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

应对重大的社会医疗挑战，既涉及人类痛苦，也涉及不断增长的医疗成本，需要从仿制和反应性医学向个性化、主动性和预防性医学的范式转变。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，从而洞察人体的动态化学。此外，在目前的状态下，提供循环生物标志物直接测量的血液传感技术不能在普通人群中进行日常监测(由于其侵入性和感染风险)。或者，可以探测其他生物流体，这些生物流体与血液共享生物标记物的分配途径，并且可以非侵入性地进入。在这方面，汗水是一个很好的候选者，因为它是生物标志物的丰富来源，最初是从血液中扩散的，可以通过可穿戴格式检索，而无需用户干预。通过在提供血液生物标志物的非侵入性替代测量方面获得合理的预测精度，可穿戴式汗液传感器允许监控个人的幸福感，并实现可操作的反馈，以改善他们的健康和表现。这项拟议的研究解决了在设备、传感器和数据分析层面上推进基于汗液的生物传感领域的关键根本瓶颈。在所提出的方法中，通过设计可编程的离子导入汗液诱导和微流控界面，将减轻混杂和污染的干扰影响。将设计一种高通量电修饰传感器开发方法，用于以微阵列格式多路构建化学多样性的传感特征，该特征将被量身定做，以准确测量身体上的汗液生物标记物。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人水平时间估计，以建立汗液读数的相关性和临床实用性。一旦达到拟议的里程碑，具有实时信息感知和传输能力的新一类生物标志物分析平台就会出现，可以促进一般人群的福祉和绩效监测。同样重要的是，设计的方法的多功能性允许使用它们，只需最小限度的重新配置，即可针对其他生物流体(间质性液体、唾液、尿液和血液)中的生物标记物。将通过这些技术收集的大量数据集将扩大我们对个人和社会健康需求的理解。将通过将外联和教育计划与研究活动协同结合起来，对未来几代科学家进行培训。不同群体的高中生/本科生将参与研究。这些研究成果将被整合到PI正在开发的生物传感课程中。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.