• 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

2020 - Reliable Identification of hERG Liability in Drug Discovery by Automated Patch Clamp

 icon sp96   SyncroPatch 384i (a predecessor model of SyncroPatch 384) and   icon pl   Patchliner poster, 64th Annual Meeting of the Biophysical Society   logo pdf   (1.3 MB)


The Comprehensive in Vitro Proarrhythmia Assay (CiPA) is focused on proarrhythmia to improve specificity compared to in vitro hERG and in vivo QT studies. Within this initiative, compounds representing high, intermediate, and low proarrhythmic risk categories were tested across multiple sites and automated patch clamp (APC) platforms. Resulting IC50 values varied between platforms, which could be due to non-specific binding of compounds in well-based platforms since they don’t maintain a constant flow of compound-containing solution to replenish losses to fluidics and well walls.
Here, we investigated non-specific binding using hydrophobic (“sticky”) compounds to assess the reliability of our experimental routine by analyzing IC50 values of CiPA compounds. We equipped a 384-well APC platform with a state-of-the-art liquid handling robot and used its serial dilution capability for compound preparation. Glass-coated compound plates were used to prevent absorption of hydrophobic compounds. After compound preparation, the user-unattended experiments were executed and IC50 values of the compounds were measured and compared to literature values.
“Sticky” compounds such as verapamil were applied either as a single concentration per recording well or cumulatively in 4 increasing concentrations. Incubation times were varied. For example, IC50 values of verapamil were 0.66 μM (CiPA step-ramp hERG protocol, 7-minute incubation time) and 0.60 μM (standard hERG protocol, 4-minute incubation time), respectively, and thus in good agreement with themselves and literature values. Incubation times below 4 minutes were too short to reach steady-state currents. Results of further compounds e.g. terfenadine, chlorpromazine, quinidine and clozapine will also be presented.
The 384-well APC system used in this study (SyncroPatch 384i) is well suited to perform safety pharmacological studies within the guidelines of the CiPA initiative. Caution has to be taken on the handling and storage conditions of the compounds, as well as exposure times of the compounds during the measurement.

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