Laser technologies have made distinguished contributions to modern industry. These have typically been realised through the important role played by lasers in the advancement of manufacturing technology in many areas such as welding, which has become an important joining technique and thus promoted the use of lasers in a wide variety of applications in the oil, gas, aerospace, aircraft, automotive, electronics and medical industries. A detailed review of previous work in the use of lasers for advanced manufacturing, and in particular, laser beam welding is given. The work reported in this thesis aims to develop a new method of laser welding. This is connected with investigations relating to the production of net shape welds for bead-on-plate welding and butt welding of mild steel plates. Based on the nature of its operation, use of a fibre laser was considered most suitable compared to other solid state lasers. Net-shape welds were demonstrated on mild steel plates using an IPG 1 kW single mode fibre laser with a maximum power output of 1000 W.The thesis shows results from experimental and modelling (based on finite element and computational fluid dynamic modelling) to validate the idea and the understanding of underlying scientific principles. The thesis is presented in the form of a collection of published work generated by the author during the course of this project. In addition, some results that are not yet published are also included. Design of experiments and statistical modelling has been used in the experimental work to understand the process parameter interactions. Microstructural and mechanical testing have been carried out to evaluate the performance of the welds. Net shaped (the weld bead is flat to the parent material surface) welds have been achieved and compared with standard welds. The understanding of net-shape weld formation and the effect of the laser welding parameters was enhanced by the theoretical modelling. The thesis concludes with a summary of scientific findings and an overview of future work.

Indiana University-Purdue University Indianapolis (IUPUI) / Suboptimal dosing of anti-microbial agents increases the likelihood of therapeutic failure and resistance. Dosing optimization, while an attractive approach to combat these issues, is difficult to implement due to the different pharmacokinetics of each individual. These limitations highlight the inadequacies of a “standardized” dosing strategy. Therapeutic drug monitoring (TDM) provides a tailored treatment for individuals while avoiding adverse side effects from compounds with a narrow therapeutic window where elevated concentrations of a drug cause organ toxicity. This strategy involves accurately measuring the concentration of the analyte and interpreting the results based on pharmacokinetic parameters. Clinicians then draw conclusions regarding dose adjustment for their patient. However, TDM is expensive and difficult to perform because measurements occur in biofluids. Rapid and robust methods are necessary to quantify antimicrobial agents at the institutional level to guide patient care toward improved outcomes in serious infection. Paper spray ionization (PS), an emerging ambient ionization technique for clinical settings, demonstrations a wide versatility both in analyte variety and applications. This technique offers a rapid, accurate method to analyze these compounds with low rates of false positives even when multiplexing. The work herein explains the method development of assays for TDM of various antimicrobial agents. Chapters two and three describe ways to improve the quantitative capability of paper spray through substrate pre-treatment, modification, and manipulation of key factors. Chapter four describes real-world applications for paper spray utility in clinical settings with the cross-validation of antifungal agents against a “gold standard” method. The final chapter, while not clinical based, describes the method development process for a LC-MS/MS assay to detect urobilinoids in fly guts.

Tooling design is crucial for the production of cost-effective and durable composite products. As part of the current search for cost reduction (by reducing capital investment, energy use and cycle time), integrally-heated tooling is one of the technologies available for ‘out-of-autoclave’ processing of advanced thermoset polymer composites. Despite their advantages, integrally-heated tools can suffer from uneven distribution of temperature, variability in heat flow rate and inconsistency in heating/cooling time. This research, therefore, investigates a number of design variables such as shape and layout of heating channels in order to improve the heating performance of an integrally-heated tool. Design of Experiments (DoE) has been carried out using Taguchi’s Orthogonal Array (OA) method to set several combinations of design parameters. Each of these design combinations has been evaluated through numerical simulation to investigate heating time and mould surface temperature variation. The simulation results suggest that the layout of the channels and their separation play a vital role in the heating performance. Signal-to-Noise (S/N) ratio and analysis of variance (ANOVA) have been applied to the results obtained to identify the optimal design combination of the integrally-heated tool. Statistical analysis reveals that the heating performance of an integrally-heated tool can be significantly improved when the channels’ layout is parallel. The shape of the channels has negligible effect and the distance between the channels should be determined based on the production requirement. According to the predicted optimal design, a developed integrally water-heated tool is manufactured. The actual thermal properties of the constituent materials of the produced tool are also measured. Then a numerical model of the experimental tool model is simulated in ANSYS software, with setting the actual material properties and boundary condition to define the temperature uniformity and heating rate of the experimental tool. Comparison of the experimental and numerical results of the experimental tool confirmed the well assigning of the boundary conditions and material properties during simulation the heated tool. The experimental results also confirmed the predicted optimal design of the integrally heated tool. Finally, in order to define its thermomechanical behaviour under the effective (in service) thermal loads, a tool model is simulated. Numerical results presented that the produced extremes of thermal deformation, elastic strain, normal and plane shear stresses, under the effective thermal loading, are within the allowable elastic limits of the participated materials.

This thesis deals with the possibility of applying the method of Design of Experiments (DoE) on specific data. In the first chapter of theoretical part, this method is described in detail. The basic principles and guidelines for the design of the experiment are written there. In the next two chapters, factorial design of the experiment and response surface design are described. The latter one includes a central composite design and Box-Behnken design. The following chapter contains practical part, which focuses on modelling firing range of ball from a catapult using the above three types of experimental design. In this work, the models are analysed together with their different characteristics. Their comparison is made by using prediction and confidence intervals and by response optimizing. The last part of the thesis comprises overall evaluation.

Work in this dissertation is motivated by reducing the design cost at the early design stage while maintaining high design accuracy throughout all design stages. It presents four key design methods to improve the performance of Efficient Global Optimization for multidisciplinary problems. First, a fidelity-calibration method is developed and applied to lower-fidelity samples. Function values analyzed by lower fidelity analysis methods are updated to have equivalent accuracy to that of the highest fidelity samples, and these calibrated data sets are used to construct a variable-fidelity Kriging model. For the design of experiment (DOE), a dynamic sampling method is developed and includes filtering and infilling data based on mathematical criteria on the model accuracy. In the sample infilling process, multi-objective optimization for exploitation and exploration of design space is carried out. To indicate the fidelity of function analysis for additional samples in the variable-fidelity Kriging model, a dynamic fidelity indicator with the overlapping coefficient is proposed. For the multidisciplinary design problems, where multiple physics are tightly coupled with different coupling strengths, multi-response Kriging model is introduced and utilizes the method of iterative Maximum Likelihood Estimation (iMLE). Through the iMLE process, a large number of hyper-parameters in multi-response Kriging can be calculated with great accuracy and improved numerical stability. The optimization methods developed in the study are validated with analytic functions and showed considerable performance improvement. Consequentially, three practical design optimization problems of NACA0012 airfoil, Multi-element NLR 7301 airfoil, and all-moving-wingtip control surface of tailless aircraft are performed, respectively. The results are compared with those of existing methods, and it is concluded that these methods guarantee the equivalent design accuracy at computational cost reduced significantly. / Doctor of Philosophy / In recent years, as the cost of aircraft design is growing rapidly, and aviation industry is interested in saving time and cost for the design, an accurate design result during the early design stages is particularly important to reduce overall life cycle cost. The purpose of the work to reducing the design cost at the early design stage with design accuracy as high as that of the detailed design. The method of an efficient global optimization (EGO) with variable-fidelity analysis and multidisciplinary design is proposed. Using the variable-fidelity analysis for the function evaluation, high fidelity function evaluations can be replaced by low-fidelity analyses of equivalent accuracy, which leads to considerable cost reduction. As the aircraft system has sub-disciplines coupled by multiple physics, including aerodynamics, structures, and thermodynamics, the accuracy of an individual discipline affects that of all others, and thus the design accuracy during in the early design states. Four distinctive design methods are developed and implemented into the standard Efficient Global Optimization (EGO) framework: 1) the variable-fidelity analysis based on error approximation and calibration of low-fidelity samples, 2) dynamic sampling criteria for both filtering and infilling samples, 3) a dynamic fidelity indicator (DFI) for the selection of analysis fidelity for infilled samples, and 4) Multi-response Kriging model with an iterative Maximum Likelihood estimation (iMLE). The methods are validated with analytic functions, and the improvement in cost efficiency through the overall design process is observed, while maintaining the design accuracy, by a comparison with existing design methods. For the practical applications, the methods are applied to the design optimization of airfoil and complete aircraft configuration, respectively. The design results are compared with those by existing methods, and it is found the method results design results of accuracies equivalent to or higher than high-fidelity analysis-alone design at cost reduced by orders of magnitude.

Os protetores solares (PS) são os grandes responsáveis pela proteção da pele quando exposta à radiação solar, por isso a importância sanitária de se otimizar o desenvolvimento deste cosmético tipo II e monitorar para que seja eficaz em seu propósito. O principal objetivo deste trabalho é aplicar os conceitos de Qualidade por Design (QbD), ferramentas estatísticas de desenho experimental (DoE - Design of Experiments) e o conceito de tecnologia analítica de processo (PAT - Process Analytical Technology) para desenvolver uma formulação e processo produtivo de um PS de modo a modernizar os processos da indústria cosmética, fazendo as análises durante o processo e eliminando o controle de qualidade final. Trata-se de um sistema de desenvolvimento sistematizado, onde se executa as ferramentas de QbD para avaliar os dados obtidos ao longo da fase experimental. Para a fase experimental, empregou-se o desenho fatorial e desenho do compósito central (CCD - Central Composite Design) como ferramenta estatística, para a execução do planejamento de experimentos (DoE - Design of Experiments). As respostas foram analisadas através da metodologia de superfície resposta (RSM - Response Surface Methodology). Tais ferramentas são fundamentais para a determinação do desenho de concepção (design space), para se obter o PS com as melhores características físico-químicas e de processo dentro do escopo delineado. Para o desenvolvimento da metodologia de análise in line, optou-se pela utilização da espectrometria UV, utilizando-se ferramentas como análise de regressão dos mínimos quadrados (PLS) devido a praticidade em transforma-la em uma ferramenta PAT, para isto, a quimiometria foi empregada para modelar sistemas que são desconhecidos e complexos, como um PS, e trazendo respostas diretas como a aprovação do produto antes de ser embalado, por exemplo. A abordagem apresentada baseia-se na construção da qualidade ao longo do desenvolvimento e otimização de PS e torna possível o monitoramento da qualidade em tempo real. / The sunscreens are great responsible for the skin protection when it is exposed to direct sunlight, so it means a great importance of health to optimize the development of type II cosmetic and monitor for it to be effective in its purpose. The objective of this work is to apply the concepts of Quality by Design and statistical tools of experimental design (DoE - Design of experiments), as well as applying the process analytical technology (PAT - Process Analytical Technology) concept for formulation and manufacturing process development of a topical sunscreen being able to modernize the cosmetic industry processing, including real time analyses and eliminating quarantine step, which waits analysis approval performed by the quality assurance, and then release the product for sale. As it is a systematic development, where critical quality attributes and risk assessment were performed to evaluate over obtained data. During experimental phase, the factorial design was used as a statistical tool for design of experiments implementation, and the responses were analyzed by response surface methodology (RSM - Response Surface Methodology). This mapping is critical to determination of the product design (design space), i.e. get sunscreen with the best physical and chemical characteristics and processing within the outlined scope. For in line methodology development, UV spectrometry was opted to be used due to less effort in sample preparation and due to great easiness to turn it into a PAT tool. For this, chemometrics was used, which brings together chemical and statistical elements to obtain three main elements: empirical modeling, multivariate modeling and chemical data, making it able to model systems that are unknown and complex, as a sunscreen, getting direct answers as product release approval before being packed, for example. The presented approach was based on the construction of quality throughout the sunscreen development and optimization making possible the real time quality monitoring.

Os protetores solares (PS) são os grandes responsáveis pela proteção da pele quando exposta à radiação solar, por isso a importância sanitária de se otimizar o desenvolvimento deste cosmético tipo II e monitorar para que seja eficaz em seu propósito. O principal objetivo deste trabalho é aplicar os conceitos de Qualidade por Design (QbD), ferramentas estatísticas de desenho experimental (DoE - Design of Experiments) e o conceito de tecnologia analítica de processo (PAT - Process Analytical Technology) para desenvolver uma formulação e processo produtivo de um PS de modo a modernizar os processos da indústria cosmética, fazendo as análises durante o processo e eliminando o controle de qualidade final. Trata-se de um sistema de desenvolvimento sistematizado, onde se executa as ferramentas de QbD para avaliar os dados obtidos ao longo da fase experimental. Para a fase experimental, empregou-se o desenho fatorial e desenho do compósito central (CCD - Central Composite Design) como ferramenta estatística, para a execução do planejamento de experimentos (DoE - Design of Experiments). As respostas foram analisadas através da metodologia de superfície resposta (RSM - Response Surface Methodology). Tais ferramentas são fundamentais para a determinação do desenho de concepção (design space), para se obter o PS com as melhores características físico-químicas e de processo dentro do escopo delineado. Para o desenvolvimento da metodologia de análise in line, optou-se pela utilização da espectrometria UV, utilizando-se ferramentas como análise de regressão dos mínimos quadrados (PLS) devido a praticidade em transforma-la em uma ferramenta PAT, para isto, a quimiometria foi empregada para modelar sistemas que são desconhecidos e complexos, como um PS, e trazendo respostas diretas como a aprovação do produto antes de ser embalado, por exemplo. A abordagem apresentada baseia-se na construção da qualidade ao longo do desenvolvimento e otimização de PS e torna possível o monitoramento da qualidade em tempo real. / The sunscreens are great responsible for the skin protection when it is exposed to direct sunlight, so it means a great importance of health to optimize the development of type II cosmetic and monitor for it to be effective in its purpose. The objective of this work is to apply the concepts of Quality by Design and statistical tools of experimental design (DoE - Design of experiments), as well as applying the process analytical technology (PAT - Process Analytical Technology) concept for formulation and manufacturing process development of a topical sunscreen being able to modernize the cosmetic industry processing, including real time analyses and eliminating quarantine step, which waits analysis approval performed by the quality assurance, and then release the product for sale. As it is a systematic development, where critical quality attributes and risk assessment were performed to evaluate over obtained data. During experimental phase, the factorial design was used as a statistical tool for design of experiments implementation, and the responses were analyzed by response surface methodology (RSM - Response Surface Methodology). This mapping is critical to determination of the product design (design space), i.e. get sunscreen with the best physical and chemical characteristics and processing within the outlined scope. For in line methodology development, UV spectrometry was opted to be used due to less effort in sample preparation and due to great easiness to turn it into a PAT tool. For this, chemometrics was used, which brings together chemical and statistical elements to obtain three main elements: empirical modeling, multivariate modeling and chemical data, making it able to model systems that are unknown and complex, as a sunscreen, getting direct answers as product release approval before being packed, for example. The presented approach was based on the construction of quality throughout the sunscreen development and optimization making possible the real time quality monitoring.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-04-12T21:33:19Z No. of bitstreams: 1 LEOPOLDO VIANA BATISTA NETO - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2575700 bytes, checksum: a10f0685285492d2302637ed070d9631 (MD5) / Made available in DSpace on 2018-04-12T21:33:19Z (GMT). No. of bitstreams: 1 LEOPOLDO VIANA BATISTA NETO - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2575700 bytes, checksum: a10f0685285492d2302637ed070d9631 (MD5) Previous issue date: 2014-08-28 / Filmes finos de Nitreto de titânio (TiN) e Nitreto de titânio-zircônio (TiZrN) foram depositados sobre substratos de aço inoxidável 316 usando o método de Sputtering RF para deposição dos filmes. O planejamento de experimentos (DOE) tem sido reconhecido como um método poderoso para otimizar um processo complexo na indústria. Os efeitos do presente estudo foram verificar a viabilidade e confiabilidade da aplicação do método DOE em processos de Sputtering RF, otimizar os parâmetros de processamento para o processo de deposição, identificando os parâmetros sensíveis que afetam a espessura da camada depositada (E.C.D) e a resistência à corrosão (Ecorr.). Para o método de Sputtering RF, dois parâmetros, a taxa e tempo de deposição foram escolhidos para serem os parâmetros do processo. Depois da deposição, a estrutura de camada depositada foi caracterizada por Difração de Raios X (DRX) e por Microscopia Eletrônica de Varredura (MEV). Após o ensaio de polarização, a corrosão foi realizada a fim de investigar a relação entre o início da corrosão e a espessura da camada depositada. A análise de variância (ANOVA) foi realizada para avaliar os parâmetros sensíveis e prever as condições ideais. Com base na análise estatística, os parâmetros mais sensíveis no processo de Sputtering RF foram tanto a taxa como o tempo de deposição do filme fino. As melhores condições de deposição foram a taxa de deposição máxima e tempo máximo. / Titanium nitride (TiN) and titanium-zirconium nitride (TiZrN) thin films were deposited on ASTM F 138 stainless steel substrates using de Sputtering RF methods. Design of experiment (DOE) has long been recognized as a powerful method to optimize a complex process in industry. The purposes of present study were to verify the feasibility and reliability of the application of DOE method on de Sputtering RF processes and optimize the processing parameters for the deposition process, in which the sensitive parameters that affected the film properties were also identified. For de Sputtering RF method, two parameters, deposition rate and time were chosen to be the operating parameters. After deposition, the thin film structure was characterized by X-ray diffraction (XRD), and high-resolution scanning electron microscopy (SEM). After the polarization test, the corrosion analysis was carried out in order to investigate the relationship between the corrosion initiation and the thickness of the deposited layer. The analysis of variance (ANOVA) was conducted to assess the sensitive parameters and predict the optimum conditions. Based on the statistical analysis, the most sensitive parameters in de Sputtering RF process were both the deposition rate and time. The optimum deposition conditions in each system were maximum deposition rate and time.

The purpose of this thesis work was to develop a headspace solid phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) method to detect volatile organic compounds (VOCs) in board samples and to statistically investigate potential correlation between chromatographic data and flavor data obtained from a trained panel. The developed method would hopefully serve as a complement to the already established routine analyses at Stora Enso and gain an increased understanding of which VOCs in the board influence its flavor properties. The impact of incubation time and adsorption time on the area under curve (AUC) was studied with a Design of Experiment screening using the software MODDE. The screening data showed a correlation between large AUC and low repeatability measured as relative standard deviation (RSD). The data was hard to fit to a model due to the large RSD values for the replicates, AUC for identified compounds as response gave an acceptable fit. The regression coefficients for the model showed that a longer adsorption time gave larger AUC, while incubation time had no significant impact on the response.  Instead of following up the screening with an optimization, the focus was shifted to improving the repeatability of the method, i.e. lowering the RSD. The high RSD was believed to mainly be the result of leakage of analytes and unstable temperature during adsorption, preventing the system from reaching equilibrium. Different heating options and capping options for the vial was tested. Septum in crimp cap ensured a gas tight seal for the vial, giving lower RSD values and larger AUC compared to the other alternatives, showing that there was indeed a leakage. Using oil bath ensured stable temperature during the adsorption and detection of a larger number of VOCs but created a temperature gradient in the vial due to it not being fully submerged in the oil. Oil bath gave larger AUC, but still high RSD due to the temperature gradient making the method sensitive to variance in fiber depth in the vial. The final method was performed with 2 g of board sample in a 20 ml headspace vial sealed with a crimp cap with septa. The incubation and adsorption were performed with the vial immersed in a 90-degree oil bath. 20 min incubation time was chosen based on the time it took to get a stable temperature gradient in the vial, and 20 minutes adsorption time was chosen as a good compromise between large AUC and low RSD. Compared to Stora Ensos routine analysis, the developed SPME method gave chromatograms with an improved signal-to-noise ratio for the base line and several more peaks with larger AUC. For the board sample used during method development, the SPME-method identified 34 VOCs, while the routine analysis only identified 12. The developed method was applied on 11 archived board samples of the same quality that were selected based on their original flavor properties, to get a large diversity of samples. Flavor analysis was performed by letting a trained flavor panel describe the flavor based on intensity and character of the water that had individually been in indirect contact with one of the 11 board sample for 24 h. Potential correlation between chromatographic data obtained with the developed method and the flavor experience described by the flavor panelists was statistically investigated with the multivariate analysis software SIMCA. The correlation study showed that a combination of 12 VOCs with short retention time are most likely the main source of off-flavor which of 5 could only be identified with the developed SPME method. VOCs with long retention time did not contribute to an off-flavor and might have a masking effect on flavor given by other VOCS, however not confirmed in this study. Furthermore, the age of the board samples proved to be a good indicator for prediction of the flavor intensity, whereas the total AUC of the samples was not. Possible correlation between detected VOCs in the samples and flavor character given by the flavor panel were seen, however the variation in the data and the sample set were too small, preventing from making conclusions on individual VOCs impact on the flavor experience. The developed HS-SPME-GC-MS method would serve as a complement to the already established routine analyses at Stora Enso and has slightly increased the understanding of which VOCs in the board influence the flavor properties