Document Type


Publication Date


Publication Title

International Journal of Molecular Sciences






10921 (1-13 pp.)




Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as “bipolar cancellation,” enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing the electric field in the pairs (180° direction change) caused 2-fold (1 Hz) or 20-fold (833 kHz) weaker electroporation than the train of single nsEPs. Reducing the angle between pulse directions in the pairs weakened cancellation and replaced it with facilitation at angles <160° (1 Hz) and <130° (833 kHz). Facilitation plateaued at about three-fold stronger electroporation compared to single pulses at 90–100° angle for both nsEP frequencies. The profound dependence of the efficiency on the angle enables novel protocols for highly selective focal electroporation at one electrode in a three-electrode array while avoiding effects at the other electrodes. Nanosecond-resolution imaging of cell membrane potential was used to link the selectivity to charging kinetics by co- and counter-directional nsEPs.


© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

Data Availability

Article states: The data presented in this study are available on request from the corresponding author.

Original Publication Citation

Kim, V., Semenov, I., Kiester, A. S., Keppler, M. A., Ibey, B. L., Bixler, J. N., Colunga Biancatelli, R. M. L. & Pakhomov, A. G. (2023). Control of the electroporation efficiency of nanosecond pulses by swinging the electric field vector direction. International Journal of Molecular Sciences, 24(13), Article 10921.


0000-0003-0699-5582 (Kim), 0000-0002-0302-1355 (Semenov), 0000-0002-1174-3876 (Colunga Biancatelli), 0000-0003-3816-3860 (Pakhomov)