A surrogate-enabled multi-objective optimisation methodology for a continuous flow Polymerase Chain Reaction (CFPCR) systems is presented, which enables the effect of the applied PCR protocol and the channel width in the extension zone on four practical objectives of interest, to be explored. High fidelity, conjugate heat transfer (CHT) simulations are combined with Machine Learning to create accurate surrogate models of DNA amplification efficiency, total residence time, total substrate volume and pressure drop throughout the design space for a practical CFPCR device with sigmoid-shape microfluidic channels. A series of single objective optimisations are carried out which demonstrate that DNA concentration, pressure drop, total residence time and total substrate volume within a single unitcell can be improved by up to $$\sim$$ ∼ 5.7%, $$\sim$$ ∼ 80.5%, $$\sim$$ ∼ 17.8% and $$\sim$$ ∼ 43.2% respectively, for the practical cases considered. The methodology is then extended to a multi-objective problem, where a scientifically-rigorous procedure is needed to allow designers to strike appropriate compromises between the competing objectives. A series of multi-objective optimisation results are presented in the form of a Pareto surface, which show for example how manufacturing and operating cost reductions from device miniaturisation and reduced power consumption can be achieved with minimal impact on DNA amplification efficiency. DNA amplification has been found to be strongly related to the residence time in the extension zone, but not related to the residence times in denaturation and annealing zones.

Polymerase Chain Reaction (PCR) is widely used in biological research labs in order to detect hereditary diseases, diagnose infectious diseases, clone genes and other purposes. This work focuses on combining CFD and response surface modelling to explore the dependence of DNA amplification on two design parameters in a single phase, continuous flow PCR microfluidic device, consisting of a serpentine-like rectangular channel with three copper wire heaters. The spacing and the width of the microchannel between the heaters are selected as the two design parameters investigated. COMSOL Multiphysics ® 5.4 is used to simulate the performance and function of the microfluidic channel, while Design of Experiments and a polyharmonic spline are used to produce the response surface. The results indicate a ∼1.4% increase at the value of [DNA] in one PCR cycle.

The invention and development of Polymerase Chain Reaction (PCR) technology have revolutionised molecular biology and molecular diagnostics. There is an urgent need to optimise the performance of these devices while reducing the total construction and operation costs. This study proposes a CFD-enabled optimisation methodology for continuous flow (CF) PCR devices with serpentine-channel structure, which enables the optimisation of DNA amplification efficiency and pressure drop to be explored while varying the width (W) and height (H) of the microfluidic (μ) channel. This is achieved by using a surrogate-enabled optimisation approach accounting for the geometrical features of a μCFPCR device by performing a series of simulations using COMSOL Multiphysics 5.4®. The values of the objectives are extracted from the CFD solutions, and the response surfaces are created using polyharmonic splines. Genetic algorithms are then used to locate the optimum design parameters. The results indicate that there is the possibility of improving the DNA concentration and the pressure drop in a PCR cycle by ~2.1 % ([W, H] = [400 μm, 50 μm]) and ~95.2 % ([W, H] = [400 μm, 80 μm]) respectively, by modifying its geometry.