Abstract
This paper reports on an investigation of mass transport of blood cells at micro-scale stenosis where local strain-rate micro-gradients trigger platelet aggregation. Using a microfluidic flow focusing platform we investigate the blood flow streams that principally contribute to platelet aggregation under shear micro-gradient conditions. We demonstrate that relatively thin surface streams located at the channel wall are the primary contributor of platelets to the developing aggregate under shear gradient conditions. Furthermore we delineate a role for red blood cell hydrodynamic lift forces in driving enhanced advection of platelets to the stenosis wall and surface of developing aggregates. We show that this novel microfluidic platform can be effectively used to study the role of mass transport phenomena driving platelet recruitment and aggregate formation and believe that this approach will lead to a greater understanding of the mechanisms underlying shear-gradient dependent discoid platelet aggregation in the context of cardiovascular diseases such as acute coronary syndromes and ischemic stroke.
Highlights
Pathological thrombus formation underlies a number of major health problems with significant economic impact
This paper presents model experiments on a microfluidic platform incorporating hydrodynamic flow focusing to examine blood cell transport investigating the mechanical flow processes governing pathological platelet aggregation at stenosis
These initial proof-of-concept experiments suggests that aggregate growth in acute stenosis can generate enhanced advective transport zones within the local flow effectively increasing platelet mass transport to the wall, further accelerating aggregate growth
Summary
Pathological thrombus formation underlies a number of major health problems with significant economic impact. The development of microtechnologies, and in particular microfluidics has enabled unprecedented control of the experimental conditions for studying the role of hemodynamics in platelet aggregation at the micro-scale [5] Application of these new microfluidic approaches; in combination with micro-imaging techniques applied to platelet function analysis has begun to challenge aspects of the existing models describing the early events that drive thrombus formation. Control of blood streams is achieved by controllably modifying the hydraulic resistance of the inlet feeders within the device, while keeping the geometrical variables of the stenosis fixed These proof-of-concept studies have enabled us to observe an enhanced advection mechanism based on a model of competing forces: the shear gradient lift force (SGLF) and wall-effect lift force (WELF), that drive platelet transport to the stenosis apex. We demonstrate that platelet aggregation is self-limiting, such that once the aggregate reaches a critical size (and shape) the re-emergence of the WELF counterbalances the SGLF leading to an overall brake on platelet transport and aggregate growth
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