Real-Time Single-Cell Monitoring of Drug Effects Using Droplet-Based Microfluidic Technology: A Proof-of-Concept Study.

Abstract

Drugs that act on ribosome biogenesis and cell proliferation play important roles in treatment of human diseases. Moreover, measurement of drug effects at a single-cell level would create vast opportunities for pharmaceutical innovation. We present in this study an original proof-of-concept study of single-cell measurement of drug effects with a focus on inhibition of ribosome biogenesis and cell proliferation, and using yeast (Saccharomyces cerevisiae) as a model eukaryotic organism. We employed a droplet-based microfluidic technology and nucleolar protein-tagged strain of the yeast for real-time monitoring of the cells. We report a comprehensive account of the ways in which interrelated pathways are impacted by drug treatment in a single-cell level. Self-organizing maps, transcription factor, and Gene Ontology enrichment analyses were utilized to these ends. This article makes a contribution to advance single-cell measurement of drug effects. We anticipate the microfluidic technology platform presented herein is well poised for future applications in personalized/precision medicine research as well as in industrial settings for drug discovery and clinical development. In addition, the study offers new insights on ribosome biogenesis and cell proliferation that should prove useful in cancer research and other complex human diseases impacted by these key cellular processes.