Blood flow in the microcirculation: model studies of the effect of drag-reducing additives

该奖项是根据2009年美国复苏和再投资法案(公法111-5)0852976格雷厄姆提供资金的，许多严重的疾病，从出血、冠状动脉疾病到糖尿病，都与血流中断有关。已经观察到，在血液中加入低浓度的被称为减阻添加剂的非常大的聚合物分子，会对血液流动产生显著的有益影响。这些聚合物之所以这样命名，是因为它们对湍流的减阻作用，但由于血液流动在很大程度上不是湍流，这些聚合物对血液流动的影响必须与湍流减阻有不同的来源。通过补充实验和模拟，研究人员旨在从根本上了解聚合物添加剂对微循环(即小血管，包括毛细血管)中血液流动的影响。实验将在模塑硅橡胶流动系统中的红细胞和聚合物添加剂悬浮液中进行，该系统模拟微循环的各个方面，以及在高度受控流动中测量流体粘度的仪器。悬浮液的粘度将在剪切和拉伸流动中表现出来--拉伸流动强烈拉伸溶液中的聚合物分子，例如在微循环中细胞之间的碰撞中出现。使用一种确定流动阻力的创新方法以及高速视频显微镜，微循环特征尺寸的通道和通道网络中流动阻力的变化将首次与流动悬浮液行为(细胞取向、分布、波动、网络中的运输)的变化相关联。将对微通道流动中的红细胞和聚合物群体进行模拟，将所有细胞和聚合物分子作为单独的实体处理在血浆中。首席研究小组开发了一种针对这样的系统的新颖、高效的模拟方法，将极大地加快计算速度。分析模拟的聚合物和细胞动力学，并将预测的动力学与实验观察进行比较，将有助于对观察到的现象进行机械的、预测性的理解。智力价值：这里提出的研究将是新颖的，因为它们构成了减阻添加剂改变血液流动机制的第一个基础研究。对实验和计算结果的并行追求将引起对聚合物和血液流动之间相互作用的全面看法。实验研究将包括开发一种新的方法来量化复杂流体在微流体几何形状中流动时的流动阻力，而计算研究将涉及首次对聚合物溶液中可变形颗粒悬浮液的颗粒级模拟。这项工作具有潜在的变革性，因为它的目标是首次为涉及血液传播聚合物添加剂的疗法的开发提供合理的基础。更广泛的影响：这项拟议的工作是与威斯康星大学麦迪逊医学院的一名肺部生理学研究员合作项目的一部分。除了将其直接应用于血液中的减阻添加剂问题外，拟议的工作还为研究微循环中的血液流动的其他重要问题奠定了基础，包括细胞形状和变形性对血液流动的影响以及血载药物输送颗粒的动力学。在这项研究过程中提出的实验和计算方法都将适用于从生物医学工程到提高石油采收率等领域的重要问题。在这项研究过程中培养的研究生将获得独特的跨学科知识，并将受到广泛公司的高度追捧。这个项目，特别是实验，也将为本科生研究人员提供宝贵的经验机会。首席调查员通过独立研究项目和国家科学基金会支持的本科生暑期研究体验项目，让本科生，特别是女性和代表性不足的少数族裔参与研究，这是一个长期的记录。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)0852976GrahamMany serious medical conditions, from hemorrhage to coronary artery disease to diabetes, are associated with disruptions in blood flow. It has been observed that dramatic beneficial effects on blood flow arise from addition to blood of low concentrations of very large polymer molecules known as drag-reducing additives. These polymers are so named because of their drag-reducing effects on turbulent flow, but since blood flow is not for the most part turbulent, the effects of these polymers on blood flow must have a separate origin from turbulent drag reduction. Through complementary experiments and simulations, the investigators aim to gain a fundamental understanding of the effects of polymer additives on blood flow in the microcirculation (i.e. the small blood vessels, including capillaries).Experiments will be performed with suspensions of red blood cells and polymer additives in molded silicone rubber flow systems that model various aspects of the microcirculation, as well as in instruments that allow measurement of fluid viscosity in highly controlled flows. The viscosity of the suspensions will be characterized in both shear and extensional flow - extensional flows strongly stretch polymer molecules in solution and arise for example during collisions between cells in the microcirculation. Using an innovative method for determining flow resistance, as well as high-speed video microscopy, changes in resistance to flow in channels and channel networks of sizes characteristic of the microcirculation will be correlated for the first time with changes in the behavior (cell orientation, distribution, fluctuations, trafficking in networks) of the flowing suspension. Simulations of populations of red blood cells and polymers in microchannel flows will be performed, with all the cells and polymer molecules treated as individual entities suspended in blood plasma. A novel, highly efficient simulation method for systems like this, developed in the principal investigator's group, will dramatically accelerate computations. Analysis of the simulated polymer and cell dynamics, and comparison of the predicted dynamics with the experimental observations will facilitate a mechanistic, predictive understanding of the observed phenomena. Intellectual Merit: The studies proposed here will be novel in that they constitute the first fundamental investigations of the mechanisms by which drag reducing additives modify blood flows. The parallel pursuit of experimental and computational results will give rise to a comprehensive view of the interaction between polymers and blood flow. The experimental investigation will involve development of a novel methodology for quantifying flow resistance during flows of complex fluids in microfluidic geometries, and the computational investigation will involve the first particle-level simulations of deformable particle suspensions in a polymer solution. This work is potentially transformative in that it aims to provide, for the first time, a rational basis for development of therapies involving blood-borne polymer additives. Broader impacts: The proposed work is part of a collaborative project with a pulmonary physiology researcher at the UW-Madison medical school. Aside from its direct application to the issue of drag reducing additives in blood, the proposed work forms the foundation for studying other important issues regarding blood flow in the microcirculation, including effects of cell shape and deformability on blood flow and the dynamics of blood-borne drug delivery particles. Both the experimental and computational methodologies advanced in the course of this research will find applicability to important problems in areas ranging from biomedical engineering to enhanced oil recovery. The graduate students educated in the course of this research will gain a uniquely interdisciplinary and will be highly sought-after by a wide-range of companies. This project, particularly the experiments, will also provide opportunities for valuable experiences for undergraduate researchers. The principal investigator has a long record of involving undergraduates, especially women and under-represented minorities, in research, through independent study projects as well as the summer Research Experience for Undergraduates programs supported by the National Science Foundation.