Computational methods for the suspensions of deformable and rigid particles and their applications to modelling of blood flows

可变形和刚性颗粒悬浮液的计算方法及其在血流建模中的应用

• 批准号: 0914788
• 负责人: Tsorng-whay Pan
• 金额: $ 34.05万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0914788&HistoricalAwards=false
• 关键词: Computational; methods; suspensions; deformable; rigid

This project focuses on developing computational methods for simulating the suspensions of deformable and rigid particles and their applications to modeling the microcirculation of blood flow and cell separation in microchannel flow. It is computationally challenging to simulate directly the three-dimensional motion and dynamics of hydrodynamically interacting red blood cells in a fluid. We will use a spring network model with its associated energy potential to model the membrane of the red blood cell. We propose to combine the spring network model with the immersed boundary methods, finite element methods and operator splitting techniques to simulate the cell-fluid and cell-cell interactions in three dimensions. We also want to combine the above proposed methodology with the distributed Lagrange multiplier/fictitious domain methods, which are closed related to the immersed boundary methods, to simulate the suspensions of cells and solid particles. Through the computational methodologies proposed by the PIs, efficient three-dimensional simulations of the red blood cells in microvessels will be performed to study the rheology of red blood cells in microcirculation, the margination dynamics of solid particles in microvessels and the cell separation in microchannels.The microcirculation, which takes place in the smallest blood vessels (i.e., arterioles, capillaries, and venules), is responsible for regulating blood flow in individual organs and for exchange between blood and tissue. Since blood contains about 40-45% red blood cells by volume, as well as platelets and leukocytes, the interactions of these formed elements play a crucial role in determining blood characteristics. Because of their large volume fraction and their aggregation capacity, red blood cells are the most important determinant of blood flow characteristics. While theories of suspension rheology generally focus on homogeneous flows in infinite domains, the important phenomena of blood flows in microcirculation depend on the combined effects of vessel geometries, cell deformabilities, wall compliance, flow shear rates, and many micro-scale chemical, physiological, and biological factors. We concentrate on the rheological aspects of flow in microcirculation involving deformable cells, cell-cell interactions and vessel geometry, which is particularly challenging theoretically and computationally. The first main application is to study the margination dynamics of solid particles in microvessels. The intravascular delivery of rigid particles for biomedical imaging and therapy is being recognized as a powerful and promising tool in cardiovarscular and oncological applications. These particles can be loaded with drug molecules and contrast agents and transported by the blood flow through the circulatory system. They are generally decorated with ligand molecules which are able to interact specifically with antigens expressed over diseased cells (or target cells). The effect of particle shape, size and density on margination propensity is needed to be analyzed in order to find the optimal design. The second main application is to study cell separation in microchannel flow. The main focus is to gain inside in the separation of healthy and sick red blood cells due to their deformability and size on a microfluidic biochip platform. Separation of soft objects is of enormous relevance in medical and biological applications, since very often a loss in deformability comes along with diseases such as malaria, diabetes mellitus or cancer, just to name a few. Hence, a microfluidic system to sort or separate cells would be of tremendous importance for both diagnostic and dialysis applications.

该项目侧重于开发模拟可变形和刚性颗粒悬浮液的计算方法，并将其应用于模拟微通道流动中的血液微循环和细胞分离。直接模拟流体中红细胞在流体动力学中相互作用的三维运动和动力学在计算上具有挑战性。我们将使用弹簧网络模型及其相关的能量势来模拟红细胞的膜。我们提出将弹簧网络模型与浸入边界法、有限元法和算子分裂技术相结合，在三维空间上模拟细胞-流体和细胞-细胞相互作用。我们还希望将上述方法与与浸入边界方法密切相关的分布式拉格朗日乘子/虚拟域方法相结合，以模拟细胞和固体颗粒的悬浮液。通过pi提出的计算方法，将对微血管中的红细胞进行有效的三维模拟，以研究微循环中红细胞的流变学，微血管中固体颗粒的边缘动力学以及微通道中的细胞分离。微循环发生在最小的血管（即小动脉、毛细血管和小静脉）中，负责调节各个器官的血液流动和血液与组织之间的交换。由于血液中含有约40-45%的红细胞，以及血小板和白细胞，这些形成元素的相互作用在决定血液特征方面起着至关重要的作用。由于其体积分数和聚集能力大，红细胞是血流特性最重要的决定因素。虽然悬浮液流变学理论通常关注无限域中的均匀流动，但微循环中血液流动的重要现象取决于血管几何形状、细胞变形能力、壁面顺应性、血流剪切率以及许多微观尺度的化学、生理和生物因素的综合影响。我们专注于微循环流动的流变学方面，涉及可变形细胞、细胞间相互作用和血管几何，这在理论上和计算上都特别具有挑战性。第一个主要应用是研究微血管中固体颗粒的边界动力学。用于生物医学成像和治疗的刚性颗粒的血管内输送被认为是心血管和肿瘤应用中强大而有前途的工具。这些颗粒可以装载药物分子和造影剂，并通过血液循环系统运输。它们通常被配体分子修饰，这些配体分子能够与病变细胞（或靶细胞）上表达的抗原特异性地相互作用。为了找到最佳设计方案，需要分析颗粒形状、大小和密度对边沿倾向的影响。第二个主要应用是研究微通道流中的细胞分离。主要焦点是在微流控生物芯片平台上获得健康和患病红细胞的分离，因为它们的可变形性和大小。软性物体的分离在医学和生物学应用中具有巨大的相关性，因为通常情况下，可变形性的丧失伴随着疟疾、糖尿病或癌症等疾病，仅举几例。因此，对细胞进行分选或分离的微流体系统对于诊断和透析的应用都是非常重要的。