High repetition frequency nanosecond pulses have been shown to be effective in generating plasma for reconfigurable RF systems. In the present work, the focus is on simulation of nanosecond pulsed discharges in Argon at 3 Torr and inter-electrode spacing of 2 cm with pulse repetition frequency of 30 kHz. The simulations have been carried out using a hybrid model, HPEM code developed by Prof. Mark J. Kushner at University of Michigan. The simulation results were compared to the experiments. Although a mismatch of results has been found, the simulations seem to capture the underlying physical phenomena. The electron temperature in the afterglow of the pulse seems to decay faster compared to the electron number density in the plasma, which is an essential feature in designing low noise plasma antennas.

The use of supercontinuum light sources in different optical measurement methods, like microscopy or optical coherence tomography, has increased significantly compared to classical wideband light sources. The development of various optical measurement techniques benefits from the high brightness and bandwidth, as well as the spatial coherence of these sources. For some applications, only a portion of the broad spectral range can be used. Therefore, an increase of the spectral power density in limited spectral regions would provide a clear advantage over spectral filtering. This study describes a method to increase the spectral power density of supercontinuum sources by amplifying the excitation wavelength inside a nonlinear photonic crystal fiber (PCF). An ytterbium doped photonic crystal fiber was manufactured by a nanopowder process (drawn by the company fiberware) and used in a fiber amplifier setup as the nonlinear fiber medium. In order to characterize the fiber’s optimum operational characteristics, group-velocity dispersion (GVD) measurements were performed on the fiber during the amplification process. For this purpose, a notch-pass mirror was used to launch the radiation of a stabilized laser diode at 976 nm into the fiber sample for pumping. The performance of the fiber was compared with a conventional PCF. Finally, the system as a whole was characterized in reference to common solid state-laser-based photonic supercontinuum light sources. An improvement of the power density up to 7.2 times was observed between 1100 nm to 1380 nm wavelengths.

Supercontinuum light sources provide a high power spectral density with a high spatial coherence. Coherent octavespanning supercontinuum can be generated in photonic crystal fibers (PCFs) by launching short pulses into the fiber. In the field of optical metrology, these light sources are very interesting. For most applications, only a small part of the entire spectrum can be utilized. In biological tissue scattering, absorption and fluorescence limits the usable spectral range. Therefore, an increase of the spectral power density in limited spectral regions would provide a clear advantage over spectral filtering. This study describes a method to increase the spectral power density of supercontinuum sources by amplifying the excitation wavelength inside a nonlinear photonic crystal fiber (PCF). An all-fiber-based setup enables higher output power and power stability. An ytterbium-doped photonic crystal fiber was manufactured by a nanopowder process (drawn by the fiberware GmbH, Germany) and used in a fiber amplifier setup as the nonlinear fiber medium. In order to characterize the fiber’s optimum operational characteristics, group-velocity dispersion (GVD) measurements were performed. The performance of the fiber-based setup was compared with a free space setup. Finally, the system as a whole was characterized in reference to common solid state-laser-based supercontinuum light sources. An improvement of the power density was observed in the spectral range between 1100 nm to 1400 nm.

Ce travail de thèse a eu pour but de développer des nouvelles sources lasers, oscillateurs et ampli?cateurs, construites autour des ?bres dopées aux ions ytterbium. Ces systèmes lasers génèrent des fortes puissances moyennes. L’oscillateur réalisé délivre des impulsions courtes (<10 ns) avec des énergies de l’ordre du milliJoule. Le système fonctionne à des cadences variables (10-100 kHz) avec un faisceau polarisé, monomode dont la largeur spectrale est inférieure à 0.1 nm. A?n d’avoir de plus fortes puissances crêtes et des impulsions courtes, deux types d’ampli?- cateurs ont été étudiés. Les résultats expérimentaux que nous avons obtenus sont en accord avec le modèle numérique développé. Le premier système ampli?e un microlaser émettant à 1064 nm dans une ?bre dopée ytterbium. Des puissances crêtes supérieures à 500 kW ont été obtenues avec des impulsions de l’ordre de la nanoseconde et une cadence comprise entre 1 kHz et 30 kHz. Le second ampli?cateur est construit autour d’un oscillateur à ?bre dopée ytterbium déclenché injecté dans une deuxième ?bre qui constitue l’ampli?cateur. L’originalité de ce système réside dans le cou- plage de deux cavités. Nous avons alors en sortie deux faisceaux cohérents, polarisés, monomode, indépendamment ajustables en énergie. En?n, nous avons utilisé les sources lasers développées, qui présentent des caractéristiques spec- trales, modales, énergétiques adéquats pour effectuer la conversion de fréquence. Des ef?cacités de l’ordre de 64 % et 38 % ont été atteintes respectivement en doublage et en triplage. Les faisceaux en sortie de ces systèmes possèdent des remarquables caractéristiques spatiales et temporelles. / This work presents the development of oscillators and ampli?ers build around new ytterbium rod type ?ber. These ?ber systems generate high average power generation. The oscillator makes it possible to deliver well linearly polarized, almost TEM 00 mode, and millijoule-level nanosecond pulses at a tunable repetition rate (10-100 kHz). The spectral bandwidth was shown to be less than 0.1 nm. To achieve higher peak power and shorter pulses, two types of ampli?ers have been developed and characterized. The experimental results we obtain, do well agree with the numerical simulations we developped. The ?rst system ampli?es in a rod type ?ber the nanosecond pulses yielded by a microlaser working at 1064 nm wavelength injected . Its provides pulses with a high peak power system (500 kW). Its repetition rate was tuned from 1 kHz to 30 kHz. The second ampli?er was built using a Q-switched ytterbium doped ?ber oscillator injected in a second ?ber which acts as ampli?er. In this original system the two cavities are coupled. It delivers two nanosecond pulses that are coherent, polarized, almost TEM00 single mode beams and that can have independently tunable pulse energies. We have shown that these oscillators and ampli?ers can be easily doubled and tripled in fre- quency. Very high ef?ciency of about 64 % and 38 % have been achieved respectively at 2? and 3?. These outputs have been to have remarquable spatial and temporal characteristics.

Il est possible de perméabiliser la membrane plasmique des cellules par des agents chimiques (tels que les polyéthylènes glycols ou le diméthylsulfoxyde) ou par des agents physiques (tels que les ultrasons ou les impulsions électriques). Cette perméabilisation peut être réversible ou non, ce qui signifie qu’après la perméabilisation, la membrane retrouve son intégrité et ses propriétés d’hémi-perméabilité ou pas. Ces techniques peuvent être utilisées pour faire rentrer des médicaments ou des acides nucléiques dans les cellules ou pour générer des fusions cellulaires. Une approche récente, la dynamique moléculaire, utilise des simulations numériques pour prédire les effets des agents perméabilisants sur les membranes à l’échelle moléculaire, et permet d’apporter de nouvelles données pour comprendre les mécanismes moléculaires, encore peu connus à ce jour.Les impulsions dites « classiques » en électroperméabilisation, de l’ordre de la dizaine de millisecondes à la centaine de microsecondes et d’amplitude de champ de l’ordre de 100 kV/m, perméabilisent la membrane plasmique uniquement. Cependant, récemment, des impulsions plus courtes, dites impulsions nanoseconde (quelques nanosecondes) et de plus grande amplitude de champ (de l’ordre de 10 MV/m) ont été utilisées et permettent d’affecter également les membranes des organites cellulaires. Les travaux de cette thèse portent dans un premier temps sur les effets perméabilisants d’un agent chimique (le diméthylsulfoxyde, DMSO) en comparant les modèles prédictifs de la dynamique moléculaire avec des expériences in vitro sur des cellules. Le modèle numérique prédit trois régimes d’action en fonction de la concentration du DMSO. Utilisé à faible concentration, il y a déformation de la membrane plasmique. L’utilisation d’une concentration intermédiaire entraîne la formation de pores membranaires et les fortes concentrations de DMSO ont pour conséquence la destruction de la membrane. Les expériences in vitro faites sur des cellules ont confirmé ces résultats en suivant l’entrée de marqueurs de perméabilisation. Cette étude a été comparée avec la perméabilisation par un agent physique (les impulsions électriques). Dans un deuxième temps, ces travaux traitent du développement et de l’utilisation d’un nouveau dispositif d’exposition des cellules aux impulsions nanoseconde qui permet d’appliquer des champs électriques très élevés et d’observer par microscopie leurs au niveau cellulaire. Pour finir, ce dispositif a été utilisé avec des impulsions nanoseconde pour générer des pics calciques dans de cellules souches mésenchymateuses qui présentent des oscillations calciques spontanées liées à leur état de différenciation. Ces pics induits sont dus à la libération de calcium stocké dans les organites et/ou à la perméabilisation de la membrane plasmique permettant l’établissement d’un flux de calcium intramembranaire. Il est aussi possible d’utiliser des impulsions microseconde pour générer des pics calciques dans ces cellules. Dans ce cas, les pics calciques ne sont dus qu’à la perméabilisation de la membrane plasmique. En jouant sur l’amplitude des champs électriques appliqués et sur la présence ou l’absence de calcium externe, il est possible de manipuler les concentrations calciques cytosoliques en mobilisant le calcium interne ou externe. Une des particularités de ces nouveaux outils est de pouvoir être déclenchés et arrêtés instantanément, sans réminiscence, contrairement aux molécules chimiques permettant de produire des pics calciques. Ces outils pourraient donc permettre de mieux comprendre l’implication du calcium dans des mécanismes comme la différenciation, la migration ou la fécondation. / It is possible to permeabilize the cellular plasma membrane by using chemical agents (as polyethylen glycols or diméthylsulfoxyde) or physical agents (as ulstrasounds or electric pulses). This permeabilization can be reversible or not, meaning that after the permeabilization, the membrane recovers its integrity and its hemi-permeable properties. These techniques can be used for the uptake of medicines or nucleic acids or to generate cellular fusions. A recent approach, the molecular dynamics, uses numerical simulations to predict the effects of permeabilizing agents at the molecular scale, allowed generating of new data to understand the molecular mechanisms that are not completely known yet.The pulses so called “classical” in electropermeabilization, from the range of the ten of milliseconds to the hundred of microseconds and with a field amplitude in the range of 100 kV/m, can only permeabilize the plasma membrane. However, more recently, shorter pulses, so called nanopulses (few nanosecondes) and with an higher field amplitude (in the range of 10 MV/m) have been used and allow to affect also cellular organelles membranes.This thesis is, in a first time, about the permeabilizing effects of a chemical gent (the diméthylsulfoxyde, DMSO) by comparing predictive models from molecular dynamics with experiments in vitro on cells. The numerical model predicts three regimes of action depending on the DMSO concentration. Used at low concentration, there is a plasma membrane deformation. The use of an intermediate concentration lead to membrane pores formation and higher DMSO concentrations resulted in membrane destruction. The experiments done in vitro on cells confirmed these results using the following of permeabilization markers. This study has been compared to permeabilization due to a physical agent (electric pulses).Secondly, it is about the development and the use of a new cell exposure device for nanopulses that permit to apply very high electric fields and to observe induced cellular effects simultaneously by microscopy.To finish, this device has been used with nanopulses to generate calcium peaks in mesenchymal stem cells that are presenting spontaneous calcium oscillations in correlation to their differentiation state.. These induced peaks are due to the release of the calcium stored in organelles and/or to plasma membrane permeabilization leading to a intramembrane calcium flux establishment. It is also possible to use microsecond pulses to generate calcium peaks in these cells. In this case, the calcium peaks are due to the plasma membrane permeabilization . By changing the amplitude of the applied electric fields and the presence or the absence of external calcium, it is possible to manipulate cytosolic calcium concentrations by mobilizing internal or external calcium. One feature of these new tools is to be triggered and stopped instantly without reminiscence, unlike chemical molecules permitting the production of calcium peaks. These tools could therefore lead to a better understanding of the involvement of calcium in mechanisms such as differentiation, migration or fertilization.

<p> In the past two decades, great interest in weakly ionized plasmas sustained by high voltage nanosecond pulsed plasmas at high repetition rates has emerged. For such plasmas, the electron number density does not significantly decay between pulses, unlike the electron temperature. Such conditions are favorable to reconfigurable plasma antennas where the low electron temperature may enable the reduction of the Johnson–Nyquist thermal noise if an antenna is operated in the plasma afterglow. Moreover, it may be possible to sustain such conditions with RF pulses. Doing so could enable a plasma antenna that transmits the driving frequency when the pulse is applied and receives other frequencies with low thermal noise between pulses.</p> <p>To study nanosecond pulsed plasmas, experiments were performed in a parallel-plate electrode configuration in argon and nitrogen gas at a pressure of several Torr and repetition frequencies of 30-75 kHz. To measure the time-resolved electron number density in the afterglow of each pulse, a custom 58.1 GHz homodyne microwave interferometer was constructed. The voltage and current measurements were made using a back current shunt (BCS). Initial analysis of the measured electron density in both plasmas indicated that the electron thermalization was much faster than the electron decay. In the nitrogen plasma, dissociative recombination with cluster ions was the dominant electron loss mechanism. However, the dissociative recombination rates of the electrons in the argon plasma suggested the presence of molecular impurities, such as water vapor. Therefore, to better understand the recombination mechanisms in argon plasma with trace amounts (0.1% or less by volume) of water vapor under the experimental conditions, a 0-D kinetic model was developed and fit to the experimental data. The influence of trace amounts of water on the electron temperature and density decay was studied by solving electron energy and continuity equations. It was found that in pure argon, Ar⁺ ions dominate while the electrons are very slow to thermalize and recombine. Including trace amounts of water impurities drastically reduces the time for electrons to thermalize and increases their rate of recombination. </p> <p>In addition to large quasi-steady electron number densities and low electron temperature in the plasma afterglow, plasmas sustained by nanosecond pulses use a lower power budget than those sustained by RF or DC supplies. The efficiency of the power budget can be characterized by measuring the ionization cost per electron, defined as the ratio of the energy deposited in a pulse to the total number of electrons created. This was experimentally determined in air and argon plasmas at 2-10 Torr sustained by 1-7 kV nanosecond pulses at repetition frequencies of 0.1-30 kHz. The number of electrons were determined from the measured electron density through microwave interferometry and assuming a plasma volume equivalent to the volume between electrodes. The energy deposited was calculated from voltage and current measurements using both a BCS as well as high frequency resistive voltage divider and fast current transformer (FCT). It was found that the ionization cost in all conditions was within a factor of three of Stoletov’s point (the theoretical minimum ionization cost) and two orders of magnitude less than RF plasma.</p><p> </p><p>Having shown that it is possible to generate high electron density, low electron temperature plasmas with nanosecond pulses, it was necessary to now create a plasma antenna prototype. Initially, commercial fluorescent light bulbs were used and ignited using surface wave excitation at various RF frequencies and powers. The S₁₁ of the antenna response was measured by a VNA through a novel coupling circuit, while the deposited power was measured using a bi-directional coupler. Next, a custom plasma antenna was created in which the pressure and gas composition could be varied. In addition to the S₁₁ and deposited power, the antenna gain, and the electron number density were also measured for a pure argon plasma antenna at pressures of 0.3-1 Torr. Varying the applied power shifts the antenna resonance frequency while increasing the excitation frequency caused an increase in measured electron density for the same deposited power. Initial tests using direct electrode excitation of a twin-tube integrated compact fluorescent light bulb with nanosecond pulses have successfully been achieved. Future efforts include designing the proper circuitry to time-gate out the large pulse voltage to facilitate safe antenna measurements in the plasma afterglow.<br></p>

We demonstrate four experimentally simple methods for measuring very complex ultrashort light pulses. Although each method is comprised of only a few optical elements, they permit the measurement of extremely complex pulses with time-bandwidth products greater than 65,000. First, we demonstrate an extremely simple frequency-resolved-optical gating (GRENOUILLE) device for measuring the intensity and phase of pulses up to ~20ps in length. In order to achieve the required high spectral resolution and large temporal range, it uses a few-cm-thick second harmonic-generation crystal in the shape of a pentagon. This has the additional advantage of reducing the device's total number of components to three. Secondly, we introduce a variation of spectral interferometry (SI) using a virtually imaged phased array and grating spectrometer for measuring long complex ultrashort pulses up to 80 ps in length. Next, we introduce a SI technique for measuring the complete intensity and phase of relatively long and very complex ultrashort pulses. It involves making multiple measurements using SI (in its SEA TADPOLE variation) at numerous delays, measuring many temporal pulselets within the pulse, and concatenating the resulting pulselets. Its spectral resolution is the inverse delay range--many times higher than that of the spectrometer used. The waveforms were measured with ~ fs temporal resolution over a temporal range of ~ns and had time-bandwidth products exceeding 65,000, which to our knowledge is the largest time-bandwidth product ever measured with ~fs temporal resolution. Finally, we demonstrate a single-shot measurement technique that temporally interleaves hundreds of measurements with ~fs temporal resolution. It is another variation of SI for measuring the complete intensity and phase of relatively long and complex ultrashort pulses in a single shot. It uses a grating to introduce a transverse time delay into a reference pulse which gates the unknown pulse by interfering it at the image plane of an imaging spectrometer. It provided ~125 fs temporal resolution and a temporal range of 70 ps using a low-resolution spectrometer.

Optical coherence tomography benefits from the high brightness and bandwidth, as well as the spatial coherence of supercontinuum (SC) sources. The increase of spectral power density (SPD) over conventional light sources leads to shorter measuring times and higher resolutions. For some applications, only a portion of the broad spectral range can be used. Therefore, an increase of the SPD in specific limited spectral regions would provide a clear advantage over spectral filtering. This study describes a method to increase the SPD of SC sources by amplifying the excitation wavelength inside of a nonlinear photonic crystal fiber (PCF). An ytterbium-doped PCF was manufactured by a nanopowder process and used in a fiber amplifier setup as the nonlinear fiber medium. The performance of the fiber was compared with a conventional PCF that possesses comparable parameters. Finally, the system as a whole was characterized in reference to common solid-state laser-based photonic SC light sources. An order-of-magnitude improvement of the power density was observed between the wavelengths from 1100 to 1350 nm.

The theoretical part of the thesis deals with the explanation of the actions that occur during the stimulation of tissues with the electric current. A significant analogy with electrical circuits is used to describe the phenomena at the molecular and cellular level. The models of membrane and cell are necessary for understanding the behaviour of more complex structures, such as tissues and organs. A considerable attention is paid to the conditions of electrical stimulation which bring about response in the stimulated area. Next, the cumulative effect of the subthreshold stimulation is analysed. The mechanisms of common treatment effects of the electrotherapeutic methods are outlined. The research results in the practical part of the thesis – the design for a microstimulator. Properties of the microstimulator and compliance with standard requirements are verified by testing the electromagnetic compatibility and electrical safety, conducted by the Institute for testing and certification, JSC. The effects of microstimulation on living organisms are experimentally investigated on horses, in collaboration with the Veterinary and Pharmaceutical University. For the first time, thermodynamic sensors are used for the objective assessment of the microstimulation therapeutic effect. These miniature sensors are placed on the horse´s front legs and monitor the changes in thermal activity while only one limb is really stimulated and the other is just considered as a reference. Comparison and statistical evaluation of the measured signals could provide a more detailed view of the thermal changes within the stimulated area, which is significantly related to blood circulation in limbs, and with the support of the reduction of edema. The course of the experiment which deals with the effect of microstimulation on edema of the horse´s legs caused by minor injuries (tendinitis, sprains, etc.), is documented in photographs or videos that are significant for possible evaluation of the effectiveness of the stimulation in this application.