Cao, Xueying, Erdemli, Gul, Urban, Laszlo, Lee, Yan, Golden, Andrew, Holmqvist, Mats, Li, Nianzhen, Chen, Quin, Nevill, Tanner, Johnson, Juliette and Ionescu-Zanetti, Christian (2011) IonFlux, a Microfluidic Patch Clamp System Evaluated with hERG Channel Physiology and Pharmacology. Assay and Drug Development Technologies.

Abstract

Ion channel assays are essential in drug discovery, not only for identifying promising new clinical compounds, but also for minimizing the likelihood of potential side effects. Both applications demand optimized throughput, cost, and predictive accuracy of measured membrane current changes evoked or modulated by drug candidates. Several competing electrophysiological technologies are available to address this demand, but important gaps remain. We describe the industrial application of a novel microfluidic-based technology that combines compounds, cells and buffers on a single, standard 96-well plate. Cell trapping, whole cell, and compound perfusion are accomplished in interconnecting microfluidic channels that are coupled to pneumatic valves, which emancipate the system from robotics, fluidic tubing and associated maintenance. IonFlux-16TM is a state-of-the-art, compact system with temperature control and continuous voltage clamp for potential application in screening for voltage and ligand-gated ion channel modulators. Here, ensemble recordings of the IonFlux system were validated with the hERG channel (stably expressed in a CHO cell line), which has established biophysical and pharmacological characteristics in other automated planar patch systems. We characterized the temperature dependence of channel activation and its reversal potential. Concentration response characteristics of known hERG blockers and control compounds obtained with the IonFlux system correlated with literature and internal data obtained on this cell line with the QPatch HT system. Based on the biophysical and pharmacological data, we conclude that the IonFlux system offers a novel, versatile, automated profiling and screening system for ion channel targets with the benefit of temperature control.

Item Type:	Article
Keywords:	IonFlux, microfluidic, hERG inhibition
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/4118