Evaluating the reliability of tumour spheroid-on-chip models for replicating intratumoural drug delivery: considering the role of microfluidic parameters

Abstract

Several tumour spheroid-on-chip models have already been proposed in the literature to conduct high throughput drug screening assays. The microfluidic configurations in these models generally depend on the strategies adopted for spheroid formation and entrapment. However, it is not clear how successful they are to mimic in vivo transport mechanisms. In this study, drug transport in different tumour spheroid-on-chip models is numerically investigated under static and dynamic conditions using porous media theory. Moreover, the treatment of a solid tumour at the initial stage of development is modelled using bolus injection and continuous infusion methods. Then, the results of tumour spheroid-on-chip, including drug concentration, cell viability, as well as pressure and fluid shear stress distributions, are compared with those of the solid tumour, assuming identical transport properties in all models. Finally, a new configuration of the microfluidic device along with the optimal drug concentrations is proposed, which can well imitate a given in vivo situation.