Monitoring "promiscuous" drug effects on single cells of multiple cell types

Abstract

Recent advances in genomics and molecular pathogenesis studies have determined that many diseases are caused by a multiplicity of factors. New drug regimens may consist of multiple biologically active agents designed to act synergistically on multiple biochemical targets. Live cell assays are becoming a standard for identifying new drug candidates with an emphasis on "homogeneous" living cell assays in which multiple cell lines are mixed and monitored simultaneously. In this study, we used a high-density single living cell array, based on an optical imaging fiber bundle microwell array, to simultaneously monitor "promiscuous" drug effects on single cells of multiple cell types. Such a capability allows for a more comprehensive understanding of how cells dynamically respond to combinatorial drug libraries or how different cellular pathways and regulation circuits respond cooperatively to drugs in individual cells.