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

项目摘要 代谢综合征作为发病率和死亡率的主要原因正在上升，影响超过三分之一的人。 所有美国成年人。如果不治疗，发展为2型糖尿病（T2 D）的患者具有发生主要糖尿病的高风险。 不良心血管事件，包括卒中、心肌梗死和心血管相关死亡。 尽管长期筛查和监测用于患者特异性预测和预防心脏代谢异常， 尽管疾病的发病率不断上升，但检测和监测代谢风险因素仍然是一个瓶颈， 肥胖症的流行--与高脂血症、高血压和糖尿病有关。由于这些原因， 开发可穿戴的分子传感器，允许无缝筛选，监测，并可能 能够及时进行干预，对于应对日益增多的心脏代谢疾病具有临床意义。 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（BCAA：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 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，我们建议开发新型激光雕刻可穿戴传感器，用于连续 基于结合高通量的新型纳米生物传感方法监测BCAA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 法这种方法将使高灵敏度和选择性传感器的大规模，低成本制造成为可能 用于连续监测人体汗液中具有临床意义的心脏代谢分析物， 浓度（如BCAA）。利用激光诱导微流体和数值模拟引导 设计优化使得能够进行有效的流体采样， 蒸发利用并发多路复用心脏代谢感知的能力，调整 基于pH值、电解质、温度和出汗率校准的电化学测量可最大限度地减少 系统的不确定性在当前一代的可穿戴传感系统中持续存在。我们将验证 使用iMSS的健康受试者的汗液/血液生物标志物的相关性，并将这些表皮 高风险患者的传感器。我们设想，iMSS系统将提供一个切入点，以确定前- 糖尿病和肥胖有转化为T2 D的风险，并将对减轻临床 主要心血管不良事件的表现。

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.