<p>Second harmonic generation (SHG) microscopy and Raman microscopy were used for qualitative and quantitative analysis of pharmaceutical materials. Prototype instruments and algorithms for sampling strategies and data analyses were developed to achieve pharmaceutical materials analysis with low limits of detection and short measurement times<br></p><p>Manufacturing an amorphous solid dispersion (ASD), in which an amorphous active pharmaceutical ingredient (API) within polymer matrix, is an effective approach to improve the solubility and bioavailability of a drug. However, since ASDs are generally metastable materials, they can often transform to produce crystalline API with higher thermodynamic stability. Analytical methods with low limits of detection for crystalline APIs were used to assess the stability of ASDs. With high selectivity to noncentrosymmetric crystals, SHG microscopy was demonstrated as an analytical tool, which exhibited a limit of detection of 10 ppm for ritonavir Form II crystals. SHG microscopy was employed for accelerated stability testing of ASDs, which provided a four-decade dynamic range of crystallinity for kinetic modeling. An established model was validated by investigating nucleation and crystal growth based on SHG images. To achieve <i>in situ</i> accelerated stability testing, controlled environment for in situstability testing (CEiST) was designed and built to provide elevated temperature and humidity, which is compatible with a commercial SHG microscope based on our research prototype. The combination of CEiST and SHG microscopy enabled assessment of individual crystal growth rates by single-particle tracking and nucleation rates for individual fields of view with low Poisson noise. In addition, SHG microscopy coupled with CEiST enabled the study of heterogeneity of crystallization kinetics within pharmaceutical materials.<br></p><p>Polymorphism of APIs plays an important role in drug formulation development. Different polymorphs of identical APIs may exhibit different physiochemical properties, e.g., solubility, stability, and bioavailability, due to their crystal structures. Moreover, polymorph transitions may take place during the manufacturing process and storage. Therefore, analytical methods with high speed for polymorph characterization, which can provide real-time feedback for the polymorphic transition, have broad applications in pharmaceutical materials characterization. Raman spectroscopy is able to determine the API polymorphism, but is hampered by the long measurement times. In this study, two analytical methods with high speed were developed to characterize API polymorphs. One is SHGmicroscopy-guided Raman spectroscopy, which achieved the speed of 10 ms/particle for clopidogrel bisulfate. Initial classification of two different polymorphs was based on SHG images, followed acquisition of Raman spectroscopyat the selected positions to determine the API crystal form. Another approach is implementing of dynamic sampling into confocal Raman microscopy to accelerate Raman image acquisition for 6-folds. Instead of raster scanning, dynamic sampling algorithm enabled acquiring Raman spectra at the most informative locations. The reconstructed Raman image of pharmaceutical materials has <0.5% loss of image quality with 15.8% sampling rate.<br></p>

Apresentamos os resultados de preparação e caracterização de cristais orgânicos (L-arginina fosfatada monohidratada - LAP - e L-lisina monohidroclorada dihidratada - L-Lys.HCl) que possuem propriedades ópticas lineares e não lineares desejáveis para aplicações tecnológicas, incluindo telecomunicações, computação óptica, armazenamento óptico de dados, processamento óptico da imagem, conversão de freqüência, entre outras. Desenvolvemos uma metodologia, simples e barata, para a eliminação de fungos e micróbios que surgem nas soluções destes compostos devido às características dos aminoácidos L-arginina e L-lisina. A adição do fungicida azida de sódio possibilitou-nos manter soluções destes compostos livres de quaisquer microorganismos na câmara de crescimento por um período de seis meses. Usando-se as técnicas de evaporação controlada do solvente a abaixamento da temperatura grandes cristais de LAP e L-Lys.HCl foram obtidos com qualidade óptica adequada para a confecção de dispositivos optoeletrônicos. Cristais de até 6 cm&sup3 de L-Lys.HCl foram pela primeira vez preparados e caracterizados opticamente. A caracterização estrutural permitiu-nos solucionar a divergência existente na indexação do difratograma de pó dos cristais de LAP e indexar os picos de difração de raios-X da L-lisina monohidroclorada dihidratada. / Growth and characterization of organic crystal (L-arginine phosphate monohydrate - LAP - and L-lysine monohydrochloride dihydrate L-Lys. HCl) with desirable linear and nonlinear optical properties for technological application including telecommunications, optical computing, optical data storage, optical image processing, harmonic frequency generation, and others are presented. We developed a simple and cheap method to eliminate fungi and microbes that arises in solution due to characteristics of L-arginine and L-lysine aminoacids. The addition of sodium azide fungicide maintained the solutions of these compounds free of microorganisms in the growth chamber for six months. Using a accurately controlled solvent evaporation technique and slow cooling technique large crystals of LAP and L-Lys.HCI were obtained with optical quality appropriate to the development of optoelectronic devices. L-Lys.HCl crystals up to 6 cm&sup3 were growth and optically characterized for the first time. The divergence in the powder diffraction indexation of LAP crystals was eliminated by structural characterization and the X-ray diffraction peaks of the L-lysine monohydrochloride diliydrate crystals were indexed.

Neste trabalho é feito um estudo da formatação de pulsos ultracurtos de laser de Ti:Safira para a geração de segundo harmônico em cristal de KDP. Para a formatação dos pulsos, é utilizado um aparato que inclui um modulador espacial de luz de cristal líquido (LC SLM), que altera unicamente a fase espectral dos pulsos. Este aparelho tem a vantagem de não introduzir perdas durante a propagação da luz, além de sua ação ser controlada via computador, através de um software em LabVIEW. Utilizando uma função senoidal, é feito um estudo das limitações do controle da geração do segundo harmônico provindas da pixelação do LC SLM, isto é, do fato de que os elementos moduladores possuem tamanhos finitos e produzem uma modulação discreta ao longo das componentes espectrais do pulso. É apresentada a geração de luz sintonizável em torno de 400 nm por duplicação de frequências de pulsos cuja fase espectral é modulada por uma soma de funções senoidais de frequências diferentes. A largura de banda do ultravioleta produzido é da ordem de 1 nm, em contraste com a largura de linha de cerca de 12 nm do segundo harmônico gerado na ausência de modulação do pulso fundamental. A sintonização é feita basicamente através de uma varredura na fase das funções moduladoras do pulso fundamental. Esse tipo de sintonização nessa região do espectro possui algumas aplicações, tais como a microscopia seletiva por dois fótons ou mesmo a espectroscopia de um fóton. Para comprovar a utilidade da geração de segundo harmônico sintonizável, é apresentada uma medida espectroscópica da transmissão em uma amostra de cloreto de európio, sendo que os resultados obtidos concordaram com as medidas da mesma amostra realizadas em um espectrofotômetro, com o mínimo de transmissão em cerca de 394 nm. / This work presents a study on the shaping of ultrashort pulses of a Ti:Sapphire laser for second harmonic generation in KDP crystals. To achieve the pulse shaping, a setup based on a phase-only crystal-based spatial light modulator (LC SLM) is used. This device has the advantage of low loss, and can be computer controlled, by means of a LabVIEW software. The use of a sinusoidal function, allows to study the limitations of the second harmonic generation due to the pixelation of the LC SLM, i. e., due to the fact that the modulating elements have finite sizes and produce a stepwise modulation along the spectral components of the pulse. The generation of tunable light around 400 nm by frequency doubling of laser pulses is presented for the case where the spectral phase is modulated by a sum of sinusoidal functions with different frequencies. The linewidth of the ultraviolet band produced is narrower than 1 nm, in contrast to the 12 nm linewidth of the non-modulated incident spectrum. The tuning is done primarily through a sweep in the phase of the modulating functions of the fundamental pulse. The possibility of tuning in this region of the spectrum has a few applications, such as in selective two-photon microscopy or even in one photon spectroscopy. To demonstrate the usefulness of tunable second harmonic generation, a spectroscopic measurement of the transmission in a sample of europium chloride is presented, and the results agreed with the measures of those performed in a spectrophotometer, with the minimal transmission occurring around 394 nm.

Graduation date: 1995

Graduation date: 1994

Renewable forms of energy are becoming increasingly important as the world quickly depletes its current energy reserves, and rapidly increases the concentration of pollutants in our environment. Solar technology based on organic semiconductors provides a promising candidate to fulfill a portion of our future energy needs in an environmentally sustainable manner. Organic semiconductors are a collection of pi-conjugated small molecules and polymers which can be implemented in photovoltaic cells that are potentially quite low cost. Currently, however, their commercial applications are limited due to a relatively low efficiency in converting sunlight into usable power. The fundamental physics of such devices must be clarified if these materials are to compete with traditional inorganic solar cells. In this dissertation, two emerging experimental tools are implemented in investigations of the internal electric fields present within operating organic photovoltaic cells. The first set of investigations utilizes the vibrational Stark effect to quantify the electric fields which often form at the interfaces between two organic semiconducting materials. Such interfaces are at the heart of the photocurrent generation process in these devices and any electric fields formed crucially alter device performance. We quantitatively determine the interfacial field present in blends of poly(3-hexylthiophene) (P3HT) and phenyl-C61-butyric acid methyl ester (PCBM) and show that this field depends strongly on annealing conditions. Finally we discuss a correlation between this interfacial electric field, crystalinity and device performance. The second set of investigations take advantage of electric field induced second harmonic generation microscopy to examine the electric potential across active organic solar cells. We again investigate blends of PCBM and P3HT as well as poly(4,4-dioctyldithieno(3,2-b:2',3'-d)silole)-2,6-diyl-alt-(2,1,3-benzothiadiazole)-4,7-diyl) (PSBTBT) and PCBM. In the former we find that the potential drop across the device shifts dramatically over time under illumination, while in the latter we find a nearly linear drop which remains constant through device operation. We then extend our examinations of PSBTBT:PCBM with EFISH by quantifying the extent of space charge accumulation throughout such devices. / text

Two applications of second harmonic generation (SHG), a nonlinear optical technique, are studied. First, Fresnel factors are used with a bond model to describe SHG from vicinal silicon at five incidence angles: 7.5°, 22°, 30°, 45°, and 52°. Second, a prototype apparatus for applying SHG to enhance imaging capabilities of optical coherence tomography, a microscopy technique used in many biological fields, is briefly described. / text

The design of nonlinear optical (NLO) molecules has become a focus of current research in telecommunications, information technologies and optical data storage. Donor-acceptor substituted dipolar molecules have been the most investigated NLO chromophores. Dipolar molecules, however, have several limitations such as low optical transparency, low thermal stability and their strong tendency to adopt anti-parallel packing in the solid state. Recently, a new class of materials based on octupolar symmetries, which lack permanent dipole moments, has been proposed for NLO applications. At a structural level, it can be shown that the basic template for 3D octupolar molecules comes to a cube with alternating charges at the corners such as donor and acceptor substituent. Despite all the various structures reported, it is worth noting that no molecules actually representing the "real" octupolar cube have been obtained so far. In this thesis, we showed that the real octupolar cube can be demonstrated by lanthanide III complexes based on ABAB type phthalocyanine featuring alternating electron donor and electron acceptor groups. These structures are characterized by UV-NIR, X-Ray and exhibit highest quadratic hyperpolarizability ever reported for an octupolar molecule. Moreover, this work was extended to nonoctupolar lanthanide homoleptic double-decker complexes based on AB3, A4, B4, T4 type phthalocyanines. It was observed that these molecules present a quite large quadratic hyperpolarizability too, but smaller than the one obtained for the Ln(ABAB)2 series, as expected.

Conjugated polymers are promising candidates for applications in all kinds of organic optoelectronic devices: OLEDs, organic field-effect transistors (OFETs) and organic photovoltaic cells. The main goal of this work was to investigate transport features of photogenerated electrical charge in pi-conjugated polymers by means of novel technique based on time-resolved electric field-induced second harmonic generation (TREFISH). TREFISH measurement setup was implemented in the laboratory of Molecular compounds physics, and applicability of the method has been verified. Measurements were performed on three different model polymers: methyl substituted ladder-type poly(para-phenylene) (MeLPPP), poly(fluorene-co-benzothiadiazole) (F8BT) and poly(spirobifluorene-co-benzothiadiazole) (PSF-BT), having different morphological and chemical structure. It has been found that motion of photogenerated charge carriers in π-conjugated polymer films experiences rapid dynamics after excitation. Different time domains of charge transport were distinguished. Initial fast transport of photogenerated charge carriers corresponds to the carrier motion along the single polymer chain or conjugated segment of the polymer chain. Slowest carrier motion phase is well described by the stochastic drift, which is attributed to interchain jumps and determines the macroscopic equilibrium mobility. Thus, the equilibrium mobility value is not applicable to the transport on nanometer scale up to tens of nanometers... [to full text] / Konjuguotieji polimerai kaip funkcinės medžiagos gali būti panaudoti įvairiuose prietaisuose: organiniuose šviestukuose, organiniuose lauko tranzistoriuose, organiniuose saulės elementuose. Šio darbo tikslas - nustatyti fotogeneruotų krūvininkų pernašos dėsningumus π – konjuguotuose polimeruose panaudojant naują žadinimo-zondavimo metodą pagrįstą išoriniu elektriniu lauku indukuota antrosios optinės harmonikos generacija. Pagrindinis dėmesys buvo skiriamas pernašos dinamikai. Molekulinių darinių fizikos laboratorijoje buvo įrengta matavimų schema ir įvertintas metodo tinkamumas krūvio pernašos tyrimams. Buvo atlikti krūvio pernašos matavimai trijuose skirtinguose konjuguotuosiuose polimeruose. Nustatyta, kad fotogeneruotų krūvininkų judris tuoj po sužadinimo yra daug didesnis lyginant su stacionaria judrio verte, o krūvio pernašos dinamiką lemia konjuguoto polimero struktūrinė hierarchija, krūvininkų judėjimas yra daugialypis, susidedantis iš greito judėjimo viena polimero grandine ar konjuguotais polimero grandinės segmentais ir lėto šokavimo tarp atskirų polimero grandinių Pirmą kartą detaliai išnagrinėta šviesa sugeneruotų krūvininkų pernašos dinamika konjuguotuose polimeruose. Darbo rezultatai suteikia žinių apie fundamentalius krūvininkų pernašos mechanizmus konjuguotuose polimeruose, kurios gali būti panaudotos kuriant organinius elektronikos prietaisus.

This research uses nonlinear Rayleigh surface waves to characterize stress corrosion cracking (SCC) damage in sensitized 304 Stainless Steel (304 SS). 304 SS is widely used in reactor pressure vessels and fuel pipelines, where a corrosive environment in combination with applied stress due to high internal pressures can cause SCC. SCC poses great risk to these structures as it initiates cracks late in the lifetime and often unexpectedly. The initiated microcracks grow and accumulate very quickly to form macroscopic cracks that lead to material failure. Welds and the nearby heat affected zones (HAZ) in the vessels and pipework are particularly affected by SCC as welding induces sensitization in the material. SCC damage results in microstructural changes such as dislocation movement and microcrack initiation that in the long term lead to reduced structural integrity and material failure. Therefore, the early detection of SCC is crucial to ensure safe operation. It has been shown that the microstructural changes caused by SCC can generate higher harmonic waves when excited harmonically. This research considers different levels of SCC damage induced in samples of sensitized 304 SS by applying stress to a specimen held in a corrosive medium (Sodium Thiosulfate). Nonlinear Rayleigh surface waves are introduced in the material and the fundamental and the second harmonic waves are measured. The nonlinearity parameter that relates the fundamental and the second harmonic amplitudes, is computed to quantify the SCC damage in each sample. The results obtained are used to demonstrate the feasibility of using nonlinear Rayleigh waves to characterize SCC damage.