Near-Wall Migration Dynamics of Erythrocytes in Vivo: Effects of Cell Deformability and Arteriolar Bifurcation

The main function of the microvasculature is transport of materials. Water and solutes are carried by blood through the microvessels and exchanged, through vessel walls, with the surrounding tissues. This transport function is highly dependent on the architecture of the microvasculature and on the biophysical behavior of blood flowing through it. For example, the hydrodynamic resistance of a microvascular network, which determines the overall blood flow for a given perfusion pressure, depends on the number, size and arrangement of microvessels, the passive and active mechanisms governing their diameters, and on the apparent viscosity of blood flowing in them. Suspended elements in blood, especially red blood cells, strongly influence the apparent viscosity, which varies with several factors, including vessel diameter, hematocrit and blood flow velocity. The distribution of blood flows and red cell fluxes within a network, which influences the spatial pattern of mass transport, is determined by the mechanics of red cell motion in individual diverging bifurcations. Here, our current understanding of the biophysical processes governing blood flow in the microvasculature is reviewed, and some directions for future research are indicated.

In blood vessels with luminal diameter less than 300 µm, red blood cells (RBCs) which are smaller in size and more deformable than leukocytes, migrate to the axial centre of the vessel due to flow velocity gradient within the vessels. This phenomenon displaces the leukocytes to the vessel wall and is aptly termed as margination. Here, we demonstrate using microfluidics that stiffer malaria-infected RBCs (iRBCs) behave similar to leukocytes and undergo margination towards the sidewalls. This provides better understanding of the hemodynamic effects of iRBCs in microcirculation and its contribution to pathophysiological outcome relating to cytoadherence to endothelium. In this work, cell margination is mimicked for the separation of iRBCs from whole blood based on their reduced deformability. The malaria infected sample was tested in a simple long straight channel microfluidic device fabricated in polydimethylsiloxane. In this microchannel, cell margination was directed along the channel width with the iRBCs aligning near each sidewall and then subsequently removed using a 3-outlet system, thus achieving separation. Tests were conducted using ring stage and late trophozoite/schizont stage iRBCs. Device performance was quantified by analyzing the distribution of these iRBCs across the microchannel width at the outlet and also conducting flow cytometry analysis. Results indicate recovery of approximately 75% for early stage iRBCs and >90% for late stage iRBCs at the side outlets. The simple and passive system operation makes this technique ideal for on-site iRBCs enrichment in resource-limited settings, and can be applied to other blood cell diseases, e.g. sickle cell anemia and leukemia, characterized by changes in cell stiffness.