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Tools for drug discovery

Ion channels get automated

Ion channels currently represent a less well charted territory of druggable targets than cell-surface receptors and enzymes, but this is changing. The electrophysiological techniques traditionally used to study ion-channel activity (one-cell, one-pipette patch clamping) are too slow for screening drug candidates, but some companies are finding ways to adapt and automate these techniques. One factor driving this development is the requirement by the regulatory authorities that all drugs must be tested for possible effects on a cardiac potassium channel (the hERG channel), which can cause cardiac arrhythmia. Compounds with adverse effects need to be weeded out as early as possible in the drug-discovery process.

The Dynaflow Pro II system from Cellectricon in Göteborg, Sweden, is based on a combination of patch clamping and microfluidics. “Dynaflow enables sequential rather than parallel testing of compounds on ion channels by high-speed translational scanning of a single patch-clamped cell across a laminar stream of solution environments,” says Mattias Karlsson, vice-president of research and development at Cellectricon.

Use of patch clamping retains the high quality of data characteristic of the technique, which is crucial in regulatory testing for the hERG channel, but the microfluidics component increases throughput compared with traditional lab methods.

Mattias Karlsson: applying microfluidics to patch-clamping. Credit: CELLECTRICON

For the highest-throughput automated patch-clamping, turn to Sophion Bioscience in Ballerup, Denmark. Sophion's QPatch HT is a 48-channel gigaseal patch-clamp system that can be used to study both voltage-gated and ligand-gated ion channels. Each channel, which patches one cell, is controlled individually, so the system consists of 48 individual low-noise patch-clamp amplifiers and pressure controllers (for individual gigaseal formation). The liquid-handling robot controls eight pipettes. The recording chambers are contained within Sophion's QPlates, which house 48 glass-coated microfluidic channels that hold about 5 µl. With the small recording volumes and a liquid-exchange time of about 100 milliseconds, it is possible to screen multiple compounds on the same cell, or perform cumulative dose–response experiments.

Npi Electronic in Tamm, Germany, has incorporated a Tecan liquid-handling system into its ScreeningTool instrument for automated, fast and precise screening of ion-channel activity using two-electrode voltage clamping of Xenopus oocytes. Drugs are delivered by a rapid (millisecond resolution) automated system into the 15-ml bath of a miniature recording chamber. Npi plans to extend ScreeningTool to other cell types.

The ICR range of spectrometers from Aurora Biomed of Vancouver, British Columbia, provides a non-electrophysiological screen for ion-channel activity. The machines use atomic absorption spectroscopy and flux assays to detect activity and can be used to study both ligand- and voltage-gated channels. The new ICR 12000 is designed for ultra-high-throughput screening of compound libraries against ion-channel targets.


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Ion channels get automated. Nature 446, 219 (2007).

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