Mechanical phenotyping of breast cell lines by in-flow deformation-dependent dynamics under tuneable compressive forces

Cell mechanical properties are powerful biomarkers for label-free phenotyping. To date, microfluidic approaches assay mechanical properties by measuring changes in cellular shape, applying extensional or shear flows or forcing cells to pass through constrictions. In general, such approaches use high-speed imaging or transit time measurements to evaluate cell deformation, while cell dynamics in-flow after stress imposition have not yet been considered. Here, we present a microfluidic approach to apply, over a wide range, tuneable compressive forces on suspended cells, which result in well distinct signatures of deformation-dependent dynamic motions. By properly conceiving microfluidic chip geometry and rheological fluid properties, we modulate applied single-cell forces, which result in different motion regimes (rolling, tumbling or tank-treating) depending on the investigated cell line. We decided to prove our approach by testing breast cell lines, with well-known mechanical properties. We measured a set of in-flow parameters (orientation angle, aspect ratio, cell deformation and cell diameter) as a backward analysis of cell mechanical response. By such an approach, we report that the highly invasive tumour cells (MDA-MB-231) are much more deformable (6-times higher) than healthy (MCF-10A) and low invasive ones (MCF-7). Thus, we demonstrate that a microfluidic design with tuneable rheological fluid properties and direct analysis of bright-field images can be suitable for the label-free mechanical phenotyping of various cell lines.