A method that utilizes nanosecond bipolar cancellation (BPC) near a quadrupole electrodes to suppress a biological response but cancels the distal BPC at the quadrupole center, i.e., cancellation of cancellation (CANCAN), may allow for a remote focused stimulation at the quadrupole center.
Objectives:
The primary object of this study was to outline the requirement of the CANCAN implementation and select an effective quadrupole configuration.
Results:
We have studied three quadrupole electrode configurations, a rod quadrupole, a plate quadrupole (Plate-Q), and a resistor quadrupole. The pulse shapes of electric fields include monophasic pulses, cancellation pulses, and additive pulses. The Plate-Q appears the best for CANCAN as it shows the highest percentage of cancellation pulses among all pulse shapes, allowing for the best spatial focus.
Conclusion:
For the region of interest characterized in the Plate-Q configuration, the maximum magnitude of bipolar field is twice as that of the unipolar field, which allows for the CANCAN demonstration that involves membrane electropermeabilization.
Get full access to this article
View all access options for this article.
References
1.
Batista-NapotnikT, RebersekM, VernierPT, et al.Effects of high voltage nanosecond electric pulses on eukaryotic cells (in vitro): A systematic review. Bioelectrochemistry, 2016; 110:1–12. DOI: 10.1016/j.bioelechem.2016.02.011
2.
NeuberJU, VargheseF, PakhomovAG, et al.Using nanosecond shocks for cardiac defibrillation. Bioelectricity, 2019; 1:240–246. DOI: 10.1089/bioe.2019.0030
3.
NuccitelliR. Nano-pulse stimulation therapy for the treatment of skin lesions. Bioelectricity, 2019; 1:235–239. DOI: 10.1089/bioe.2019.0027
4.
NuccitelliR. Application of pulsed electric fields to cancer therapy. Bioelectricity, 2019; 1:30–34. DOI: 10.1089/bioe.2018.0001
5.
IbeyBL, UlleryJC, PakhomovaON, et al.Bipolar nanosecond electric pulses are less efficient at electropermeabilization and killing cells than monopolar pulses. Biochem Biophys Res Commun, 2014; 443:568–573. DOI: 10.1016/j.bbrc.2013.12.004
6.
PakhomovAG, SemenovI, XiaoS, et al.Cancellation of cellular responses to nanoelectroporation by reversing the stimulus polarity. Cell Mol Life Sci, 2014; 71:4431–4441. DOI: 10.1007/s00018-014-1626-z
7.
GianulisEC, CasciolaM, XiaoS, et al.Electropermeabilization by uni- or bipolar nanosecond electric pulses: The impact of extracellular conductivity. Bioelectrochemistry, 2018; 119:10–19. DOI: 10.1016/j.bioelechem.2017.08.005
8.
GianulisEC, LeeJ, JiangC, et al.Electroporation of mammalian cells by nanosecond electric field oscillations and its inhibition by the electric field reversal. Sci Rep, 2015; 5:13818. DOI: 10.1038/srep13818
9.
PakhomovAG, GrigoryevS, SemenovI, et al.The second phase of bipolar, nanosecond-range electric pulses determines the electroporation efficiency. Bioelectrochemistry, 2018; 122:123–133. DOI: 10.1016/j.bioelechem.2018.03.014
10.
ValdezCM, BarnesRAJr., RothCC, et al.Asymmetrical bipolar nanosecond electric pulse widths modify bipolar cancellation. Sci Rep, 2017; 7:16372. DOI: 10.1038/s41598-017-16142-6
11.
SözerEB, VernierPT. Modulation of biological responses to 2 ns electrical stimuli by field reversal. Biochim Biophys Acta Biomembr, 2019; 1861:1228–1239. DOI: https://doi.org/10.1016/j.bbamem.2019.03.019
12.
ValdezCM, BarnesRJr., RothCC, et al.The interphase interval within a bipolar nanosecond electric pulse modulates bipolar cancellation. Bioelectromagnetics, 2018; 39:441–450. DOI: 10.1002/bem.22134
13.
PolajžerT, Dermol–ČerneJ, ReberšekM, et al.Cancellation effect is present in high-frequency reversible and irreversible electroporation. Bioelectrochemistry, 2020; 132:107442. DOI: https://doi.org/10.1016/j.bioelechem.2019.107442
14.
GowrishankarTR, SternJV, SmithKC, et al.Nanopore occlusion: A biophysical mechanism for bipolar cancellation in cell membranes. Biochem Biophys Res Commun, 2018; 503:1194–1199. DOI: 10.1016/j.bbrc.2018.07.024
15.
MerlaC, PakhomovAG, SemenovI, et al.Frequency spectrum of induced transmembrane potential and permeabilization efficacy of bipolar electric pulses. Biochim Biophys Acta Biomembr, 2017; 1859:1282–1290. DOI: 10.1016/j.bbamem.2017.04.014
16.
SchoenbachKH, PakhomovAG, SemenovI, et al.Ion transport into cells exposed to monopolar and bipolar nanosecond pulses. Bioelectrochemistry, 2015; 103:44–51. DOI: 10.1016/j.bioelechem.2014.08.015
17.
GianulisEC, CasciolaM, ZhouC, et al.Selective distant electrostimulation by synchronized bipolar nanosecond pulses. Sci Rep, 2019; 9:13116. DOI: 10.1038/s41598-019-49664-2
18.
HellerLC, JaroszeskiMJ, CoppolaD, et al.Optimization of cutaneous electrically mediated plasmid DNA delivery using novel electrode. Gene Therapy, 2007; 14:275–280. DOI: 10.1038/sj.gt.3302867
19.
RebersekM, FaurieC, KanduserM, et al.Electroporator with automatic change of electric field direction improves gene electrotransfer in-vitro. Biomed Eng Online, 2007; 6:25. DOI: 10.1186/1475–1925X-6-25
20.
SemenovI, XiaoS, KangD, et al.Cell stimulation and calcium mobilization by picosecond electric pulses. Bioelectrochemistry, 2015; 105:65–71. DOI: 10.1016/j.bioelechem.2015.05.013
21.
BeebeSJ, FoxPM, RecLJ, et al.Nanosecond, high-intensity pulsed electric fields induce apoptosis in human cells. FASEB J, 2003; 17:1493–1495. DOI: 10.1096/fj.02-0859fje
22.
PaulW. Electromagnetic traps for charged and neutral particles. Rev Mod Phys, 1990; 62:531–540. DOI: 10.1103/RevModPhys.62.531
23.
VoldmanJ, TonerM, GrayML, et al.Design and analysis of extruded quadrupolar dielectrophoretic traps. J Electrostat, 2003; 57:69–90. DOI: 10.1016/S0304-3886(02)00120-1
24.
WangY, WanczekKP. Generation of an exact three-dimensional quadrupole electric field and superposition of a homogeneous electric field within a common closed boundary with application to mass spectrometry. J Chem Phys, 1993; 98:2647–2652. DOI: 10.1063/1.464145
25.
RyanHA, HirakawaS, YangE, et al.High-voltage, multiphasic, nanosecond pulses to modulate cellular responses. IEEE Trans Biomed Circuits Syst, 2018; 12:338–350. DOI: 10.1109/TBCAS.2017.2786586
BoW, SilkunasM, MangalanathanU, et al.Probing nanoelectroporation and resealing of the cell membrane by the entry of Ca2+ and Ba2+ ions. Int J Mol Sci, 2020; 21:3386. DOI: 10.3390/ijms21093386
28.
ReillyJP. Neuroelectric mechanisms applied to low frequency electric and magnetic field exposure guidelines—Part I: Sinusoidal waveforms. Health Phys, 2002; 83:341–355. DOI: 10.1097/00004032-200209000-00004
29.
CasciolaM, XiaoS, ApollonioF, et al.Cancellation of nerve excitation by the reversal of nanosecond stimulus polarity and its relevance to the gating time of sodium channels. Cell Mol Life Sci, 2019; 76:4539–4550. DOI: 10.1007/s00018-019-03126-0
30.
PakhomovAG, XiaoS, NovickijV, et al.Excitation and electroporation by MHz bursts of nanosecond stimuli. Biochem Biophys Res Commun, 2019; 518:759–764. DOI: 10.1016/j.bbrc.2019.08.133
