IonWorks™ HT: A New High-Throughput Electrophysiology Measurement Platform

Abstract

To address the throughput restrictions of classical patch clamp electrophysiology, Essen Instruments has developed a platebased electrophysiology measurement platform. The instrument is an integrated platform that consists of computer-controlled fluid handling, recording electronics, and processing tools capable of voltage clamp whole-cell recordings from thousands of individual cells per day. To establish a recording, the system uses a planar, multiwell substrate (a PatchPlate™). The system effectively positions 1 cell into a hole separating 2 fluid compartments in each well of the substrate. Voltage control and current recordings from the cell membrane are made subsequent to gaining access to the cell interior by applying a permeabilizing agent to the intracellular side. Based on the multiwell design of the PatchPlate™, voltage clamp recordings of up to 384 individual cells can be made in minutes and are comparable to measurements made using traditional electrophysiology techniques. An integrated pipetting system allows for up to 2 additions of modulation agents. Typical throughput, measurement fidelity, stability, and comparative pharmacology of a recombinant voltage-dependent sodium channel (hNav1.3) and a voltage-gated potassium channel (hKv1.5) exogenously expressed in CHO cells are presented. The IonWorks™ HT device can be used in biophysical and pharmacological profiling of ion channels in an environment compatible with high-capacity screening. (Journal of Biomolecular Screening 2003:50-64)

Novel cell-free high-throughput screening method for pharmacological tools targeting K + channels

“…None of the methods currently used-electrophysiology (17,18), cell-based assays such as Tl + flux assays/membrane potential dye assays/yeast growth assays (19)(20)(21), and binding/inhibitor competition assays (22,23)fulfill all three of the above criteria. We developed and present here an assay that does fulfill these criteria.…”

Profiling Diverse Compounds by Flux- and Electrophysiology-Based Primary Screens for Inhibition of Human Ether-à-go-go Related Gene Potassium Channels

“…[19][20][21] The primary approach has involved the use of surrogate ions such as rubidium (Rb þ ) or thallium (Tl þ ), which may be detected by atomic absorption spectrometry 22,23 or fluorescent dyes. 8,10,11 With the advent of automated patch-clamps, 6,[24][25][26][27] it is now possible to consider whether the more direct measurements of channel electrophysiological activity obtained from the automated patch-clamp justifies its higher implementation cost in high-throughput screens. It is therefore important to obtain more specific and quantitative information to assess the cost and benefit comparatives between assays employing electrophysiological methods versus surrogate ion flux measurements.…”

Targeting the serotonin 2C receptor for the treatment of obesity and type 2 diabetes

“…Two different approaches to achieving automation of manual patch clamp electrophysiology have recently emerged taking advantage of the socalled planar array of multi-well configurations in either a plate-or chipbased format allowing for multiple parallel recordings replacing the single channel recording typical of manual patch clamp. The IonWorks platform (Schroeder et al, 2003) was the first major innovation to be introduced and although this technology did not recapitulate the tight gigaohm seal quality typical of manual recordings, a number of assays have been successfully transferred onto this platform. Most notably, it has been possible to screen small compound libraries using the IonWorks (John et al, 2007), representing perhaps the best example of how such technologies have revolutionized ion channel screening as such a feat would be unimaginable with manual recording approaches.…”