Passos, Andreas; (2020) The effect of red blood cell deformability on microscale blood flows. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The non-Newtonian nature of blood arises from the presence of suspended formed elements which are the red blood cells (RBCs), white blood cells (WBCs) and platelets. Red blood cells or erythrocytes are the predominant constituent elements of blood, hence their role on haemodynamics is of great importance. Their remarkable deformability enables their flow in microvessels and is vital to oxygen delivery to tissue. Different diseases, such as malaria, sickle cell anaemia, diabetes etc. affect the mechanical properties and mainly the deformability of RBCs leading to pathological conditions and disorders in the microcirculation. However, the exact role of RBC deformability in microvascular flows has not been established hitherto. In this study, the role of red blood cell deformability on microscale haemodynamics was examined by perfusing artificially hardened RBCs in straight and bifurcating microchannels mimicking the microvasculature. RBC microchannel flows were resolved using brightfield micro-PIV methods. Advanced image processing routines were implemented in MATLAB to simultaneously determine the velocity and haematocrit distributions for a range of flow rates and feed haematocrit conditions. At low feed haematocrits (5%) hardened RBCs were found to be more dispersed in the straight microchannel flows compared to healthy RBCs, consistent with reports of decreased migration of hardened cells. At high haematocrits (25%) hardened RBCs produced less blunted velocity profiles compared to healthy RBCs, implying a reduction in the shear thinning behaviour of the suspensions. However, the haematocrit profiles appeared to also be sharper indicating some complex interactions between hardened cells. These findings were supported by cell tracking experiments which produced similar cell distributions for fluorescent hardened RBCs in a hardened RBC suspension, in contrast to observed margination of the same cells when suspended in healthy RBCs suspensions. Experiments with higher aspect microchannels confirmed the same trends, indicating that the latter were not due to confinement. The extent of RBC aggregation – indicated by the bluntness of the velocity and haematocrit profiles as well as the standard deviation of the image intensity – was found to be decreased in flows of hardened RBCs, compared to healthy ones in the whole range of the measured flow rates. RBC flows showed a higher level of heterogeneity in the bifurcating microchannels with both haematocrit and velocity profiles downstream of the T-junction bifurcation, exhibiting skewness the extent of which depended on the flow ratio between branches and RBC properties. RBC aggregation appeared to affect the non-uniformity of the haematocrit and velocity distributions downstream the bifurcation to a larger extent than RBC hardening which showed smaller variations compared to healthy non-aggregated RBC suspensions. Finally, the parent branch flow rate affected the redistribution of RBCs downstream of the bifurcation producing less skewed distributions with increasing flow rate. The thesis elucidated the physics of RBCs flows with impaired deformability providing thus the fundamental knowledge that is required for the development of medical diagnostic tools able to capture and assess the severity of diseases associated with impaired RBC deformability.

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