Dewetting and Rewetting in Marangoni Driven Spreading on Complex Liquid Films

该项目的目标是改善阻塞性肺病患者的气溶胶药物输送系统。 基于气溶胶的药物的分布受到肺部气流的强烈影响。 控制含药气溶胶液滴的大小和密度可以确保药物深入渗透并均匀分布在整个肺部。 然而，当肺被过多的粘液沉积物或气道收缩阻塞时，气流模式改变，并且气溶胶液滴存款沉积在阻塞物上或阻塞物的上游。本项目将研究一种替代策略，在气雾剂液滴降落在肺气道表面后最大限度地分散药物。 表面活性剂分子将结合到气溶胶液滴中，使得液滴着陆后液滴附近的表面张力将沿肺表面沿着变化。 表面张力的梯度将在衬在气道上的薄气道表面液体（ASL）膜中引起流动。ASL中的流动将携带药物通过障碍物。 然而，如果表面张力梯度超过临界值，ASL膜可能破裂，在下层组织上留下干燥的斑块，这将减少药物分散。该项目将评估影响膜破裂的现象，并解决其对药物转运的影响。这项研究的结果将提供设计气溶胶所需的基础知识，这些气溶胶将增强许多阻塞性肺病的药物分布，包括囊性纤维化，肺炎和急性或慢性肺部感染。 本科生和研究生将加入一个多学科团队开展研究，并指导中学生谁将执行实验探索医学物理过程，根据卡内基梅隆大学/科尔法克斯物理概念拓展计划。该项目将解决两个未研究的现象，在模型系统，代表了至关重要的马兰戈尼流流体动力学气溶胶为基础的药物输送。 第一个是提示最近发现的详细结构的两层ASL。 ASL的底层由密集的粘蛋白链组成，类似于流体饱和的多孔介质。 假设在上部流体层和多孔介质之间的界面处的滑动延迟去湿，并且流体流出多孔介质可以促进再润湿。 实验和建模将量化下层孔隙率如何影响不同厚度和不同表面张力梯度的膜的去湿和再湿过渡。 第二种现象涉及几何和重力的耦合作用。 在平面几何形状中，去湿转变由Marangoni或表面张力梯度、应力和重力应力的平衡决定。 重力取向对马兰戈尼强迫去湿的影响以前没有被考虑过，即使存在多个取向的马兰戈尼流的内壁上的圆柱形管道。 实验和建模将量化去湿过渡如何随沉积轨迹，圆柱体半径和圆柱体取向在Marangoni流动内的薄膜涂层圆柱形管，模仿肺气道。 一种光学技术将被用来跟踪定量的演变膜的高度配置文件，并揭示发生去湿或再湿。 这将是再加上单独的措施，可溶性染料（药物模拟）平流的马兰戈尼流。 为该项目开发的模型将在实验可及的条件下进行测试，然后用于预测在更典型的肺条件下的行为。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This goal of this project is to improve aerosol-based drug delivery systems for people with obstructive lung disease. The distribution of aerosol-based drugs is strongly affected by airflows in the lung. Controlling the size and density of drug-containing aerosol droplets can ensure drugs penetrate deep and distribute uniformly throughout the lungs. However, airflow patterns are altered when lungs are obstructed by excess mucus deposits or airway constrictions, and aerosol droplets deposit on or upstream of obstructions. This project will investigate an alternative strategy that maximizes dispersal of drugs after the aerosol droplets have landed on the lung airway surface. Surfactant molecules will be incorporated into the aerosol droplets so that the surface tension near droplets after they land will vary along the lung surface. The gradient in surface tension will induce a flow in the thin airway surface liquid (ASL) films that line the airways. Flow in the ASL will carry drugs past obstructions. However, if the surface tension gradient exceeds a critical value, the ASL film may rupture, leaving a dry patch on underlying tissue that would diminish drug dispersal. This project will assess phenomena that influence film rupture and address its effects on drug transport. The results of this research will provide the fundamental knowledge needed to design aerosols that will enhance distribution of drugs for many obstructive lung diseases, including cystic fibrosis, pneumonia, and acute or chronic pulmonary infections. Undergraduates and graduate students will join a multidisciplinary team to carry out the research and to mentor middle school students who will perform experiments exploring physical processes in medicine, under the Carnegie Mellon/Colfax Physics Concepts Outreach Program.This project will address two unstudied phenomena in model systems that represent the crucial Marangoni flow hydrodynamics for aerosol-based drug delivery. The first is prompted by a recent discovery of the detailed structure of the two-layer ASL. Consisting of densely tethered mucin chains, the bottom layer of the ASL resembles a fluid-saturated porous medium. Slip at the interface between the upper fluid layer and the porous medium is hypothesized to retard dewetting, and fluid flow out of the porous medium may promote rewetting. Experiments and modeling will quantify how the lower layer porosity affects dewetting and rewetting transitions for films of varying thickness and varying surface tension gradients. The second phenomenon addresses the coupled roles of geometry and gravity. In a planar geometry, the dewetting transition is dictated by a balance of Marangoni, or surface tension gradient, stresses and gravitational stresses. The effect of gravitational orientation on Marangoni forced dewetting has not been considered previously even though multiple orientations are present for Marangoni flows on the inner wall of a cylindrical conduit. Experiments and modeling will quantify how dewetting transitions vary with deposition locus, cylinder radius and cylinder orientation in Marangoni flows inside a film-coated cylindrical tube that mimics a lung airway. An optical technique will be used to track quantitatively the evolution of film height profiles and reveal occurrences of dewetting or rewetting. This will be coupled with separate measures of soluble dye (a drug mimic) advection by the Marangoni flow. Models developed for the project will be tested in experimentally accessible conditions and then used to predict behaviors in the conditions more typical of the lung.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.