Ion Channel Drug Discovery and Research: The Automated Nano-Patch- ClampO Technology

Abstract

Unlike the genomics revolution, which was largely enabled by a single technological advance (high throughput sequencing), rapid advancement in proteomics will require a broader effort to increase the throughput of a number of key tools for functional analysis of different types of proteins. In the case of ion channels -a class of (membrane) proteins of great physiological importance and potential as drug targets- the lack of adequate assay technologies is felt particularly strongly. The available, indirect, high throughput screening methods for ion channels clearly generate insufficient information. The best technology to study ion channel function and screen for compound interaction is the patch clamp technique, but patch clamping suffers from low throughput, which is not acceptable for drug screening. A first step towards a solution is presented here. The nano patch clamp technology, which is based on a planar, microstructured glass chip, enables automatic whole cell patch clamp measurements. The Port-a-Patch is an automated electrophysiology workstation, which uses planar patch clamp chips. This approach enables high quality and high content ion channel and compound evaluation on a one-cell-at-a-time basis. The presented automation of the patch process and its scalability to an array format are the prerequisites for any higher throughput electrophysiology instruments.

Bioluminescence Methodology for the Detection of Protein–Protein Interactions Within the Voltage-Gated Sodium Channel Macromolecular Complex

“…5,82 The LCA is a rapid and effective method that could be employed for compound screening identification, hit validation, and hit-to-lead transition toward drug discovery development against Nav channels and other challenging transmembrane ion channels. 83 The new generation of the split-luciferase reporters based on the heterocomplementation of green and red luciferase 84 extends the capability of the assay to detect three-way combinations of interacting partners, providing even broader possibilities for studying the ion channel interactome.…”

Differential Inhibition of Inducible T Cell Cytokine Secretion by Potent Iron Chelators

“…Significant technological advances have been made in recent years by a number of companies to automate the gold-standard patch clamp technique for assaying ion channel function. [18][19][20][21][22][23] The PatchXpress ® is a multiwell instrument that uses planar electrodes to enable the flexibility and high-quality data achievable in conventional patch clamping. This is, in part, due to the ability of the SealChip 16 ™ planar electrodes to form GOhm seals with cell membranes with high frequency.…”

Cell segmentation and pipette identification for automated patch clamp recording

“…Due to these challenging issues, several groups started incorporating automated systems to current patch clamping so as to reduce the operation time, complexity, and cost. The automated patch clamp technology was previously reported for the integrative analysis of molecular, anatomical, and electrophysiological properties of a single cell [10]. The planar patch clamp is another kind of patch clamp systems that provides the automatic recording of cells [11].…”