Supplement: Hemolysis Prediction Software Development

血细胞损伤的多尺度预测模型及实验验证 这项建议旨在开发一个多尺度模型来表征复杂流动下的血细胞损伤。 条件。血液损伤是各种润血医疗器械的重要关注点。在文学中，鲜血 损伤判据通常是通过对实验溶血数据进行经验拟合来获得的 设备，但对血细胞损伤的细胞尺度过程知之甚少，这阻碍了准确的 普通医疗器械中血液损伤的评价。这项提议的目标是研究血细胞。 使用计算建模和实验相结合的方法在分子和细胞水平上进行损伤。 具体地说，我们将开发一个多尺度模型，将分子尺度的毛孔形成与细胞膜联系起来 损伤和血红蛋白释放。 多尺度计算模型将首次应用于研究不同尺度的胞体流动。 同时考虑流体力学和膜的通道几何形状和临床相关装置 破坏动力学。具体来说，我们计划： 1)建立多尺度红细胞膜损伤模型。一种局域的粗粒分子 高应力区的动力学模型将与基于网络的细胞膜并行连接 模特。 2)通过浸没边界法将细胞膜损伤模型与局部流体流动相耦合 研究细胞变形、孔洞形成和膜破裂。这种计算模型将应用于 预测具有不同几何形状和流动条件的通道中的血细胞损伤。一个广义的元胞 将开发水平的血细胞损伤模型。 3)使用AFM测量、微流控测试和 库埃特式血液剪切器。将执行一些设计的测试来评估细胞损伤，基于 分析受控应力历史下单个细胞的血红蛋白，并与模拟结果进行比较。 最后，开发的血液损伤模型将被应用于研究脑室辅助装置中的溶血。 所提出的多尺度模型可以将细胞膜的微尺度状态直接关联到局部 在具有复杂几何形状和流动条件的设备中，应力以及预测单元损伤。这种模型可以 作为血液生物医学设备设计和优化的预测工具。

Multiscale Predictive Modeling of Blood Cell Damage with Experimental Verification This proposal aims to develop a multiscale model to characterize blood cell damage under complex flow conditions. Blood damage is an important concern for various blood wetting medical devices. In literature, blood damage criterion is typically obtained through empirical fitting of experimental hemolysis data in a specific device, yet little is known about cellular scale process of blood cell damage, which hinders the accurate evaluation of blood damage in a general medical device. The goal of this proposal is to study blood cell damage at molecular and cellular level using combined computational modeling and experimental approaches. Specifically, we will develop a multiscale model that links molecular scale pores formation to cell membrane damage and hemoglobin release. The multiscale computational modeling will be applied for the first time to study of cellular flow over various channel geometries and clinically relevant devices with consideration of both hydrodynamics and membrane damage dynamics. Specifically, we plan to: 1) Develop a multiscale red blood cell membrane damage model. A localized coarse-grained molecular dynamics model at the high stress region will be concurrently linked with a network based cellular membrane model. 2) Couple the cell membrane damage model with local fluid flow through Immersed Boundary method to study cell deformation, pore formation and membrane rupture. Such computational model will be applied to predict blood cell damages in a channels with different geometries and flow conditions. A generalized cellular level blood cell damage model will be developed. 3) Verify the developed multiscale blood cell damage model using AFM measurements, microfluidic tests, and Couette-type blood-shearing devices. A few designed tests will be performed to evaluate cell damage based on hemoglobin analysis of individual cells under controlled stress history and compared to the simulation results. Finally, the developed blood damage model will be applied to study hemolysis in a ventricular assist device. The proposed multi-scale model can directly correlate the microscale state of the cell membrane to local stresses as well as predict cell damage in device with complex geometry and flow condition. Such model could serve as a predictive tool for hematologic biomedical device design and optimization.