Microfluidic constriction-based mechanoprofiling of alginate microgels and bladder cancer cells

Microfluidic devices have emerged as a powerful tool for mechanical characterization of dispersed cell populations. To assess the performance of the devices, monodisperse Ca-alginate gel beads with a similar mean size as the cells were fabricated by microfluidic picoinjection and characterized by a parallel array of constriction segments in a microfluidic device, where the constriction segments had cross-section less than the beads. The transit times of these monodisperse gel beads showed limited variation for a given formulation, and an increase in transit time with changes in gel bead composition is expected to yield a larger elastic modulus. Alongside, we compare distributions of mechanical parameters obtained by atomic force microscopy (AFM) with mechanically relevant parameters obtained by microfluidic constriction using bladder cancer cell lines HCV29 and T24. The data from AFM using a tipless cantilever show that the median overall Young’s modulus of the T24 cells was 155 Pa, which is about 32% of the median value of 490 Pa for the HCV29 cells. The median values of the transit times through 300 μm long constrictions with cross-section of either 7x7 μm 2 or 10x10 μm 2 showed a similar ratio between the cell types as the overall Young’s modulus determined by AFM. Within a certain range of Taylor deformation, the narrower transit time distribution for gel beads as compared to a broader transit-time distribution of cells reflects heterogeneity in their mechanical properties. The wider distributions of the transit times (from microfluidic constriction) as compared to the distribution of overall mechanical properties (AFM) were discussed in terms of differences in the onset of nonlinear and/or stress-induced stiffening of the cells in the two types of cell characterization. This study shows that a direct comparison between distributions of parameters reflecting mechanical properties obtained by constriction studies with AFM requires careful consideration of deformation regimes. • Forced translocation of homogeneously sized Ca-alginate gel beads in constriction channels show homogenous transition time. • Forced translocation of cell dispersions in constriction channels show large variation in transition time. • Variations in cell transition time in constriction channels are due to heterogeneity in size, elastic modulus and possibly non-linear force-deformation relationship. • There are possible differences in deformation modes in constriction of cells as compared to controlled deformation in AFM.