• Our CiPA Instruments

    HESI FDA BAA study: "Assessing variability and reproducibility of manual and automated patch clamp platforms"

  • CiPA hERG Protocol

    This protocol was used for hERG studies on the Patchliner and SyncroPatch 384PE.

  • HTS CiPA hERG Assay

    Effects of Cisapride using the CiPA hERG protocol on the SyncroPatch 384PE

  • Myocyte & Ion Channel Effects

    Arrhythmic Field potentials in iPSC-derived Cardiomyocytes (CardioExcyte 96) and hERG current inhibition (SyncroPatch 384PE)

  • Gigaseal HTS patch clamp

    CiPA-specified cardiac ion channels recorded at high throughput

  • Gigaseal HTS patch clamp

    High throughput recordings of cardiac ion channels at physiological temperature

  • CardioExcyte 96 screening tool

    CardioExcyte 96 with integrated liquid handling for cardiac safety screening

2022 - Translating the Measurement of Herg Kinetics and Drug Block for Cipa to a High Throughput Platform

icon sp96 SyncroPatch 384PE (a predecessor model of the SyncroPatch 384 instrument) pre-print publication in SSRN (2022)

Authors:
Windley M.J., Farra J., Vandenberg J.I., Hill A.P.

Journal:
SSRN (2022) doi:10.2139/ssrn.4065593


Abstract: 

The Comprehensive in vitro Proarrhythmic Assay (CiPA) has promoted use of in silico models of drug effects on cardiac repolarization to improve proarrhythmic risk prediction. These models contain a pharmacodynamic component describing drug binding to hERG channels that required in vitro data for kinetics of block, in addition to potency, to constrain them. To date, development and validation has been undertaken using data from manual patch-clamp. To enable the application of this approach at scale this requires the development of a high-throughput, automated patch-clamp (APC) implementation. Here, we present a comprehensive analysis of the implementation of the Milnes, or
CiPA dynamic protocol, on an APC platform, including automated quality control and data analysis. Kinetics and potency of block were assessed for bepridil, cisapride, terfenadine and verapamil with data retention/QC pass rate of 21.8%. The variability in IC50 and kinetics between manual and APC was comparable to that seen between sites/platforms in previous APC studies of potency. Whilst the experimental success is less than observed in screens of potency alone, it is still significantly greater than manual patch. With appropriate consideration of protocol design, including sweep length, number of repetitions, and leak correction, this protocol can be applied on APC to acquire data comparable to manual patch clamp.


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