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

这个R61/R33项目将把一种新型的激光打印可穿戴传感器技术从实验室推向 改进高危深静脉监测方案的商业化首次临床应用 血栓形成(DVT)。本建议是对RFA-HL-20-024催化剂：产品定义的回应。该项目 是由Actuated Medical Inc.(AMI)、宾夕法尼亚州环宇拉里·程实验室合作的 和好时医疗中心(HMC)。AMI已通过国际标准化组织13485认证、食品药品监督管理局注册和食品药品监督管理局 符合GCP和GMP标准。这里开发的传感器将在宾夕法尼亚州贝尔方特的AMI工厂生产。 项目方法：程实验室(PSU)开发了一种灵活的传感器平台，该平台成本低，不 需要昂贵的设备来制造，可以直接穿在皮肤上或融入衣服中。 这些传感器可以配置为测量温度、应变、皮肤水份、电生理和其他 信号。这套传感器是在程博士的博士工作基础上构建的，他创造了可伸缩的健康传感器 监控、近场通信天线和人机界面。初步临床目标：DVT 是一种血液凝块在周围静脉深处形成的情况，通常是在下肢。这 疾病会导致腿部肿胀和疼痛，但更重要的是，血栓有移位和移位的风险。 肺(肺栓塞)、冠状动脉或脑(中风)，可能导致死亡。虽然很多人 存在降低风险的治疗方法，如抗凝剂，但慢性监测的选择寥寥无几。这 Project开发了一种可穿戴的无线方法，用于监控DVT形成的高危患者。假设。 基于石墨烯的热传感器压缩带可以成功地监测闭塞或深静脉血栓的形成 通过微妙的大血管和微血管对皮肤的热效应。明确的目标。目标1- 演示用于血流监测的外形尺寸的传感器制造。里程碑/验收标准： 热传感器的温度分辨率为≤0.04C，可准确检测流量或无流量状态 在体外的毛细管中。灵活的射频天线显示出足够的带宽来适应温度- 对应于≥的独立调频0.25C。目标2-过渡到制造及更高版本 批量处理。里程碑/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&lt；0.04°C传感器测量结果 至少8/10个设备，测量的5天重复性显示没有统计学上的显著差异 (稳健性/重复性)。目的3-临床前外周血栓形成研究。里程碑/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% 急性临床前研究中的小腿静脉阻塞(每条腿静脉阻塞4例)。目标4(R33)-过渡到设计 冰冻。里程碑/验收标准：传感器达到对移动至关重要的设计冻结控制 监管部门的批准。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.