Ion channel pharmacology under flow: automation via well-plate microfluidics

Assay and Drug Development Technologies
C Ian SpencerCristian Ionescu-Zanetti

Abstract

Automated patch clamping addresses the need for high-throughput screening of chemical entities that alter ion channel function. As a result, there is considerable utility in the pharmaceutical screening arena for novel platforms that can produce relevant data both rapidly and consistently. Here we present results that were obtained with an innovative microfluidic automated patch clamp system utilizing a well-plate that eliminates the necessity of internal robotic liquid handling. Continuous recording from cell ensembles, rapid solution switching, and a bench-top footprint enable a number of assay formats previously inaccessible to automated systems. An electro-pneumatic interface was employed to drive the laminar flow of solutions in a microfluidic network that delivered cells in suspension to ensemble recording sites. Whole-cell voltage clamp was applied to linear arrays of 20 cells in parallel utilizing a 64-channel voltage clamp amplifier. A number of unique assays requiring sequential compound applications separated by a second or less, such as rapid determination of the agonist EC(50) for a ligand-gated ion channel or the kinetics of desensitization recovery, are enabled by the system. In addition, the system was validated...Continue Reading

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Sep 11, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Martje W G D M de GrootMilou M L Dingemans
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Jan 12, 2021·EMBO Molecular Medicine·Mihyun BaeEunjoon Kim

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