1,720,984 research outputs found
A numerical design of versatile microchambers for nsPEFs experiments
No full textThe emergence of nanosecond pulsed electric fields (nsPEFs) for intracellular electro-manipulation experiments implies the application of extremely short (ns) high intensity (MV/m) electric field pulses. Specific pulse generators and miniaturized applicators are necessary to properly deliver this category of voltage signals to biological loads. In this context, we propose the design of a versatile nsPEFs applicator, developed following the guidelines typical of microwave propagating systems. The designed microchamber is suitable for in vitro exposure to undistorted pulses with duration down to 1-3 ns during single and multi cell experiments. Further features are: high efficiency (above 0.95), high cell viability by the integration of microfluidic components, real time monitoring of the biological sample and of the pulse propagation. These features can be considered as designing rules for new nanosecond and sub-nanosecond applicators, to ensure experimental repeatability and reproducibility when the impact of propagation on pulse signals is no more negligibl
A microdosimetric study of electropulsation on multiple realistically shaped cells. Effect of Neighbours
No full textOver the past decades, the effects of ultrashort-pulsed electric fields have been used to investigate their action in many medical applications (e.g. cancer, gene electrotransfer, drug delivery, electrofusion). Promising aspects of these pulses has led to several in vitro and in vivo experiments to clarify their action. Since the basic mechanisms of these pulses have not yet been fully clarified, scientific interest has focused on the development of numerical models at different levels of complexity: atomic (molecular dynamic simulations), microscopic (microdosimetry) and macroscopic (dosimetry). The aim of this work is to demonstrate that, in order to predict results at the cellular level, an accurate microdosimetry model is needed using a realistic cell shape, and with their position and packaging (cell density) characterised inside the medium
Numerical estimation of a 10 nanosecond pulse effects on non-uniformly distributed liposomes
No full textNano-systems, often used in biomedical applications for the treatment of a broad category of illnesses, represent one of the nanomedicine approaches recently proposed to target specific drugs only in the region where the disease has been developed. Recently the use of this technique has been proposed with electropulsation, hence taking advantage of the enhanced permeabilization of the cell membrane and simultaneously control the release of the encapsulated drug by the nano-system. In this work, we focus our attention on the study of liposomes nano-systems controlled by the nanosecond pulses electric fields through a microdosimetric approach. The aim is to analyse the electric field necessary to porate a nonuniform distribution of 400 nm liposomes. The work has been carried out by randomly placing 30 liposomes between two electrodes with the application of a 10 nano-second electric field pulse
Microdosimetric Study for Nanosecond Pulsed Electric Fields on a Cell Circuit Model with Nucleus
No full textRecently, scientific interest in electric pulses, always more intense and shorter and able to induce biological effects on both plasma and nuclear membranes, has greatly increased. Hence, microdosimetric models that include internal organelles like the nucleus have assumed increasing importance. In this work, a circuit model of the cell including the nucleus is proposed, which accounts for the dielectric dispersion of all cell compartments. The setup of the dielectric model of the nucleus is of fundamental importance in determining the transmembrane potential (TMP) induced on the nuclear membrane; here, this is demonstrated by comparing results for three different sets of nuclear dielectric properties present in the literature. The results have been compared, even including or disregarding the dielectric dispersion of the nucleus. The main differences have been found when using pulses shorter than 10 ns. This is due to the fact that the high spectral components of the shortest pulses are differently taken into account by the nuclear membrane transfer functions computed with and without nuclear dielectric dispersion. The shortest pulses are also the most effective in porating the intracellular structures, as confirmed by the time courses of the TMP calculated across the plasma and nuclear membranes. We show how dispersive nucleus models are unavoidable when dealing with pulses shorter than 10 ns because of the large spectral contents arriving above 100 MHz, i.e., over the typical relaxation frequencies of the dipolar mechanism of the molecules constituting the nuclear membrane and the subcellular cell compartments
Exploring the applicability of nano-poration for remote control in smart drug delivery systems
No full textSmart drug delivery systems represent an interesting tool to significantly improve the efficiency and the precision in the treatment of a broad category of diseases. In this context, a drug delivery mediated by nanosecond pulsed electric fields seems a promising technique, allowing for a controlled release and uptake of drugs by the synergy between the electropulsation and nanocarriers with encapsulated drugs. The main concern about the use of electroporation for drug delivery applications is the difference in dimension between the liposome (nanometer range) and the cell (micrometer range). The choice of liposome dimension is not trivial. Liposomes larger than 500 nm of diameter could be recognized as pathogen agents by the immune system, while liposomes of smaller size would require external electric field of high amplitudes for the membrane electroporation that could compromise the cell viability. The aim of this work is to theoretically study the possibility of a simultaneous cell and liposomes electroporation. The numerical simulations reported the possibility to electroporate the cell and a significant percentage of liposomes with comparable values of external electric field, when a 12 nsPEF is use
Feasibility for Microwaves Energy to Affect Biological Systems Via Nonthermal Mechanisms: A Systematic Approach
No full textThe understanding of possible nonthermal bio-effects has been an open question during the last five decades. In this paper, the authors present a critical literature review of the models of the interaction mechanisms, together with an overview of all the publications finding positive results for in vitro and in vivo studies. The systematic approach consisted of pooling together the positive studies on the basis of the endpoints and the biological systems, to identify specific plausible targets of the action of the electromagnetic fields and the related pathways. Such a classification opens the way to the discussion of some hypotheses of interaction mechanisms considered as first transduction step. The authors conclude that only through a multiscale methodology it is possible to perform a comprehensive study of the nonthermal effects, based on affordable and realistic in silico models
Novel Passive Element Circuits for Microdosimetry of Nanosecond Pulsed Electric Fields
No full textMicrodosimetric models for biological cells have assumed increasing significance in the development of nanosecond pulsed electric field technology for medical applications. In this paper, novel passive element circuits, able to take into account the dielectric dispersion of the cell, are provided. The circuital analyses are performed on a set of input pulses classified in accordance with the current literature. Accurate data in terms of transmembrane potential are obtained in both time and frequency domains for different cell models. In addition, a sensitivity study of the transfer function for the cell geometrical and dielectric parameters has been carried out. This analysis offers a new, simple, and efficient tool to characterize the nsPEFs action at the cellular level. © 2012 IEEE
Microdosimetric model of a single cell for nanosecond pulsed electric fields: an experimental method of validation
No full textInnovative Flexible Electrodes for Electroporation
No full textElectroporation is one of the most effective and still best promising electric-based techniques in anticancer therapy.
In this context the possibility that the tumoral tissue is completely wrapped from the electrode seems strategical to increase the effectiveness of the treatments. In this work the possibility of a flexible electrode, based on MEMS technology and able to reach some millimetres penetration below the electrode surface is shown
Numerical estimation of a 10 nanosecond pulse effects on non-uniformly distributed liposomes
No full textNano-systems, often used in biomedical applications for the treatment of a broad category of illnesses, represent one of the nanomedicine approaches recently proposed to target specific drugs only in the region where the disease has been developed. Recently the use of this technique has been proposed with electropulsation, hence taking advantage of the enhanced permeabilization of the cell membrane and simultaneously control the release of the encapsulated drug by the nano-system. In this work, we focus our attention on the study of liposomes nano-systems controlled by the nanosecond pulses electric fields through a microdosimetric approach. The aim is to analyse the electric field necessary to porate a non-uniform distribution of 400 nm liposomes. The work has been carried out by randomly placing 30 liposomes between two electrodes with the application of a 10 nano-second electric field puls
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