The article presents a droplet-based microfluidic technology for high-throughput screening of single mammalian cells. This integrated platform encapsulates single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil, enabling digital manipulation at high throughput. The authors validate the technology by conducting a cytotoxicity screen using human monocytic U937 cells. They develop a droplet viability assay to quantify cell viability and growth within intact droplets, demonstrating high viability over 4 days. An optically coded droplet library is also developed to identify droplet compositions during the assay read-out. Using this technology, they screen a drug library for its cytotoxic effects on U937 cells. The droplet microfluidic platform is modular, robust, and suitable for various applications, including high-throughput single-cell analyses, combinatorial screening, and small sample analyses. The system's key features include precise cell encapsulation, high-throughput droplet generation and manipulation, and the possibility of combinatorial screening.The article presents a droplet-based microfluidic technology for high-throughput screening of single mammalian cells. This integrated platform encapsulates single cells and reagents in independent aqueous microdroplets (1 pL to 10 nL volumes) dispersed in an immiscible carrier oil, enabling digital manipulation at high throughput. The authors validate the technology by conducting a cytotoxicity screen using human monocytic U937 cells. They develop a droplet viability assay to quantify cell viability and growth within intact droplets, demonstrating high viability over 4 days. An optically coded droplet library is also developed to identify droplet compositions during the assay read-out. Using this technology, they screen a drug library for its cytotoxic effects on U937 cells. The droplet microfluidic platform is modular, robust, and suitable for various applications, including high-throughput single-cell analyses, combinatorial screening, and small sample analyses. The system's key features include precise cell encapsulation, high-throughput droplet generation and manipulation, and the possibility of combinatorial screening.