title: New easy-to-use hybrid system for extracellular potential and impedance recordings.
abstract: The need for predictive, in vitro cardiac safety screening drives further development of automated, high-throughput-compatible drug evaluation based on cardiac cell preparations. Recently, pluripotent stem cells are evaluated as a new, more predictive model for cardiovascular risk assessment pertaining to in vitro assays. We present a new screening platform, the CardioExcyte 96, a hybrid instrument that combines impedance (cell contractility) with extracellular field potential (EFP) recordings. The electrophysiological measurements are noninvasive, label free and have a temporal resolution of 1 ms. This hybrid technology addresses the lack of easy-to-use high-throughput screening for in vitro assays and permits the reliable investigation of short- and long-term pharmacological effects. Several models of cardiomyocyte preparations were successfully validated for use with the CardioExcyte96. Furthermore, the pharmacological effects of a number of reference compounds were evaluated. Compound effects on cell monolayers of human-induced pluripotent stem cell-derived cardiomyocytes are evaluated using a quasi-simultaneous hybrid recording mode that combines impedance and EFP readouts. A specialized software package for rapid data handling and real-time analysis was developed, which allows for comprehensive investigation of the cellular beat signal. Combining impedance readouts of cell contractility and EFP (microelectrode array-like) recordings, the system opens up new possibilities in the field of in vitro cardiac safety assessment.
authors.affiliation: Nanion Technologies GmbH, Munich, Germany.
authors.forename: Leo
authors.initials: L
authors.lastname: Doerr
authors.affiliation: Nanion Technologies GmbH, Munich, Germany ulrich.thomas@nanion.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thomas
authors.affiliation: Nanion Technologies GmbH, Munich, Germany.
authors.forename: David R
authors.initials: DR
authors.lastname: Guinot
authors.affiliation: Nanion Technologies Inc., Livingston, NJ.
authors.forename: Corina T
authors.initials: CT
authors.lastname: Bot
authors.affiliation: Nanion Technologies GmbH, Munich, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Stoelzle-Feix
authors.affiliation: Nanion Technologies GmbH, Munich, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Beckler
authors.affiliation: Nanion Technologies GmbH, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: George
authors.affiliation: Nanion Technologies GmbH, Munich, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Fertig
mesh_terms: D003584:Cytological Techniques / Q000295:instrumentation / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D055724:Electrophysiological Phenomena / Q000187:drug effects*; D057166:High-Throughput Screening Assays / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D012984:Software
keywords: CiPA initiative; HTS; MEA; arrhythmia; automated biology; cardiac; high-throughput screening; impedance pharmacology; microelectrode array; stem cells