Microfluidic-enabled self-organized tumor model for in vitro cytotoxicity assessment of doxorubicin.

Abstract

The advent of microfluidic technologies has enabled a better recapitulation of in vitro tumor model with higher biological relevance over conventional monolayer assays. This work built upon a microfluidic system that supported the spontaneous aggregate formation of tumoral cells under flow-induced dynamic physical forces in a confined microchamber without additional matrix materials. Our findings indicated that fluidic streams significantly modulated the biological and architectural features of human breast adenocarcinoma cell (MCF-7), human hepatocarcinoma cell (HepG2), and human cervix adenocarcinoma cell (HeLa) with cell-type-dependent variation. The microfluidic platform was further integrated with a fluorescence detection and imaging system, allowing for non-invasive monitoring of cellular accumulation and spatial distribution of a chemotherapeutic agent, doxorubicin (DOX). The cytotoxic effects of DOX of various concentrations were determined and compared in MCF-7 cells in conventional two-dimensional (2D) static and microfluidic culture conditions. Dose-dependent response to DOX was noticed in both cultures, whereas tumor micronodules grown in microfluidic devices demonstrated significantly lower sensitivity to DOX at increased concentration. Our platform owns promising potentials as a universal modality for bridging traditional 2D cell cultures and in vivo experimentation for preclinical anticancer drug screening.