Menegon A.1, Agus V.2, Crespi D.2, Rolland J.F.2, Redaelli L.2, Scarabottolo L.2, Seneci P.3, Mazzocchi N.1, Imberti M.4, Poli C., Lanati A.5, Grohovaz F.1,6 1. SanRaffaele Scientific Institute, Milan; 2. Axxam SpA, Bresso (MI); 3. University of Milan, Milan; 4. OPEN Sistemi srl – Cremona; 5. Valore Qualità, Pavia; 6. San Raffaele University, Milan. Numerous top-selling drugs are ion-channel modulators. Unfortunately, the screening of candidate molecules for ion channels is mostly based on optical approaches that measure, as final readout, a cascade of events rather than direct channel activation. Overall these approaches are compatible with high throughput requirements but can be poorly predictive. Alternative methods, such as manual or automated patch clamp technologies, are valuable but expensive and time consuming. The poster illustrates the validation of a new Optical Method for Ion Channel Screening patented in Europe and pending acceptance in the USA (EP2457088, WO2011009825, US13/386225). This innovative approach, based on the study of ion channel conductance by a fluorescence-based approach, was implemented in a fully automated system built according to EC standards. When this platform was tested on different ion channel targets, the results were in good agreement with those reported in literature by gold standard approaches (manual and automated patch clamp). Finally, the platform was challenged with a small library of candidate molecules acting on the P2RX7 ion channel and the results were compared with those obtained by FLIPR and QPatch. Also in this case, the results were comparable with those obtained by the established screening approaches. Overall, we demonstrate that this new platform allows the study of different ion channels, independently of the way they are operated, of their specific permeability, and of the extent of the ionic flux sustained at rest. This innovative platform provides an excellent compromise of cost per data point, throughput and prediction power in drug screening.