CAREER: Rationale Design of Autonomous Biomimetic Wearable Sensor for Personalized Molecular Monitoring of Long COVID

2019冠状病毒病大流行已经颠覆了数十亿人的生活，在全球传播了数亿例病例。最近的研究表明，大量康复患者（即使是最初症状轻微或无症状的患者）会出现长期的新冠肺炎后并发症。据报道，我们体内的许多类型的生物标志物分子与这些后疫情密切相关。由于目前的COVID-19大流行在全球范围内仍未得到控制，因此迫切需要开发可穿戴传感器来监测个人在家的健康状况。目前，大多数医疗检查都是基于血液检查，需要进行侵入性抽血和门诊体检。人体汗液中含有丰富的化学物质，包括可以反映人体生理状态的化学物质。与血液测试相比，汗液分析可以作为日常生活中持续健康监测的非侵入性和更有吸引力的候选方法。可穿戴式汗液传感器可以在人们的日常活动中对长期与新冠病毒相关的生物标志物进行个性化监测。这种技术可以帮助人们更好地了解covid后的情况，以及如何治疗这些长期影响的患者。该项目旨在开发一种可穿戴生物传感器平台，该平台可以有效地提取和采样活动中的汗液，并对广谱生物标志物进行原位、无创分子分析，以实现长COVID的个性化分子监测。该项目将解决可穿戴传感器领域的多个研究挑战。首先，为实现与新冠病毒相关的多种痕量汗液生物标志物的可穿戴监测，将开发一种独特的基于人工生物受体的可穿戴分子传感策略。这种生物传感方法将通过计算和实验方法进行优化。其次，考虑到目前的可穿戴式汗液传感器大多依靠运动来获取汗液，不适合日常在家使用或久坐不动的个体，本项目将开发完全集成的微流控可穿戴系统，用于自主汗液感应、高效汗液采样和跨活动的原位多路分析。最后，将在长冠状病毒感染者中对可穿戴传感器进行体内评估，对冠状病毒后并发症进行回顾性和前瞻性监测。可穿戴式汗液生物传感器持续收集的目前无法获得的分子信息可能会对公共卫生产生深远的影响，并极大地促进我们对循环生物标志物在长期COVID中的作用的基本理解，以减少对COVID后并发症的易感性。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 COVID-19 pandemic has upended the lives of billions of people, spreading globally to hundreds of million cases. Recent studies show that a large number of recovered patients (even those with initially mild or no symptoms) will have prolonged post-COVID complications (long COVID). Many types of biomarker molecules in our body are reported to be closely linked to these post-COVID conditions. As the current COVID-19 pandemic remains uncontrolled around the world, there is a pressing need for developing wearable sensors to monitor an individual’s health status at home. Most of the medical examinations are currently based on blood tests that require invasive blood draws and physical clinic visits. Human sweat contains a wealth of chemicals including that can reflect the body’s physiological state. Compared with blood tests, sweat analyses could serve as a non-invasive and more attractive candidate for continuous health monitoring in daily life. Wearable sweat sensors could allow personalized monitoring of long-COVID-related biomarkers in people’s daily activities. Such technology could help people better understand post-COVID conditions and how to treat the patients with these longer-term effects.This project aims to develop a wearable biosensor platform that can efficiently extract and sample sweat across activities, and perform in situ, non-invasive molecular analysis of a broad spectrum of biomarkers toward personalized molecular monitoring of long COVID. This project will address multiple research challenges in the wearable sensor field. Firstly, to enable wearable monitoring of a variety of trace-level sweat biomarkers related to long COVID, a unique wearable molecular sensing strategy will be developed based on artificial bioreceptors. This biosensing approach will be optimized with both computational and experimental approaches. Secondly, considering that current wearable sweat sensors mostly rely on exercise to access sweat and are not suitable for daily at-home uses or for sedentary individuals, this project will develop the fully integrated microfluidic wearable system for autonomous sweat induction, efficient sweat sampling, and in situ multiplexed analysis across activities. Lastly, in vivo evaluation of the wearable senor will be performed in patients with long COVID for retrospective and prospective monitoring in post-COVID complications. The currently unavailable molecular information collected continuously by the wearable sweat biosensors could have a profound public health impact and greatly facilitate our fundamental understanding of the roles of circulating biomarkers in long COVID to reduce susceptibility to post-COVID complications.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.