Optogenetics meets automated patch clamp

Channelrhodopsins have revolutionised the rapid, contactless modulation of action potentials, driving major advances in both neuroscience and cardiac research. In parallel, the automated patch clamp (APC) technique has emerged as a powerful platform for drug screening. Yet, its integration with optogenetic approaches remains uncommon in routine practice. In this study, we present technological innovations and establish proof of concept for the direct activation of channelrhodopsins during APC. We validate the approach with the Na⁺-selective channelrhodopsin NCR1 2.0 and the highly Na⁺/Ca²⁺-conductive variant XXM 2.0. These channels are gaining increasing relevance, as Na⁺ and/or Ca²⁺-dependent signalling plays pivotal roles in cancer biology and the development of anti-cancer therapeutics. The combined application of optogenetics and APC offers a transformative approach to drug screening, opening new avenues for biomedical innovation. This vision also includes further optical manipulations such as uncaging of substances and molecular photoswitches in photopharmacology, which form synergistic approaches with APC.