This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)
0852976 Graham
Many 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.
