Towards a high-throughput drug discovery platform for the screening of GPCR targets in cells

G-protein-coupled receptors (GPCRs) play a key role in physiologic and pathologic processes via signal transduction pathways that convert extracellular information into intracellular functions. The identification of drugs that target GPCRs usually relies on functional, cell-based assays. Here, the binding of a test compound to a receptor alters the conformation of the associated G-protein, initiating a cascade of events. The magnitude of the response is typically measured by monitoring key elements in the cascade (e.g., calcium) with fluorescent dyes or with luminescent reporter proteins (e.g., aequorin). The goal of this project is to develop cell microchips for the screening of drugs that act upon GPCRs. The basic unit of the chip will be composed of: i) 15-100 micron-sized test sites where the cells are placed and contacted with the candidate drug via a microfluidic network, and ii) independent, micron-sized amorphous silicon photodetectors that convert the photons of generated light into an electric current and that can be arrayed.