High throughput optical sensor arrays for drug screening

摘要

In the world of drug discovery, high throughput whole cell assays are a critical step in discovering therapeutically relevant drug compounds [1]. This report details the development of several novel sensor systems capable of detecting cellular ion flux in multi-well plate format. Optodes are employed as the primary sensors, which are an optically based ion selective polymer. These assays utilize both potassium and sodium selective optodes to provide real time measurements of extracellular ion concentration, which can yield extremely valuable information regarding compound induced cellular activity [2]. Individual assay formats have been specifically tailored for use with both adherent and suspended cell lines. For adherent cell lines, the optode based sensor system was evaluated using an HEK 293 cell model. To evoke cellular activity, the cells were exposed to Isoproterenol and Forskolin, which are known to elicit intracellular cyclic AMP production. The assay proved robust in detecting long term drug induced extracellular potassium flux. Ion flux magnitude was used to generate EC50 values of 1.185 nM and 66.5 nM for Isoproterenol and Forskolin, respectively. These values correlate closely with reported values that were attained with assays using intracellular calcium as the active biomarker [3-5].