<p>Radiation induced bystander effects have given the cancer risk analysis a whole new paradigm. However the actual mechanism involved in producing the effects is still not clear. The basic bystander signal is assumed to be a biological signal. In this study we proposed and tried to quantify the presence of a physical signal in the form of electromagnetic radiation that can trigger a biological response in the bystander cells. In bystander effect studies where the cells are exposed to very low fluence of charged particles there could be several regions that can produce electromagnetic radiation due to the process of atomic/molecular excitations and relaxations. We focused on quantifying the number of ultraviolet photons emitted when charged particles pass through different media that have relevance to radiation biology experiments. The choice of UV photons was made due to the reason that its effects on living cells are very well documented. For this purpose we developed a system which employed the technique of single photon counting to measure the light emitted from samples irradiated under vacuum by a charged particle beam. Photon counting was done using a fast photomultiplier tube (Hamamatsu R7400p) with a peak cathode response at 420 nm wavelength.</p> <p>In the early set of “proof of principle experiments” we tested polystyrene targets for ion beam induced luminescence. Polystyrene is one of the materials that are used as a cell substrate for radiation biology experiments. The luminescence yield from polystyrene was measured in terms of absolute value i.e. number of photons per second per unit solid angle. The output appeared to have a non-linear behavior with the incident Ion fluence: it rose exponentially to an asymptotic value. We irradiated the samples with beam energies varying from 1 MeV to 2.0 MeV and showed saturation at or before an incident fluence rate of 3×10¹³ H⁺/cm²s. The average saturation value for the photon output was found to be 40 × 10⁶ cps. Some measurements were performed using filters to study the emission at specific wavelengths. In the case of filtered light measurements, the photon output was found to saturate at 28×10³, 10×10⁶, and 35×10⁶ cps for wavelengths of 280±5 nm, 320±5 nm and 340±5 nm respectively. Using the IBIL signal evolution characteristics with the ion fluence we determined the ions produce a damage having a cross section of the order of 10^-14 cm² in polystyrene. The average radiant intensity was found to increase at wavelengths of 280 nm and 320 nm when the proton energy was increased. Having found an evidence of a significant production of UV in ion irradiated, biologically relevant, material we extended this study further into the measurements from other relevant materials in radiation biology.</p> <p>Here charged particle irradiation was performed using positively charged protons (H⁺) ranging in energy from 1.2 MeV to 2.2 MeV at a fluence rate of 2.7×10¹⁰ protons mm^-2s^-1.The materials chosen for this study were polypropylene, Mylar, Teflon, and Cellophane as they are all materials commonly used in radiation biology experiments as cell substrates or containers. In addition, we performed measurements of two NIST standard materials derived from living cells: oyster tissue and citrus leaves. These materials were measured as a powder.</p> <p>All the container materials were found to emit UV frequency photons at emission levels that are significant enough to warrant further investigation of the potential biological consequences. In addition, the NIST standard reference materials oyster tissue and citrus leaves also emitted UV when irradiated. This suggested that biological materials may themselves emit UV at significant levels when irradiated with charged particles.</p> <p>We established this further by irradiated cells with β-particles. Cells were plated in Petri-dishes of two different sizes, having different thicknesses of polystyrene (PS) substrate. Exposure of the cell substrates (polystyrene) only resulted in the production of 1035 photons per unit activity in μCi of ⁹⁰Y which was equivalent to an exposure of 840 <em>β</em>-particles/cm² to the substrate. For a collimated electron beam exposure, we observed 158-167 photons per unit μCi (18 β-particles per cm² on the substrate) for different thicknessesof the substrate. Upon irradiating HPV-G cells plated on the PS dishes we determined that the luminescence gradually increased with the increasing exposure of β-particles; reaching up to 250 % of that of the luminescence without any cells for an activity of 180 μCi. For general irradiation conditions we found statistically significant difference in luminescence output for varying cellular densities with cells only and with the application of medium on top of the cells. The colourless medium increased the total luminescence yield while the coloured medium decreased it. When the cells were irradiated using a collimated beam of electrons it was found that the luminescence decreases with the increasing cellular density thus providing an evidence of re-absorption of photons within the surroundings.</p> <p>After establishing the fact that charged particles induce light emission from the materials that have a relevance to the radiation biology experiments. We extended our study further to find out other sources of radiation that could affect the dose distribution in radiation biology experiments. In radiation biology experiments the low doses of radiation are usually delivered usingamicrobeam charged particle accelerator. Microbeams delivers a highly localized and small dose to the biological medium by using a set of collimators that confine the charged particle beam to a very narrow (micron level) region. Since the collimation block a significant proportion of the beam therefore there is a chance of the production of low energy x-rays and secondary electrons. We used Monte Carlo simulations to investigate the production of particle induced x-rays and secondary electrons in the collimation system and its possible effects on the final dose delivery to the biological medium. We found no evidence of the escape of x-rays or secondary electrons from the collimation system for proton energies of up to 3 MeV. The thickness of the collimators was sufficient to reabsorb all the generated low energy x-rays and secondary electrons. However if the proton energy exceeds 3 MeV then a significant proportion of 10 keV and 59 keV (K-α) x-rays can be emitted by the collimator. Further it was established that due to the phase space distribution of particles in various orientations with the beam axis there are significant chances of hitting non-targetted cells in microbeams that employ a collimator to confine the beam.This may happen due to the beam particles travelling obliquely with the beam axis thus passing the collimator edge and hitting the non-targetted cells. Another reason could be the scatter of beam particles inside the collimator.</p> <p>The evidence of the production of UV in materials relevant to the radiation biology experiments suggest that the conclusions and hypotheses derived from some radiation bystander experiments need to be re-thought, as charged particle irradiation leads to some level of UV emission in experimental materials which may be the cause of some “non-targeted” effects.</p> / Doctor of Philosophy (PhD)

Les microfaisceaux (MBs) de rayons X générés par un synchrotron permettent de délivrer des doses de radiation très élevées, jusqu'à plusieurs centaines de gray (Gy), sans pour autant induire de dommages tissulaires irréversibles dans les zones avoisinant la lésion. La réactivité du réseau vasculaire à se régénérer grâce aux cellules endothéliales, est probablement un mécanisme clef dans la radio-tolérance des tissus sains, puisqu'il permet une recolonisation rapide des zones tissulaires lésées. Cette méthode permet ainsi de reproduire de façon non invasive une incision chirurgicale précise du cortex tout en préservant son architecture. Cette caractéristique présente un intérêt certain et permet d'envisager le développement de nouveaux modèles neurobiologiques expérimentaux ouvrant la voie à des traitements innovants pour de nombreux troubles cérébraux. Durant cette thèse, les microfaisceaux ont été utilisés sur la structure corticale et l'hippocampe de rats. Concernant le cortex, les MBs ont été appliqués au niveau du cortex sensori-moteur (taille 100 µm/600 µm, of 400 µm/1200 µm crête à crête, dose pics - vallèe de 360-240 Gy/150-100 Gy) chez des rats males Wistar sains ainsi que chez des rats développant des attaques cérébrales consécutivement à l'injection corticale d'Acide Kaïnique (KA). Suite aux traitements par MBs, les performances motrices étaient évaluées par le test du Rotarod et les structures corticales étudiées par immunohistochimie grâce au marquage par NeuN et GFAP des neurones et astrocytes matures. Aucun déficit neurologique n'a été observé chez les rats sains soumis au protocole de traitement par MBs et une diminution significative (normalement là il faut mettre des statistiques ou au moins les avoir sinon tu peux dire diminution importante) de la durée des crises de convulsions a pu être observée chez les rats KA. L'incidence des MBs (9 microfaisceaux de 75 μm de largeur séparés de 400 μm crête à crête, dose d'entrée: 1000 Gy) délivrés au niveau de l'hippocampe de rats Wistar sains a été comparée avec un traitement par rayons X de 10 Gy délivré uniformément. Le but de cette expérience était d'évaluer l'impact d'un traitement par microfaisceaux par rapport aux techniques d'irradiation conventionnelles. Pour cela, une évaluation quantitative (i) comparative a été faite sur la neurogénèse grâce à l'utilisation de marqueurs cellulaires (BrdU et Ki-67). Une étude (ii) a aussi été menée sur le long terme (1 an) pour mettre en évidence la corrélation entre la neurogénèse, les troubles de l'apprentissage et de la mémoire. Une préservation des cellules prolifératives a été observée au sein du groupe traité par MBs. Les transsections de l'hippocampe de rats par MBs n'induisent pas de troubles significatifs (là aussi, il faut avoir des stat ou alors utiliser troubles marquants) du comportement de plus, l'observation histologique et immunohistochimique des tissus a permis de mettre en évidence la conservation de sa structure.Le travail effectué au cours de cette thèse confirme que le traitement spécifique de zones radiosensibles du cerveau par les microfaisceaux est sûr et permet d'améliorer le pronostique des animaux traités par rapport aux techniques conventionnelles. Ainsi, le développement d'appareils permettant de délivrer des faisceaux de rayons submillimétriques capables de générer une destruction précise et limitée au niveau du cortex ou de l'hippocampe pourra permettre une prise en charge innovante plus sûre de nombreuses pathologies fonctionnelles cérébrales comme l'épilepsie ou certaines douleurs. / Synchrotron-generated X-ray microplanar beams (microbeams, MBs) are characterized by the ability to avoid widespread tissue damage following delivery of doses ranging from hundreds to over a thousand of Grays. The resistance of normal tissues to high doses of MBs is likely related to the fast repair of the microvessels and to the wide interface between normal and irradiated tissue, allowing fast recolonization of the microbeam ablated columns of tissue. The preservation of the cortical architecture following high-dose microbeam irradiation and the ability to induce non-invasively the equivalent of a surgical cut over the cortex is of great interest for the development of novel experimental models in neurobiology and new treatment avenues for a variety of brain disorders. In this Thesis microbeams transections were delivered to the rat cortex and hippocampus. MBs cortical transections were delivered to the sensory motor cortex (size 100 µm/600 µm, center-to-center distance of 400 µm/1200 µm, peak-valley doses of 360-240 Gy/150-100 Gy) of Wistar male healthy rats and rats developing seizures following cortical injections of Kainic Acid (KA)-. The motor performances following sensorimotor cortex transections was assessed by rotarod test. The effect of microbeam transections on cortical architecture was assessed by immunohistology with NeuN and GFAP, markers of mature neurons and astrocytes. No neurological deficit was observed in healthy animals undergoing sensorimotor cortex microbeam transections. Convulsive seizure duration was markedly reduced following transections in KA rats. MBs hippocampal transections (75 µm thickness, 400 c-t-c distance and 600 Gy as peak entrance dose) were performed in adult healthy Wistar rats. MBs transections were compared with an uniformly delivered X-ray dose (broad beam, BB) at 10 Gy. Our aims were to quantify (i) the impact of microbeams versus conventional irradiation on neurogenesis (using proliferative cells markers such as BrdU and Ki-67), and (ii) to investigate on a long term (1 year) the correlation between neurogenesis and impairments in learning and memory. Preservation of proliferative cells in the microbeam treated group were observed. Microbeam transections delivered to the hippocampus did not induce significant behavioral impairment histological and immunohistochemical findings showed a preserved hippocampal structure with evidence of higly precise transections diving the hippocampus in columns. This work confirms the safe delivery of high doses of radiation to specific and radiosensitive parts of the brain, if performed using microbeams Additionally, the development of clinical devices delivering submillimetric beams able to generate cortical or hippocampal transections might become a new powerful new tool for the clinical treatment of epilepsy, pain and other functional brain disorders.

In line with the rising demand for smarter solutions and embedded systems, Microelectromechanical systems (MEMS) have gained increasing importance for digital computing devices and Internet-of-Things (IoT) applications, most notably for mobile wearable devices. This achievement is driven by MEMS resonators' inherent properties such as simplicity, sensitivity, reliability, and low power consumption. Hence, they are being explored for ultra-low-power computing machines. Several fundamental digital logic gates, switching, and memory devices have been demonstrated based on MEMS microstructures' static and dynamic behavior. The interest of researchers in using MEMS resonators is due to seeking an alternative approach to circumvent the notable current leakage and power density problems of complementary metal-oxide-semiconductor (CMOS) technology. The continuous miniaturization of CMOS has increased the operating speed and reduces the size of the device. However, this has led to a relative increase in the leakage energy. This drawback in CMOS has renewed the interest of researchers in mechanical digital computations, which can be traced back to the work of Charles Babbage in 1822 on calculating engines. This dissertation presents axially-loaded and coupled-MEMS resonators investigations to demonstrate memory elements and different logic functions. The studies in this dissertation can be categorized majorly into three parts based on the implementation of logic functions using three techniques: electrothermal frequency tunability, electrostatic frequency modulations, and activation/deactivation of the resonant frequency. Firstly, the influence of the competing effects of initial curvature and axial loads on the mechanical behavior of MEMS resonator arches are investigated theoretically to predict the tunability of arches under axial loads. Then, the concept of electrothermal frequency tunability is used to demonstrate fundamental 2-bit logic gates. However, this concept consumes a considerable amount of energy due to the electrothermal technique. Next, the dynamic memory element and combinational logic functions are demonstrated using the concept of electrostatic frequency modulation. Though this approach is energy efficient compared to the electrothermal technique, it does not support the cascadability of MEMS resonator-based logic devices. Lastly, complex multifunctional logic gates are implemented based on selective modes activation and deactivation, resulting in significant improvement in energy efficiency and enabling cascadability of MEMS resonator-based logic devices.

abstract: One type of assistive device for the blind has attempted to convert visual information into information that can be perceived through another sense, such as touch or hearing. A vibrotactile haptic display assistive device consists of an array of vibrating elements placed against the skin, allowing the blind individual to receive visual information through touch. However, these approaches have two significant technical challenges: large vibration element size and the number of microcontroller pins required for vibration control, both causing excessively low resolution of the device. Here, I propose and investigate a type of high-resolution vibrotactile haptic display which overcomes these challenges by utilizing a ‘microbeam’ as the vibrating element. These microbeams can then be actuated using only one microcontroller pin connected to a speaker or surface transducer. This approach could solve the low-resolution problem currently present in all haptic displays. In this paper, the results of an investigation into the manufacturability of such a device, simulation of the vibrational characteristics, and prototyping and experimental validation of the device concept are presented. The possible reasons of the frequency shift between the result of the forced or free response of beams and the frequency calculated based on a lumped mass approximation are investigated. It is found that one of the important reasons for the frequency shift is the size effect, the dependency of the elastic modulus on the size and kind of material. This size effect on A2 tool steel for Micro-Meso scale cantilever beams for the proposed system is investigated. / Dissertation/Thesis / Doctoral Dissertation Systems Engineering 2019

The first objective of this dissertation is to present hybrid numerical-analytical approaches and reduced-order models to simulate microelectromechanical systems (MEMS) in multi-physics fields. These include electric actuation (AC and DC), squeeze-film damping, thermoelastic damping, and structural forces. The second objective is to investigate MEMS phenomena, such as squeeze-film damping and dynamic pull-in, and use the latter to design a novel RF-MEMS switch. In the first part of the dissertation, we introduce a new approach to the modeling and simulation of flexible microstructures under the coupled effects of squeeze-film damping, electrostatic actuation, and mechanical forces. The new approach utilizes the compressible Reynolds equation coupled with the equation governing the plate deflection. The model accounts for the slip condition of the flow at very low pressures. Perturbation methods are used to derive an analytical expression for the pressure distribution in terms of the structural mode shapes. This expression is substituted into the plate equation, which is solved in turn using a finite-element method for the structural mode shapes, the pressure distributions, the natural frequencies, and the quality factors. We apply the new approach to a variety of rectangular and circular plates and present the final expressions for the pressure distributions and quality factors. We extend the approach to microplates actuated by large electrostatic forces. For this case, we present a low-order model, which reduces significantly the cost of simulation. The model utilizes the nonlinear Euler-Bernoulli beam equation, the von K´arm´an plate equations, and the compressible Reynolds equation. The second topic of the dissertation is thermoelastic damping. We present a model and analytical expressions for thermoelastic damping in microplates. We solve the heat equation for the thermal flux across the microplate, in terms of the structural mode shapes, and hence decouple the thermal equation from the plate equation. We utilize a perturbation method to derive an analytical expression for the quality factor of a microplate with general boundary conditions under electrostatic loading and residual stresses in terms of its structural mode shapes. We present results for microplates with various boundary conditions. In the final part of the dissertation, we present a dynamic analysis and simulation of MEMS resonators and novel RF MEMS switches employing resonant microbeams. We first study microbeams excited near their fundamental natural frequencies (primary-resonance excitation). We investigate the dynamic pull-in instability and formulate safety criteria for the design of MEMS sensors and RF filters. We also utilize this phenomenon to design a low-voltage RF MEMS switch actuated with a combined DC and AC loading. Then, we simulate the dynamics of microbeams excited near half their fundamental natural frequencies (superharmonic excitation) and twice their fundamental natural frequencies (subharmonic excitation). For the superharmonic case, we present results showing the effect of varying the DC bias, the damping, and the AC excitation amplitude on the frequency-response curves. For the subharmonic case, we show that if the magnitude of the AC forcing exceeds the threshold activating the subharmonic resonance, all frequency-response curves will reach pull-in. / Ph. D.

Les microfaisceaux d’ions ont, au cours de ces dernières décennies, montré leur efficacité dansl’étude des effets des rayonnements ionisants sur le vivant notamment concernant les effets des faiblesdoses ou l’étude de l’effet de proximité. Le CENBG dispose depuis 2003 d’un dispositif permettant la micro-irradiation ciblée d’échantillons biologiques vivants. Les applications des microfaisceaux dans ce domainese sont récemment diversifiées et des études plus fines sur les mécanismes de réparation desdommages ADN radio-induits aux échelles cellulaire et multicellulaire sont devenues possibles via lesévolutions en imagerie par fluorescence et en biologie cellulaire. Ces approches ont nécessité une évolutionimportante de l'instrumentation de la ligne de micro-irradiation du CENBG qui a été entièrementredessinée et reconstruite dans un souci d’optimisation d’apport de nouvelles fonctionnalités. Les objectifsde mes travaux ont été i) la mise en service du dispositif, ii) la caractérisation des performances dusystème, iii) la mise en place de protocoles pour l’irradiation ciblée à dose contrôlée aux échelles cellulaireet multicellulaire, in vitro et in vivo, et le suivi en ligne des conséquences précoces de cette irradiation,iv) la modélisation des irradiations afin d’interpréter les observables biologiques au regard des donnéesphysiques calculées.Ces travaux ont permis i) de caractériser les performances du dispositif : une taille de faisceau d’environ2 μm sur cible et une précision de tir de ± 2 μm, de développer des systèmes de détection d’ions pour uncontrôle absolu de la dose délivrée, ii) d’induire des dommages ADN fortement localisés in vitro, et devisualiser en ligne le recrutement de protéines impliquées dans la réparation de ces dommages,iii) d’appliquer ces protocoles pour générer des dommages ADN in vivo au sein d’un organisme multicellulaireau stade embryonnaire, Caenorhabditis elegans.Ces résultats ouvrent la voie vers des expériences plus fines sur la ligne de micro-irradiation ciblée duCENBG pour étudier les effets de l’interaction des rayonnements ionisants avec le vivant, aux échellescellulaire et multicellulaire, in vitro et in vivo. / The main goal of radiobiology is to understand the effects of ionizing radiations on the living.These past decades, ion microbeams have shown to be important tools to study for example the effects oflow dose exposure, or the bystander effect. Since 2003, the CENBG has been equipped with a system toperform targeted micro-irradiation of living samples. Recently, microbeams applications on this subjecthave diversified and the study of DNA repair mechanisms at the cellular and multicellular scales, in vitroand in vivo, has become possible thanks to important evolutions of fluorescence imaging techniques andcellular biology. To take into account these new approaches, the CENBG micro-irradiation beamline hasbeen entirely redesigned and rebuilt to implement new features and to improve the existing ones. My PhDobjectives were i) commissioning the facility, ii) characterizing the system on track etch detectors, and onliving samples, iii) implementing protocols to perform targeted irradiations of living samples with a controlleddelivered dose, at the cellular and multicellular scales, and to visualize the early consequencesonline, iv) modelling these irradiations to explain the biological results using the calculated physical data.The work of these past years has allowed us i) to measure the performances of our system: a beam spotsize of about 2 μm and a targeting accuracy of ± 2 μm, and to develop ion detection systems for an absolutedelivered dose control, ii) to create highly localized radiation-induced DNA damages and to see onlinethe recruitment of DNA repair proteins, iii) to apply these protocols to generate radiation-induced DNAdamages in vivo inside a multicellular organism at the embryonic stage: Caenorhabditis elegans.These results have opened up many perspectives on the study of the interaction between ionizing radiationsand the living, at the cellular and multicellular scales, in vitro and in vivo.

The continuing quest for higher performance levels of modern gas turbine engines has been accompanied by the demand for higher engine operating temperatures. The use of Thermal Barrier Coatings (TBCs) enabled gas turbines to operate at higher temperatures by protecting the blade material (nickel superalloy) while operating in extreme environments. The TBC system typically consists of a bond coat for protection of the nickel–based superalloy against oxidation followed by a top coat consisting of a thermally insulating zirconia-yttria. In addition to the complex gradation in phases, the coatings are subjected to continuous oxidation with service exposure, mechanical loading on rotating parts, fatigue, thermal mis-match and temperature gradients. Hence, the study of failure mechanisms of TBCs become important in deciding operational reliability and service life of the coating. As there are many systems in which the operating temperatures are not high enough to warrant the use of the top coat (ceramic layer), the study of failure mechanisms in superalloys coated with only the bond coat continue to be of great interest. The present work concentrates on the fracture behavior of NiAl bond coats on nickel superalloy and seeks to evaluate the fracture toughness of the coating through the use of micro-machined samples. A review of the relevant literature indicated that while a considerable body of work exists on bulk tests of failure (spalling, splitting, etc.), not much has been reported in the open literature on the evaluation of basic quantities such as the toughness of the coating itself. The present thesis seeks to establish a protocol for the evaluation of toughness and crack propagation mechanisms in coatings through a combination of micro-sample testing that allows fracture to be correlated with location in the film and the use of an analytical model to quantitatively evaluate stress intensity factors in a bi-material system. A system of NiAl coating produced by pack aluminizing is studied for the fracture properties of the coating. Specimen geometries are optimized to enable micro-cracks to be machined and propagated in a low load testing system, such as a depth sensing indenter, so that crack lengths (and position relative to the interface) can be correlated with load. To enable linear elastic theory to be used, dimensions are determined that allow fracture before general yielding. A three point bending test using miniaturized micro-beam specimens of ~ 4 X 0.3 X 0.3 mm is found to be suitable for the above purpose. The technique is a challenging one that requires focused ion beam machining (FIB) along with careful handling and alignment of small samples. The coatings are characterized for their microstructure by electron microscopy to identify compositional variation across the thickness and to determine the thickness of the coating and inter diffusion zone (IDZ). The crack advancement is monitored with increments of loading and the stress intensity factor is evaluated using a program written in “MAPLE” for an edge crack subjected to bending in a bilayered material. Surprisingly, fracture in this system is found to be stable owing to a gradual increase in toughness from the coating surface to the interface. Such an increase from less than 2 to more than 9 MPa m0.5 may be due to the increasing Ni/Al ratio across the thickness of the bond coat. Crack branching is observed as the crack approaches the IDZ and the reasons for such behaviour are not fully understood. This work establishes the viability of this technique to determine fracture properties in highly graded coated systems and may be readily extended to more complex coating architectures and other forms of loading such as cyclic, mixed mode, etc.