Abstract
This work examines improvements in the heating and cooling step, known as thermal cycling, which is critical to Polymerase Chain Reaction (PCR) technology by investigating the thermal performance of different approaches to changing the reaction temperature. This research explores the feasibility of using different temperature liquids to control the temperature of a 96-well block. PCR is a widely used technique for amplifying and detective sensitive analytes in clinical, life science, and molecular diagnostic applications since it can offer sensitive results at low cost and quick turnaround times. This investigation specifically would be focused on markets where the time to receive an answer from a test is critical, with the thermal cycling step often being the most time consuming. A numerical analysis was performed to investigate modeling different temperature fluids through fluid channels in the reaction block and the subsequent heat transfer rates that could be achieved using computational fluid dynamics (CFD) software. The goal of this study is to evaluate the thermal performance of passing different temperature fluids through fluid channels in a reaction block that supports the standard 96-well plate geometry and how it compares to current on-market thermoelectric-based systems. Other studies have explored other methods of improving heat transfer rates such as reducing the reaction volumes, reducing the contact area, or using different heating methods all of which require very low reaction volumes and/or lower sample capacity. Here we seek to study a method which would support larger volumes while maintaining standard 96 sample capacity. Simulation results show a temperature ramp rate increase of 2-3X using the fluid-based approach compared to the thermoelectric-based approach, while maintaining similar thermal uniformity across the surface of the reaction block. Experimental validation was conducted for the model using a prototype of the system which showed some losses in comparison due to the simulation results. Despite this, the validation showed good agreement with average ramp rates of 4.54°C/s in heating and -5.89°C/s in cooling, comparable thermal uniformity across the heating surface, and was within 10% error of simulation results while demonstrating heating efficiency of 45% and cooling coefficient of performance (COP) value of 1.13. This method could potentially serve to guide work towards decreasing thermal cycling times which ultimately would provide clinicians and researchers results faster for time-sensitive applications.