This work deals with a preparation of superparamagnetic nano- and microparticles with hydrophilic surfaces for bioapplications. The wok is divided into three parts in consonance with experimentally solved problem. First part describes a choice and an optimalization of synthesis of iron oxides nanoparticles with appropriate toxicological, morphological and physico-chemical properties, which surface can be post synthetically modified. Maghemite - γ-Fe2O3 particles were prepared by consequent oxidation of mangnetite - Fe3O4 as an initial substance for a preparation of materials for diagnostics and separations. A conventional alkaline coprecipitation method of magnetite preparation was modified to produce nanoparticles with narrowed size distribution without use of surfactants during their synthesis. Prepared maghemite nanoparticles were cca. 6 nm in diameter and their saturation magnetization was Ms ~ 70 A·m2 ·kg-1 . Such observed value is far higher in comparison with the state of the art and argues thus a proposition the Ms depends not on the preparation method, but only on the nanoparticles size. Maghemite nanoparticles morphology was evaluated by picture analysis of SEM and TEM micrographs, hydrodynamic size and zetapotential was measured with DLS. The structure of the maghemite was confirmed with...

[Truncated abstract] In the past decade, the synthesis of superparamagnetic iron oxide nanoparticles (SPIONs) has received considerable attention due to their potential applications in biomedical fields. However, success in size and shape control of the SPIONs has been mostly achieved through organic routes using large quantities of toxic or/and expensive precursors in organic reaction medium at high reaction temperature. This has limited the biomedical applications of SPIONs and therefore, development of a synthetic method under aqueous condition that is reproducible, scalable, environmentally benign, and economically feasible for industrial production is of paramount importance in order to fully realise their practical applications. Spinning Disc Processing (SDP) has been used to synthesise superparamagnetic magnetite (Fe3O4) nanoparticles at room temperature via a modified chemical precipitation method under continuous flow condition and offer a potential alternative to be applied to SPIONs production. SDP has extremely rapid mixing under plug flow conditions, effective heat and mass transfer, allowing high throughput with low wastage solvent efficiency. The synthesis process involves passing ammonia gas over a thin aqueous film of Fe2+/3+ which is introduced through a jet feed close to the centre of a rapidly rotating disc (500-2500 rpm). Synthetic parameters such as precursor concentrations, temperature, flow rate, disc speed, and surface texture influence the particle sizes. ... Magnetic silica microspheres are receiving great attention for possible applications in magnetic targeting drug delivery, bioseparation and enzyme isolation. However, the current available methods for preparation suffer from the setback of low loading of Fe3O4 nanoparticles in the silica microsphere, which result in low magnetic moment, thereby limiting their practical applications. Therefore it is of considerable importance to develop new alternative synthetic methods for fabricating magnetic silica microspheres with high magnetic nanoparticles loading. Superparamagentic Fe3O4 nanoparticles (8-10 nm diameter) and curcumin have been encapsulated in mesoporous silica in a simple multiplestep self assembly approach process with high Fe3O4 nanoparticles loading (37%). The synthesis involves loading of curcumin in the Cetyltrimethylammonium bromide (CTAB) micellar rod in the presence of superparamagnetic Fe3O4 nanoparticles via a parallel synergistic approach. The synthesised magnetic mesoporous silica composite material is stable, superparamagnetic with high saturation magnetisation before and after curcumin leaching experiment. Under physiological pH in phosphate buffer, the curcumin is slowly released over several days. These magnetic mesoporous silica are expected to have great potential as targeted drug delivery systems.

Materials on the nanoscale have very interesting properties. Hence, they are commonly used for a variety of applications such as drug delivery, bio-imaging and sensing devices. Moreover, coating these particles with other materials forming core@shell or Janus particles can further enhance their properties. However, for the particles to be used in medical and electronic devices, their properties such as size, shape and composition need to be precisely controlled. In this PhD., an emulsification technique was chosen to investigate the synthesis of nanoparticles; it is a simple process, does not require any harsh chemicals or temperature and is fast. Emulsification occurs when two or more immiscible liquids and surfactants are mixed. Here, emulsion droplets were produced using a microfluidic device which allowed for the creation of uniform droplets. These were employed as templates to synthesise and assemble nanomaterials. The main aim of the Ph.D. was to develop a droplet based synthesis process to generate nanoparticles and then assemble them into core@shell particles. This Ph.D., starts by synthesising Fe3O4 nanoparticles (~ 12 nm) and assembling them into microparticles (~ 1µm 2µm) using emulsion droplets as microreactors. By tuning the surfactant, droplet size and evaporation rate of the dispersed phase, microparticles of varying shapes and sizes, such as spherical or crumbled shapes, were produced. When these particles are compared with the commercially available particles, the magnetic content of the in-house particles, or sometimes referred to as Loughborough University Enterprises Ltd. (LUEL), are much higher and more uniform, hence resulting in faster separation when used for extraction of analytes. LUEL particles were supplied as part of commercial collaboration. The use of Pickering emulsions were then explored to create core@shell particles using gold nanoparticles instead of a surfactant to produce gold shells and the addition of pre-synthesised Fe3O4 nanoparticles results in Fe3O4@Au core@shell particles. This is the first time Pickering emulsions were used to produce Fe3O4@Au core@shell particles (~ 1.5 µm) within a microfluidic device. However, the shells were not uniform in thickness. In order to improve the coverage, nanoparticles were synthesised in situ at the droplet interface. By placing the gold chloride (AuCl4-) in the continuous phase and by varying the concentration of the electron donor in hexane droplet, single crystal gold nanoparticles and platelets were formed. The reaction is spontaneous at room temperature, creating gold nanoparticles at the interface of the emulsion droplet. The size and shape of the gold nanoparticles were controlled by varying the concentration of the reactants and the size of the droplets. By adding pre-synthesised particles (Fe3O4 nanoparticles) to the droplet, Au@Fe3O4 core@shell particles were formed with an approximate size of 250 nm. The same concept of forming core@shell particles using gold nanoparticles was further expanded by using other metal ions; palladium and silver. Unlike gold, palladium and silver only formed spherical nanoparticles, no platelets were observed. The addition of preformed iron oxide nanoparticles to the palladium results in core@shell particles. However, in the case of silver, no core@shell particles were formed. The study of the rate of reaction was conducted to understand the details of the mechanism. Overall, the process developed in this Ph.D. study allows for the facile synthesis of core@shell particles in a rapid, high throughput reaction. In the future, it is believed it could be scaled up for commercial purposes.

Atualmente, as nanopartículas superparamagnéticas despertam enorme interesse científico devido sua grande variedade de aplicações em biomedicina, tanto na área de diagnóstico quanto no tratamento de enfermidades. Embora muitos materiais vem sendo estudados, os óxidos de ferro (magnetita e maghemita) apresentam maiores avanços nos estudos para aplicações em medicina. A preferência por óxidos de ferro se deve a baixa toxicidade destas partículas quando comparado as nanopartículas metálicas ou ligas. Entretanto, as nanopartículas destes óxidos possuem baixas magnetizações de saturação que diminuem ainda mais com as sucessivas etapas de recobrimento necessárias para conferir funcionalidade a estas partículas. Desse modo, há uma necessidade atual para o desenvolvimento de nanopartículas superparamagnéticas com elevada magnetização, baixa toxicidade e maior facilidade de funcionalização da sua superfície com biopolímeros e agentes funcionalizantes. Neste trabalho, nanopartículas superparamagnéticas de cobalto metálico e ferrita de cobalto foram sintetizadas e suas propriedades magnéticas foram comparadas com a magnetita. Nanopartículas de cobalto foram escolhidas, pois seu elevado comportamento ferromagnético é menor apenas que o ferro metálico, além do baixo custo de seus reagentes. As nanopartículas magnéticas foram sintetizadas pelos métodos de microemulsão e decomposição térmica (baseado no método poliol) e suas composições química, estrutural, tamanho e distribuição de tamanho foram devidamente determinadas. Além disso, as nanopartículas de cobalto metálico e ferrita de cobalto foram recobertas com ouro utilizando o método de crescimento mediado por semente. Os sistemas microemulsionados utilizados neste trabalho não foram eficientes nem na síntese de nanopartículas estáveis de cobalto metálico nem no seu esperado controle morfológico. Já o método de decomposição térmica resultou em um rigoroso controle de composição química, estrutural e morfológico para as diferentes nanopartículas sintetizadas. O recobrimento com ouro foi efetivo na proteção do núcleo magnético e adicionalmente conferiu estabilidade, baixa toxicidade e bifuncionalidade às nanopartículas magnéticas através do seu fenômeno de ressonância plasmônica de superfície o qual foi preservado na nanoestrutura core@shell. O comportamento superparamagnético das nanopartículas de cobalto metálico recobertas com ouro e sua elevada magnetização de saturação foram expressivamente intensificadas quando comparadas as nanopartículas de magnetita sem recobrimento. Portanto, as nanopartículas sintetizadas neste trabalho apresentam propriedades de superfície e magnéticas otimizadas demonstrando um bom potencial para aplicações em biomedicina como sensores bifuncionais óptico-magnético. / Superparamagnetic nanoparticles have been extensively studied because its wide range of biomedical applications in both diagnostic and therapy areas. Although different materials are currently investigated, superparamagnetic iron oxides nanoparticles (SPION), magnetite and maghemite, are the most extensively studied for applications in medicine. The lower toxicity profile of the SPION becomes the most attractive than metal or alloys nanoparticles. Nevertheless, iron oxides nanoparticles have low saturation magnetization, which further decreases due to successive coats to provide their functionality, leading the actual demand to develop superparamagnetic nanoparticles with high magnetization, low toxicity and easy surface functionalization with biocompatible agents. In this work, superparamagnetic nanoparticles of metallic cobalt and cobalt ferrite were synthesized and their magnetic properties were compared with the magnetite SPION. Cobalt nanoparticles were chosen because present high ferromagnetic behavior among chemical elements, second only to iron, besides their low cost. The magnetic nanoparticles were synthesized by both microemulsion and thermal decomposition (based on the polyol process) methods and their chemical composition, structure, size and size distribution were properly characterized. In addition, the ferrite and metallic cobalt nanoparticles were coated with gold by using the seed-mediated growth method. The used microemulsion systems were not efficient enough to synthesize stable metallic nanoparticles and to promote the expected morphological control even to ferrites. Instead, the thermal decomposition processes resulted in rigorous control of chemical compositional, structure and morphology in all different prepared samples. Au-coating process was effective to protect the magnetic nuclei also giving additional stability, low toxicity and a bifunctionality to the magnetic nanoparticle since their surface plasmon resonance phenomenon was preserved in the core@shell nanostructure. The superparamagnetic behavior of the Au-coated cobalt nanoparticle was preserved and their saturation magnetization was significantly increased compared with the naked magnetite SPION. In conclusion, the synthesized nanoparticles present enhanced magnetic and surface properties showing good potential to be used in biomedical application as bifunctional optical-magnetic sensor.

Esta tese descreve o desenvolvimento de aplicações de nanopartículas superparamagnéticas de magnetita, devidamente funcionalizadas, nas seguintes áreas: Sensoriamento - As nanopartículas superparamagnéticas foram utilizadas em conjunto com um pequeno sistema analítico especialmente desenvolvido para esse trabalho, na análise de diversos metais pesados de grande relevância ambiental. O ponto de destaque da metodologia é o grande incremento em intensidade do sinal analítico em função da pré-concentração que pode ser realizada mediante utilização das nanopartículas superparamagnéticas e aplicação de um campo magnético externo. Remediação ambiental - A grande afinidade das nanopartículas por diversos materiais foi aproveitada na obtenção de um sistema de remediação ambiental que combina as propriedades magnéticas das nanopartículas e as propriedades adsorventes de carvão ativado. Esse sistema foi testado em contaminantes orgânicos e inorgânicos e permite uma maneira eficiente e inovadora de remoção de contaminantes em meio aquoso. Nanohidrometalurgia magnética - Os efeitos de pré-concentração de nanopartículas superparamagnéticas modificadas foram utilizados para melhorar a eficiência dos processos hidrometalúrgicos atuais para produção de cobre metálico a partir de minérios com baixa concentração do metal, chegando - se ao estado da arte da técnica. / This thesis describes the development of applications of superparamagnetic magnetite nanoparticles, properly functionalized, in the following areas: Sensing - The superparamagnetic nanoparticles were used in conjunction with a small analytical system specially developed in this work for analysis of several heavy metals of great environmental significance. The important point of this methodology is the general increase in intensity of the analytical signal as a function of pre-concentration may be performed by use of superparamagnetic nanoparticles under the influence of an external magnetic field. Environmental Remediation - The high affinity of nanoparticles for various materials was used to obtain an environmental remediation system that combines the properties of magnetic nanoparticles and the properties of activated carbon adsorbents. This system was tested in organic and inorganic contaminants and provides a novel and efficient removal of contaminants in the aqueous medium. Magnetic Nanohydrometalurgy - The effects of pre-concentration fro the funcionalized superparamagnetic nanoparticles modified were used to improve the efficiency of the actual hydrometallurgical processes used for production of metallic copper from ores with low concentration of metal, showing good perspectives of improving the state of the art of this technique.

Esta tese descreve o desenvolvimento de aplicações de nanopartículas superparamagnéticas de magnetita, devidamente funcionalizadas, nas seguintes áreas: Sensoriamento - As nanopartículas superparamagnéticas foram utilizadas em conjunto com um pequeno sistema analítico especialmente desenvolvido para esse trabalho, na análise de diversos metais pesados de grande relevância ambiental. O ponto de destaque da metodologia é o grande incremento em intensidade do sinal analítico em função da pré-concentração que pode ser realizada mediante utilização das nanopartículas superparamagnéticas e aplicação de um campo magnético externo. Remediação ambiental - A grande afinidade das nanopartículas por diversos materiais foi aproveitada na obtenção de um sistema de remediação ambiental que combina as propriedades magnéticas das nanopartículas e as propriedades adsorventes de carvão ativado. Esse sistema foi testado em contaminantes orgânicos e inorgânicos e permite uma maneira eficiente e inovadora de remoção de contaminantes em meio aquoso. Nanohidrometalurgia magnética - Os efeitos de pré-concentração de nanopartículas superparamagnéticas modificadas foram utilizados para melhorar a eficiência dos processos hidrometalúrgicos atuais para produção de cobre metálico a partir de minérios com baixa concentração do metal, chegando - se ao estado da arte da técnica. / This thesis describes the development of applications of superparamagnetic magnetite nanoparticles, properly functionalized, in the following areas: Sensing - The superparamagnetic nanoparticles were used in conjunction with a small analytical system specially developed in this work for analysis of several heavy metals of great environmental significance. The important point of this methodology is the general increase in intensity of the analytical signal as a function of pre-concentration may be performed by use of superparamagnetic nanoparticles under the influence of an external magnetic field. Environmental Remediation - The high affinity of nanoparticles for various materials was used to obtain an environmental remediation system that combines the properties of magnetic nanoparticles and the properties of activated carbon adsorbents. This system was tested in organic and inorganic contaminants and provides a novel and efficient removal of contaminants in the aqueous medium. Magnetic Nanohydrometalurgy - The effects of pre-concentration fro the funcionalized superparamagnetic nanoparticles modified were used to improve the efficiency of the actual hydrometallurgical processes used for production of metallic copper from ores with low concentration of metal, showing good perspectives of improving the state of the art of this technique.

Nano-sized particles are widely regarded as a tool to study biological events at cellular and molecular levels. However, there are only a few imaging modalities that can visualize interactions between nanoparticles and living cells. A new technique -- pulsed magneto-motive ultrasound imaging, capable of in-vivo imaging of magnetic nanoparticles at improved depth and in real-time is introduced in this study. In pulsed magneto-motive ultrasound imaging, an external high-strength pulsed magnetic field is applied to induce motion within magnetically labeled tissue and ultrasound is used to detect the induced internal tissue motion. A laboratory prototype of a pulsed magneto- motive ultrasound imaging system was built, tested and optimized through modeling and experimental studies using tissue-mimicking phantoms, ex-vivo tissue samples and in- vivo mouse tumor model. The results demonstrated a sufficient contrast between normal and iron-laden tissue labeled with ultra-small magnetic nanoparticles. Finally, further modifications and research directions are discussed which can eventually lead to development of a clinically applicable pulsed magneto-motive ultrasound imaging system. / text

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Porphyrins are very attractive system to study self-assembly due to its basic structure, chemical and thermal stability, synthetic versatility and important technological applications. This work presents the development of self-assembled systems meso-porphyrin derived from cardanol, the major constituent of the LCC. We were developed Langmuir and Langmuir-Blodgett (LB) thin films and superparamagnetic nanosystems coated with meso-porphyrin. The Langmuir films showed molecular area mean of the 177 à 2 confirmed by compressibility modulus. The 700 nm band observed in the Langmuir films supports the coexistence of monomers and dimers similar to the spectra of the solution (CHCl3/CH3COOH). The Brewster angle microscopy measurements showed formation of bright block domains with different sizes and shapes for the monolayer that disappears after surface pressure starts to increase. The UVâvis spectra of the Langmuir films and FTIR reflection of the LangmuirâBlodgett films (LB) indicated that the molecules exhibit preferential orientation with the parallel planes to the water (Langmuir) and in the substrate (LB). The LB film of 5 layers showed better response as electrode and has been tested as a promethazine sensor. Magnetic Fe 3 O 4 nanoparticles with an average size of 11 nm were coated with oleic acid layer and a meso-porphyrin layer to producing a novel superparamagnetic fluorescent nanosystem. Also were obtained systems coated with meso-porphyrins metallated with Co2+, Ni2+, Cu2+ and Zn2+ ions. The systems were characterized by TEM, FT-IR, TGA, vibrating sample magnetometry, UV-Vis, fluorescence and confocal miscroscopy. The systems showed good thermal stability, excellent magnetization and nanosized dimensions. / Porfirinas sÃo sistemas muito atrativos para estudos de automontagem graÃas a suaestrutura ba se, estabilidadequÃmica e tÃrmica, versatilidade sintÃtica e importantes aplicaÃÃes tecnolÃgicas. Este trabalho tem por finalidade apresentar o desenvolvimento de sistemas automontados da meso-porfirina derivada do cardanol, constituinte majoritÃrio do LCC. Foram desenvolvidos filmes finos de Langmuir e Langmuir-Blodgett (LB) e aplicado como sensor eletroquÃmico para prometazina e nanossistemas superparamagnÃticos revestidos com a meso-porfirina. Os filmes de Langmuir apresentaram Ãrea molecular mÃdia de 177 à 2 , confirmado pelo mÃdulo de compressibilidade. A banda centrada em λ = 700 nm observados nos filmes suporta a coexistÃncia de monÃmeros e dÃmeros semelhantes aos espectros em soluÃÃo de CHCl3/CH3COOH. A microscopia do Ãngulo de Brewster mostrou domÃnios com blocos brilhantes de diferentes tamanhos e formas para a monocamada que desapareceram apÃs o aumento da pressÃo de superfÃcie. Os espectros de UV-vis dos filmes e FT-IR no modo reflexÃo dos filmes de Langmuir-Blodgett (LB) indicaram que as molÃculas apresentam orientaÃÃo preferencial com os planos paralelos à Ãgua (no Langmuir) e no substrato (LB). O filme LB de 5 camadas apresentou melhor resposta como eletrodo e foi testado como um sensor de prometazina. As nanopartÃculas magnÃticas de Fe 3 O 4 com tamanho mÃdio de 11 nm foram revestidos com uma camada de Ãcido oleico seguido da meso-porfirina produzindo um novo nanossistema superparamagnÃtico fluorescente. Foram obtidos tambÃm os sistemas revestidos com porfirinas metaladas com os Ãons Co2+, Ni2+, Cu2+ e Zn2+, os quais foram caracterizados por MET, FT-IR, anÃlise termogravimÃtrica, magnetometria de amostra vibrante, UV-Vis, emissÃo de fluorescÃncia e miscroscopia confocal. Os resultados mostraram que os sistemas apresentaram boa estabilidade tÃrmica, comportamento superparamagnÃtico e dimensÃes nanomÃtricas.

Atualmente, as nanopartículas superparamagnéticas despertam enorme interesse científico devido sua grande variedade de aplicações em biomedicina, tanto na área de diagnóstico quanto no tratamento de enfermidades. Embora muitos materiais vem sendo estudados, os óxidos de ferro (magnetita e maghemita) apresentam maiores avanços nos estudos para aplicações em medicina. A preferência por óxidos de ferro se deve a baixa toxicidade destas partículas quando comparado as nanopartículas metálicas ou ligas. Entretanto, as nanopartículas destes óxidos possuem baixas magnetizações de saturação que diminuem ainda mais com as sucessivas etapas de recobrimento necessárias para conferir funcionalidade a estas partículas. Desse modo, há uma necessidade atual para o desenvolvimento de nanopartículas superparamagnéticas com elevada magnetização, baixa toxicidade e maior facilidade de funcionalização da sua superfície com biopolímeros e agentes funcionalizantes. Neste trabalho, nanopartículas superparamagnéticas de cobalto metálico e ferrita de cobalto foram sintetizadas e suas propriedades magnéticas foram comparadas com a magnetita. Nanopartículas de cobalto foram escolhidas, pois seu elevado comportamento ferromagnético é menor apenas que o ferro metálico, além do baixo custo de seus reagentes. As nanopartículas magnéticas foram sintetizadas pelos métodos de microemulsão e decomposição térmica (baseado no método poliol) e suas composições química, estrutural, tamanho e distribuição de tamanho foram devidamente determinadas. Além disso, as nanopartículas de cobalto metálico e ferrita de cobalto foram recobertas com ouro utilizando o método de crescimento mediado por semente. Os sistemas microemulsionados utilizados neste trabalho não foram eficientes nem na síntese de nanopartículas estáveis de cobalto metálico nem no seu esperado controle morfológico. Já o método de decomposição térmica resultou em um rigoroso controle de composição química, estrutural e morfológico para as diferentes nanopartículas sintetizadas. O recobrimento com ouro foi efetivo na proteção do núcleo magnético e adicionalmente conferiu estabilidade, baixa toxicidade e bifuncionalidade às nanopartículas magnéticas através do seu fenômeno de ressonância plasmônica de superfície o qual foi preservado na nanoestrutura core@shell. O comportamento superparamagnético das nanopartículas de cobalto metálico recobertas com ouro e sua elevada magnetização de saturação foram expressivamente intensificadas quando comparadas as nanopartículas de magnetita sem recobrimento. Portanto, as nanopartículas sintetizadas neste trabalho apresentam propriedades de superfície e magnéticas otimizadas demonstrando um bom potencial para aplicações em biomedicina como sensores bifuncionais óptico-magnético. / Superparamagnetic nanoparticles have been extensively studied because its wide range of biomedical applications in both diagnostic and therapy areas. Although different materials are currently investigated, superparamagnetic iron oxides nanoparticles (SPION), magnetite and maghemite, are the most extensively studied for applications in medicine. The lower toxicity profile of the SPION becomes the most attractive than metal or alloys nanoparticles. Nevertheless, iron oxides nanoparticles have low saturation magnetization, which further decreases due to successive coats to provide their functionality, leading the actual demand to develop superparamagnetic nanoparticles with high magnetization, low toxicity and easy surface functionalization with biocompatible agents. In this work, superparamagnetic nanoparticles of metallic cobalt and cobalt ferrite were synthesized and their magnetic properties were compared with the magnetite SPION. Cobalt nanoparticles were chosen because present high ferromagnetic behavior among chemical elements, second only to iron, besides their low cost. The magnetic nanoparticles were synthesized by both microemulsion and thermal decomposition (based on the polyol process) methods and their chemical composition, structure, size and size distribution were properly characterized. In addition, the ferrite and metallic cobalt nanoparticles were coated with gold by using the seed-mediated growth method. The used microemulsion systems were not efficient enough to synthesize stable metallic nanoparticles and to promote the expected morphological control even to ferrites. Instead, the thermal decomposition processes resulted in rigorous control of chemical compositional, structure and morphology in all different prepared samples. Au-coating process was effective to protect the magnetic nuclei also giving additional stability, low toxicity and a bifunctionality to the magnetic nanoparticle since their surface plasmon resonance phenomenon was preserved in the core@shell nanostructure. The superparamagnetic behavior of the Au-coated cobalt nanoparticle was preserved and their saturation magnetization was significantly increased compared with the naked magnetite SPION. In conclusion, the synthesized nanoparticles present enhanced magnetic and surface properties showing good potential to be used in biomedical application as bifunctional optical-magnetic sensor.

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