High-accuracy adaptive simulations of a Petri dish exposed to electromagnetic radiation

This paper analyses numerically the electric field distribution of a liquid contained in a Petri dish when exposed to electromagnetic waves excited in a rectangular waveguide. Solutions exhibit high-gradients due to the presence of the dielectric liquid contained in the dish. Furthermore, electromagnetic fields within the dielectric have a dramatically lower value than on the remaining part of the domain, which difficults its simulation. Additionally, various singularities of different intensity appear along the boundary of the Petri dish. To properly reproduce and numerically study those effects, we employ a highly-accurate hp-adaptive finite element method. Results of this study demonstrate that the electric field generated within the circular Petri dish is non-homogeneous, and thus, a better shape, size, or location of the dish is needed to achieve an equally distributed radiation enabling the uniform growth of cell cultives

High-accuracy adaptive modeling of the energy distribution of a meniscus-shaped cell culture in a Petri dish

Cylindrical Petri dishes embedded in a rectangular waveguide and exposed to a polarized electromagnetic wave are often used to grow cell cultures. To guarantee the success of these cultures, it is necessary to enforce that the specific absorption rate distribution is sufficiently high and uniform over the Petri dish. Accurate numerical simulations are needed to design such systems. These simulations constitute a challenge due to the strong discontinuity of electromagnetic material properties involved, the relative low field value within the dish cultures compared with the rest of the domain, and the presence of the meniscus shape developed at the liquid boundary. The latter greatly increases the level of complexity of the model in terms of geometry and intensity of the gradients/singularities of the field solution. In here, we employ a three-dimensional (3D) hp-adaptive finite element method using isoparametric elements to obtain highly accurate simulations. We analyze the impact of the geometrical modeling of the meniscus shape cell culture in the hp-adaptivity. Numerical results showing the error convergence history indicate the numerical difficulties arisen due to the presence of a meniscus-shaped object. At the same time, the resulting energy distribution shows that to consider such meniscus shape is essential to guarantee the success of the cell culture from the biological point of view

A summary of my twenty years of research according to Google Scholars

I am David Pardo, a researcher from Spain working mainly on numerical analysis applied to geophysics. I am 40 years old, and over a decade ago, I realized that my performance as a researcher was mainly evaluated based on a number called \h-index". This single number contains simultaneously information about the number of publications and received citations. However, dif- ferent h-indices associated to my name appeared in di erent webpages. A quick search allowed me to nd the most convenient (largest) h-index in my case. It corresponded to Google Scholars. In this work, I naively analyze a few curious facts I found about my Google Scholars and, at the same time, this manuscript serves as an experiment to see if it may serve to increase my Google Scholars h-index

A summary of my twenty years of research according to Google Scholars

I am David Pardo, a researcher from Spain working mainly on numerical analysis applied to geophysics. I am 40 years old, and over a decade ago, I realized that my performance as a researcher was mainly evaluated based on a number called \h-index". This single number contains simultaneously information about the number of publications and received citations. However, dif- ferent h-indices associated to my name appeared in di erent webpages. A quick search allowed me to nd the most convenient (largest) h-index in my case. It corresponded to Google Scholars. In this work, I naively analyze a few curious facts I found about my Google Scholars and, at the same time, this manuscript serves as an experiment to see if it may serve to increase my Google Scholars h-index

Single-Proton Irradiation of Living Cells - Development of New Tools for Low-Dose Radiation Research

A Single-Ion Hit Facility (SIHF) consists of a custom-build facility based in particle accelerators which offers irradiation controlling the number of delivered particles with a precise targeting localization. The irradiation spot can be confined down to the nanometre scale allowing the irradiation of subcellular compartments with a single particle. Therefore, these facilities have become a very powerful tool for biological applications specifically to study low-dose radiation effects on living cells. A SIHF has been created at the Lund Nuclear Microprobe (LNM-SIHF) and, in order to make it operational, several tools were fabricated. These tools included the necessary software for cell recognition, custom-designed Petri-type dishes suitable for cell culture and irradiation, and other tools which allow the evaluation of the system. Additionally, the importance of reactive oxygen species (ROS) in bystander cells after non-targeted proton irradiation was investigated on the human hepatoma cell line (HepG2). In-house implemented software, SeACell, provides on-line cell recognition and localization in a short time and high efficiency without the use of cell-staining dyes. The program was developed using IDL 6.2 language, and includes automated and manual targeting selection through a user-friendly interface. In addition, table colour display and filter drop-down menus were added to improve the quality of the input image if required. Custom-designed irradiation dishes permit controlling the cells growth position by confining them through limiting structures on the floor of the dish and therefore, facilitating repeated access to the cell position. The epoxy-based photopolymer SU-8 was patterned by UV lithography technique producing irradiation dishes, with a supporting layer of approximately 5 microns thick where 5 microns height walls were used to form the limiting structure. The entire structure contains 400 squares that can be located by a row letter and column number printed outside the grid. Other tools were manufactured by UV large exposure and the SU-8 photoresist: an artificial cell sample, which offered a semi-realistic scenario to test the system's capability, and a calibration sample used to establish the coordinates of the irradiation point in all the microscopes in which the cells were inspected. Also, two Ni dot arrays were fabricated using electron beam lithography to test the targeting accuracy of the system

Measurement and mathematical modeling of hyperthermia induced bioeffects in pancreatic cancer cells

Doctor of PhilosophyDepartment of Electrical and Computer EngineeringPunit PrakashSurgical resection is the standard of care for pancreatic cancer, although treatment outcomes remain poor, and a large fraction of the patient population are not surgical candidates. Minimally invasive interventions employing non-ionizing energy, such as image-guided thermal ablation, are under investigation for treatment of unresectable tumors and potentially for debulking and downstaging tumors. Tissue regions at the periphery of an ablation zone are exposed to sub-ablative thermal profiles (referred to as “mild hyperthermia”), which may induce a range of bioeffects including change in perfusion, immune modulation, and others. Bioeffects induced by heating are a function of intensity of heating and duration of thermal exposure. This dissertation presents a suite of tools for integrated in vitro experimental studies and modeling for characterizing bioeffects following thermal exposure to pancreatic cancer cells. An instrumentation platform was developed for exposing monolayer cell cultures to temperatures in the range 42–50°C for 3–60 minutes. The platform was employed to determine the Arrhenius kinetic parameters of thermal injury to pancreatic cancer cells (i.e. loss in viability) following heating. When coupled with bioheat transfer models, these parameters facilitate investigations of thermal injury profiles in pancreatic tumors following thermal exposure with practical devices. There has been growing interest in exploring the potential of thermal therapies for modulating tumor—immune system interactions, due in part to release of damage associated molecular patterns (DAMPs) from stressed tumor cells and their role in recruiting and activating antigen presenting cells. The in vitro thermal exposure platform was further expanded to allow for experimental measurement of extracellular DAMPs released from murine pancreatic cancer cells following heating to temperatures in the range 42 – 50°C for 3-60 mins. A model predicting the dynamics of heat-induced DAMPs release was developed and may inform the design of experiments investigating the role of heat in modulating the anti-tumor immune response. While in vitro experiments on monolayers are informative, 3D cell cultures (e.g., spheroid, organoids) provide an experimental platform accommodating multiple cell types in an environment that may be more representative of tumors in vivo. Furthermore, while the water-bath based in vitro platform applied for monolayers is well suited to achieving near-uniform temperature profiles, in vivo delivery of hyperthermia often yields a gradient of temperatures that is not achieved through water-bath based heating. Thus, an in vitro platform for exposing cells in 3D culture (co-culture of multiple cell populations) to 2.45 GHz microwave hyperthermia was developed. The platform includes a printed patch antenna and associated thermal management elements and was applied to study changes in gene expression profile of a 3D culture of pancreatic cancer cells and fibroblasts. This non-contact microwave heating approach may help enable additional studies for exploring the bioeffects of heat on cancer cells

Study and development of a novel radio frequency electromedical device for the treatment of peri-implantitis: experimental performance analysis, modelling of the electromagnetic interaction with tissues and in vitro and in vivo evaluation

La peri-implantite (PI) è una grave patologia che interessa tessuti peri-implantari molli e duri. Ad oggi, la prevenzione è l’unico mezzo per contrastarla. Recentemente, è stata sperimentata una terapia basata sulla somministrazione di corrente elettrica a radio frequenza (successo: 81%). Il trattamento è stato simulato numericamente, fornendo le distribuzioni di corrente (EC) e campo elettrico (EF) nei tessuti: l’effetto anti-infiammatorio è attribuibile alla EC, quello di rigenerazione ossea al EF. Sono state considerate le misure di bioimpedenza (BM) per individuare le infiammazioni; numericamente si sono osservati cambiamenti nel modulo di impedenza del 4-20% (secondo diversi parametri), anche più alti sperimentalmente (35% infiammazione, 56% PI). Le BM permettono quindi di identificare il tessuto da trattare. Per la ripetibilità, sono state considerate radici di denti naturali, numericamente e sperimentalmente; l’ordine di grandezza è lo stesso (qualche kΩ), anche se ci sono differenze legate alle condizioni di misura. La variabilità intra-soggetto è il 10% in uno stesso giorno, fino al 26% in giorni diversi; quella inter-soggetto è più alta. La sicurezza elettrica è stata attentamente esaminata e si sono individuate le direttive applicabili (IEC 60601-1, 60601-1-2 and 60601-2-2). Sono stati fatti test in vitro per valutare l’effetto della terapia sulla vitalità cellulare: non c’è un significativo aumento della necrosi (vitalità: 85% test, 94% controlli), l’effetto negativo principale è l’apoptosi. Sono stati numericamente indagati possibili effetti termici: non sono stati individuati riscaldamenti nocivi dei tessuti. Si è progettato un nuovo dispositivo (PeriCare®) per trattare la PI, con parti diagnostica (BM) e terapeutica. Si stanno progettando elettrodi specifici e realizzando il prototipo. Si sta compilando il fascicolo tecnico e pianificando i test di conformità, in vista della certificazione. Il dispositivo medico dovrebbe entrare nel mercato entro l’anno.Peri-implantitis is a severe disease affecting hard and soft peri-implant tissues. At present, prevention is the only means to contrast it. Recently, a therapy based on the administration of radio frequency electric current was experimented (success rate: 81%). The treatment was numerically simulated, providing the electric current (EC) and field (EF) distributions in peri-implant tissues: the anti-inflammatory effect can be associated to EC, the bone regeneration to the EF. Bioimpedance measurements (BM) were investigated to detect inflammation; changes in the measured impedance modulus are equal to 4-20% (depending on different parameters) from numerical results, also more evident experimentally (35% inflammation, 56% peri-implantitis). So, BM could allow to detect the tissue to be treated. To evaluate the repeatability, natural tooth roots were numerically and experimentally measured; the order of magnitude is the same (some kΩ), even if there are differences probably due to the measurement conditions. Intra-subject variability was of 10% in the same day, but up to 26% in different days; inter-subject variability was higher. The electrical safety was accurately taken into account. The applicable directives were individuated (IEC 60601-1, 60601-1-2 and 60601-2-2). In vitro tests were carried out to evaluate the effect of the therapy on cell vitality: there is not a significant increase in necrosis (vitality: 85% tests, 94% controls), the main negative effect is apoptosis. Possible thermal effects were numerically investigated: no dangerous tissue heating was observed. A new device for the peri-implantitis treatment, PeriCare®, was designed, with diagnostic (BM) and therapeutic parts. Proper electrodes are being designed and the prototype is being realized. The technical file is being compiled and the conformity verification tests are being planned towards the certification process. Hopefully, the medical device will be placed into the market within this year

Computation of electromagnetic fields in assemblages of biological cells using a modified finite difference time domain scheme. Computational electromagnetic methods using quasi-static approximate version of FDTD, modified Berenger absorbing boundary and Floquet periodic boundary conditions to investigate the phenomena in the interaction between EM fields and biological systems.

yesThere is an increasing need for accurate models describing the electrical behaviour of individual biological cells exposed to electromagnetic fields. In this area of solving linear problem, the most frequently used technique for computing the EM field is the Finite-Difference Time-Domain (FDTD) method. When modelling objects that are small compared with the wavelength, for example biological cells at radio frequencies, the standard Finite-Difference Time-Domain (FDTD) method requires extremely small time-step sizes, which may lead to excessive computation times. The problem can be overcome by implementing a quasi-static approximate version of FDTD, based on transferring the working frequency to a higher frequency and scaling back to the frequency of interest after the field has been computed. An approach to modeling and analysis of biological cells, incorporating the Hodgkin and Huxley membrane model, is presented here. Since the external medium of the biological cell is lossy material, a modified Berenger absorbing boundary condition is used to truncate the computation grid. Linear assemblages of cells are investigated and then Floquet periodic boundary conditions are imposed to imitate the effect of periodic replication of the assemblages. Thus, the analysis of a large structure of cells is made more computationally efficient than the modeling of the entire structure. The total fields of the simulated structures are shown to give reasonable and stable results at 900MHz, 1800MHz and 2450MHz. This method will facilitate deeper investigation of the phenomena in the interaction between EM fields and biological systems. Moreover, the nonlinear response of biological cell exposed to a 0.9GHz signal was discussed on observing the second harmonic at 1.8GHz. In this, an electrical circuit model has been proposed to calibrate the performance of nonlinear RF energy conversion inside a high quality factor resonant cavity with known nonlinear device. Meanwhile, the first and second harmonic responses of the cavity due to the loading of the cavity with the lossy material will also be demonstrated. The results from proposed mathematical model, give good indication of the input power required to detect the weakly effects of the second harmonic signal prior to perform the measurement. Hence, this proposed mathematical model will assist to determine how sensitivity of the second harmonic signal can be detected by placing the required specific input power

Tunable Terahertz Metamaterials with Germanium Telluride Components

Terahertz (THz) technology is an emerging field with many exciting applications. THz waves can be used to locate explosives and illicit drugs in security applications, or DNA and other molecule resonances in medical applications. THz frequencies represent the next level of modern, high-speed computing, but they also can be used for covert battlefield communications links. Metamaterials are an integral part of THz technology because they can be used to create exotic material properties—permittivities and permeabilities—in a part of the frequency spectrum that is otherwise rather empty and passive. This work aims to acquire a fuller understanding of THz metamaterials in terms of background and theory, and then use this understanding to create a few novel, actively tunable structures using the phase-change material germanium telluride