Dans le premier chapitre de cette thèse, nous introduisons le concept de nanodot organique (OND) comme une alternative aux quantum dots (QDs). Ces nano émetteurs «tout organique» sont préparés par synthèse bottom-up et contrôle,à l’échelle du nanoobjet, de la réponse optique par confinement du chromophore au sein d’une structure dendritique. Ceci conduit à des nanoobjets présentant une brillance exceptionnelle à un ou deux photons en faisant des composés d’intérêt majeur pour l’imagerie in vivo. Le deuxième chapitre décrit la synthèse et la caractérisation de la première famille d’OND hydrophiles. Deux types d’absorbeurs à deux photons ont été sélectionnés car présentant des propriétés optiques et des structures différentes. Ensuite, l’hydro solubilité a été assurée par l’accrochage de groupes H2N(CH2)2NEt2 à la périphérie. Dans les chapitres 3 et 4, nous proposons une alternative aux OND cationiques par greffage de chaîne polyéthylèneglycol à la périphérie. Ceci améliore la solubilité et la biocompatibilité. Un OND hydrosoluble bimodal pouvant être utilisé en IRM du19Fet imagerie de fluorescence est également préparé. Dans ce chapitre l’étude par RMN et par imagerie confocale de trois dendrimères à cœur cyclophosphazène est également décrite. Finalement, le chapitre 5 décrit la préparation de systèmes synergique agissant en tandem pour la photo libération d’un substrat «en cage». Nous avons démontré qu’en combinant une antenne collectrice avec des unités encagées,il est possible d’obtenir une libération efficace de molécules actives. Par ingénierie moléculaire nous avons préparé trois systèmes synergiques différents: (i) Une triade symétrique basée sur un chromophore portant des chaîne hydrophile TEG et connecté à unités PPG encageant une unité glutamate (ii) Une dyade comportant un chromophore et une unité PPG au sein d’une architecture phosphorée, finalement (iii) une unité dendritique portant une unité encageante et 5 absorbeurs à deux photons / In the first chapter of this dissertation, we introduce the concept of organic nanodot (OND) as an alternative to quantum dots (QDs).These purely organic nanoemitters are obtained from a rational and bottom-up route based on the control, at the single nano-object level, of the optical responses via the covalent confinement of optimized chromophores within dendrimericarchitectures. This led to tuneable nano-objects which show record one-and two-photon brightness and have been shown to be a major interest for in vivoimaging.The second chapter describes the synthesis and structural characterization of the first family of ONDwith hydrophilic properties. Two different 2P absorber modules were selected for this aim, displaying different structural and optical properties. Then, the water solubility will be ensured by linking H2N(CH2)2NEt2.at the periphery. In Chapter 3and 4we propose an alternative to the cationic ONDs by replacing the external layer, with polyethylene glycol (neutral). This synthetic approach favorsthe hydrosolubility, and the compatibility in biological environment. Awater-soluble organic nanodot-based probethat could be used for both 19F MRI and optical fluorescence imagingis alsoprepared. In the same chapter, confocal imaging and NMR studies of three types of dendrimers with a cyclotriphosphazene core are described.Finally, the aim of chapter 5is the synthesis of synergic systems acting in tandem for the photorelease of a caged substrate. We demonstrate that combining a light harvesting antenna group with uncaging subunits leads to the efficient release of active molecules. Molecular engineering allowed us to prepare three different synergic systems, (i) a symmetrical tandem triad structure, based on one chromophore bearing hydrophilic TEG chains, which is directly connected to two PPG units caging one molecule of glutamate respectively, (ii) a dyad system bearing one chromophore and one PPG in phosphorus scaffold, finally (iii) a dendritic scaffold bearing 6 available position that was coated both with one equivalent ofuncaging moietyand the remaining positions with 2P absorbing modules.

The objective of this thesis was to develop novel technologies for measuring the physical characteristics of high-speed pulse trains, for use in performance monitoring applications. This thesis describes the development of three separate techniques that perform measurements in either the time domain, frequency domain or the phase space of the optical signal. The first section investigates phase-sensitive pulse measurement techniques. A high- resolution SHG-FROG apparatus was custom-designed to measure 40GHz RZ pulse trains, from which an operational characterisation of a Mach-Zehnder modulator (MZM) was realised. A numerical model of a nonlinear pulse compressor was developed to compress 40GHz RZ pulses from 8.5ps down to 3.4ps. These pulses were time-division multiplexed to 80GHz, and phase-retrievals of the 80GHz pulse trains were measured. A comparison between the techniques of SHG-FROG and linear spectrogram has been undertaken for 10GHz pulse sources, exposing SHG-FROG's weaknesses at this particular repetition rate. The second section investigates a simple, time-averaged, nonlinear detection technique. Two-photon absorption in a GaAs/InGaAs quantum-well laser diode was used to measure the duty cycle (and by extension, the pulse duration) of a range of pulse sources. This technique was further developed to measure the extinction ratio of NRZ pulse trains. Additionally, the pulse duration of a mode-locked laser source was measured using the nonlinear absorption in a 1-m length of As2Se3 Chalcogenide glass fiber. This demonstrates that the nonlinear properties of this glass may well find application in future instrumentation. The third section investigates the development of an ultra-high resolution swept heterodyne spectrometer. This spectrometer was used to spectrally-distinguish repetitive 8-bit NRZ patterns at 2.5Gbit/s. It was also used to measure the chirp parameter of an X-cut LiNbO3 MZM, revealing a chirp parameter of απ/2 < 0.1 across a modulation band- width of 250-2500MHz. Additionally, the distinctive CW spectrum of a DFB laser diode was measured. Analysis of the measured CW spectrum yielded a linewidth enhancement factor of α≃ 1.8 and also the relative intensity noise of the DFB laser diode.

Gesunde sowie qualitativ hochwertige Nahrungsmittel sind wichtige Voraussetzungen, um einerseits die Lebensmittelsicherheit entlang der Wertschöpfungskette (Wachstum, Verarbeitung, Lagerung und Transport) und andererseits einen vorbeugenden Verbraucherschutz zu gewährleisten. Die Belastung der Nahrung mit Rückständen jeglicher Art war in letzter Zeit häufig Mittelpunkt heftiger öffentlicher Diskussionen. Zahlreiche Untersuchungen haben gezeigt, dass unter bestimmten Bedingungen durch Pilze gebildete Giftstoffe, so genannte Mykotoxine, die Ernteprodukte belasten und es bei deren Verzehr durch Menschen oder Tiere zu Vergiftungen kommen kann. Die FAO schätzt, dass etwa 25% der Weltproduktion von Nahrungsmitteln mit Mykotoxinen kontaminiert und in 20% der Getreideernte der Europäischen Union messbare Konzentrationen an Mykotoxinen detektierbar sind. Damit die Lebensmittelsicherheit weiterhin gewährleistet bleibt, werden neben den Routinemethoden schnellere und zerstörungsfreie Methoden benötigt, um die Lebensmittel direkt vor Ort auf Schimmelpilze und deren Mykotoxine zu untersuchen. In dieser Arbeit wird das Potenzial von ausgewählten optisch-basierten spektroskopischen Methoden für die in-situ bzw. in-line Detektion von Schimmelpilzen sowie Mykotoxinen in Getreide(produkten) untersucht. Es werden Absorptions- und Reflexionsmethoden einerseits und Fluoreszenztechniken andererseits eingesetzt. Die spektroskopischen Methoden werden dabei auf Proben unterschiedlicher Komplexität angewandt - beginnend mit der Untersuchung der photophysikalischen Eigenschaften der reinen Mykotoxine in Lösung über künstlich mit verschiedenen Mykotoxinen kontaminierten Getreideproben bis hin zu mit Pilzen befallenem Getreide und hochveredelte Lebensmittel (Wein und Bier) als Proben höchster Komplexität. / Problems of food safety have led to an increasing concern regarding contamination of foods and feeds with mycotoxins and the relevant toxigenic fungi, mainly Aspergillus, Penicillium and Fusarium genera. There is a real need for rapid, sensitive and inexpensive sensors for the detection of toxigenic fungi and mycotoxins, both in the field and after harvest in order to obtain real-time monitoring data on contamination and this assist in food safety assessment. This will result in an enormous cost saving to the farmers as well as to agro-food industry through the prevention and reduction of product recalls and reduced treatment costs. The German Ministry of Education and Research (BMBF) has provided funding of more than 1.9 million Euros from July 2006 to December 2009 for the large joint project "ProSeso.net2" on the development of innovative sensor-based techniques and processes in the field of food quality and safety. In this research-project "Exploration of sustainability potentials by use of sensor-based technologies and integrated assessment models in the production chain of plant related food" 13 partners from universities, non-university institutions and industry cooperate within seven subprojects. The expected results shall contribute to maintain freshness and improve safety of the food production chain. In the subproject “Indicators and sensor technology for the identification of mycotoxin producing fungi in the processing of grain” spectroscopic methods are tested for in-situ and in-line detection of moulds and/or mycotoxins. This presentation focuses on some possible spectroscopic methods for the rapid detection of mycotoxins and fungi on grains. Methods based on one- and two-photon-induced fluorescence spectroscopy are highly attractive because of their outstanding sensitivity and selectivity. In order to utilize a fluorescence technique for the analysis of the mycotoxins in food and feedstuff as well as for basic research on the fungal metabolism, the photochemistry and photophysics of the mycotoxins and fungi need to be elucidated in detail, especially the influence of solvent parameters such as polarity and pH value. Consequently, for a sensitive and selective spectroscopic analysis, it is indispensable to take the specific photophysic of the known mycotoxins into account in order to minimize serious limitations upon sensitivity, selectivity, and accuracy of a potential fluorescence-based sensing application. The spectroscopic techniques are complemented by chemometric tools (Principle Component Analysis) to extract the desired chemical information, e.g. with respect to presence of contaminations. The combination of data obtained from different spectroscopic methods (such as optimal excitation and emission wavelength, fluorescence decay times, and fluorescence quantum efficiency) on the one hand side and NIR spectroscopy on the other side shows promising results for the qualitative as well as quantitative identification of mycotoxins grains. Moreover, NIR reflectance spectra yield additional information on ingredients, moisture content, and the presence (or absence) of fungi in the sample.

No description available.

The main theme of this thesis is to study effects of different environments on geometric and electronic structures, as well as optical responses, of molecules using time-(in)dependent density functional theory. Theoretical calculations have been carried out for properties that can be measured by conventional and advanced experimental techniques, including one-photon absorption (OPA), two-photon absorption (TPA), surface-enhanced Raman scattering (SERS) and second order nonlinear optical (NLO) response. The obtained good agreement between the theory and the experiment allows to further extract useful information about inter- and intra-molecular interactions that are not accessible experimentally. By comparing calculated one-photon absorption spectra of aluminum phthalocyanine chloride (AlPcCl) and AlPcCl -water complexes with the corresponding experiments, detailed information about the interaction between water molecules and AlPcCl, and geometric changes of AlPcCl molecule has been obtained. Effects of aggregation on two-photon absorption spectra of octupolar molecules have been examined. It is shown that the formation of clusters through inter-molecular hydrogen bonding can drastically change profiles of TPA spectra. It has also demonstrated that a well designed molecular aggregate/cluster, dendrimer, can enhance the second order nonlinear optical response of the molecules. In collaboration with experimentalists, a series of end-capped triply branched dendritic chromophores have been characterized, which can lead to large enhancement of the second order NLO property when the dipoles of the three branches in the dendrimers are highly parallelized. Surface-enhanced Raman scattering has made the detection of single molecules on metal surface become possible. Chemically bonded molecule-metal systems have been extensively studied. We have shown in a joint experimental and theoretical work that stable Raman spectra of a non-bonding molecule, perylene, physically adsorbed on Ag nano-particles can also be observed at low temperature. It is found that the local enhanced field has a tendency to drive molecule toward a gap of two closely lying nano-particles. The trapped molecule can thus provide a stable Raman spectrum with high resolution when its thermal motion is reduced at low temperature. For the ever growing size of molecular complexes, there is always the need to develop new computational methods. A conceptually simple but computationally efficient method, named as central insertion scheme (CIS), is proposed that allows to calculate electronic structure of quasi-periodic system containing more than 100,000 electrons at density functional theory levels. It enables to monitor the evolution of electronic structure with respect to the size of the system. / QC 20100823

Inter-molecular interactions have significant influences on linear and nonlinear optical properties of molecules including one- and two-photon absorptions, emissions, and various high order nonlinear polarizations. The related investigation has become an active and challenging research area. The theoretical structure-to-property relationship obtained from quantum chemical calculations of single organic conjugated molecules often can not be directly applied to real materials in condensed phases. One has to consider the effect of environment, that is, inter-molecular interactions, where the model systems experience in real experiments or applications. The change of molecular conformations under all kinds of interactions and its effects on linear and nonlinear optical properties are the central issue of this thesis. Special attentions have been paid to symmetrical diamino substituted distyrylbenzene chromophores with different torsional angles, two dipolar merocyanine dyes of various orientations, two isomers of a V-shaped 2-hydroxypyrimidine derivative and their various dimers, and the structural fluctuations of interacting polar chromophores in solutions. Quantum chemical methods in combination with molecular dynamics simulations have been employed to study molecular conformations and optical properties in solutions, in particular the solvent and aggregation effects on one- and two-photon absorption. More specifically, time-dependent density functional theory has been used for all electronic calculations, while the polarizable continuum model and supermolecule approach have also been employed to take into account solvent effects. Moreover, the propagation of an ultrashort laser pulse through a one-dimensional asymmetric organic molecular medium which possesses large permanent dipole moments has been simulated by solving full Maxwell-Bloch equations using predictor-corrector finite-difference time-domain method. We have focused on the supercontinuum generation of spectra and the formation of attosecond pulses. / QC20100630

<p>Synaptic plasticity is the leading candidate for the cellular/molecular basis of learning and memory. One of the key molecules involved in synaptic plasticity is Calcium/calmodulin-dependent Kinase II (CaMKII). Synaptic plasticity can be expressed at a single dendritic spine independent of its neighboring dendritic spines. Here, we investigated how long the activity of CaMKII lasts during synaptic plasticity of single dendritic spines. We found that CaMKII activity lasted ~2 minutes during synaptic plasticity and was restricted to the dendritic spines undergoing synaptic plasticity while nearby dendritic spines did not show any change in the level of CaMKII activity. Our experimental data argue against the persistent activation of CaMKII in dendritic spines undergoing synaptic plasticity and suggest that the activity of CaMKII is a spine-specific biochemical signal necessary for synapse-specificity of synaptic plasticity. We provide a biophysical explanation of how spine-specific CaMKII activation can be achieved during synaptic plasticity. We also found that CaMKII is activated by highly localized calcium influx in the proximity of Voltage-dependent Calcium Channels (VDCCs) and a different set of VDCCs and their respective Ca2+ nanodomains are responsible for the differential activation of CaMKII between dendritic spines and dendritic shafts.</p> / Dissertation

This thesis is concerned with the fabrication methodology of polymeric photonic crystals operating in the visible to near infrared regions and the correlation between the chemical deposition morphologies and the resultant photonic stopband enhancements of photonic crystals. Multiphoton lithography (MPL) is a powerful approach to the fabrication of polymeric 3D micro- and nano-structures with a typical minimum feature size ~ 200 nm. The completely free-form 3D fabrication capability of MPL is very well suited to the formation of tailored photonic crystals (PCs), including structures containing well defined defects. Such structures are of considerable current interest as micro-optical devices for their filtering, stop-band, dispersion, resonator, or waveguiding properties. More specifically, the stop-band characteristics of polymer PCs can be finely controlled via nanoscale changes in rod spacings and the chemical functionalities at the polymer surface can be readily utilized to impart new optical properties. Nanoscale features as small as 65 ± 5 nm have been formed reproducibly by using 520 nm femtosecond pulsed excitation of a 4,4'-bis(di-n-butylamino)biphenyl chromophore to initiate crosslinking in a triacrylate blend. Dosimetry studies of the photoinduced polymerization were performed on chromophores with sizable two-photon absorption cross-sections at 520 and 730 nm. These studies show that sub-diffraction limited line widths are obtained in both cases with the lines written at 520 nm being smaller. Three-dimensional multiphoton lithography at 520 nm has been used to fabricate polymeric woodpile photonic crystal structures that show stop bands in the visible to near-infrared spectral region. 85 ± 4 nm features were formed using swollen gel photoresist by 730 nm excitation MPL. An index matching oil was used to induce chemical swelling of gel resists prior to MPL fabrication. When swollen matrices were subjected to multiphoton excitation, a similar excitation volume is achieved as in normal unswollen resins. However, upon deswelling of the photoresist following development a substantial reduction in feature size was obtained. PCs with high structural fidelity across 100 µm × 100 µm × 32 layers exhibited strong reflectivity (>60% compared to a gold mirror) in the near infrared region. The positions of the stop-bands were tuned by varying the swelling time, the exposure power (which modifies the feature sizes), and the layer spacing between rods. Silver coatings have been applied to PCs with a range of coverage densities and thicknesses using electroless deposition. Sparse coatings resulted in enhanced reflectivity for the stop band located at ~5 µm, suggesting improved interface reflectivity inside the photonic crystal due to the Ag coating. Thick coatings resulted in plasmonic bandgap behavior with broadband reflectivity enhancement and PC lattice related bandedge at 1.75 µm. Conformal titania coatings were grown onto the PCs via a surface sol-gel method. Uniform and smooth titania coatings were achieved, resulting in systematically red-shifted stopbands from their initial positions with increasing thicknesses, corresponding to the increased effective refractive index of the PC. High quality titania shell structures with modest stopbands were obtained after polymer removal. Gold replica structures were obtained by electroless deposition on the silica cell walls of naturally occurring diatoms and the subsequent silica removal. The micron-scaled periodic hole lattice originated from the diatom resulted in surface plasmon interferences when excited by infrared frequencies. The hole patterns were characterized and compared with hexagonal hole arrays fabricated by focused ion beam etching of similarly gold plated substrate. Modeling of the hole arrays concluded that while diatom replicas lack long-ranged periodicity, the local hole to hole spacings were sufficient to generate enhanced transmission of 13% at 4.2 µm. The work presented herein is a step towards the development of PCs with new optical and chemical functionalities. The ability to rapidly prototype polymeric PCs of various lattice parameters using MPL combined with facile coating chemistries to create structures with the desired optical properties offers a powerful means to produce tailored high performance photonic crystal devices.

Intravital microscopy such as in vivo imaging of brain dynamics is often performed with custom-built microscope setups controlled by custom-written software to meet specific requirements. Continuous technological advancement in the field has created a need for new control software that is flexible enough to support the biological researcher with innovative imaging techniques and provide the developer with a solid platform for quickly and easily implementing new extensions. Here, we introduce HelioScan, a software package written in LabVIEW, as a platform serving this dual role. HelioScan is designed as a collection of components that can be flexibly assembled into microscope control software tailored to the particular hardware and functionality requirements. Moreover, HelioScan provides a software framework, within which new functionality can be implemented in a quick and structured manner. A specific HelioScan application assembles at run-time from individual software components, based on user-definable configuration files. Due to its component-based architecture, HelioScan can exploit synergies of multiple developers working in parallel on different components in a community effort. We exemplify the capabilities and versatility of HelioScan by demonstrating several in vivo brain imaging modes, including camera-based intrinsic optical signal imaging for functional mapping of cortical areas, standard two-photon laser-scanning microscopy using galvanometric mirrors, and high-speed in vivo two-photon calcium imaging using either acousto-optic deflectors or a resonant scanner. We recommend HelioScan as a convenient software framework for the in vivo imaging community. / <p>Paid Open Access</p>

In vivo real-time data of ultrasound and microbubble assisted blood-brain barrier disruption is centrally based on low-resolution magnetic resonance images. Additional information can be gained using online microscopic monitoring. This study presents the first ever in vivo two-photon microscopy, four-dimensional data sets of ultrasound and microbubble assisted blood-brain barrier disruption. It characterized the threshold pressures and mechanical index needed to disrupt the vasculature with 800 kHz ultrasound, and found three different leakage constants from the compromised vasculature. Furthermore, using numerical models, an ultrasound array was designed and optimized to perform specifically with our two-photon microscope. It was fabricated, fully characterized, and its performance met both the required pressure field profile and the pressure values needed for our in vivo two-photon microscopy experiments. This array is an important step in microscopically characterizing ultrasound and microbubble assisted blood-brain barrier disruption.