Dissertations / Theses on the topic 'Spectrosocpy'

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A espectroscopia de Raman intensificada por superfície (SERS, termo em inglês Surfaceenhanced Raman Spectroscopy) é uma técnica promissora que mostra a sensibilidade para a detecção da interação de biomoléculas que são importantes para detecção precoce de doenças. O vírus da imunodeficiência humana (HIV) têm sido um grande problema por várias décadas. Existem vários métodos de deteção baseados na interação específica de anticorpos, tais como, o ELISA e os testes rápidos (TR's). No entanto, novas estratégias têm sido desenvolvidas para rápido diagnóstico do vírus HIV, e uma prova de conceito de detecção do peptídeo p17-1 foi descrito neste trabalho. A proteina matriz p17 é uma essencial proteína no ciclo de replicação do vírus HIV. As fases iniciais da replicação do vírus envolve a pré integração do complexo do DNA no núcleo do p17 desempenhando um papel na ligação de RNA viral e transporte para a membrana. Neste trabalho foram descritos duas plataformas SERS para a detecção do vírus HIV baseado no peptide p17 -1 (sequência LSGGELDRWEKIRLPGG). O anticorpo foi imobilizado em um substrato de ouro usando duas diferentes camadas automontadas (SAM). A primeira SAM, os substratos de ouro foram imersos em uma solução aquosa de 11 mercaptoundecanóico (MUA). Na segunda SAM, os substratos foram imersos em uma mistura aquosa de politietileno glicol (SHPEG- COOH e SH-PEG-CH3). Aqui serão chamados de SAM-MUA e SAM-PEG, respectivamente. Ambas as SAM's foram imersas emu ma solução de anticorpo (anti-p17) e foram descritas como plataforma d captura MUA e PEG. Ambas plataformas foram funcionalizadas com o peptídeo p17-1. Sondas SERS foram preparadas com nanopartículas de ouro e revestidas com uma molécula Raman reporter (azul de Nilo A) e funcionalizadas com um anticorpo anti-p17. Estas estruturas (sonda SERS e plataformas de captura) formam um ensaio sanduíche...
Surface-enhanced Raman Scattering (SERS) technique offers great promises for simplified and sensitive detection of biomolecular interactions that are relevant for early disease diagnostics. Human immunodeficiency virus (HIV) has been a problem for decades. There are several methods of diagnostics based on antibodies specific reactions, such as enzyme-linked immunosorbent assays (ELISAs) and rapid test (RT). However, new strategies have been developed for rapid HIV diagnostics and, as a proof-of-concept, peptide p17-1 was considered here. The matrix protein p17 is a structural protein that is essential in the life cycle of the retrovirus The early stages of the virus replication involve the pre integration of the DNA complex into the nucleus P17 plays a role in RNA viral binding and transport to the membrane. Here were describe two new SERS platform for HIV detection based on peptide p17-1 (sequence LSGGELDRWEKIRLPGG). The antibody anti-p17 was immobilized in a planar gold surface using two differents self-assembled (SAM) techniques. First SAM, were obtained by immersion of the surface into ethanolic solution of 11-Mercaptoundecanoic acid (MUA). Second SAM were obtained by immersion in aqueous solution aquous mixtures of (SH-PEG-COOH/SH-PEG-CH3) and polyethylene glycol (PEG,). Here were describe the two platforms as SAM-MUA and SAMPEG, respectively. Both SAM's were immersed in a solution containing the anti-p17. Samples at this step were called capture platform-MUA and capture platform-PEG. Both capture platforms were funcionalizated with the peptide p17-1. SERS probes were prepared with gold nanoparticles coated with a Raman reporter molecule (Nile Blue A) and, functionalized with an anti-p17. These structures (SERS probe and capture platforms) allow for a sandwich assay, a strategy regularly used for high-sensitivity detection. The light blue color in the SERS mapping represents peptide strong...

Ionic conductivity of metal oxides is critical for the function of a broad range of different components, such as electrolytes in solid oxide fuel cells and alloys designed for high temperature applications. In both cases the ionic conductivity can be studied by in situ impedance spectroscopy, which is also able to reveal information on the dielectric properties of the metal oxides, and in some cases the influence of their microstructure. The focus of this thesis is on impedance spectroscopy measurements of α-alumina in the temperature range 400-1000 °C. This metal oxide has found extensive use as the protective scale on heat resistant alloys. Some unpublished work on oxygen ion conductivity of yttria-stabilized zirconia is also included.

The low electrical conductivity of α-alumina can be a source for errors and misinterpretations during impedance spectroscopy measurements. A major disturbance originates from leakage currents that appear in the experimental setup. These leakage currents are due to conduction through the gas phase around the sample, conduction on the sample surface, or poor insulation in the sample holder. It was shown that below 700 °C, conduction on the sample surface could severely distort the measurement. The magnitude of the distortions appeared to be sensitive to the type of electrodes used. The use of a so-called guard electrode was shown to effectively block the surface conduction in the measurements.

Conductivity of metal oxides is known to be dependent on their microstructure. Generally it is believed that ionic conductivity is favoured along grain boundaries and dislocations. The influence of microstructure on conductivity was studied for α-alumina in the temperature range 400-1000 °C. The conductivity of a series of highly pure and dense samples with narrow grain size distributions was measured by impedance spectroscopy. It appeared that the activation energy for conduction increased with decreasing grain size.

Results based purely on impendence spectroscopy have some inherently weaknesses. For instance no information on the nature of the charge carrier can be found. Therefore the charge transport in single crystalline α-alumina was simulated by the molecular dynamics method. The results from the simulation were then compared to results from impedance measurements on single crystalline α-alumina. From the simulation it turned out that diffusion of aluminium ions had lower activation energy than diffusion of oxygen. The activation energy of oxygen was close to the measured activation energy, and the mobility of oxygen was higher than for aluminium. Therefore the dominating charge carrier was suggested to be oxygen ions.

The determination of the plasma confinement propertiesdemand data as the electron temperature, the ionic and electrondensity profiles and the radiative emissivity profiles. Thefocus of this thesis is the importance of radial profiles inspectroscopic diagnostics applied to the EXTRAP-T2Rreversed-field pinch.

EXTRAP-T2R is a resistive shell reversed-field pinch with amagnetic field shell penetration time much longer than therelaxation cycle time scale. Significant improvements inconfinement properties derived by quantitative plasmaspectroscopy in the vacuum ultraviolet are observed compared tothe previous device EXTRAP-T2. The low level of magneticturbulence and the good magnetic surfaces in the edge regionexplain this observed improvement. A current profile controlexperiment reduces the stochastic transport, which is connectedto the dynamo, and improves the confinement in EXTRAP-T2R evenmore.

A comparison of the electron temperature estimated by usinga ratio of line intensities from the same ionization stage ofoxygen and the Thomson scattering system shows that thedifference is explained by the different spatial dependence ofthe excited state populations and the corresponding emissivityof these spectral lines. A collisional radiative model givesestimates for radial profiles of impurities which are notmeasured in EXTRAP-T2R. The estimated profiles can in turn beused to determine the radial profile of the effective ioncharge, the emissivity and finally the radiative power. Asinput, the model uses radial profiles.

Neutral hydrogen is predominantly present in the boundaryregion of the plasma. Spectroscopic investigations in this areashow very asymmetric spectral lines of hydrogen due to themovement of atoms. The velocity of the hydrogen atoms dependson the type of plasma-wall interaction and their measurementhelps to identify the different interaction processes. Theexistence of hydrogen molecules in the edge complicates theinterpretation of the line shapes and on the determination ofthe particle confinement time.

Keywords:Reversed-field pinch, EXTRAP-T2R, quantitativeplasma spectroscopy, VUV spectroscopy, line-integrated electrontemperature, oxygen, profiles, confinement properties, powerbalance, hydrogen, particle confinement time.

This thesis discusses in general terms the theory and application of time-differential perturbed angular correlation gamma-ray spectroscopy (TDPAC) to the study of solid state physics. The technique yields valuable information on the electric field gradients experienced by radionuclides which have been substituted for nonradioactive isotopes or inserted as impurities into various inorganic compounds. The indium halides are examined in a series of experiments. The first applications of this technique to the study of graphite intercalation compounds are discussed.
Science, Faculty of
Physics and Astronomy, Department of
Graduate

Le but de ce travail de thèse a été de développer à MIRC en une capacité à observer deux aspects clefs du métabolisme cérébral chez le rongeur par spectroscopie RMN des noyaux X : le métabolisme mitochondrial du glucose à partir de l’observation du 13C et la synthèse d’ATP par observation du 31P. Ces développements s’inscrivent à la fois dans une recherche fondamentale pour améliorer notre compréhension du signal RMN et raffiner son analyse ainsi que du métabolisme cérébral chez les sujets sains. Ils s’inscrivent aussi dans une recherche translationnelle avec la possibilité d’évaluer certains aspects du métabolisme comme potentiels biomarqueurs de maladies neurodégénératives. Ces travaux ont pu être réalisés à très haut champ (11.7T) permettant d’obtenir un meilleur rapport signal à bruit. Dans un premier temps, nous présenterons le développement d’une séquence de transfert de saturation pour la mesure des flux de synthèse d’adénosine triphosphate (ATP) et de phosphocréatine (PCr). Cette séquence a été optimisée pour sélectionner avec un module de localisation ISIS le signal émis par le cerveau uniquement. Avec l’augmentation de la résolution spectrale à haut champ, cette séquence a pu être utilisée pour caractériser le phosphate inorganique extracellulaire, et prévenir un biais de quantification possible à plus bas champ. De plus, elle a permis l’observation de l’adaptation du métabolisme cérébral chez les rats transgéniques BACHD, modèles de la maladie de Huntington. Ces rats présentent une augmentation d’environ 10% de la concentration de PCr permettant de pallier à leur plus faible taux de synthèse d’ATP qui lui est diminué de moitié. Dans un second temps, la mise en place d’un pipeline automatisé d’analyse des données a permis d’explorer le modèle métabolique bicompartimental de la consommation de glucose observée en spectroscopie 13C, qui prend en compte le cycle de Krebs dans les neurones et les astrocytes. Deux corrections majeures ont été apportées au modèle traditionnel permettant d’expliquer les dynamiques à moyen et long termes. La première est la mise en évidence d’un pool de glutamate vésiculaire agissant comme tampon temporel au marquage du glutamate, la seconde est la présence d’une dilution 6 fois plus importante de pyruvate vers les astrocytes que vers les neurones. Ces résultats viennent renforcer les hypothèses entourant le couplage métabolique entre ces deux types cellulaires. Ces hypothèses ont pu être testées après l’optimisation d’une séquence d’acquisition du signal RMN des noyaux 13C par transfert de polarisation (DEPT), testée in vivo dans le cerveau du rat sain. Finalement, l’utilisation combinée de la spectroscopie 31P et 13C a été appliquée chez le rat sous intoxication chronique au 3-NP, une toxine inhibant le cycle de Krebs et utilisée comme modèle de la maladie de Huntington
The aim of this thesis was to develop at MIRCen new capabilities to observe two key aspects of energy metabolism in rodent brains using X nuclei NMR spectroscopy: glucose consumption with 13C spectroscopy and adenosine triphosphate (ATP) synthesis with 31P measurements. These developments will be used to both expand general understanding of brain metabolism in healthy subjects but also provide technical tools to search for biomarkers in translational projects of drug development applied to neurodegenerative diseases. This work was done at very high field (11.7T) where signal to noise could be maximized. In the first part, we present the optimization of saturation transfer sequence to measure ATP synthesis rate as well as phosphocreatine (PCr) synthesis rate. With ISIS module, the signal was localized to a voxel containing only the brain, eliminating outside source of signal. With the higher spectral resolution offered by high fields, a second, extracellular pool of Pi was characterized which could prevent possible biases in flux quantification of ATP synthesis. This sequence was also applied to measure metabolic adaptation of BACHD rat models (models of Huntington’s disease, HD) where it was found that the 10% increase in PCr concentration could palliate the ATP synthase activity that is halved in this model. In the second part, we present how deeper analysis of 13C data using automatic differential equation writing script was used to better understand the bicompartmental model of glucose degradation to glutamate and glutamine, which accounts for TCA cycle in neurons and astrocytes. Two major corrections were made to the traditional model, to fit mid- and long-term unexplained dynamics. Looking at glutamate and glutamine isotopomer labeling dynamics, the necessity of adding a vesicular glutamate temporal buffer was made evident. The distinction between astrocytic and neuronal pyruvate dilution also showed that astrocytes use up to 6 times more pyruvate than neurons showing intricate metabolic coupling between the two cell types. These results have then been tested in vivo after optimization of the ISIS-DEPT sequence to observe 13C labeling in the rat brain. Finally, experiments combining 31P and 13C spectroscopy were performed on rats chronically intoxicated with 3-NP, a toxin inhibiting TCA cycle which is used as a model of HD

Aujourd’hui encore, malgré l’utilisation de techniques spectrochimiques de référence, l’aspect quantitatif de la spectroscopie sur plasma induit par laser (LIBS) reste largement en friche du fait d’effets de matrice incapacitants. La LIBS sans étalonnage (CF-LIBS) est une des façons considérées par la communauté scientifique afin de relever ce défi. Malgré ses postulats d’idéalité du plasma (ETL, homogénéité et stationnarité du plasma), à l’heure actuelle peu d’études extensives ont été développées afin de réaliser une évaluation critique de la méthode. A l’aide d’outils théoriques (modèle collisionnel-radiatif développé pour l’Aluminium, Argon et Cadmium) et expérimentaux (expérience de Diffusion Thomson) tirant leur origine de la physique des plasmas, ainsi que de cas pratiques d’analyses, nous tenterons d’établir le cahier des charges le plus favorable à l’analyse quantitative par CF-LIBS. L’application de cette méthode à l’analyse d’échantillons complexes (minéraux et sols pollués) sera discutée à l’aune de nos résultats et des connaissances actuellement disponibles en la matière
Despite the existence of many benchmarked spectrochemical analysis techniques in the field of Laser-Induced Breakdown Spectroscopy (LIBS), the quantitative analysis holds of the laser induced plasma still holds a huge number of analytical drawbacks, the occurrence of matrix effects not being the slightest among those ones.Calibration-Free LIBS was historically developped to address specifically those aspects, and has already reached a high level of maturation for the analysis of simple metallic or soil samples. Unfortynately, in spite of the strong assumptions that need to be necesserily considered in the CF-LIBS algorithm (such as Local Thermodynamic Equilibrium, and the homogeneity and stationnarity of the plasma), only a few number of contributions have been devoted to the critical assessment of the latter postulates to date. Thanks to the help of several case tests and theoretical (collisionnal-radiative model depicting aluminum, argon and cadmium plasmas) and experimental concepts originating from the field of plasma physics (Thomson-Scattering experiments intended to validate our results), we will focus our study on the research and development of novel experimental criteria that would allow an experimentalist to set up and analyze a CF-LIBS experiment in the least unfavourable theoretical and experimental conditions.We will eventually apply our new considerations on the prediction of the CF-LIBS analysis efficiency, coming to the specific field of interest of analysis of geophysical samples (such as soils polluted by heavy metals). A special interest will be paid on the latest developments appearing nowadays in the field of LIBS, and devote a part of our debate on the expectancies that will have to be fulfilled in order to highen the analysis potential of LIBS

The observation of graphene’s extraordinary electrical properties has stirred great interest in two dimensional (2D) materials. The rapid pace of discovery for low dimensional materials with exciting properties continue with graphene allotropes, multiple polymorphs of borophene, germanene, and many others. The future of 2D materials goes beyond synthesis and characterization of free standing materials and on to the construction of heterostructures or sophisticated multilayer devices. Knowledge about the resulting local structure and composition of such systems will be key to understanding and optimizing their performance characteristics. 2D materials do not have a repeating crystal structure which can be easily characterized using bulk methods and therefore a localized high resolution method is needed. Electron microscopy is well suited for characterizing 2D materials as a repeating coherent structure is not necessary to produce a measureable signal as may be the case for diffraction methods. A unique opportunity for fine local scale measurements in low dimensional systems exists with a specific class of materials known as ferecrystals, the rotationally disordered relative of misfit layer compounds. Ferecrystals provide an excellent test system to observe effects at heterostructure interfaces as the whole film is composed of interdigitated two dimensional layers. Therefore bulk methods can be used to corroborate local scale measurements. From the qualitative interpretation of high resolution scanning transmission electron microscope (STEM) images to the quantitative application of STEM energy dispersive X-ray spectroscopy (EDX), this thesis uses numerous methods electron microscopy. The culmination of this work is seen at the end of the thesis where atomically resolved STEM-EDX hyperspectral maps could be used to measure element specific atomic distances and the atomically resolved fractional occupancies of a low dimensional alloy. These local scale measurements are corroborated by additional experimental data. The input of multiple techniques leads to improved certainty in local scale measurements and the applicability of these methods to non-ferecrystal low dimensional systems.

In this thesis methodological developments have been made for the description of flexible conjugated dyes in room temperature spectrum calculations. The methods in question target increased accuracy and efficiency by combining classical molecular dynamics (MD) simulations with time-dependent response theory spectrum calculations. For absorption and fluorescence spectroscopies a form of conformational averaging is used, where the final spectrum is obtained as an average of spectra calculated for geometries extracted from ground and excited state MD simulations. For infrared and Raman spectroscopies averaged spectra are calculated based on individual spectra, obtained for zero-temperature optimized molecular structures, weighted by conformational statistics from MD trajectories. Statistics for structural properties are also used in both cases to gain additional information about the systems, allowing more efficient utilization of computational resources. As it is essential that the molecular mechanics description of the system is highly accurate for methods of this nature to be effective, high quality force field parameters have been derived, describing the molecules of interest in either the MM3 or CHARMM force fields. These methods have been employed in the study of three systems. The first is a platinum(II) actylide chromophore used in optical power limiting materials, for which a ultraviolet/visible absorption spectrum has been calculated. The second is a family of molecular probes called luminescent conjugated oligothiophenes, used to detect and characterize amyloid proteins, for which both absorption and fluorescence spectra have been calculated. Finally, infrared and Raman spectra have been calculated for a group of branched oligothiophenes used in organic solar cells. In addition, solvation effects have been studied for conjugated poly\-eletrolytes in water, resulting in the development of two solvation models suitable for this class of molecules. The first uses a quantum meachanics/molecular mechanics (QM/MM) description, in which the solute mole\-cule is described using accurate quantum mechanical methods while the surrounding water molecules are described using point charges and polarizable point dipoles. The second discards the water entirely and removes the ionic groups of the solute. The QM/MM model provides highly accurate results while the cut-down model gives results of slightly lower quality but at a much reduced computational cost. Finally, a study of protein-dye interactions has been performed, with the goal of explaining changes in the luminescence properties of the LCO chromophores when in the presence of amyloid proteins. Results were less than conclusive.

In electrochemical oxidation treatment of wastewater, the electrode material is an important parameter in optimizing oxidative electrochemical processes, since the mechanism and products of several anodic reactions are known to depend on the anode material. The electrochemical oxidation of benzaldehyde, nitrobenzene and m-cresol on bare boron-doped diamond (BDD) electrode was investigated. Cytochrome c was then electrochemically immobilsed onto the functionalized BDD electrode by cyclic voltammetry. Oxidation and reduction reaction mechanism of each flavonoid was studied. There was one oxidation and reduction peaks for quercitin and catechin respectively, and two oxidation and two reduction peaks for rutin. The cytochrome c modified BDD electrode showed good sensitivity for all three flavonoids and low detection limits i.e. 0.42 to 11.24 M as evaluated at oxidation and reduction peaks, respectively.

Les métaux lourds et les radionucléides sont présents dans différents écosystèmes du monde à cause de contaminations naturelles ou des activités anthropiques. L’utilisation de micro-organismes pour restaurer ces écosystèmes pollués, processus connu sous le nom de bioremédiation, suscite beaucoup d’intérêt, spécialement aux pH proches de la neutralité. Les minéraux de fer qui encroûtent les bactéries neutrophiles du fer, notamment les Oxydes de Fer Biogéniques (BIOS en anglais), ont une structure très faiblement cristalline, qui en plus de leur grande surface et réactivité font d’eux d’excellents supports pour le piégeage de polluants inorganiques. Dans cette thèse nous avons étudié les différents mécanismes de piégeage de l’uranium uranium par la bactérie neutrophile Sphaerotilus natans, choisie comme modèle bactérien de micro-organismes du fer capables de filamenter en formant des gaines. S. natans peut croître sous forme de cellules individuelles ou formant des filaments. Ces derniers ont été utilisés pour étudier la biosorption d’U(VI) et sa sorption sur les BIOS. De plus, la sorption d’U(VI) sur les analogues abiotiques de ces minéraux de fer a été testée. Afin d’utiliser les filaments de S. natans pour piéger l’U(VI), il était nécessaire d’identifier les facteurs induisant la filamentation de S. natans. L’influence de l’oxygène a été établie en utilisant des techniques de biologie moléculaire et nos résultats ont démontré que tandis qu’en condition d’oxygène saturé elle croît sous forme de cellules individuelles, une diminution modérée d’oxygène à ~ 3 mg O2.L-1 la fait croître sous la forme désirée, des filaments de S. natans.Les BIOS attachés aux filaments de S. natans ainsi que ses analogues abiotiques ont été analysés pas XAS au seuil K du Fe. Les deux matériaux identifiés sont des phosphates de fer(III) amorphes avec une faible proportion de fer(II), qui présentent une réactivité élevée pour le piégeage de polluants inorganiques. L’EXAFS au seuil LIII de l’U a montré la même structure pour les couches O, tandis que celles P, Fe et C étaient différentes en fonction des sorbants. Une étude intégrée qui combine des techniques expérimentales avec des calculs de spéciation a permis de décrire les isothermes d’adsorption de l’U(VI) en utilisant un modèle de complexation de surface. Ces résultats suggèrent que les groupes phosphoryles et carboxyles sont les groupes fonctionnels principaux pour la biosorption d’U(VI) par des filaments de S. natans. Les résultats de cette thèse vont aider à comprendre les processus contrôlant l’immobilisation de l’U(VI), soit par la biosorption sur S. natans, la sorption sur les BIOS ou la sorption sur les phosphates de fer, et en conséquence le devenir de l’U en conditions neutres
Heavy metals and radionuclides are present in some ecosystems worldwide due to natural contaminations or anthropogenic activities. The use of microorganisms to restore those polluted ecosystems, a process known as bioremediation, is of increasing interest, especially under near-neutral pH conditions. Iron minerals encrusting neutrophilic iron-related bacteria, especially Bacteriogenic Iron Oxides (BIOS), have a poorly crystalline structure, which in addition to their large surface area and reactivity make them excellent scavengers for inorganic pollutants. In this PhD work we studied the different mechanisms of uranium scavenging by the neutrophilic bacterium Sphaerotilus natans, chosen as a model bacterium for iron-related sheath-forming filamentous microorganisms. S. natans can grow as single cells and filaments. The latter were used to investigate U(VI) biosorption and U(VI) sorption onto BIOS. In addition, uranium sorption onto the abiotic analogues of such iron minerals was assessed. In order to use S. natans filaments for U(VI) scavenging, it was necessary to identify factors inducing S. natans filamentation. The influence of oxygen was ascertained by using molecular biology techniques and our results revealed that while saturated oxygen conditions resulted in single cell growth, a moderate oxygen depletion to ~ 3 mg O2.L-1 led to the desired filamentous growth of S. natans. BIOS attached to S. natans filaments as well as the abiotic analogues were analysed by XAS at Fe K-edge. Both materials were identified as amorphous iron(III) phosphates with a small component of Fe(II), with a high reactivity towards scavenging of inorganic pollutants. In addition, EXAFS at the U LIII-edge revealed a common structure for the O shells, while those for P, Fe and C were different for each sorbent. An integrated approach combining experimental techniques and speciation calculations made it possible to describe U(VI) adsorption isotherms by using a surface complexation model. These results suggested the role of phosphoryl and carboxyl groups as the main functional groups involved in the U(VI) biosorption by S. natans. The results of this PhD work will help to better understand the processes governing U(VI) immobilization, either by S. natans biosorption, sorption onto BIOS or sorption onto iron phosphates, an thus the fate of uranium in near-neutral pH environments

This thesis describes the development and applications of an extension of DWS which enables the recovery of ‘localized’ mechanical properties, in a specified region of a complex jelly-like object which is inhomogeneous, marked out by the focal volume of an ultrasound transducer, also called the region-of-interest (ROI). Introduction of the sinusoidal forcing creates a sinusoidal phase variation in the detected light in a DWS experiment which modulates the measured intensity autocorrelation, g2 (τ ). Decay in the modulation depth with τ is used to recover the visco-elastic spectrum of the material in the ROI. En route to this, growth of the mean-squared dis- placement (MSD) with time is extracted from the modulation depth decay, which was verified first by the usual DWS experimental data from an homogeneous object with properties matching those in the ROI of the inhomogeneous object and then those obtained by solving the generalized Langevin equation (GLE) modelling the dynamics of a typical scattering centre in the ROI. A region-specific visco-elastic spectral map was obtained by scanning the inhomogeneous object by the ultrasound focal volume. Further, the resonant modes of the vibrating ROI were measured by locating the peaks of the modulation depth variation in g2(τ ) with respect to the ultrasound frequency. These resonant modes were made use of to recover elasticity of the material of the object in the ROI. Using a similar strategy, it was also shown that flow in pipe can be detected and flow rate computed by ‘tagging’ the photons passing through the pipe with a focussed ultrasound beam. It is demonstrated, both through experiments and simulations that the ultrasound-assisted technique devel- oped is better suited to both detect and quantitatively assess flow in a background of Brownian dynamics than the usual DWS. In particular, the MSD of particles in the flow, which shows forth a super-diffusive dynamics with MSD growing following τ α with α < 2, is captured over larger intervals of τ than was possible using existing methods. On the theoretical front, the main contribution is the derivation of the GLE, with multiplicative noise modulating the interaction ‘spring constant’. The noise is derived as an average effect of the micropolar rotations suffered by the ‘bath’ particles on the ‘system’ particle modelled. It has been shown that the ‘local’ dynamics of the system particle is nontrivially influenced by the dynamics, both translation and rotation, of ‘nonlocal’ bath particles.

This thesis describes the development and applications of an extension of DWS which enables the recovery of ‘localized’ mechanical properties, in a specified region of a complex jelly-like object which is inhomogeneous, marked out by the focal volume of an ultrasound transducer, also called the region-of-interest (ROI). Introduction of the sinusoidal forcing creates a sinusoidal phase variation in the detected light in a DWS experiment which modulates the measured intensity autocorrelation, g2 (τ ). Decay in the modulation depth with τ is used to recover the visco-elastic spectrum of the material in the ROI. En route to this, growth of the mean-squared dis- placement (MSD) with time is extracted from the modulation depth decay, which was verified first by the usual DWS experimental data from an homogeneous object with properties matching those in the ROI of the inhomogeneous object and then those obtained by solving the generalized Langevin equation (GLE) modelling the dynamics of a typical scattering centre in the ROI. A region-specific visco-elastic spectral map was obtained by scanning the inhomogeneous object by the ultrasound focal volume. Further, the resonant modes of the vibrating ROI were measured by locating the peaks of the modulation depth variation in g2(τ ) with respect to the ultrasound frequency. These resonant modes were made use of to recover elasticity of the material of the object in the ROI. Using a similar strategy, it was also shown that flow in pipe can be detected and flow rate computed by ‘tagging’ the photons passing through the pipe with a focussed ultrasound beam. It is demonstrated, both through experiments and simulations that the ultrasound-assisted technique devel- oped is better suited to both detect and quantitatively assess flow in a background of Brownian dynamics than the usual DWS. In particular, the MSD of particles in the flow, which shows forth a super-diffusive dynamics with MSD growing following τ α with α < 2, is captured over larger intervals of τ than was possible using existing methods. On the theoretical front, the main contribution is the derivation of the GLE, with multiplicative noise modulating the interaction ‘spring constant’. The noise is derived as an average effect of the micropolar rotations suffered by the ‘bath’ particles on the ‘system’ particle modelled. It has been shown that the ‘local’ dynamics of the system particle is nontrivially influenced by the dynamics, both translation and rotation, of ‘nonlocal’ bath particles.

The clinical evaluation of people with possible myocardial infarction (MI) is often limited by atypical symptoms and inconclusive initial electrocardiograms. A recent consensus from the American College of Cardiology has redefined acute MI to include cardiac markers as central to diagnosis. To address this clinical need, a sensitive microfluidic surface-enhanced Raman spectroscopy (SERS) nanochannel-based optical device is being developed for ultimate use as a point-of-care device for the simultaneous measurement of MI blood biomarkers. The device can provide enhancements of the Raman signal of the analyte measured of up to 1013 using a mechanical aggregation technique at the interface of nanofluidic structures enabling repeatable SERS measurements. Specifically in this research iterations of a sensitive, low volume SERS platform technology were designed that provided quantitative information across a specific range. With the SERS platforms studied, not only were SERS enhancements of up to 1013 achieved but also imprecision values of less than 10% across the 10-50 pM range using a ratiometric approach and qualitative detection down to 100 aM was achieved. Beyond assessment of SERS substrates, assay designs were investigated and characterized including, label-free techniques and competitive immunoassay formats. Lastly, detecting the SERS signal of multiplexed reporter molecules was investigated. By identifying the analyte and assay constraints the design and optimization of future assays will be aided using this SERS platform technology.