DV has a diffusion time tV, in the thickness direction
Data Source
AI summary
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.