Microchamber Setup Characterization for Nanosecond Pulsed Electric Field Exposure

Intracellular structures of biological cells can be disturbed by exposure to nanosecond pulsed electric field (nsPEF). A microchamber-based delivery system mounted on a microscope setup for real-time exposure to nsPEF is studied in this paper. A numerical and experimental characterization of the delivery system is performed both in frequency and time domains. The microchamber delivery system presents a high impedance compared to classical 50 Ω loads. Its frequency behavior and limits are investigated using an in-house finite-difference time-domain (FDTD) simulator and through experimental measurements. High-voltage measurements for two nsPEF generators are carried out. The applied pulse voltage measured across the microchamber electrodes is ~1 kV, corresponding to ~10 MV/m electric fields in the microchamber. Depending on the nsPEF generator used, the measured pulse durations are equal to 3.0 and 4.2 ns, respectively. The voltage distribution provided by FDTD simulations indicates a good level of homogeneity across the microchamber electrodes. Experimental results include permeabilization of biological cells exposed to 3.0-ns, 10-MV/m PEFs.

[1]  M. Jaroszeski,et al.  Clinical applications of electrochemotherapy. , 1999, Advanced drug delivery reviews.

[2]  Martin A. Gundersen,et al.  Scalable, compact, nanosecond pulse generator with a high repetition rate for biomedical applications requiring intense electric fields , 2009, 2009 IEEE Pulsed Power Conference.

[3]  Juergen F Kolb,et al.  Long‐lasting plasma membrane permeabilization in mammalian cells by nanosecond pulsed electric field (nsPEF) , 2007, Bioelectromagnetics.

[4]  Ravindra P. Joshi,et al.  Ultrashort electrical pulses open a new gateway into biological cells , 2004 .

[5]  M. Bureau,et al.  High-efficiency gene transfer into skeletal muscle mediated by electric pulses. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  Laura Marcu,et al.  Pulse generators for pulsed electric field exposure of biological cells and tissues , 2003 .

[7]  Allen Taflove,et al.  Computational Electrodynamics the Finite-Difference Time-Domain Method , 1995 .

[8]  Phumin Kirawanich,et al.  An FDTD Interaction Scheme of a High-Intensity Nanosecond-Pulsed Electric-Field System for In Vitro Cell Apoptosis Applications , 2010, IEEE Transactions on Plasma Science.

[9]  B. Veyret,et al.  Dosimetric analysis of a 900-MHz rat head exposure system , 2004, IEEE Transactions on Microwave Theory and Techniques.

[10]  Vincent Couderc,et al.  Microstrip-based nanosecond pulse generators: Numerical and circuital modeling , 2010, 2010 IEEE MTT-S International Microwave Symposium.

[11]  Laura Marcu,et al.  Fluorescence microscopy imaging of electroperturbation in mammalian cells. , 2006, Journal of biomedical optics.

[12]  Laura Marcu,et al.  In vitro and in vivo evaluation and a case report of intense nanosecond pulsed electric field as a local therapy for human malignancies , 2007, International journal of cancer.

[13]  J. Bérenger Three-Dimensional Perfectly Matched Layer for the Absorption of Electromagnetic Waves , 1996 .

[14]  Vincent Couderc,et al.  A 10-$\Omega$ High-Voltage Nanosecond Pulse Generator , 2010, IEEE Transactions on Microwave Theory and Techniques.

[15]  K. Yee Numerical solution of initial boundary value problems involving maxwell's equations in isotropic media , 1966 .

[16]  J. Weaver,et al.  Electroporation: A general phenomenon for manipulating cells and tissues , 1993, Journal of cellular biochemistry.

[17]  Damijan Miklavcic,et al.  Blumlein Configuration for High-Repetition-Rate Pulse Generation of Variable Duration and Polarity Using Synchronized Switch Control , 2009, IEEE Transactions on Biomedical Engineering.

[18]  Caterina Merla,et al.  Characterization of a 50-Ω Exposure Setup for High-Voltage Nanosecond Pulsed Electric Field Bioexperiments , 2011, IEEE Transactions on Biomedical Engineering.

[19]  Martin A Gundersen,et al.  Nanosecond electric pulse-induced calcium entry into chromaffin cells. , 2008, Bioelectrochemistry.

[20]  Fei Wang,et al.  Diode Opening Switch Based Nanosecond High Voltage Pulse Generators for Biological and Medical Applications , 2007, IEEE Transactions on Dielectrics and Electrical Insulation.

[21]  Laura Marcu,et al.  Ultrashort pulsed electric fields induce membrane phospholipid translocation and caspase activation: differential sensitivities of Jurkat T lymphoblasts and rat glioma C6 cells , 2003 .

[22]  Juergen F Kolb,et al.  Membrane permeabilization and cell damage by ultrashort electric field shocks. , 2007, Archives of biochemistry and biophysics.

[23]  R. O. Price,et al.  Plasma membrane voltage changes during nanosecond pulsed electric field exposure. , 2006, Biophysical journal.

[24]  L. Marcu,et al.  Electrode microchamber for noninvasive perturbation of mammalian cells with nanosecond pulsed electric fields , 2005, IEEE Transactions on NanoBioscience.

[25]  Laura Marcu,et al.  Nanosecond pulsed electric fields perturb membrane phospholipids in T lymphoblasts , 2004, FEBS letters.

[26]  H. Akiyama,et al.  Biological effects of narrow band pulsed electric fields , 2007, IEEE Transactions on Dielectrics and Electrical Insulation.

[27]  A. Kuthi,et al.  Compact Subnanosecond Pulse Generator Using Avalanche Transistors for Cell Electroperturbation Studies , 2007, IEEE Transactions on Dielectrics and Electrical Insulation.

[28]  H. Akiyama,et al.  250 kV sub-nanosecond pulse generator with adjustable pulse-width , 2007, IEEE Transactions on Dielectrics and Electrical Insulation.

[29]  Allen Taflove,et al.  FD-TD modeling of digital signal propagation in 3-D circuits with passive and active loads , 1994 .

[30]  T. Heeren,et al.  The Effect of Intense Subnanosecond Electrical Pulses on Biological Cells , 2008, IEEE Transactions on Plasma Science.

[31]  Juergen F Kolb,et al.  Nanosecond pulsed electric field generators for the study of subcellular effects , 2006, Bioelectromagnetics.

[32]  K. Schoenbach,et al.  Submicrosecond intense pulsed electric field effects on intracellular free calcium: mechanisms and effects , 2004, IEEE Transactions on Plasma Science.

[33]  S. Hagness,et al.  Quantification of electroporative uptake kinetics and electric field heterogeneity effects in cells. , 2008, Biophysical journal.

[34]  Vincent Couderc,et al.  Kilovolt, Nanosecond, and Picosecond Electric Pulse Shaping by Using Optoelectronic Switching , 2010, IEEE Photonics Technology Letters.

[35]  A. Kuthi,et al.  A linear, single-stage, nanosecond pulse generator for delivering intense electric fields to biological loads , 2009, IEEE Transactions on Dielectrics and Electrical Insulation.

[36]  Bernard Jecko,et al.  Modelling of dielectric losses in microstrip patch antennas: application of FDTD method , 1992 .

[37]  Jean-Pierre Berenger,et al.  A perfectly matched layer for the absorption of electromagnetic waves , 1994 .

[38]  M. Rols,et al.  Mechanisms of cell membrane electropermeabilization: a minireview of our present (lack of ?) knowledge. , 2005, Biochimica et biophysica acta.

[39]  Shu Xiao,et al.  Bioelectric Effects of Intense Nanosecond Pulses , 2007, IEEE Transactions on Dielectrics and Electrical Insulation.

[40]  P. Thomas Vernier,et al.  Cardiac myocyte excitation by ultrashort high-field pulses. , 2009, Biophysical journal.