A microfluidic device with passive air-bubble valves for real-time measurement of dose-dependent drug cytotoxicity through impedance sensing

The monitoring and evaluation of cell behaviors under various concentrations of diffusible molecules or drugs are important in drug screening and in many other types of biological studies. In the current study, a novel polydimethylsiloxane (PDMS)-based microfluidic device was established for the real-time monitoring of drug-induced cytotoxicity using electric cell-substrate impedance sensing (ECIS). This device consists of the following three components: a drug gradient generator, planar air-bubble valves, and parallel cell culture cavities that are combined with impedance-sensing electrodes. The gradient generator allows for the simultaneous administration of multiple drug doses to test the functional cytotoxicity, and the incorporated impedance sensing enables the dynamic, automatic and quantitative measurement of in vitro dose-dependent drug responses. The air-bubble valve presented here allows the automatic closure of the valve without the need for any external valve-control instrument. As a proof-of-concept demonstration, this device was applied to dynamically monitor the effects of the anticancer drug cisplatin on apoptosis in four cancer cell lines, which may be useful for drug discovery and other biological studies that require automated analysis combined with concentration gradients.