Integrating a Concentration Gradient Generator and a Single-Cell Trapper Array for High-Throughput Screening the...

We herein develop a concentration gradient generator (CGG) on a microfluidic chip for diluting different nanoparticles. Specifically designed compact disk (CD)-shaped microchannels in the CGG module could thoroughly mix the flowing solutions and generate a linear concentration gradient of nanoparticles without aggregation. We combine the CGG with a single-cell trapper array (SCA) on microfluidics to evaluate the concentration-dependent bioeffects of the nanoparticles. The precise control of the spatiotemporal generation of nanoparticle concentration on the CGG module and the single-cell-level monitoring of the cell behaviors on the SCA module by a high-content system in real time, render the CGG-SCA system a highly precise platform, which can exclude the average effect of cell population and reflect the response of individual cells to the gradient concentrations accurately. In addition, the CGG-SCA system provides an automated platform for high-throughput screening of nanomedicines with high precision and low sample consumption.