Three-gradient constructions in a flow-rate insensitive microfluidic system for drug screening towards personalized treatment

Abstract

Research and development of innovative targeted therapies is a great challenge in the fight against cancer. Although many treatment methods are currently available, there is no simple and effective system for promptly conducting anti-cancer drug screening and dose-response evaluation of the cancer patients to the drug. Herein, we developed an easy and compact flow rate independent microfluidic chip that can rapidly construct three concentration gradients of multiple solutes based on Dean flow under a wide range of flow rates. Chemical gradient dynamics were investigated systematically and quantitatively. Three stable, accurate, and controllable drug gradients were generated to evaluate treatments of two tumor cell lines (MCF-7 and HepG2). Results showed the dose- and time-dependent antitumor effects of the drugs, indicating the suitability of the proposed system to evaluate the individual actions and interactions of the anti-cancer drugs (doxorubicin and cisplatin) on one tumor cell line under the same conditions. In addition, cell viability in the microfluidic chip under gradient conditions showed a linear relationship to the viability of the traditional culture experiment. In summary, our microfluidic device can be used to develop insensitive techniques to operational conditions for simultaneously establishing multi-drug concentration gradients, which has the potential to promote the development of specific drug screening tools for targeting multiple vulnerabilities of tumor cells and evaluating the most effective personalized treatment technique.