Integrated Photonic Platforms for Quantum Technology: A Review

Quantum information processing has conceptually changed the way we process and transmit information. Quantum physics, which explains the strange behaviour of matter at the microscopic dimensions, has matured into a quantum technology that can harness this strange behaviour for technological applications with far-reaching consequences, which uses quantum bits (qubits) for information processing. Experiments suggest that photons are the most successful candidates for realising qubits, which indicates that integrated photonic platforms will play a crucial role in realising quantum technology. This paper surveys the various photonic platforms based on different materials for quantum information processing. The future of this technology depends on the successful materials that can be used to universally realise quantum devices, similar to silicon, which shaped the industry towards the end of the last century. Though a prediction is implausible at this point, we provide an overview of the current status of research on the platforms based on various materials.Comment: 48 pages, 3 figure

Optimized Biosignals Processing Algorithms for New Designs of Human Machine Interfaces on Parallel Ultra-Low Power Architectures

The aim of this dissertation is to explore Human Machine Interfaces (HMIs) in a variety of biomedical scenarios. The research addresses typical challenges in wearable and implantable devices for diagnostic, monitoring, and prosthetic purposes, suggesting a methodology for tailoring such applications to cutting edge embedded architectures. The main challenge is the enhancement of high-level applications, also introducing Machine Learning (ML) algorithms, using parallel programming and specialized hardware to improve the performance. The majority of these algorithms are computationally intensive, posing significant challenges for the deployment on embedded devices, which have several limitations in term of memory size, maximum operative frequency, and battery duration. The proposed solutions take advantage of a Parallel Ultra-Low Power (PULP) architecture, enhancing the elaboration on specific target architectures, heavily optimizing the execution, exploiting software and hardware resources. The thesis starts by describing a methodology that can be considered a guideline to efficiently implement algorithms on embedded architectures. This is followed by several case studies in the biomedical field, starting with the analysis of a Hand Gesture Recognition, based on the Hyperdimensional Computing algorithm, which allows performing a fast on-chip re-training, and a comparison with the state-of-the-art Support Vector Machine (SVM); then a Brain Machine Interface (BCI) to detect the respond of the brain to a visual stimulus follows in the manuscript. Furthermore, a seizure detection application is also presented, exploring different solutions for the dimensionality reduction of the input signals. The last part is dedicated to an exploration of typical modules for the development of optimized ECG-based applications

Graphene Integrated Metamaterial Devices for Terahertz Modulation

Terahertz (THz) research has experienced impressive progress in recent decades, with unique applications emerging in fields such as spectroscopy, communications, and imaging, all of which require fast and accurate control of the THz radiation properties. To unlock the full potential of THz radiation, it is essential to develop a catalogue of high speed, electrically controllable modular THz devices, which can be implemented with standardised sources to build versatile THz systems. Due to THz frequencies lying outside of the typical operation range for the mature microwave and photonic technologies, alternative approaches are required to solve the unique engineering problems associated with operating in this frequency regime. This thesis will look to design and develop novel device architectures using metamaterial arrays to strongly couple with THz radiation, whilst implementing electrically tunable graphene to modify the strength and nature of this interaction, leading to active control of the amplitude, phase, polarisation and frequency of THz radiation. Chapter 1 discusses two THz sources: THz time-domain spectroscopy (THz-TDS) and THz quantum cascade lasers (THz-QCLs). A range of THz modulator architectures will then be discussed, focusing on the methods which involve converting passive metamaterial arrays into actively tunable devices, including the implementation of microelectromechanical systems (MEMS), photoactive semiconductors, and electrostatically tunable graphene. Chapter 2 outlines the basic device design principles for the graphene integrated metamaterial devices shown in this thesis. The steps to build a basic split ring resonator (SRR) and graphene amplitude modulator device are discussed, starting with the design process using finite element electromagnetic simulation, before outlining the fabrication steps required to build the device, and finally performing the experimental procedure to test the device performance in a THz-TDS system. The SRR/graphene device discussed in this chapter demonstrates amplitude modulation depths in the region of 12 %, achieved by electrostatically tuning the graphene conductivity using a voltage range of 30 V. Chapter 3 investigates more sophisticated graphene integrated metamaterial devices which involve lithographically selecting targeted areas of the metamaterial structure to be actively tuned by graphene. More interesting modulation effects, such as resonant frequency tuning, are achieved by integrating a coupled resonator metamaterial array with targeted graphene damping. A continuous tuning of the resonant frequency over a 60 GHz range, and binary tuning of over 200 GHz are achieved. Due to the highly dispersive nature of the coupled resonator array, dramatic phase and group delay modulation effects are also demonstrated. Chapter 4 builds on the work from chapter 3, converting the coupled resonator and graphene devices into polarisation modulators by adding an intrinsic chirality into the metamaterial design. Two different devices are designed and fabricated, both achieving electrical control over the polarisation angle and ellipticity of the transmitted radiation. Polarisation tuning of up to 30 degrees is experimentally confirmed, with linear radiation successfully converted into perfectly circular radiation, achieving an ellipticity tuning range from 0.6 to 1.0. Chapter 5 discusses the implementation of the active devices described in the previous chapters with quantum cascade lasers, for the conversion of a standard THz source into a highly versatile amplitude, polarisation and frequency controllable modular THz system. MHz modulation speeds of QCLs are achieved by directing a QCL output through the polarisation devices, with the polarisation angle actively tuned by up to 9 degrees. Dramatic modulation effects are achieved by externally coupling radiation back into a QCL using the devices as electrically tunable mirrors in an external cavity configuration. 100 % amplitude modulation of the QCL is achieved using this method, and the frequency of THz output is also successfully manipulated, with 20 GHz binary tuning of the laser output achieved. Chapter 6 discusses future methods which could be used to enhance the modulation depths of the devices described in this thesis. A modified reflection modulation scheme is proposed and theoretically described which could greatly enhance the tuning range of the modulators. Preliminary TDS experiments are performed showing near 100 % amplitude modulation depths by employing this modulation scheme. Further to this, a continuous π/2 phase tuning range is achieved, corresponding to a 10 times improvement compared to the standard transmission and reflection modulation schemes. A modified QCL feedback scheme is also described which could utilize this enhanced phase modulation to achieve continuous tuning of the QCL output over 10s of GHz. A similar scheme is simulated to produce greatly enhanced polarization modulation depths with nearly 90 degrees polarization angle tuning, and near linear to perfectly circular polarisation modulation predicted. A potential modular TDS set-up is also proposed which involves implementing the polarisation modulators into the standard set-up, for fast material birefringence characterisation

Optical manipulation and advanced analysis of cells using an innovative optofluidic platform

This doctoral research project aims to analyse complex processes of living cells using Digital Holographic Microscopy (DHM) as a three-dimensional (3D) imaging tool. DHM is a real-time, high-throughput, label-free and quantitative phase imaging technique which permits advanced cell analysis in microfluidic environment. In particular, an innovative optofluidic platform is implemented, composed of a DHM modulus and aided by holographic optical tweezers (HOT) for optical manipulation and a fluorescence modulus. This platform has been used for blood disease screening, cell manipulation studies and tracking of migrating cells. In this thesis, three main topics have been investigated. The first topic focuses on diagnostics, which plays several critical roles in healthcare. Here a novel and cost-effective approach for detecting real blood disorders such as iron-deficiency anaemia and thalassemia at lab-on-chip scale is shown. In addition, cell dynamics studies were performed by DHM. In particular, a study regarding the temporal evolution of cell morphology and volume during blue light exposure is reported. The second topic aims to investigate cell mechanics. To this end, the capabilities of HOT were used to enable the generation and the independent high-precision control of an arbitrary number of 3D optical traps. The combination of HOT and DHM provides the possibility to manipulate cells, detect nano-mechanical cell response in the pN range, and reveal cytoskeleton formation. To confirm the formation of the cytoskeleton structures after the stimulation, a fluorescence imaging system was used as control. Finally, the third topic focuses on cell manipulation using an innovative electrode-free dielectrophoretic approach (DEP) for investigating smart but simple strategies for orientation and immobilization of biological samples such as bacteria and fibroblast. In particular, the light-induced DEP is achieved using ferroelectric iron- doped lithium niobate crystal as substrate. In this way, a dynamic platform that can dynamically regulate the cell response has been developed. In this case, DHM is going to be used as a time-lapse imaging tool for the characterization of dynamic cell processes. In conclusion, the results show that DHM is a highly relevant method that allows novel insights into dynamic cell biology, with applications in cancer research and toxicity testing. In addition, this study could pave the way for detecting and quantifying circulating tumor cells and for providing multidimensional information on tumour metastasis. In this framework, the optofluidic platform is a promising tool for both identification and characterization of “foreign” cancer cells in the blood stream in order to achieve an early diagnosis

The role and regulation of FOXO3a in cancer and chemotherapy resistance

Drug resistance is the major impediment to the success of cancer therapy. The PI3K/AKT pathway mediates a plethora of cellular functions, including cell survival, proliferation and differentiation. However, increased activation of this pathway has been correlated with drug resistance mechanisms. This pathway regulates the activity of FOXO transcription factors in a negative manner through AKT-dependent phosphorylations. The modulation of FOXO activity leads to a variety of cellular outputs, including cell cycle arrest and apoptosis that define this transcription factor as a tumour suppressor. Importantly, FOXO has also been shown to mediate the effect of many anti-cancer drugs, suggesting that it has an additional role in drug sensitivity and resistance. With this work, by studying the PI3K/AKT/FOXO axis in breast cancer, I have characterised its impact in drug sensitivity and resistance. I found that this axis is deregulated in breast cancer resistant cells. By extending my in vitro findings to clinical samples, I further elucidated the potential role of AKT and FOXO3a as indicators and predictors of treatment response in breast cancer. In addition, I have also characterised three novel downstream targets of FOXO3a - FOXP1, FOXM1 and VEGF – with important roles towards breast cancer progression and in the development of drug-resistance. By characterising these FOXO3a effectors, I unravelled a potential general mechanism by which FOXO3a represses gene target expression

3D in vitro cancer models for drug screening: A study of glucose metabolism and drug response in 2D and 3D culture models

Current drug screening protocols use in vitro cancer cell panels grown in 2D to evaluate drug response and select the most promising candidates for further in vivo testing. Most drug candidates fail at this stage, not showing the same efficacy in vivo as seen in vitro. An improved first screening that is more translatable to the in vivo tumor situation could aid in reducing both time and cost of cancer drug development. 3D cell cultures are an emerging standard for in vitro cancer cell models, being more representative of in vivo tumour conditions. To overcome the translational challenges with 2D cell cultures, 3D systems better model the more complex cell-to-cell contact and nutrient levels present in a tumour, improving our understanding of cancer complexity. Furthermore, cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg, and possibly related to changes in nutrient access. However, there are few reports on how 3D cultures differ metabolically from 2D cultures, especially when grown in physiological glucose conditions. Along with this, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Therefore, the aim of this work was to investigate the effect of culture conditions on response to metabolic drugs and study the metabolism of 3D spheroid cultures in detail. To achieve this, multiple cancer cell lines were studied in high and low glucose concentrations and in 2D and 3D cultures. We found that glucose concentration is important at a basic level for growth properties of cell lines with different metabolic phenotypes and it affects sensitivity to metformin. Furthermore, metformin is able to shift metabolic phenotype away from OXPHOS dependency. There are significant differences in glucose metabolism of 3D cultures compared to 2D cultures, both related to glycolysis and oxidative phosphorylation. Spheroids have higher ATP-linked respiration in standard nutrient conditions and higher non-aerobic ATP production in the absence of supplemented glucose. Multi-round treatment of spheroids is able to show more robust response than standard 2D drug screening, including resistance to therapy. Results from 2D cultures both over and underestimate drug response at different concentrations of 5-fluorouracil (5-FU). A higher maximum effect of 5-FU is seen in models with lower OCR/ECAR ratios, an indication of a more glycolytic metabolic phenotype. In conclusion, both culture method and nutrient conditions are important consideration for in vitro cancer models. There is good reason to not maintain in vitro cultures in artificially high glucose conditions. It can have downstream affects on drug response and likely other important metrics. If possible, assays should also be implemented in 3D. If not in everyday assays, at least as a required increase in complexity to validate 2D results. Finally, metabolism even in the small scope presented here, is complex in terms of phenotypic variation. This shows the importance of metabolic screening in vitro to better understand the effects of these small changes and to model how a specific tumor may behave based on its complex metabolism

Charged Domain Walls in Ferroelectric Single Crystals

Charged domain walls (CDWs) in proper ferroelectrics are a novel route towards the creation of advancing functional electronics. At CDWs the spontaneous polarization obeying the ferroelectric order alters abruptly within inter-atomic distances. Upon screening, the resulting charge accumulation may result in the manifestation of novel fascinating electrical properties. Here, we will focus on electrical conduction. A major advantage of these ferroelectric DWs is the ability to control its motion upon electrical fields. Hence, electrical conduction can be manipulated, which can enrich the possibilities of current electronic devices e.g. in the field of reconfigurability, fast random access memories or any kind of adaptive electronic circuitry. In this dissertation thesis, I want to shed more light onto this new type of interfacial electronic conduction on inclined DWs mainly in lithium niobate/LiNbO3 (LNO). The expectation was: the stronger the DW inclination towards the polar axis of the ferroelectric order and, hence, the larger the bound polarization charge, the larger the conductivity to be displayed. The DW conductance and the correlation with polarization charge was investigated with a multitude of experimental methods as scanning probe microscopy, linear and nonlinear optical microscopy as well as electron microscopy. We were able to observe a clear correlation of the local DW inclination angle with the DW conductivity by comparing the three-dimensional DW data and the local DW conductance. We investigated the conduction mechanisms on CDWs by temperature-dependent two-terminal current-voltage sweeps and were able to deduce the transport to be given by small electron polaron hopping, which are formed after injection into the CDWs. The thermal activated transport is in very good agreement with time-resolved polaron luminescence spectroscopy. The applicability of this effect for non-volatile memories was investigated in metal-ferroelectric-metal stacks with CMOS compatible single-crystalline films. These films showed unprecedented endurance, retention, precise set voltage, and small leakage currents as expected for single crystalline material. The conductance was tuned and switched according to DW switching time and voltage. The formation of CDWs has proven to be extremely stable over at least two months. The conductivity was further investigated via microwave impedance microscopy, which revealed a DW conductivity of about 100 to 1000 S/m at microwave frequencies of about 1 GHz.:1 INTRODUCTION 1 I THEORETICAL BASICS 5 2 FUNDAMENTALS 7 2.1 Ferroelectricity 7 2.1.1 Spontaneous polarization 8 2.1.2 Domains and domain walls 9 2.1.3 Charged domain walls 13 2.1.4 Conductive domain walls 16 2.2 Visualization of ferroelectric domains and domain walls 21 2.2.1 Light microscopy 22 2.2.2 Second-harmonic generation microscopy 22 2.2.3 Cherenkov second-harmonic generation microscopy 25 2.2.4 Optical coherence tomography 28 2.2.5 Piezo-response force microscopy 30 2.2.6 Ferroelectric lithography 31 2.2.7 Further methods 34 2.3 Lithium niobate and tantalate 37 2.3.1 General Properties 37 2.3.2 Stoichiometry 38 2.3.3 Optical properties 40 2.3.4 Intrinsic and extrinsic defects 43 2.3.5 Polarons 47 2.3.6 Ionic conductivity 51 3 METHODS 53 3.1 Sample Preparation 53 3.1.1 Poling stage 53 3.1.2 Thermal treatment 56 3.1.3 Ion slicing of LNO crystals 57 3.2 Atomic force microscopy 59 3.2.1 Non-contact and contact mode AFM microscopy 59 3.2.2 Piezo-response force microscopy (PFM) 60 3.2.3 Conductive atomic force microscopy (cAFM) 62 3.2.4 Scanning microwave impedance microscopy (sMIM) 63 3.2.5 AFM probes 66 3.3 Laser scanning microscope 67 3.4 Time-resolved luminescence spectroscopy 71 3.5 Energy-resolved photoelectron emission spectromicroscopy 72 II EXPERIMENTS 75 4 RESULTS 77 4.1 Three-dimensional profiling of domain walls 78 4.1.1 Randomly poled LNO and LTO domains 78 4.1.2 Periodically Poled Lithium Niobate 81 4.1.3 AFM-written Domains 83 4.1.4 Thermally treated LNO 84 4.1.5 Laser-written domains 86 4.2 Polarization charge textures 90 4.2.1 Random domains in Mg:LNO and Mg:LTO 90 4.2.2 Thermally-treated LNO 92 4.3 Quasi-phase matching SHG 92 4.4 Photoelectron microspectroscopy 97 4.5 Activated polaron transport 101 4.6 High voltage treated LNO 113 4.7 Conductive domain walls in exfoliated thin-film LNO 115 4.7.1 Conductance maps 116 4.7.2 Resistive switching by conductive domain walls 120 4.8 Microwave impedance microscopy 134 4.8.1 Finite-element method simulation 134 4.8.2 Scanning microwave impedance microscopy 136 5 conclusion & outlook 143 III EPILOGUE 147 a APPENDIX 149 a.1 Laser ablation dynamics on LNO surfaces 149 a.2 XPS across a conductive DW in LNO 150 a.3 XRD of thin-film exfoliated LNO 151 a.4 Domain writing in exfoliated thin-film LNO 152 a.5 Retention in conductance at DWs in thin-film exfoliated LNO 155 a.6 sMIM on DWs in thin-film exfoliated LNO 157 a.7 Domain inversion evolution under a tip by phase-field modeling 159 a.8 Current transients in exfoliated LNO 161 a.9 Surface acoustic wave excitation damping at DWs 162 a.10 Influence of UV illumination on domains in Mg:LNO 162 Acronyms 165 Symbols 169 List of figures 172 List of tables 176 Bibliography 177 Publications 225 Erklärung 233Geladene Domänenwände (DW) in reinen Ferroelektrika stellen eine neue Möglichkeit zur Erzeugung zukünftiger, funktionalisierter Elektroniken dar. An geladenen DW ändert sich die Polarisation sehr abrupt - innerhalb nur weniger Atomabstände. Sofern die dadurch hervorgerufene Ladungsträgeranreicherung elektrisch abgeschirmt werden kann, könnte dies zu faszinierenden elektrischen Eigenschaften führen. Wir möchten uns hierbei jedoch auf die elektrische Leitfähigkeit beschränken. Ein großer Vorteil für die Anwendung leitfähiger DW ist deren kontrollierte Bewegung unter Einwirkung elektrischer Felder. Dies ermöglicht die Manipulation das Ladungstransports, welches zum Beispiel im Bereich der Rekonfigurierbarkeit, schneller Speicherbauelemente und jeder Art von adaptiven elektronischen Schaltungen Anwendung finden kann. In dieser Dissertationsschrift möchte ich diesen neuen Typus grenzflächiger elektronischen Ladungstransports an geladenen DW hauptsächlich am Beispiel von Lithiumniobat/-LiNbO3 (LNO) untersuchen. Die Annahme lautete hierbei: umso stärker die DW zur ferroelektrischen Achse geneigt ist, also desto stärker die gebundene Polarisationsladung und folglich die elektrische DW-Leitfähigkeit. Die elektrische DW-Leitfähigkeit und die Korrelation mit der Polarisationsladung wurde mit verschiedenen experimentellen Methoden wie Rasterkraftmikroskopie, linearer und nichtlinearer optischer Mikroskopie als auch Elektronenmikroskopie untersucht. Es konnte eine klare Korrelation durch Vergleich der dreidimensionalen DW-Aufzeichnungsdaten mit der lokalen Leitfähigkeit gezeigt werden. Wir haben weiterhin den Leitfähigkeitsmechanismus an geladenen DW mittels temperaturabhängiger Strom-Spannungskennlinien untersucht und konnten hierbei einen Hopping-Transport kleiner Elektronenpolaronen nachweisen, welche nach Elektroneninjektion in die geladene DW generiert werden. Der thermisch aktivierte Ladungsträgertransport ist in guter Übereinstimmung mit zeitaufgelöster Polaron-Lumineszenzspektroskopie. Die Anwendbarkeit dieses Effektes für nicht-volatile Speicherbauelemente wurde an Metall-Ferroelektrika-Metall Schichtstrukturen mit CMOS-kompatiblen einkristalliner Filmen untersucht. Die Filme zeigen bisher nichtgesehene Durchhalte- und Speichervermögen, genau definierte Schaltspannung sowie sehr geringe Leckageströme wie dies für einkristalline Materialsysteme erwartet wird. Die Leitfähigkeit konnte mittels entsprechender Wahl der elektrischen Schaltzeiten und -spannungen zielgerichtet manipuliert und geschalten werden. Es konnte darüber hinaus gezeigt werden, dass die hergestellten geladenen DW über eine Zeitspanne von mindestens zwei Monaten stabil sind und hierbei leitfähig bleiben. Die Leitfähigkeit der DW wurde weiterhin mittels Mikrowellenimpedanzmikroskopie untersucht. Dabei konnten DW-Leitfähigkeiten von 100 bis 1000 S/m für Mikrowellenfrequenzen von etwa 1GHz ermittelt werden.:1 INTRODUCTION 1 I THEORETICAL BASICS 5 2 FUNDAMENTALS 7 2.1 Ferroelectricity 7 2.1.1 Spontaneous polarization 8 2.1.2 Domains and domain walls 9 2.1.3 Charged domain walls 13 2.1.4 Conductive domain walls 16 2.2 Visualization of ferroelectric domains and domain walls 21 2.2.1 Light microscopy 22 2.2.2 Second-harmonic generation microscopy 22 2.2.3 Cherenkov second-harmonic generation microscopy 25 2.2.4 Optical coherence tomography 28 2.2.5 Piezo-response force microscopy 30 2.2.6 Ferroelectric lithography 31 2.2.7 Further methods 34 2.3 Lithium niobate and tantalate 37 2.3.1 General Properties 37 2.3.2 Stoichiometry 38 2.3.3 Optical properties 40 2.3.4 Intrinsic and extrinsic defects 43 2.3.5 Polarons 47 2.3.6 Ionic conductivity 51 3 METHODS 53 3.1 Sample Preparation 53 3.1.1 Poling stage 53 3.1.2 Thermal treatment 56 3.1.3 Ion slicing of LNO crystals 57 3.2 Atomic force microscopy 59 3.2.1 Non-contact and contact mode AFM microscopy 59 3.2.2 Piezo-response force microscopy (PFM) 60 3.2.3 Conductive atomic force microscopy (cAFM) 62 3.2.4 Scanning microwave impedance microscopy (sMIM) 63 3.2.5 AFM probes 66 3.3 Laser scanning microscope 67 3.4 Time-resolved luminescence spectroscopy 71 3.5 Energy-resolved photoelectron emission spectromicroscopy 72 II EXPERIMENTS 75 4 RESULTS 77 4.1 Three-dimensional profiling of domain walls 78 4.1.1 Randomly poled LNO and LTO domains 78 4.1.2 Periodically Poled Lithium Niobate 81 4.1.3 AFM-written Domains 83 4.1.4 Thermally treated LNO 84 4.1.5 Laser-written domains 86 4.2 Polarization charge textures 90 4.2.1 Random domains in Mg:LNO and Mg:LTO 90 4.2.2 Thermally-treated LNO 92 4.3 Quasi-phase matching SHG 92 4.4 Photoelectron microspectroscopy 97 4.5 Activated polaron transport 101 4.6 High voltage treated LNO 113 4.7 Conductive domain walls in exfoliated thin-film LNO 115 4.7.1 Conductance maps 116 4.7.2 Resistive switching by conductive domain walls 120 4.8 Microwave impedance microscopy 134 4.8.1 Finite-element method simulation 134 4.8.2 Scanning microwave impedance microscopy 136 5 conclusion & outlook 143 III EPILOGUE 147 a APPENDIX 149 a.1 Laser ablation dynamics on LNO surfaces 149 a.2 XPS across a conductive DW in LNO 150 a.3 XRD of thin-film exfoliated LNO 151 a.4 Domain writing in exfoliated thin-film LNO 152 a.5 Retention in conductance at DWs in thin-film exfoliated LNO 155 a.6 sMIM on DWs in thin-film exfoliated LNO 157 a.7 Domain inversion evolution under a tip by phase-field modeling 159 a.8 Current transients in exfoliated LNO 161 a.9 Surface acoustic wave excitation damping at DWs 162 a.10 Influence of UV illumination on domains in Mg:LNO 162 Acronyms 165 Symbols 169 List of figures 172 List of tables 176 Bibliography 177 Publications 225 Erklärung 23

Protein Kinases

Proteins are the work horses of the cell. As regulators of protein function, protein kinases are involved in the control of cellular functions via intricate signalling pathways, allowing for fine tuning of physiological functions. This book is a collaborative effort, with contribution from experts in their respective fields, reflecting the spirit of collaboration - across disciplines and borders - that exists in modern science. Here, we review the existing literature and, on occasions, provide novel data on the function of protein kinases in various systems. We also discuss the implications of these findings in the context of disease, treatment, and drug development

Design and Implementation of Apodized and Unapodized Frequency Converters in Bulk Aperiodically Poled Nonlinear Materials

Cette thèse porte sur l’étude, la conception et la fabrication de convertisseurs de fréquences à large bande pour la génération efficace de seconde harmonique (SHG) et de somme de fréquences (SFG) sur des dispositifs non-linéaires en quasi-accord de phase (QPM). Les dispositifs de QPM comprennent des réseaux de domaines inversés, qui fournissent un accord de phase non critique pour la conversion de fréquences dans les matériaux non-linéaires. Pour créer des cristaux à QPM, le coefficient non-linéaire de second ordre est périodiquement inversé à l’aide d’une méthode de polarisation périodique. Avec d’excellentes propriétés telle sa non-linéarité, le cristal de niobate de lithium (LN), utilisé pour les simulations et la fabrication de ces travaux de recherche, est un des meilleurs candidats pour les dispositifs à QPM. Les matériaux périodiquement polarisés uniformément tel le niobate de lithium périodiquement polarisé (PPLN), possèdent une largeur de bande d'acceptation spectrale et thermique étroite. La largeur de bande étroite limite la conversion de fréquences pour une longueur d’onde spécifique d’un laser pompe et nécessite l’utilisation d’un contrôleur de température pour maximiser l’efficacité de conversion. En addition, les conversions de fréquences pour plusieurs longueurs d’onde simultanément ainsi que le réglage de la longueur d’onde de pompe sans réglage de température sont restreints par les PPLN uniformes. Les réseaux à pas variable (chirped) et step-chirped dans le LN ont été récemment proposés pour pallier la limitation de la bande passante des doubleurs de fréquences basés sur la SHG. Les réseaux chirped peuvent être conçus pour obtenir une largeur de bande souhaitée et enlever la nécessité de l'installation du régulateur de température dans le montage expérimental. Cependant, ces dispositifs souffrent d'ondulations et de fluctuations dans leurs réponses spectrales. L'application d'apodisation sur les réseaux chirped est proposée pour diminuer les ondulations dans la réponse de ces dispositifs, dans lesquels les changements de coefficient non linéaire effectif en fonction de la longueur converge vers zéro au niveau des rebords du réseau. Dans cette thèse, les méthodes d’ingénieries non linéaires effectives appropriées pour supprimer des ondulations des convertisseurs à large bande sont explorées. La mise en oeuvre d'une fonction d'apodisation souhaitée sur les convertisseurs à large bande basés sur la variation du rapport cyclique est examinée en profondeur. La dépendance de la phase du champ électrique sur la génération de seconde harmonique à l’endroit de la région polarisée dans un réseau apériodique est explorée théoriquement.----------Abstract This thesis focuses on research study, design and fabrication of broadband frequency converters based on second harmonic generation (SHG) and sum frequency generation (SFG) in nonlinear quasi-phase-matched (QPM) devices. QPM devices based on domain-inverted gratings provide noncritical phase matching for frequency conversion in nonlinear media. For creating QPM crystals, the second-order nonlinear coefficient is periodically reversed by periodic poling method. Lithium niobate (LN) crystal with excellent properties such as high nonlinearity is one of the best candidates for QPM devices, which has been used for the simulations and fabrication in this research work. Conventional uniform periodically poled materials such as periodically poled lithium niobate (PPLN) crystals possess a narrow spectral and thermal acceptance bandwidth. The narrow bandwidth limits the frequency conversion for a specified pump wavelength and necessitates the use of a temperature controller to maximize the efficiency. In addition, uniform gratings restrict simultaneous frequency conversion for several wavelengths and tunability of the pump wavelength without temperature tuning. Therefore, chirped and step-chirped gratings in LN were recently proposed to overcome the bandwidth limitation of frequency doublers based on SHG. Chirped gratings can be engineered to obtain the desired bandwidth and remove the necessity of controlling the temperature in the experimental set-up. However, these devices suffer from ripples and fluctuations in their spectral responses. Applying apodization in chirped grating is suggested to diminish the ripples in the response of these devices, in which the effective nonlinear coefficient changes, as a function of length, smoothly to zero at the edges of the grating. In this dissertation, methods for engineering proper effective nonlinearity are explored to suppress ripples of broadband converters. Implementation of a desired apodization function on broadband converters based on duty ratio variation is deeply examined. The dependence of SH electrical field phase on the place of poled region in an apreriodic grating is explored theoretically. It has been demonstrated for the first time that the spectral conversion bandwidth of apodized chirped frequency doublers depends on the place of the poled region within the period of gratings. The proper design to minimize the ripples and achieve a desired nonlinearity function for an apodized chirped grating has been proposed which improves the tolerance to fabrication errors