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

职业：传染病科学：在多尺度上整合人类上呼吸道内的吸入运输力学原理

• 批准号: 2339001
• 负责人: Saikat Basu
• 金额: $ 54.04万
• 依托单位: South Dakota State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-01 至 2028-12-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2339001&HistoricalAwards=false
• 关键词: CAREER; Contagion; Science; Integration; inhaled

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.

对呼吸道病原体的空气传播的研究构成了一个快速扩大的领域，主要集中在受感染宿主中的颗粒物的驱逐状态及其在密闭空间中的分散体。在很大程度上被忽略的是与呼吸腔内吸入转运相关的液体物理。它在将含病毒的颗粒引导到沿着人类上部气道的易感染区域中起着至关重要的作用。因此，该项目旨在从解剖上逼真的上呼吸道域内的各种时空尺度上全面了解含有病原体的颗粒物的吸入空中运输。这项工作还将通过将流体动力学洞察力与病毒学和流行病学参数相结合来描述呼吸道感染发作的力学。研究技术和发现将被融合到两个教育模块中：（i）为美国原住民中学的教师和学生提供指导框架，以及（ii）与校园护理计划的合作伙伴关系，以在呼吸保健方面传播流体力学的观点。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）将结合一个创新的美术段，展示了绘画和草图在科学通信中的作用。该项目的总体目标是启用流动物理学建模，以吸入人类的人类互动式式式式式式式式互联网。复杂的腔形态为特征，其特征是膨胀，收缩，T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。场不稳定性可以显着影响粒子轨迹。知道危险的吸入粒径优先降落在感染组织部位的危险颗粒大小，因此在那里运送病原体，这是疾病扩散建模的关键。该项目通过三个研究目标解决了这一知识差距：（1）将大型涡流模拟数据与降低的数学建模整合在一起，从而在曲折的曲折和分支空间内传播的小规模涡流主导的不稳定性效应的参数描述； （2）利用拉格朗日跟踪到计算上模拟物理模仿含有病原体的颗粒的惰性颗粒的平均对流传输，然后分析带有缩放的参数和样本实验验证的Air-Arway内部区域沉积趋势，并在3D刻画的解剖学库中使用单粘膜Aerososol Aerososol Sperrays分析。 （3）将流体动力学与跨学科输入结合在尺寸分布和吸入颗粒的嵌入式病毒粒子浓度上，以评估病原体特异性参数，即感染触发病毒负荷（感染剂量）和安全暴露阈值。预期的发现有望建立一种新型的多尺度方法，用于基于力学的呼吸道疾病发作的建模。该项目由流体动力学计划和既定的竞争研究（EPSCOR）共同资助。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，认为值得通过评估来获得支持。