In silico experiments (numerical simulations) are a valuable tool for non-invasive research of the influences of tissue properties, electrode placement and electric pulse delivery scenarios in the ...process of electroporation. The work described in this article was aimed at introducing time dependent effects into a finite element model developed specifically for electroporation. Reference measurements were made ex vivo on beef liver samples and experimental data were used both as an initial condition for simulation (applied pulse voltage) and as a reference value for numerical model calibration (measured pulse current). The developed numerical model is able to predict the time evolution of an electric pulse current within a 5% error over a broad range of applied pulse voltages, pulse durations and pulse repetition frequencies. Given the good agreement of the current flowing between the electrodes, we are confident that the results of our numerical model can be used both for detailed in silico research of electroporation mechanisms (giving researchers insight into time domain effects) and better treatment planning algorithms, which predict the outcome of treatment based on both spatial and temporal distributions of applied electric pulses.
Electroporation is a phenomenon caused by externally applied electric field of an adequate strength and duration to cells that results in the increase of cell membrane permeability to various ...molecules, which otherwise are deprived of transport mechanism. As accurate coverage of the tissue with a sufficiently large electric field presents one of the most important conditions for successful electroporation, applications based on electroporation would greatly benefit with a method of monitoring the electric field, especially if it could be done during the treatment. As the membrane electroporation is a consequence of an induced transmembrane potential which is directly proportional to the local electric field, we propose current density imaging (CDI) and magnetic resonance electrical impedance tomography (MREIT) techniques to measure the electric field distribution during electroporation. The experimental part of the study employs CDI with short high-voltage pulses, while the theoretical part of the study is based on numerical simulations of MREIT. A good agreement between experimental and numerical results was obtained, suggesting that CDI and MREIT can be used to determine the electric field during electric pulse delivery and that both of the methods can be of significant help in planning and monitoring of future electroporation based clinical applications.
High-intensity pulsed electromagnetic fields (HI-PEMFs) can be used for contactless permeabilization of biological cells and, thus, exploited for drug and gene delivery or other biomedical ...applications. Nevertheless, the availability of applicable technological setups is almost non-existent. In this article, we present a new prototype of the HI-PEMF generator, which can be used for contactless permeabilization of cells in vitro . The generator is based on high dI/dt silicon controlled rectifier (SCR) switches and is capable to generate magnetic field pulses up to 7 T and electric fields >10 V/cm in a volume comparable to standard in vitro procedures for electroporation. Three different applicators (inductors) were studied, and the influence on the output pulse is presented, including the thermal analysis. Based on the results, the optimal inductor was selected and experimentally tested on Chinese hamster ovary (CHO) cells in basic permeabilization propidium iodide (PI) experiments. The generator circuit, parameters, characteristics, and recommendations for future HI-PEMF systems are provided.
The electroporation effect on tissue can be assessed by measurement of electrical properties of the tissue undergoing electroporation. The most prominent techniques for measuring electrical ...properties of electroporated tissues have been voltage-current measurement of applied pulses and electrical impedance tomography (EIT). However, the electrical conductivity of tissue assessed by means of voltage-current measurement was lacking in information on tissue heterogeneity, while EIT requires numerous additional electrodes and produces results with low spatial resolution and high noise. Magnetic resonance EIT (MREIT) is similar to EIT, as it is also used for reconstruction of conductivity images, though voltage and current measurements are not limited to the boundaries in MREIT, hence it yields conductivity images with better spatial resolution. The aim of this study was to investigate and demonstrate the feasibility of the MREIT technique for assessment of conductivity images of tissues undergoing electroporation. Two objects were investigated: agar phantoms and ex vivo liver tissue. As expected, no significant change of electrical conductivity was detected in agar phantoms exposed to pulses of all used amplitudes, while a considerable increase of conductivity was measured in liver tissue exposed to pulses of different amplitudes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
6.
Current density imaging during tissue electroporation Bajd, F; Kranjc, M; Miklavčič, D ...
Prilozi - Makedonska akademija na naukite i umetnostite. Oddelenie za biološki i medicinski nauki,
2012, Letnik:
33, Številka:
1
Journal Article
Delivery of externally applied electric pulses on the target tissue during electroporation increases membrane permeability and induces electric currents in the tissue. To optimize electroporation ...parameters, the current density and with it associated electric field distributions can be monitored by means of current density imaging (CDI) and magnetic resonance electric impedance tomography (MREIT).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Blumlein generators are used in different applications such as radars, lasers, and also recently in various biomedical studies, where the effects of high-voltage nanosecond pulses on biological cells ...are evaluated. In these studies, it was demonstrated that by applying high-voltage nanosecond pulses to cells, plasma membrane and cell organelles are permeabilized. As suggested in a recent publication, the repetition rate and polarity of nanosecond high-voltage pulses could have an important effect on the electropermeabilization process, and consequently, on the observed phenomena. Therefore, we designed a new Blumlein configuration that enables a higher repetition rate of variable duration of either bipolar or unipolar high-voltage pulses. We achieved a maximal pulse repetition rate of 1.1 MHz. However, theoretically, this rate could be even higher. We labeled endocytotic vesicles with lucifer yellow and added propidium iodide to a cell suspension for testing the cell plasma membrane integrity, so we were able to observe the permeabilization of endocytotic vesicles and the cell plasma membrane at the same time. The new design of pulse generator was built, verified, and also tested in experiments. The resulting flexibility and variability allow further in vitro experiments to determine the importance of the pulse repetition rate and pulse polarity on membrane permeabilization - both of the cell plasma membrane as well as of cell organelle membranes.
The authors have investigated a panel of parameters for immunotoxicity that may be incorporated in routine screening for toxicity of pharmaceuticals. This panel comprises serum immunoglobulin ...concentrations, cellularity of bone marrow, weights and histopathology of thymus, spleen, and lymph nodes, histopathology of Peyers′ patches, and FACScan analysis of lymphocyte subpopulations in the spleen, in addition to parameters of toxicity to other systems. To study the value of these assays for pharmaceuticals, the authors used the immunosuppressants azathioprine (AZP) and cyclosporin A (CsA) as model compounds with known immunotoxic activity. In two separate experiments, rats were treated by daily gastric intubation with 0, 5, 12.5, and 25 mg AZP/kg body wt or 0, 1.25, 5, and 20 mg CsA/ kg body wt. In the AZP study, the histopathology of the thymus and the spleen were valuable parameters of immunotoxicity, since these organs showed microscopic alterations at relatively low dose levels. In the CsA experiment, both the histopathology of the thymus and the data provided by FACScan analysis were sensitive indicators of immunotoxicity detecting effects at the lowest dose level employed, The data indicate that the lymphoid system is the most sensitive target of toxicity after AZP or CsA administration. The authors conclude that their test battery yielded immunotoxicity profiles of AZP and CsA in rats that were consistent with published findings in the literature, indicating the usefulness of the test battery employed.
In an ideal tritium system, we would be able to remove all polymer components due the damage incurred by the resulting beta decay and reduce the required maintenance of the systems and its ...components. However, polymers are an integral material used within the Tritium Facility in sealing, joining, and containment and are used in several different systems within the process. With the loss of certain capabilities, such as the Normetex pump, it is necessary to identify and/or develop polymers that can better withstand exposure to beta radiation in tritium environments. This article reviews the various polymer resins and formulations that are used in a tritium environment, their properties, and their performance.
Induction heating is a complex interplay of electromagnetic, thermal and metallurgic phenomena. It is therefore not surprising that only few numerical optimization approaches for solving induction ...heating problems have been published. The aim of our study was to determine the optimal coil position and the optimal amplitude and frequency of the electric current in order to attain the desired temperature profile in a non-ferromagnetic steel cylinder workpiece. The finite-element numerical modeling in combination with genetic algorithm optimization method was used for this purpose. The heated workpiece was surrounded by a copper coil consisting of four loops. In our calculations the workpiece's temperature-dependent material properties were taken into account. Using a genetic algorithm the following parameters were optimized: position of the single-coil loop, the amplitude and the frequency of the electric current in the coil. Our numerical model was experimentally validated by comparison of measurement and simulation results. The optimized solution and the global optimum had comparable temperature profiles due to a better selection of the electric current parameters compared to the profile obtained by solving the problem intuitively. We demonstrated that the proposed approach can be used for planning of induction heating of steel materials at low-energy consumption and high time-efficiency.
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