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 ? 0.04C 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 ? 0.25C.
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 < 0.04C 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.
Relevance ? Deep vein thrombosis (DVT), a subset of venous thromboembolism, is a condition in which blood clots form deep within peripheral veins, typically in the lower extremities. This disease can cause swelling, vascular damage, and pain. More critically, when clots dislodge and travel through the blood stream they may lodge in lung, heart, or brain vessels and lead to death. Though treatments such as anticoagulants are available to mitigate risk, there are few options for chronic or continuous monitoring. This project develops a wearable approach for monitoring at-risk patients for DVT formation. More generally, the project matures a novel flexible sensor platform technology for cost-effective monitoring for a broad range of medical conditions.