Design of a Microfluidic System for Red Blood Cell Aggregation Investigation

Abstract

The purpose of this paper is to design a microfluidic apparatus capable of providing controlled flow conditions suitable for red blood cell (RBC) aggregation analysis. The linear velocity engendered from the controlled flow provides constant shear rates used to qualitatively analyze RBC aggregates. The design of the apparatus is based on numerical and experimental work. The numerical work consists of 3D numerical simulations performed using a research computational fluid dynamics (CFD) solver, Nek5000, while the experiments are conducted using a microparticle image velocimetry system. A Newtonian model is tested numerically and experimentally, then blood is tested experimentally under several conditions (hematocrit, shear rate, and fluid suspension) to be compared to the simulation results. We find that using a velocity ratio of 4 between the two Newtonian fluids, the layer corresponding to blood expands to fill 35% of the channel thickness where the constant shear rate is achieved. For blood experiments, the velocity profile in the blood layer is approximately linear, resulting in the desired controlled conditions for the study of RBC aggregation under several flow scenarios.

Controlled Microfluidic Environment for Dynamic Investigation of Red Blood Cell Aggregation

“…In order to test different shear rates, change the pump flowrate. This maintains the same appropriate ratio (4 in this case) between the two branches 19 ( Figures 2 and 3). Wait for the flow to reach steady state before acquiring the measurements: visually inspect the high speed camera images for a smooth flow.…”

“…For successful testing and aggregate detection, it is crucial to determine the appropriate velocity ratio between the two fluids at the microchannel entry. This ratio is very important to obtain an optimal blood layer thickness where the velocity profile is quasi-linear 19 .…”

Microfluidic-based speckle analysis for sensitive measurement of erythrocyte aggregation: A comparison of four methods for detection of elevated erythrocyte aggregation in diabetic rat blood

“…10,27 By employing the Mehri's image-processing method and micro-particle image velocimetry (micro-PIV) technique, information about the size and flow velocity of RBC aggregates in the micro channel were simultaneously measured. 28,29 Although direct assessment techniques can figure out the size and dynamic motions of rouleaux, the hematocrit of blood samples should be adjusted to less than 10% for accurate quantification of EA. 12,30 Consequently, the degree of EA has mostly been measured indirectly under various physiological conditions.…”

A microfluidic erythrocyte sedimentation rate analyzer using rouleaux formation kinetics

“…This process is reversible, and cells can be dispersed individually when a disaggregating shear rate is applied to the cells (Baskurt et al 2011b;Lim et al 2010;Mehri et al 2014;Shin et al 2009). Aggregation is a critical factor for the determination of blood viscosity (Chien et al 1967) and hematocrit level (Deng et al 1993;Xu et al 2008); hence, it is physiologically relevant to in vivo microcirculation of blood (Baskurt et al 2011a;Baskurt and Meiselman 2013;Tuma et al 2011).…”

“…After finding the appropriate concentration levels, the performance of the microfluidic system was successfully demonstrated. Disaggregation of the cells within the microfluidic chips at the start of the test is critical, which is determined by the applied shear rate on the cells (Baskurt et al 2011b;Lim et al 2010;Mehri et al 2014;Shin et al 2009). We have shown computationally and experimentally that the choice/design of the mechanical unit, which is a pinch valve in this presented work, is critical to obtain adequate shear rate and therefore to perform a successful measurement.…”