High-throughput, Multiplexed, Commercialized Ion Channel Drug Screening

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Project Summary Ion channels are integral membrane proteins that control the flux of ions through cellular membranes and they are often responsive to voltages and ligands, resulting in an active/open state or inactive/closed state. Furthermore, ion channels are involved nearly all physiological processes, including cell-cell communication, muscle contraction, neuronal firing, osmotic stress responses, etc., and dysfunction of these proteins has been related to several human diseases such as asthma, hypertension, diabetes, some cancers, and congenital heart failure, to name a few examples. Because of their important role in disease and potential as drug targets, there is a great deal of interest in characterizing ion channel response, especially regarding drug interactions. However, there remain very pressing issues regarding the ability to develop target-specific drugs that do not modulate the activity of other (non-target) ion channels. This process is quite difficult as most ion channels that have the potential to bind drug-like molecules remain understudied. During this program, Electronic BioSciences, Inc. (EBS) will develop and demonstrate an automated, multiplexed, fluidic-based system that will allow multiple ion channels and drug targets to be screened simultaneously with state-of-the-art noise-performance/resolution at the single-channel level. A tool such as the one proposed here, capable of broad, high-throughput commercial drug screening (i.e., many ion channels and many drugs), will help expand the pool of information needed to design and characterize new high-affinity/high-specificity drugs for improved patient care.