scholarly journals Capacitive coupling increases the accuracy of cell-specific tumour ablation by electric fields

2019 ◽  
Author(s):  
Terje Wimberger ◽  
Verena K. Köhler ◽  
Eva K. Ehmoser ◽  
Klemens J. Wassermann
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Cellular Response ◽  
Irreversible Electroporation ◽  
Capacitive Coupling ◽  
Specific Lysis ◽  
Size Dependent ◽  
High K ◽  
High K Dielectric ◽  
Mcf 7

AbstractIrreversible electroporation holds great potential for cell-specific lysis due to the size-dependent susceptibility of cells to externally imposed electric fields. Previous attempts at selective cell lysis lead to significant overlap between affected populations and struggle with inconsistent biological outcome. We propose that charge transfer at the electrode-liquid interface is responsible by inducing multifactorial effects originating from both the electric field and electrochemical reactions. A promising remedy is the coating of electrodes with a high-k dielectric layer. The resulting capacitive coupling restores the selective potential of electric field mediated lysis in a microfluidic setup. Initial experiments show the consistent depletion of erythrocytes from whole blood while leaving leukocytes intact. The same is true for the reproducible and selective depletion of Jurkat and MCF-7 cells in a mixture with leukocytes. Unexpectedly, the observed order of lysis cannot be correlated with cell size. This implies that the cellular response to capacitive coupling features a selective characteristic that is different from conventional lysis configurations.

High-k Dielectric Passivation: Novel Considerations Enabling Cell Specific Lysis Induced by Electric Fields

2016 ◽  
Vol 8 (33) ◽  
pp. 21228-21235 ◽  
Author(s):  
Klemens J. Wassermann ◽  
Sven Barth ◽  
Franz Keplinger ◽  
Christa Noehammer ◽  
Johannes R. Peham
Keyword(s):  
Electric Fields ◽  
Specific Lysis ◽  
High K ◽  
High K Dielectric

scholarly journals Cytoskeletal Disruption after Electroporation and Its Significance to Pulsed Electric Field Therapies

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1132 ◽  
Author(s):  
Philip M. Graybill ◽  
Rafael V. Davalos
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Pulsed Electric Field ◽  
Current Understanding ◽  
Vascular Effects ◽  
Cell Substrate ◽  
Membrane Effects ◽  
Cytoskeletal Disruption

Pulsed electric fields (PEFs) have become clinically important through the success of Irreversible Electroporation (IRE), Electrochemotherapy (ECT), and nanosecond PEFs (nsPEFs) for the treatment of tumors. PEFs increase the permeability of cell membranes, a phenomenon known as electroporation. In addition to well-known membrane effects, PEFs can cause profound cytoskeletal disruption. In this review, we summarize the current understanding of cytoskeletal disruption after PEFs. Compiling available studies, we describe PEF-induced cytoskeletal disruption and possible mechanisms of disruption. Additionally, we consider how cytoskeletal alterations contribute to cell–cell and cell–substrate disruption. We conclude with a discussion of cytoskeletal disruption-induced anti-vascular effects of PEFs and consider how a better understanding of cytoskeletal disruption after PEFs may lead to more effective therapies.

Directed Growth of Fungal Hyphae in an Electric Field

1990 ◽  
Vol 45 (3-4) ◽  
pp. 306-314 ◽  
Author(s):  
Hans Gruler ◽  
Neil A. R. Gow
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Linear Response ◽  
Cellular Response ◽  
Tube Length ◽  
Angle Distribution ◽  
Directional Growth ◽  
Growth Coefficient ◽  
Directed Growth ◽  
Germ Tubes

Abstract The galvanotropic response of the mycelial fungus Neurospora crassa is investigated. The angle distribution function of growing hyphae is described by a generating function which contains two non-trivial terms; one for directional growth and one for bidirectional growth. The following results were obtained, (i) Germ tubes grew towards the anode, (ii) The cellular response was linear for small sized cells and weaker electric fields. The galvanotropic constant, KGROW, which describes the linear response, was small for short germ tubes or hyphae (AGROW-1 = -20 V -cm-1 for I0 = 10 |am) and large for longer cells (AGROW-1 = -1 -7 V ·cm-1 for I0 = 100 μm). The growth coefficient KP of (-18.5 mV) describes the response independent of cell size. The linear response is explained by the field-induced distribution of charged membrane- bound proteins essential for galvanotropism. (iii) For E > E0 = 3.8 V ·cm-1, the linear response is inhibited (inhibition coefficient K1 = 1.11). The inhibition is explained by field-induced changes of the membrane potential, (iv) The galvanotropic response of longer hyphae was bidirectional. The cells grew on average perpendicular to the applied field. The bidirectional response is proportional to Er with a bidirectional growth coefficient K2 of -(0.25 V)-2. The bidirectional growth is explained by the inhibition of the directed growth process. The transition from anode-directed to bidirectional growth was a function of the applied electric field as well as of the tube length (directed growth for E2-l0< 4.4V2·cm-1 and bidirectional growth for E2·l0> 4.4 V2· cm-1).

Endovascular Nonthermal Irreversible Electroporation: A Finite Element Analysis

2010 ◽  
Vol 132 (3) ◽  
Author(s):  
Elad Maor ◽  
Boris Rubinsky
Keyword(s):  
Finite Element ◽  
Electric Field ◽  
Electric Fields ◽  
Joule Heating ◽  
Arterial Wall ◽  
Thermal Damage ◽  
Irreversible Electroporation ◽  
Phospholipid Bilayer ◽  
Tissue Ablation ◽  
Nonthermal Irreversible Electroporation

Tissue ablation finds an increasing use in modern medicine. Nonthermal irreversible electroporation (NTIRE) is a biophysical phenomenon and an emerging novel tissue ablation modality, in which electric fields are applied in a pulsed mode to produce nanoscale defects to the cell membrane phospholipid bilayer, in such a way that Joule heating is minimized and thermal damage to other molecules in the treated volume is reduced while the cells die. Here we present a two-dimensional transient finite element model to simulate the electric field and thermal damage to the arterial wall due to an endovascular NTIRE novel device. The electric field was used to calculate the Joule heating effect, and a transient solution of the temperature is presented using the Pennes bioheat equation. This is followed by a kinetic model of the thermal damage based on the Arrhenius formulation and calculation of the Henriques and Moritz thermal damage integral. The analysis shows that the endovascular application of 90, 100 μs pulses with a potential difference of 600 V can induce electric fields of 1000 V/cm and above across the entire arterial wall, which are sufficient for irreversible electroporation. The temperature in the arterial wall reached a maximum of 66.7°C with a pulse frequency of 4 Hz. Thermal damage integral showed that this protocol will thermally damage less than 2% of the molecules around the electrodes. In conclusion, endovascular NTIRE is possible. Our study sets the theoretical basis for further preclinical and clinical trials with endovascular NTIRE.

scholarly journals Modeling of Inactivation of Biofilm Composing Bacteria with Low Intensity Electric Field: Prediction of Lowest Intensity and Mechanism

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Mokhamad Tirono ◽  
Suhariningsih
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Staphylococcus Epidermidis ◽  
Treatment Time ◽  
Irreversible Electroporation ◽  
Pockels Effect ◽  
Low Intensity ◽  
Reversible Electroporation ◽  
Effect Of Treatment ◽  
Number Of Bacteria

Sterilization using high-intensity electric fields is detrimental to health if safety is inadequate, so it is necessary to study the possibility of sterilization using low-intensity electric fields. This study aims to determine the lowest electric field intensity and treatment time to deactivate the bacteria that make up the biofilms and explain the mechanism of inactivation. The study samples were biofilms from the bacteria Pseudomonas aeruginosa and Staphylococcus epidermidis grown on the catheter. The modeling formula was developed from the Pockels effect and the Weibull distribution with the treatment using a square pulse-shaped electric field with a pulse width of 50 μs and an intensity of 2.0-4.0 kV/ cm. The results showed that the threshold for irreversible electroporation of both samples occurred in the treatment using an electric field with an intensity of 3.5 kV/cm and 3.75 kV/ cm, respectively, where the size and type of Gram of bacteria influenced. Moreover, the time of the treatment had an effect when irreversible electroporation occurred. However, when there was reversible electroporation, the effect of treatment time on the reduction in the number of bacteria was not significant. Also, changes in conductivity affected the reduction in the number of bacteria when reversible electroporation occurred.

scholarly journals Towards Solid Tumor Treatment by Nanosecond Pulsed Electric Fields

2009 ◽  
Vol 8 (4) ◽  
pp. 289-306 ◽  
Author(s):  
Axel T. Esser ◽  
Kyle C. Smith ◽  
T. R. Gowrishankar ◽  
James C. Weaver
Keyword(s):  
Cell Death ◽  
Electric Field ◽  
Spatial Scale ◽  
Electric Fields ◽  
Solid Tumor ◽  
Irreversible Electroporation ◽  
Pulsed Electric Fields ◽  
Underlying Mechanism ◽  
Tumor Ablation ◽  
Nanosecond Pulsed Electric Fields

Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism inducing apoptosis, we use a multicellular system model (spatial scale 100 μm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.

The Effect of Small Intestine Heterogeneity on Irreversible Electroporation Treatment Planning

2014 ◽  
Vol 136 (9) ◽  
Author(s):  
Mary Phillips
Keyword(s):  
Finite Element ◽  
Small Intestine ◽  
Electric Field ◽  
Treatment Planning ◽  
Electric Fields ◽  
Irreversible Electroporation ◽  
Experimental Results ◽  
Heterogeneous Structure ◽  
Element Analysis

Nonthermal irreversible electroporation (NTIRE) is an ablation modality that utilizes microsecond electric fields to produce nanoscale defects in the cell membrane. This results in selective cell death while preserving all other molecules, including the extracellular matrix. Here, finite element analysis and experimental results are utilized to examine the effect of NTIRE on the small intestine due to concern over collateral damage to this organ during NTIRE treatment of abdominal cancers. During previous studies, the electrical treatment parameters were chosen based on a simplified homogeneous tissue model. The small intestine, however, has very distinct layers, and a more realistic model is needed to further develop this technology for precise clinical applications. This study uses a two-dimensional finite element solution of the Laplace and heat conduction equations to investigate how small intestine heterogeneities affect the electric field and temperature distribution. Experimental results obtained by applying NTIRE to the rat small intestine in vivo support the heterogeneous effect of NTIRE on the tissue. The numerical modeling indicates that the electroporation parameters chosen for this study avoid thermal damage to the tissue. This is supported by histology obtained from the in vivo study, which showed preservation of extracellular structures. The finite element model also indicates that the heterogeneous structure of the small intestine has a significant effect on the electric field and volume of cell ablation during electroporation and could have a large impact on the extent of treatment. The heterogeneous nature of the tissue should be accounted for in clinical treatment planning.

scholarly journals Ih interacts with somato-dendritic structure to determine frequency response to weak alternating electric field stimulation

2018 ◽  
Vol 119 (3) ◽  
pp. 1029-1036 ◽  
Author(s):  
Enrique H. S. Toloza ◽  
Ehsan Negahbani ◽  
Flavio Fröhlich
Keyword(s):  
Electric Field ◽  
Electric Fields ◽  
Cellular Response ◽  
Current Injection ◽  
Field Stimulation ◽  
Electric Field Stimulation ◽  
Cation Current ◽  
Network Oscillations ◽  
Alternating Electric Field

Transcranial current stimulation (tCS) modulates brain dynamics using weak electric fields. Given the pathological changes in brain network oscillations in neurological and psychiatric illnesses, using alternating electric field waveforms that engage rhythmic activity has been proposed as a targeted, network-level treatment approach. Previous studies have investigated the effects of electric fields at the neuronal level. However, the biophysical basis of the cellular response to electric fields has remained limited. Here, we characterized the frequency-dependent response of different compartments in a layer V pyramidal neuron to exogenous electric fields to dissect the relative contributions of voltage-gated ion channels and neuronal morphology. Hyperpolarization-activated cation current (Ih) in the distal dendrites was the primary ionic mechanism shaping the model’s response to electric field stimulation and caused subthreshold resonance in the tuft at 20 ± 4 Hz. In contrast, subthreshold Ih-mediated resonance in response to local sinusoidal current injection was present in all model compartments at 11 ± 2 Hz. The frequencies of both resonance responses were modulated by Ih conductance density. We found that the difference in resonance frequency between the two stimulation types can be explained by the fact that exogenous electric fields simultaneously polarize the membrane potentials at the distal ends of the neuron (relative to field direction) in opposite directions. Our results highlight the role of Ih in shaping the cellular response to electric field stimulation and suggest that the common model of tCS as a weak somatic current injection fails to capture the cellular effects of electric field stimulation. NEW & NOTEWORTHY Modulation of cortical oscillation by brain stimulation serves as a tool to understand the causal role of network oscillations in behavior and is a potential treatment modality that engages impaired network oscillations in disorders of the central nervous system. To develop targeted stimulation paradigms, cellular-level effects must be understood. We demonstrate that hyperpolarization-activated cation current (Ih) and cell morphology cooperatively shape the response to applied alternating electric fields.

scholarly journals The Effect of Electrochemotherapy on Breast Cancer Cell Lines

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Danijela Cvetković ◽  
Aleksandar Cvetković ◽  
Nenad Filipović
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Electric Field ◽  
Cell Lines ◽  
Current Knowledge ◽  
Irreversible Electroporation ◽  
Breast Cancer Cell Lines ◽  
High Concentration ◽  
Cytotoxic Effects ◽  
Mcf 7

Abstract Despite advances in treatment, breast cancer remains one of the leading causes of death, and obviously new approaches to the treatment are needed. Due to minimal side effects, unlike more aggressive forms of therapy such as chemotherapy and radiotherapy, the application of irreversible electroporation-electrochemotherapy represents a new modality in the treatment of cancer. Electrochemotherapy uses an electric field (375 V cm -1) to allow increased absorption of chemotherapeutic drugs selectively in tumor cells. Accordingly, the total dose of these agents can be significantly reduced and numerous side effects can be avoided in this way. The Real Time Cell Analysis-RTCA-xCELLigence system was used to monitor the cytotoxic effects of the treatment. The results confirmed the justification of the use of paclitaxel in chemotherapy and showed cytotoxic effects of paclitaxel which were time and dose-dependent in both cell lines. When paclitaxel was administered in combination with an electric field, in both cell lines, the results showed a greater cytotoxic effect compared to the same treatment without electrochemotherapy. MCF-7 cells are more sensitive to electrochemotherapy treatment with paclitaxel compared to MDA-MB-231. Electrochemotherapy using paclitaxel in MCF-7 cells had a 6.4-fold higher cytotoxicity compared to the treatment only with paclitaxel. The results obtained support the current knowledge of the benefits of electrochemotherapy. It has been shown that electrochemotherapy can significantly increase the effects of paclitaxel in the tested cell lines. In this way, a very high concentration of chemotherapeutics in the targeted tissue was achieved, which represents localized chemotherapy.

Study Of Ta2O5 Based MOS Capacitors, With Tantalum Oxidized In O2:NH3 Ambient.

2002 ◽  
Vol 716 ◽  
Author(s):  
Pallavi Krishnamoorthi ◽  
A N Chandorkar
Keyword(s):  
Electric Fields ◽  
Interface Layer ◽  
Electrical Characteristics ◽  
Ftir Analysis ◽  
Leakage Currents ◽  
Mos Capacitors ◽  
High K ◽  
Order Of Magnitude ◽  
Xrd Studies ◽  
High K Dielectric

AbstractTantalum Pentaoxide, an alternative to SiO2, as a high-k dielectric for DRAM and MOS applications, faces the problem of interface mismatch at silicon. SiO2 or Si3N4 interfacial layer could help in overcoming this problem. The higher band offsets of these materials also help in the reduction of leakage currents at low electric fields. Here we study the physical and electrical characteristics of Ta, oxidized in O2:NH3 ambient, and without any other interface layer. This is done to check if N/H moves to the interface, and thus improves the electrical properties. XRD studies of the film, showed the presence of Ta2O5. Peaks corresponding to TaSi2, un-oxidized tantalum and TaN were also found in the film. But the intensity of these peaks decreased with the reduction of NH3 content. Thus a higher oxygen content could reduce the content of TaN and unoxidized tantalum. FTIR analysis however showed strong Ta=O and Si-O peaks. For the MOS capacitors, due to the presence of resistive components, the maximum capacitance was reduced, compared to that of pure Ta2O5 films. Oxide charges in the films were observed to be around 1.9E10 cm-2. But the traps in these films were found to be almost negligible as observed from the negligible hysteresis in the C-V characteristics. Films with N/H showed lesser oxide charges by an order of magnitude, as compared to pure Ta2O5 films.

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