INTRODUCTION

Cell-based assays are now well established in nearly all stages of drug discovery and development. Indeed, they are commonly applied to all the critical steps of the process from receptor target identification and validation, compound screening and structure–activity relationship (SAR) through to toxicology. This is due in a large part to their functional nature and their ability to introduce biological complexity to the drug discovery process at a much lower cost than in vivo testing. Additionally, these assays have been successfully scaled to meet the throughput needs of screening labs. Cellular assays complement and extend the knowledge of the more mechanistic interactions of receptors and ligands as understood from biochemical assays. Indeed, cell-based assays are commonly used iteratively with biochemical assays to inform the process and direct screening efforts.

Label-free cell-based assays are gaining broader acceptance in screening labs, as they provide novel read-outs of cellular signaling and carry with them many practical advantages to the drug discovery workflow. For example, the lack of labels greatly simplifies assay development, removing many steps, each of which requires optimization. Effort is also saved in the engineering of chimeric or tagged molecules, which are often altered to the point that they no longer maintain natural function, leaving results somewhat in question relative to the native biology of the system being tested.

Electrical impedance assays are novel label-free assays that fit well into the screening workflow. Originally used to study the basic physical properties of materials, impedance technology has evolved over time to yield instrumentation for the biophysical evaluation of living cells.