CAREER: Wearable Biomarker Analysis for Point-of-Person Monitoring

要应对巨大的社会医疗挑战，包括人类痛苦和不断增长的医疗成本，就需要从通用和反应性医学向个性化，主动和预防性医学转变。因此，可穿戴生物监测技术在促进人们对健康生活方式的认识和采用以预防疾病并实现可操作的反馈方面发挥着关键作用。目前，商业化的可穿戴传感器和物联网设备只能跟踪身体活动和生命体征，无法非侵入性地获取分子水平的生物标志物信息，以提供对人体动态化学的洞察。此外，在目前的状态下，提供循环生物标志物的直接测量的基于血液的传感技术不能在一般人群中进行扩展，以进行个人日常监测（由于其侵入性和感染风险）。或者，可以探测其他生物流体，其与血液共享生物标志物分配途径，并且可以非侵入性地进入。在这方面，汗液是一个很好的候选者，因为它是最初从血液中扩散的生物标志物的丰富来源，并且可以以可穿戴的形式进行检索，而无需用户干预。通过在提供血液生物标志物的非侵入性代理测量中获得合理水平的预测准确性，可穿戴汗液传感器允许监测个人的健康状况，并实现可操作的反馈以改善他们的健康和表现。 拟议的研究解决了在设备、传感器和数据分析层面推进基于汗液的生物传感领域的关键瓶颈。在所提出的方法中，通过设计可编程的离子电渗汗液诱导和微流体接口，将减轻混杂因素和污染的干扰影响。将设计高通量电修饰传感器开发方法，用于以微阵列格式多重构建化学多样的感测特征，其将被定制以准确测量身体上的汗液生物标志物。此外，将开发一个分析框架，以提供汗液生物标志物的不失真测量，从而提供血液生物标志物水平的个体水平时间估计，以建立汗液读数的相关性和临床实用性。在实现拟议的里程碑后，一类具有实时信息传感和传输能力的新生物标志物分析平台出现，可以促进一般人群的福祉和性能监测。同样重要的是，所设计的方法的多功能性允许它们以最小的重新配置用于靶向其他生物流体（间质液、唾液、尿液和血液）中的生物标志物。通过这些技术收集的大型数据集将扩大我们对个人和社会健康需求的理解。未来几代科学家将通过将外联和教育计划与研究活动协同结合的方式接受培训。高中/本科生的多元化社区将参与研究。研究成果将被整合到PI正在开发的生物传感课程中。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。

Addressing the grand societal healthcare challenges, regarding both human suffering and the ever-growing cost of healthcare, necessitates a paradigm shift from generic and reactive medicine to personalized, proactive, and preventive medicine. Accordingly, wearable biomonitoring technologies play a critical role in promoting awareness and adoption of healthy lifestyles for disease prevention and enabling actionable feedback. Currently, commercialized wearable sensors and Internet of Things devices are only capable of tracking physical activities and vital signs, and fail to non-invasively access molecular-level biomarker information to provide insight into the body's dynamic chemistry. Also, at the current state, blood-based sensing techniques that provide direct measurements of circulating biomarkers cannot be scaled across the general population for point-of-person daily monitoring (due to their invasive nature and risk of infection). Alternatively, other biofluids can be probed, which share biomarker partitioning pathways with blood and can be accessed non-invasively. In this regard, sweat is an excellent candidate, because it is a rich source of biomarkers that originally diffused from blood and can be retrieved in a wearable format and without user intervention. By attaining reasonable level of predictive accuracy in providing non-invasive proxy measures of blood biomarkers, wearable sweat sensors allow for monitoring the well-being of individuals and enable actionable feedback to improve their health and performance. The proposed research addresses fundamental bottlenecks critical to advancing the field of sweat-based biosensing at device, sensor, and data analytics levels. In the proposed approach, by devising programmable iontophoretic sweat induction and microfluidic interfaces, the interfering effects of confounders and contamination will be mitigated. A high throughput electro-modification sensor development methodology will be devised for the multiplexed construction of chemically diverse sensing features in microarray formats, which will be tailored to accurately measure sweat biomarkers on body. Furthermore, an analytical framework will be developed to provide undistorted measures of the sweat biomarkers, thus rendering individual-level temporal estimates of blood biomarker levels to establish the correlation and clinical utility of sweat readings. Upon achieving the proposed milestones, a new class of biomarker analysis platforms, with real-time information sensing and transmission capabilities, emerge that can facilitate general population well-being and performance monitoring. Equally important, the versatility of the devised methodologies allows for their use, with minimal reconfiguration, to target biomarkers in other biofluids (interstitial fluid, saliva, urine, and blood). The large data sets that will be collected through these technologies will expand our understanding of personal and societal health needs. Future generations of scientist will be trained by synergistically integrating the outreach and education plans with research activities. A diverse community of high school/undergraduate students will participate in research. The research findings will be integrated in the biosensing courses that the PI is developing.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.