Dewetting and Rewetting in Marangoni Driven Spreading on Complex Liquid Films

这个项目的目标是改善阻塞性肺病患者的气雾剂给药系统。气溶胶类药物的分布受到肺部气流的强烈影响。控制含药雾滴的大小和密度，可以保证药物深入肺部，均匀分布。然而，当肺部被过多的粘液沉积或气道收缩阻塞时，气流模式就会改变，气溶胶液滴沉积在阻塞物上或上游。该项目将研究一种替代策略，在气溶胶滴降落在肺气道表面后，最大限度地分散药物。表面活性剂分子将被纳入气溶胶液滴中，因此液滴降落后，液滴附近的表面张力将沿肺表面变化。表面张力的梯度会引起气道表面液体（ASL）薄膜的流动。在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，这将减少药物的扩散。该项目将评估影响薄膜破裂的现象，并解决其对药物运输的影响。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部疾病（包括囊性纤维化、肺炎和急性或慢性肺部感染）的药物分布。本科生和研究生将加入一个多学科团队进行研究，并指导中学生进行实验，探索医学中的物理过程，这是卡内基梅隆大学/科尔法克斯物理概念推广计划的一部分。该项目将解决模型系统中两个尚未研究的现象，这些现象代表了气溶胶基药物输送的关键马兰戈尼流流体动力学。第一个是由最近发现的两层手语的详细结构引起的。ASL的底层由紧密系留的粘蛋白链组成，类似于流体饱和的多孔介质。假设上流体层与多孔介质界面处的滑移会阻碍脱湿，而流体从多孔介质中流出可能会促进再润湿。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薄膜的脱湿和再湿转变。第二个现象涉及几何和重力的耦合作用。在平面几何中，脱湿过渡是由马兰戈尼（Marangoni）或表面张力梯度、应力和重力应力的平衡决定的。尽管在圆柱形管道内壁上存在多种马兰戈尼流取向，但重力取向对马兰戈尼强迫脱湿的影响尚未被考虑。实验和建模将量化马兰戈尼流在模拟肺气道的涂膜圆柱形管内的脱湿过渡如何随沉积轨迹、圆柱体半径和圆柱体方向而变化。光学技术将用于定量跟踪薄膜高度分布的演变，并揭示脱湿或再湿的发生。这将与马兰戈尼流的可溶性染料（一种药物模拟物）平流的单独测量相结合。为该项目开发的模型将在实验条件下进行测试，然后用于预测更典型的肺条件下的行为。该奖项反映了美国国家科学基金会的法定使命，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.