Metal nanostructures exhibit a wide variety of interesting physical and chemical properties, which can be tailored by altering their size, morphology, composition, and environment. Gold and silver nanostructures have received considerable attention for many decades because of their widespread use in applications such as catalysis, photonics, electronics, optoelectronics, information storage, chemical and biological sensing, surface plasmon resonance and surface-enhanced Raman scattering (SERS) detection. This thesis is composed of three main parts about the synthesis, characterization and SERS applications of shape-controlled and surface modified noble metal nanoparticles. The first part is related to a simple synthesis of shape controlled solid gold, hollow gold, silver, gold-silver core-shell, hollow gold-silver double-shell nanoparticles by applying aqueous solution chemistry. Nanoparticles obtained were used for SERS detection of dye molecules like brilliant cresyl blue (BCB) and crystal violet (CV) in aqueous system. v The second part involves the synthesis of surface modified silver nanoparticles for the detection of dopamine (DA) molecules. Determination of a dopamine molecule attached to a iron-nitrilotriaceticacid modified silver (Ag-Fe(NTA)) nanoparticles by using surface-enhanced resonance Raman scattering (SERRS) was achieved. The Ag-Fe (NTA) substrate provided reproducibility and excellent sensitivity. Experimental results showed that DA was detected quickly and accurately without any pretreatment in nM levels with excellent discrimination against ascorbic acid (AA) (which was among the lowest value reported in direct SERS detection of DA). In the third part, a lanthanide series ion (Eu3+) containing silver nanoparticle was prepared for constructing a molecular recognition SERS substrate for the first time. The procedure reported herein, provides a simple way of achieving reproducible and sensitive SERS spectroscopy for organophosphates (OPP) detection. The sensing of the target species was confirmed by the appearance of an intense SERS signal of the methyl phosphonic acid (MPA), a model compound for nonvolatile organophosphate nerve agents, which bound to the surface of the Ag-Eu3+ nanostructure. The simplicity and low cost of the overall process makes this procedure a potential candidate for analytical control processes of nerve agents.

Raman spectroscopy offers much better spectral selectivity but its usage has been limited by its poor sensitivity. The discovery of surface-enhanced Raman scattering (SERS) effect, which results in increased sensitivities of up to 108-fold for some compounds, has eliminated this drawback. A new SERS active substrate was developed in this study. Silver nanoparticle-doped polyvinyl alcohol (PVA) coated SERS substrate prepared through chemical and electrochemical reduction of silver particles dispersed in the polymer matrix. Performances of the substrates were evaluated with some biologically important compounds. The specific detection of DNA has gained significance in recent years since increasingly DNA sequences of different organisms are being assigned. Such sequence knowledge can be employed for identification of the genes of microorganisms or diseases. In this study, specific proteasome gene sequences were detected both label free spectrophotometric detection and SERS detection. In label free spectrophotometic detection, proteasome gene probe and complementary target gene sequence were attached to the gold nanoparticles separately. Then, the target and probe oligonucleotide-modified gold solutions were mixed for hybridization and the shift in the surface plasmon absorption band of gold nanoparticles were followed. SERS detection of specific nucleic acid sequences are mainly based on hybridization of DNA targets to complementary probe sequences, which are labelled with SERS active dyes. In this study, to show correlation between circulating proteasome levels and disease state we suggest a Raman spectroscopic technique that uses SERGen probes. This novel approach deals with specific detection of elevated or decreased levels of proteasome genes&rsquo / transcription in patients as an alternative to available enzyme activity measurement methods. First, SERGen probes were prepared using SERS active labels and specific proteasome gene sequences. Then DNA targets to complementary SERGen probe sequences were hybridized and SERS active label peak was followed.

Over the last 50 years, flow cytometry has evolved from a modest cell counter into an invaluable analytical tool that measures an ever-expanding variety of phenotypes. Flow cytometers interrogate passing samples with laser light and measure the elastically scattered photons to ascertain information about sample size, granularity, and basic morphology. Obtaining molecular information, however, requires the addition of exogenous fluorescent labels. These labels, although a power tool, have numerous challenges and limitations such as large emission spectra and cellular toxicity. To move beyond fluorescent labels in microscopy, a variety of techniques that probe the intrinsic Raman vibrations within a sample have been developed, such as coherent anti-Stokes Raman scattering (CARS) and Raman microspectroscopy. In this dissertation, I present the first development of a label-free flow cytometer that measures the elastically scattered photons and probes the intrinsic Raman vibrations of passing samples using multiplex coherent anti-Stokes Raman scattering (MCARS). MCARS, a coherent Raman technique that probes a large region of the Raman spectrum simultaneously, provides rich molecularly-sensitive information. Furthermore, I present its application to sorting polymer microparticles and its use in two example biological applications: monitoring lipid bodies within cultures of Saccharomyces cerevisiae, a model yeast with numerous human homologs, and monitoring the affect of nitrogen starvation on Phaeodactylum tricornutum, a diatom, which is being genetically engineered to efficiently produce biofuels.

The understanding of molecular effects in nanoscale environments is becoming increasingly relevant for various emerging fields. These include spectroscopy for molecular identification as well as in finding molecules for energy harvesting. Theoretical quantum chemistry has been increasingly useful to address these phenomena to yield an understanding of these effects. In the first part of this dissertation, we study the chemical effect of surface-enhanced Raman scattering (SERS). We use quantum chemistry simulations to study the metal-molecule interactions present in these systems. We find that the excitations that provide a chemical enhancement contain a mixed contribution from the metal and the molecule. Moreover, using atomistic studies we propose an additional source of enhancement, where a transition metal dopant surface could provide an additional enhancement. We also develop methods to study the electrostatic effects of molecules in metallic environments. We study the importance of image-charge effects, as well as field-bias to molecules interacting with perfect conductors. The atomistic modeling and the electrostatic approximation enable us to study the effects of the metal interacting with the molecule in a complementary fashion, which provides a better understanding of the complex effects present in SERS. In the second part of this dissertation, we present the Harvard Clean Energy project, a high-throughput approach for a large-scale computational screening and design of organic photovoltaic materials. We create molecular libraries to search for candidates structures and use quantum chemistry, machine learning and cheminformatics methods to characterize these systems and find structure-property relations. The scale of this study requires an equally large computational resource. We rely on distributed volunteer computing to obtain these properties. In the third part of this dissertation we present our work related to the acceleration of electronic structure methods using graphics processing units. This hardware represents a change of paradigm with respect to the typical CPU device architectures. We accelerate the resolution-of-the-identity Moller-Plesset second-order perturbation theory algorithm using graphics cards. We also provide detailed tools to address memory and single-precision issues that these cards often present.

The effective diagnosis of leukemia subtypes requires the detection of multiple cell surface markers. Current methods of detection use mostly fluorophores, which are limited by their large spectral bandwidths, photobleaching, and incompatibility with histological stains used for morphological assessments. Antibody-conjugated Surface enhanced Raman scattering (SERS) nanoparticles is an alternative tool that overcomes these limitations. A current drawback of SERS is the lack of available tools to analyze the bioconjugation of antibodies to nanoparticles following EDC/sulfo-NHS cross-linking, which produces inconsistent results and determines the efficacy of SERS probe targeting. This study uses the flow cytometry approach to evaluate SERS particles by incorporating FITC and DyLight650 secondary antibodies. Flow cytometry was also used to assess targeting of particles to markers on LY10 cells and CLL cells and to detect SERS signals by inserting a 710 BP 10nm FWHM filter specific for MGITC.

The effective diagnosis of leukemia subtypes requires the detection of multiple cell surface markers. Current methods of detection use mostly fluorophores, which are limited by their large spectral bandwidths, photobleaching, and incompatibility with histological stains used for morphological assessments. Antibody-conjugated Surface enhanced Raman scattering (SERS) nanoparticles is an alternative tool that overcomes these limitations. A current drawback of SERS is the lack of available tools to analyze the bioconjugation of antibodies to nanoparticles following EDC/sulfo-NHS cross-linking, which produces inconsistent results and determines the efficacy of SERS probe targeting. This study uses the flow cytometry approach to evaluate SERS particles by incorporating FITC and DyLight650 secondary antibodies. Flow cytometry was also used to assess targeting of particles to markers on LY10 cells and CLL cells and to detect SERS signals by inserting a 710 BP 10nm FWHM filter specific for MGITC.

The PhD dissertation is organized in two parts. In the first part, we present an experimental study of stimulated Raman scattering in a silicon-on-insulator (SOI) nanowire. We demonstrate that the Raman amplification of a narrow-band Stokes wave experiences a saturation effect for high pump intensities because of self phase modulation of the pump beam. Moreover, an analytical model is presented that describes the experimental results remarkably well. The model furthermore provides an estimation of the Raman gain coefficient γR of silicon. The second part is devoted to the experimental study of stimulated Raman scattering in a doubly resonant planar GaAs microcavity. The nonlinear measurements clearly show some totally unexpected results. We experimentally demonstrate that the relaxation of the electrons in the conduction band of GaAs is significantly modified through the interaction with coherently excited Raman phonons.

Microscopy techniques have been developed and refined over multiple decades, but innovation around single photon modalities has slowed. The advancement of the utility of information acquired, and minimum resolution available is seemingly reaching an asymptote. The fusion of light microscopy and well-studied nonlinear processes has broken through this barrier and enabled the collection of vast amounts of additional information beyond the topographical information relayed by traditional microscopes. Through nonlinear imaging modalities, chemical information can also be extracted from tissue. Nonlinear microscopy also can beat the resolution limit caused by diffraction, and offers up three-dimensional capabilities. The power of nonlinear imaging has been demonstrated by countless research groups, solidifying it as a major player in biomedical imaging. The value of a nonlinear imaging system could be enhanced if a reduction in size would permit the insertion into bodily cavities, as has been demonstrated by linear imaging endoscopes. The miniaturization of single photon imaging devices has led to significant advancements in diagnostics and treatment in the medical field. Much more information can be extracted from a patient if the tissue can be imaged in vivo, a capability that traditional, bulky, table top microscopes cannot offer. The development of new technologies in optics has enabled the miniaturization of many critical components of standard microscopes. It is possible to combine nonlinear techniques with these miniaturized elements into a portable, hand held microscope that can be applied to various facets of the biomedical field. The research demonstrated in this thesis is based on the selection, testing and assembly of several miniaturized optical components for use as a nonlinear imaging device. This thesis is the first demonstration of a fibre delivered, microelectromechanical systems mirror with miniaturized optics housed in a portable, hand held package. Specifically, it is designed for coherent anti-Stokes Raman scattering, second harmonic generation, and two-photon excitation fluorescence imaging. Depending on the modality being exploited, different chemical information can be extracted from the sample being imaged. This miniaturized microscope can be applied to diagnostics and treatments of spinal cord diseases and injuries, atherosclerosis research, cancer tumour identification and a plethora of other biomedical applications. The device that will be revealed in the upcoming text is validated by demonstrating all designed-for nonlinear modalities, and later will be used to perform serialized imaging of myelin of a single specimen over time.

Many biological processes, pathogens, and pharmaceuticals act upon, cellular membranes. Accordingly, cell membrane mimics are attractive targets for biosensing, with research, pathology, and pharmacology applications. Lipid bilayers represent a versatile sensor functionalization platform providing antifouling properties, and many receptor integration options, uniquely including transmembrane proteins. Bilayer-coated sensors enable the kinetic characterization of membrane/analyte interactions. Addressed theoretically and experimentally is the self-assembly of model membranes on plasmonic sensors. Two categories of plasmonic sensors are studied in two parts. Part I aims to deposit raft-forming bilayers on planar nanoaperture arrays suitable for multiplexing and device integration. By vesicle fusion, planar bilayers are self-assembled on thiol-acid modified flame-annealed gold without the need for specific lipid head-group requirements. Identification of coexisting lipid phases is accomplished by AFM imaging and force spectroscopy mapping. These methods are successfully extended to metallic, plasmon-active nanohole arrays, nanoslit arrays and annular aperture arrays, with coexisting phases observed among the holes. Vis-NIR transmission spectra of the arrays are measured before and after deposition, indicating bilayer detection. Finally, the extraction of membrane proteins from cell cultures and incorporation into model supported bilayers is demonstrated. These natural membrane proteins potentially act as lipid-bound surface receptors. Part II aims to encapsulate in model lipid bilayers, metallic nanoparticles, which are used as probes in surface enhanced Raman spectroscopy. Three strategies of encapsulating particles, and incorporating Raman-active dyes are demonstrated, each using a different dye: malachite green, rhodamine-PE, and Tryptophan. Dye incorporation is verified by SERS and the bilayer is visualized and measured by TEM, with support from DLS and UV-Vis spectroscopy. In both parts, lipid-coated sensors are successfully fabricated and characterized. These results represent important and novel solutions to the functionalization of plasmonic surfaces with biologically relevant cell membrane mimics.

Made available in DSpace on 2014-06-11T19:23:29Z (GMT). No. of bitstreams: 0 Previous issue date: 2005-08-26Bitstream added on 2014-06-13T19:29:33Z : No. of bitstreams: 1 simoes_rd_me_bauru.pdf: 3082806 bytes, checksum: b44fcfd386ae934a75a9814336462470 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O principal objetivo deste trabalho de mestrado foi a obtenção e caracterização estrutural de um material com propriedades físico-químicas compatíveis com aquelas requeridas por um biomaterial. Filmes contendo diferentes volumes de látex de borracha natural em uma massa fixa de poli(fluoreto de vinilideno) (PVDF), na forma de pó foram fabricados por compressão/aquecimento de uma mistura de ambos os materiais sem o uso de qualquer solvente. Este é um fator importante considerando o uso destes filmes no futuro próximo como biomateriais em diferentes aplicações (indução do crescimento do tecido ósseo, por exemplo), uma vez que os solventes convencionais usados para dissolver o PVDF têm se mostrado tóxicos ao organismo humano. Os filmes foram submetidos a um tratamento via descarga corona de forma que amostras com e sem tal tratamento foram caracterizadas através das técnicas de espectroscopia vibracional via espalhamento Raman e absorção no infravermelho (FTIR), análise térmica via termogravimetria (TG), calorimetria exploratória diferencial (DSC) e análise dinâmico-mecânica (DMA) e microscopias ótica e eletrônica (MEV). As medidas termomecânicas mostraram que os filmes obtidos possuem características mecânicas similares àquelas encontradas no osso humano e boa estabilidade térmica considerando-se a aplicação desejada. As medidas via espectroscopia vibracional indicaram que o PVDF e o látex não interagem quimicamente, compondo uma blenda polimérica. Além disto, os resultados obtidos via micro-Raman mostraram que o aumento da quantidade de látex na blenda permite uma melhor dispersão deste látex na matriz de PVDF quando da produção dos filmes... / The main goal of this work was to obtain and characterize structurally a material with physical-chemical properties compatible with those required for a biomaterial. Films containing different volumes of latex of natural rubber in a fixed mass of poly (vinylidene fluoride) (PVDF) powder were fabricated by compressing/annealing a mixture of both materials without using any solvent. This is an important issue having in mind to use these films in the future as biomaterials in different applications (growing of the bone tissue, for instance) once the solvents used to dissolve the PVDF are toxic to human being. The films were submitted to a corona discharge treatment in a way that samples with and without such treatment were characterized using micro-Raman scattering and Fourier transform infrared absorption (FTIR) spectroscopies, thermo-mechanical techniques using thermogravimetry (TG), differential scanning calorimetry (DSC) and dynamical-mechanical analysis (DMA) and optical and scanning electron microscopies (SEM). The thermo-mechanical measurements revealed that the films present mechanical properties close to that found for the human bone and high thermal stability considering the desired applications. The vibrational spectroscopies showed that the latex and PVDF do not interact chemically leading to the formation of a polymeric blend. Besides, the results recorded using the micro-Raman technique revealed that the higher the amount of latex in the blend, the better the miscibility between both materials. In terms of morphology, the blend surface is formed by two domains: one is rougher and contains the latex well dispersed into the PVDF matrix while the other is smoother and contains both materials as well but in a less homogeneous dispersion. However, as the volume of latex is increased from 0.3 to 1.0 mL, the smoother domains become rarer to be found... (Complete abstract, click electronic address below)