Development of Endothelialised Microfluidic Platform for Cancer invasion and Thrombosis

Abstract

Thrombosis is a complex process involving vascular injury, platelet activation, and coagulation cascades, contributing to major clinical complications including myocardial infarction, stroke, and cancer-associated thrombosis (CAT). Conventional experimental models fail to capture the dynamic interplay of hemodynamic forces, cellular interactions, and molecular signalling that regulate thrombus formation in human vasculature. This thesis addresses these limitations through the development and application of microfluidic platforms.

Chapter 1 critically reviews thrombosis mechanisms and platelet function diagnostics, focusing on shear-dependent platelet adhesion, flow disturbance–driven aggregation, and platelet–endothelium interactions. Key limitations of existing assays—including high sample requirements, limited physiological relevance, and poor standardisation—are identified, and a framework for harmonising microfluidic thrombosis assays is proposed.

Chapter 2 describes the engineering of endothelialised microfluidic devices that replicate vascular environments under defined biophysical conditions. Using geometrically optimised post-array channels and tunable shear stress, these platforms reproduce platelet activation, aggregation, and fibrin formation. A patient-specific Vein-Chip integrating cerebral venous sinus anatomy derived from magnetic resonance venography is introduced to model Virchow’s triad with spatial resolution.

Chapter 3 presents a three-dimensional spheroid–microvasculature-on-chip system and the high-throughput INVADE platform for analysing tumour intravasation, endothelial barrier disruption, and invasion dynamics.

Chapter 4 applies these platforms to study CAT mechanisms, demonstrating shear-dependent activation of cryptic tissue factor signalling under flow.

Together, this thesis establishes a modular and scalable microfluidic toolkit bridging mechanistic thrombosis research with translational applications.