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

Published online by Cambridge University Press:  27 May 2019

I. W. Davies ,
C. Merla ,
A. Casciati ,
M. Tanori ,
A. Zambotti ,
M. Mancuso ,
J. Bishop ,
M. White ,
C. Palego  and
C. P. Hancock
I. W. Davies*
Affiliation:
School of Computer Science and Electronic Engineering, University of Bangor, Bangor, UK Creo Medical, Bath, UK
C. Merla
Affiliation:
Division of Health Protection Technologies, ENEA-Casaccia, Rome 00123, Italy
A. Casciati
Affiliation:
Division of Health Protection Technologies, ENEA-Casaccia, Rome 00123, Italy
M. Tanori
Affiliation:
Division of Health Protection Technologies, ENEA-Casaccia, Rome 00123, Italy
A. Zambotti
Affiliation:
Division of Health Protection Technologies, ENEA-Casaccia, Rome 00123, Italy
M. Mancuso
Affiliation:
Division of Health Protection Technologies, ENEA-Casaccia, Rome 00123, Italy
J. Bishop
Affiliation:
Creo Medical, Bath, UK
M. White
Affiliation:
Creo Medical, Bath, UK
C. Palego
Affiliation:
School of Computer Science and Electronic Engineering, University of Bangor, Bangor, UK
C. P. Hancock
Affiliation:
School of Computer Science and Electronic Engineering, University of Bangor, Bangor, UK Creo Medical, Bath, UK
*
Author for correspondence: I. W. Davies, E-mail: eeu25b@bangor.ac.uk
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Abstract

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.

Keywords

Circuit design and applicationsEM field theory and numerical techniquesmedical and biological effectspassive components and circuitsSi-based devices and IC technologies
Type
EuMW 2018
Information
International Journal of Microwave and Wireless Technologies , Volume 11 , Special Issue 7: MIKON 2018 / EuMW 2018 (Part II) , September 2019 , pp. 645 - 657
Copyright
Copyright © Cambridge University Press and the European Microwave Association 2019 

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References

1.Sundararajan, R (2014) Electroporation-Based Therapies for Cancer from Basics to Clinical Applications. Waltham, MA: Woodhead Pub.Google Scholar
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, 1945–1954.Google Scholar
3.General Optimization Guide for Electroporation. Btxonline.com, 2018. [Online]. Available at https://www.btxonline.com/media/wysiwyg/education_page/Electroporation%20Optimization%20Guide.pdf.Google Scholar
4.Weaver, J (2000) Electroporation of cells and tissues. IEEE Transactions on Plasma Science 28, 24–33.Google Scholar
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, 1409–1415.Google Scholar
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, 14–23.Google Scholar
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. 40–41.Google Scholar
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. 78–79.Google Scholar
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. 80–81.Google Scholar
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. 83–84.Google Scholar
11.Schoenbach, K, Nuccitelli, R and Beebe, S (2006) Zap. IEEE Spectrum 43, 20–26.Google Scholar
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, 351–360.Google Scholar
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, 1088–1109.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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, 873–877.Google Scholar
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. 106–108. doi: 10.1109/IMBIOC.2018.8428941.Google Scholar
19.Cancer Research UK. Cancerreasearchuk.org, 2018. [Online]. Available at http://www.cancerreasearchuk.org.Google Scholar
20.Brain Tumor: Statistics | Cancer.Net. Cancer.Net, 2018. [Online]. Available at https://www.cancer.net/cancer-types/brain-tumor/statistics.Google Scholar
21.Brain tumor prognosis | The Brain Tumor Charity. Thebraintumourcharity.org, 2018. [Online]. Available at http://www.thebraintumourcharity.org.Google Scholar
22.Cardiff University. Cardiff University, 2018. [Online]. Available at https://www.cardiff.ac.uk/cancer-stem-cell/research/about-cancer-stem-cells.Google Scholar
23.The Stem Cell Theory of Cancer | Ludwig Center | Stanford Medicine. Med.stanford.edu, 2018. [Online]. Available at https://med.stanford.edu/ludwigcenter/overview/theory.html.Google Scholar
24.MicroPulser™ Electroporator | Life Science Research | Bio-Rad. Bio-rad.com, 2018. [Online]. Available at http://www.bio-rad.com/en-uk/product/micropulser-electroporator?ID=83527990-34fb-4b33-b955-ca53b57bf8b9.Google Scholar
25.Electroporators | VWR. Uk.vwr.com, 2018. [Online]. Available at https://uk.vwr.com/store/product/2993634/electroporators.Google Scholar
26.BTX™ ECM™ 399 Exponential Decay Wave Electroporator. Fisher Scientific, 2018. [Online]. Available at https://www.fishersci.be/shop/products/btx-harvard-apparatus-ecm-399-exponential-decay-wave-electroporator/15427220.Google Scholar
27.FID GmbH – Products – FPG-N Series – Nanosecond High Voltage Pulsers. Fidtechnology.com, 2018. [Online]. Available at http://www.fidtechnology.com/products/fpg-nanosecond.html.Google Scholar
28.High Voltage Pulse Generators & Pulsers | Directed Energy. Directedenergy.com, 2018. [Online]. Available at https://directedenergy.com/high-voltage-pulsers/.Google Scholar
29.Avtech Electrosystems Ltd. Avtechpulse.com, 2018. [Online]. Available http://www.avtechpulse.com/?gclid=EAIaIQobChMI-eagoo3e3gIVBbftCh0AgwzSEAAYAiAAEgIJHPD_BwE.Google Scholar
30.M. Inc. High Voltage Power Supplies｜Matsusada Precision Inc. Matsusada.com, 2018. [Online]. Available at https://www.matsusada.com/lp/psel/hvps.html?gclid=EAIaIQobChMI-eagoo3e3gIVBbftCh0AgwzSEAAYASAAEgJBo_D_BwE.Google Scholar
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, 15312–15325. doi: 10.18632/oncotarget.24521.Google Scholar
32.Google Scholar. Scholar.google.co.uk, 2019. [Online]. Available at https://scholar.google.co.uk/scholar?q=nanosecond+high+voltage+pulse+generator+electroporation&hl=en&as_sdt=0%2C5&as_ylo=2017&as_yhi=2020.Google Scholar
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, 820–825.Google Scholar
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, 1192–1197.Google Scholar
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. 423–428. Vol. 1.Google Scholar
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, 1048–1054.Google Scholar
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, 607–613.Google Scholar
38.Reberšek, M and Miklavčič, D (2011) Advantages and disadvantages of different concepts of electroporation pulse generation. Automatika 52, 12–19.Google Scholar
39.C2M1000170D, Silicon Carbide Power MOSFET C2M MOSFET Technology (2015) N-Channel Enhancement Mode. Cree, pp. 1–11. Available at https://www.wolfspeed.com/downloads/dl/file/id/173/product/13/c2m1000170d.pdf.Google Scholar
40.GT40WR21, Silicon N-Channel IGBT. TOSHIBA, 2018 [Online]. Available at https://docs-emea.rs-online.com/webdocs/1436/0900766b81436c34.pdf.Google Scholar
41.TSC5802D, High Voltage Fast-Switching NPN Power Transistor. Taiwan Semiconductor, 2018 [Online]. Available at https://docs-emea.rs-online.com/webdocs/1445/0900766b81445ef6.pdf.Google Scholar
42.TLP352, TLP352F Photocouplers, GaAlAs Infrared LED & Photo IC. TOSHIBA, 2011, pp. 1–21.Google Scholar
43.Boylestad, R, Nashelsky, L and Li, L (1998) Electronic Devices and Circuit Theory, 7th Edn. New Jersey: Prentice Hall.Google Scholar
44.Severns, R (1985) Siliconix Power Application Handbook. Santa Clara, California: Siliconix incorporated.Google Scholar
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, 1182–1190.Google Scholar
46.C2M1000170D 1000mΩ 1700-V SiC MOSFET | Wolfspeed. Wolfspeed.com, 2018. [Online]. Available at https://www.wolfspeed.com/power/products/sic-mosfets/c2m1000170d.Google Scholar
47.FS40, FS Series Isolated, proportional DC to HV DC converters, XPPower, 2011, pp. 1–9.Google Scholar
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, 4079–4085.Google Scholar
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 https://zenodo.org/record/1157784#.Wm9N3a5l-po.Google Scholar
50.Gene Pulser®/MicroPulser™ Electroporation Cuvettes, 0.1cm gap #1652089 | Life Science Research | Bio-Rad. Bio-rad.com, 2018. [Online]. Available at http://www.bio-rad.com/en-uk/sku/1652089-gene-pulser-micropulser-electroporation-cuvettes-0-1-cm-gap.Google Scholar
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, 207–214.Google Scholar
52.Tektronix (2018) TDS5000B Series - Digital Phosphor Oscilloscopes Read This First | Tektronix, Tek.com, 2018. [Online]. Available: https://www.tek.com/oscilloscope/tds5054b-manual/tds5000b-series-1.Google Scholar
53.PPE 5kV (2018) Glasgow: Teledyne LeCroy, pp. 1–2. [Online]. Available at http://cdn.teledynelecroy.com/files/manuals/ppe_5kv_user_manual.pdf.Google Scholar
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.Google Scholar
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, 2015–2022.Google Scholar
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, 1022–1034.Google Scholar