A Tubing-Free, Microfluidic Platform for the Realization of Physiologically Relevant Dosing Curves on Cellular Models

Abstract

We present a microfluidic tilting platform with gravity-driven flow that enables culturing of three-dimensional microtissues under in vivo-like drug dosing regimens. In contrast to traditional, constant dosing regimens, the chip allows for gradual changes in substance concentrations. Dosing gradients are generated through an asymmetric Y-junction of microfluidic channels of different widths. Changes in the chip operation parameters, e.g., different tilting angles, enable to alter the drug dosage on demand. The concentration changes over time matched the predicted values, and preformed microtissues could be cultured in the chip system for at least 24 h. The chip represents an easy-to-handle tool for toxicity and efficacy testing of transient drug concentrations changes.