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April 26, 2022Nature Communications73 citationsOpen Access

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes

ZJZeinab JahedYYYang YangCTChing‐Ting Tsai

Key Result

Vertically-aligned nanocrown electrodes achieved a >99% success rate in obtaining intracellular access through electroporation for parallel and robust recording of cardiomyocytes.

Structured PICO

P
Population
human pluripotent stem-cell-derived cardiomyocytes (hPSC-CMs) and U2OS cells
I
Intervention
Vertically-aligned nanocrown electrodes (180-nm-deep and 450-nm-deep) for intracellular action potential recording via electroporation
C
Comparator
Solid nanopillar electrodes
O
Outcome
Electroporation success rate, initial iAP amplitude, and maintenance of intracellular accesssurrogate

Nanocrown electrodes enable highly reliable, parallel, and prolonged intracellular action potential recordings in cardiomyocytes, offering a robust platform for preclinical proarrhythmia drug screening.

Main Result

Absolute Event Rate: 99.35% vs 93.83%

Limitations

  • Amplifier system has limited charge injection capacity, limiting simultaneous electroporation to 4-6 cells.
  • Recordings mostly limited to 15 minutes to avoid adverse effects to cells outside the incubator.
  • The amplifier system used has limited charge injection capacity and usually limits simultaneous electroporation to 4-6 cells.

Abstract

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

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Cite This Study

Jahed et al. (2022) studied Cardiomyocyte electrophysiology. Nanocrown electrodes vs. Nanopillar electrodes was evaluated on Electroporation success rate. Vertically-aligned nanocrown electrodes achieved a >99% success rate in obtaining intracellular access through electroporation for parallel and robust recording of cardiomyocytes.

synapsesocial.com/papers/6a0507deccdd74096c344716https://doi.org/10.1038/s41467-022-29726-2
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