Abstract
A unique aspect of electrostimulation (ES) with nanosecond electric pulses (nsEP) is the inhibition of effects when the polarity is reversed. This bipolar cancellation feature makes bipolar nsEP less efficient at biostimulation than unipolar nsEP. We propose to minimize stimulation near pulse-delivering electrodes by applying bipolar nsEP, whereas the superposition of two phase-shifted bipolar nsEP from two independent sources yields a biologically-effective unipolar pulse remotely. This is accomplished by electrical compensation of all nsEP phases except the first one, resulting in the restoration of stimulation efficiency due to cancellation of bipolar cancellation (CANCAN-ES). We experimentally proved the CANCAN-ES paradigm by measuring YO-PRO-1 dye uptake in CHO-K1 cells which were permeabilized by multiphasic nsEP (600 ns per phase) from two generators; these nsEP were synchronized either to overlap into a unipolar pulse remotely from electrodes (CANCAN), or not to overlap (control). Enhancement of YO-PRO-1 entry due to CANCAN was observed in all sets of experiments and reached ~3-fold in the center of the gap between electrodes, exactly where the unipolar pulse was formed, and equaled the degree of bipolar cancellation. CANCAN-ES is promising for non-invasive deep tissue stimulation, either alone or combined with other remote stimulation techniques to improve targeting.
Highlights
Electrical stimulation (ES) is one of the most universal approaches to manipulate biological functions
The transcranial magnetic stimulation (TMS) is a non-invasive procedure that became a breakthrough in neural stimulation and therapies[17,23,24,25,26,27], but with its own limitations including limited penetration[28,29] and challenges in targeting[28]
The pulse duration, number, and repetition rate were kept constant throughout the study, whereas the peak amplitude, the number of phases, and phase amplitude ratios were varied as outlined for each experiment
Summary
Electrical stimulation (ES) is one of the most universal approaches to manipulate biological functions. Non-invasive ES modalities such as transcutaneous electrical nerve stimulation[9,20,21,22] and transcranial direct current stimulation[9] deliver the electric field indiscriminately to the tissue volume between electrodes. The transcranial magnetic stimulation (TMS) is a non-invasive procedure that became a breakthrough in neural stimulation and therapies[17,23,24,25,26,27], but with its own limitations including limited penetration[28,29] and challenges in targeting[28]. Out of various disc and ring electrode configurations for transcranial electrostimulation, the concentric ring configuration, which comprises a cathode ring surrounding an anode disc electrode, provided the highest spatial focality, at the expense of increased current demand and poor penetration depth[30]. In spite of its drawbacks, the concentric ring was subsequently developed into a 4 × 1 ring electrode array, with 4 cathode electrodes surrounding a single anode electrode, and has been employed for high-definition, targeted neurostimulation[31,34,35,36]
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