A. Fowler, N. Seifrt, V. Acker, T. Woehrle, C. Kilpert, and A. De Saizieu. (2006) “A Nonradioactive High-Throughput/High-Content Assay for Measurement of the Human Serotonin Reuptake Transporter Function In Vitro.” JBS. 11(8): 1027-1034.

Researchers at Novartis Pharmaceuticals (Basel, Switzerland) created an assay to evaluate human serotonin reuptake transporter (hSERT) activity with the fluorescent hSERT substrate (4-(4-(dimehtylamino)-styrl)-N-methylpyridinium, ASP). This ASP assay was created to use high content methodology, namely the Thermo Scientific Cellomics ArrayScan V^TI HCS Reader (Thermo Fisher Scientific, Pittsburgh, PA), to read ASP intensity inside hSERT-expressing HEK-293 cells. Since hSERT activity is a key drug target for anti-depressant drugs, this high content assay was able to evaluate over 2,000 new compounds and 80 plant extracts for anti-depressant efficacy. Furthermore, the high content screening platform allowed the scientists to normalize ASP fluorescence to cell number for comparison purposes across treatments, to simultaneously screen for cytotoxic drugs by multiplexing the experiments with a cell membrane permeability dye, and to investigate compounds’ effects on gross cellular morphology.