Margination refers to the migration of particles toward blood vessel walls during blood flow. Understanding the mechanisms that lead to margination will aid in tailoring the attributes of drug-carrying particles for effective drug delivery. Most previous studies evaluated the margination propensity of these particles via an adhesion mechanism, i.e., by measuring the number of particles that adhered to the channel wall. Although particle adhesion and margination are related, adhesion also depends on other factors. In this study, we quantified the margination propensity of particles of varying diameters (0.53, 0.84, and 2.11 mm) and apparent wall shear rates (30, 61, and 121 s À1 ) by directly tracking fluorescent particles flowing through a microfluidic channel. The margination parameter, M, is defined as the total number of particles found within the cell-free layers normalized by the total number of particles that passed through the channel. In this study, an M-value of 0.2 indicated no margination, which was observed for all particle sizes in water. In the case of blood, larger particles were found to have higher M-values and thus marginated more effectively than smaller particles. The corresponding M-values at the device outlet were 0.203, 0.223, and 0.285 for 0.53-, 0.84-, and 2.11-mm particles, respectively. At the inlet, the M-values for all particle sizes in blood were <0.2, suggesting that non-fully-developed flow and constriction may lead to demargination. For particle velocities transverse to the flow direction (v y ), all particle sizes showed a larger standard deviation of v y as well as a higher effective diffusivity when the particles were suspended in blood relative to water. These higher values are attributed to collisions between the blood cells and particles, further supporting recent simulation results. In terms of flow rates, for a given particle size, the higher the flow rate, the higher the M-value.

Abstract. "Margination" refers to the movement of particles in flow toward the walls of a channel. The term was first coined in physiology for describing the behavior of white blood cells (WBCs) and platelets in blood flow. The margination of particles is desirable for anticancer drug delivery because it results in the close proximity of drug-carrying particles to the endothelium, where they can easily diffuse into cancerous tumors through the leaky vasculature. Understanding the fundamentals of margination may further lead to the rational design of particles and allow for more specific delivery of anticancer drugs into tumors, thereby increasing patient comfort during cancer treatment. This paper reviews existing theoretical and experimental studies that focus on understanding margination. Margination is a complex phenomenon that depends on the interplay between inertial, hydrodynamic, electrostatic, lift, van der Waals, and Brownian forces. Parameters that have been explored thus far include the particle size, shape, density, stiffness, shear rate, and the concentration and aggregation state of red blood cells (RBCs). Many studies suggested that there exists an optimal particle size for margination to occur, and that nonspherical particles tend to marginate better than spherical particles. There are, however, conflicting views on the effects of particle density, stiffness, shear rate, and RBCs. The limitations of using the adhesion of particles to the channel walls in order to quantify margination propensity are explained, and some outstanding questions for future research are highlighted.

Stroke is a leading cause of death globally and is caused by stenoses, abnormal narrowings of blood vessels. Recently, there has been an increased interest in shear-activated particle clusters for the treatment of stenosis, but there is a lack of literature investigating the impact of different stenosis geometries on particle margination. Margination refers to the movement of particles toward the blood vessel wall and is desirable for drug delivery. The current study investigated ten different geometries and their effects on margination. Microfluidic devices with a constricted area were fabricated to mimic a stenosed blood vessel with different extent of occlusion, constricted length, and eccentricity (gradualness of the constriction and expansion). Spherical fluorescent particles with a diameter of 2.11 μm were suspended in blood and tracked as they moved into, through, and out of the constricted area. A margination parameter, M, was used to quantify margination based on the particle distribution after velocity normalization. Experimental results suggested that a constriction leads to an enhanced margination, whereas an expansion is responsible for a decrease in margination. Further, margination was found to increase with increasing percent occlusion and constriction length, likely a result of higher shear rate and longer residence time, respectively. Margination decreases as the stenosis geometry becomes more gradual (eccentricity increases) with the exception of a sudden constriction/expansion geometry. The findings demonstrate the importance of geometric effects on margination and call for detailed numerical modeling and geometric characterization of the stenosed areas to fully understand the underlying physics.