A patient-specific vessel-on-chip platform for rapid prediction of thrombotic risks

Abstract

Cardiovascular thrombosis remains a leading cause of death and disability, yet existing laboratory tests cannot capture the combined influence of vascular geometry, haemodynamic forces, and individual blood coagulability described by Virchow’s triad. This thesis builds an end-to-end translational pipeline, from digital vessel reconstruction to microengineered chips, that delivers a personalised, point-of-care clot prediction platform.

The journey begins with the creation of a generalisable computational biomechanics framework capable of reconstructing full-wall vasculature directly from confocal images or clinical datasets, laying the digital groundwork for the subsequent organ-scale application.

Leveraging this reconstruction framework, the thesis introduces the “Movable Typing” soft stereolithography technique to fabricate full-lumen, endothelialised Vein-Chips that precisely replicate cerebral venous sinus anatomy derived from magnetic resonance venography. Under physiological venous flow, healthy chips show negligible thrombogenesis, whereas endothelial-inflamed chips exhibit extensive platelet-fibrin interplay characteristics.

The fabrication strategy is next scaled to patient-specific carotid bifurcations. A custom mechanical clip system (second patent) and treated glass substrates cut total build time to <2 h with a near 100% success rate. The chips are then functionalised with endothelium, inflamed, or laser-ablated (third patent) to mimic plaque rupture. Given that each chip accommodates autologous or drug-spiked blood, the platform supports first-in-field, multi-patient antithrombotic screening.

At last, a benchtop, semi-automated manufacturing platform was established to fabricate complex three-dimensional vascular microfluidic chips using biocompatible materials. It clarifies how VWF conformational control governs initiation, how αIIbβ3 ligands differentially support growth versus stability, and how pulsatility exposes thrombus failure modes.