Skip to main content Accessibility help
×
Home

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)...

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.

Copyright

Corresponding author

Author for correspondence: I. W. Davies, E-mail: eeu25b@bangor.ac.uk

References

Hide All
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. Btxonline.com, 2018. [Online]. Available at https://www.btxonline.com/media/wysiwyg/education_page/Electroporation%20Optimization%20Guide.pdf.
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. Cancerreasearchuk.org, 2018. [Online]. Available at http://www.cancerreasearchuk.org.
20.Brain Tumor: Statistics | Cancer.Net. Cancer.Net, 2018. [Online]. Available at https://www.cancer.net/cancer-types/brain-tumor/statistics.
21.Brain tumor prognosis | The Brain Tumor Charity. Thebraintumourcharity.org, 2018. [Online]. Available at http://www.thebraintumourcharity.org.
22.Cardiff University. Cardiff University, 2018. [Online]. Available at https://www.cardiff.ac.uk/cancer-stem-cell/research/about-cancer-stem-cells.
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.
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.
25.Electroporators | VWR. Uk.vwr.com, 2018. [Online]. Available at https://uk.vwr.com/store/product/2993634/electroporators.
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.
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.
28.High Voltage Pulse Generators & Pulsers | Directed Energy. Directedenergy.com, 2018. [Online]. Available at https://directedenergy.com/high-voltage-pulsers/.
29.Avtech Electrosystems Ltd. Avtechpulse.com, 2018. [Online]. Available http://www.avtechpulse.com/?gclid=EAIaIQobChMI-eagoo3e3gIVBbftCh0AgwzSEAAYAiAAEgIJHPD_BwE.
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.
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 https://www.wolfspeed.com/downloads/dl/file/id/173/product/13/c2m1000170d.pdf.
40.GT40WR21, Silicon N-Channel IGBT. TOSHIBA, 2018 [Online]. Available at https://docs-emea.rs-online.com/webdocs/1436/0900766b81436c34.pdf.
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.
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. Wolfspeed.com, 2018. [Online]. Available at https://www.wolfspeed.com/power/products/sic-mosfets/c2m1000170d.
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 https://zenodo.org/record/1157784#.Wm9N3a5l-po.
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.
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, Tek.com, 2018. [Online]. Available: https://www.tek.com/oscilloscope/tds5054b-manual/tds5000b-series-1.
53.PPE 5kV (2018) Glasgow: Teledyne LeCroy, pp. 12. [Online]. Available at http://cdn.teledynelecroy.com/files/manuals/ppe_5kv_user_manual.pdf.
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.

Keywords

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed