In this report you get to read about the goals, problems and end result, how the group took on the different areas and what boundaries we had. You will get an understanding of our background and what research we had to do.Furthermore the implementation of Artificial Intelligence combined with the optical spectrum and what obstacles we faced during the project. Finally you will read about our results, the improvement points we had on the project and what we would have done differently if we redid the project. How we succeeded in transforming the script and what could have been done to finish the AI. The group has worked together with Uppsala University and Peafowl Plasmonics to transform, optimize and implement Artificial Intelligence to regulate a pump to a microfluidic reactor. The microfluidic reactor is automated by a genetic algorithm which is the core of the project. The main goals of the project was to transform the code from 32-bit to 64-bit, fit the optical spectrum and implement AI to the GA. To reach the goals the project was divided into different stages; data collection, implementation, verification and presentation. The implementation started with the transformation which was successful when all the correct files were given, and the code could run in 64-bit in the laboratory in Ångström. Furthermore, when the TOOLBOX for the optical spectrum in MATLAB were working for both spherical and nonspherical particles, this part of the project was concluded. The last part about the AI implementation was not successful due to time and problems with lack of knowledge about the subject of AI. However, a conclusion could be drawn about the optimal way to implement the AI to the GA, where the strategy was to first run the GA to collect data, and then run the GA and artificial Neural Network in parallel.

O design de materiais na escala nanométrica está levando a sistemas com novas propriedades e aplicações as mais diversas, como em sistemas de diagnóstico e de tratamento inteligentes e sustentáveis. Melhorar a eficiência dos tratamentos de doenças através do desenvolvimento de fármacos mais eficientes e com menos efeitos colaterais, e agentes de contraste e de diagnóstico mais específicos e sensíveis para monitoramento preventivo precoce, é um dos principais objetivos da Nanomedicina. Todavia, a química de superfície necessária para realizar tais reações de funcionalização/conjugação de moléculas ainda está longe de ser adequadamente controlada, particularmente considerando-se a complexidade das biomoléculas e a estabilidade coloidal. Assim, nesta tese foram desenvolvidos processos de conjugação de nanopartículas de óxido de ferro (SPIONs) com um ou mais agentes co-funcionalizantes, gerando partículas mono, bi e multifuncionalizadas dispersáveis em meio aquoso. Os esforços foram concentrados no desenvolvimento de sistemas de diagnóstico e de entrega de fármacos baseados em nanopartículas, cujas propriedades precisam ser ajustadas pela conjugação de biomoléculas e espécies bioativas em sua superfície, num verdadeiro trabalho de engenharia a nível nanométrico/molecular. De fato, nanopartículas modificadas com moléculas co-funcionalizantes estabilizantes (glicerol-fosfato, glicose-fosfato, fosforiletanolamina, dopamina e tiron), agentes de vetorização que direcionam o nanoconjugado a células-alvo tumorais (ácido fólico e biotina), bem como com fármacos como metotrexato e ibuprofeno foram preparadas, e o efeito das mesmas sobre a eficiência de incorporação por células tumorais (HeLa e MCF-7) estudada. Os estudos de atividade biológica in vitro foram realizados em parceria com o Laboratório de Processos Fotoinduzidos e Interfaces (LPFI-IQUSP). Os resultadosobtidos confirmaram a possibilidade de se controlar a atividade biológica das nanopartículas por meio dos agentes funcionalizantes, abrindo perspectivas interessantes para o desenvolvimento de nanoagentes multifuncionais para teranóstica, conjugados com agentes de vetorização específicos (particularmente anticorpos e aptâmeros), além de agentes de contraste (radiofármacos, fluoróforos, contraste para IRM, etc.) e moléculas terapêuticas (antitumorais, anti-inflamatórios, dentre outros). Entretanto, diversos são os problemas associados aos processos químicos envolvendo a produção e funcionalização desses nanomateriais por processos convencionais em batelada, que tendem a ser demorados e apresentam dificuldade de controle dos parâmetros de reação e baixa reprodutibilidade, dificultando o escalonamento produtivo e a comercialização dos eventuais produtos. Uma estratégia promissora é o uso de reatores microfluídicos com projeto de canais adequado, além de atuadores e sensores que, juntos garantam excelente controle de processos e baixo consumo de energia e de reagentes. Assim, também foram desenvolvidos reatores microfluídicos para produção e funcionalização de nanopartículas de ouro, de forma a tornar os processos químicos programáveis, mais eficientes, controláveis e econômicos, em parceria com o Laboratório de Micromanufatura do Instituto de Pesquisas Tecnológicas (LMI-BIONANO/IPT). Essa parte do desenvolvimento foi realizando empregando a tecnologia de microfabricação em Low Temperature Co-fired Ceramics (LTCC), uma tecnologia versátil que possibilita a produção de dispositivos de diferentes geometrias em materiais cerâmicos de baixa reatividade e de baixo custo. Esses dispositivos podem tornar os processos de produção de nanopartículas multifuncionais dispersáveis suficientemente simples, versáteis e reprodutíveis para atender aos altos padrões de qualidade exigidos para produtos voltados para aplicações biomédicas / Materials design at nanoscale is leading us to intelligent systems with new properties and applications, such as more efficient diagnostic and treatment systems. Improving the treatment of diseases by the development of more specific and efficient drugs, displaying fewer or no side effects, conjugated with sensitive contrast/diagnostic agents for early preventive monitoring and treatment is one of the main goals of the Nanomedicine. However, the knowledge on surface chemistry required to perform such molecular functionalization/conjugation reactions still is far from being adequately controlled, particularly considering the complexity of biomolecules and reaching colloidal stability. Thus, in this thesis, processes of conjugation of iron oxide nanoparticles (SPIONs) with one or more co-functionalizing agents have been developed so as to generate mono, bi and multi-particles dispersible in aqueous medium. Efforts were specifically focused on the development of drug delivery and diagnostic systems based on nanoparticles whose properties must be adjusted by the conjugation of biomolecules and bioactive species on their surface, in a truly nano/molecular scale engineering work. In fact, nanoparticles modified with stabilizing co-functionalizing molecules (glycerolphosphate, glucose-phosphate, phosphorylethanolamine, dopamine and tiron), targeting agents (folic acid and biotin) to guide itself and concentrate in specific tumor cells, as well as with drugs such as methotrexate and ibuprofen were prepared, and their effect on the efficiency of uptake by tumor cells (HeLa and MCF-7) studied. In vitro biological activity studies were performed in collaboration with the Laboratory of Photo Induced Processes and Interfaces (LPFI-IQUSP). The results confirmed the possibility of controlling the biological activity of nanoparticles by anchoring suitable functionalizing agents in an additive way, opening interesting new perspectives for the development ofmultifunctional theranostics nanoagents, conjugated with specific vectorization agents (particularly antibodies and aptamers), as well as diagnostic (radiopharmaceuticals, fluorophores, MRI contrast, etc.) and therapeutic agents (antitumor, anti-inflammatory, among others). However, there are several problems associated with the production and functionalization of these nanomaterials by conventional batch processes, which tend to be time consuming and difficult to control, as confirmed by their low reproducibility, making it difficult to produce and commercialize the eventual products. A promising strategy is the use of microfluidic reactors with suitable channel designs, as well as actuators and sensors that, together, ensure excellent process control and low energy and reagent consumption. Thus, microfluidic reactors were also developed for the production and functionalization of gold nanoparticles in order to make chemical processes more predictable, efficient, controllable and economical, in partnership with the Micromanufacturing Laboratory of the Institute of Technological Research (LMI-BIONANO/IPT). This part of the development was accomplished by employing the Low Temperature Co-fired Ceramics (LTCC) microfabrication technology, a versatile technology that enables the production of devices of different geometries in ceramic materials of low reactivity and of low cost. These devices can make the production processes of dispersible multifunctional nanoparticles simple, versatile and reproducible enough to meet the high standards of quality required for products for biomedical applications