[Show abstract][Hide abstract] ABSTRACT: The objective was to use carbon nanotubes (CNT) coupled with near-infrared radiation (NIR) to induce hyperthermia as a novel non-ionizing radiation treatment for primary brain tumors, glioblastoma multiforme (GBM). In this study, we report the therapeutic potential of hyperthermia-induced thermal ablation using the sequential administration of carbon nanotubes (CNT) and NIR. In vitro studies were performed using glioma tumor cell lines (U251, U87, LN229, T98G). Glioma cells were incubated with CNTs for 24 h followed by exposure to NIR for 10 min. Glioma cells preferentially internalized CNTs, which upon NIR exposure, generated heat, causing necrotic cell death. There were minimal effects to normal cells, which correlate to their minimal uptake of CNTs. Furthermore, this protocol caused cell death to glioma cancer stem cells, and drug-resistant as well as drug-sensitive glioma cells. This sequential hyperthermia therapy was effective in vivo in the rodent tumor model resulting in tumor shrinkage and no recurrence after only one treatment. In conclusion, this sequence of selective CNT administration followed by NIR activation provides a new approach to the treatment of glioma, particularly drug-resistant gliomas.
[Show abstract][Hide abstract] ABSTRACT: In this work two-photon absorption laser-induced fluorescence was used to measure oxygen atom (O) concentrations in streamer discharge afterglow in a variety of fuel/air mixtures in order to account for the O reaction pathways in transient plasma ignition. It is demonstrated that O atoms are generated in high concentration (~5 × 1017 cm−3) directly below the high-voltage anode in a point-to-plane geometry. The corresponding lifetimes in air were on the order of hundreds of microseconds. Fuel chemistry provides consumption pathways via chain branching reactions even without sustained combustion, and the corresponding O-atom lifetimes were much shorter than in air and dependent on the fuel concentration. At the richest conditions, corresponding to a fuel–air equivalence ratio of 2.4, O lifetimes were on the order a few microseconds or less. These experimental results are compared to modelling estimates in order to better understand the role of atomic oxygen in the chemical processes leading to ignition.
Journal of Physics D Applied Physics 07/2013; 46(30):305202. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Achieving effective ignition of reacting mixtures using nanosecond pulsed discharge non-equilibrium transient plasma (TP), requires that the effects of several experimental parameters be quantified and understood. Among them are the electrode geometry, the discharge location especially in non-premixed systems, and the relative ignition performance by spark and TP under the same experimental conditions. In the present investigation, such issues were addressed experimentally using a cylindrical constant volume combustion chamber and a counterflow flame configuration coupled with optical shadowgraph that enables observation of how and where the ignition process starts. Results were obtained under atmospheric pressure and showed that the electrode geometry has a notable influence on ignition, with the needle-to-semicircle exhibiting the best ignition performance. Furthermore, it was determined that under non-premixed conditions discharging TP in the reactants mixing layer was most effective in achieving ignition. It was also determined that in the cases considered, the TP induced ignition initiates from the needle head where the electric field and electron densities are the highest. In the case of a spark, however, ignition was found to initiate always from the hot region between the two electrodes. Comparison of spark and TP discharges in only air (i.e. without fuel) and ignition phenomena induced by them also suggest that in the case of TP ignition is at least partly non-thermal and instead driven by the production of active species. Finally, it was determined that single pulsed TP discharges are sufficient to ignite both premixed and non-premixed flames of a variety of fuels ranging from hydrogen to heavy fuels including F-76 diesel and IFO380 bunker fuel even at room temperature.
Journal of Physics D Applied Physics 05/2013; 46(20):205201. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pulsed electric fields are used to permeabilize cell membranes in biotechnology and the clinic. Although molecular and continuum models provide compelling representations of the mechanisms underlying this phenomenon, a clear structural link between the biomolecular transformations displayed in molecular dynamics (MD) simulations and the micro- and macroscale cellular responses observed in the laboratory has not been established. In this paper, plasma membrane electropermeabilization is characterized by exposing Jurkat T lymphoblasts to pulsed electric fields less than 10ns long (including single pulse exposures), and by monitoring the resulting osmotically driven cell swelling as a function of pulse number and pulse repetition rate. In this way, we reduce the complexity of the experimental system and lay a foundation for gauging the correspondence between measured and simulated values for water and ion transport through electropermeabilized membranes. We find that a single 10 MV/m pulse of 5ns duration produces measurable swelling of Jurkat T lymphoblasts in growth medium, and we estimate from the swelling kinetics the ion and water flux that follows the electropermeabilization of the membrane. From these observations we set boundaries on the net conductance of the permeabilized membrane, and we show how this is consistent with model predictions for the conductance and areal density of nanoelectropulse-induced lipid nanopores.
Biochimica et Biophysica Acta 04/2013; 1828:1715-1722. · 4.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nanosecond scale pulsed high voltage discharges in air/fuel mixtures can generate radicals which in turn have been shown to improve combustion efficiency in gasoline fueled internal combustion engines. We are exploring the possibility to extend such transient plasma generation and expected radical species generation to the range of pressures encountered in compression-ignition (diesel) engines having compression ratios of ~20:1, thereby improving lean burning efficiency and extending the range of lean combustion. Our preliminary experiments on streamer propagation velocities have shown deviations from simple (pd = const.) based similarity law in the pressure range of 1-8 bar in synthetic air . Here we report the results of streamer propagation experiments in the extended range of air pressures, 6-18 bar. In order to extend our work to 18 bar, the gap size is reduced to 1.75 mm. Optical data obtained from PI-MAX 3 ICCD camera is complemented with electrical measurements to deduce average streamer velocities.
Pulsed Power Conference (PPC), 2013 19th IEEE; 01/2013
[Show abstract][Hide abstract] ABSTRACT: Pulsed electric field permeabilization of living cell membranes forms the basis for widely used biotechnology protocols and an increasing number of therapeutic applications. Experimental observations of artificial membranes and whole cells and molecular and analytical models provide evidence that a membrane-spanning, hydrophilic, conductive pore can form in nanoseconds. An external electric field lowers the energy barrier for this stochastic process, reducing the mean time for pore formation and increasing the pore areal density. Molecular dynamic simulations reveal the key role played by interfacial water in electropermeabilization. These model systems, validated in the laboratory, are deepening our understanding of the factors governing pore initiation, construction, and lifetime, knowledge that will translate to enhanced utilization of this method in biomedicine and bioengineering.
Proceedings of the IEEE 01/2013; 101(2):494-504. · 6.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The use of nonequilibrium plasma generated by nanosecond discharges to ignite fuel/air mixtures, known as transient plasma ignition (TPI), has been shown to effectively reduce ignition delay and improve engine performance relative to spark ignition for combustion engines. While this method is potentially useful for many engine applications, at present the underlying physics are poorly understood. This work uses coherent anti-Stokes Raman spectroscopy (CARS) to measure the rotational and vibrational excitation of nitrogen molecules in the discharge afterglow in a variety of fuel/air mixtures outside the limits of combustion in order to elucidate the thermal behaviour of TPI. The time evolution of relative populations of vibrationally excited states of nitrogen in the electronic ground state are reported for each gas mixture; it is shown that generation of these vibrationally excited states is inefficient during the discharge in air but that generation occurs at a high rate roughly 5 µs following the discharge; with the addition of fuels vibrationally excited states are observed during the discharge but an increase in population is still seen at 5 µs. Possible mechanisms for this behaviour are discussed. In addition, rotational temperature increases of at least 500 K are reported for all gas mixtures. The effect of this temperature increase on ignition, reaction rates, and thermal energy pathways are discussed.
Journal of Physics D Applied Physics 11/2012; 45(49):495401. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Understanding of the dynamics of nanosecond scale pulse discharges in
air at multiatmospheric pressure is essential for the development of
transient plasma enhanced combustion in internal combustion engines.
Here we report the result of our experimental investigation of
cathode-directed streamer discharges in synthetic air at pressures
ranging from 1 to 20 bar. Two pulse generators with maximum pulse
amplitudes of 50 kV and 65 kV, pulse width of approximately 12 ns and 85
ns and pulse rise times of 5 ns and 50 ns are used to generate
streamers. The electrodes are coaxial with various radial gaps up to
11.75 mm. The discharge chamber is evacuated and backfilled with
synthetic dry air at room temperature. Optical data is obtained from
PI-MAX 3 ICCD camera with 3 ns gate width. The streamer propagation
velocity variation with applied voltage, different pressures and reduced
electric field, E/P, will be shown. Preliminary results indicate that
the (pd) similarity law is violated at high pressures in agreement with
other recent experiments .[4pt]  ``Nanosecond Scale Discharge
Dynamics in High Pressure Air,'' Pierre Tardiveau, Nicolas Moreau,
Francois Jorand, Christian Postel, St'ephane Pasquiers, and Pierre
Vervisch, IEEE Trans. on Plasma Sci., Vol. 36, No. 4, 2008.
[Show abstract][Hide abstract] ABSTRACT: Pseudospark switches have been successfully employed in a variety of pulsed power applications including high-power electron beam sources, high-power microwaves, and transient plasma ignition for pulsed detonation engines. For applications such as these, advances that improve and simplify triggering are important. Here, magnesium was investigated as a photocathode candidate for optically triggered pseudospark switches, also called back-lighted thyratrons (BLTs). A Mg foil on the back surface of a copper BLT cathode reduced trigger delay and jitter by one order of magnitude when a 5 ns, 3 mJ light pulse at 266-nm wavelength was incident at the back of the cathode at a constant switch voltage of 4.1 kV. Delays less than 150 ns were obtained. An increased photoemission due to the lower work function of magnesium is considered as the main reason for the improvement in trigger delay and jitter for the BLT system. Mg-based cathodes are promising for development of compact optical triggering units with low optical energy sources for BLTs.
[Show abstract][Hide abstract] ABSTRACT: Nanosecond pulsed electric fields (nsPEF) induce apoptotic pathways in human cancer cells. The potential therapeutic effective of nsPEF has been reported in cell lines and in xenograft animal tumor model. The present study investigated the ability of nsPEF to cause cancer cell death in vivo using carcinogen-induced animal tumor model, and the pulse duration of nsPEF was only 7 and 14 nano second (ns). An nsPEF generator as a prototype medical device was used in our studies, which is capable of delivering 7-30 nanosecond pulses at various programmable amplitudes and frequencies. Seven cutaneous squamous cell carcinoma cell lines and five other types of cancer cell lines were used to detect the effect of nsPEF in vitro. Rate of cell death in these 12 different cancer cell lines was dependent on nsPEF voltage and pulse number. To examine the effect of nsPEF in vivo, carcinogen-induced cutaneous papillomas and squamous cell carcinomas in mice were exposed to nsPEF with three pulse numbers (50, 200, and 400 pulses), two nominal electric fields (40 KV/cm and 31 KV/cm), and two pulse durations (7 ns and 14 ns). Carcinogen-induced cutaneous papillomas and squamous carcinomas were eliminated efficiently using one treatment of nsPEF with 14 ns duration pulses (33/39 = 85%), and all remaining lesions were eliminated after a 2nd treatment (6/39 = 15%). 13.5% of carcinogen-induced tumors (5 of 37) were eliminated using 7 ns duration pulses after one treatment of nsPEF. Associated with tumor lysis, expression of the anti-apoptotic proteins Bcl-xl and Bcl-2 were markedly reduced and apoptosis increased (TUNEL assay) after nsPEF treatment. nsPEF efficiently causes cell death in vitro and removes papillomas and squamous cell carcinoma in vivo from skin of mice. nsPEF has the therapeutic potential to remove human squamous carcinoma.
PLoS ONE 01/2012; 7(8):e43891. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A pulsed, tapered cylindrical plasma jet, several centimeter long and
<2 mm in diameter, has been generated by a concentric tubular device
for root canal disinfection. This plasma dental probe is typically
powered with ˜100 ns, 1 kHz, multi-kilovolt electric pulses and
filled with 5 SLPM (standard liter per minute) He/(1%)O2
flow. We report here an in vitro study of the antimicrobial effect of
the room temperature plasma jet against monolayer Enterococcus faecalis
biofilms on bovine dentins. Resultant colony-forming unit counts were
associated with changes in bacterial cell morphology observed using
scanning electron microscopy (SEM) following the treatment and control.
Treatment of dentin discs cultivated with E. faecalis monolayer biofilms
with the plasma (average power ≈ 1 W) for 5 min resulted in 92.4%
kill (P < 0.0001). Severe disruption of the cell membranes was
observed for the plasma treatment group, while the morphology of the
cells remained intact for the negative control group. In addition, a
pilot ex vivo test was conducted to examine the bactericidal effect of
the plasma against saliva-derived biofilms cultivated in human root
canals. Conspicuous biofilm disruption and cleared dentinal surfaces
were observed in the canal after the plasma treatment for 5 min. We
conclude that this non-thermal pulsed plasma-based technology is a
potential alternative or supplement to existing protocols for root
Plasma for Bio-Decontamination, Medicine and Food Security. 01/2012;
[Show abstract][Hide abstract] ABSTRACT: Rapid pulsing from high voltage, high current pulsed power supplies is challenging for a number of reasons, chief among them is the lack of solid state switches capable of switching desired voltage and current with sufficiently fast turn on and turn off times. To address this issue, a switching system composed of power MOSFETs arranged in a cascode configuration has been developed. This system is capable of switching 500 V at 1 kA with turn on time less than 10 ns and a maximum di/dt of 1×1010 A/s. It has been used as the primary switch in multiple pulse generators and has operated at pulsed repetition rates as high as 100 kHz. In these initial tests, repetition rate was limited only by the charging circuitry. Given sufficiently robust charging, this design is capable of operating at repetition rates as high as 1 MHz in an architecture that produces 10 kV, 5 ns pulses. The first prototype of this system has been completed and characterized; the results from measurements designed to extract time resolved switch parasitics are reported. In light of the successful implementation of this prototype, design of the next iteration of this modular cascade switch is planning stages. Emphasis is placed on usability, with the intention of producing a fully shielded “black box” that is easily integrated into the front end switching system of existing pulsed power supplies.
Power Modulator and High Voltage Conference (IPMHVC), 2012 IEEE International; 01/2012
[Show abstract][Hide abstract] ABSTRACT: The use of streamers for the ignition of fuels, also known as transient
plasma ignition (TPI), has been shown in a variety of engines to improve
combustion through decreased ignition delay, increased lean burn
capability and increased energy release relative to conventional spark
ignition. The mechanisms behind these improvements, however, remain
poorly understood. Temperature measurements by optical emission
spectroscopy demonstrate that ignition by TPI is a nonthermal process,
and thus is almost entirely dependent on the production and presence of
electron impact-created active species in the discharge afterglow. Of
particular interest are active oxygen species due to their relatively
long lifetimes at high pressures and the pivotal role they play in
combustion reactions. In order to elucidate the oxygen pathways, here we
report the investigation of the temporal evolution of the populations of
atomic oxygen and ozone by use of two-photon absorption laser induced
fluorescence (TALIF) and UV absorption, respectively. Experimental
results are presented and compared to kinetic modeling of the streamers.
Future experiments are proposed to better understand the physics behind
[Show abstract][Hide abstract] ABSTRACT: Nanosecond, high-voltage electric pulses (nsEP) induce permeabilization of the plasma membrane and the membranes of cell organelles, leading to various responses in cells including cytochrome c release from mitochondria and caspase activation associated with apoptosis. We report here evidence for nsEP-induced permeabilization of mitochondrial membranes in living cells. Using three different methods with fluorescence indicators-rhodamine 123 (R123), tetramethyl rhodamine ethyl ester (TMRE), and cobalt-quenched calcein-we have shown that multiple nsEP (five pulses or more, 4 ns duration, 10 MV/m, 1 kHz repetition rate) cause an increase of the inner mitochondrial membrane permeability and an associated loss of mitochondrial membrane potential. These effects could be a consequence of nsEP permeabilization of the inner mitochondrial membrane or the activation of mitochondrial membrane permeability transition pores. Plasma membrane permeabilization (YO-PRO-1 influx) was detected in addition to mitochondrial membrane permeabilization.
[Show abstract][Hide abstract] ABSTRACT: Pulsed electric fields with nanosecond duration and high amplitude have effects on biological subjects and bring new venue in disease diagnosis and therapy. To address this respect, we investigated the responses of paired tumor and normal human skin cells - a basal cell carcinoma (BCC) cell line, and its sister normal cell line (TE) - to nanosecond, megavolt-per-meter pulses. When BCC (TE 354.T) and TE (TE 353.SK) cells, cultured under standard conditions, were exposed to 30 ns, 3 MV/m, 50 Hz pulses and tested for membrane permeabilization, viability, morphology, and caspase activation, we found that nanoelectropulse exposure: 1) increased cell membrane permeability in both cell lines but to a greater extent in BCC cells than in normal cells; 2) decreased cell viabilities with BCC cells affected more than normal cells; 3) induced morphological changes in both cell lines including condensed and fragmented chromatin with enlarged nuclei; 4) induced about twice as much caspase activation in BCC cells compared to normal cells. We concluded that in paired tumor and normal skin cell lines, the response of the tumor cells to nanoelectropulse exposure is stronger than the response of normal cells, indicating the potential for selectivity in therapeutic applications.
Technology in cancer research & treatment 06/2011; 10(3):281-6. · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pseudospark switches have been successfully employed in a variety of pulsed power applications including high power electron beam sources, high power microwaves, and transient plasma ignition for pulsed detonation engines [1-3]. Investigation of magnesium, copper and molybdenum photocathode candidates for optically triggered pseudospark switches, also called back-lighted thyratrons (BLTs), has shown that magnesium has a higher quantum efficiency (up to 1.5×10-5) under BLT-relevant pressure conditions, compared to copper or molybdenum . Magnesium, copper and molybdenum-based BLT cathodes were experimentally studied. A compact UV laser with an intensity of 3 mJ, and optical power density of 8.5×106 W/cm2 per pulse was used as the optical triggering source for these studies. It was demonstrated that both the delay and the jitter of the switch were shortened more than an order of magnitude when the Mg foil was present at the cathode. The electron emission mechanisms contributing to this improvement in delay and jitter for the BLT system are discussed.
[Show abstract][Hide abstract] ABSTRACT: The effects of nanoelectropulses on intracellular structures are reported in this work. The real-time investigation is performed by means of a system consisting of a fluorescence microscope, an EMCCD camera and a photomultiplier tube.
[Show abstract][Hide abstract] ABSTRACT: form only given. The use of streamers for the ignition of fuels, also known as transient plasma ignition (TPI), has been shown in a variety of engines to improve combustion through decreased ignition delay and increased energy release relative to conventional spark ignition. The mechanisms behind these improvements, however, remain poorly understood. Of particular interest are the relative roles of thermal effects of the streamer afterglow compared to electronically excited species in initiating combustion. Here we report investigation of gas heating due to dissociation, relaxation, and recombination of active plasma species and present temperature measurements in the afterglow of the streamers by using a second probing discharge in conjunction with optical emission spectroscopy. Experimental results are presented and compared to modeling of the streamers. Future experiments are proposed to better understand the role of streamer kinetics in TPI.
IEEE International Conference on Plasma Science 01/2011;
[Show abstract][Hide abstract] ABSTRACT: In this paper athree-stage pulse generator architecture capable of generating high voltage, high current pulses is reported and system issues are presented. Design choices and system dynamics are explained both qualitatively and quantitatively with discussion sections followed by the presentation of closed-form expressions and numerical analysis that provide insight into the system’s operation. Analysis targeted at optimizing performance focuses on diode opening switch pumping, energy efficiency, and compensation of parasitic reactances. A compact system based on these design guidelines has been built to output 8 kV, 5 ns pulses into 50 Ω. Output risetimes below 1 ns have been achieved using two different compression techniques. At only 1.5 kg, this light and compact system shows promise for a variety of pulsed power applications requiring the long lifetime, low jitter performance of a solid state pulse generator that can produce fast, high voltage pulses at high repetition rates.
IEEE Transactions on Dielectrics and Electrical Insulation 01/2011; 18(4):1228-1235. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transient plasma ignition, a method of fuel-air ignition involving streamer discharges produced by nanosecond high-voltage pulses, is attractive, and that it reduces ignition delay, increases the burning rate, and can ignite leaner mixtures compared with the traditional spark ignition. In this paper, images of the transient plasma discharges and subsequent flame development in a C2H4-air mixture were captured using a single-lens reflex camera and a high-speed camera, respectively.