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Articles 1 - 16 of 16
Full-Text Articles in Biomedical
Peculiarities Of Neurostimulation By Intense Nanosecond Pulsed Electric Fields: How To Avoid Firing In Peripheral Nerve Fibers, Vitalii Kim, Emily Gudvangen, Oleg Kondratiev, Luis Redondo, Shu Xiao, Andrei G. Pakhomov
Peculiarities Of Neurostimulation By Intense Nanosecond Pulsed Electric Fields: How To Avoid Firing In Peripheral Nerve Fibers, Vitalii Kim, Emily Gudvangen, Oleg Kondratiev, Luis Redondo, Shu Xiao, Andrei G. Pakhomov
Bioelectrics Publications
Intense pulsed electric fields (PEF) are a novel modality for the efficient and targeted ablation of tumors by electroporation. The major adverse side effects of PEF therapies are strong involuntary muscle contractions and pain. Nanosecond-range PEF (nsPEF) are less efficient at neurostimulation and can be employed to minimize such side effects. We quantified the impact of the electrode configuration, PEF strength (up to 20 kV/cm), repetition rate (up to 3 MHz), bi- and triphasic pulse shapes, and pulse duration (down to 10 ns) on eliciting compound action potentials (CAPs) in nerve fibers. The excitation thresholds for single unipolar but not …
Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori
Nanosecond Pulsed Electric Fields Induce Endoplasmic Reticulum Stress Accompanied By Immunogenic Cell Death In Murine Models Of Lymphoma And Colorectal Cancer, Alessandra Rossi, Olga N. Pakhomova, Peter A. Mollica, Maura Casciola, Uma Mangalanathan, Andrei G. Pakhomov, Claudia Muratori
Bioelectrics Publications
Depending on the initiating stimulus, cancer cell death can be immunogenic or non-immunogenic. Inducers of immunogenic cell death (ICD) rely on endoplasmic reticulum (ER) stress for the trafficking of danger signals such as calreticulin (CRT) and ATP. We found that nanosecond pulsed electric fields (nsPEF), an emerging new modality for tumor ablation, cause the activation of the ER-resident stress sensor PERK in both CT-26 colon carcinoma and EL-4 lymphoma cells. PERK activation correlates with sustained CRT exposure on the cell plasma membrane and apoptosis induction in both nsPEF-treated cell lines. Our results show that, in CT-26 cells, the activity of …
Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller
Moderate Heat Application Enhances The Efficacy Of Nanosecond Pulse Stimulation For The Treatment Of Squamous Cell Carcinoma, Chelsea M. Edelblute, Sigi Guo, Embo Yang, Chunqi Jiang, Karl Schoenbach, Richard Heller
Bioelectrics Publications
Nanosecond pulse stimulation as a tumor ablation therapy has been studied for the treatment of various carcinomas in animal models and has shown a significant survival benefit. In the current study, we found that moderate heating at 43°C for 2 minutes significantly enhanced in vitro nanosecond pulse stimulation-induced cell death of KLN205 murine squamous cell carcinoma cells by 2.43-fold at 600 V and by 2.32-fold at 900 V, as evidenced by propidium iodide uptake. Furthermore, the ablation zone in KLN205 cells placed in a 3-dimensional cell-culture model and pulsed at a voltage of 900 V at 43°C was 3 times …
Electroporation By Subnanosecond Pulses, Iurii Semenov, Shu Xiao, Andrei G. Pakhomov
Electroporation By Subnanosecond Pulses, Iurii Semenov, Shu Xiao, Andrei G. Pakhomov
Bioelectrics Publications
Electropermeabilization of cell membranes by micro- and nanosecond-duration stimuli has been studied extensively, whereas effects of picosecond electric pulses (psEP) remain essentially unexplored. We utilized whole-cell patch clamp and Di-8-ANEPPS voltage-sensitive dye measurements to characterize plasma membrane effects of 500 ps stimuli in rat hippocampal neurons (RHN), NG108, and CHO cells. Even a single 500-ps pulse at 190kV/cm increased membrane conductance and depolarized cells. These effects were augmented by applying brief psEP bursts (5–125 pulses), whereas the rate of pulse delivery (8Hz–1kHz) played little role. psEP-treated cells displayed large inward current at negative membrane potentials but modest or no conductance …
Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong
Intracellular Ros Mediates Gas Plasma-Facilitated Cellular Transfection In 2d And 3d Cultures, Dehui Xu, Biqing Wang, Yujing Xu, Zeyu Chen, Qinjie Cui, Yanjie Yang, Hailan Chen, Michael G. Kong
Bioelectrics Publications
This study reports the potential of cold atmospheric plasma (CAP) as a versatile tool for delivering oligonucleotides into mammalian cells. Compared to lipofection and electroporation methods, plasma transfection showed a better uptake efficiency and less cell death in the transfection of oligonucleotides. We demonstrated that the level of extracellular aqueous reactive oxygen species (ROS) produced by gas plasma is correlated with the uptake efficiency and that this is achieved through an increase of intracellular ROS levels and the resulting increase in cell membrane permeability. This finding was supported by the use of ROS scavengers, which reduced CAP-based uptake efficiency. In …
Generation Of Bipolar Nanosecond Pulses, Sambasiva Rao Rajulapati
Generation Of Bipolar Nanosecond Pulses, Sambasiva Rao Rajulapati
Electrical & Computer Engineering Theses & Dissertations
Bipolar pulse generation has been studied using transmission line technology, which was mainly used for monopolar pulse generation. In this thesis, low impedance, high current, nanosecond pulse generators were designed, constructed and tested. Five transmission lines were connected in parallel, so the impedance was 10 n. The transmission lines were switched by a spark gap switch operated in air. The closing of the switch creates a matched condition on one side of the transmission lines and a short circuit on the other side of the transmission lines. When the transmission lines are precharged, one of the two waves in opposite …
Calcium-Mediated Pore Expansion And Cell Death Following Nanoelectroporation, Olga N. Pakhomova, Betsy Gregory, Iurii Semenov, Andrei G. Pakhomov
Calcium-Mediated Pore Expansion And Cell Death Following Nanoelectroporation, Olga N. Pakhomova, Betsy Gregory, Iurii Semenov, Andrei G. Pakhomov
Bioelectrics Publications
Opening of long-lived pores in the cell membrane is the principal primary effect of intense, nanosecond pulsed electric field (nsPEF). Here we demonstrate that the evolution of pores, cell survival, the time and the mode of cell death (necrotic or apoptotic) are determined by the level of external Ca2+ after nsPEF. We also introduce a novel, minimally disruptive technique for nsEP exposure of adherent cells on indium tin oxide (ITO)-coated glass coverslips, which does not require cell detachment and enables fast exchanges of bath media. Increasing the Ca2+ level from the nominal 2–5 μM to 2 mM for …
Recruitment Of The Intracellular Ca2+ By Ultrashort Electric Stimuli: The Impact Of Pulse Duration, Iurii Semenov, Shu Xiao, Olga N. Pakhomova, Andrei G. Pakhomov
Recruitment Of The Intracellular Ca2+ By Ultrashort Electric Stimuli: The Impact Of Pulse Duration, Iurii Semenov, Shu Xiao, Olga N. Pakhomova, Andrei G. Pakhomov
Bioelectrics Publications
Nanosecond-duration electric stimuli are distinguished by the ability to permeabilize intracellular membranes and recruit Ca2+ from intracellular stores. We quantified this effect in non-excitable cells (CHO) using ratiometric Ca2+ imaging with Fura-2. In a Ca2+-free medium, 10-, 60-, and 300-ns stimuli evoked Ca2+ transients by mobilization of Ca2+ from the endoplasmic reticulum. With 2 mM external Ca2+, the transients included both extra- and intracellular components. The recruitment of intracellular Ca2+ increased as the stimulus duration decreased. At the threshold of 200–300 nM, the transients were amplified by calcium-induced calcium release. We …
Subnanosecond Exposure Systems For Biological Studies, Jongbong Nah
Subnanosecond Exposure Systems For Biological Studies, Jongbong Nah
Electrical & Computer Engineering Theses & Dissertations
The research of bioelectrics has expanded to subnanosecond pulse region and entered a new domain of biophysics of cell interaction with ultra-short and intense electric fields. As subnanosecond pulses may be delivered by antennas to the human body and is very attractive to the medical community, the study of subnanosecond pulse effects calls for exposure systems for both cells and tissues. Two systems were designed in the scope of this thesis, used for cells and tissues respectively. The exposure system designed for cell exposure is a cuvette consisting of two parallel aluminum gaps. This cuvette is placed in a coaxial …
The Use Of An In Vitro 3d Melanoma Model To Predict In Vivo Plasmid Transfection Using Electroporation, Benadette Marrero, Richard Heller
The Use Of An In Vitro 3d Melanoma Model To Predict In Vivo Plasmid Transfection Using Electroporation, Benadette Marrero, Richard Heller
Bioelectrics Publications
A large-scale in vitro 3D tumor model was generated to evaluate gene delivery procedures in vivo. This 3D tumor model consists of a "tissue-like" spheroid that provides a micro-environment supportive of melanoma proliferation, allowing cells to behave similarly to cells in vivo. This functional spheroid measures approximately 1 cm in diameter and can be used to effectively evaluate plasmid transfection when testing various electroporation (EP) electrode applicators. In this study, we identified EP conditions that efficiently transfect green fluorescent protein (GFP) and interleukin 15 (IL-15) plasmids into tumor cells residing in the 3D construct. We found that plasmids …
Oxidative Effects Of Nanosecond Pulsed Electric Field Exposure In Cells And Cell-Free Media, Olga N. Pakhomova, Vera A. Khorokhorina, Angela M. Bowman, Raminta Rodaitė-Riševičienė, Gintautas Saulis, Shu Xiao, Andrei G. Pakhomov
Oxidative Effects Of Nanosecond Pulsed Electric Field Exposure In Cells And Cell-Free Media, Olga N. Pakhomova, Vera A. Khorokhorina, Angela M. Bowman, Raminta Rodaitė-Riševičienė, Gintautas Saulis, Shu Xiao, Andrei G. Pakhomov
Bioelectrics Publications
Nanosecond pulsed electric field (nsPEF) is a novel modality for permeabilization of membranous structures and intracellular delivery of xenobiotics. We hypothesized that oxidative effects of nsPEF could be a separate primary mechanism responsible for bioeffects. ROS production in cultured cells and media exposed to 300-ns PEF (1–13 kV/cm) was assessed by oxidation of 2′, 7′-dichlorodihydrofluoresein (H2DCF), dihidroethidium (DHE), or Amplex Red. When a suspension of H2DCF-loaded cells was subjected to nsPEF, the yield of fluorescent 2′,7′dichlorofluorescein (DCF) increased proportionally to the pulse number and cell density. DCF emission increased with time after exposure in nsPEF-sensitive Jurkat …
Bioelectric Applications For Treatment Of Melanoma, Stephen J. Beebe, Karl H. Schoenbach, Richard Heller
Bioelectric Applications For Treatment Of Melanoma, Stephen J. Beebe, Karl H. Schoenbach, Richard Heller
Bioelectrics Publications
Two new cancer therapies apply bioelectric principles. These methods target tumor structures locally and function by applying millisecond electric fields to deliver plasmid DNA encoding cytokines using electrogene transfer (EGT) or by applying rapid rise-time nanosecond pulsed electric fields (nsPEFs). EGT has been used to locally deliver cytokines such as IL-12 to activate an immune response, resulting in bystander effects. NsPEFs locally induce apoptosis-like effects and affect vascular networks, both promoting tumor demise and restoration of normal vascular homeostasis. EGT with IL-12 is in melanoma clinical trials and nsPEFs are used in models with B16F10 melanoma in vitro and in …
Simulations Of Nanopore Formation And Phosphatidylserine Externalization In Lipid Membranes Subjected To A High-Intensity, Ultrashort Electric Pulse, Q. Hu, R. P. Joshi, K. H. Schoenbach
Simulations Of Nanopore Formation And Phosphatidylserine Externalization In Lipid Membranes Subjected To A High-Intensity, Ultrashort Electric Pulse, Q. Hu, R. P. Joshi, K. H. Schoenbach
Bioelectrics Publications
A combined MD simulator and time dependent Laplace solver are used to analyze the electrically driven phosphatidylserine externalization process in cells. Time dependent details of nanopore formation at cell membranes in response to a high-intensity (100kV∕cm), ultrashort (10ns) electric pulse are also probed. Our results show that nanosized pores could typically be formed within about 5ns. These predictions are in very good agreement with recent experimental data. It is also demonstrated that defect formation and PS externalization in membranes should begin on the anode side. Finally, the simulations confirm that PS externalization is a nanopore facilitated event, rather than the …
Stimulation Of Capacitative Calcium Entry In Hl-60 Cells By Nanosecond Pulsed Electric Fields, Jody A. White, Peter F. Blackmore, Karl H. Schoenbach, Stephen J. Beebe
Stimulation Of Capacitative Calcium Entry In Hl-60 Cells By Nanosecond Pulsed Electric Fields, Jody A. White, Peter F. Blackmore, Karl H. Schoenbach, Stephen J. Beebe
Bioelectrics Publications
Nanosecond pulsed electric fields (nsPEFs) are hypothesized to affect intracellular structures in living cells providing a new means to modulate cell signal transduction mechanisms. The effects of nsPEFs on the release of internal calcium and activation of calcium influx in HL-60 cells were investigated by using real time fluorescent microscopy with Fluo-3 and fluorometry with Fura-2. nsPEFs induced an increase in intracellular calcium levels that was seen in all cells. With pulses of 60 ns duration and electric fields between 4 and 15 kV/cm, intracellular calcium increased 200-700 nM, respectively, above basal levels (similar to100 nM), while the uptake of …
Time Domain Dielectric Spectroscopy Analysis Of Hl-60 Cell Suspensions After Microsecond And Submicrosecond Pulsed Electric Fields, Allen Laurence Garner
Time Domain Dielectric Spectroscopy Analysis Of Hl-60 Cell Suspensions After Microsecond And Submicrosecond Pulsed Electric Fields, Allen Laurence Garner
Electrical & Computer Engineering Theses & Dissertations
Pulsed electric fields (PEF's) above a certain voltage threshold cause electroporation for microsecond pulses and intracellular effects for submicrosecond pulses. Models describing these effects often depend on the electrical properties of the cell, which are altered by the PEF. Time domain dielectric spectroscopy was used to provide data for these models and to measure changes in the conductivity of HL-60 cell suspensions due to single 50 μs and 10 ns PEF's of the same energy. For 1.1 kV/cm, 50 μs pulses, the conductivity rose within a minute after the pulse and dropped dramatically approximately forty minutes after the pulse. For …
The Effects Of Intense Submicrosecond Electrical Pulses On Cells, Jingdong Deng, Karl H. Schoenbach, E. Stephen Buescher, Pamela S. Hair, Paula M. Fox, Stephen J. Beebe
The Effects Of Intense Submicrosecond Electrical Pulses On Cells, Jingdong Deng, Karl H. Schoenbach, E. Stephen Buescher, Pamela S. Hair, Paula M. Fox, Stephen J. Beebe
Bioelectrics Publications
A simple electrical model for living cells predicts an increasing probability for electric field interactions with intracellular substructures of both prokaryotic and eukaryotic cells when the electric pulse duration is reduced into the submicrosecond range. The validity of this hypothesis was verified experimentally by applying electrical pulses (durations 100 μs– 60 ns, electric field intensities 3–150 kV/cm) to Jurkat cells suspended in physiologic buffer containing propidium iodide. Effects on Jurkat cells were assessed by means of temporally resolved fluorescence and light microscopy. For the longest applied pulses, immediate uptake of propidium iodide occurred consistent with electroporation as the cause of …