A “DropChip” cell array for DNA and siRNA transfection combined with drug screening

Abstract

We have developed a “DropChip” microarray for multiplexed cell-based assays to perform information-rich high-throughput screening. This microarray features cell culture nanoliter droplets on a glass slide; the culture’s size, shape, and location are accurately controlled by surface tension. We report parallel gene expression and gene silencing analyses on the same array, combining nucleic acid transfection, anti-cancer drug screening, and cell cultures. In particular, we analyzed the synergic effects of siRNA and cisplatin on cancerous cells. With up to 100 cells per drop, we could carry out the detection and analysis of cell behavior at the individual cell level, using high-resolution fluorescence microscopy and automated image analysis. Nucleic and chemical compounds require early multiplexed testing using nanomolar quantities. The NanoDrop technology is a unique solution to perform cell-based assay in nanoliter drops, providing a major decrease of cost and time, as well as a precise description of the behavior of several cell types in a single test at the single cell level. This novel cell array format could enable highly informative functional genomic studies and large scale in vitro toxicity testing.