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.

该 R61/R33 项目将把新型激光打印可穿戴传感器技术从实验室推向实用化 商业化，首次临床应用改善高风险深静脉监测选项 血栓形成（DVT）。该提案是对 RFA-HL-20-024 Catalyze：产品定义的回应。项目 是 Actuated Medical Inc (AMI) 与宾夕法尼亚州立大学 Huanyu Larry Cheng 实验室之间的合作 大学 (PSU) 和好时医疗中心 (HMC)。 AMI 已通过 ISO 13485 认证、FDA 注册和 FDA 符合 GCP 和 GMP。这里开发的传感器将在 AMI 位于宾夕法尼亚州贝尔丰特的工厂生产。 项目方法：Cheng Lab (PSU) 开发了一种灵活的传感器平台，该平台成本低廉，无需 需要昂贵的设备来制造，并且可以直接佩戴在皮肤上或融入衣服中。 这些传感器可配置为测量温度、应变、皮肤水合作用、电生理学和其他 信号。该传感器组基于程博士的博士研究成果，为健康领域创建了可拉伸传感器 监控、近场通信天线和人机界面。初始临床目标：DVT 是一种在外周静脉深处（通常是下肢）形成血栓的疾病。这 该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 肺部（肺栓塞）、冠状动脉或大脑（中风），可能导致死亡。虽然很多 存在减轻风险的治疗方法，例如抗凝剂，但长期监测的选择很少。这 该项目开发了一种可穿戴式无线方法，用于监测高危患者的 DVT 形成情况。假设。 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 通过对皮肤的微妙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传感器制造。里程碑/接受标准： 热传感器的温度分辨率为 ≤ 0.04°C，可准确检测流量或无流量状态 在体外毛细管中。灵活的射频天线具有足够的带宽来适应温度变化 相关频率调制对应≥ 0.25°C。目标 2 – 向制造业及更高层次转型 体积处理。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可传输 < 0.04°C 的传感器测量值 至少 8/10 台设备，并且 5 天的测量重复性显示没有统计学上的显着差异 （稳健性/可重复性）。目标 3 – 临床前外周血栓形成研究。里程碑/接受标准： 展示成功检测 50% 和 100% 的受控过程传感器和设备设计/布局 急性临床前研究中腿部静脉阻塞（每次阻塞 N=4）。目标 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制对于通过至关重要 监管批准。演示与 >95% 的传感器的无线通信。