CAREER: The Contagion Science: Integration of inhaled transport mechanics principles inside the human upper respiratory tract at multi scales

呼吸道病原体的空气传播研究是一个迅速扩大的领域，主要集中在从受感染宿主排出颗粒及其在密闭空间中的扩散。在很大程度上被忽视的是与吸入运输在呼吸腔内有关的流体物理。它在引导携带病毒的颗粒沿着人体上呼吸道到达感染易发区域方面起着至关重要的作用。因此，该项目旨在全面了解在解剖学上真实的上呼吸道域中，吸入的携带病原体的颗粒在不同时空尺度上的空中运输。这项工作还将通过将流体动力学见解与病毒学和流行病学参数相结合来描述呼吸道感染发病的机制。研究技术和结果将融入两个教育模块：(i)为地区印第安高中的教师和学生提供指导框架，以及（ii）与校园护理计划建立伙伴关系，传播呼吸护理的流体力学观点。模块（ii）还将有助于验证研究范式的生理现实主义，而模块(i)将纳入一个创新的美术部分，展示绘画和素描在科学传播中的作用。该项目的总体目标是使人体上呼吸道吸入致病性颗粒运输的流动物理建模成为可能。复杂的腔体形态，以扩张、收缩、T形和y形分支以及狭窄的组织间隙为特征，导致复杂的吸入气流模式。场的不稳定性对粒子的运动轨迹有显著的影响。了解优先降落在感染组织部位的有害吸入颗粒大小，从而将病原体运送到那里，是疾病传播建模的关键。该项目通过三个研究目标来解决这一知识缺口：(1)将大涡模拟数据与降阶数学建模相结合，推导出上呼吸道常见的弯曲和分支空间内小尺度涡主导的不稳定性效应的参数描述；(2)利用拉格朗日跟踪计算模拟惰性颗粒的平均平流输送，模拟吸入的携带病原体的颗粒，然后用缩放参数分析气道内区域沉积趋势，并在单分散气溶胶喷雾的3d打印解剖模型中进行样本实验验证；(3)将流体动力学推断与吸入颗粒物的大小分布和包埋病毒粒子浓度的跨学科输入相结合，评估病原体特异性参数，即引发感染的病毒载量（感染剂量）和安全暴露阈值。预期的发现准备建立一种新的多尺度方法，用于基于力学的呼吸系统疾病发病模型。该项目由流体动力学计划和建立计划共同资助，以刺激竞争研究（EPSCoR）。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。

The study of airborne transmission of respiratory pathogens constitutes a rapidly expanding field, predominantly focusing on the expulsion regimes of particulates from infected hosts and their dispersion in confined spaces. Largely overlooked has been the fluid physics associated with inhaled transport within the respiratory cavity. It plays a crucial role in directing virus-laden particulates to infection-prone regions along the human upper airway. This project thus aims to derive a comprehensive understanding of inhaled aerial transport of pathogen-bearing particulates across various spatio-temporal scales within anatomically realistic upper airway domains. The work will also delineate the mechanics of respiratory infection onset by integrating fluid dynamics insights with virological and epidemiological parameters. Research techniques and findings will be blended into two educational modules: (i) a mentorship framework for teachers and students at regional Native American high schools, and (ii) a partnership with the on-campus nursing program to disseminate fluid mechanics perspectives on respiratory care. Module (ii) will also help authenticate the physiological realism of the research paradigm, while module (i) will incorporate an innovative fine arts segment showcasing the role of paintings and sketches in science communication.The overarching goal of this project is to enable flow physics modeling for inhaled transport of pathogenic particulates within the human upper respiratory tract. The intricate cavity morphology, characterized by expansions, contractions, T- and Y-shaped branches, and narrow inter-tissue crevices, results in complex inhaled airflow patterns. The field instabilities can significantly impact the particle trajectories. Knowing the hazardous inhaled particle sizes that preferentially land at the infective tissue sites, hence ferrying the pathogens there, is key for disease spread modeling. The project addresses this knowledge gap through three research goals: (1) integrating Large Eddy Simulation data with reduced-order mathematical modeling to derive a parametric description of small-scale vortex-dominated instability effects within tortuous and branched spaces common in the upper airway; (2) utilizing Lagrangian tracking to computationally simulate mean advective transport of inert particles that physically mimic inhaled pathogen-bearing particulates, followed by analysis of the intra-airway regional deposition trends with scaling arguments and sample experimental validations in 3D-printed anatomical casts with monodisperse aerosol sprays; and (3) combining fluid dynamics inferences with cross-disciplinary inputs on size distribution and embedded virion concentration of the inhaled particulates to evaluate pathogen-specific parameters, namely the infection-triggering viral load (infectious dose) and safe exposure thresholds. Anticipated findings are poised to establish a novel multi-scale approach for mechanics-based modeling of respiratory disease onset. This project is jointly funded by Fluid Dynamics Program and the Established Program to Stimulate Competitive Research (EPSCoR).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.