• 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 - Cross-site and cross-platform variability of automated patch clamp assessments of drug effects on human cardiac currents in recombinant cells

icon pl   Patchliner and   icon sp96   SyncroPatch 384PE (a predecessor model of the SyncroPatch 384i instrument) publication in Nature Scientific Reports (2020)

Authors:
Kramer J., Himmel H.M., Lindqvist A., Stoelzle-Feix S., Chaudhary K.W., Li D., Bohme G.A., Bridgland-Taylor M., Hebeisen S., Fan J., Renganathan M., Imredy J., Humphries E.S.A, Brinkwirth N., Strassmaier T., Ohtsuki A., Danker T., Vanoye C., Polonchuk L., Fermini B., Pierson J.B. & Gintant G.

Journal:

Nature Sci Rep 10, 5627 (2020) doi: 10.1038/s41598-020-62344-w 


Abstract: 

Automated patch clamp (APC) instruments enable efficient evaluation of electrophysiologic effects of drugs on human cardiac currents in heterologous expression systems. Differences in experimental protocols, instruments, and dissimilar site procedures affect the variability of IC50 values characterizing drug block potency. This impacts the utility of APC platforms for assessing a drug’s cardiac safety margin. We determined variability of APC data from multiple sites that measured blocking potency of 12 blinded drugs (with different levels of proarrhythmic risk) against four human cardiac currents (hERG [IKr], hCav1.2 [L-Type ICa], peak hNav1.5, [Peak INa], late hNav1.5 [Late INa]) with recommended protocols (to minimize variance) using five APC platforms across 17 sites. IC50 variability (25/75 percentiles) differed for drugs and currents (e.g., 10.4-fold for dofetilide block of hERG current and 4-fold for mexiletine block of hNav1.5 current). Within-platform variance predominated for 4 of 12 hERG blocking drugs and 4 of 6 hNav1.5 blocking drugs. hERG and hNav1.5 block. Bland-Altman plots depicted varying agreement across APC platforms. A follow-up survey suggested multiple sources of experimental variability that could be further minimized by stricter adherence to standard protocols. Adoption of best practices would ensure less variable APC datasets and improved safety margins and proarrhythmic risk assessments.


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