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

用于长期监测高危患者静脉血栓栓塞的可穿戴石墨烯柔性传感器

• 批准号: 10062073
• 负责人: Roger Brooks Bagwell
• 金额: $ 39.15万
• 依托单位: ACTUATED MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-20 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062073
• 关键词: Acute; Adhesions; Adhesives; Affect; Age; Anticoagulants; Appointment; Biological; Blood; Blood Vessels; Blood capillaries; Blood coagulation; Blood flow; Brain; Cessation of life; Chemicals; Chronic; Clinical; Clinical Research; Clothing; Coagulation Process; Collaborations; Communication; Coronary artery; Deep Vein Thrombosis; Development; Device Designs; Devices; Diagnosis; Disease; Early Diagnosis; Elastomers; Elderly; Electrophysiology (science); Equipment; Exhibits; Freezing; Frequencies; Funding; Future; Gases; Goals; Health; Heart; Hydration status; Illinois; In Vitro; Individual; Laboratories; Lasers; Lead; Leg; Lower Extremity; Lung; Measurement; Measures; Medical; Medical center; Monitor; Outcome; Pain; Patients; Pennsylvania; Peripheral; Phase; Physiological; Preclinical Testing; Price; Process; Production; Pulmonary Embolism; Resolution; Risk; Semiconductors; Signal Transduction; Skin; Skin Temperature; Speed; Stream; Stretching; Stroke; Swelling; System; Technology; Temperature; Textiles; Thrombosis; Translations; Travel; Tube; Universities; User-Computer Interface; Vascular Diseases; Veins; Visit; Wireless Technology; Work; base; clinical application; commercialization; cost; cost effective; design; flexibility; graphene; high risk; improved; in vivo; innovation; laboratory equipment; light weight; lithography; mechanical properties; monitoring device; novel; operation; pre-clinical; preclinical study; research clinical testing; response; sensor; sensor technology; van der Waals force; venous thromboembolism; wearable sensor technology; wireless communication

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.

这个R61/R33项目将使新型激光打印的可穿戴传感器技术从实验室转移到 商业化，首次临床应用，用于改善高风险深静脉的监测选项 血栓形成（DVT）。该建议是对RFA-HL-20-024催化的回应：产品定义。项目 是宾夕法尼亚州的Huanyu Larry Cheng Lab的Actiet Medical Inc（AMI）之间的合作 大学（PSU）和好时医学中心（HMC）。 AMI是ISO 13485认证，FDA注册和FDA GCP和GMP符合符合性。这里开发的传感器将在宾夕法尼亚州AMI Bellefonte设施中生产。 项目方法：Cheng Lab（PSU）开发了一个低成本的灵活传感器平台，没有 需要昂贵的设备来制造，并且可以直接戴在皮肤上或整合到衣服上。 这些传感器可以配置为测量温度，应变，皮肤水合，电生理学和其他 信号。该传感器集建在Cheng博士的博士工作基础上，为健康创造可拉伸的传感器 监测，近场通信的天线和人机界面。最初的临床目标：DVT 是通常在下肢的外周静脉内深处形成血块的情况。这 疾病会导致腿部肿胀和疼痛，但更重要的是，凝块风险披露和搬迁 肺（肺栓塞），冠状动脉或大脑（中风）可能导致死亡。虽然很多 存在治疗以减轻风险，例如抗凝剂，几乎没有慢性监测的选择。这 项目开发了一种可穿戴的无线方法，用于监测高危患者的DVT形成。假设。 基于石墨烯的热传感器压缩带可以成功监视闭塞或DVT形成 通过微妙的大血管和微血管热影响皮肤。具体目标。目标1 - 展示以血流监测的形式形式制造的传感器制造。里程碑/接受标准： 热传感器显示温度分辨率≤0.04ºC，并且准确检测流量或没有流量状态 在体外毛细管中。柔性RF天线暴露了足够的带宽以适应温度 相关频率调制对应于≥0.25ºC。目标2 - 过渡到制造业和更高的 音量处理。里程碑/接受标准：RF带宽和温度的分辨率 - 制造级传感器天线传输的依赖频移<0.04ºC传感器测量值 至少8/10个设备和5天的测量可重复性显示没有统计学上的显着差异 （鲁棒性/可重复性）。 AIM 3 - 临床前周围血栓形成研究。里程碑/接受标准： 演示成功检测到50％和100％的受控过程传感器和设备设计/布局 急性临床前研究中的腿静脉的闭合（每个阻塞n = 4）。 AIM 4（R33） - 过渡到设计 冻结。里程碑/验收标准：传感器达到设计冻结控件，至关重要 监管批准。用> 95％的传感器演示无线通信。