Effect of in-plane and out-of-plane bifurcated microfluidic channels on the flow of aggregating red blood cells.

The blood flow through our microvascular system is a renowned difficult process to understand because the complex flow behavior of blood is intertwined with the complex geometry it has to flow through. Conventional 2D microfluidics has provided important insights, but progress is hampered by the limitation of 2-D confinement. Here we use selective laser-induced etching to excavate non-planar 3-D microfluidic channels in glass that consist of two generations of bifurcations, heading towards more physiological geometries. We identify a cross-talk between the first and second bifurcation only when both bifurcations are in the same plane, as observed in 2D microfluidics. Contrarily, the flow in the branch where the second bifurcation is perpendicular to the first is hardly affected by the initial distortion. This difference in flow behavior is only observed when red blood cells are aggregated, due to the presence of dextran, and disappears by increasing the distance between both generations of bifurcations. Thus, 3-D structures scramble in-plane flow distortions, exemplifying the importance of experimenting with truly 3D microfluidic designs in order to understand complex physiological flow behavior.

Competition between deformation and free volume quantified by 3D image analysis of red blood cell.

Cells in living organisms are subjected to mechanical strains caused by external forces like overcrowding, resulting in strong deformations that affect cell function. We study the interplay between deformation and crowding of red blood cells (RBCs) in dispersions of nonabsorbing rod-like viruses. We identify a sequence of configurational transitions of RBC doublets, including configurations that can only be induced by long-ranged attraction: highly fluctuating T-shaped and face-to-face configurations at low, and doublets approaching a complete spherical configuration at high, rod concentrations. Complementary simulations are used to explore different energy contributions to deformation as well as the stability of RBC doublet configurations. Our advanced analysis of 3D reconstructed confocal images of RBC doublets quantifies the depletion interaction and the resulting deformation energy. Thus, we introduce a noninvasive, high-throughput platform that is generally applicable to investigate the mechanical response of biological cells to external forces and characterize their mechanical properties.