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1 – 10 of 25Bruno Bisceglia, Francesca de Terlizzi, Antonio Scaglione and Nicola Francesco Tallarino
Electrochemotherapy (ECT) is an outstanding technique for treatment of tumor nodules which is currently used for treatment of skin metastases, and now it is being developed for…
Abstract
Purpose
Electrochemotherapy (ECT) is an outstanding technique for treatment of tumor nodules which is currently used for treatment of skin metastases, and now it is being developed for treatment of internal organs such as, bone, liver, etc. In this work the authors' goal was finding a simple and proper needles configuration, allowing electroporation of whole cancer cell membranes, possibly minimizing direct cell death of healthy tissue.
Design/methodology/approach
This work shows numerical analysis of the ECT of a deep-seated tumor, like in bone tissue of human limb. The tumor is excited by a sequence of square-wave electric pulses (5 kHz), inducing a 1,000 V/cm electric field through a suitable configuration of 30 mm long steel needle electrodes inserted in a part of limb long 20 cm. Treated element is numerically modeled in a very simplified 3D geometry. All materials are assumed as homogeneous, linear and isotropic mediums.
Findings
Electrochemotherapy is based on the local application of short and intense electric pulses that transiently permeabilizes neoplastic cells membrane, thus allowing cytotoxicity increase of a chemotherapeutic drug, bleomycin, and reducing its dosage. The local field in target tissues depends on geometry and position of electrodes, that have to be placed according cancer shape and size, and excited by electric pulses of opportune amplitude. Current efforts are aimed to test whether electric pulses can be applied to bone through invasive needles without affecting the recovery of osteogenetic activity.
Originality/value
The results of the simulation study can help to establish the appropriate geometric and electric setup for treatment of bone metastases in clinical ECT trials. This paper reports results from different needles configurations and show that a proper needle positioning allows complete electroporation of the whole tumor
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Borja López-Alonso, Pablo Briz, Hector Sarnago, José M. Burdio and Oscar Lucia
This paper aims to study the feasibility of proposed method to focus the electroporation ablation by mean of multi-output multi-electrode system.
Abstract
Purpose
This paper aims to study the feasibility of proposed method to focus the electroporation ablation by mean of multi-output multi-electrode system.
Design/methodology/approach
The proposed method has been developed based on a previously designed electroporation system, which has the capabilities to modify the electric field distribution in real time, and to estimate the impedance distribution. Taking into consideration the features of the system and biological tissues, the problem has been addressed in three phases: modeling, control system design and simulation testing. In the first phase, a finite element analysis model has been proposed to reproduce the electric field distribution within the hepatic tissue, based on the characteristics of the electroporation system. Then, a control strategy has been proposed with the goal of ensuring complete ablation while minimizing the affected volume of healthy tissue. Finally, to check the feasibility of the proposal, several representative cases have been simulated, and the results have been compared with those obtained by a traditional system.
Findings
The proposed method achieves the proposed goal, as part of a complex electroporation system designed to improve the targeting, effectiveness and control of electroporation treatments and serve to demonstrate the feasibility of developing new electroporation systems capable of adapting to changes in the preplanning of the treatment in real-time.
Originality/value
The work presents a thorough study of control method to multi-output multi-electrode electroporation system by mean of a rigorous numerical simulation.
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Jaime A. Ramirez, William P.D. Figueiredo, Joao Francisco C. Vale, Isabela D. Metzker, Rafael G. Santos, Matheus S. Mattos, Elizabeth R.S. Camargos and David A. Lowther
– This paper aims to investigate the electroporation phenomenon in a single cell exposed to ultra short (μs) and high voltage (kV) electric pulses.
Abstract
Purpose
This paper aims to investigate the electroporation phenomenon in a single cell exposed to ultra short (μs) and high voltage (kV) electric pulses.
Design/methodology/approach
The problem is addressed by two complementary approaches. First, numerical simulations based on an asymptotic approximation derived from the Smoluchowski theory are used to calculate the pore generation, growth and size evolution at the membrane of a spherical cell model, immersed in a suspension medium and consisting of cytoplasm and membrane. The numerical calculations are solved using the finite difference method. Second, an in vitro experiment with LLC-MK2 cells is carried out in which electroporation was monitored with molecules of propidium iodide. This part also comprehended the design and manufacturing of a portable electric pulse generator capable of providing rectangular pulses with amplitude of 1,000 V and duration in the range of 1-μs to 100-μs. The pulse generator is composed of three modules: a high voltage DC source, a control module, and an energy storage and high voltage switching.
Findings
The numerical simulations considered a 5-μm radius cell submitted to a 500 kV/m rectangular electric pulse for 1-μs. The results indicate the formation of around 3,500 pores at the cell membrane, most of them, around 950, located at the poles of the cell aligned to the applied electric pulse, with radii sizes varying from 0.5-nm to 13-nm. The in vitro experiment considered exposition of LLC-MK2 cells to pulses of 200 V, 500 V, and 700 V, and 1-μs. Images from fluorescence microscopy exhibit the LLC-MK2 cells with intense red, a strong evidence of the electroporation.
Originality/value
The work presents a thorough study of the electroporation phenomenon combining two complementary approaches, a rigorous numerical simulation and a detailed in vitro experiment.
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Luca G. Campana, Paolo Di Barba, Fabrizio Dughiero, Michele Forzan, Maria Evelina Mognaschi, Rudy Rizzo and Elisabetta Sieni
In electrochemotherapy, flexible electrodes, composed by an array of needles, are applied to human tissues to treat large surface tumors. The positioning of the needles in the…
Abstract
Purpose
In electrochemotherapy, flexible electrodes, composed by an array of needles, are applied to human tissues to treat large surface tumors. The positioning of the needles in the tissue depends on the surface curvature. The parallel needle case is preferred, as their relative inclinations strongly affect the actual distribution of electric field. Nevertheless, in some case, small inclinations are unavoidable. The purpose of this paper is to study the electric field distribution for non-parallel needles.
Design/methodology/approach
The effect of electrode position is evaluated systematically by means of numerical models and experiments on phantoms for two different angles (5° and 30°) and compared with the case of parallel needles. Potato model was used as phantom, as this tissue becomes dark after few hours from electroporation. The electroporation degree was gauged from the color changings on the potatoes.
Findings
The distribution of electric field in different needle configuration is found by means of finite element analysis (FEA) and experiments on potatoes. The electric field level of inclined needles was compared with parallel needle case. In particular, the electric field distribution in the case of inclined needles could be very different with respect to the one in the case of parallel needles. The degree of enhancement for different inclinations is visualized by potato color intensity. The FEA suggested that the needle parallelism has to be maintained as possible as if the tips are closer to each other, the electric field intensity could be different with respect to the one in the case of parallel needles.
Originality/value
This paper analyzes the effect of inclined electrodes considering also the non-linearity of tissues.
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Andreas Rosin, Michael Hader, Corinna Drescher, Magdalena Suntinger, Thorsten Gerdes, Monika Willert-Porada, Udo S. Gaipl and Benjamin Frey
This paper aims to investigate in a self-designed closed loop reactor process conditions for thermal inactivation of B16 melanoma cells by microwave and conventional heating.
Abstract
Purpose
This paper aims to investigate in a self-designed closed loop reactor process conditions for thermal inactivation of B16 melanoma cells by microwave and conventional heating.
Design/methodology/approach
Besides control experiments (37°C), inactivation rate was determined in the range from 42°C to 46°C. Heating was achieved either by microwave radiation at 2.45 GHz or by warm water. To distinguish viable from dead cells, AnnexinV staining method was used and supported by field effect scanning electron microscopy (FE-SEM) imaging. Furthermore, numerical simulations were done to get a closer look into both heating devices. To investigate the thermal influence on cell inactivation and the differences between heating methods, a reaction kinetics approach was added as well.
Findings
Control experiments and heating at 42°C resulted in low inactivation rates. Inactivation rate at 44°C remained below 12% under conventional, whereas it increased to >70% under microwave heating. At 46°C, inactivation rate attained 68% under conventional heating; meanwhile, even 88% were determined under microwave heating. FE-SEM images showed a porous membrane structure under microwave heating in contrast to mostly intact conventional heated cells. Numerical simulations of both heating devices and a macroscopic Arrhenius approach could not sufficiently explain the observed differences in inactivation.
Originality/value
A combination of thermal and electrical effects owing to microwave heating results in higher inactivation rates than conventional heating achieves. Nevertheless, it was not possible to determine the exact mechanisms of inactivation under microwave radiation.
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Discusses applications of genetic engineering including some whichare already used commercially. Outlines some of the technicalcomplexities of gene transfer in plants. Touches on…
Abstract
Discusses applications of genetic engineering including some which are already used commercially. Outlines some of the technical complexities of gene transfer in plants. Touches on the regulation of gene transfer technology.
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Huiling Chen, Liguo Shuai, Weihang Zhu and Mei Miao
This paper aims to investigate the perception threshold (PT) of electrotactile stimulation under non-steady contact condition (NSCC) which is rarely considered in previous reports…
Abstract
Purpose
This paper aims to investigate the perception threshold (PT) of electrotactile stimulation under non-steady contact condition (NSCC) which is rarely considered in previous reports mainly because of the difficulty with experimental control. Three factors of NSCC are involved, including the current alternating frequency, the tapping interval of stimulation and the stimulating area of skin. The study is aimed at providing the basic PT data for design and application of wearable and portable electrotactile device.
Design/methodology/approach
The up-down method was selected to assess PT, and 72 experimental scenarios were constructed. During the study, we developed an experimental platform with the function of data record and programmable current stimulation. With psychophysical experiment, more than 10,000 data were collected. Furthermore, statics analysis and ANOVA test were opted for exploring the main factor influencing PT.
Findings
NSCC has different PTs on each body location, and PT has a positive correlation with frequency. In general, PT in NSCC is significantly lower than that in SCC. In some cases, it can be lower by more than 60 per cent. In addition, women have a lower PT than men across all age groups, and the younger is generally more sensitive than the older in electro-sensation.
Research limitations/implications
Limited factors of NSCC were considered in this study. Contact time and break interval should be investigated in the future work.
Practical implications
The paper includes implications for the development of smart electrotactile device.
Originality/value
This paper fulfills a challenge in assessing the PT under NSCC.
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Sebastian Böhmelt, Nils Kielian, Michael Hagel, Marcus Stiemer, Marvin-Lucas Henkel and Markus Clemens
The purpose of this paper is to present the implementation of a balanced domain decomposition approach for the numerical simulation of large electro-quasistatic (EQS) systems in…
Abstract
Purpose
The purpose of this paper is to present the implementation of a balanced domain decomposition approach for the numerical simulation of large electro-quasistatic (EQS) systems in biology. The numerical scheme is analyzed and first applications are discussed.
Design/methodology/approach
The scheme is based on a finite element discretization of the individual domains obtained by decomposition and a physically consistent inter-domain coupling realized via Robin boundary conditions. The proposed algorithms can efficiently be implemented on a highly parallelized computing grid.
Findings
The feasibility and applicability of the method is proven. Further, a couple of technical details are found that increase the efficiency of the method.
Originality/value
The presented method offers an enhanced geometrical flexibility and extensibility to simulate larger cell systems with higher model resolution compared to other methods presented in the literature. The presented analysis provides an understanding of the balanced coupling scheme for large EQS systems.
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Juan C. Vanegas-Acosta, V. Lancellotti and A.P.M. Zwamborn
Electric fields (EFs) are known to influence cell and tissue activity. This influence can be due to thermal or non-thermal effects. While the non-thermal effects are still matter…
Abstract
Purpose
Electric fields (EFs) are known to influence cell and tissue activity. This influence can be due to thermal or non-thermal effects. While the non-thermal effects are still matter of discussion, thermal effects might be detrimental for cell and tissue viability due to thermal damage, this fact being exploited by applications like hyperthermia and tissue ablation. The paper aims to discuss these issues.
Design/methodology/approach
In this work the authors investigate the influence of thermal damage in the consolidation of bone formation during electrostimulation (ES). The authors introduce a mathematical model describing the migration of osteoprogenitor cells, the thermal variation, the thermal damage accumulation and the formation of new bone matrix in an injury (fracture) site.
Findings
Numerical results are in agreement with experimental data and show that EFs more intense than 7.5 V/cm are detrimental for the viability of osteoprogenitor cells and the formation of new bone.
Originality/value
The model is suitable to conduct dosimetry studies in support of other different ES techniques aimed at improving bone and soft tissues repair.
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Genetic modification techniques have transformed the scope ofbiotechnology. Describes the new technology and its potential uses inthe food industry. Safety is an important…
Abstract
Genetic modification techniques have transformed the scope of biotechnology. Describes the new technology and its potential uses in the food industry. Safety is an important consideration and there are European Community and British legislative safeguards for human and environmental safety. Proposed EC legislation on novel foods, as drafted, contains equivalent provisions. There are wider questions about use of genetic modification in food and these have been addressed by a Government Committee on the Ethics of Genetic Modification and Food Use. Consideration has also been given by the Food Advisory Committee to the question of labelling.
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