Search for: All records

The splenic interendothelial slits fulfill the essential function of continuously filtering red blood cells (RBCs) from the bloodstream to eliminate abnormal and aged cells. To date, the process by which 8 $\mathrm{\mu }$m RBCs pass through 0.3 $\mathrm{\mu }$m-wide slits remains enigmatic. Does the slit caliber increase during RBC passage as sometimes suggested? Here, we elucidated the mechanisms that govern the RBC retention or passage dynamics in slits by combining multiscale modeling, live imaging, and microfluidic experiments on an original device with submicron-wide physiologically calibrated slits. We observed that healthy RBCs pass through 0.28 $\mathrm{\mu }$m-wide rigid slits at 37 °C. To achieve this feat, they must meet two requirements. Geometrically, their surface area-to-volume ratio must be compatible with a shape in two tether-connected equal spheres. Mechanically, the cells with a low surface area-to-volume ratio (28% of RBCs in a 0.4 $\mathrm{\mu }$m-wide slit) must locally unfold their spectrin cytoskeleton inside the slit. In contrast, activation of the mechanosensitive PIEZO1 channel is not required. The RBC transit time through the slits follows a $-$1 and $-$3 power law with in-slit pressure drop and slip width, respectively. This law is similar to that of a Newtonian fluid in a two-dimensional Poiseuille flow, showing that the dynamics of RBCs is controlled by their cytoplasmic viscosity. Altogether, our results show that filtration through submicron-wide slits is possible without further slit opening. Furthermore, our approach addresses the critical need for in vitro evaluation of splenic clearance of diseased or engineered RBCs for transfusion and drug delivery. 

We derived equations and closed-form solutions of transit time for a viscous droplet squeezing through a small circular pore with a finite length at microscale under constant pressures. Our analyses were motivated by the vital processes of biological cells squeezing through small pores in blood vessels and sinusoids and droplets squeezing through pores in microfluidics. First, we derived ordinary differential equations (ODEs) of a droplet squeezing through a circular pore by combining Sampson flow, Poiseuille flow, and Young–Laplace equations and took into account the lubrication layer between the droplet and the pore wall. Second, for droplets wetting the wall with small surface tension, we derived the closed-form solutions of transit time. For droplets with finite surface tension, we solved the original ODEs numerically to predict the transit time. After validations against experiments and finite element simulations, we studied the effects of pressure, viscosity, pore/droplet dimensions, and surface tension on the transit time. We found that the transit time is inversely linearly proportional to pressure when the surface tension is low compared to the critical surface tension for preventing the droplet to pass and becomes nonlinear when it approaches the critical tension. Remarkably, we showed that when a fixed percentage of surface tension to critical tension is applied, the transit time is always inversely linearly proportional to pressure, and the dependence of transit time on surface tension is nonmonotonic. Our results provided a quick way of quantitative calculations of transit time for designing droplet microfluidics and understanding cells passing through constrictions.