Impact of flagellated and elongated morphological phenotypes on the focusing behaviours of biological cells in inertial microfluidic devices

Abstract

Inertial microfluidics has demonstrated tremendous potential to impact biological - and notably medical - fields, by offering a highly versatile, portable and cost-effective approach to cell focusing and sorting. While the range of applications of inertial devices spans medical diagnostics, bioprocessing or water engineering to mention a few, translation is still impeded by the lack of clear understanding of cell interactions in such devices. This often leads to bespoke designs that take years of development and characterisation for one targeted application, and limited tools for informed optimisation. A more fundamental knowledge of inertial behaviours is key to future translational works and impact, by enabling a deeper understanding of inertial forces in biological systems. Towards this goal, this paper focuses on high-throughput morphological phenotyping of the single-celled, flagellated parasite Leishmania mexicana to better understand how variations in cell body length, width and flagellated status impact the focusing patterns of highly non-spherical cells in curved inertial devices. Some of the key findings in this study include i) not all organelles, such as flagella, will alter focusing if the body shape is conserved, ii) the impact of cell shape is specific to a channel design and slight changes in e.g., cell confinement can completely change focusing patterns, iii) elongated prolate-like cells align in different orientations depending on their lateral position with a curved channel and iv) despite variabilities observed in focusing patterns for elongated versus rounder cell phenotypes, large morphological variations can be completely overcome at high Reynolds numbers so that all phenotypes tightly focus at a single position (here towards the channel outer wall). This last finding, in particular, may open new avenues for highly efficient cell enrichment processes, such as for the detection of pathogens in water.