High-throughput cell-based screening system with on-chip dilution stage

A microchip-based approach for performing a complete and automated drug-screening assay on living cells is presented. Cells are trapped and immobilized in a small 0.5-μl-volume incubation chamber by means of orifice microstructures and are subsequently incubated with drug dilutions ranging over three orders of magnitude. The microsystem includes a perforated silicon chip embedded in a larger elastomer substrate, which features the microfluidic network and the incubation chamber. This article describes the modeling and the fabrication of the microchip components, immobilization of normal human dermal fibroblasts (NHDFs) and a screening experiment with cultured NHDFs, which have been exposed to a fluorescent cell tracker.