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格雷厄姆许多严重的医疗条件，从出血到冠状动脉疾病到糖尿病，都与血流中断有关。 已经观察到，向血液中添加低浓度的称为减阻添加剂的非常大的聚合物分子引起对血液流动的显著有益效果。这些聚合物之所以如此命名是因为它们对湍流的减阻作用，但由于血液流动大部分不是湍流的，因此这些聚合物对血液流动的影响必须与湍流减阻有单独的来源。通过补充实验和模拟，研究人员的目标是获得聚合物添加剂对微循环中血液流动的影响的基本了解（即小血管，包括毛细血管）。实验将在模塑硅橡胶流动系统中用红细胞和聚合物添加剂的悬浮液进行，该系统模拟微循环的各个方面，以及在允许在高度受控的流动中测量流体粘度的仪器中。悬浮液的粘度将在剪切和拉伸流动中表征-拉伸流动强烈拉伸溶液中的聚合物分子，并且例如在微循环中细胞之间的碰撞期间出现。使用一种创新的方法来确定流动阻力，以及高速视频显微镜，在通道和微循环的尺寸特征的通道网络中流动阻力的变化将首次与流动悬浮液的行为（细胞取向，分布，波动，网络中的贩运）的变化相关。微通道流动中的红细胞和聚合物群体的模拟将被执行，所有的细胞和聚合物分子被视为悬浮在血浆中的单个实体。一种新的，高效的模拟方法，这样的系统，在主要研究者的小组开发，将大大加快计算。模拟的聚合物和细胞动力学的分析，并与实验观察的预测动力学的比较，将有助于所观察到的现象的机理，预测的理解。智力优势：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流的机制的第一个基本调查。实验和计算结果的并行追求将引起聚合物和血流之间的相互作用的全面看法。实验研究将涉及开发一种新的方法，用于量化在微流体几何形状的复杂流体流动过程中的流动阻力，和计算研究将涉及第一个粒子级模拟的可变形颗粒悬浮液中的聚合物溶液。这项工作具有潜在的变革性，因为它旨在首次为开发涉及血液传播聚合物添加剂的疗法提供合理的基础。更广泛的影响：拟议的工作是与威斯康星大学麦迪逊分校医学院肺生理学研究人员合作项目的一部分。除了直接应用于血液中的减阻添加剂问题外，所提出的工作还为研究微循环中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液载药颗粒的动力学。在这项研究的过程中，先进的实验和计算方法将发现从生物医学工程领域的重要问题的适用性，以提高石油采收率。在本研究过程中教育的研究生将获得独特的跨学科，并将受到广泛的公司的高度追捧。这个项目，特别是实验，也将为本科研究人员提供宝贵的经验。首席研究员有参与本科生，特别是妇女和代表性不足的少数民族，在研究，通过独立的研究项目，以及夏季研究经验的本科生计划由国家科学基金会支持的长期记录。

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.