Liquid biopsy has the potential to revolutionise the way we diagnose and manage cancer, avoiding expensive and invasive traditional biopsies and enabling frequent analysis of the tumour’s molecular profile. Droplet digital PCR (ddPCR) is a promising route to realising this technique.

Successfully developing a ddPCR device requires the designer to create and control tiny (picolitre) droplets with great precision, for example maintaining a consistent droplet size and frequency of droplet generation. Often the microfluidic design of a droplet generating chip is refined through an iterative experimental approach to both geometry and materials, which, though effective, is hampered by the need for multiple physical prototypes, which can be both costly and time-consuming.

Computational Fluid Dynamics (CFD) is a powerful simulation tool used to numerically model problems involving fluid flow which can be used to reduce the number of prototypes needed to develop a diagnostics device and provide deeper insight into the underlying mechanics of fluid systems.

To illustrate this potential, we have used CFD to simulate a droplet generating chip. This is a complex transient 3d problem involving multiple fluids and surface tension and is thus challenging to simulate, but brings physical insights that would be impractical or impossible to realise with ordinary experimental techniques. As an example we can interrogate the fluid velocity and pressure fields to determine the detailed dynamics of droplet formation and use this to inform our design decisions.

Comparison with experiments gives us confidence in our approach, as can be seen from the comparable frequency and visual analogues in the droplet generating process (see animation below). Going forward, this allows us to investigate properties that would be difficult or expensive to analyse physically, such as a change of chip material, different fluid and surfactant combinations or tweaks to the channel geometry.

Although not always appropriate and to be wielded with expertise and caution in equal measure, computer-aided engineering tools such as this are invaluable in situations where additional physical insight can accelerate design or where the cost of frequent prototyping becomes exorbitant.

We use our expertise in CFD to streamline our diagnostic device development process, providing physical insight to arrive at an optimised solution faster and reducing the overhead of costly prototypes through simulation-lead microfluidic design. Get in touch to see how we can help you develop your technology in liquid biopsy.

Dan Cowen

Dan is a Senior Engineer in the Medical Technology division.