Technological development in Therapeutic applications of alternating electric fields: Review

A number of bacteria, virus and other unhealthy cells need to be killed for getting rid of them. For more than a century antibiotics have been effectively used for killing bacterial pathogens and chemical drugs against the cancer cells. However, there are bacteria and cancer cells that are drug resistant. This may have to be overcome by other stronger drugs, higher dosage. These can have detrimental side effects. Other non drug methods to aid the effect of these drugs have always been in research. Electrochemotherapy, a method of using electric fields along with the drug to be used topically has been one of the successful approaches. One of the most recent methods of Tumor Treating Frequencies (TTF) for a brain cancer has been FDA approved. This article details the use of TTF. The article also details some other latest research where alternating fields are used as antibacterial agents

Effective active learning strategies I have used in University class room

In this paper I summarize the various activities used in class room and laboratory teaching of first and second year engineering. These activities can be grouped under ‘active learning’. I describe the activities and the various attributes associated with each activity along with the advantages of using the mentioned activity model instead of simply a single ended lecturing model. Although most of these have erupted from an urge to increase students learning while making the topics increasingly interesting for them, most of these strategies have been researched out globally as effective teaching practices. Traditionally lecturers may think that they are doing active learning when questions are asked and a few students always answer or discussions amongst the same group of people take place from time to time. Although this includes student participation, it is engaging only a small fraction of a big class which is not optimum in terms of benefit to the class as whole and individuals of the class. Active learning is taking place in your class when you ask a question, pose a problem, or throw some type of challenge at them; ask your students to work individually or in pairs or small groups to come up with a response; give them some set time to do it; stop them, and invite one or more individuals or groups to share their responses with the class. The teacher as an expert can further comment on the answer if required. This paper concludes with a number of proven methods of including active learning strategies in first and second year Physics/electronics engineering class. Reference to global research about these strategies is included

Teaching electric field topic with computer visualization

Electromagnetic field is undoubtedly one of the most difficult course in the undergraduate courses for electronics/physics degrees. The difficulty arises from the fact that electromagnetic fields are not visible unlike some other concepts in mechanical engineering where one deals with concrete objects. Students generally find it hard to grasp the ideas as these ideas are abstract and their learning cannot be supported through simple experiments in which they can handle objects and see what is happening. Visualisation of electric field lines and equipotential contours in several different scenarios can be demanding to imagine. There are mathematical ways to calculate however these methods can be equally or more challenging. For the first instance before mathematics of the electric fields is introduced if the electric field lines can be viewed as an output of a simple computer model it can be very beneficial to students for their understanding and retaining/creating their interest and enthusiasm in the subject. Since several parameters in the model can be changed very easily, effects of those parameters on electric field lines can be viewed. The main objective of this article is to demonstrate some such simple modelling possibilities using the available software package

Dynamic Electroporation Modelling

In this thesis, modelling and simulation of the effects of electric fields on a single spherical cell are undertaken. Of interest is the effect that different electric field waveforms have on the induced transmembrane potential of the cell and by consequence the electropermeabilization of the cell membrane in terms of pore density or the fraction of the cell area that the pores occupy. Conventional biotechnology processes of electroporation make use of unipolar electric field pulses, which are known to generate undesirable conditions such as asymmetrical electropermeabilization. These electrical protocols also contribute to lower efficiencies in electroporation based applications (in terms of uptake of molecules in the cell) by being sensitive to cell radii. Until recently, theoretical models of electroporation have lagged behind the experimental research. In order to optimize the efficiency of electroporation, it is important to consider as many biological and physical aspects as possible and it is a necessity that a variety of electric pulse parameters be tested. Thus a comprehensive model which can predict electropermeabilization as a result of any form of applied electric field and other important electroporation parameters is necessary. None of the existing theoretical modelling studies present simulations of dynamic electroporation modelling as a cell response to bipolar electric field wave-shapes. Developing such a model is the aim of this thesis. In this thesis two numerical models are developed. These models consider electroporation as a dynamic process and include the non-linear dynamic effects of membrane electropermeabilization. The first model assumes all pores are identical and small (0.76~nm radius) and is capable of simulating transmembrane potential and pore density temporally and spatially, given any form of applied electric field and other important electroporation system parameters such as external medium, membrane, and cytoplasm complex dielectric properties. The piece-wise step response model presented here is used to simulate cell response to several different applied electric field wave-shape pulses.% including a unipolar square wave, bipolar square wave, bipolar sine wave, bipolar rectangular wave (rectangular pulse train), and a bipolar triangular wave. Additional results from the first model demonstrate how the efficiency of electroporation related applications can be significantly improved by appropriately adjusting the parameters of the applied electric field and the extracellular conductivity. Emphasis is given on the normalization of the degree of electroporation (in terms of pore density) for two cell radii (7.5~$\mu$m and 15~$\mu$m). Although, these results gave a fair indication of the extent of electroporation in terms of pore density, the approximation that all pores have the same size, and do not change with time, may not be appropriate. There is a need to model electroporation so as to reflect the growth or shrinkage of pores with time, as well as efficiently handle arbitrary waveshapes of electric fields. The additional information about pore radius evolution gives a more realistic picture of the extent of electroporation, especially if one is to model for longer time (longer than 1~$\mu$s) or if an application necessarily required existence of larger pores (radius lager than 1~nm) rather than just the total pore area. Pore radius and pore numbers affect the transmembrane potential, which in turn affects pore density and pore radius. Literature includes information on spatial and temporal aspects of pore radius evolution. However, the electric fields used in these models were limited to unipolar DC pulses and details of temporal and spatial evolution of transmembrane potential and pore radius have not been reported. The second model developed in this thesis simulates spatial and temporal aspects of pore radius as an effect of any given form of applied electric field (including unipolar or bipolar), and other important electroporation system parameters. The transmembrane potential and pore radii as function of time and angular position about the cell membrane are presented. The results show that pore radii tend to be more normalized when an AC (bipolar) field is used when compared to a DC (unipolar) field (pore radii ranging from 1~nm to 8~nm for DC protocol compared with 1~nm to 3.4~nm for AC protocol when the pulse amplitude used in both cases is such as to give a similar fractional pore area at the end of 2~$\mu$s). Additional simulation results from this model are used to compare the extent of electroporation in response to sinusoidal AC (bipolar) electric field pulses of two different frequencies in a range of extracellular conductivity for two different cell radii (7.5~$\mu$m and 15~$\mu$m). It is observed that a higher frequency (1~MHz) bipolar sinusoidal applied electric field pulse reduces the relative difference in fractional pore area for the two cell sizes compared to a lower frequency (100~kHz) pulse. Nevertheless for the high frequency, a significantly higher amplitude is required to create the same level of average fractional pore area. Asymmetry of fractional pore area between the two hemispheres of the cell is observed for both field protocols

Modelling single cell electroporation with bipolar pulse parameters and dynamic pore radii

We develop a model of single spherical cell electroporation and simulate spatial and temporal aspects of the transmembrane potential and pore radii as an effect of any form of applied electric field. The extent of electroporation in response to sinusoidal electric pulses of two different frequencies in a range of extracellular conductivity for two different cell radii are compared. Results show that pore radii tend to be more normalized for AC fields. The relative difference in fractional pore area is reduced by the use of a 1 MHz sinusoidal applied electric field over a 100 kHz field

Development of a multispectral imaging system for apple firmness prediction

Multispectral imaging has been studied in recent years as a means of assessing fruit firmness. Here we report on the development of a static multispectral imaging system (MSI) that was used to validate the potential of the technique for high-speed commercial grading. The system consists of a high-performance CMOS camera, four lasers, electronically controlled shutters and a location control system. It captures four spectral scattering images on the fruit. In this study 100 ‘Royal Gala’ apples have been measured using the static MSI. The MSI measurements were applied on the intact apple and also on a flat surface of internal flesh exposed by removing a thick skin slice. The scattering profiles were fitted with a standard light diffusion model and a heuristic modified Lorentzian model. The results showed that the correlations between penetrometer firmness and model parameters were poor, with the correlation coefficient, R, ranging from 0.4 to 0.8 in the best circumstance of the flat surface measurements. Although multivariate models can improve the correlations, this work suggests that laser scattering information on its own is not sufficient to predict the firmness

Drug delivery by electroporation: Review

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Most common routes of administration include the preferred non-invasive peroral (through the mouth), topical (skin), transmucosal (nasal, buccal/sublingual, vaginal, ocular and rectal) and inhalation routes. Current effort in the area of drug delivery include the development of targeted delivery in which the drug is only active in the target area of the body (for example, in cancerous tissues) and sustained release formulations in which the drug is released over a period of time in a controlled manner from a formulation. This is achieved by combining electroporation with the input of drugs at a location. This paper reviews the process of electroporation and then further discusses the electrochemotherapy, one of the most upcoming application of electroporation in biotechnology

Non-linear time domain model of electropermeabilization: Effect of extracellular conductivity and applied electric field parameters

This paper describes simulation results obtained from a previously reported numerical model for a single cell exposed to an arbitrary waveform electric field pulse. This paper concentrates on how the efficiency of electroporation related applications can be significantly improved by appropriately adjusting the parameters of applied electric field and conductivity of the external medium, σe. Emphasis is given here on the normalization of the degree of electroporation for a range of cell radii. The simulated results indicate that it may be difficult for cells of substantially different sizes to be close to uniformly electroporated if surrounded by media with a conductivity higher than around 5*10⁻³ S/m for 100 kHz bipolar pulses, or 0.2 S/m for 1 MHz bipolar pulses. To achieve as normalized as possible electroporation for the radii/size variation required in any particular application, using a lower σe would be preferable. There is, however, a limit to how low the external conductivity can be made, as the applied electric field amplitude must stay within practical limits. Considering 3*10¹³ pores/m² as a nominal pore density N for approximately optimum electroporation, σe could be as low as 0.08 S/m for a 7.5 µm cell radius with a peak electric field of 1.2*10⁵V/m (depending on the pulse shape and frequency). For a 15 µm cell radius, σe could be as low as 0.05 S/m (depending on the pulse shape and frequency). It is seen that the relative difference of N between the two cell sizes investigated is consistently lower for a bipolar sine wave electric field compared to a bipolar square wave electric field, even though the square wave electric field peak amplitude is always lower for an equivalent N

Wine maturation using high electric field

Wine maturation can take a long time and consumes storage space which can be a drawback while considering commercial aspect of wine making. In the past scientists have carried out experiments on maturing wine quickly using ultrasounds or gamma radiations. This study reports about maturing wine with high electric field at different frequencies applied for a short time duration. The electric field intensity and the frequency of the field along with the exposure time of wine to this field seem to be important parameters that could affect the the treated wine. Results obtained are encouraging and have a potential for commercial interest