Ion channels are membrane proteins that allow the selective movement of charged molecules through cellular membranes. Many disease states, such as cystic fibrosis, muscular dystrophies, hypertension, and cardiac arrhythmias are caused by ion channel pathologies. Ion channels have been identified by the drug discovery industry as excellent targets for therapeutic intervention but because of the technical hurdles involved in developing quality, high- throughput functional ion channel assays, the development of ion channel drugs has been disappointing. Photoswitch Biosciences has developed technology, which allows attaching small nanomachines to ion channels enabling rapid and reversible control of these proteins by light. The Specific Aims of this proposed Phase II SBIR project are: (1) generation of several stable cell lines expressing photoswitched ion channels, accessory channels, and test channels; (2) produce three functional prototype instruments for sale to early access collaborators. As part of Specific Aim 2 we will evaluate illumination and detection strategies and implement the most appropriate. The first commercial products to be developed will be all-optical ion channel assays and instruments for high- throughput ion channel drug discovery. The use of all-optical technology for ion channel assays has several advantages over existing techniques: (1) Elimination of liquid additions for channel activation, (2) Highly scalabl for high-throughput ion channel drug discovery, (3) Price per datapoint is at least 100X less than automated electrophysiology, (4) Channel activation is almost 100X faster than KCl addition. The most important benefit of this new ion channel assay technology is the ability to rapidly and reliably control membrane potential. This control of membrane potential allows for the development of scalable high-throughput state-dependent assays, which is impossible with current technology. This breakthrough technology will finally allow the full exploitation of ion channels as drug targets.