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Understanding drug extravasation from the leaky vasculature to tumour sites based on the enhanced permeability and retention effect (EPR) is of critical importance for designing and improving drug delivery efficiency. This paper reports a tumour–vasculature microfluidic device consisting of two microchannels (top channel and bottom channel) separated by a porous membrane. To investigate drug extravasation, a numerical two-phase mixture model was developed and validated using experimental results. This is the first time that a two-phase mixture model is used to investigate drug extravasation through the simulated leaky vasculature in a microfluidic device. After the flow structures and drug distribution were numerically examined, the effects of parameters including the velocity of blood flow, drug concentration, and the degree of blood vessel leakiness as represented by the membrane porosity were systematically investigated. This numerical model offers a powerful tool to study drug extravasation through leaky vasculature, and the simulated results provide useful insights into drug extravasation and drug accumulation at tumour sites.READ MORE