Why are microfluidics important in medical technologies?

Microfluidics has been a rapidly growing field within a range of engineering disciplines over the past few decades, with applications running from thermal control of microelectronic devices to chemical process engineering, and even simple fluid-based computational logic!

But nowhere has the precision control of tiny quantities of fluid found more uses than in the medical sciences. Thousands of centimetre- or even millimetre-scale devices have been developed for use in high-value drug production, emulsion generation, cytometry, drug detection, drug dosing, cellular analysis, cancer detection, or a whole range of other specialised diagnostic applications.

Microfluidic devices are characterised by the handling of very small quantities of fluid, either as continuous flow in a channel, storage in microwells, or as droplets on a chip; typical volumes range of femto- to picolitres (10^-15– 10^-12 L)! Because the manufacturing processes for many microfluidic systems were originally developed in the semiconductor industry, they also lend themselves well to the direct integration of micromachined sensors and actuators: Labs-on-a-Chip!

In diagnostics as well as pharmaceutical production, one clear advantage of a microfluidic approach is a reduction in the consumption of expensive reagents and catalysts (i.e. platinum, palladium, rhodium). Similarly, a reduction in the generation of waste products is desirable because handling may be non-trivial, either requiring complex and energy intensive processes for breakdown into non-toxic substances or specialised long-term storage. If microfluidics can reasonably be employed, costs may be reduced not only on the input and waste effluents, but also on other peripheral process factors such as capital costs due to reactor modularity, energy efficiency, or better process control.

Microfluidic platforms significantly increase the fluid surface-to-volume ratio, which provides a range of process-control advantages. One of these is rapid mixing; where two reagent streams come into contact, for example at a T-junction, complete and homogeneous mixing occurs on a far faster scale than in macro-scale mixing. In many applications this is critical because incompletely mixed reagents may allow undesired side-reactions to occur. Additionally, this rapid mixing plus the small channel size allows for a high degree of thermal control. Highly exothermic or even explosive reactions may be carried out safely because only a small absolute amount of heat is generated, and it is quickly removed. Consistent temperatures in the fluids leads to more consistent yields, whether in production or in diagnostics.

While microfluidic platforms offer a range of safety, cost, and process-control advantages, there are challenges which remain topics of ongoing research and engineering development.

One of these areas is in quantifying the effects of manufacturing tolerances. Because the channels are so small, deviations from a designed cross-section profile may have an outsized effect of factors such as pressure drop or mixing behaviour. Another area which often presents challenges is in multiphase flows. In microdroplet generators, two immiscible fluids meet at a junction, with highly repeatable droplet size distributions resulting; these are often used in emulsions for drug encapsulation and dosing. Similarly, microbubbles may be used for gas-liquid reactions that require extremely fast mixing. Solids entrained in a flow similarly allow for enhanced process control, such as at the surface of catalyst particles in production or single-cell sorting in diagnostics. 

The physics of these multiphase microfluidic processes can be extremely complex! Generating the desired droplet or bubble size requires a lot of fine-tuning of channel shapes and sizes, as well as pressures and flow rates. Biological cells or catalyst particles may clump or stick to walls, forming blockages, so it’s important to understand channel and particle surface properties, and whether flow patterns will reduce adhesion and blocking risks. 

Because of the complexity of these processes, physical device manufacture and test can become expensive and time-consuming. Computational modelling, while not a replacement for physical testing, can greatly reduce development time and costs. Correlation of modelling results with existing experimental data can give confidence in the fundamentals of a baseline model and can then help accelerate new design iterations.

Xi Engineering Consultants has extensive experience in Finite Element Simulation with COMSOL Multiphysics for a broad range of engineering applications, including microfluidics. Xi has been working on several medical related projects with the most recent one being LUMICKS (Amsterdam, Netherlands) on the design and characterisation of Lab-on-a-Chip devices incorporating acoustic cell-manipulation capabilities in microchannels for single-cell cancer detection diagnostics. Indeed, this is another medtech success story as we met at the 2021 show and began developing collaboration ideas since!

Xi Engineering will be at stand B37 at Med-Tech Innovation Expo 2022 on 8th-9th June at the NEC, Birmingham. For more information visit www.med-techexpo.com.