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Non-Invasive Picosecond Pulse System for Electrostimulation

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Non-Invasive Picosecond Pulse System for Electrostimulation Old Dominion University ODU Digital Commons Electrical & Computer Engineering Theses & Dissertations Electrical & Computer Engineering Spring 2018 Non-Invasive Picosecond Pulse System for Electrostimulation Ross Aaron Petrella Old Dominion University, [email protected] Follow this and additional works at: https://digitalcommons.odu.edu/ece_etds Part of the Biomedical Engineering and Bioengineering Commons, and the Electromagnetics and Photonics Commons Recommended Citation Petrella, Ross A.. "Non-Invasive Picosecond Pulse System for Electrostimulation" (2018). Doctor of Philosophy (PhD), Dissertation, Electrical & Computer Engineering, Old Dominion University, DOI: 10.25777/ystf-ry94 https://digitalcommons.odu.edu/ece_etds/29 This Dissertation is brought to you for free and open access by the Electrical & Computer Engineering at ODU Digital Commons. It has been accepted for inclusion in Electrical & Computer Engineering Theses & Dissertations by an authorized administrator of ODU Digital Commons. For more information, please contact [email protected]. NON-INVASIVE PICOSECOND PULSE SYSTEM FOR ELECTROSTIMULATION by Ross Aaron Petrella B.S. May 2014, Virginia Commonwealth University A Dissertation Submitted to the Faculty of Old Dominion University in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY BIOMEDICAL ENGINEERING OLD DOMINION UNIVERSITY May 2018 Approved by: Shu Xiao (Director) Dean Krusienski (Member) Shirshak Dhali (Member) Patrick Sachs (Member) ABSTRACT NON-INVASIVE PICOSECOND PULSE SYSTEM FOR ELECTROSTIMULATION Ross Aaron Petrella Old Dominion University, 2018 Director: Dr. Shu Xiao Picosecond pulsed electric fields have been shown to have stimulatory effects, such as calcium influx, activation of action potential, and membrane depolarization, on biological cells. Because the pulse duration is so short, it has been hypothesized that the pulses permeate a cell and can directly affect intracellular cell structures by bypassing the shielding of the membrane. This provides an opportunity for studying new biophysics. Furthermore, radiating picosecond pulses can be efficiently done by a compact antenna because the antenna size is comparable to the pulse width. However, all of the previous bioelectric studies regarding picosecond pulses have been conducted in vitro, using electrodes. There is not yet a device which can non-invasively deliver picosecond-pulsed electric fields to neurological tissue for therapeutic applications. It is unclear whether a radiated electric field at a given penetration depth can reach the threshold to cause biological effects. In this dissertation, a picosecond- pulsed electric field system designed for the electrosimulation of neural cells is presented. This begins with the design of an ultra- wideband biconical dielectric rod antenna. It consists of a dielectrically loaded V-conical launcher which feeds a cylindrical waveguide. The waveguide then transitions into a taper, which acts like a lens to focus the energy in the tissue target. To describe the antenna delivery of picosecond pulses to tissues, the initial performance was simulated using a 3-layer tissue model and then a human head model. The final model was shown iii to effectively deliver pulses of 11.5 V/m to the brain for a 1 V input. The spot size of the stimulation is on the order of 1 cm. The electric field was able to penetrate to a depth of 2 cm, which is equal to the pulse width of a 200 ps pulse. The antenna was constructed and characterized in free space in time domain and in frequency domain. The experimental results have a good agreement with the simulation. The ultimate biological application relies on adequate electric field. To reach a threshold electric field for effective stimulation, the antenna should be driven by a high voltage, picosecond-pulsed power supply, which, in our case, consists of a nanosecond charging transformer, a parallel-plate transmission line, and a picosecond discharging switch. This transformer was used to charge a parallel-plate transmission line, with the antenna as the load. To generate pulses with a rise time of hundreds of picoseconds, an oil switch with a millimeter gap was used. For the charging, a dual resonance pulse transformer was designed and constructed. The novel aspect of this transformer is has a fast charge time. It was shown to be capable of producing over 100 kV voltages in less than 100 ns. After the closing of the peaking switch and the picosecond rise time generation, the antenna was able to create an electric field of 600 V/cm in the air at a distance of 3 cm. This field was comparable to the simulation. Higher voltage operation was met with dielectric breakdown across the insulation layer that separates the high voltage side and the ground side. Before the designed antenna is used in vivo, it is critical to determine the biological effect of picosecond pulses. This is especially important if we focus on stimulatory effects, which require that the electric field intensity be close to the range that the antenna system can deliver. Toward that end, neural stem cells were chosen to study iv for the proliferation, metabolism, and gene expression. Instead of using the antenna, the electrodes were used to deliver the pulses to the cells. In order to treat enough cells for downstream analyses, the electrodes were mounted on a 3-D printer head, which could be moved freely and could be controlled accurately by programming. The results show that pulses on the order of 20 kV/cm affect the proliferation, metabolism, and gene expression of both neural and mesenchymal stem cells, without reducing viability. In general, we came to the conclusion that picosecond pulses can be a useful stimulus for a variety of applications, but the possibility of using antennas to directly stimulate tissue functions relies on the development of a pulsed power system, high voltage insulation, and antenna material. v Copyright, 2018, by Ross Aaron Petrella, All Rights Reserved. vi This dissertation is dedicated to my parents Ralph and Laura Petrella. vii ACKNOWLEDGMENTS Along my journey, I have received help from many people whom I would like to personally acknowledge. First is my adviser, Dr. Shu Xiao. Thank you for your guidance, your instruction, and our many discussions. You have made my experience one of joy in discovery. I also extend my deepest appreciation to my committee members Dr. Dean Krusienski, Dr. Shirshak Dhali, and Dr. Patrick Sachs for sharing their insight and for their interest in my work. Next, I would like to acknowledge my colleagues in the Pulse Power and Antenna Lab as well as in the Molecular Diagnostics Lab, especially Khiem Huynh, Dr. Peter Mollica, and Martina Zamponi. Thank you for your help over many long hours. Finally, I would like to thank all of those people who loved and supported me along the way. This includes Vance Petrella, Rebecca Petrella, and Shani Levit. viii NOMENCLATURE V Electric Potential, V I Current, A PEF Pulsed Electric Field, (No Units) psPEF Picosecond Pulsed Electric Field, (No Units) E Electric Field, V/m C Capacitance, F L Inductance, H k Coupling Coefficient, (No Units) ω Angular Frequency, Rad/s f Frequency, Hz λ Wavelength, m τ Charge Time, s ix TABLE OF CONTENTS Page LIST OF TABLES .............................................................................................................. x LIST OF FIGURES ........................................................................................................... xi 1. INTRODUCTION: FOUNDATIONS OF PICOSECOND ELECTRIC FIELDS ......... 1 1.1 PICOSECOND PULSED ELECTRIC FIELD EFFECTS ............................... 1 1.2 ANTENNAS FOR PICOSECOND STIMULATION OF TISSUE ................. 6 1.3 TOPIC OF THE DISSERTATION .................................................................. 9 2. BICONICAL DIELECTRIC ROD ANTENNA ........................................................... 11 2.1 ELECTROMAGNETIC WAVES IN TISSUE ............................................. 12 2.2 AN IN VIVO BICONICAL DIELECTRIC ROD ANTENNA DESIGN ...... 15 2.3 ANTENNA CONSTRUCTION AND CHARACTERIZATION .................. 34 3. DUAL RESONANCE PULSE TRANSFORMER POWER SUPPLY ........................ 42 3.1 THE DUAL RESONANCE CIRCUIT ........................................................... 43 3.2 AN ULTRAFAST CHARGE TIME PULSE TRANSFORMER ................... 46 3.3 OTHER PULSE TRANSFORMER CONSTRUCTION................................ 60 3.4 COMBINED ANTENNA AND TRANSFORMER SYSTEM ...................... 61 4. STIMULATION OF NEURAL STEM CELLS ........................................................... 68 4.1 A 3-D PRINTER SYSTEM FOR PULSE STIMULATION .......................... 69 4.2 BIOLOGICAL ASSAYS ................................................................................ 75 4.3 DISCUSSION OF BIOLOGICAL RESULTS ............................................... 84 5. ASSESMENT OF NON-CONTACT PICOSECOND PULSES .................................. 89 5.1 COMPARISON OF EXPERIMENTS ............................................................ 89 5.2 A PATH FOR THE BICONICAL DIELECTRIC ROD ANTENNA ............ 91 6. CONCLUSIONS........................................................................................................... 94 6.1 FUTURE DIRECTIONS ................................................................................ 94 6.2 SUMMARY OF WORK................................................................................. 95 REFERENCES ................................................................................................................
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