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使用解析的计算流体动力学-离散单元法(CFD-DEM)模拟对生物微流控应用中的溶血进行预测。

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

作者信息

Porcaro Carmine, Saeedipour Mahdi

机构信息

Department of Particulate Flow Modelling, Johannes Kepler University, A-4040 Linz, Austria; Linz Institute of Technology (LIT), Johannes Kepler University, A-4040 Linz, Austria; Christian Doppler Laboratory for Multi-scale Modelling of Multiphase Processes, Johannes Kepler University, A-4040 Linz, Austria.

Department of Particulate Flow Modelling, Johannes Kepler University, A-4040 Linz, Austria; Linz Institute of Technology (LIT), Johannes Kepler University, A-4040 Linz, Austria.

出版信息

Comput Methods Programs Biomed. 2023 Apr;231:107400. doi: 10.1016/j.cmpb.2023.107400. Epub 2023 Feb 4.

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.

摘要

背景与目的

溶血,即红细胞(RBC)中的血红蛋白泄漏,是临床检测中错误结果的主要来源之一,尤其是在涉及被动微流控技术时。这是由于微小的特征尺寸可能导致红细胞强烈变形。在用于细胞分选和血浆分离的芯片实验室设备的设计和优化中,溶血预测至关重要。这项工作的目的是为此提供一种数值模拟工具,该工具适用于具有可承受计算成本的实际规模生物微流控设备。

方法

血液被建模为生物细胞(主要是红细胞)在液体血浆中的悬浮液,血浆被假定为牛顿不可压缩载液。因此,细胞和载液的物理过程通过一种称为解析计算流体动力学 - 离散单元法(CFD - DEM)的浸入边界概念耦合。在这种方法中,通过有限体积法对纳维 - 斯托克斯方程进行数值求解,并添加一个额外的惩罚项来考虑红细胞的存在。通过求解线性和角动量守恒的牛顿方程和欧拉方程来更新红细胞的位置和速度。为了模拟红细胞变形,采用了一种降阶模型,其中每个红细胞由一组通过虚拟数值键连接的重叠刚性球体表示,其属性经过调整以再现红细胞粘弹性膜的属性。这种耦合方法允许获取细胞水平信息,并便于使用基于应变的溶血模型。

结果

模拟了不同的微通道几何形状和血液血细胞比容,以探索这些因素对红细胞损伤的影响。进行统计分析以从数值模拟中提取相关生物物理量,如通道出口处的溶血指数分布。最后,研究了载液粘度与细胞间相互作用的关系。

结论

模拟结果表明,微通道中溶血的发生几乎与血细胞比容值无关,这意味着使用低血细胞比容值有可能加快计算速度。然而,将全血粘度用于载液会使溶血指数值高估近一个数量级。

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