Hanging-drop networks for in vitro dose-response studies on 3D tumor microtissues

Abstract

This paper presents an analytical platform, based on an inverted, completely open microfluidic system. Interconnected hanging drops form underneath a structured PDMS surface, and 3D tumor microtissues can be cultured in these hanging drops over several days. Continuous perfusion and the integration of a gradient generator enable on-chip dose-response studies. Microscopy readout allows for continuously monitoring the effects of different doses of anti-cancer drugs. Colon cancer microtissues (HCT116) were used to compare the IC50 and IC85 of 5-Fluorouracil (5-FU) under static conditions in a well plate and under perfusion conditions in the hanging-drop network and revealed significant differences. Values of perfused systems more closely matched the reported in vivo doses.