Hydrogel-based diffusion chip with Electric Cell-substrate Impedance Sensing (ECIS) integration for cell viability assay and drug toxicity screening

Abstract

In this study, we have provided a novel analytical integration between hydrogel-based cell chip and Electric Cell-substrate Impedance Sensing (ECIS) technique to apply to a high-throughput, real-time cell viability assay and drug screening. For simulating the drug diffusion model, we have developed a hydrogel-based tissue-mimicking structure with microfluidic channel, without unwanted flow, to generate a gradient concentration with long-term stability. Along the gradient line, four individual micro-electrodes were installed to record the impedance signal changes, which result from the cell viability under drug effects. By watching for cellular impedance changes, we successfully estimated the cytotoxicity of the treatment corresponding to the various concentration values of stimuli, generated by the diffusion process along the channel. Reliable IC50 values and time-dose relationships were also achieved. With the feature of real-time monitoring capability, the advantages of non-invasion, label-free detection, time saving and simple manipulation, our integrative device has become a promising high throughput cell-based on-chip platform for cell viability assay and drug screening.

Keywords: Cellular cytotoxicity; Diffusion; ECIS; Electrical measurement; Hydrogel; Micro-electrode.