Multi-parameter ion channel screening: mechanism-of-action data directly from HTS

著者: Juha Kammonen, Anthony Lawrence and Jonathan Mann

High-throughput automated patch clamp (APC) is quickly emerging as the new gold standard technology for screening compounds against ion channel targets. The latest APC platforms, such as the Qube, enable true giga-seal quality data generation, comparable to conventional patch clamp.

Traditional plate-based screening technologies rarely allowed for analysis of multiple parameters to detect potential differences in the mechanism of action of novel compounds. Using multiple data analysis cursors in the Sophion Analyzer software, it’s possible to gain valuable insight into compound activities on a particular ion channel target, which may translate into different results in further in vivo experiments. This also increases the value of APC data, as multiple parameters can be extracted from each well for both data quality control as well as hit detection.

Here we present Qube data for a 10,000 compound pilot screen for a sodium channel activator project, with analysis for multiple hit parameters, demonstrating the ability of the assay to detect novel compounds with different mechanisms of action.