Magneto-Permeabilization of Viable Cell Membrane Using High Pulsed Magnetic Field

Abstract

In this work we present novel experimental data of the magnetic permeabilization of the mammalian cells in high pulsed magnetic fields up to 16.4 T. Two designs of the multilayer solenoid type pulsed inductors, which were adapted for the biological experiments are presented. The induced electric field is analyzed using the finite element method analysis. The experimental methodology and the pulsed magnetic field setups are overviewed. The experimental results with mouse myeloma cell line Sp2/0 in pulsed magnetic field after pulse bursts and single pulse treatment are presented. The SYTOX ® Green dye was used for the estimation of the permeabilization process efficacy. It has been shown that the 16.4 T sub-millisecond low (< 1.1×10 5 T/s) dB/dt magnetic field pulses do not cause any observable dye uptake changes using the proposed methodology. The short repetitive microsecond range pulses (dB/dt > 0.8×10 6 T/s) result in an average up to 2.6±0.5% increase of the dye uptake.

Membrane permeabilization of mammalian cells using bursts of high magnetic field pulses

“…However the effect does not depend on the conductance or the uniformity of the sample and at the same time is contactless ( Grainys et al, 2012 ; Kardos & Rabussay, 2012 ; Towhidi et al, 2012 ; Shankayi, Firoozabadi & Mansurian, 2013 ; Kranjc et al, 2016 ). The proof of concept has been confirmed both in vitro ( Towhidi et al, 2012 ; Shankayi et al, 2014 ; Novickij et al, 2015 ) and in vivo for the PEMF mediated transport of small molecules (e.g., cisplatin, platinum) ( Kranjc et al, 2016 ) and large molecules (e.g., DNA) ( Kardos & Rabussay, 2012 ). Currently however, the efficacy of the PEMF treatment is inferior to electroporation.…”

“…Namely, the electric field that is induced by the time-varying magnetic field is lower by several orders of magnitude than the electric field causing membrane permeabilization in conventional electroporation experiments ( Lucinskis et al, 2014 ; Kranjc et al, 2016 ). The permeabilization effect is likely to occur during multiple high dB/dt, where dB/dt denotes the time change of the magnetic flux density ( B ) ( Van Bree et al, 2013 ; Novickij et al, 2015 ), or during application of long train of microsecond pulses ( Towhidi et al, 2012 ; Shankayi et al, 2014 ; Kranjc et al, 2016 ).…”

“…Improvement of pulse generation, systematic research and parametric analysis may result in a novel contactless method that could be an attractive alternative to the conventional electroporation. Previously, it was shown that the repetitive (40 Hz) high dB/dt (8 × 10 5 T/s) magnetic fields up to 3 T induce permeabilization of only a small fraction of the cells ( Novickij et al, 2015 ). However, Towhidi et al (2012) have shown that the application of lower frequency pulses increases the treatment efficacy.…”

Electrochemotherapy by pulsed electromagnetic field treatment (PEMF) in mouse melanoma B16F10 in vivo

“… 36 However, the application of stronger magnetic field (up to 16.4 T) did not result in better membrane permeabilization. 35 The membrane permeabilization seems to be dependent more on the shape, number and frequency of generated pulses 34 - 36 in addition to the amplitude of induced electric field, similar to the conventionally generated bipolar pulses. 44 In addition, bipolar pulses were demonstrated two times more effective as monopolar and almost equally effective as conventional square wave pulses.…”

“…large number of 25 up to 800 the μs long magnetic field pulses applied at frequencies from 25 Hz up to 40 Hz and strength from 725 V/m up to 160 kV/m. 30 , 35 , 36 Furthermore, its use as electroporation tool was shown in an approach for drug as well as for plasmid DNA delivery. 36 , 37 Thus, such electromagnetic induction with alternating currents has the potential for simple contactless tissue electroporation, used for electrochemotherapy and gene electrotransfer.…”