An update on the advancing high-throughput screening techniques for patch clamp-based ion channel screens: implications for drug discovery

ABSTRACT

Introduction: Automated patch clamp (APC) devices have become commonplace in many industrial and academic labs. Their ease-of-use and flexibility have ensured that users can perform routine screening experiments and complex kinetic experiments on the same device without the need for months of training and experience. APC devices are being developed to increase throughput and flexibility.

Areas covered: Experimental options such as temperature control, internal solution exchange and current clamp have been available on some APC devices for some time, and are being introduced on other devices. A comprehensive review of the literature pertaining to these features for the Patchliner, QPatch and Qube and data for these features for the SyncroPatch 384/768PE, is given. In addition, novel features such as dynamic clamp on the Patchliner and light stimulation of action potentials using channelrhodosin-2 is discussed.

Expert opinion: APC devices will continue to play an important role in drug discovery. The instruments will be continually developed to meet the needs of HTS laboratories and for basic research. The use of stem cells and recordings in current clamp mode will increase, as will the development of complex add-ons such as dynamic clamp and optical stimulation on high throughput devices.

KEYWORDS:

• Automated patch clamp
• drug discovery
• high throughput screening (HTS)
• dynamic clamp
• ion channels
• Patchliner
• SyncroPatch 384/768PE
• stem cells

Article highlights

• Automated patch clamp devices are now addressing the needs of high throughput screening laboratories in terms of throughput and cost per data point.

• Temperature control is an important feature in drug discovery, not least because some compounds show different potencies at physiological temperature versus room temperature and some ion channels are activated by heat or cold.

• Internal solution exchange is an underexploited advantage of automated patch clamp devices. Some devices require a break in the recording for internal solution exchange to occur, e.g. Patchliner and Qube, whereas some perform true perfusion of the internal solution, e.g. the SyncroPatch 384/768PE.

• Human induced pluripotent stem cell-derived cardiomyocytes are becoming an increasingly important cell type for safety testing, particularly in the light of the CiPA initiative. It is important to be able to record from hiPSCs in both voltage and current clamp modes at high throughput.

• As some important cardiac ion channels appear to be missing, or expressed at very low levels in hiPSC-CMs (e.g. I_K1), dynamic clamp has been employed on the Patchliner to introduce electronically modelled I_K1.

• Optical stimulation of excitable cells using ChR2 and photoswitching of compounds using visible light are becoming important features in electrophysiology. Combining optical stimulation with HTS automated patch clamp is likely to be an important advancement in the future.

Acknowledgments

We thank Takara Bio for providing the Cellartis Cardiomyocytes and Teun de Boer for valuable input in the dynamic clamp experiments. We also thank Dirk Trauner, Martin Sumser and Nils Winter for the photoswitch compound and NCardia for the Cor.4U cardiomyocytes and Xpress.4U kit for expression of ChR2.

Declaration of interest

N Fertig is the CEO of Nanion Technologies while all other authors are employees of Nanion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This manuscript has not been funded.