Laser-Engraved Wearable Sweat Sensors to Detect and Monitor Cardiometabolic Disease

项目总结 代谢综合征是导致发病率和死亡率的主要原因，影响了三分之一以上。 在所有美国成年人中。如果不治疗，患2型糖尿病(T2D)的患者患重大疾病的风险很高 心血管不良事件，包括中风、心肌梗死和心血管相关死亡。 尽管慢性筛查和监测对心脏代谢的患者特异性预测和预防 疾病，仍然存在一个瓶颈，以检测和监测代谢风险因素背后的上升 肥胖流行--与高脂血症、高血压和糖尿病有关。出于这些原因， 开发可穿戴的分子传感器，允许无缝筛选、监测和潜在地 能够及时干预，对于应对日益流行的心脏代谢性疾病具有临床意义。 在这个项目中，我们建议持续监测一组关键的代谢生物标志物，包括葡萄糖、 尿酸、支链氨基酸(支链氨基酸：亮氨酸、异亮氨酸和缬氨酸)和胰岛素 集成分子传感系统(IMSS)我们假设心脏代谢的无缝检测 生物标志物加速了我们识别糖尿病前期肥胖患者代谢危险因素的能力 用于早期营养干预，以减少美国的健康差距。除了与我们现有的 葡萄糖和尿酸传感器，我们建议开发新型的激光雕刻可穿戴传感器，用于连续 基于高通量相结合的新型纳米生物传感方法监测支链氨基酸和胰岛素 激光制造石墨烯、基于分子印迹的人工抗体和原位传感器再生 技术。这种方法将能够大规模、低成本地制造高灵敏度和高选择性的传感器 用于连续监测超低浓度下人体汗液中有临床意义的心脏代谢分析物 浓度(如支链氨基甲酸)。激光诱导微流控技术的应用及数值模拟导引 优化设计可实现高效的流体采样，并将感测延迟和流体的影响降至最低 蒸发。利用并行多路心脏代谢检测的力量，调整 基于pH、电解质、温度和出汗率校准的电化学测量最小化 系统的不确定性持续存在于当前一代可穿戴传感系统中。我们将验证 健康受试者汗液和血液生物标志物的相关性研究 传感器传给高危患者。我们设想，IMSS系统将提供一个入口点，以识别预 糖尿病和肥胖有转换为T2D的风险，并将对缓解临床症状具有翻译意义 主要不良心血管事件的表现。

PROJECT SUMMARY Metabolic syndrome is on the rise as the leading cause of morbidity and mortality, affecting more than a third of all U.S. adults. If untreated, patients who develop type 2 diabetes mellitus (T2D) are at high-risk for major adverse cardiovascular events, including stroke, myocardial infarction, and cardiovascular related deaths. Despite chronic screening and monitoring for patient-specific prediction and prevention for cardiometabolic disease, there remains a bottleneck to detect and monitor the metabolic risk factors underlying the rising epidemic of obesity-associated with hyperlipidemia, hypertension, and diabetes. For these reasons, developing wearable molecular sensors, which allow for seamless screening, monitoring, and potentially enables timely intervention, is clinically significant to confront the rising endemic of cardiometabolic disorders. In this project, we propose to continuously monitor a panel of key metabolic biomarkers including glucose, uric acid, branched-chain amino acids (BCAAs: leucine, isoleucine, and valine), and insulin using an integrated Molecular Sensing System (iMSS). We hypothesize that seamless detection of cardiometabolic biomarkers accelerates our capacity to identify metabolic risk factors in our prediabetic patients with obesity for early nutrition intervention to reduce health disparities in the U.S. In addition to integrating with our existing glucose and uric acid sensors, we propose to develop novel laser-engraved wearable sensors for continuous monitoring of BCAAs and insulin based on a novel nanobiosensing approach that combines high-throughput laser-fabricated graphene, molecular imprinting based ‘artificial antibody’, and in situ sensor regeneration technique. This approach will enable large-scale, low-cost fabrication of highly sensitive and selective sensors for continuous monitoring of clinical meaningful cardiometabolic analytes in human sweat at ultralow concentrations (such as BCAAs). The use of laser-induced microfluidics and numerical simulation-guided design optimization enables efficient fluid sampling with minimized effects from the sensing delay and fluid evaporation. Harnessing the power of concurrent multiplexed cardiometabolic sensing, adjusted electrochemical measurements based on pH, electrolytes, temperature, and sweat rate calibration minimize the systematic uncertainties persisted in the current generation of wearable sensing systems. We will validate the correlation of the sweat/blood biomarkers in healthy subjects using the iMSS and deploy these epidermal sensors to the high-risk patients. We envision that the iMSS system will provide an entry point to identify pre- diabetes and obesity at risk for conversion to T2D, and will have translational significance to mitigate clinical manifestation of major adverse cardiovascular events.