Automated Electrophysiology Assays

Excerpt

Technological breakthroughs in electrophysiological techniques, such as development of voltage-clamp and patch clamp, have enabled direct measurements of membrane currents in single cells. The low throughput of traditional electrophysiology, however has limited its use in the drug discovery process. High-throughput, non-electrophysiology based primary assays were used successfully but lack key information content, such as voltage dependence and kinetics, and may not be suitable for all ion channels. Most importantly, non-electrophysiological assays lack the ability to accurately control membrane potential, preventing the selective targeting of disease relevant conformational states of voltage-gated channels. For these reasons, substantial efforts were devoted to the development of instruments capable of automated electrophysiological recording at moderate- to high-throughput.

Early on, a number of different approaches were investigated (1). The field quickly settled on planar substrates, and in 2002 two automated electrophysiology instruments came on the market: PatchXpress^® and IonWorks™ HT developed at Axon Instruments and Essen BioSciences, respectively, and later sold to Molecular Devices. Several other manufacturers launched their automated instruments in subsequent years; most notably Sophion (QPatch), Nanion (Patchliner^®) and Fluxion (IonFlux). Based on learnings obtained with first generation devices, a new set of second generation instruments was developed in more recent years.

Instruments differ substantially in the composition of the patch plate, the configuration of the electrodes, liquid handling methods, and the software used to control the experiment and analyze data, and these features are discussed in greater detail below. Each platform has its strengths and weaknesses, and consideration should be given to the intended purpose before a device is purchased.