Hemolysis prediction in bio-microfluidic applications using resolved CFD-DEM simulations

Abstract

Background and objective: Hemolysis, namely hemoglobin leakage from red blood cells (RBCs), is one of the major sources of incorrect results in clinical tests, especially when passive microfluidics is involved. This is due to small characteristic dimensions which could cause strong RBCs deformation. Prediction of hemolysis is essential in the design and optimization of lab-on-a-chip devices for cell sorting and plasma separation. The aim of this work is to provide a numerical simulation tool this purpose applicable to real-scale bio-microfluidic devices with affordable computational cost.

Methods: Blood is modelled as a suspension of biological cells, mainly RBCs, in liquid plasma assumed as a Newtonian, incompressible carrier fluid. Therefore, the physics of cells and carrier fluid is coupled by means of an immersed boundary concept known as resolved CFD-DEM. In this approach, the Navier-Stokes equations are numerically solved through a finite volume method with an additional penalty term to account for the presence of RBCs. RBCs' positions and velocities are updated by solving Newton and Euler equations for conservation of linear and angular momentum. To model the RBCs deformation, a reduced-order model is employed, where each RBC is represented by a clump of overlapping rigid spheres connected by fictional numerical bonds, whose properties are tuned to reproduce the ones of RBCs viscoelastic membrane. This coupled approach allows access to cell-level information and facilitates the usage of strain-based hemolysis models.

Results: Different micro-channel geometries and blood hematocrits are simulated, to explore the influence of these factors on RBCs damage. Statistical analysis is performed to extract relevant biophysical quantities from numerical simulations such as hemolysis index distribution at the channel exit. Finally, the effect of carrier fluid viscosity is studied in relation to cell-cell interactions.

Conclusions: Simulation results show that hemolysis occurrence is almost independent of the hematocrit values in the microchannel, implying the possibility to speed up calculation using low hematocrit values. Nevertheless, using whole blood viscosity for the carrier fluid overestimates the value of the hemolysis index by almost one order of magnitude.

Keywords: Blood flow simulation; Cell damage; Cell-resolved simulation; Immersed boundary method; Red blood cell mechanics.