Wearable, Graphene-based Flexible Sensors for Chronic Monitoring of Venous Thromboembolism for High-Risk Patients

这个R61/R33项目将把一种新颖的激光打印可穿戴传感器技术从实验室推向 商业化，首次临床应用，改善高风险深静脉的监测选项 血栓形成（DVT）。本提案是对RFA-HL-20-024催化剂：产品定义的回应。项目 是Actuated Medical Inc（AMI）与宾夕法尼亚州Huanyu Larry Cheng实验室的合作 大学（PSU）和好时医疗中心（HMC）。AMI已通过ISO 13485认证，FDA注册， 符合GCP和GMP要求。这里开发的传感器将在AMI的贝莱丰特，宾夕法尼亚州的设施。 项目方法：Cheng实验室（PSU）开发了一种灵活的传感器平台，该平台成本低， 需要昂贵的设备来制造，并且可以直接穿在皮肤上或结合到衣服中。 这些传感器可以被配置为测量温度、应变、皮肤水合作用、电生理学等。 信号.这套传感器是建立在郑博士的博士工作创造可伸缩传感器的健康 监测、近场通信天线和人机界面。初始临床目标：DVT 血栓形成是一种在外周静脉深处形成血块的疾病，通常在下肢。这 疾病会导致腿部肿胀和疼痛，但更重要的是，血栓有移位和重新定位的风险， 肺（肺栓塞）、冠状动脉或脑（中风），可能导致死亡。尽管许多 虽然存在减轻风险的治疗方法，如抗凝血剂，但慢性监测的选择很少。这 该项目开发了一种可穿戴的无线方法，用于监测DVT形成的高危患者。假说. 基于石墨烯的热传感器压缩带可以成功监测闭塞或DVT形成 通过对皮肤的细微的大血管和微血管热效应。具体目标。目标1 - 演示用于血流监测的形状因子传感器制造。Milestone/验收标准： 热传感器的温度分辨率为≤ 0.04ºC，可准确检测是否有流 在体外的毛细管中。灵活的射频天线具有足够的带宽，以适应温度- 对应于≥ 0.25ºC的相关频率调制。目标2 -向制造业及更高层次过渡 卷处理。微波/验收标准：射频带宽和温度分辨率- 制造级传感器天线的相关频移传输< 0.04ºC传感器测量值， 至少8/10件器械，5天测量重复性显示无统计学显著差异 （耐用性/可重复性）。目的3 -临床前外周血栓形成研究。Milestone/验收标准： 演示受控过程传感器和设备设计/布局，成功检测50%和100% 急性临床前研究中腿部静脉闭塞（每种闭塞N=4）。目标4（R33）-过渡到设计 不许动Military/验收标准：传感器达到设计冻结控制，这对通过至关重要 监管批准。演示与>95%的传感器进行无线通信。

This R61/R33 project will move a novel laser-printed wearable sensor technology from laboratory toward commercialization with a first clinical application of improving monitoring options for high-risk Deep Vein Thrombosis (DVT). This proposal is in response to RFA-HL-20-024 Catalyze: Product Definition. The project is a collaboration between Actuated Medical Inc (AMI), the Huanyu Larry Cheng lab at The Pennsylvania State University (PSU), and Hershey Medical Center (HMC). AMI is ISO 13485 certified, FDA-Registered, and FDA GCP & GMP compliant. The sensors developed here will be manufactured in AMI’s Bellefonte, PA facility. Project Approach: The Cheng Lab (PSU) has developed a flexible sensor platform that is low-cost, does not require expensive equipment to manufacture, and can be worn directly on the skin or integrated into clothing. These sensors can be configured to measure temperature, strain, skin hydration, electrophysiologic, and other signals. This sensor set is built upon Dr. Cheng’s doctoral work creating stretchable sensors for health monitoring, antennas for near-field communication, and human-machine interfaces. Initial Clinical Goal: DVT is a condition in which blood clots form deep within peripheral veins, typically in the lower extremities. This disease can cause leg swelling and pain, but more importantly, the clots risk dislodgement and relocation in the lungs (pulmonary embolism), coronary arteries, or brain (stroke), possibly leading to death. Though many treatments exist to mitigate risk, such as anticoagulants, there are few options for chronic monitoring. This project develops a wearable, wireless approach for monitoring at-risk patients for DVT formation. Hypothesis. A graphene-based thermal sensor compression band can successfully monitor occlusion or DVT formation through subtle macrovascular and microvascular thermal effects on the skin. Specific Aims. Aim 1 – Demonstrate Sensor Fabrication in Form Factor for Blood Flow Monitoring. Milestones/Acceptance Criteria: Thermal sensors demonstrate temperature resolution of ≤ 0.04ºC and accurately detect flow or no flow status in capillary tubes in vitro. Flexible RF antennas exhibit sufficient bandwidth to accommodate temperature- dependent frequency modulation corresponding of ≥ 0.25ºC. Aim 2 – Transition to Manufacturing and Higher Volume Processing. Milestones/Acceptance Criteria: RF bandwidth and resolution of temperature- dependent frequency shift of manufacturing-level sensor antenna transmits < 0.04ºC sensor measurements for at least 8/10 devices, and 5 day repeatability of measurements shows no statistically significant differences (robustness/repeatability). Aim 3 – Preclinical Peripheral Thrombosis Study. Milestones/Acceptance Criteria: Demonstrate controlled process sensor and device design/layout that successfully detects 50% and 100% occlusions of leg vein (N=4 for each blockage) in acute preclinical study. Aim 4 (R33) – Transition to Design Freeze. Milestones/Acceptance Criteria: Sensors reaches Design Freeze controls critical for moving through Regulatory approval. Demonstrate wireless communication with >95% of sensors.