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Title:
Focal electrostimulation based on swinging the vector direction of nanosecond pulses
Authors:
Kim Vitalii, Pakhomov Andrei G. -
Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Abstract:
The efficiency of cell treatments using nanosecond electric pulses (nsEP) can be either reduced or enhanced by delivering a subsequent nsEP in the opposite or the same direction, respectively. These features of nsEP stimulation are known as bipolar cancellation and temporal summation. In a recent study, we quantified how the efficiency of electroporation with nsEP pairs depends on the change in the electric field direction from 0° to 180°. Our experiments with electroporation of BPAE cell monolayers by 0.833 kHz 600-ns pulses showed maximum bipolar cancellation (13-fold vs a unipolar pulse) at 180° vector change. At angles less than 90°-120°, the cancellation was replaced by summation, resulting in up to a 3-fold stronger effect.
The strong dependence of electroporation on the angle between nsEP vectors has led to a unique electroporation pattern in triangular electrode arrays. Electroporation was restricted to the area near the apex electrode, which served as ground and was never energized, while 600-ns pulses were alternately applied to base electrodes. Electroporated cells formed a comet-shaped region pointing from the apex electrode towards the base (referred to as focal electroporation). Similarly, we applied the focal electrostimulation approach to excite smooth muscle cells in a monolayer. Excitation measured by Ca2+ mobilization was observed near the apex electrode but not at two base electrodes, despite the stronger electric field there.
The focal stimulation was further tested in a 3D cell model, using a pyramid electrode configuration where the apex electrode served as a ground while diagonal pairs of base electrodes were energized in alternation with unipolar nsEP. Similarly to the triangular array, individual nsEP applied to the diagonal pairs of base electrodes coalesced into a “long” pulse near the apex, while remaining counter-directional and inefficient at the base. Experiments in a potato (as a 3D cell model) demonstrated a comet-shaped ablation near the apex electrode only. Ongoing experiments are focused on focal electroporation in rabbit liver using the pyramid electrode configuration.
The new technique holds the potential for targeted focal electroporation (tumor ablation) and electrostimulation (brain stimulation) of deep-seated tissues, with one electrode placed at the target location while the return electrodes remain on the skin.
Keywords:
electroporation; electropermeabilization; nanosecond pulses; nsEP; focal electroporation;
Refs:
Topic 1:
1. Biological responses (molecular, subcellular, cellular and intercellular)
Topic 2:
8. Cell and tissue stimulation, wound healing
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