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2006 - Establishment of Cell-Free Electrophysiology for Ion Transporters: Application for Pharmacological Profiling

Icon N1   SURFE²R ONE (a predecessor model of SURFE²R N1) publication in Journal of Biomolecular Screening (2006)

Authors:
Geibel S., Flores-Herr N., Licher T., Vollert H.

Journal:
Journal of Biomolecular Screening (2006) 11(3):262–268


Abstract:

Ion transporters are emerging targets of increasing importance to the pharmaceutical industry because of their relevance to a wide range of numerous indications of cardiovascular, metabolic, and inflammatory diseases. However, traditional iontransporter assay technologies using radioactive or fluorescent ligands and substrates or manual patch clamping suffer from several problems: limited sensitivity and robustness, significant numbers of false positives and false negatives, and cost. The authors describe a novel method for the measurement of ion transporters using cell-free electrophysiology based on the SURFE²R (surface electrogenic event reader) technology platform. The main advantages of the method described here are high sensitivity and simple handling. Material for assays is mainly a simplemembrane preparation, which can be stored over weeks and months. Thus, the application of the method does not depend on a permanently running cell-culture lab. The application of the technology itself uses a bench-top system and chips loaded with membrane fragments. The SURFE²R technology was used to establish an Na+/Ca2+-exchanger assay. The assay performance, as judged by the Z' value of 0.73 and the signal-to-background ratio of 7.6, suggests that this is a reliable and robust assay. The authors compared the technology with patch-clamp experiments: Themeasurement of activity of 17 different inhibitors and the determination of an IC 50value indicated a good correlation between SURFE²R technology and patch clamp results. Using the SURFE²R technology, results were obtainedwith 20 times higher throughput and required less-qualified personnel compared with manual patch clamping.


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