Design and Characterization of New Luminescent Sensors and Labels

The aim of this Ph.D. project has been the design and characterization of new and more efficient luminescent tools, in particular sensors and labels, for analytical chemistry, medical diagnostics and imaging. Actually both the increasing temporal and spatial resolutions that are demanded by those branches, coupled to a sensitivity that is required to reach the single molecule resolution, can be provided by the wide range of techniques based on luminescence spectroscopy. As far as the development of new chemical sensors is concerned, as chemists we were interested in the preparation of new, efficient, sensing materials. In this context, we kept developing new molecular chemosensors, by exploiting the supramolecular approach, for different classes of analytes. In particular we studied a family of luminescent tetrapodal-hosts based on aminopyridinium units with pyrenyl groups for the detection of anions. These systems exhibited noticeable changes in the photophysical properties, depending on the nature of the anion; in particular, addition of chloride resulted in a conformational change, giving an initial increase in excimeric emission. A good selectivity for dicarboxylic acid was also found. In the search for higher sensitivities, we moved our attention also to systems able to perform amplification effects. In this context we described the metal ion binding properties of three photoactive poly-(arylene ethynylene) co-polymers with different complexing units and we highlighted, for one of them, a ten-fold amplification of the response in case of addition of Zn2+, Cu2+ and Hg2+ ions. In addition, we were able to demonstrate the formation of complexes with Yb3+ an Er3+ and an efficient sensitization of their typical metal centered NIR emission upon excitation of the polymer structure, this feature being of particular interest for their possible applications in optical imaging and in optical amplification for telecommunication purposes. An amplification effect was also observed during this research in silica nanoparticles derivatized with a suitable zinc probe. In this case we were able to prove, for the first time, that nanoparticles can work as “off-on” chemosensors with signal amplification. Fluorescent silica nanoparticles can be thus seen as innovative multicomponent systems in which the organization of photophysically active units gives rise to fruitful collective effects. These precious effects can be exploited for biological imaging, medical diagnostic and therapeutics, as evidenced also by some results reported in this thesis. In particular, the observed amplification effect has been obtained thanks to a suitable organization of molecular probe units onto the surface of the nanoparticles. In the effort of reaching a deeper inside in the mechanisms which lead to the final amplification effects, we also attempted to find a correlation between the synthetic route and the final organization of the active molecules in the silica network, and thus with those mutual interactions between one another which result in the emerging, collective behavior, responsible for the desired signal amplification. In this context, we firstly investigated the process of formation of silica nanoparticles doped with pyrene derivative and we showed that the dyes are not uniformly dispersed inside the silica matrix; thus, core-shell structures can be formed spontaneously in a one step synthesis. Moreover, as far as the design of new labels is concerned, we reported a new synthetic approach to obtain a class of robust, biocompatible silica core-shell nanoparticles able to show a long-term stability. Taking advantage of this new approach we also showed the synthesis and photophysical properties of core-shell NIR absorbing and emitting materials that proved to be very valuable for in-vivo imaging. In general, the dye doped silica nanoparticles prepared in the framework of this project can conjugate unique properties, such as a very high brightness, due to the possibility to include many fluorophores per nanoparticle, high stability, because of the shielding effect of the silica matrix, and, to date, no toxicity, with a simple and low-cost preparation. All these features make these nanostructures suitable to reach the low detection limits that are nowadays required for effective clinical and environmental applications, fulfilling in this way the initial expectations of this research project.

Design and synthesis of novel non peptidomimtic beta-secretase inhibitors in the treatment of Alzheimer's disease

The aspartic protease BACE1 (β-amyloid precursor protein cleaving enzyme, β-secretase) is recognized as one of the most promising targets in the treatment of Alzheimer's disease (AD). The accumulation of β-amyloid peptide (Aβ) in the brain is a major factor in the pathogenesis of AD. Aβ is formed by initial cleavage of β-amyloid precursor protein (APP) by β-secretase, therefore BACE1 inhibition represents one of the therapeutic approaches to control progression of AD, by preventing the abnormal generation of Aβ. For this reason, in the last decade, many research efforts have focused at the identification of new BACE1 inhibitors as drug candidates. Generally, BACE1 inhibitors are grouped into two families: substrate-based inhibitors, designed as peptidomimetic inhibitors, and non-peptidomimetic ones. The research on non-peptidomimetic small molecules BACE1 inhibitors remains the most interesting approach, since these compounds hold an improved bioavailability after systemic administration, due to a good blood-brain barrier permeability in comparison to peptidomimetic inhibitors. Very recently, our research group discovered a new promising lead compound for the treatment of AD, named lipocrine, a hybrid derivative between lipoic acid and the AChE inhibitor (AChEI) tacrine, characterized by a tetrahydroacridinic moiety. Lipocrine is one of the first compounds able to inhibit the catalytic activity of AChE and AChE-induced amyloid-β aggregation and to protect against reactive oxygen species. Due to this interesting profile, lipocrine was also evaluated for BACE1 inhibitory activity, resulting in a potent lead compound for BACE1 inhibition. Starting from this interesting profile, a series of tetrahydroacridine analogues were synthesised varying the chain length between the two fragments. Moreover, following the approach of combining in a single molecule two different pharmacophores, we designed and synthesised different compounds bearing the moieties of known AChEIs (rivastigmine and caproctamine) coupled with lipoic acid, since it was shown that dithiolane group is an important structural feature of lipocrine for the optimal inhibition of BACE1. All the tetrahydroacridines, rivastigmine and caproctamine-based compounds, were evaluated for BACE1 inhibitory activity in a FRET (fluorescence resonance energy transfer) enzymatic assay (test A). With the aim to enhancing the biological activity of the lead compound, we applied the molecular simplification approach to design and synthesize novel heterocyclic compounds related to lipocrine, in which the tetrahydroacridine moiety was replaced by 4-amino-quinoline or 4-amino-quinazoline rings. All the synthesized compounds were also evaluated in a modified FRET enzymatic assay (test B), changing the fluorescent substrate for enzymatic BACE1 cleavage. This test method guided deep structure-activity relationships for BACE1 inhibition on the most promising quinazoline-based derivatives. By varying the substituent on the 2-position of the quinazoline ring and by replacing the lipoic acid residue in lateral chain with different moieties (i.e. trans-ferulic acid, a known antioxidant molecule), a series of quinazoline derivatives were obtained. In order to confirm inhibitory activity of the most active compounds, they were evaluated with a third FRET assay (test C) which, surprisingly, did not confirm the previous good activity profiles. An evaluation study of kinetic parameters of the three assays revealed that method C is endowed with the best specificity and enzymatic efficiency. Biological evaluation of the modified 2,4-diamino-quinazoline derivatives measured through the method C, allow to obtain a new lead compound bearing the trans-ferulic acid residue coupled to 2,4-diamino-quinazoline core endowed with a good BACE1 inhibitory activity (IC50 = 0.8 mM). We reported on the variability of the results in the three different FRET assays that are known to have some disadvantages in term of interference rates that are strongly dependent on compound properties. The observed results variability could be also ascribed to different enzyme origin, varied substrate and different fluorescent groups. The inhibitors should be tested on a parallel screening in order to have a more reliable data prior to be tested into cellular assay. With this aim, preliminary cellular BACE1 inhibition assay carried out on lipocrine confirmed a good cellular activity profile (EC50 = 3.7 mM) strengthening the idea to find a small molecule non-peptidomimetic compound as BACE1 inhibitor. In conclusion, the present study allowed to identify a new lead compound endowed with BACE1 inhibitory activity in submicromolar range. Further lead optimization to the obtained derivative is needed in order to obtain a more potent and a selective BACE1 inhibitor based on 2,4-diamino-quinazoline scaffold. A side project related to the synthesis of novel enzymatic inhibitors of BACE1 in order to explore the pseudopeptidic transition-state isosteres chemistry was carried out during research stage at Università de Montrèal (Canada) in Hanessian's group. The aim of this work has been the synthesis of the δ-aminocyclohexane carboxylic acid motif with stereochemically defined substitution to incorporating such a constrained core in potential BACE1 inhibitors. This fragment, endowed with reduced peptidic character, is not known in the context of peptidomimetic design. In particular, we envisioned an alternative route based on an organocatalytic asymmetric conjugate addition of nitroalkanes to cyclohexenone in presence of D-proline and trans-2,5-dimethylpiperazine. The enantioenriched obtained 3-(α-nitroalkyl)-cyclohexanones were further functionalized to give the corresponding δ-nitroalkyl cyclohexane carboxylic acids. These intermediates were elaborated to the target structures 3-(α-aminoalkyl)-1-cyclohexane carboxylic acids in a new readily accessible way.

Design and fabrication of MOMS-based ultrasonic probes for minimally invasive endoscopic applications

A Micro-opto-mechanical systems (MOMS) based technology for the fabrication of ultrasonic probes on optical fiber is presented. Thanks to the high miniaturization level reached, the realization of an ultrasonic system constituted by ultrasonic generating and detecting elements, suitable for minimally invasive applications or Non Destructive Evaluation (NDE) of materials at high resolution, is demonstrated. The ultrasonic generation is realized by irradiating a highly absorbing carbon film patterned on silicon micromachined structures with a nanosecond pulsed laser source, generating a mechanical shock wave due to the thermal expansion of the film induced by optical energy conversion into heat. The short duration of the pulsed laser, together with an appropriate emitter design, assure high frequency and wide band ultrasonic generation. The acoustic detection is also realized on a MOMS device using an interferometric receiver, fabricated with a Fabry-Perot optical cavity realized by means of a patterned SU-8 and two Al metallization levels. In order to detect the ultrasonic waves, the cavity is interrogated by a laser beam measuring the reflected power with a photodiode. Various issues related to the design and fabrication of these acoustic probes are investigated in this thesis. First, theoretical models are developed to characterize the opto-acoustic behavior of the devices and estimate their expected acoustic performances. Tests structures are realized to derive the relevant physical parameters of the materials constituting the MOMS devices and determine the conditions theoretically assuring the best acoustic emission and detection performances. Moreover, by exploiting the models and the theoretical results, prototypes of acoustic probes are designed and their fabrication process developed by means of an extended experimental activity.

Design and optimization of components and processes for plasma sources in advanced material treatments

The research activities described in the present thesis have been oriented to the design and development of components and technological processes aimed at optimizing the performance of plasma sources in advanced in material treatments. Consumables components for high definition plasma arc cutting (PAC) torches were studied and developed. Experimental activities have in particular focussed on the modifications of the emissive insert with respect to the standard electrode configuration, which comprises a press fit hafnium insert in a copper body holder, to improve its durability. Based on a deep analysis of both the scientific and patent literature, different solutions were proposed and tested. First, the behaviour of Hf cathodes when operating at high current levels (250A) in oxidizing atmosphere has been experimentally investigated optimizing, with respect to expected service life, the initial shape of the electrode emissive surface. Moreover, the microstructural modifications of the Hf insert in PAC electrodes were experimentally investigated during first cycles, in order to understand those phenomena occurring on and under the Hf emissive surface and involved in the electrode erosion process. Thereafter, the research activity focussed on producing, characterizing and testing prototypes of composite inserts, combining powders of a high thermal conductibility (Cu, Ag) and high thermionic emissivity (Hf, Zr) materials The complexity of the thermal plasma torch environment required and integrated approach also involving physical modelling. Accordingly, a detailed line-by-line method was developed to compute the net emission coefficient of Ar plasmas at temperatures ranging from 3000 K to 25000 K and pressure ranging from 50 kPa to 200 kPa, for optically thin and partially autoabsorbed plasmas. Finally, prototypal electrodes were studied and realized for a newly developed plasma source, based on the plasma needle concept and devoted to the generation of atmospheric pressure non-thermal plasmas for biomedical applications.

Design and Characterization of Curved and Spherical Flexure Hinges for Planar and Spatial Compliant Mechanisms

A flexure hinge is a flexible connector that can provide a limited rotational motion between two rigid parts by means of material deformation. These connectors can be used to substitute traditional kinematic pairs (like bearing couplings) in rigid-body mechanisms. When compared to their rigid-body counterpart, flexure hinges are characterized by reduced weight, absence of backlash and friction, part-count reduction, but restricted range of motion. There are several types of flexure hinges in the literature that have been studied and characterized for different applications. In our study, we have introduced new types of flexures with curved structures i.e. circularly curved-beam flexures and spherical flexures. These flexures have been utilized for both planar applications (e.g. articulated robotic fingers) and spatial applications (e.g. spherical compliant mechanisms). We have derived closed-form compliance equations for both circularly curved-beam flexures and spherical flexures. Each element of the spatial compliance matrix is analytically computed as a function of hinge dimensions and employed material. The theoretical model is then validated by comparing analytical data with the results obtained through Finite Element Analysis. A case study is also presented for each class of flexures, concerning the potential applications in the optimal design of planar and spatial compliant mechanisms. Each case study is followed by comparing the performance of these novel flexures with the performance of commonly used geometries in terms of principle compliance factors, parasitic motions and maximum stress demands. Furthermore, we have extended our study to the design and analysis of serial and parallel compliant mechanisms, where the proposed flexures have been employed to achieve spatial motions e.g. compliant spherical joints.

Synthesis and biological activity of new functionalized epothilones for prodrug design and tumor targeting

Epothilones are potent antiproliferative agents, which have served as successful lead structures for anticancer drug discovery. However, their therapeutic efficacy would benefit greatly from an increase in their selectivity for tumor cells, which may be achieved through conjugation with a tumor-targeting moiety. Three novel epothilone analogs bearing variously functionalized benzimidazole side chains were synthesized using a strategy based on palladium-mediated coupling and macrolactonization. The synthesis of these compounds is described and their in vitro biological activity is discussed with respect to their interactions with the tubulin/microtubule system and the inhibition of human cancer cell proliferation. The additional functional groups may be used to synthesize conjugates of epothilone derivatives with a variety of tumor-targeting moieties.

Planar magneto-photonic and gradient-photonic structures : crystals and metamaterials.

In the field of photonics, two new types of material structures, photonic crystals and metamaterials, are presently of great interest. Both are studied in the present work, which focus on planar magnetic materials in the former and planar gradient metamaterials in the latter. These planar periodic structures are easy to handle and integrate into optical systems. The applications are promising field for future optical telecommunication systems and give rise to new optical, microwave and radio technologies. The photonic crystal part emphasizes the utilization of magnetic material based photonic crystals due to its remarkable magneto-optical characteristics. Bandgaps tuning by magnetic field in bismuth-gadolinium-substituted lutetium iron garnet (Bi0.8 Gd0.2 Lu2.0 Fe5 O12) based one- dimensional photonic crystals are investigated and demonstrated in this work. Magnetic optical switches are fabricated and tested. Waveguide formulation for band structure in magneto photonic crystals is developed. We also for the first time demonstrate and test two- dimensional magneto photonic crystals optical. We observe multi-stopbands in two- dimensional photonic waveguide system and study the origin of multi-stopbands. The second part focus on studying photonic metamaterials and planar gradient photonic metamaterial design. We systematically study the effects of varying the geometry of the fishnet unit cell on the refractive index in optical frequency. It is the first time to design and demonstrate the planar gradient structure in the high optical frequency. Optical beam bending using planar gradient photonic metamaterials is observed. The technologies needed for the fabrication of the planar gradient photonic metamaterials are investigated. Beam steering devices, shifter, gradient optical lenses and etc. can be derived from this design.

Conceptual design and simulation of a water Cherenkov muon veto for the XENON1T experiment

XENON is a dark matter direct detection project, consisting of a time projection chamber (TPC) filled with liquid xenon as detection medium. The construction of the next generation detector, XENON1T, is presently taking place at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy. It aims at a sensitivity to spin-independent cross sections of 2 10-47 c 2 for WIMP masses around 50 GeV2, which requires a background reduction by two orders of magnitude compared to XENON100, the current generation detector. An active system that is able to tag muons and muon-induced backgrounds is critical for this goal. A water Cherenkov detector of ~ 10 m height and diameter has been therefore developed, equipped with 8 inch photomultipliers and cladded by a reflective foil. We present the design and optimization study for this detector, which has been carried out with a series of Monte Carlo simulations. The muon veto will reach very high detection efficiencies for muons (>99.5%) and showers of secondary particles from muon interactions in the rock (>70%). Similar efficiencies will be obtained for XENONnT, the upgrade of XENON1T, which will later improve the WIMP sensitivity by another order of magnitude. With the Cherenkov water shield studied here, the background from muon-induced neutrons in XENON1T is negligible.

Multifunctional Coordination Compounds: Design and Properties

Cleverly designed molecular building blocks provide chemists with the tools of a powerful molecular-scale construction set. They enable them to engineer materials having a predictable order and useful solid-state properties. Hence, it is in the realm of supramolecular chemistry to follow a strategy for synthesizing materials which combine a selected set of properties, for instance from the areas of magnetism, photophysics and electronics. As a successful approach, host/guest solids which are based on extended anionic, homo- and bimetallic oxalato-bridged transition-metal compounds with two-and three-dimensional connectivities have been investigated. In this report, a brief review is given on the structural aspects of this class of compounds followed by a presentation of a thermal and magnetic study for two distinct, heterometallic oxalato-bridged layer compounds.

Contribution to the Analysis, Design and Assessment of Compact Antenna Test Ranges At Millimeter Wavelengths - Contribución al Análisis, Diseño y Caracterización de Sistemas de Medida de Antenas en Rango Compacto para Frecuencias Milimétricas

This Doctoral Thesis entitled Contribution to the analysis, design and assessment of compact antenna test ranges at millimeter wavelengths aims to deepen the knowledge of a particular antenna measurement system: the compact range, operating in the frequency bands of millimeter wavelengths. The thesis has been developed at Radiation Group (GR), an antenna laboratory which belongs to the Signals, Systems and Radiocommunications department (SSR), from Technical University of Madrid (UPM). The Radiation Group owns an extensive experience on antenna measurements, running at present four facilities which operate in different configurations: Gregorian compact antenna test range, spherical near field, planar near field and semianechoic arch system. The research work performed in line with this thesis contributes the knowledge of the first measurement configuration at higher frequencies, beyond the microwaves region where Radiation Group features customer-level performance. To reach this high level purpose, a set of scientific tasks were sequentially carried out. Those are succinctly described in the subsequent paragraphs. A first step dealed with the State of Art review. The study of scientific literature dealed with the analysis of measurement practices in compact antenna test ranges in addition with the particularities of millimeter wavelength technologies. Joint study of both fields of knowledge converged, when this measurement facilities are of interest, in a series of technological challenges which become serious bottlenecks at different stages: analysis, design and assessment. Thirdly after the overview study, focus was set on Electromagnetic analysis algorithms. These formulations allow to approach certain electromagnetic features of interest, such as field distribution phase or stray signal analysis of particular structures when they interact with electromagnetic waves sources. Properly operated, a CATR facility features electromagnetic waves collimation optics which are large, in terms of wavelengths. Accordingly, the electromagnetic analysis tasks introduce an extense number of mathematic unknowns which grow with frequency, following different polynomic order laws depending on the used algorithmia. In particular, the optics configuration which was of our interest consisted on the reflection type serrated edge collimator. The analysis of these devices requires a flexible handling of almost arbitrary scattering geometries, becoming this flexibility the nucleus of the algorithmia’s ability to perform the subsequent design tasks. This thesis’ contribution to this field of knowledge consisted on reaching a formulation which was powerful at the same time when dealing with various analysis geometries and computationally speaking. Two algorithmia were developed. While based on the same principle of hybridization, they reached different order Physics performance at the cost of the computational efficiency. Inter-comparison of their CATR design capabilities was performed, reaching both qualitative as well as quantitative conclusions on their scope. In third place, interest was shifted from analysis - design tasks towards range assessment. Millimetre wavelengths imply strict mechanical tolerances and fine setup adjustment. In addition, the large number of unknowns issue already faced in the analysis stage appears as well in the on chamber field probing stage. Natural decrease of dynamic range available by semiconductor millimeter waves sources requires in addition larger integration times at each probing point. These peculiarities increase exponentially the difficulty of performing assessment processes in CATR facilities beyond microwaves. The bottleneck becomes so tight that it compromises the range characterization beyond a certain limit frequency which typically lies on the lowest segment of millimeter wavelength frequencies. However the value of range assessment moves, on the contrary, towards the highest segment. This thesis contributes this technological scenario developing quiet zone probing techniques which achieves substantial data reduction ratii. Collaterally, it increases the robustness of the results to noise, which is a virtual rise of the setup’s available dynamic range. In fourth place, the environmental sensitivity of millimeter wavelengths issue was approached. It is well known the drifts of electromagnetic experiments due to the dependance of the re sults with respect to the surrounding environment. This feature relegates many industrial practices of microwave frequencies to the experimental stage, at millimeter wavelengths. In particular, evolution of the atmosphere within acceptable conditioning bounds redounds in drift phenomena which completely mask the experimental results. The contribution of this thesis on this aspect consists on modeling electrically the indoor atmosphere existing in a CATR, as a function of environmental variables which affect the range’s performance. A simple model was developed, being able to handle high level phenomena, such as feed - probe phase drift as a function of low level magnitudes easy to be sampled: relative humidity and temperature. With this model, environmental compensation can be performed and chamber conditioning is automatically extended towards higher frequencies. Therefore, the purpose of this thesis is to go further into the knowledge of millimetre wavelengths involving compact antenna test ranges. This knowledge is dosified through the sequential stages of a CATR conception, form early low level electromagnetic analysis towards the assessment of an operative facility, stages for each one of which nowadays bottleneck phenomena exist and seriously compromise the antenna measurement practices at millimeter wavelengths.

Novel Inductor‐less Conversion Strategy Based on Multiphase Transformer‐Coupled Converters: Analysis, Design and Applications

There are many the requirements that modern power converters should fulfill. Most of the applications where these converters are used, demand smaller converters with high efficiency, improved power density and a fast dynamic response. For instance, loads like microprocessors demand aggressive current steps with very high slew rates (100A/mus and higher); besides, during these load steps, the supply voltage of the microprocessor should be kept within tight limits in order to ensure its correct performance. The accomplishment of these requirements is not an easy task; complex solutions like advanced topologies - such as multiphase converters- as well as advanced control strategies are often needed. Besides, it is also necessary to operate the converter at high switching frequencies and to use capacitors with high capacitance and low ESR. Improving the dynamic response of power converters does not rely only on the control strategy but also the power topology should be suited to enable a fast dynamic response. Moreover, in later years, a fast dynamic response does not only mean accomplishing fast load steps but output voltage steps are gaining importance as well. At least, two applications that require fast voltage changes can be named: Low power microprocessors. In these devices, the voltage supply is changed according to the workload and the operating frequency of the microprocessor is changed at the same time. An important reduction in voltage dependent losses can be achieved with such changes. This technique is known as Dynamic Voltage Scaling (DVS). Another application where important energy savings can be achieved by means of changing the supply voltage are Radio Frequency Power Amplifiers. For example, RF architectures based on ‘Envelope Tracking’ and ‘Envelope Elimination and Restoration’ techniques can take advantage of voltage supply modulation and accomplish important energy savings in the power amplifier. However, in order to achieve these efficiency improvements, a power converter with high efficiency and high enough bandwidth (hundreds of kHz or even tens of MHz) is necessary in order to ensure an adequate supply voltage. The main objective of this Thesis is to improve the dynamic response of DC-DC converters from the point of view of the power topology. And the term dynamic response refers both to the load steps and the voltage steps; it is also interesting to modulate the output voltage of the converter with a specific bandwidth. In order to accomplish this, the question of what is it that limits the dynamic response of power converters should be answered. Analyzing this question leads to the conclusion that the dynamic response is limited by the power topology and specifically, by the filter inductance of the converter which is found in series between the input and the output of the converter. The series inductance is the one that determines the gain of the converter and provides the regulation capability. Although the energy stored in the filter inductance enables the regulation and the capability of filtering the output voltage, it imposes a limitation which is the concern of this Thesis. The series inductance stores energy and prevents the current from changing in a fast way, limiting the slew rate of the current through this inductor. Different solutions are proposed in the literature in order to reduce the limit imposed by the filter inductor. Many publications proposing new topologies and improvements to known topologies can be found in the literature. Also, complex control strategies are proposed with the objective of improving the dynamic response in power converters. In the proposed topologies, the energy stored in the series inductor is reduced; examples of these topologies are Multiphase converters, Buck converter operating at very high frequency or adding a low impedance path in parallel with the series inductance. Control techniques proposed in the literature, focus on adjusting the output voltage as fast as allowed by the power stage; examples of these control techniques are: hysteresis control, V 2 control, and minimum time control. In some of the proposed topologies, a reduction in the value of the series inductance is achieved and with this, the energy stored in this magnetic element is reduced; less stored energy means a faster dynamic response. However, in some cases (as in the high frequency Buck converter), the dynamic response is improved at the cost of worsening the efficiency. In this Thesis, a drastic solution is proposed: to completely eliminate the series inductance of the converter. This is a more radical solution when compared to those proposed in the literature. If the series inductance is eliminated, the regulation capability of the converter is limited which can make it difficult to use the topology in one-converter solutions; however, this topology is suitable for power architectures where the energy conversion is done by more than one converter. When the series inductor is eliminated from the converter, the current slew rate is no longer limited and it can be said that the dynamic response of the converter is independent from the switching frequency. This is the main advantage of eliminating the series inductor. The main objective, is to propose an energy conversion strategy that is done without series inductance. Without series inductance, no energy is stored between the input and the output of the converter and the dynamic response would be instantaneous if all the devices were ideal. If the energy transfer from the input to the output of the converter is done instantaneously when a load step occurs, conceptually it would not be necessary to store energy at the output of the converter (no output capacitor COUT would be needed) and if the input source is ideal, the input capacitor CIN would not be necessary. This last feature (no CIN with ideal VIN) is common to all power converters. However, when the concept is actually implemented, parasitic inductances such as leakage inductance of the transformer and the parasitic inductance of the PCB, cannot be avoided because they are inherent to the implementation of the converter. These parasitic elements do not affect significantly to the proposed concept. In this Thesis, it is proposed to operate the converter without series inductance in order to improve the dynamic response of the converter; however, on the other side, the continuous regulation capability of the converter is lost. It is said continuous because, as it will be explained throughout the Thesis, it is indeed possible to achieve discrete regulation; a converter without filter inductance and without energy stored in the magnetic element, is capable to achieve a limited number of output voltages. The changes between these output voltage levels are achieved in a fast way. The proposed energy conversion strategy is implemented by means of a multiphase converter where the coupling of the phases is done by discrete two-winding transformers instead of coupledinductors since transformers are, ideally, no energy storing elements. This idea is the main contribution of this Thesis. The feasibility of this energy conversion strategy is first analyzed and then verified by simulation and by the implementation of experimental prototypes. Once the strategy is proved valid, different options to implement the magnetic structure are analyzed. Three different discrete transformer arrangements are studied and implemented. A converter based on this energy conversion strategy would be designed with a different approach than the one used to design classic converters since an additional design degree of freedom is available. The switching frequency can be chosen according to the design specifications without penalizing the dynamic response or the efficiency. Low operating frequencies can be chosen in order to favor the efficiency; on the other hand, high operating frequencies (MHz) can be chosen in order to favor the size of the converter. For this reason, a particular design procedure is proposed for the ‘inductorless’ conversion strategy. Finally, applications where the features of the proposed conversion strategy (high efficiency with fast dynamic response) are advantageus, are proposed. For example, in two-stage power architectures where a high efficiency converter is needed as the first stage and there is a second stage that provides the fine regulation. Another example are RF power amplifiers where the voltage is modulated following an envelope reference in order to save power; in this application, a high efficiency converter, capable of achieving fast voltage steps is required. The main contributions of this Thesis are the following: The proposal of a conversion strategy that is done, ideally, without storing energy in the magnetic element. The validation and the implementation of the proposed energy conversion strategy. The study of different magnetic structures based on discrete transformers for the implementation of the proposed energy conversion strategy. To elaborate and validate a design procedure. To identify and validate applications for the proposed energy conversion strategy. It is important to remark that this work is done in collaboration with Intel. The particular features of the proposed conversion strategy enable the possibility of solving the problems related to microprocessor powering in a different way. For example, the high efficiency achieved with the proposed conversion strategy enables it as a good candidate to be used for power conditioning, as a first stage in a two-stage power architecture for powering microprocessors.

Efficient design and optimization of bio-photonic sensing cells (BICELLs) for label free biosensing

In previous works we demonstrated the benefits of using micro–nano patterning materials to be used as bio-photonic sensing cells (BICELLs), referred as micro–nano photonic structures having immobilized bioreceptors on its surface with the capability of recognizing the molecular binding by optical transduction. Gestrinone/anti-gestrinone and BSA/anti-BSA pairs were proven under different optical configurations to experimentally validate the biosensing capability of these bio-sensitive photonic architectures. Moreover, Three-Dimensional Finite Difference Time Domain (FDTD) models were employed for simulating the optical response of these structures. For this article, we have developed an effective analytical simulation methodology capable of simulating complex biophotonic sensing architectures. This simulation method has been tested and compared with previous experimental results and FDTD models. Moreover, this effective simulation methodology can be used for efficiently design and optimize any structure as BICELL. In particular for this article, six different BICELL's types have been optimized. To carry out this optimization we have considered three figures of merit: optical sensitivity, Q-factor and signal amplitude. The final objective of this paper is not only validating a suitable and efficient optical simulation methodology but also demonstrating the capability of this method for analyzing the performance of a given number of BICELLs for label-free biosensing.

Comparative study of auxetic geometrics by means of computer-aided design and engineering

Auxetic materials (or metamaterials) are those with a negative Poisson ratio (NPR) and display the unexpected property of lateral expansion when stretched, as well as an equal and opposing densification when compressed. Such geometries are being progressively employed in the development of novel products, especially in the fields of intelligent expandable actuators, shape morphing structures and minimally invasive implantable devices. Although several auxetic and potentially auxetic geometries have been summarized in previous reviews and research, precise information regarding relevant properties for design tasks is not always provided. In this study we present a comparative study of two-dimensional and three-dimensional auxetic geometries carried out by means of computer-aided design and engineering tools (from now on CAD–CAE). The first part of the study is focused on the development of a CAD library of auxetics. Once the library is developed we simulate the behavior of the different auxetic geometries and elaborate a systematic comparison, considering relevant properties of these geometries, such as Poisson ratio(s), maximum volume or area reductions attainable and equivalent Young's modulus, hoping it may provide useful information for future designs of devices based on these interesting structures.

Ventilation system design and large scale fire tests

The design, construction and operation of the tunnels of M-30, the major ring road in the city of Madrid (Spain), represent a very interesting project in wich a wide variety of situations -geometrical, topographical, etc.- had to be covered, in variable conditions of traffic. For that reasons, the M-30 project is a remarkable technical challenge, which, after its completion, turned into an international reference. From the "design for safety" perspective, a holistic approach has been used to deal with new technologies, integration of systems and development of the procedures to reach the maximum level. However, one of the primary goals has been to achieve reasonable homogeneity characteristics which can permit operate a netword of tunels as one only infraestructure. In the case of the ventilation system the mentioned goals have implied innovative solutions and coordination efforts of great interest. Consequently, this paper describes the principal ideas underlying the conceptual solution developed focusing on the principal peculiarities of the project.

Design and Validation of an Optimized MB-OFDM Ultra Wideband Transceiver System

Esta tesis está incluida dentro del campo del campo de Multiband Orthogonal Frequency Division Multiplexing Ultra Wideband (MB-OFDM UWB), el cual ha adquirido una gran importancia en las comunicaciones inalámbricas de alta tasa de datos en la última década. UWB surgió con el objetivo de satisfacer la creciente demanda de conexiones inalámbricas en interiores y de uso doméstico, con bajo coste y alta velocidad. La disponibilidad de un ancho de banda grande, el potencial para alta velocidad de transmisión, baja complejidad y bajo consumo de energía, unido al bajo coste de implementación, representa una oportunidad única para que UWB se convierta en una solución ampliamente utilizada en aplicaciones de Wireless Personal Area Network (WPAN). UWB está definido como cualquier transmisión que ocupa un ancho de banda de más de 20% de su frecuencia central, o más de 500 MHz. En 2002, la Comisión Federal de Comunicaciones (FCC) definió que el rango de frecuencias de transmisión de UWB legal es de 3.1 a 10.6 GHz, con una energía de transmisión de -41.3 dBm/Hz. Bajo las directrices de FCC, el uso de la tecnología UWB puede aportar una enorme capacidad en las comunicaciones de corto alcance. Considerando las ecuaciones de capacidad de Shannon, incrementar la capacidad del canal requiere un incremento lineal en el ancho de banda, mientras que un aumento similar de la capacidad de canal requiere un aumento exponencial en la energía de transmisión. En los últimos años, s diferentes desarrollos del UWB han sido extensamente estudiados en diferentes áreas, entre los cuales, el protocolo de comunicaciones inalámbricas MB-OFDM UWB está considerado como la mejor elección y ha sido adoptado como estándar ISO/IEC para los WPANs. Combinando la modulación OFDM y la transmisión de datos utilizando las técnicas de salto de frecuencia, el sistema MB-OFDM UWB es capaz de soportar tasas de datos con que pueden variar de los 55 a los 480 Mbps, alcanzando una distancia máxima de hasta 10 metros. Se esperara que la tecnología MB-OFDM tenga un consumo energético muy bajo copando un are muy reducida en silicio, proporcionando soluciones de bajo coste que satisfagan las demandas del mercado. Para cumplir con todas estas expectativas, el desarrollo y la investigación del MBOFDM UWB deben enfrentarse a varios retos, como son la sincronización de alta sensibilidad, las restricciones de baja complejidad, las estrictas limitaciones energéticas, la escalabilidad y la flexibilidad. Tales retos requieren un procesamiento digital de la señal de última generación, capaz de desarrollar sistemas que puedan aprovechar por completo las ventajas del espectro UWB y proporcionar futuras aplicaciones inalámbricas en interiores. Esta tesis se centra en la completa optimización de un sistema de transceptor de banda base MB-OFDM UWB digital, cuyo objetivo es investigar y diseñar un subsistema de comunicación inalámbrica para la aplicación de las Redes de Sensores Inalámbricas Visuales. La complejidad inherente de los procesadores FFT/IFFT y el sistema de sincronización así como la alta frecuencia de operación para todos los elementos de procesamiento, se convierten en el cuello de la botella para el diseño y la implementación del sistema de UWB digital en base de banda basado en MB-OFDM de baja energía. El objetivo del transceptor propuesto es conseguir baja energía y baja complejidad bajo la premisa de un alto rendimiento. Las optimizaciones están realizadas tanto a nivel algorítmico como a nivel arquitectural para todos los elementos del sistema. Una arquitectura hardware eficiente en consumo se propone en primer lugar para aquellos módulos correspondientes a núcleos de computación. Para el procesado de la Transformada Rápida de Fourier (FFT/IFFT), se propone un algoritmo mixed-radix, basado en una arquitectura con pipeline y se ha desarrollado un módulo de Decodificador de Viterbi (VD) equilibrado en coste-velocidad con el objetivo de reducir el consumo energético e incrementar la velocidad de procesamiento. También se ha implementado un correlador signo-bit simple basado en la sincronización del tiempo de símbolo es presentado. Este correlador es usado para detectar y sincronizar los paquetes de OFDM de forma robusta y precisa. Para el desarrollo de los subsitemas de procesamiento y realizar la integración del sistema completo se han empleado tecnologías de última generación. El dispositivo utilizado para el sistema propuesto es una FPGA Virtex 5 XC5VLX110T del fabricante Xilinx. La validación el propuesta para el sistema transceptor se ha implementado en dicha placa de FPGA. En este trabajo se presenta un algoritmo, y una arquitectura, diseñado con filosofía de co-diseño hardware/software para el desarrollo de sistemas de FPGA complejos. El objetivo principal de la estrategia propuesta es de encontrar una metodología eficiente para el diseño de un sistema de FPGA configurable optimizado con el empleo del mínimo esfuerzo posible en el sistema de procedimiento de verificación, por tanto acelerar el periodo de desarrollo del sistema. La metodología de co-diseño presentada tiene la ventaja de ser fácil de usar, contiene todos los pasos desde la propuesta del algoritmo hasta la verificación del hardware, y puede ser ampliamente extendida para casi todos los tipos de desarrollos de FPGAs. En este trabajo se ha desarrollado sólo el sistema de transceptor digital de banda base por lo que la comprobación de señales transmitidas a través del canal inalámbrico en los entornos reales de comunicación sigue requiriendo componentes RF y un front-end analógico. No obstante, utilizando la metodología de co-simulación hardware/software citada anteriormente, es posible comunicar el sistema de transmisor y el receptor digital utilizando los modelos de canales propuestos por IEEE 802.15.3a, implementados en MATLAB. Por tanto, simplemente ajustando las características de cada modelo de canal, por ejemplo, un incremento del retraso y de la frecuencia central, podemos estimar el comportamiento del sistema propuesto en diferentes escenarios y entornos. Las mayores contribuciones de esta tesis son: • Se ha propuesto un nuevo algoritmo 128-puntos base mixto FFT usando la arquitectura pipeline multi-ruta. Los complejos multiplicadores para cada etapa de procesamiento son diseñados usando la arquitectura modificada shiftadd. Los sistemas word length y twiddle word length son comparados y seleccionados basándose en la señal para cuantización del SQNR y el análisis de energías. • El desempeño del procesador IFFT es analizado bajo diferentes situaciones aritméticas de bloques de punto flotante (BFP) para el control de desbordamiento, por tanto, para encontrar la arquitectura perfecta del algoritmo IFFT basado en el procesador FFT propuesto. • Para el sistema de receptor MB-OFDM UWB se ha empleado una sincronización del tiempo innovadora, de baja complejidad y esquema de compensación, que consiste en funciones de Detector de Paquetes (PD) y Estimación del Offset del tiempo. Simplificando el cross-correlation y maximizar las funciones probables solo a sign-bit, la complejidad computacional se ve reducida significativamente. • Se ha propuesto un sistema de decodificadores Viterbi de 64 estados de decisión-débil usando velocidad base-4 de arquitectura suma-comparaselecciona. El algoritmo Two-pointer Even también es introducido en la unidad de rastreador de origen con el objetivo de conseguir la eficiencia en el hardware. • Se han integrado varias tecnologías de última generación en el completo sistema transceptor basebanda , con el objetivo de implementar un sistema de comunicación UWB altamente optimizado. • Un diseño de flujo mejorado es propuesto para el complejo sistema de implementación, el cual puede ser usado para diseños de Cadena de puertas de campo programable general (FPGA). El diseño mencionado no sólo reduce dramáticamente el tiempo para la verificación funcional, sino también provee un análisis automático como los errores del retraso del output para el sistema de hardware implementado. • Un ambiente de comunicación virtual es establecido para la validación del propuesto sistema de transceptores MB-OFDM. Este método es provisto para facilitar el uso y la conveniencia de analizar el sistema digital de basebanda sin parte frontera analógica bajo diferentes ambientes de comunicación. Esta tesis doctoral está organizada en seis capítulos. En el primer capítulo se encuentra una breve introducción al campo del UWB, tanto relacionado con el proyecto como la motivación del desarrollo del sistema de MB-OFDM. En el capítulo 2, se presenta la información general y los requisitos del protocolo de comunicación inalámbrica MBOFDM UWB. En el capítulo 3 se habla de la arquitectura del sistema de transceptor digital MB-OFDM de banda base . El diseño del algoritmo propuesto y la arquitectura para cada elemento del procesamiento está detallado en este capítulo. Los retos de diseño del sistema que involucra un compromiso de discusión entre la complejidad de diseño, el consumo de energía, el coste de hardware, el desempeño del sistema, y otros aspectos. En el capítulo 4, se ha descrito la co-diseñada metodología de hardware/software. Cada parte del flujo del diseño será detallado con algunos ejemplos que se ha hecho durante el desarrollo del sistema. Aprovechando esta estrategia de diseño, el procedimiento de comunicación virtual es llevado a cabo para probar y analizar la arquitectura del transceptor propuesto. Los resultados experimentales de la co-simulación y el informe sintético de la implementación del sistema FPGA son reflejados en el capítulo 5. Finalmente, en el capítulo 6 se incluye las conclusiones y los futuros proyectos, y también los resultados derivados de este proyecto de doctorado. ABSTRACT In recent years, the Wireless Visual Sensor Network (WVSN) has drawn great interest in wireless communication research area. They enable a wealth of new applications such as building security control, image sensing, and target localization. However, nowadays wireless communication protocols (ZigBee, Wi-Fi, and Bluetooth for example) cannot fully satisfy the demands of high data rate, low power consumption, short range, and high robustness requirements. New communication protocol is highly desired for such kind of applications. The Ultra Wideband (UWB) wireless communication protocol, which has increased in importance for high data rate wireless communication field, are emerging as an important topic for WVSN research. UWB has emerged as a technology that offers great promise to satisfy the growing demand for low-cost, high-speed digital wireless indoor and home networks. The large bandwidth available, the potential for high data rate transmission, and the potential for low complexity and low power consumption, along with low implementation cost, all present a unique opportunity for UWB to become a widely adopted radio solution for future Wireless Personal Area Network (WPAN) applications. UWB is defined as any transmission that occupies a bandwidth of more than 20% of its center frequency, or more than 500 MHz. In 2002, the Federal Communications Commission (FCC) has mandated that UWB radio transmission can legally operate in the range from 3.1 to 10.6 GHz at a transmitter power of －41.3 dBm/Hz. Under the FCC guidelines, the use of UWB technology can provide enormous capacity over short communication ranges. Considering Shannon’s capacity equations, increasing the channel capacity requires linear increasing in bandwidth, whereas similar channel capacity increases would require exponential increases in transmission power. In recent years, several different UWB developments has been widely studied in different area, among which, the MB-OFDM UWB wireless communication protocol is considered to be the leading choice and has recently been adopted in the ISO/IEC standard for WPANs. By combing the OFDM modulation and data transmission using frequency hopping techniques, the MB-OFDM UWB system is able to support various data rates, ranging from 55 to 480 Mbps, over distances up to 10 meters. The MB-OFDM technology is expected to consume very little power and silicon area, as well as provide low-cost solutions that can satisfy consumer market demands. To fulfill these expectations, MB-OFDM UWB research and development have to cope with several challenges, which consist of high-sensitivity synchronization, low- complexity constraints, strict power limitations, scalability, and flexibility. Such challenges require state-of-the-art digital signal processing expertise to develop systems that could fully take advantages of the UWB spectrum and support future indoor wireless applications. This thesis focuses on fully optimization for the MB-OFDM UWB digital baseband transceiver system, aiming at researching and designing a wireless communication subsystem for the Wireless Visual Sensor Networks (WVSNs) application. The inherent high complexity of the FFT/IFFT processor and synchronization system, and high operation frequency for all processing elements, becomes the bottleneck for low power MB-OFDM based UWB digital baseband system hardware design and implementation. The proposed transceiver system targets low power and low complexity under the premise of high performance. Optimizations are made at both algorithm and architecture level for each element of the transceiver system. The low-power hardwareefficient structures are firstly proposed for those core computation modules, i.e., the mixed-radix algorithm based pipelined architecture is proposed for the Fast Fourier Transform (FFT/IFFT) processor, and the cost-speed balanced Viterbi Decoder (VD) module is developed, in the aim of lowering the power consumption and increasing the processing speed. In addition, a low complexity sign-bit correlation based symbol timing synchronization scheme is presented so as to detect and synchronize the OFDM packets robustly and accurately. Moreover, several state-of-the-art technologies are used for developing other processing subsystems and an entire MB-OFDM digital baseband transceiver system is integrated. The target device for the proposed transceiver system is Xilinx Virtex 5 XC5VLX110T FPGA board. In order to validate the proposed transceiver system in the FPGA board, a unified algorithm-architecture-circuit hardware/software co-design environment for complex FPGA system development is presented in this work. The main objective of the proposed strategy is to find an efficient methodology for designing a configurable optimized FPGA system by using as few efforts as possible in system verification procedure, so as to speed up the system development period. The presented co-design methodology has the advantages of easy to use, covering all steps from algorithm proposal to hardware verification, and widely spread for almost all kinds of FPGA developments. Because only the digital baseband transceiver system is developed in this thesis, the validation of transmitting signals through wireless channel in real communication environments still requires the analog front-end and RF components. However, by using the aforementioned hardware/software co-simulation methodology, the transmitter and receiver digital baseband systems get the opportunity to communicate with each other through the channel models, which are proposed from the IEEE 802.15.3a research group, established in MATLAB. Thus, by simply adjust the characteristics of each channel model, e.g. mean excess delay and center frequency, we can estimate the transmission performance of the proposed transceiver system through different communication situations. The main contributions of this thesis are: • A novel mixed radix 128-point FFT algorithm by using multipath pipelined architecture is proposed. The complex multipliers for each processing stage are designed by using modified shift-add architectures. The system wordlength and twiddle word-length are compared and selected based on Signal to Quantization Noise Ratio (SQNR) and power analysis. • IFFT processor performance is analyzed under different Block Floating Point (BFP) arithmetic situations for overflow control, so as to find out the perfect architecture of IFFT algorithm based on the proposed FFT processor. • An innovative low complex timing synchronization and compensation scheme, which consists of Packet Detector (PD) and Timing Offset Estimation (TOE) functions, for MB-OFDM UWB receiver system is employed. By simplifying the cross-correlation and maximum likelihood functions to signbit only, the computational complexity is significantly reduced. • A 64 state soft-decision Viterbi Decoder system by using high speed radix-4 Add-Compare-Select architecture is proposed. Two-pointer Even algorithm is also introduced into the Trace Back unit in the aim of hardware-efficiency. • Several state-of-the-art technologies are integrated into the complete baseband transceiver system, in the aim of implementing a highly-optimized UWB communication system. • An improved design flow is proposed for complex system implementation which can be used for general Field-Programmable Gate Array (FPGA) designs. The design method not only dramatically reduces the time for functional verification, but also provides automatic analysis such as errors and output delays for the implemented hardware systems. • A virtual communication environment is established for validating the proposed MB-OFDM transceiver system. This methodology is proved to be easy for usage and convenient for analyzing the digital baseband system without analog frontend under different communication environments. This PhD thesis is organized in six chapters. In the chapter 1 a brief introduction to the UWB field, as well as the related work, is done, along with the motivation of MBOFDM system development. In the chapter 2, the general information and requirement of MB-OFDM UWB wireless communication protocol is presented. In the chapter 3, the architecture of the MB-OFDM digital baseband transceiver system is presented. The design of the proposed algorithm and architecture for each processing element is detailed in this chapter. Design challenges of such system involve trade-off discussions among design complexity, power consumption, hardware cost, system performance, and some other aspects. All these factors are analyzed and discussed. In the chapter 4, the hardware/software co-design methodology is proposed. Each step of this design flow will be detailed by taking some examples that we met during system development. Then, taking advantages of this design strategy, the Virtual Communication procedure is carried out so as to test and analyze the proposed transceiver architecture. Experimental results from the co-simulation and synthesis report of the implemented FPGA system are given in the chapter 5. The chapter 6 includes conclusions and future work, as well as the results derived from this PhD work.