  Nanoparticles delivering drugs, disseminating cancer cells, and red blood
cells (RBCs) during splenic filtration must deform and pass through the
sub-micrometer and high aspect ratio interstices between the endothelial cells
lining blood vessels. The dynamics of passage of particles/cells through these
slit-like interstices remain poorly understood because the in vitro
reproduction of slits with physiological dimensions in devices compatible with
optical microscopy observations requires expensive technologies. Here, novel
microfluidic PDMS devices containing high aspect ratio slits with
sub-micrometer width are molded on silicon masters using a simple, inexpensive,
and highly flexible method combining standard UV lithography and anisotropic
wet etching. These devices enabled revealing novel modes of deformations of
healthy and diseased RBCs squeezing through splenic-like slits (0.6--2 um 5--10
um 1.6--11 $\mu$m3) under physiological interstitial pressures. At the slit
exit, the cytoskeleton of spherocytic RBCs seemed to be detached from the lipid
membrane whereas RBCs from healthy donors and patients with sickle cell disease
exhibited peculiar tips at their front. These tips disappeared much slower in
patients' cells, allowing estimating a threefold increase in RBC cytoplasmic
viscosity in sickle cell disease. Measurements of time and rate of RBC
sequestration in the slits allowed quantifying the massive trapping of
spherocytic RBCs.
