Blood flow dynamics on a rotating microfluidic platform

Abstract

The viscosity of blood has long been used as an indicator in the understanding and treatment of disease, and the advent of modern viscometers allows its measurement with ever-improving clinical convenience. However, these advances have not been matched by theoretical developments that can yield a quantitative understanding of blood's microrheology and its possible connection to relevant biomolecules. Whole blood (plasma and formed elements together) behaves as a non-Newtonian fl uid. The eff ective viscosity of blood decreases with increasing shear. Relative viscosity of blood is dependent on the concentration of formed elements as well as on the tube diameter in which the flow is being studied. Further, it is also dependent on the endothelial wall characteristics of the tube. This variation of viscosity with shear manifests itself in the bulk fl ow characters like volumetric fl ow rate, ow pattern, valve characteristics at capillary joints etc. A major contributor to this behaviour of blood are the red blood cells (RBCs) or erythrocytes, which occupy 45% of the blood volume. Blood plasma which constitutes the highest fraction of blood 52% is primarily Newtonian. Upon infection with malaria, the deformability of RBCs change. The deformability is reduced upon infection with P. falciparum and enhanced upon infection with P.vivax. Our primary focus in this work is P. falciparum which is the most popular strain of parasite and also the most lethal. We studied the eff ect of di fference in physical parameters like viscosity arising out of malarial infection or the like to study diff erences in bulk fl ow characteristics on a centrifugally actuated microfl uidic platform. While there has been substantial amount of work done on dependence of apparent viscosity of blood on hematocrit and tube diameter; there has been no work done , whatsoever, for studying our concerned bulk ow properties in capillary fl ow based on these dependences. We are concerned with three basic bulk fl ow properties which are aff ected by blood rheology and capillary design. These are the burst frequency, volumetric fl ow rate and capillary filling time. In this work only the rest two of these properties are extensively studied. Based on these di fferences, we propose to build a new inexpensive, rapid point-of-care diagnostic device using a CD based micro fluidic platform for diagnosing malaria solely based on rheology dependent fl ow parameters. In preparation for the same, microfl uidic experiments were conducted using normal blood, malarial blood and blood with hardened RBCs(treated with glutaraldehyde) to measure the frequency of fl ow burst and volumetric flow rate. Simultaneously, extensive CFD simulations were performed using a fi nite element method to develop a theoretical or rather, mathematical framework to replicate the experimental observations. Experimental measurements show marked di fference in the targeted flow parameters for normal and malaria infected blood/blood with hardened RBCs. The numerical model developed was successfully validated against the experimental observations and existing literature for normal blood at diff erent RBC concentrations. A Newtonian model with higher zero shear viscosity was used to simulate fl ow of blood with hardened cells which gave a reasonably good match with the experimental data under several assumptions. Extensive experiments need to be performed on malaria infected blood to design an appropriate numerical framework for simulating the same taking into consideration RBC deformability in a continuum Euler-Euler flow model, i.e., without taking particle dynamics of RBCs, eff ectively reducing the computational expense and expertise requirement. This framework could further be extended to normal blood for better estimation of flow properties.