Innovative Microfluidic and Wearable Device for CVD Modelling and Prevention

Abstract

Thrombotic diseases, a major subset of cardiovascular diseases, are significant contributors to global morbidity, mortality, and economic burden. They play a critical role in conditions such as ischemic heart disease, ischemic stroke, and venous thromboembolism (VTE). Effective treatment of these diseases is essential for reducing cardiovascular complications worldwide. Advanced technologies, such as microfluidic platforms and innovative drug delivery systems, have been increasingly utilized to investigate disease mechanisms and develop therapeutic strategies. However, the development of these advanced technologies still faces several challenges. For example, in microfluidic systems that replicate vascular microenvironments, there are significant differences between biomechanical forces and physiological microenvironments. Similarly, drug delivery systems still suffer from issues like bulkiness or poor patient compliance. This thesis presents the development of innovative microfluidic and microneedle-based systems aimed at addressing these challenges by improving disease modeling, enabling precise drug delivery, and advancing personalized medicine. By integrating deformable microfluidic vascular models and wearable microneedle patches with intelligent control systems, this work provides a comprehensive framework for addressing critical challenges in thrombosis research and chronic disease management.

First, a pressure-responsive deformable microchannel system was developed to mimic the mechanical and hemodynamic properties of human blood vessels. Fabricated using soft lithography, the system features ultrathin elastic membranes that replicate vascular compliance, cyclic strain, and pulsatile flow. These features allow the system to reproduce the dynamic mechanical stimuli experienced by blood vessels in vivo, including the interplay between blood pressure, shear stress, and vessel wall deformation. These artificial vascular models are capable of mimicking the in vivo microenvironment, allowing endothelial cells to respond to physiological mechanical stimuli. Furthermore, a three-dimensional stenosis model was developed to simulate the flow disturbances often associated with thrombosis and atherosclerosis. The platform also incorporates flow control systems to generate physiologically relevant flow patterns, enabling precise modeling of disturbed flows that frequently lead to thrombosis. The deformable microchannels can be easily integrated with traditional microfluidic systems to construct more complex and physiologically accurate in vitro models. This deformable microfluidic platform serves as a robust model for studying thrombosis formation, platelet activation, and drug interactions under physiologically relevant conditions, bridging the gap between oversimplified in vitro models and the complex in vivo environment.

To overcome the limitations of traditional drug delivery methods, a wearable microneedle patch system was developed for precise, minimally invasive, and sustained drug administration. The system integrates hollow microneedles, a piezoelectric pump, a microfluidic module, and Bluetooth-enabled electronics to enable controlled drug release and real-time monitoring. The hollow microneedles penetrate the stratum corneum with minimal discomfort, delivering drugs directly into the dermis. The piezoelectric pump provides pressure-driven control of the drug release rate, while the microfluidic module incorporates check valves and capacitors to maintain stable pressure and prevent backflow. The wearable device’s electronics allow for closed-loop feedback control and wireless communication, enabling precise regulation of drug delivery and remote monitoring via mobile devices. In vitro studies using porcine skin demonstrated the microneedle patch’s ability to penetrate the skin barrier and efficiently deliver drugs, with pressure and treatment duration significantly influencing delivery rates and dose control. In vivo pharmacokinetic studies in rats using enoxaparin sodium, a low molecular weight heparin, revealed that the microneedle patch achieves sustained zero-order drug release, maintaining therapeutic plasma concentrations for extended periods compared to traditional subcutaneous injections. Furthermore, in a pulmonary embolism mouse model, the microneedle patch system significantly reduced mortality by providing continuous anticoagulant protection, demonstrating its potential for preventing VTE.

This thesis highlights the transformative potential of combining microfluidic vascular models and microneedle-based drug delivery systems to advance thrombosis research and personalized healthcare. The deformable microchannel system provides an effective platform for studying vascular biomechanics and thrombosis under physiologically relevant conditions, while the wearable microneedle patch offers a versatile, patient-friendly solution for sustained and personalized drug delivery. Future directions include enhancing biosensing integration to enable real-time diagnostics and expanding the clinical applications of these systems to other chronic and acute medical conditions. Together, these innovations pave the way for the development of next-generation biomedical devices that address critical needs in disease modeling, drug delivery, and precision medicine.

Date of Award	6 May 2025
Original language	English
Awarding Institution	City University of Hong Kong
Supervisor	Dong SUN (Supervisor) & Xinge YU (Supervisor)