A NOVEL DROPLET-BASED PLATFORM FOR TUMOR SINGLE-CELL ENCAPSULATION AND METASTATIC MULTICELLULAR CLUSTER MODELLING
Metastasis is the leading cause of cancer-related mortality, with circulating tumour cell clusters exhibiting higher metastatic potential than single cells. This thesis introduces a microfluidic-based platform for the controlled generation and culturing of single cells and multicellular CTC cluster models within physiologically relevant, biomechanically challenging 3D environments that mimics cancer microenvironment. The platform improves droplet stability, nutrient exchange, and long-term culture capacity. It incorporates inertial focusing and on-chip sample enrichment techniques to enhance cell loading efficiency and reduce variability. Functional analysis revealed the influence of biophysical stress on viability, migration, and expression of adhesion and survival markers such as plakoglobin and BCL-2. This approach provides a robust tool for advancing mechanistic understanding of metastasis with high-throughput and precise environmental control. This bridges the fields of engineering microfabrication and cancer mechanobiology, offering a scalable and physiologically accurate model to study the dynamic behaviours of tumour clusters under biomechanical stress conditions.
Modelling, Mechanobiology, CTC, Cancer, Microfluidics, Droplets
Networked Digital Library of Theses and Dissertations