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的研究构成了一个迅速扩大的领域，主要集中在从受感染的主机和他们在密闭空间中的分散颗粒的驱逐制度。最常被忽视的是与呼吸腔内吸入运输相关的流体物理学。它在将携带病毒的微粒引导到沿着人体上呼吸道的易感染区域中起着至关重要的作用。因此，该项目的目的是获得一个全面的了解，在解剖学上现实的上呼吸道领域内的各种时空尺度的病原体携带颗粒物的吸入空中运输。这项工作还将通过将流体动力学的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。研究技术和研究结果将被融入两个教育模块：（一）教师和学生在区域美洲原住民高中的导师框架，以及（二）与校园护理计划的合作伙伴关系，以传播流体力学对呼吸护理的观点。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）将包括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实现人体上呼吸道内致病颗粒吸入运输的流动物理建模。复杂的腔形态，其特征在于扩张、收缩、T形和Y形分支以及狭窄的组织间缝隙，导致复杂的吸入气流模式。场的不稳定性可以显著地影响粒子的轨迹。了解优先降落在感染组织部位的有害吸入颗粒尺寸，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模型相结合，以获得上气道中常见的曲折和分支空间内小尺度涡主导不稳定性效应的参数描述;（2）利用拉格朗日跟踪来计算模拟物理上模拟吸入的携带病原体的颗粒的惰性颗粒的平均平流输送，随后通过缩放参数分析气道内区域沉积趋势，并在具有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;以及（3）将流体动力学推断与关于吸入颗粒的尺寸分布和包埋病毒体浓度的跨学科输入相结合以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。预期的研究结果有望建立一种新的多尺度方法，用于呼吸系统疾病发病的力学建模。该项目由流体动力学计划和刺激竞争研究的既定计划（EPSCoR）共同资助。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。

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.