Silicon photonics is one of the most exciting and fastest growing photonic technologies in recent years. The salient feature of this technology is its compatibility with the mature silicon IC manufacturing based on complementary metal-oxide semiconductor (CMOS) processes widely used in microelectronic industry. Another motivation is the availability of high-quality silicon-on-insulator (SOI) planar waveguide circuits that offer strong optical confinement due to the high index contrast between silicon (n=3.45) and SiO2 (n=1.45). This opens up miniaturization and very large scale integration of photonic devices allowing photonic integrated circuits for a wide range of applications and markets, from optical telecommunications to bio-photonic devices or precise fibre sensors. Optical modulators are key building-blocks for high speed signal transmission and information processing in any photonic interconnection solution. The work developed in this thesis, as part of the objectives of the European project HELIOS in which it is framed, is essentially focused on realizing compact and efficient modulators integrated on silicon chips. The thesis consists of three main chapters as well as the concluding section on the work accomplished. Chapter one is aimed at giving a general description of the benefits of using silicon photonics, showing its challenges and opportunities as well as at giving a deeply overview of all issues related to the electro-optic modulation. Chapter two is devoted to develop silicon modulators with high features for digital applications. Specifically, new optical structures different to the conventional ones are presented with the aim of enhancing the modulation performance or at least several critical parameters in the modulation. Chapter three is dedicated to the analog applications. The concept of microwave photonics is described as well as different researches carried out in the analog scope for application in the field of integrated microwave photonics, all of them using CMOS-compatible electro-optic silicon modulators which validate the potential of silicon photonics as a promising approach for enabling the development of integrated microwave photonics applications. Finally, conclusions on the work realized are provided in Chapter 4. / La fotónica de silicio es una de las tecnologías fotónicas que está experimentando un crecimiento más excitante y rápido en los últimos años. La característica más destacada de esta tecnología es su compatibilidad con las maduras técnicas de fabricación de circuitos integrados de silicio basadas en los procesos ¿complementary metal-oxide semiconductor¿ (CMOS) ampliamente utilizados en la industria microelectrónica. Otra motivación es la disponibilidad de circuitos de guía de ondas planas de silicio sobre aislante (SOI) de alta calidad que ofrecen un fuerte confinamiento óptico debido al alto contraste índices entre el silicio (n=3,45) y el SiO2 (n = 1,45). Esto abre las puertas a la miniaturización y a la integración a gran escala de dispositivos fotónicos lo que resulta en circuitos fotónicos integrados para una amplia gama de aplicaciones y mercados, desde telecomunicaciones ópticas a dispositivos bio-fotónicos o sensores de fibra precisos. Los moduladores ópticos son elementos básicos fundamentales para la transmisión de señales a alta velocidad y el procesado de información en cualquier solución de interconexión fotónica. El trabajo desarrollado en esta tesis, como parte del los objetivos del proyecto Europeo HELIOS en el que está enmarcada, se centra fundamentalmente en realizar moduladores compactos y eficientes, integrados en chips de silicio. La tesis consiste en 3 capítulos principales así como una sección de conclusiones del trabajo conseguido. El capítulo uno está destinado a dar una descripción general de los beneficios del uso de la fotónica de silicio, mostrando sus retos y oportunidades, así como a dar una visión profunda de todos los aspectos relacionados con la modulación electro-óptica. El capítulo dos está dedicado a desarrollar moduladores de silicio de altas prestaciones para aplicaciones digitales. Específicamente, se presentan nuevas estructuras ópticas diferentes a las convencionales con el objetivo de mejorar el rendimiento de la modulación o al menos algunos parámetros críticos en la modulación. El tercer capítulo se dedica a las aplicaciones analógicas. Se describe el concepto de la fotónica de microondas, así como diferentes investigaciones llevadas a cabo en el ámbito analógico para su aplicación en el campo de la fotónica integrada de microondas, todas ellas usando moduladores electro-ópticos de silicio compatibles con los procesos de fabricación CMOS, lo que valida el potencial de la fotónica de silicio como un prometedor enfoque para permitir el desarrollo de aplicaciones de la fotónica integrada de microondas. Por último, las conclusiones sobre el trabajo realizado se proporcionan en el Capítulo 4. / Gutiérrez Campo, AM. (2013). Development of integrated silicon photonics modulation devices for digital and analog applications [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/33330 / TESIS

Orientador: Claudio Kitano / Resumo: Sistemas ópticos operando em altas frequências utilizam modulação externa do laser, em especial através de moduladores baseados no efeito eletroóptico linear, onde se aplicam guias de ondas de dimensões reduzidas com eletrodos planares. Assim, é importante e conveniente determinar as propriedades e a distribuição do campo elétrico modulador de modo a conhecer outras características da estrutura, como resposta em frequência e potência de modulação. Neste trabalho, isto foi feito através do método de abordagem de domínio espectral. Contudo, este método apresenta imprecisões em estruturas com assimetria de eletrodos, aplicando-se então o método das imagens, clássico no eletromagnetismo, aliado à técnica de abordagem de domínio espectral. Esta nova abordagem permite a obtenção de funções de base adequadas à análise de parâmetros como o campo elétrico, assim como os demais parâmetros característicos dos guias de ondas planos. Este trabalho apresenta esta abordagem e seus resultados comparando-os à simples translação das funções de base para estruturas simétricas, validando a técnica proposta, bem como se propõe a desenvolver um conjunto de rotinas numéricas utilizando para isso o software Matlab. Através do processo de desenvolvimento das rotinas numéricas são apresentadas as dificuldades e metodologias de solução para implementação do método automatizado. Além de permitir a automatização de todo o processo de cálculo, minimizando a interferência humana, neste trabalho também é de... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

abstract: Optical metasurfaces, i.e. artificially engineered arrays of subwavelength building blocks supporting abrupt and substantial light confinement, was employed to demonstrate a novel generation of devices for circularly polarized detection, full-Stokes polarimetry and all-optical modulation with ultra-compact footprint and chip-integrability. Optical chirality is essential for generation, manipulation and detection of circularly polarized light (CPL), thus finds many applications in quantum computing, communication, spectroscopy, biomedical diagnosis, imaging and sensing. Compared to natural chiral materials, chiral metamaterials and metasurfaces enable much stronger chirality on subwavelength scale; therefore, they are ideal for device miniaturization and system integration. However, they are usually associated with low performance due to limited fabrication tolerance and high dissipation mainly caused by plasmonic materials. Here, a bio-inspired submicron-thick chiral metamaterial structure was designed and demonstrated experimentally with high contrast (extinction ratio >35) detection of CPL with different handedness and high efficiency (>80%) of the overall device. Furthermore, integration of left- and right-handed CPL detection units with nanograting linear polarization filters enabled full-Stokes polarimetry of arbitrarily input polarization states with high accuracy and very low insertion loss, all on a submillimeter single chip. These unprecedented highly efficient and high extinction ratio devices pave the way for on-chip polarimetric measurements. All-optical modulation is widely used for optical interconnects, communication, information processing, and ultrafast spectroscopy. Yet, there’s deficiency of ultrafast, compact and energy-efficient solutions all in one device. Here, all-optical modulation of light in the near- and mid-infrared regimes were experimentally demonstrated based on a graphene-integrated plasmonic nanoantenna array. The remarkable feature of the device design is its simultaneous near-field enhancement for pump and probe (signal) beams, owing to the localized surface plasmon resonance excitation, while preserving the ultrafast photocarrier relaxation in graphene. Hence, a distinct modulation at 1560nm with record-low pump fluence (<8μJ/cm^2) was reported with ~1ps response time. Besides, relying on broadband interaction of graphene with incident light, a first-time demonstration of graphene-based all-optical modulation in mid-infrared spectral region (6-7μm) was reported based on the above double-enhancement design concept. Relying on the tunability of metasurface design, the proposed device can be used for ultrafast optical modulation from near-infrared to terahertz regime. / Dissertation/Thesis / Doctoral Dissertation Electrical Engineering 2020

Neuronal nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that are necessary in memory and cognition. They are pentameric and consist of α and β subunits. They are most commonly heteromeric but, can sometimes be homomeric. nAChRs are activated by many ligands including nicotine (exogenous) and acetylcholine (endogenous).nAChRs are located on hippocampal interneurons. The interneurons, although sparse, control the synchronous firing of the pyramidal cells. However, the hippocampal interneuron structure and function is quite diverse and not fully characterized. Therefore, we sought to quantify nAChR subunit mRNA levels using real-time PCR of CA1 hippocampal interneurons.Surprisingly we found that the α3 and β2 mRNA subunits were the highest expressed and highest co-expressed subunits. Additionally, the α4 mRNA subunit was the lowest expressed of the subunits detected. The α4 subunit is one of the most pharmacologically targeted nAChR subunits and is found throughout the rest of the brain at much higher levels than the α3 mRNA subunit. Upon PCR analysis two subpopulations of the α3 and β2 subunits emerged: those that contained 3X more α3 than β2 and those that contained 3X more β2 than α3. Therefore, we hypothesized that two likely α3β2 nAChR stoichiometries are present in hippocampal interneurons. We differentiated their kinetic properties using electrophysiology.Additionally, like the α4 subunit, the α7 subunit is highly targeted in cognitive therapeutics. Since, the α7 subunit is the most characterized nAChR subunit, there are current efforts to develop allosteric modulators of the α7 subunit. The α7 subunit is found at moderate levels within hippocampal interneurons and remains a valid target. Current treatment options for Alzheimer's disease, and other dementias are limited and only mildly effective. Therefore, we sought to characterize the effect of 3-furan-2-yl-N-p-tolyl-acrylamide (PAM-2) on α7.Furthermore, there are no current methods to distinguish the α7 from the α7β2 nAChRs during whole cell electrophysiological recordings. Therefore, we also characterized the PAM-2 effect on α7β2 nAChRs. Our results highlight at least 2 ways PAM-2 can be used to differentiate α7 from the α7β2 during whole-cell recordings.

Precise engineering of genomes holds great promise to advance our understanding of gene function and biotechnological applications. DNA double strand breaks are repaired via imprecise non-homologous end joining repair or via precise homology-directed repair processes. Therefore, we could harness the DSBs to engineer the genomes with a variety of genetic outcomes and with singlebase- level precision. The major barrier for genome engineering was the generation of site-specific DNA DSBs. Programmable DNA enzymes capable of making a complete and site-specific cut in the genome do not exist in nature. However, these enzymes can be made in in vitro as chimeric fusions of two modules, a DNA binding module and a DNA cleaving module. The DNA cleaving module can be programmed to bind to any user-defined sequence and the DNA cleaving module would generate DSBs in the target sequence. These enzymes called molecular scissors include zinc finger nucleases (ZFNs) and transcriptional activator like effector nucleases (TALENs). The programmability of these enzymes depends on protein engineering for DNA binding specificity which may be complicated, recourse intensive and suffer from reproducibility issues. Recently, clustered regularly interspaced palindromic repeats (CRISPR)/ CRISPR associated endonuclease 9 (Cas9) an adaptive immune system of bacterial and archaeal species has been developed for genome engineering applications. CRISPR/Cas9 is an RNA-guided DNA endonuclease and can be reprogrammed through the engineering of single guide RNA molecule (sgRNA). CRISPR/Cas9 activity has been shown across eukaryotic species including plants. Although the engineering of CRISPR/Cas9 is quite predictable and reproducible, there are many technological challenges and improvements that need to be made to achieve robust, specific, and efficient plant genome engineering. Here in this thesis, I developed a number of technologies to improve specificity, delivery and expression and heritability of CRISRP/Cas9-modification in planta. Moreover, I used these technologies to answer basic questions to understand the molecular underpinning of the interplay between splicing and abiotic stress. To improve Cas9 specificity, I designed and constructed a chimeric fusion between catalytically dead Cas9 (dCas9) and FOKI catalytic DNA cleaving domain (dCas9.FoKI). This synthetic chimeric fusion enzyme improved Cas9 specificity which enable precision genome engineering. Delivery of genome engineering reagents into plant cells is quite challenging, I developed a virus-based system to deliver sgRNAs into plants which facilitates plant genome engineering and could bypass the need for tissue culture in engineering plant genomes. To improve the expression of the CRISPR/Cas9 machinery in plant species, I developed a meiotically-driven expression of CRISPR/Cas9 which improved genome editing and heritability of editing in seed progeny, thereby facilitating robust genome engineering applications. To understand the molecular basis of the interplay between splicing stress and abiotic stress, I used the CRISPR/Cas9 machinery to engineer components of the U2snRNP complex coupled which chemical genomics to understand the splicing stress regulation in response to abiotic stress conditions. Finally, I harnessed the technological improvements and developments I have achieved with CRISPR/Cas9 system to develop a directed evolution platform for targeted trait engineering which expands and accelerates trait discovery and engineering of plant species resilient to climate change conditions.

Optical phase microscopy provides a view of objects that have minimal to no effect on the detected intensity of light that are unobservable by standard microscopy techniques. Since its inception just over 60 years ago that gave us a vision to an unseen world and earned Frits Zernike the Nobel prize in physics in 1953, phase microscopy has evolved to find various applications in biological cell imaging, crystallography, semiconductor failure analysis, and more. Two common and commercially available techniques are phase contrast and differential interference contrast (DIC). In phase contrast method, a large portion of the unscattered light that accounts for the majority of the light passing unaffected through a transparent medium is blocked to allow the scattered light due to the object to be observed with higher contrast. DIC is a self-referenced interferometer that transduces phase variation to intensity variation. While being established as fundamental tools in many scientific and engineering disciplines, the traditional implementation of these techniques lacks the ability to provide the means for quantitative and repeatable measurement without an extensive and cumbersome calibration. The rapidly growing fields in modern biology meteorology and nano-technology have emphasized the demand for a more robust and convenient quantitative phase microscopy. The recent emergence of modern optical devices such as high resolution programmable spatial light modulators (SLM) has enabled a multitude of research activities over the past decade to reinvent phase microscopy in unconventional ways. This work is concerned with an implementation of a DIC microscope containing a 4-f system at its core with a programmable SLM placed at the frequency plane of the imaging system that allows for employing Fourier pair transforms for wavefront manipulation. This configuration of microscope provides a convenient way to perform both wavefront shearing with quantifiable arbitrary shear amount and direction as well as phase stepping interferometry by programming the SLM with a series of numerically generated patterns and digitally capturing interferograms for each step which are then used to calculate the objects phase gradient map. Wavefront shearing is performed by generating a pattern for the SLM where two phase ramp patterns with opposite slopes are interleaved through a random selection process with uniform distribution in order to mimic the simultaneous presence of the ramps on the same plane. The theoretical treatment accompanied by simulations and experimental results and discussion are presented in this work.

This paper presents a modulator driver realized as a breakdown voltage doubler which can provide a high output swing of 7.6 Vpp,diff for load impedances as low as 30 Ω, thus overcoming the limitation imposed by the collector-emitter breakdown voltage. The open-collector design gives an important degree of freedom regarding the modulator load to be driven, while significantly reducing the circuit's power consumption. The driver is capable of running at 30 Gb/s while dissipating 1 W of DC power. Thanks to the inductorless design, the active area occupied by the circuit is only 0.28 mm × 0.23 mm. The driver was realized in a 250 nm SiGe BiCMOS technology.

A true linearized interferometric intensity modulator for pulsed light has been proposed and experimentally presented in this thesis. This has been achieved by introducing a mode-locked laser into one of the arms of a Mach-Zehnder interferometer and injection-locking it to the input light (which is pulsed and periodic). By modulating the injection-locked laser, and combining its output light with the light from the other arm of interferometer in quadrature, one can achieve true linearized intensity modulator. This linearity comes from the arcsine phase response of the injection-locked mode-locked laser (as suggested by steady-state solution of Adler's equation) when it is being modulated. Mode-locked lasers are fabricated using a novel AlGaInAs-InP material system. By using the BCB for planarization and minimizing the metal pad size and directly modulating the laser, we have achieved very effective fundamental hybrid mode-locking at the repetition rate of ~ 23 GHz. This laser also provided the short pulses of 860 fs and 280 fs timing jitter integrated from 1 Hz- 100 MHz. The linearized intensity modulator has been built by using two identical two-section mode-locked lasers with the same length, one as the slave laser in one of the arms of the Mach-Zehnder interferometer injection-locked to the other one as the master which is the input light to the modulator. A low V? of 8.5 mV is achieved from this modulator. Also the current of the gain section or the voltage of the saturable absorber section of the slave laser has been used to apply the modulation signal. A spur free dynamic range of 70 dB.Hz2/3 is achieved when modulating the modulator through the saturable absorber. Modulating the saturable absorber provides a reduced third-order intermodulation tone with respect to modulating the gain. This is simply because of the unwanted amplitude modulation created when modulating the gain section current. Finally an improved design is proposed and demonstrated to improve the modulator performance. This is achieved by introducing a third section to the laser. Using the impurity free vacancy disordering technique the photoluminescence peak of this section is blue-shifted selectively and therefore there would not be any absorption in that passive section. By applying the modulation signal to this passive section rather than applying it to the gain section or saturable absorber section, the amplitude and phase modulation could be decoupled. The experimental results have presented here and an almost six-fold reduction in V? and 5 dB improvement in spur free dynamic range have been achieved. The proposed and demonstrated configuration as an analog optical link has the potential to increase the performance and resolution of photonic analog-to-digital converters.

The development of compact imaging systems capable of transmitting high-resolution images in real-time while covering a wide field-of-view (FOV) is critical in a variety of military and civilian applications: surveillance, threat detection, target acquisition, tracking, remote operation of unmanned vehicles, etc. Recently, optical foveated imaging using liquid crystal (LC) spatial light modulators (SLM) has received considerable attention as a potential approach to reducing size and complexity in fast wide-angle lenses. The fundamental concept behind optical foveated imaging is reducing the number of elements in a fast wide-angle lens by placing a phase SLM at the pupil stop to dynamically compensate aberrations left uncorrected by the optical design. In the recent years, considerable research and development has been conducted in the field of optical foveated imaging based on the LC SLM technology, and several foveated optical systems (FOS) prototypes have been built. However, most research has been focused so far on the experimental demonstration of the basic concept using off the shelf components, without much concern for the practicality or the optical performance of the systems. Published results quantify only the aberration correction capabilities of the FOS, often claiming diffraction limited performance at the region of interest (ROI). However, these results have continually overlooked diffraction effects on the zero-order efficiency and the image quality. The research work presented in this dissertation covers the methods and results of a detailed theoretical research study on the diffraction analysis, image quality, design, and optimization of fast wide-angle FOSs based on the current transmissive LC SLM technology. The amplitude and phase diffraction effects caused by the pixelated aperture of the SLM are explained and quantified, revealing fundamental limitations imposed by the current transmissive LC SLM technology. As a part of this study, five different fast wide-angle lens designs that can be used to build practical FOSs were developed, revealing additional challenges specific to the optical design of fast wide-angle systems, such as controlling the relative illumination, distortion, and distribution of aberrations across a wide FOV. One of the lens design examples was chosen as a study case to demonstrate the design, analysis, and optimization of a practical wide-angle FOS based on the current state-of-the-art transmissive LC SLM technology. The effects of fabrication and assembly tolerances on the image quality of fast wide-angle FOSs were also investigated, revealing the sensitivity of these fast well-corrected optical systems to manufacturing errors. The theoretical study presented in this dissertation sets fundamental analysis, design, and optimization guidelines for future developments in fast wide-angle FOSs based on transmissive SLM devices.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder involving a mutation in the CF transmembrane conductance regulator protein (CFTR), which causes dysfunctional transport of chloride ions across cell membranes. CF affects multiple body systems and a few of its symptoms include chronic cough, difficulty breathing, obstructive airway disease, bacterial pulmonary infections, maldigestion, malabsorption, pancreatitis, and male infertility. Until recently, treatment options have been limited to alleviating symptoms, but a new classification of drugs, CFTR modulators, provide an opportunity to slow the progression of the disease and improve clinical outcomes. The effect of CFTR modulators may be attributed to the reduction of persistently colonizing bacteria in CF lungs. Though, the effects of modulators on microbial communities colonizing the CF lung remains unknown, specifically with common respiratory pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus. Particularly, previous CF studies have been limited in scope due to focusing on only one type of modulator and by using low-yield sequencing techniques. To address this gap, we seek to study the changes in CF respiratory pathogens of patients initiating CFTR modulator therapy at Nemours Hospital using long-read metagenomic sequencing (Oxford Nanopore) of longitudinally collected respiratory samples. We have optimized a protocol for host DNA depletion and microbial metagenomic sequencing to characterize the respiratory microbiome. This study focuses on utilizing these sequencing data to compare the microbiome among two healthy controls to pre-CFTR-treatment microbial communities of two recruited pediatric CF patients.