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Push–pull configuration of high-power MOSFETs for generation of nanosecond pulses for electropermeabilization of cells

  • I. W. Davies (a1) (a2), C. Merla (a3), A. Casciati (a3), M. Tanori (a3), A. Zambotti (a3), M. Mancuso (a3), J. Bishop (a2), M. White (a2), C. Palego (a1) and C. P. Hancock (a1) (a2)...


A power MOSFET-based push–pull configuration nanosecond-pulse generator has been designed, constructed, and characterized to permeabilize cells for biological and medical applications. The generator can deliver pulses with durations ranging from 80 ns up to 1 µs and pulse amplitudes up to 1.4 kV. The unit has been tested for in vitro experiments on a medulloblastoma cell line. Following the exposure of cells to 100, 200, and 300 ns electric field pulses, permeabilization tests were carried out, and viability tests were conducted to verify the performance of the generator. The maximum temperature rise of the biological load was also calculated based on Joule heating energy conservation and experimental validation. Our results indicate that the developed device has good capabilities to achieve well-controlled electro-manipulation in vitro.


Corresponding author

Author for correspondence: I. W. Davies, E-mail:


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1.Sundararajan, R (2014) Electroporation-Based Therapies for Cancer from Basics to Clinical Applications. Waltham, MA: Woodhead Pub.
2.Silve, A, Vezinet, R and Mir, L (2012) Nanosecond-duration electric pulse delivery in vitro and in vivo: experimental considerations. IEEE Transactions on Instrumentation and Measurement 61, 19451954.
3.General Optimization Guide for Electroporation., 2018. [Online]. Available at
4.Weaver, J (2000) Electroporation of cells and tissues. IEEE Transactions on Plasma Science 28, 2433.
5.Edd, JF, Horowitz, L, Davalos, RV, Mir, LM and Rubinsky, B (2006) In vivo results of a new focal tissue ablation technique: irreversible electroporation. IEEE Transactions on Biomedical Engineering 53, 14091415.
6.Kotnik, T, Kramar, P, Pucihar, G, Miklavčič, D and Tarek, M (2012) Cell membrane electroporation – part 1: the phenomenon. IEEE Electrical Insulation Magazine 28, 1423.
7.Denzi, A, Merla, C, Caramazza, L, De Angelis, A, Apollonio, F and Liberti, M (2018) Microdosimetry in Biomedical Applications: Importance of Realistic Models at the Cellular and Subcellular Levels. EMF-Med 2018 Book of Abstract, pp. 4041.
8.Consales, C, Merla, C, Benassi, B, Muscat, A, Garcia-Sanchez, T, Marino, C and Mir, LM (2018) Oxidative and Epigenetic Effects of Ultra-short Pulsed electric Fields on Neuronal-like Cells. EMF-Med 2018 Book of Abstract, pp. 7879.
9.Merla, C, Garcia-Sanchez, T, Muscat, A, Consales, C, Benassi, B, Andre, FM, Marino, C and Mir, LM (2018) Nanosecond pulsed electric fields modulate Ca2+ fluxes in SH-SY5Y neuroblastoma cell line. EMF-Med 2018 Book of Abstract, pp. 8081.
10.Botha, S, Lopez, B, Muscat, A, Lucía, Ó, Sarnago, H, Naval, A, Burdio, JM, García-Sánchez, T, Mir, LM and Andre, F (2018) Long term control of cytosolic calcium oscillations in Mesenchymal Stem Cells using repeated electric pulses. EMF-Med 2018 Book of Abstract, pp. 8384.
11.Schoenbach, K, Nuccitelli, R and Beebe, S (2006) Zap. IEEE Spectrum 43, 2026.
12.Nuccitelli, R, Pliquett, U, Chen, X, Ford, W, James Swanson, R, Beebe, S, Kolb, J and Schoenbach, K (2006) Nanosecond pulsed electric fields cause melanomas to self-destruct. Biochemical and Biophysical Research Communications 343, 351360.
13.Schoenbach, K, Hargrave, B, Joshi, R, Kolb, J, Nuccitelli, R, Osgood, C, Pakhomov, A, Stacey, M, Swanson, R, White, J, Xiao, S, Zhang, J, Beebe, S, Blackmore, P and Buescher, E (2007) Bioelectric Effects of Intense Nanosecond Pulses. IEEE Transactions on Dielectrics and Electrical Insulation 14, 10881109.
14.Swanson, R, Chen, X, Nuccitelli, R, Beebe, S, Pliquett, U, Ford, W, Kolb, J, Zheng, S and Schoenbach, K (2007) Melanoma Morphology Change & Apoptosis Induced by Multiple Nanosecond Pulsed Electric Fields, 2007 International Conference on Electromagnetics in Advanced Applications, Torino, pp. 1036–1039. doi: 10.1109/ICEAA.2007.4387486.
15.Skeate, J, Da Silva, D, Chavez-Juan, E, Anand, S, Nuccitelli, R and Kast, W (2018) Nano-pulse stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response. PLoS ONE 13, e0191311.
16.Nuccitelli, R, Kreis, M, Athos, B, Lui, K, Berridge, C, Nuccitelli, P and Epstein, E (2013) PPPS-2013: Nanoelectroablation for human carcinoma therapy. in IEEE International Conference on Plasma Science (ICOPS), San Francisco, CA, USA, p. 1.
17.Krishnaswamy, P, Kuthi, A, Vernier, P and Gundersen, M (2007) Compact subnanosecond pulse generator using avalanche transistors for cell electroperturbation studies. IEEE Transactions on Dielectrics and Electrical Insulation 14, 873877.
18.Davies, IW, Merla, C, Zambott, A, Bishop, J, Palego, C and Hancock, CP (2018) Electropermeabilization of Isolated Cancer Stem Cells with a Novel and Versatile Nanosecond Pulse Generator. 2018 IEEE International Microwave Biomedical Conference (IMBioC), Philadelphia, PA. pp. 106108. doi: 10.1109/IMBIOC.2018.8428941.
19.Cancer Research UK., 2018. [Online]. Available at
20.Brain Tumor: Statistics | Cancer.Net. Cancer.Net, 2018. [Online]. Available at
21.Brain tumor prognosis | The Brain Tumor Charity., 2018. [Online]. Available at
22.Cardiff University. Cardiff University, 2018. [Online]. Available at
23.The Stem Cell Theory of Cancer | Ludwig Center | Stanford Medicine., 2018. [Online]. Available at
24.MicroPulser™ Electroporator | Life Science Research | Bio-Rad., 2018. [Online]. Available at
25.Electroporators | VWR., 2018. [Online]. Available at
26.BTX™ ECM™ 399 Exponential Decay Wave Electroporator. Fisher Scientific, 2018. [Online]. Available at
27.FID GmbH – Products – FPG-N Series – Nanosecond High Voltage Pulsers., 2018. [Online]. Available at
28.High Voltage Pulse Generators & Pulsers | Directed Energy., 2018. [Online]. Available at
29.Avtech Electrosystems Ltd., 2018. [Online]. Available
30.M. Inc. High Voltage Power Supplies|Matsusada Precision Inc., 2018. [Online]. Available at
31.Gong, C, Valduga, J, Chateau, A, Richard, M, Pellegrini-Moïse, N, Barberi-Heyob, M, Chastagner, P and Boura, C (2018) Stimulation of medulloblastoma stem cells differentiation by a peptidomimetic targeting neuropilin-1. Oncotarget 9, 1531215325. doi: 10.18632/oncotarget.24521.
33.Behrend, M, Kuthi, A, Gu, X, Vernier, P, Marcu, L, Craft, C and Gundersen, M (2003) Pulse generators for pulsed electric field exposure of biological cells and tissues. IEEE Transactions on Dielectrics and Electrical Insulation 10, 820825.
34.Kuthi, A, Gabrielsson, P, Behrend, M, Vernier, P and Gundersen, M (2005) Nanosecond pulse Generator using fast recovery diodes for cell electromanipulation. IEEE Transactions on Plasma Science 33, 11921197.
35.Wijetunga, P, Gu, X, Vernier, T, Kuthi, A, Behrend, M and Gundersen, MA (2003) Electrical modeling of pulsed power systems for biomedical applications. Digest of Technical Papers. PPC-2003. 14th IEEE International Pulsed Power Conference (IEEE Cat. No.03CH37472), Dallas, TX, USA, pp. 423428. Vol. 1.
36.Sanders, J, Kuthi, A, Wu, Y, Vernier, P and Gundersen, M (2009) A linear, single-stage, nanosecond pulse generator for delivering intense electric fields to biological loads. IEEE Transactions on Dielectrics and Electrical Insulation 16, 10481054.
37.Novickij, V, Grainys, A, Butkus, P, Tolvaišienė, S, Švedienė, J, Paškevičius, A and Novickij, J (2016) High-frequency submicrosecond electroporator. Biotechnology & Biotechnological Equipment 30, 607613.
38.Reberšek, M and Miklavčič, D (2011) Advantages and disadvantages of different concepts of electroporation pulse generation. Automatika 52, 1219.
39.C2M1000170D, Silicon Carbide Power MOSFET C2M MOSFET Technology (2015) N-Channel Enhancement Mode. Cree, pp. 111. Available at
40.GT40WR21, Silicon N-Channel IGBT. TOSHIBA, 2018 [Online]. Available at
41.TSC5802D, High Voltage Fast-Switching NPN Power Transistor. Taiwan Semiconductor, 2018 [Online]. Available at
42.TLP352, TLP352F Photocouplers, GaAlAs Infrared LED & Photo IC. TOSHIBA, 2011, pp. 121.
43.Boylestad, R, Nashelsky, L and Li, L (1998) Electronic Devices and Circuit Theory, 7th Edn. New Jersey: Prentice Hall.
44.Severns, R (1985) Siliconix Power Application Handbook. Santa Clara, California: Siliconix incorporated.
45Kogure, H, Kobayashi, H, Takahashi, Y, Myono, T, Sato, H, Kimura, Y, Onaya, Y and Tanaka, K (2002) Analysis of CMOS ADC nonlinear input capacitance. IEICE Ttransactions on Electronics 85, 11821190.
46.C2M1000170D 1000mΩ 1700-V SiC MOSFET | Wolfspeed., 2018. [Online]. Available at
47.FS40, FS Series Isolated, proportional DC to HV DC converters, XPPower, 2011, pp. 19.
48.Merla, C, El-Amari, S, Kenaan, M, Liberti, M, Apollonio, F, Arnaud-Cormos, D, Couderc, V and Leveque, P (2010) A 10-Ω high-voltage nanosecond pulse generator. IEEE Transactions on Microwave Theory and Techniques 58, 40794085.
49.Merla, C, Casciati, A, Tanori, M, Tanno, B and Mancuso, M (2018) SUMCASTEC_180123_NA_protocolWP3_protocol_.pdf_Rome_. Merla_Partners and public_NA. Zenodo. [Online]. Available at
50.Gene Pulser®/MicroPulser™ Electroporation Cuvettes, 0.1cm gap #1652089 | Life Science Research | Bio-Rad., 2018. [Online]. Available at
51.Kenaan, M, Amari, S, Silve, A, Merla, C, Mir, L, Couderc, V, Arnaud-Cormos, D and Leveque, P (2011) Characterization of a 50-Ω exposure setup for hgh-voltage nanosecond pulsed electric field bioexperiments. IEEE Transactions on Biomedical Engineering 58, 207214.
52.Tektronix (2018) TDS5000B Series - Digital Phosphor Oscilloscopes Read This First | Tektronix,, 2018. [Online]. Available:
53.PPE 5kV (2018) Glasgow: Teledyne LeCroy, pp. 12. [Online]. Available at
54.Moreau, D, Lefort, C, Burke, R, Leveque, P and O'Connor, R (2015) Rhodamine B as an optical thermometer in cells focally exposed to infrared laser light or nanosecond pulsed electric fields. Biomedical Optics Express 6, 4105.
55.Kohler, S, O'Connor, R, Vu, T, Leveque, P and Arnaud-Cormos, D (2013) Experimental microdosimetry techniques for biological cells exposed to nanosecond pulsed electric fields using microfluorimetry. IEEE Transactions on Microwave Theory and Techniques 61, 20152022.
56.García-Sánchez, T, Merla, C, Fontaine, J, Muscat, A and Mir, L (2018) Sine wave electropermeabilization reveals the frequency-dependent response of the biological membranes. Biochimica et Biophysica Acta (BBA) – Biomembranes 1860, 10221034.



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