Rozprawy doktorskie na temat „Potential of nano and micro particles”

Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2008.
Title from electronic title page (viewed Jun. 26, 2009). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Chemistry." Discipline: Chemistry; Department/School: Chemistry.

Les systèmes à délivrance de médicaments sont des technologies conçues pour administrer des molécules actives de façon optimisée afin d’améliorer leurs effets thérapeutiques tout en minimisant les effets secondaires. En effet, ces systèmes permettent une libération au niveau d’une cible thérapeutique. Les particules de type «cage» ont récemment attiré une attention particulière en raison de leur capacité accrue à (co)incorporer et à protéger des molécules actives vis-à-vis de dégradations in vivo. Les cyclodextrines (CDs) sont des exemples type de molécules "cage", possédant une cavité hydrophobe et une surface extérieure hydrophile. Nous avons élaboré tout d’abord des assemblages supramoléculaires à base de CDs d'environ 100 nm par une méthode douce consistant à mélanger deux solutions aqueuses de polymères neutres : 1) polymère de β-CD et 2) dextrane greffé avec la benzophénone, molécule invitée formant des complexes d’inclusion avec les CDs. La procédure de préparation « verte» en une seule étape rend la formulation attractive, malgré sa relativement faible capacité d’encapsulation (5%pds). Afin d'améliorer cete charge, nous avons élaboré des particules hybrides organiques-inorganiques (MOFs) à base de CDs. Avantageusement, les CD-MOF comportent non seulement des cavités de CD, mais aussi de larges pores engendrés lors l’auto-assemblage de CDs. Le lansoprazole a été incorporé avec succès (23%pds) dans les CD-MOFs et nous avons montré que chaque CDs était capable d’accueillir une molécule de principe actif. Cependant, l’inconvénient majeur des CD-MOFs est leur faible stabilité en milieu aqueux, limitant leur domaine d’application. Une modification de surface est apparue donc nécessaire pour améliorer leur stabilité. Notre stratégie a été d’incorporer les CD-MOFs dans des matrices d'acide polyacrylique (PAA). Des microsphères composites d’environ 650 nm ont été élaborées avec succès et ont permis une bonne stabilité et une libération prolongée sur plus de 48 h. Avantageusement, ces particules composites n’étaient pas toxiques in vitro même à des concentrations élevées. Ainsi, nous nous sommes orientés vers l’étude comparative de MOFs plus stables dans l’eau, à base de trimesate de fer. Les MIL-100 (Fe) (Material of Institute Lavoisier) figurent parmi les premiers MOF étudiés en tant que nanomédicaments (nanoMOFs). Ces particules, parfaitement stables dans l'eau, se dégradent dans des milieux contenant des phosphates en perdant rapidement leur caractère cristallin et leurs ligands constitutifs. De façon étonnante, nous avons constaté que malgré leur dégradation, ces MOFs conservent leur taille intacte. Une analyse approfondie basée sur la microscopie de Raman a permis d’obtenir des informations pertinentes sur la morphologie et la composition chimique de particules individuelles. Ainsi, il a été montré qu’un front d'érosion délimitait nettement un cœur intact et une coquillé inorganique érodée. Cependant, ni l’encapsulation ni la modification de surface des MOFs n’altérait leur intégrité. Enfin, nous avons étudié la co-encapsulation de deux molécules actives utilisées en combinaison (amoxicilline et clavulanate de potassium) dans les nanoMOFs stables à base de MIL-100 (Fe). Les antibiotiques ont été incorporées par imprégnation et chaque molécule s’est localisée préférentiellement dans un compartiment (large ou petite cage) corroborant parfaitement les simulations par modélisation moléculaire. De plus, il a été découvert, de manière surprenante, qu’un grand nombre de nanoMOFs se localisait au voisinage des bactéries (S.aureus) dans des cellules infectées. En se dégradant dans ces cellules, les nanoMOFs contenant les antibiotiques ont réduit de manière importante la charge bactérienne intracellulaire. Ces études révèlent le potentiel des particules de type «cage» pour une incorporation efficace de molécules actives et leur libération contrôlée et ouvrent de nombreuses possibilités d’application
Drug delivery systems are engineered technologies to administer pharmaceutical ingredients to improve their therapeutic effects, aiming at minimizing their side effects by means of targeted delivery and/or controlled release. “Cage” particles recently drew special attention since they could act as “drug containers” which potentially load large amount of drugs, improve their stability and offer the possibilities to co-encapsulate synergetic drugs. Cyclodextrins (CDs) are typical “cage” molecules with a hydrophobic cavity and a hydrophilic outer surface. Taking advantage of the host-guest interactions between β-CD and benzophenone (Bz), CD based nanoparticles (CD-NPs) were the first formulation investigated. CD-NPs of around 100 nm were instantaneously produced by mixing two aqueous solutions of neutral polymers: 1) poly-CD containing β-CDs, and 2) Bz grafted Dex (Dex-Bz). The “green” and facile preparation procedure makes it attractive formulation, whereas its limitation lies on the low drug payloads (~ 5 wt%). In order to improve the drug loading capacity of CDs, porous CD based metal organic frameworks (CD-MOFs) were synthesized, which contain not only CD cavities, but also large pores built up by CDs self-assembly. Lansoprazole (LPZ) was incorporated in CD-MOF microcrystals (~ 6 µm) reaching payloads as high as 23.2 ± 2.1% (wt). Remarkably, each CD cavity was able to host a drug molecule, offering new opportunities for the use of CD-MOFs for drug delivery purposes. However, these particles disassembled in aqueous media, which limits their application for oral and intravenous administration. Surface modification is therefore necessary to improve their stability in water. The drug loaded CD-MOF nanocrystals (~ 650 nm) were successfully embedded in polyacrylic acid (PAA) polymer matrices. The composite microspheres exhibited spherical shapes and sustained drug release over a prolonged period of time (over 48 h). Drug loaded MOF/PAA composite microspheres were not toxic in vitro (cell viability ~ 90%) even at very high concentrations up to 17.5 mg/mL. MOF/PAA composite microspheres constitute an efficient and pharmaceutically acceptable MOF-based carrier for sustained drug release. However, the process of surface modification was complicated and lead to larger particles and reduced drug payloads. Water-stable MOFs are a novel type of hybrid particles, showing a high potential as drug carriers. Iron trimesate MOFs, namely, MIL-100 (Fe) (MIL stands for Material of Institute Lavoisier) was among the first nano-scaled MOFs used for drug delivery. These particles were stable in water but degraded in phosphate buffer saline (PBS) losing their crystallinity and constitutive trimesate linkers. However, it was discovered that they kept their morphology intact. A thorough analysis based on Raman microscopy was carried on to gain insights on both the morphology and chemical composition of individual particles. It was evidenced the formation of a sharp erosion front during particle degradation. Noteworthy, the MOFs did not degrade during drug loading nor surface modification. Co-encapsulation of two synergic antibiotics (amoxicillin and potassium clavulanate) in MIL-100 (Fe) nanoMOFs was achieved following a “green” procedure by soaking nanoMOFs in aqueous solutions of both drugs. Molecular modelling showed that each drug preferentially located in a separate nanoMOF compartment. Surprisingly, nanoMOFs were prone to co-localize with bacteria once internalized in infected macrophages. NanoMOFs acted synergistically with the entrapped drugs to kill intracellular S. aureus, in vitro. These results pave the way towards the design of engineered nanocarriers in which each component synergistically plays a role in fighting the disease. These studies unravel the potential of “cage” particles for efficient drug entrapment and controlled release and open numerous possibilities for applications

We present a study of the manipulation of micro-particles and the formation of optically bound structures of particles in evanescent wave traps. Two trapping geometries are considered: the first is a surface trap where the evanescent field above a glass prism is formed by the interference of a number of laser beams incident on the prism-water interface; the second uses the evanescent field surrounding a bi-conical tapered optical fibre that has been stretched to produce a waist of sub-micron diameter. In the surface trap we have observed the formation of optically bound one- and two-dimensional structures of particles and measured the binding spring constant by tracking particle motion and the extent of the particle’s Brownian fluctuations. Additionally, we have measured the inter-particle separations in the one-dimensional chain structures and characterised the geometry of the two-dimensional arrays. In the tapered optical fibre trap we demonstrated both particle transport for long distances along the fibre, and the formation of stable arrays of particles. We present the fabrication of tapered optical fibres using the 'heat-and-pull` technique, and evanescent wave optical binding of micro-particles to the taper. Calculations of the distribution of the evanescent field surrounding a tapered fibre are also presented. We show that the combination of modes can give control over the locations of the trapping sites. Additionally, we show how the plasmon resonance of metallic nano-particles can be exploited to enhance the optical trapping force, and suggest how a bi-chromatic nano-fibre trap for plasmonic particles may be implemented. In both experiments we implement video microscopy to track the particle locations and make quantitative measures of the particle dynamics. The experimental studies are complemented by light scattering calculations based on Mie theory to infer how the geometries of the particle structures are controlled by the underlying incident and scattered optical fields.

Micro- and nanoscale particles have recently become the focus of a great deal of research interest due to their wide-ranging potential in a number of applications. This thesis concerns the interaction of small particles with the 157nm wavelength vacuum ultraviolet, VUV, emission from a molecular fluorine gas, F₂, laser. The laser system is introduced and an overview of laser ablation of polymers is presented. Small particles of different materials and sizes, supported on polymeric substrates, are irradiated at a wavelength of 157nm. The silica particles are transparent to the 157nm radiation, which leads to a lens effect. The polystyrene, silicon carbide and silver particles are opaque to the 157nm radiation, leading to a substrate-shielding effect. The lens effect results in the focussing of the incident laser beam into a hotspot at the interface between the particle and the substrate. The enhancement leads to the removal of substrate material underneath the particle to form a dimple on the surface of the substrate. The substrate-shielding effect leads to the removal of the substrate material around the opaque particle while the underlying material is left behind. This forms a polymeric support structure, with the seeding particle attached to the top. The shape of the seeding particle dictates the shape of the support structure, for example spherical particles seed composite conical structures and cylindrical particles seed linear prismatic structures. The polystyrene and silver particles are seen to undergo shape and size transformations as a result of laser irradiation. This is discussed in terms of mass loss through heating. Finite Element Method modelling is used to investigate and support the experimental results. Fluorescent polystyrene particles are also irradiated at a wavelength of 157nm. They retain their fluorescence after irradiation and exhibit Whispering Gallery Mode resonances, ideal for high-sensitivity sensing applications and Lab-on-a-Chip microreactors.

The rapid advancement of drug delivery systems (DDS) has raised the possibility of using functional engineered nano/micro-particles as drug carriers for the administration of active pharmaceutical ingredients (APIs) to the affected area. The major goals in designing these functional particles are to control the particle size, the surface properties and the pharmacologically active agents release in order to achieve the site-specification of the drug at the therapeutically optimal rate and dose regimen. Two different equipment (i.e. glass capillary microfluidic device and micro-engineered membrane dispersion cell) were utilised in this study for the formation of functional nano/micro-particles by antisolvent precipitation method. This method is based on micromixing/direct precipitation of two miscible liquids, which appear as a straightforward method, rapid and easy to perform, does not require high stirring rates, sonication, elevated temperatures, surfactants and Class 1 solvents can be avoided. Theoretical selection of a good solvent and physicochemical interaction between solvent-water-polymer with the aid of Bagley s two-dimensional graph were successfully elucidated the nature of anti-solvent precipitation method for the formation of desired properties of functional pharmaceutical nano/micro-engineered particles. For the glass capillary microfluidic experiment, the organic phase (a mixture of polymer and tetrahydrofuran/acetone) was injected through the inner glass capillary with a tapered cross section culminated in a narrow orifice. The size of nanoparticles was precisely controlled by controlling phase flow rates, orifice size and flow configuration (two- phase co-flow or counter-current flow focusing). The locations at which the nanoparticles would form were determined by using the solubility criteria of the polymer and the concentration profiles found by numerical modelling. This valuable results appeared as the first computational and experimental study dealing with the formation of polylactide (PLA) and poly(ε-caprolactone) (PCL) nanoparticles by nanoprecipitation in a co-flow glass capillary device. The optimum formulations and parameters interactions involved in the preparation of paracetamol encapsulated nanoparticles (PCM-PCL NPs) using a co-flow microfluidic device was successfully simulated using a 25-full factorial design for five different parameters (i.e. PCL concentration, orifice size, flow rate ratios, surfactant concentration and paracetamol amount) with encapsulation efficiency and drug loading percentage as the responses. PCM-loaded composite NPs composed of a biodegradable poly(D,L-lactide) (PLA) polymer matrix filled with organically modified montmorillonite (MMT) nanoparticles were also successfully formulated by antisolvent nanoprecipitation in a microfluidic co-flow glass capillary device. The incorporation of MMT in the polymer matrix improved the drug encapsulation efficiency and drug loading, and extended the rate of drug release in simulated intestinal fluid (pH 7.4). The encapsulation of MMT and PCM in the NPs were well verified using transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDS), x-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). PCL drug-carrier nanoparticles were also produced by rapid membrane micromixing combined with nanoprecipitation in a stirred cell employing novel membrane dispersion. The size of the NPs was precisely controlled by changing the aqueous-to-organic volumetric ratio, stirring rate, transmembrane flux, the polymer content in the organic phase, membrane type and pore morphologies. The particle size decreased by increasing the stirring rate and the aqueous-to-organic volumetric ratio, and by decreasing the polymer concentration in the aqueous phase and the transmembrane flux. The existence of the shear stress peak within a transitional radius and a rapid decline of the shear stress away from the membrane surface were revealed by numerical modelling. Further investigation on the PCL nanoparticles loaded immunosuppressive rapamycin (RAPA) drug were successfully synthesised by anti-solvent nanoprecipitation method using stainless steel (SS) ringed micro-engineered membrane. Less than 10 μm size of monohydrate piroxicam (PRX) micro-crystals also was successfully formed with the application of anti-solvent precipitation method combined with membrane dispersion cell that has been utilised in the formation of functional engineered nanoparticles. This study is believed to be a new insight into the development of integrated membrane crystallisation system.

Strain engineering is used as a means of manufacturing micro- and nano- scale particles with the ability to reversibly alter their geometry from three dimensional tubes to two dimensional flat layers. These particles are formed from a bi-layer of two dissimilar materials, one of which is the elastomeric material polydimethylsiloxane (PDMS), deposited under stress on a sacrificial substrate. Upon the release of the bi-layer structure from the substrate, interfacial residual stress is released resulting in the formation of tubes or coils. These particles possess the ability to dramatically alter their geometry and, consequently, change some properties that are reversible and can be triggered by a stimulus. This work focuses on the material selection and manufacturing of the bi-layer structures used to create the responsive particles and methods for characterizing and controlling the responsive nature of the particles. Furthermore, the potential of using these particles for a capture/release application is explored, and a systematic approach to scale up the manufacturing process for such particles is provided. This includes addressing many of the problems associated with fabricating ultra-thin layers, tuning the size of the particles, understanding how the stress accumulated at the interface of a bi-layer structure can be used as a tool for triggering a response as well as developing methods (i.e. experiments and applications) that allow the demonstration of this response.

Production of polymeric magnetic micro and nano-particles is a rapidly emerging area in pharmaceutical and biomedical science. In this thesis, the capability of the electrohydrodynamic atomization (EHDA) process for preparing biodegradable polymeric magnetic particles with different sizes was explored. The EHDA processing method offers several advantages over conventional coprecipitation and emulsification techniques for the preparation of magnetic particles. Most significant are the process efficiency and preservation of the iron oxide nanoparticles and/or therapeutic agents functionality, as complex multistep processing involving harsh solvents, additives and elevated temperatures or pressure are avoided. The first part of the thesis describes a detailed investigation of how the size, morphology and shape of the particles generated can be controlled through the operating parameters; specifically the flow rate and applied voltage. The particle diameter was greatly influenced by flow rate and applied voltage. The mean size of the particles changed from1.6µ m to 17.8µm as the flow rate increased from 100µl/min-1 to 400µl/min-1. The research also focuses on the effects of these parameters on the jetting modes of the E H DA process, in particular the con-jet mode operation. Magnetic nanospheres were also produced using single needle processing with mean size of 56nm with a corresponding polydispersivity index of 16%. Nanospheres exhibited a high saturation magnetization at room temperature (67emu/g). Chlorotoxin, a scorpion venom was chosen as the therapeutic agent model because it is non-toxic, non-immunogenic along with other favourable characteristics such as small size high stability and most importantly only binds to tumour cells and not healthy cells. Scorpion venom loaded magnetic microspheres were produced using single needle processing, with a particle size of 2µm. This work demonstrates a powerful method of generating micro and nano magnetic polymeric particles, with control over the size of particles prepared.

Many useful organic molecules such as drugs are poorly soluble in water. Novel ways of the deployment of these molecules are as stable nanodispersions. In our research we aim to produce a method for the creation of nanoparticles via a technique called emulsion-evaporation. These techniques include the creation of emulsions, ~olymerisation and A.,. .•••• ,. • freeze-drying. The production of these nanoparticles in-situ with templated porous polymers by these techniques was used. This avoids the problem of nanoparticle aggregation. These nanoparticles can be released into an aqueous medium by diffusing out of the porous scaffold or by a stimuli-sensitive trigger. We describe here the preparation of porous poly N-isopropylacrylamide. The swelling of the polymer and contraction above a solution temperature were explored for the uptake and release of polymeric colloids. The thesis discusses the application of readily soluble aqueous nanodispersions prepared by using a polyvinyl alcohol/sodium dodecyl sulphate (PVA/SDS) monolith prepared by emulsion templating. The monoliths can be prepared with the in-situ formation of drug nanoparticles which, readily solubilises the drug as nanodispersions. The thesis continues to explore stimuli as a method for the release of the organic nanoparticles: a chitosan based emulsion templated monolith was prepared which can release the formed nanoparticles from the scaffolds via control of pH. Finally, the use of a disulphide crosslinked polymer was explored for the release of organic nanoparticles. The particles could be released from the polymer by using a disulphide bond "cleaver" which degrades the polymer and thus releasing the internal organic nanoparticles. ii

In this thesis, the capability of the electrohydrodynamic atomization (EHDA) process for preparing drug delivery carriers consisting of biodegradable polymeric particles with different sizes and shapes was explored. The first part of the thesis describes a detailed investigation of how the size, morphology and shape of the particles generated can be controlled through the operating parameters; specifically the flow rate, applied voltage and the properties of the solutions. Diameter and shape of the particles were greatly influenced by viscosity and applied voltage. The mean size of the particles changed from 340 nm to 4.4 μm as the viscosity increased from 2.5 mPa s to 11 mPa s. Also, using more concentrated polymer solution (30 wt%) and higher applied voltage (above 14 kV) were found to be ideal for promoting chain entanglement and shape transition from spherical to oblong to a more needle-like shape. Estradiol-loaded micro and nanoparticles were produced with mean sizes ranging from 100 nm to 4.5 μm with an encapsulation efficiency ranging between 65% to 75%. The in vitro drug release profiles of the particles started with an initial short burst phase and followed by a longer period characterised by a lower release rate. Two strategies were developed to tailor these profiles. First, ultrasound was explored as a non-invasive method to stimulate “on demand” drug release from carrier particles. Systematic investigations were carried out to determine the effect of various ultrasound exposure parameters on the release rate in particular output power, duty cycle and exposure time. These three exposure parameters were seen to have a significant enhancing effect upon the drug release rate (up to 14%). The second strategy explored was coating the surface of the particles with chitosan and gelatin. This enabled control and reduction of the prominence ‘burst release’ phase without affecting other parts of the release profile. Coating the particle surface with 1 wt% chitosan solution considerably reduces the initial release by 62%, 60% and 42% for PLGA 2 wt%, 5 wt% and 10 wt%, respectivly in the first 72 hours This work demonstrates a powerful method of generating micro and nano drug-loaded polymeric particles, with modified release behaviour and with control over the initial release.

In the present thesis Supramolecular chemistry is exploited to approach applications in the area of Nanomedicine, and it is, focused on the design and preparation of different micro and nanotools for sensing and therapy, in living cells. Initially, the combination of silicon surface chemistry with the incorporation of bioactive molecules has been investigated in order to obtain a potentially microtool suitable for cell tagging. Furthermore, the design and synthesis of organic compounds as intracellular chemosensors was also explored. On the other hand, this report also includes the synthesis and characterization of dissymmetrical porphyrin derivatives and their subsequent incorporation to metal nanoparticles (gold and iron oxide) for their use in photodynamic therapy (PDT), due to their capacity to produce reactive oxygen species after irradiation, inducing the cell death. The preparation of novel metallo-porphyrins as components of molecular machines was also achieved. First, the formation of self-assembled monolayers (SAM) on polysilicon surfaces was investigated, using different silanes to obtain a functionalization protocol which can be easily repetitive and effective. Thus, three silanes with different functional groups, an aldehyde, an epoxide and an activated ester, have been tested to prepare a SAM and subsequently, prompting us to immobilize a bioactive molecule. Different parameters of the functionalization methodology have been examined, such as the silanization time, deposition method, the type of solvent and silane concentration. Once the SAM formation was optimized, the immobilization of the protein what germ agglutinin (WGA) was achieved, because its ability of cell membrane recognition. The WGA used, included a fluorescent dye (Texas red) to be able to characterize the immobilization of the protein on a silicon surface by fluorescence microscopy, and similar successful results were obtained in the three different silanes used. The same methodology (SAM formation and WGA immobilization) was subsequent applied in silicon encoded microparticles designed for tagging cells. Experiments using mouse embryos have been performed to determine the extracellular adhesion level of the encoded microparticles, resulting above 90 % in all cases. Proper immobilization of WGA protein was the key factor in cell labeling, because WGA recognizes specifically certain carbohydrates expressed in the external membrane (zona pellucida) of the embryo. Synthesis and immobilization of an aminoanthracene derivative as pH sensor was carried out, and its subsequent immobilization on silicon microparticles was achieved. Fluorescence spectroscopy measurements demonstrated that the aminoanthracene derivative immobilized on silicon microparticles could be a potential microtool for sense intracellular pH. Fluorescence spectroscopy experiments showed an important increase at acid pH, whereas from pH 7 to pH 12 the fluorescence emission was very low. On the other hand, aminoanthracene incorporating an aza-crown ether was also prepared as a possible candidate for calcium sensing. Preliminary studies using fluorescence spectroscopy, demonstrated a good selectivity for calcium in comparison with other cations such as magnesium, sodium and potassium. Dissymmetrical porphyrin derivatives have been synthesized and then immobilized on gold and iron oxide nanoparticles, obtaining water soluble metallic nanoparticles incorporating the photosensitizer. The capacity to produce singlet oxygen to induce the cell death following irradiation was investigated, resulting porphyrin immobilized gold or iron oxide nanoparticles. Thus, the prepared porphyrin derivatives and their corresponding nanotools exhibited a high formation of singlet oxygen, resulting nanotools potentially suitable for PDT. Otherwise, anti-erbB2 antibody, a specific antibody for a membrane receptor overexpressed in breast cancer cells, was immobilized onto water soluble porphyrin-gold nanoparticles. Preliminary experiments in a breast cancer cell line, demonstrated the capacity of the porphyrin-antibody-gold nanoparticle to produce the cell death following irradiation. Finally a metallo-porphyrins derivative was synthesized and characterize as a promising component for molecular rotors.
El diseño y la preparación, mediante la utilización de procesos de biofuncionalización de micro / nanosistemas que puedan tener aplicación en células vivas es un tema de actualidad en campos como la Nanobiotecnología y la Nanomedicina. De este modo, en la presente tesis se ha estudiado el proceso de biofuncionalización de micropartículas de polisilicio, para actuar como etiquetas celulares, debido al interés que genera la posibilidad de poder etiquetar células vivas y así conocer el comportamiento de las células de manera individual. Sucesivamente, también se ha estudiado la preparación de quimiosensores de dos parámetros intracelulares (pH y calcio) basados en compuestos con capacidad de variar la intensidad de su fluorescencia, según cambios del medio. Concretamente, se ha trabajado en la síntesis e inmovilización de derivados del aminoantraceno en micropartículas de silicio como posibles candidatos para obtener microherramientas capaces de detectar cambios en el pH o en la concentración de calcio intracelulares. Por otro lado, la tesis también describe la preparación de nanosistemas para su aplicación en terapia fotodinámica. La terapia fotodinámica (PDT) se basa en el uso de moléculas específicas (fotosensibilizadores), que en presencia de luz (generalmente un láser), activan el proceso de la muerte celular debido a la formación de radicales libres de oxígeno. La combinación de la utilización de nanopartículas modificadas con un fotosensibilizador resulta un reto interesante que podría mejorar la terapia antitumoral, disminuyendo sus efectos secundarios. Concretamente, en la tesis se describe la preparación de nuevos fotosensibilizadores derivados de porfirinas, con el fin ser incorporados a nanopartículas de óxido de hierro y de oro. También se detalla el estudio de la capacidad de los nuevos nanosistemas obtenidos de producir oxígeno singlete como elemento inductor de la apoptosis celular, y resultados preliminares in vivo indican su potencial aplicación en PDT. Estos estudios, demuestran la posibilidad de dichos nanosistemas para ser usados en terapia fotodinámica. Por último, también se han sintetizado derivados de metalo-porfirinas como componentes de rotores moleculares.

S'ha realitzat un estudi sobre els mecanismes de formació de micropartícules polimèriques i les seves pel•lícules granulars, a partir de l'assecat de microgotes de electrosprays. L'estudi se centra en diferents solucions de tres polímers insolubles en aigua: polimetil(metacrilat), poliestirè, i etil cel•lulosa. L'assecat d'aquests electrosprays dóna lloc a diverses morfologies de partícula, que han estat determinades mitjançant microscòpia d'escombrat electrònic, i han estat caracteritzades en funció del solvent, concentració del polímer, el seu pes molecular, i la humitat relativa ambient. Les morfologies obtingudes inclouen una varietat d'estructures de partícula globulars i filamentoses, que, a humitat relativa elevada, poden desenvolupar porositat. Aquestes característiques morfològiques han estat explicades mitjançant models qualitatius que involucren fenòmens fluid dinàmics i sobre separació de fases, presents en sistemes relacionats amb els estudiats. Un dels fenòmens fluid dinàmics involucrats clau són les inestabilitats coulòmbiques de gotes elèctricament carregades. A més, la interacció de no solvent de l'aigua en la precipitació del polímer pot donar lloc a textures poroses sobre la superfície de les partícules. Les diferents formes de textura han estat explicades en referència als fenòmens de breath figure formation (BFF), i a la inversió de fases induïda per vapor (vapor induced phase separation, o VIPS). També hem estudiat el creixement de les pel•lícules granulars formades a partir de les partícules polimèriques. Demostrem que la càrrega elèctrica transportada per les partícules cap a la pel•lícula influeix fortament en la dinàmica de creixement d’aquesta. Un millor coneixement dels mecanismes estudiats en aquesta tesi hauria de permetre dissenyar nous processos de manufactura de partícules i recobriments basats en electrospray. Se ha realizado un estudio sobre los mecanismos de formación de micropartículas poliméricas y sus películas granulares, a partir del secado de microgotas de electropras. El estudio se centra en diferentes soluciones de tres polímeros insolubles en agua: polimetil(metacrilato), poliestireno, y etil celulosa. El secado de estos electrosprays da lugar a diversas morfologías de partícula, que han sido determinadas mediante microscopía de barrido electrónico, y han sido car
Se ha realizado un estudio sobre los mecanismos de formación de micropartículas poliméricas y sus películas granulares, a partir del secado de microgotas de electropras. El estudio se centra en diferentes soluciones de tres polímeros insolubles en agua: polimetil(metacrilato), poliestireno, y etil celulosa. El secado de estos electrosprays da lugar a diversas morfologías de partícula, que han sido determinadas mediante microscopía de barrido electrónico, y han sido caracterizadas en función del solvente, concentración del polímero, su peso molecular, y la humedad relativa ambiente. Las morfologías obtenidas incluyen una variedad de estructuras de partícula globulares y filamentosas, que, a humedad relativa elevada, pueden desarrollar porosidad. Estas características morfológicas han sido explicadas mediante modelos cualitativos que involucran fenómenos fluido dinámicos y sobre separación de fases, presentes en sistemas relacionados con los estudiados. Uno de los fenómenos fluido dinámicos involucrados clave son las inestabilidades coulómbicas de gotas eléctricamente cargadas. Además, la interacción de no solvente del agua en la precipitación del polímero puede dar lugar a texturas porosas sobre la superficie de las partículas. Los diferentes tipos de texturas han sido explicadas en referencia a los fenómenos de breath figure formation (BFF), y a inversión de fases inducida por vapor (vapor induced phase separation, o VIPS). También hemos estudiado el crecimiento de las películas granulares formadas a partir de las partículas poliméricas. Demostramos que la carga eléctrica transportada por las partículas hacia la película influye fuertemente en la dinámica de crecimiento de ésta. Un mejor conocimiento de los mecanismos estudiados en esta tesis debería permitir diseñar nuevos procesos de manufactura de partículas y recubrimientos basados en electrospray.
A study has been made of the mechanisms underlying the formation of polymeric microparticles and of their granular films, by drying of electrospray microdroplets. The study is focused on different solutions of three water-insoluble polymers: polymethyl(methacrylate), polystyrene, and ethyl cellulose. The drying of such electrosprays result in diverse particle morphologies, which have been determined by scanning electron microscopy, and have been characterized as a function of the solvent, polymer concentration, polymer molecular weight, and ambient relative humidity. The morphologies obtained include a variety of globular and filamented particle structures, which, at elevated relative humidity, can develop porosity. These morphological features have been explained using qualitative models involving fluid dynamic and phase separation phenomena which are known to occur in closely related systems. One of the key fluid dynamic phenomena involved is the coulombic instability of electrically charged droplets. In addition, the non-solvent interaction of water on the precipitation of the polymer can lead to porous textures on the particles surfaces. The different kinds of textures have been explained by reference to breath-figure formation (BFF) and vapor induced phase separation (VIPS) phenomena. We have also studied the growth of the granular films of such polymer particles. We show that the electrical charge transported by the particles to the film have a strong influence on the film growth dynamics. The better understanding of the mechanisms studied in this thesis, should help design new manufacturing processes of particles and coatings based on electrospray.

L'amélioration des propriétés mécaniques des métaux et des alliages purs peut être obtenue par l'introduction de particules de céramique dispersées de manière appropriée dans le matériau. Ces particules peuvent agir comme sites de germination améliorant la réduction de la taille des cristallites (grains). La dispersion de ces matières nucléantes présente des défis du fait de leur tendance à la sédimentation et à l'agglomération. Des particules de taille nanométrique peuvent également améliorer les propriétés mécaniques par plusieurs mécanismes de renforcement du type Orowan ou aux joints de grains. L'utilisation de l'agitation électromagnétique est un moyen de disperser des particules et de produire des changements dans la microstructure du matériau. L'agitation électromagnétique induite peut augmenter le nombre de sites de nucléation disponibles lors de la solidification en rompant les bras des dendrites nouvellement formées au niveau du front de solidification. Le champ de température dans le matériau fondu peut également être homogénéisé par son action. Le faible gradient de température produit dans le métal liquide peut favoriser la croissance des dendrites équiaxes. Dans cette étude, un four de type Bridgman a été utilisé pour produire des matériaux contenant des raffineurs de grains et des particules de renforcement. Le four a été équipé d'un électro-aimant de Bitter capable de produire un champ magnétique glissant (CMG). Grâce à l'agitation électromagnétique, l’écoulement induit disperse les particules et produit des changements effectifs dans la microstructure des matériaux étudiés. Les expériences ont été confrontées par des simulations numériques réalisées par l'Université de Greenwich et le laboratoire SIMaP. Les expériences effectuées en dispersant les microparticules de SiC dans la matrice de magnésium pur montrent que la distribution des particules dans le matériau est fortement régie par l'orientation verticale du champ magnétique appliqué (vers le haut ou vers le bas). Les résultats de la simulation numérique et des expériences sur la dispersion des particules sont en accord. L’agitation électromagnétique promeut un affinage des grains dans le cas de l’aluminum pur. Une tendance contraire est observée sur les alliages. Le CMG est utilisé pour disperser les particules de taille nanométrique et micrométrique. La dispersion des particules micrométriques utilisées dans les alliages de magnésium et d’aluminium n’ont d’influence ni sur l’affinage des grains ni sur le renforcement mécanique. Cependant, les expériences avec des nanoparticules ont montré une amélioration de la résistance au fluage
Improvement in mechanical properties of pure metals and alloys can be achieved by the introduction of ceramic particles appropriately dispersed within the material. These particles can act as nucleation sites enhancing the reduction of the crystallite (grain) size. The dispersion of these nucleant materials presents challenges due to their tendency to sediment and to agglomerate. Particles of nanometric size can also produce the improvement of mechanical properties by several reinforcement mechanisms such as Orowan or grain boundary strengthening. The use of electromagnetic stirring can provide a method to disperse particles and produce changes in the microstructure of the material. The induced stirring can increase the number of nucleation points available during solidification breaking the arms of the new formed dendrites at the solidification front. The temperature field in the molten material can be also homogenized by the action of the electromagnetic stirring. The small temperature gradient produced in the liquid metal can promote the growing of equiaxed dendrites. In this study a Bridgman type furnace has been used to produce materials containing grain refiners and reinforcement particles. The furnace has been equipped with a Bitter coil electromagnet capable to produce a travelling magnetic field (TMF). The electromagnetic stirring provides an induced flow which is used to disperse the particles and produced measurable changes in the microstructure of the materials studied. The experiments carried out were supported with numerical simulations performed by University of Greenwich and Simap laboratory. Experiments performed dispersing SiC microparticles into pure magnesium matrix showed that particle concentration patterns in the material are strongly governed by the vertical orientation of the magnetic field applied (upwards vs downwards). The observed patterns of dispersion obtained from the experiments presented a good agreement with the patterns predicted by the numerical simulation. The effects of the electromagnetic stirring in the grain refining of pure aluminium showed positive results whereas the alloys subjected to stirring presented grain growth. The TMF was used to disperse particles of micrometric and nanometric size. The dispersion of microparticles in magnesium and aluminium alloys did not produce improvements in either grain refinement or mechanical properties. However, the experiments performed dispersing nanoparticles in magnesium alloy showed the improvement of creep resistance

Soil washing is a treatment process that has been used extensively for toxicant extraction, yet the process does not detoxify the mobilized pollutants per se. The more common detoxification processes include redox reactions that are mediated by zero-valent metals (ZVMs). Reduction of Cr(VI) to Cr(III) is desirable, as the latter specie is toxicologically innocuous to most living organisms and also has a low mobility and bioavailability. The main goals of this project included the development of an efficient treatment for the extraction and inactivation of toxic inorganic anions using ZVMs from contaminated soils. A variety of micron-sized ZVMs (Al, Cu, Fe, Mg, Ni, Si, and Zn); metallic mixtures (Pd/Fe, Ag/Fe, Cu/Fe, Zn/Fe, Co/Fe, Mg/Fe, Ni/Fe, Al/Fe, Si/Fe, Pd/Cu, Pd/Zn, Pd/Cu/Fe, Pd/Zn/Fe, and Zn/Cu/Fe); Cu and Fe nano-sized particles (NPs), and selected nano-sized bimetallic analogs (Pd/Fe, Cu/Fe and Pd/Cu) were evaluated for reactivity towards the reduction of Cr(VI) in a surfactant preparation (Tween® 20) under a selection of reaction conditions. At circum neutral pHs, a rapid inactivation of the surface was observed for almost all the tested metals whereas complete reduction of Cr(VI) was achieved at acidic pH only by using Cu, Fe, Mg, or Zn. Relative to the reactivity of the zero-valent iron, the tested bimetallic mixtures (Pd/Fe > Pd/Zn> Ag/Fe > Ni/Fe> Zn/Fe > Pd/Cu > Cu/Fe) appreciably increased the pseudo-first order rate constant. The Zn/Cu/Fe, represented a cost-effective preparation providing comparable or improved kinetic parameters relative to the more expensive palladized bimetallic mixtures. The results suggest that the cementation of a noble metal serves not only as a reaction accelerator but also provides protection of the ZVM surface impeding its rapid inactivation. A considerable increase in reactivity (up to 100-fold) was observed with NPs. The formation of clusters of polymeric structures provided a
Le lavage de sols est un processus de traitement qui a été employé intensivement pour l'extraction des produits toxiques, néanmoins le processus ne détoxique pas les polluants mobilisés. Les procédés plus communs de désintoxication incluent les réactions rédox qui sont négociées par les métaux nullivalents (MNVs). La réduction de Cr(VI) au Cr(III) est souhaitable, car la dernière espèce est moins toxique pour la plupart des êtres vivants, et a également une basse mobilité et disponibilité biologique. Les objectifs principaux de ce projet ont inclus le développement d'une méthode efficace pour l'extraction et la détoxication des anions inorganiques toxiques utilisant MNVs dès sols contaminés.Une série de micro-MNVs (Al, Cu, Fe, Mg, Ni, Si, et Zn); de combinaison métalliques (Pd/Fe, Ag/Fe, Cu/Fe, Zn/Fe, Co/Fe, Mg/Fe, Ni/Fe, Al/Fe, Si/Fe, Pd/Cu, Pd/Zn, Pd/Cu/Fe, Pd/Zn/Fe, et Zn/Cu/Fe); de nano-particules (NPs) de Cu et Fe ; ainsi que des NPs bimétalliques (Pd/Fe, Cu/Fe et Pd/Cu) ont été évalués sur la réactivité vers la réduction de Cr(VI) dans une préparation d'agent tensioactif (Tween® 20) sous différentes conditions de réaction. Aux pHs près de la neutralité, on a observé une inactivation rapide de la surface pour presque tous les métaux examinés tandis que la réduction totale de Cr(VI) a été réalisée au pH acide seulement en employant le Cu, le Fe, le magnésium, ou le Zn. Au regard à la réactivité du fer nullivalente, les préparations bimétalliques testées (Pd/Fe > Pd/Zn> Ag/Fe > Ni/Fe> Zn/Fe > Pd/Cu > Cu/Fe) ont sensiblement augmentés la constante de vélocité de pseudo-première taux. La préparation métallique Zn/Cu/Fe, représente un mélange métallique rentable fournissant des paramètres cinétiques comparables ou améliorés par comparaison aux mélanges bimétalliques plus chers qui possèdent du palladium. Les résultats suggèrent, que la cémentation

In this thesis, the synthesis of nano-micro particles of crystalline inorganic materials and four different applications involving their use, are presented . Inorganic particles have been synthesized following two main criteria: i) the particle’s dimensions, specific surface area and crystalline phase of the product have been optimized for the practical application; ii) both the synthesis and application should be based on a simple procedure, environmental low impact, economical affordability. In particular, Titanium dioxide nanoparticles have been synthesized by sol-gel hydrolysis of Titanium(IV) isopropoxide in an isopropyl alcohol/water solution. The isopropyl alcohol contained in the solvent mixture act as a capping agent stabilizing the forming nanometric particles, and play also a role in the suspension stability. Synthesized Titanium dioxide reveals good photocatalytic properties directly as synthesized, without needing further thermal treatment. Photoactive Titanium dioxide have been used for NOx pollutants abatement on waste gases produced by a working plant and as self-cleaning coating on photovoltaic Silicon panels, showing good results. Crystalline calcium phosphate nano and micro particles, in particular Hydroxyapatite, Brushite, Monetite and Mg-doped β-Tricalcium phosphate have been synthesized. Two applications of the synthesized Calcium phosphates are reported, both based on the drug delivery concept. Hydroxyapatite nanocrystals were used to adsorbe and retain on their surface anticancer drugs based on a Platinum complex, and release them in response to a pH variation. Phytotherapics active elements have been stabilized by physisorption on Calcium phosphates particles surface. The administration of the obtained suspensions shows good results in terms of plant’s healing, using a lower amount of phytotherapic elements compared to the commercial products.
In questa tesi sono riportate sintesi e caratterizzazione di nano-micro particelle di materiale cristallino inorganico, e quattro loro applicazioni. Le particelle inorganiche sono state preparate seguendo due criteri principali: i) le proprietà chimico-fisiche delle particelle devono essere ottimizzate in funzione dell’applicazione; ii) sintesi e applicazione devono essere basate su procedure semplici, con basso impatto ambientale ed economicamente sostenibili. In particolare, nano particelle di Titanio biossido sono state sintetizzate tramite reazione di idrolisi di Titanio(IV) isopropossido in una soluzione di acqua a alcol isopropilico. L’alcol isopropilico presente nella miscela di solventi agisce da agente cappante stabilizzando le nanoparticelle in formazione e dimostra un ruolo nella stabilità della sospensione. Il Titanio biossido prodotto ha rivelato buone proprietà foto catalitiche senza bisogno di ulteriori trattamenti termici. Il Titanio biossido foto attivo è stato applicato con buoni risultati nell’abbattimento di NOx dalle emissioni di uno stabilimento e come strato autopulente su dei pannelli fotovoltaici. Sono state sintetizzate nano e micro particelle di calcio fosfati cristallini, nello specifico Idrossiapatite, Brushite, Monetite and β-Tricalcio fosfato Mg-sostituito. Ne sono riportate due applicazioni, entrambe basate sul concetto di drug delivery. Nanocristalli di Idrossiapatite sono stati utilizzati per adsorbire e ritenere sulla loro superficie farmaci chemioterapici basati su complessi di Platino, e successivamente rilasciare il farmaco in risposta ad una variazione di pH. Alcuni principi attivi fitoterapici sono stai stabilizzati tramite fisisorbimento sulla superficie di particelle di Calcio fosfati in sospensione. La loro applicazione ha dimostrato buoni risultati curativi sulle piante, utilizzando quantitativi di principio attivo molto ridotti rispetto ai prodotti commerciali.

In this thesis, the synthesis of nano-micro particles of crystalline inorganic materials and four different applications involving their use, are presented . Inorganic particles have been synthesized following two main criteria: i) the particle’s dimensions, specific surface area and crystalline phase of the product have been optimized for the practical application; ii) both the synthesis and application should be based on a simple procedure, environmental low impact, economical affordability. In particular, Titanium dioxide nanoparticles have been synthesized by sol-gel hydrolysis of Titanium(IV) isopropoxide in an isopropyl alcohol/water solution. The isopropyl alcohol contained in the solvent mixture act as a capping agent stabilizing the forming nanometric particles, and play also a role in the suspension stability. Synthesized Titanium dioxide reveals good photocatalytic properties directly as synthesized, without needing further thermal treatment. Photoactive Titanium dioxide have been used for NOx pollutants abatement on waste gases produced by a working plant and as self-cleaning coating on photovoltaic Silicon panels, showing good results. Crystalline calcium phosphate nano and micro particles, in particular Hydroxyapatite, Brushite, Monetite and Mg-doped β-Tricalcium phosphate have been synthesized. Two applications of the synthesized Calcium phosphates are reported, both based on the drug delivery concept. Hydroxyapatite nanocrystals were used to adsorbe and retain on their surface anticancer drugs based on a Platinum complex, and release them in response to a pH variation. Phytotherapics active elements have been stabilized by physisorption on Calcium phosphates particles surface. The administration of the obtained suspensions shows good results in terms of plant’s healing, using a lower amount of phytotherapic elements compared to the commercial products.
In questa tesi sono riportate sintesi e caratterizzazione di nano-micro particelle di materiale cristallino inorganico, e quattro loro applicazioni. Le particelle inorganiche sono state preparate seguendo due criteri principali: i) le proprietà chimico-fisiche delle particelle devono essere ottimizzate in funzione dell’applicazione; ii) sintesi e applicazione devono essere basate su procedure semplici, con basso impatto ambientale ed economicamente sostenibili. In particolare, nano particelle di Titanio biossido sono state sintetizzate tramite reazione di idrolisi di Titanio(IV) isopropossido in una soluzione di acqua a alcol isopropilico. L’alcol isopropilico presente nella miscela di solventi agisce da agente cappante stabilizzando le nanoparticelle in formazione e dimostra un ruolo nella stabilità della sospensione. Il Titanio biossido prodotto ha rivelato buone proprietà foto catalitiche senza bisogno di ulteriori trattamenti termici. Il Titanio biossido foto attivo è stato applicato con buoni risultati nell’abbattimento di NOx dalle emissioni di uno stabilimento e come strato autopulente su dei pannelli fotovoltaici. Sono state sintetizzate nano e micro particelle di calcio fosfati cristallini, nello specifico Idrossiapatite, Brushite, Monetite and β-Tricalcio fosfato Mg-sostituito. Ne sono riportate due applicazioni, entrambe basate sul concetto di drug delivery. Nanocristalli di Idrossiapatite sono stati utilizzati per adsorbire e ritenere sulla loro superficie farmaci chemioterapici basati su complessi di Platino, e successivamente rilasciare il farmaco in risposta ad una variazione di pH. Alcuni principi attivi fitoterapici sono stai stabilizzati tramite fisisorbimento sulla superficie di particelle di Calcio fosfati in sospensione. La loro applicazione ha dimostrato buoni risultati curativi sulle piante, utilizzando quantitativi di principio attivo molto ridotti rispetto ai prodotti commerciali.

Thesis (Ph. D.)--Textile and Fiber Engineering, Georgia Institute of Technology, 2007.
Committee Chair: Kumar, Satish; Committee Member: Carr, Wallace; Committee Member: Graham, Samuel; Committee Member: Griffin, Anselm; Committee Member: Yao, Donggang.

Increasingly global warming and air pollution caused by the consumption of fossil fuel have imposed the priority of using green energy. As a result, the use of rechargeable lithium-ion batteries (LIBs) has increased rapidly Olivine-structured LiFePO4 is considered as one of the most promising positive electrode materials owing to its significant advantages of nontoxicity, low cost of raw materials, good structural stability at high temperature, excellent safety performance, and relatively high theoretical specific capacity (170 mAhg-1) with a flat discharge-charge potential (3.45V vs. Li+/Li). Therefore, LiFePO4 battery becomes a reliable material for energy storage system used in hybrid electric vehicles (HEVs), full electric vehicles (EVs), plug-in hybrid electric vehicles (PHEVs), and portable devices. However, the poor rate performance of LiFePO4, resulting from its intrinsic low Li+ diffusivity (10-17 to 10-14 cm2s-1) and low electronic conductivity (10-9 to 10-8 S cm-1), has become a technical bottleneck to confine its widely practical applications. Following previous studies, a systematic study on controllable preparation of LiFePO4 positive electrode material with nanoscale size, or hierarchical micro/nano mesoporous structure has been carried out using various synthesis methods, including impinging stream reaction (ISR), ultrasonic-intensified impinging stream reaction (UISR), two-step co-precipitation method, and two-step hydrothermal method (UIHT). The physical and chemical properties of as-synthesized products are measured by XRD, FTIR, SEM, TEM, BET, Mastersizer, CV, and charge-discharge test. Based on these observations, the relationship among particle morphology, electrochemical performance, and impacts of fluid dynamics is evaluated in this work.

Cancer is the second most frequent cause of death in the world today and a huge global problem for the society. Current drug delivery systems used in the treatment of cancer suffer from a number of problematic issues, like poor plasma half-life and poor release profile of therapeutic agents. To overcome these limitations, recent research has focused on using calcium carbonate(CaCO3) micro/nanoparticles as carrier-based systems to improve drug therapies and clinical outcomes. The present study investigates and evaluates a newly developed Reverse Micelle method for generating micro/nanometre scale CaCO3 powders for potential use as a drug carrier platform. XRD spectroscopy revealed the CaCO3 was in the form of calcite and it had a mean crystallite size of 9.3nm. However, the study found the Reverse Micelle method had a preference to produce larger micrometre scale particles instead of only nanometre scale particles. Both SEM and particle analysis revealed 45.46% of the particles were between 8 and 16μm and the mean particle size was 10μm.The resulting calcite ultra-powders were found to have a relatively low specific surface area of around 0.577 m2 g−1 and also found to display poor adsorption behaviour towards Rhodamine B. To explain this behaviour, the study suggests water present in the washing and centrifuging stage promotes the dissolution and re-crystallisation, thus, promoting further growth of the calcite particles. In addition, the FT-IR analysis suggests surfactant residue, persistent even after extensive washing, is responsible for the poor adsorption behaviour of the calcite powders. However, in spite of the shortcomings, the present research has established the Proof of Concept for the innovative Reverse Micelle method. And the results from the research were used to apply for an Australian Innovation Patent, which was subsequently granted. Thus, validating the Proof of Concept and the quality of the research carried out as part of the present work.

Dans ce travail de thèse a été réalisé la synthèse de micro- et nano-particules de polyuréthane en milieux aqueux par les techniques de polyaddition en suspension et de polyaddition en miniemulsion sans catalyseur (procédés de synthèse économiques et respectueux de l'environnement). Le polyuréthane a été synthétisé à partir d'un polyol d'origine naturel et biodégradable. Un principe actif modèle (lévofloxacin) a été encapsulé dans les nano- et micro-particules. L'efficacité d'encapsulation et le profil de libération de ce principe actif ont été déterminés par la spectroscopie de fluorescence. La morphologie des particules a été analysée par MEB et MET et la formation du polyuréthane a été confirmée par FTIR. La technique de diffusion de la lumière a été utilisée pour déterminer la taille, la morphologie des particules et pour suivre la cinétique de la dégradation enzymatique de ces particules dans différents milieux (acides et basiques).

De nos jours, l'idée qu'une molécule puisse être utilisée comme élément actif dans un dispositif électronique stimule l'activité scientifique des laboratoires de chimie et de physique dans le monde entier. Les demandes technologiques en termes de capacité de stockage d'informations sont en croissance exponentielle et repose maintenant sur le développement des nanosciences. L'objectif consiste à stocker les données aussi rapidement que possible dans un dispositif aussi petit que possible. Une des stratégies les plus prometteuses est basée sur le concept de bistabilité moléculaire : la commutation entre deux états électroniques de la molécule de la même manière qu'un interrupteur binaire. Il est ainsi possible de passer d'une manière réversible et de façon détectable d'un état (OFF = 0) à un autre état (ON = 1) sous l'influence d'un stimulus externe contrôlé. Le phénomène de transition de spin (TS) qui commute le système entre états haut spin (HS) et bas spin (BS) est un exemple typique de bistabilité moléculaire. Les deux états peuvent être distingués par des propriétés magnétiques, optiques et structurelles différentes ; ces modifications pouvant être provoquées par différent stimuli comme la température, la lumière, la pression, un champ magnétique ou l'inclusion d'une molécule invitée. Lorsque les changements structurels associés à la transition de spin sont transmis d'une manière coopérative à travers les molécules du réseau, les transitions se produisent de manière abrupte et éventuellement s'accompagnent de boucle d'hystérésis (transition du premier ordre). Ainsi, les matériaux moléculaires à transition de spin devraient offrir de nombreuses possibilités en termes d'applications dans le domaine de l'électronique, le stockage de l'information, l'affichage numérique, la photonique et le photo-magnétisme. Parmi les différentes familles de composés, les polymères de coordination suscitent beaucoup d'intérêts en raison de leur bistabilité proche de la température ambiante. Le choix judicieux des ligands et des contre-anions permet de moduler les propriétés finales de ces composés, et même dans certains cas, de combiner de manière synergétique des propriétés physiques différentes. Le travail développé dans ces travaux de thèse vise à répondre aux différentes questions liées au défi des polymères de coordination à base de matériaux à transition de spin à l'échelle nanométrique. La synthèse de matériaux inorganiques bistables, leur développement dans des nanoparticules, des couches minces, leur organisation ainsi que leurs propriétés physiques sont présentés. Les matériaux à l'échelle microscopique ont généralement les mêmes propriétés physiques que celles mesurées à l'échelle macroscopique. Cependant, à l'échelle nanométrique, les matériaux peuvent présenter des propriétés physiques qui sont différentes de celles des composés massifs. Il est donc impératif de mieux comprendre les phénomènes liés à la diminution de la taille pour développer les nanotechnologies. L'étude fondamentale de ces nanomatériaux est nécessaire et représente aujourd'hui un défi majeur et essentiel pour le développement d'applications futures. Le développement de matériaux à l'échelle nanométrique à travers le contrôle de certains modèles systématiques permet d'améliorer notre compréhension sur les effets spécifiques à l'échelle nanométrique. Par exemple, dans le cas des complexes à transition de spin, la question la plus importante est : comment influence la réduction de taille des matériaux sur la température de transition, la coopérativité et la largeur de la boucle d'hystérésis ? Dans ce contexte, cette thèse est consacrée à la conception et à la synthèse de nano- et microparticules à transition de spin de différentes tailles et de différentes morphologies. Pour ce faire, nous avons développé la technique des micelles inverses et adopté de nouvelles approches de synthèse innovantes en l'absence de matrice
Nowadays, the idea that molecule can be used as an active element in an electronic device stimulates scientific activity of chemistry and physics laboratories worldwide. The information storage capacity from technological demands is growing exponentially, which relies much on the development of nanosciences. The objective is to store data as quickly as possible in a device as small as possible. One of the most promising strategies is based on the concept of molecular bistability, the switching between two electronic states of a molecule in the same way that a binary switch. It is thus possible to pass in a reversible and detectable manner from one state (OFF = 0) to another state (ON = 1) under the influence of a controlled external stimulus. The spin transition (ST) phenomenon that switches the system between high spin (HS) and low spin (LS) states is a typical example of molecular bistability. The two states can be distinguished with different magnetic, optical and structural properties and can be induced by an external perturbation like the temperature, the light, the pressure, a magnetic field or the inclusion of a guest molecule. When the structural changes associated with the spin transition are transmitted in a cooperative manner across the network molecules, the transitions will occur with steepness and possibly accompanied by hysteresis loop (the first order transition). So, spin transition molecular materials should offer many opportunities in terms of applications in the field of electronics, information storage, digital display, photonics and photo-magnetism. Among the different families of compounds, coordination polymers arouse much interest due to their bistability near room temperature. The judicious choice of ligands and counter-anions make possible to modulate the final properties of these compounds and even in some cases to synergistically combine different physical properties. The work developed in this thesis attempt to address the different issues related to the challenge of coordination polymers based nanoscale materials with spin transition. The synthesis of inorganic bistable materials, their development in micro- and nanoparticles, thin layers, their organization and their physical properties are shown. The materials in the microscopic scale have mostly the same physical properties as those measured at the macroscopic scale. However, at the nanoscale, materials can exhibit physical properties that are far from those of bulk compounds. It is therefore imperative to understand more about the phenomena related to material size decrease to develop nanotechnology. The fundamental study of these nanomaterials is necessary and represents a major challenge today, which is of prime importance for the development of future applications. The development of nanoscale materials through the control of certain systematic models permits to improve our understanding of specific effects at the nanoscale. For example, in the case of spin crossover complex, the most important question is: how downsizing effect influences the transition temperature, the cooperativity and the width of hysteresis loop? In this context, this thesis is devoted to the design and the synthesis of various size spin crossover nano and micro-materials with different morphologies. To accomplish this, we developed the reverse-micelle technique and adopted innovative matrix-free synthetic approaches

Cette thèse présente le développement de tests immunologiques innovants, rapides et sensibles combinant des nanoparticules superparamagnétiques (SPN) fonctionnalisées et des micro-aimants : nos immuno-essais magnétiques exploitent les forts gradients de champ magnétique de ces micro-aimants pour capturer les complexes immunologiques liés aux SPN. L’attraction magnétique est souvent utilisée en biotechnologies car elle peut générér des forces capables de capturer des molécules d’intérêt. Les immuno-essais sur billes utilisent habituellement des aimants centi- et millimétriques pour capturer des micro-particules. Réduire la taille des particules magnétiques est très intéressant pour réduire les cinétiques de réactions, tout en diminuant les phénomènes de sédimentation et d’agrégation. Cette réduction d’échelle des particules permet aussi d’augmenter la surface de réaction et ainsi d’augmenter la sensibilité des tests. Cependant les aimants millimétriques génèrent des gradients faibles qui capturent difficilement les SPN, trop mobiles. Les micro-aimants de l’Institut Néel génèrent des forts gradients locaux et ainsi des forces magnétiques importantes. Ces technologies innovantes sont utilisées dans cette thèse pour développer des immuno-essais rapides tirant profit de la réduction d’échelle des particules et des aimants, par rapport aux technologies commerciales.Dans un premier temps, nous avons développé un test immunologique magnétique (MagIA) colorimétrique, comme approche innovante du test ELISA. Nous avons réalisé une preuve de concept pour la détection d’anticorps dirigé contre l’ovalbumine et comparé les résultats avec ceux de tests ELISA. Le test MagIA optimisé présente une limite de détection et une zone dynamique similaires au test ELISA développé avec les mêmes réactifs biologiques. Les micro-aimants fabriqués selon la méthode de micro-magnetic imprinting sont intégrés à bas coût dans les micro-puits des plaques multi-puits ELISA, et permettent la capture efficace des complexes immunologiques couplés aux SPN. La méthode est générique est permet de réaliser des tests ELISA en 30 minutes avec le même équipement.Nous avons ensuite développé un test magnétique immunologique avec une détection fluorescente locale tirant profit des propriétés de capture locale des SPN sur les micro-aimants. Ce test permet la quantification de la molécule d’intérêt en à peine 15 minutes sans étape de lavage. Une preuve de concept réalisée sur la détection de l’anticorps anti-ovalbumine a été réalisée, avec des anticorps de détection fluorescents et des micro-aimants fabriqués selon la méthode de thermo-magnetic patterning. La mesure différentielle entre le signal fluorescent provenant des complexes immunologiques couplés aux SPN localisées sur les micro-aimants, et le signal non spécifique (à l’extérieur des micro-aimants) permet la quantification d’une molécule. Ce test MLFIA (magnetically localized FIA) possède des performances jusqu’à 100 fois meilleures que les tests ELISA standard, pour la détection d’anticorps anti-ovalbumine en PBS. Le test MLFIA a ensuite été transféré à la détection de paramètres cliniques tels que la protéine C réactive, l'ostéopontine, et les sérologies de la toxoplasmose (IgG et IgM). La comparaison des résultats avec des méthodes automatisées a montré d’excellentes corrélations. Le test MLFIA présente plusieurs avantages : il est versatile, compatible avec les milieux biologiques, utilise de faibles volumes et requiert peu d’énergie. Ces résultats ouvrent la voie à une nouvelle génération de tests immunologiques sensibles et nous développons désormais un lecteur miniature pour le diagnostic portable
This thesis reports the development of innovative, sensitive and fast immunoassays combining functionalized superparamagnetic nanoparticles (SPN) and micro-magnets. Our magnetic immunoassays exploit high gradients generated by micro-magnets to capture immune-complexes captured on SPN. Magnetic attraction is widely used in biotechnology, because it provides long-range forces able to capture molecules of interest. Bead-based immunoassays use common centimetre-scale magnets to attract micro-particles. Those magnets generate low magnetic gradients and struggle to capture superparamagnetic nano-particles, which are too small and mobile to be efficiently trapped. Down-scaling the size of magnetic particles is very interesting since it allows diffusion-based transport to perform faster reactions, while avoiding particle sedimentation and aggregation. Furthermore, it increases the reaction surface, which improves the sensitivity of immunoassays. Thanks to the scaling law effects micro-magnets from Institut Néel generate high local gradients and therefore large magnetic volume forces: we use this innovative technology to develop fast immuno-assays that take advantage of a radical size reduction, compared to commercial technology.We first developed a colorimetric magnetic immunoassay (MagIA) as a new approach to standard ELISA. A proof-of-concept based on colorimetric quantification of anti-ovalbumin antibody in buffer was performed and compared with conventional ELISAs. After optimization, MagIA exhibits a limit of detection and dynamic range similar to ELISAs developed using the same biochemical tools. Micromagnets made by the micro-magnetic imprinting method can be fully integrated in multi-well plates at low cost, allowing the efficient capture of immuno-complexes carried by SPNs. The method is generic and performs magnetic ELISA in 30 min.We then developed a magnetically localized fluorescent immunoassay (MLFIA) exploiting the local capture of SPN on micro-magnets. The differential measurement of fluorescence localized on and besides micro-magnet arrays allows the detection and quantification of a molecule in only 15 minutes without fluid handling. We present a proof of concept based on the detection of monoclonal antibody anti-ovalbumin. Functionalized nanoparticles are incubated with fluorescent detection antibody and the sample containing the molecule to be detected. After a single incubation step, the nanoparticles are captured on micro-magnets made by thermo-magnetic patterning. Fluorescence is then read under a microscope. Differential measurement between the signal from the immunological complex localised on the micro-magnets and the non-specific signal localised besides micro-magnets allows the quantification of mAb anti-OVA. The performance of MLFIA was compared with conventional ELISA and exhibits a limit of detection up to 100 times better for anti-OVA mAb in PBS. For further validation, MLFIA was used to measure clinical parameters: we developed a sandwich assay to detect C-reactive protein, and a serology for Toxoplasma gondii immunoglobulin G and M or osteopontin in human samples. Comparisons with data obtained with routine clinical automatized methods show excellent correlation. Our MLFIA technology presents several key advantages: it is compatible with biological media (serum, plasma), uses small volumes and requires little energy. It also is versatile and thus can be used to detect any antigen or antibody in complex media. We are currently developing a portable prototype for point-of-care diagnostics. The results will open the way to a new generation of sensitive immunological lab-on-chip

Le but de cette étude est de concevoir, fabriquer et caractériser une puce microfluidique afin de mettre en oeuve la capture de nanoparticules magnétiques fonctionnalisées en vue de la reconnaissance d’anticorps spécifiques (couplage d’une très grande spécificité et sensibilité). Après avoir modélisé et simulé les performances de la microbobine intégrée dans le canal de la puce microfluidique en prenant soin de limiter la température du fluide à 37°C, la capture devant être effective, le microsystème est fabriqué en salle blanche en utilisant des procédés de fabrication collective. La fabrication du microdispositif en PDMS a aussi donné lieu à l’optimisation de procédés de modification de surface afin d’assurer la ré-utilisation du microdispositif (packaging réversible) et la limitation de l’adsorption non spécifique. L’immobilisation des anticorps su les billes (300 nm) a été menée à l’intérieur du canal en utilisant un protocole de type ELISA éprouvé. Le procédé a montré qu’il était également efficient pour cet environnement puisque nous avons pu mettre ne évidence la capture de nanoparticules
In this study, a concept of microfluidic chip with embedded planar coils is designed and fabricated for the aim of trapping effectively functionalized magnetic nanobeads and immobilizing antibody (IgG type). The planar coils as a heart of microfluidic chip is designed with criterion parameters which are optimized from simulation parameters of the maximum magnetic field, low power consumption and high power efficiency by FE method. The characterization of microcoils such as effectively nanobeads (300 nm) at low temperature (<37oC) is performed and confirmed. The channel network in PDMS material is designed for matching with entire process (including mixing and trapping beads) in microfluidic chip. A process of PDMS’s surface modification is also carried out in the assemble step of chip in order to limit the non-specific adsorption of many bio substances on PDMS surface. The microfluidic chip assemble is performed by using some developed techniques of reversible packaging PDMS microfluidic chip (such as stamping technique, using non-adhesive layer, oxygen plasma combining with solvent treatment). These packaging methods are important to reused microchip (specially the bottom substrate) in many times. The immobilization of antibody IgG-type is performed inside microfluidic chip following the standard protocol of bead-based ELISA in micro test tube. The result showed that IgG antibodies are well grafted on the surface of carboxyl-beads (comparing to result of standard protocol); these grafted antibodies are confirmed by coupling them with labeled second antibody (Fab-FITC conjugation)

Dans les prochaines années, les traitements des maladies graves (cancer, pathologies du cerveau, etc) pourraient fortement bénéficier des progrès en science des matériaux et des nanotechnologies. Du point de vue médical, il est bien connu que les cellules cancéreuses ont tendance à développer des résistances aux chimiothérapies dont les effets secondaires limitent considérablement l'efficacité des traitements. Pour ces raisons, la recherche de thérapies alternatives ciblant les cellules cancéreuses sans affecter les tissus sains est actuellement l'un des domaines les plus actifs de recherche sur le cancer. Dans ce contexte, les nanoparticules magnétiques reçoivent un intérêt croissant pour diverses applications biomédicales allant du diagnostic au traitement ciblé. En effet, grâce à leur possibilité d'actionnement contrôlé à distance par des champs magnétiques externes, les particules magnétiques ont la capacité d'exercer des forces ou couples localisés sur des espèces biologiques ciblées.Ce travail de thèse décrit une approche basée sur l'action mécanique de particules magnétiques bio-fonctionnalisées sur des cellules cancéreuses. Lorsque ces particules sont liées aux cellules cancéreuses, l'application d'un champ magnétique alternatif externe induit l'oscillation des particules, qui transmet alors une force mécanique aux cellules cancéreuses.Les particules magnétiques utilisées pour cette application ont fait l'objet d'un long développement. Contrairement aux particules magnétiques conventionnelles synthétisées par des voies chimiques (« bottom-up »), les particules étudiées dans cette thèse ont été spécialement conçues par des techniques développées pour la micro/nanoélectronique (« top-down »). Ainsi, deux types de particules magnétiques ont été comparés ; des particules antiferromagnétiques synthétiques (SAF) constituées d'empilements de couches magnétiques et des microparticules constituées d'une couche magnétique unique avec une configuration de vortex magnétique.Une fois ces particules mises en solution, les phénomènes d'auto-polarisation qui contribuent à l'agglomération / dispersion de ces particules par les interactions magnétostatiques ont été comparés, ainsi que les couples mécaniques que ces deux types de particules magnétiques peuvent générer sur les cellules cancéreuses lorsqu'elles sont soumises à un champ magnétique externe.Bien que les particules SAF génèrent de plus grands couples, remplacer les constituants de l'empilement magnétique par des matériaux biocompatibles reste délicat, ce qui n'est pas le cas de leurs homologues en vortex magnétique, facilement réalisables avec des oxydes de fer.En exploitant les propriétés des vortex magnétiques en NiFe, nous avons développé une approche pour la destruction ciblée des cellules cancéreuses du carcinome rénal humain. Les tests menés in-vitro montrent que ce stimulus magnéto-mécanique créé deux effets dramatiques : une diminution significative du taux de cellules cancéreuses vivantes, et l'initiation du processus d'apoptose (ou mort cellulaire programmée) et ce, en appliquant de faibles valeurs de champs (~100 Oe c'est-à-dire 10mT) à de très faibles fréquences (~ 20 Hz). Des études pour la quantification de la mort cellulaire par cytométrie en flux ont été menées. Les résultats déjà obtenus bien qu'au stade « preuve de concept » sont très encourageants pour le futur des nouvelles thérapies du cancer
In the coming years, the treatment of serious diseases (cancer, brain diseases, etc.) could benefit more intensely from advances in materials science and nanotechnology. From the medical point of view, it is well known that cancer cells tend to develop resistance to chemotherapy, and the side effects encountered seriously limit the effectiveness of treatments. For these reasons, the search for alternative therapies that target cancer cells without affecting healthy tissues is currently one of the most active areas of research on cancer. In this context, magnetic nanoparticles are receiving an increasing interest in a variety of applications ranging from biomedical diagnostic to targeted treatments. Indeed, due to their remote actuation by external magnetic fields, the magnetic particles have the ability to locally perform actuations on targeted biological species.This thesis describes an approach based on interfacing cancer cells with bio-functionalized magnetic particles. When these particles are bound to the cancer cells, applying an external alternating magnetic field induces the particles oscillations, which then transmits a mechanical stress to the cancer cells.For this application, specific magnetic particles were prepared. Unlike conventional magnetic particles made by chemical routes ("bottom-up"), the particles studied in this thesis have been specially designed by techniques used in micro / nanoelectronics ("top-down"). Thus, two types of magnetic particles were compared; synthetic antiferromagnetic particles (SAF) consisting of magnetic multilayer stacks and microparticles consisting of a single magnetic layer with a magnetic vortex configuration.Once these particles released in a solution, the self-polarization phenomenon that contributes to the agglomeration / dispersion of these particles by magnetostatic interactions were compared for both types of particles as well as the mechanical torques that they can exert on cancer cells when subjected to an external magnetic field.Although SAF particles generate higher torques, finding biocompatible materials that may replace the constituents of the magnetic stack remains difficult, while vortex-particles would be easier to make in magnetic iron oxides.By exploiting the properties of NiFe magnetic vortices, we have developed an approach for the targeted destruction of the human renal carcinoma cells. The tests launched in vitro show that the magneto-mechanical stimulus creates two dramatic effects: a significant decrease in the rate of alive cancer cells, and the initiation of the apoptosis (programmed cell death). These results were achieved by applying low field values (~ 100 Oe i.e.10mT) at low frequencies (~ 20 Hz). Studies for the quantification of cell death by flow cytometry were conducted. The results already obtained even at the stage of "proof of Concept" are very encouraging for new perspectives of cancer therapies

Addition of nano particles to cooling fluids has shown marked improvement in the heat transfer capabilities. Nanofluids, liquids that contain dispersed nanoparticles, are an emerging class of fluids that have great potential in many applications. There is a need to understand the fundamental behavior of nano dispersed particles with respect to their agglomeration characteristics and how it relates to the heat transfer capability. Such an understanding is important for the development and commercialization of nanofluids. In this work, the stability of nano particles was studied by measuring the zeta potential of colloidal particles, particle concentration and size. Two different sizes of silica nano particles, 10 nm and 20 nm are used in this investigation at 0.2 vol. % and 0.5 vol. % concentrations. The measurements were made in deionized (DI) water, buffer solutions at various pH, DI water plus HCl acid solution (acidic pH) and DI water plus NaOH solution (basic pH). The stability or instability of silica dispersions in these solutions was related to the zeta potential of colloidal particles and confirmed by particle sizing measurements and independently by TEM observations. Low zeta potentials resulted in agglomeration as expected and the measured particle size was greater. The heat transfer characteristics of stable or unstable silica dispersions using the above solutions were experimentally determined by measuring heat flux as a function of temperature differential between a nichrome wire and the surrounding fluid. These experiments allowed the determination of the critical heat flux (CHF), which was then related to the dispersion characteristics of the nanosilica in various fluids described above. The thickness of the diffuse layer on nano particles was computed and experimentally confirmed in selected conditions for which there was no agglomeration. As the thickness of the diffuse layer decreased due to the increase in salt content or the ionic content, the electrostatic force of repulsion cease to exist and Van der Waal's force of agglomeration prevailed causing the particles to agglomerate affecting the CHF. The 10nm size silica particle dispersions showed better heat transfer characteristics compared to 20nm dispersion. It was also observed that at low zeta potential values, where agglomeration prevailed in the dispersion, the silica nano particles had a tendency to deposit on the nickel chromium wire used in CHF experiments. The thickness of the deposition was measured and the results show that with a very high deposition, CHF is enhanced due to the porosity on the wire. The 10nm size silica particles show higher CHF compared to 20nm silica particles. In addition, for both 10nm and 20nm silica particles, 0.5 vol. % concentration yielded higher heat transfer compared to 0.2 vol. % concentration. It is believed that although CHF is significantly increased with nano silica containing fluids compared to pure fluids, formation of particle clusters in unstable slurries will lead to detrimental long time performance, compared to that with stable silica dispersions.
M.S.M.S.E.
Department of Mechanical, Materials and Aerospace Engineering;
Engineering and Computer Science
Materials Science and Engineering

Spherical micro- and nano-particles have found widespread use in many various applications from paint to cosmetics to medicine. Due to the multiplicity of desired particle material(s), structure, size range, and functionality, many approaches exist for generating such particles. Bottom-up methods such as chemical synthesis have a high yield and work with a wide range of materials; however, these processes typically lead to large polydispersity and cannot produce structured particles. Top-down approaches such as microfluidics overcome the polydispersity issue and may produce a few different structures in particles, but at lower rates and only at the micro-scale. A method that can efficiently produce uniformly-sized, structured particles out of a variety of materials and at both the micro- and nano-scales does not yet exist. Over the past few years, I have developed an in-fiber particle fabrication method that relies on a surface tension-driven fluid instability, the Plateau-Rayleigh capillary instability (PRI). Thermal treatment of a multimaterial core/cladding fiber induces the PRI, causing the initially intact core to break up into a periodic array of uniformly-sized spherical particles. During this time, I have demonstrated that this method can produce particles from both polymers and glasses, in a multiplicity of structures, and from diameters of over 1 mm down to 20 nm. Furthermore, by using a stack-and-draw method, a high density of cores may be incorporated into a single fiber, making the in-fiber PRI approach a highly scalable process. Finally, I have shown that it is possible to add dopants to the particles to give them functionality. By structuring the particles, it is thus possible to fabricate multi-functional particles whose functionalities may be allocated arbitrarily throughout the volume of the particles.
Ph.D.
Doctorate
Optics and Photonics
Optics and Photonics
Optics and Photonics

Orientador: Mário Tanomaru Filho
Banca: José Mauricio dos Santos Nunes Reis
Banca: Josette Camilleri
Banca: Marcos Húngaro Duarte
Banca: Loise Pedrosa Salles
Resumo: O cimento Portland é constituído por silicato de cálcio e a associação com aditivos e veículos conferem características que podem viabilizar seu uso como cimento endodôntico. No entanto, o cimento Portland não apresenta radiopacidade própria, o que torna necessário a adição de um agente radiopacificador à mistura para ser utilizado como material dentário. O objetivo deste estudo foi avaliar as propriedades físico-químicas e mecânicas, o potencial bioativo e caracterizar a interface dentina-cimento de cimentos endodônticos experimentas à base de cimento Portland (ES) contendo nano ou micro partículas de óxido de zircônio ou óxido de nióbio. O tempo de presa, resistência à compressão, escoamento, espessura de filme, radiopacidade, solubilidade e estabilidade dimensional foram avaliadas de acordo com a norma ISO 6876:2012, enquanto que a liberação de fomaldeído foi avaliada por meio de cromatografia gasosa. A resistência de união dentinária foi avaliada por meio de teste push-out e tanto a caracterização da microestrutura dos cimento quanto a análise do potencial bioativo foram realizadas utilizando energia dispersiva de raios-x, difractometria e espectroscopia infravermelha. A interface dentina-cimento foi avaliada com relação à penetração de microesferas fluorescentes e examinada em microscopia confocal e microscopia eletrônica de varredura associada à escaneamento por energia dispersiva de raios-x linear. Os dados foram submetidos aos testes ANOVA e Tukey (p < 0,05). Com exceção da radiopacidade, os ES apresentaram propriedades físico-químicas de acordo com as especificações ISO 6876, adequada resistência de união à dentina, potencial bioativo e promoveram selamento coronário e interação química com a dentina.
Abstract: Portland Cement is composed by calcium silicate and the association with additives or vehicles, may confer characteristics to enable the use of this cement as root canal sealer. However, Portland cement lacks in radiopacity which requires the addition of a radiopacifying agent to the mixture to be used as dental material. The purpose of this study was to assess the physicochemical and mechanical properties, the bioactivy potential and to characterize the dentin-sealers interfaces of Portland-based experimental root canal sealers (ES) containing nano or micro particles of zirconium oxide or niobium oxide. Setting time, compressive strength, flow ability, film thickness, radiopacity, solubility and dimensional stability were evaluated according to ISO 6876:2012 standards, whereas formaldehyde realease was investigated using gas-cromatography. Dentin bond strength was evaluated by push-out test and the sealer's microestruture and bioactivity potential were perfomed using X-ray energy espectroscopy, X-ray diffractometry and infrared spectroscopy. Dentin-sealers interface was assessed with respect to fluorescent microspheres penetration and it was also examined using confocal microscope and scanning electron microscope coupled to X-ray energy dispersive line scans. Data were analyzed by ANOVA and Tukey post-hoc test (p < 0.05). With the exception of radiopacity, ES showed physicochemical properties according to ISO 6876:2012 specifications, adequate dentin bond strength, great bioactivity potential and promoted coronal sealing and chemical interaction with dentin.
Doutor

碩士
正修科技大學
化工與材料工程研究所
96
First, to preparation the nano gold particles with batch, and found the best reactants and conditions from preparation the nano gold particles. To preparation the nano gold particles with three kinds of microfluidic﹑T type reactor and AA sprinkle-nozzle in this study. The nano gold particles determined the particle size with nano zetasizer. To compare the nano gold particle size with this four kinds. To analyze the optical character and examine the nano gold particles with ultraviolet-visible spectrophotometer and fluorimeter. At last, to examine the nano gold particle size and shape with transmission electron microscope. The best condition to preparation the nano gold particles with batch for the smallest particle size is around 6 nm；The microfluidic already made can achieve about 21 of X/Y ; the nano gold particle size composed by microfluidic is around 100 nm in min; the nano gold particle size composed by T type reactor is around 1-3 nm in min; the nano gold particle size composed by AA sprinkle-nozzle is around 1-3 nm in min; The ultraviolet-visible spectrophotometer have peak in 520 nm, and it have the character of surface plasmon resonance; The fluorimeter can be known nano gold particle contained Au5﹑Au8 and Au13. TEM can be known round nano gold particle size below 10nm.

碩士
國立成功大學
化學工程學系碩博士班
98
Chitosan micro/nanoparticles have been successfully produced using the electrohydrodynamic atomization (EHDA). In this study, the choices of solvent play an important role. Trifluoroacetic acid (TFA) has been used as the solvent for chitosan because of the lower value of surface tension. The effect of applied voltage, distance between the electrodes and flow rate on the morphology and the particle size distribution were investigated systematically. A chitosan solution having a low concentration could be used to prepare chitosan particles during a suitable electric distance. The size of the fabricated particles decreased with increasing applied voltage as well as decreasing flow rate. By using Taguchi Methods, the strategy for a controlled size and narrow size distribution were developed. A suitable scaling law, which allow for prediction of the size of the produced polymer particles based on the polymer weight fraction and electrohydrodynamic atomization process parameters, were formulated and tested. The relative error value was -8.15 %.

碩士
國立成功大學
微機電系統工程研究所
93
This paper describes a method for self-assembly of micro/nano particle by using dielectrophoretic force. In this paper of parameters, including voltage and frequency of driving signal are studied to optimize the performance of the particle assembly. 25μm and 10μm diameter latex particles are chosen in this study. CCD camera is used to record image sequence.Electrodes are fabricated by using Micro Electro Mechanical System technology being particle assembly. Before bonding of polydimethylsiloxane (PDMS) film. O2 plasma is used to treat dielectrophoretic self-assembly chip surfaces, which cause the surface becoming hydrophilic. The experimental results show that the latex particle are assembled in 200μm and 500μm assembly region with driving signal V = 20(V)、f = 1.125 (MHz)、V = 250(V) and f = 1.125 (MHz). Quadrupole electrodes are excited with alternating voltages, and latex particle are assembled in the 400μm × 400μm assembly region, which is defined by PDMS film. Finally, a driving signal with voltage of V = 6.75(V) and frequency of f = 1.125 (MHz) are found to be optimize condition for the latex particle assembly. Hexapole electrodes are excited with a driving signal with voltage of V = 6.75(V) and frequency of f = 1.125 (MHz), and latex particle are assembled in the 100μm × 100μm assembly region.The experimental results under this driving signal, the latex particles can self-assembly into a organized structure which can provide beneficial guide for self-assembly of micro particle into form.

碩士
國立成功大學
工程科學系
103
The rapid development of human society so that environmental issues become increasingly prominent, which the air quality in Taiwan and tropical cyclones have a considerable impact on Taiwan's meteorological environment. Taiwan summer tropical cyclone is a higher fre-quency of occurrence of severe weather, all areas of life in Taiwan will have a significant impact. This study use WRF(Weather Research and Forecasting)and Coupled chemical systems (WRF-Chem3.5),that is the latest release Non-hydrostatic equilibrium mesoscale numerical prediction model in this study and use Fick's laws of diffusion to calculate mo-lecular diffusion coefficient of molecular diffusion capacity of the physical substance. In this study, the rear section of Taiwan EPA air quality data written WRF-Chem Simulation. Simulation of April 20, 2015 to the distribution of pollutants every other day,using gas phase chemistry model simulations of SO2, NO2, CO, O3, PM10, PM2.5 and other pollu-tants, the use of aerosol model simulations of PM10 and PM2.5,Find PM10 and PM2.5 aerosol model of forecasting of PM10 and PM2.5 Compared to the gas phase chemistry is accurate,But the simulated value significantly higher in the station observations.

碩士
南台科技大學
化學工程系
92
This study contains three sections. The first section is study of rigid poly (vinyl chloride) compounds blending with clay. The second section is study of rigid poly (vinyl chloride) compounds blending with micro/nano-CaCO3. The third section is study of high density polyethylene blending with micro/nano-CaCO3. In the first section, PVC/clay nanocomposites were successfully prepared by a Haake torque rheomix and examined by XRD and TEM. The fusion properties showed that the fusion time and the fusion temperature were increased, but the fusion torque was decreased, with the content of organic clay was increased. The opposite effect was occurred when the untreated clay was used. From the thermal results, the glass transition temperature of nanocomposite was increased and the thermal stability was decreased. From the mechanical property analyses, it showed that the clay improved the yield strength and elongation of two kinds of PVC/clay nanocomposites. The Young’s modulus of PVC/untreated-clay nanocomposite was increased. On the other hand, the organic clay had the opposite effects due to the organic chemical between the silicate layers and resulted in the Young’s modulus decreasing. In the second section, the fusion properties showed that the loading torque, the loading temperature, and the fusion torque were decreased with the content of calcium carbonate was increased. But the fusion time and fusion percolation threshold were increased with the content of calcium carbonate was increased. The effect of the nano-CaCO3 was more significant than that of the micro-CaCO3. From the thermal properties, Tg and thermal stability of PVC/CaCO3 nanocomposites were increased with the content of nano-CaCO3. The 10phr nano-CaCO3 had the best result. On the other hand, the micro-CaCO3 caused the opposite results. The SEM morphology results showed that CaCO3 were dispersed in the composite and resulted in voids. The PVC/nano-CaCO3 nanocomposites exhibited lightweight and good properties. In the third section, the variation is different kind of CaCO3, the content of CaCO3, and powder or pellet type HDPE. The fusion properties showed that the lower loading torque and the higher fusion time resulting from the HDPE powder. The HDPE/nano-CaCO3 nanocomposites displayed the higher loading torque and the shorter fusion time than those of the HDPE/micro-CaCO3 composites. From the TGA results, it showed the thermal stability of HDPE/nano- or micro- CaCO3 composites were improved, especially for the nano-CaCO3. From the DSC non-isothermal crystallization analysis, the crystallization temperature of HDPE was increased with the content of CaCO3 was increased. It implied the crystallization rate of HDPE was increased. The crystallinity of HDPE was decreased with the content of CaCO3 was increased. The melting point of HDPE was decreased due to its crystallinity was decreased.

This thesis described the development of new strategies for the preparation of micro- and nano-structured polymer materials. In particular, this thesis focused on: i) the synthesis of polymer particles in microreactors, and ii) the self-assembly of inorganic nanorods. First, this thesis presented the synthesis of polymer particles and capsules with pre-determined sizes and narrow size distributions (CV<2%) in continuous microfluidic reactors. The method includes (i) the emulsification of monomers in a microfluidic flow-focusing device and (ii) in-situ solidification of droplets via photopolymerization. This microfluidic synthesis provides a novel strategy for the control over the shapes, compositions, and morphologies of polymer particles. In particular, we demonstrated the control over particle shapes by producing polymer ellipsoids, disks, rods, hemispheres, plates, and bowls. We produced polymer particles loaded with dyes, liquid crystals, quantum dots, and magnetic nanoparticles. We generated core-shell particles, microcapsules, Janus and three-phasic polymer particles. Control over the number of cores per droplet was achieved by manipulating the flow rates of liquids in the microchannels. We further investigated the hydrodynamic mechanism underlying the emulsification of droplets, which helps in guiding scientists and engineers to utilize this technique. Second, we described the self-assembly of inorganic nanorods by using a striking analogy between amphiphilic ABA triblock copolymers and the hydrophilic nanorods tethered with hydrophobic polystyrene chains at both ends. We organized metal nanorods in structures with various geometries such as nanorings, nanochains, bundles, bundled nanochains, and nanospheres by tuning solely the quality of solvents. The self-assembly was tunable and reversible. This approach paved the way for the organization of anisotropic nanoparticles by using the strategies that are well-established for the self-assembly of block copolymers. We further described a systematic study of the self-assembly of polymer-tethered gold nanorods as a function of solvent composition in the system and the molecular weight of the polystyrene blocks. We found that the structure of the polymer pom-poms played an important role on the organization of polymer-tethered gold NRs. The 'supramolecular' assembly was governed by the competition between the end-to-end and side-by-side association of NRs and resulted in the controlled variation of the plasmonic properties of NRs, reflected in a 3-D plasmonic graph.

碩士
國立清華大學
化學工程學系
98
Coating solutions with a significant amount of solid particles added are not unusual for many industrial applications. Products such as backlit films, diffusers for LCD panels, CIGS solar cells are just a few examples. Two issues arise for delivering such solutions, i.e. the solutions may have yield stress and particle sedimentations may appear in the manifolds for conventional coat-hanger or T-dies. There are experimental evidences that clearly indicate that particle sedimentation can be serious in the manifold on the die. A die that can maintain relatively high shear ratse in the manifold can improve this precipitation problem. The purpose of this research is to design a coat-hanger die which has a shallow manifold with rectangular cross-sectional area. Therefore, flow field with high shear rate can be achieved. Due to the high cost of traditional coat-hanger die, this research also propsed a new idea-using two easily-replaced shims to make a die, this design can effectively reduce the cost of manufacture. Both the theoretical modeling and the experimental verifications were carried out for die design. The coating solutions were assumed to obey the Bingham viscoplastic model. A mathematical model based on the 1D lubrication approximation, 2D Hele-Shaw flow and 3D flow simulations were developed to predict the performance of the new design, the computer-aided solutions by the finite difference (FDM) and the finite element method (FEM) could be obtain. The performance of the design based on the lubrication approach is in agreement with the 3D simulation and experimental results, therefore the new die can develop uniform flow and no stagnent zone can exist in the end of the manifold, so that the sedimentation can be avoided. We also compared the sedimentation and uniformity of our design to a commercial T-die and fishtail die experimentally, the results indicated the performance of our design is excellent, sedimentation and uniformity problem appeared in both the T die and fishtail die. The design of our research can be applied to the wet coating process of CIGS solar cell & TCO films.

碩士
國立臺灣大學
環境工程學研究所
99
This study investigated the recovery of magnetic micro-nano particles using high-gradient magnetic separator (HGMS). The major system parameters examined, include: inlet concentration of magnetic particles (MP) in the solution (CLF,i), volumetric flow rate (QL), magnetic field gradient (▽H), particle size (dp) and other parameters, such as packing density of magnetic media filled in the magnetic separation chamber (ρF). The separation efficiency(ηM), effective separation time (tB) and saturation time of separation chamber by the system parameters were evaluate. The mainly target particles studied were superparamagnetic particles of SM (SiO2/Fe3O4). For exploring the effects of particle size ,the magnetic Fe3O4 particles with sizes of 5-20,20-30 and 40-60 nm were employed. The magnetic SM particles were prepared using the sol-gel method, yielding the saturation magnetization of 23.19 emu g-1and particle size of 70-80 nm. The results indicate that a lower QL offers a longer tB and a better ηM for the HGMS. Also, a lower CLF,i of MP allows a large capture radius of magnetic media (rCF), resulting in a longer and a better ηM.The magnetic separation chamber filled with the magnetic media with a high ρF, provides higher magnetic field strength H and magnetic field gradient ▽H for the external magnetic field, and thus a higher ηM. Further, the capture of magnetic particles size with larger tends to reach saturation more easily. Therefore, the limitation of particle size should be considered for the capture of MP using HGMS. The multi-wire dynamic model was employed to simulate the performances of HGMS. Comparisons of experimental data and prediction indicate satisfactory agreement. The model can be used to predict the tB, optimum QL and other operating parameters, as well as the breakthrough curves. The results illustrate that the saturated magnetic matrix capacity of separation chamber is inversely proportional to the QL and CLF,i, however, is proportional to the magnetic field gradient. In practice, the model can be applied to simulate the real plant operation. The results may be used for the proper control of switching the magnetic field, thus avoiding the excessive loss of magnetic particles, and the secondary pollution to the environment.

The present Thesis focuses on the thermodynamic and dynamic behaviour of anisotropically interacting colloids by means of theoretical and numerical techniques. Colloidal suspensions, i.e. micro-- and nano--sized particles dispersed in a continuous phase, are a topic of great interest in several fields, including material science, soft matter and biophysics. Common in everyday life in the form of soap, milk, cream, etc., colloids have been used for decades as models for atomic and molecular systems, since both classes of systems share many features like critical phenomena, crystallisation and glass transition. Experimental investigation of colloidal systems is made easier by the large size of colloids, which makes it possible to employ visible light as an experimental probe to investigate these systems. Moreover, since the mass of the particles controls the timescales of the dynamics, relaxation times of colloidal suspensions, ranging from seconds to years, orders of magnitude larger than their atomic counterparts, are more easily experimentally accessible. By exploiting this intrinsic slowness, with respect to molecular liquids, present day experimental techniques make it possible to follow in time trajectories of ensembles of particles with tools like confocal microscopy, thus effectively allowing to reconstruct the whole phase space trajectory of the system. In addition, it is also possible to manipulate single and multiple objects using techniques like optical tweezers, magnetic tweezers and atomic force microscopy. With single-molecule force spectroscopy one can arrange particles in ordered structures or measure properties like stiffness or mechanical responses (as in pulling experiments on RNA and DNA strands of particles and aggregates). A remarkable difference between the molecular and the colloidal world is that in the former the interactions between the basic constituents are fixed by nature, while in the latter the effective potential between two particles can be controlled by accurately designing and synthesizing the building blocks or tuned by changing the properties of the solvent. In the last decade many new sophisticated techniques for particle synthesis have been developed and refined. These recent advances allow for the creation of an incredible variety of non-spherically, i.e. anisotropically, interacting building blocks. The anisotropy can arise from shape, surface patterning, form of the interactions or a combination thereof. Examples are colloidal cubes, Janus particles, triblock Janus particles, patchy particles, magnetic spheres and many others. The recent blossoming of experimental, theoretical and numerical studies and research on the role of the anisotropy has highlighted the richness of phenomena that these systems exhibit. Relevant examples for the present Thesis are valence-limited building blocks, i.e colloids with a maximum number of bound neighbours, and non-spherical particles with an aspect ratio, i.e. the ratio of the width of a particle to its height, significantly different from $1$. The simplest example of valence-limited colloids is given by the so-called \textit{patchy} particles: colloids decorated with attractive spots (patches) on the surface. If the width and the range of the patches are chosen in such a way that each patch can form no more than one bond, then the total number of bound first neighbours per particle $M$ can not exceed the number of patches. For particles interacting through short-ranged isotropic potentials, $M \approx 12$. It has been shown that changing the valence $M$ has dramatic effects, both qualitative and quantitative, on the dynamic and thermodynamic properties of such systems. At high densities patchy colloids can self-assemble into a large variety of crystal structures, depending on valence, geometry and external parameters. We will mostly focus on low-density systems. The second class of systems pertinent to the present work comprises anisotropically shaped particles that, depending on the aspect ratio and the values of the external parameters, can exhibit liquid crystal phases which may display orientational long-range order. Nematic, in which there is no translational order, smectic, in which particles are ordered in layers and thus exhibit translational order in one dimension, and columnar phases, in which particles self-assemble into cylindrical aggregates which can in turn become nematic or form two-dimensional lattices, do not exist in isotropic systems, since the anisotropy in shape is a prerequisite for the breaking of the orientational symmetry. Liquid crystals, discovered at the end of the 19th century have been thoroughly investigated for decades, leading to technological breakthroughs like LCD displays. Recently it has been suggested that liquid crystal phases occurring in dense solutions of short DNA double strands could have played a role in the prebiotic chemical generation of complementary H-bonded molecular assemblies. The main goal of the present Thesis is to study the structural, thermodynamic and, to a lesser extent, dynamic properties of systems interacting through anisotropic potentials at low densities and temperatures. In particular, we focus on the low-density phase behaviour of valence-limited systems. We use a variegated approach, comprising state-of-the-art Monte Carlo and Molecular Dynamics techniques and theoretical approaches, to analyse and shed some light on the effect of the anisotropy on the phase diagram and on the dynamics of such systems. As the effect of the valence on the phase diagram plays a major role in the models investigated throughout this Thesis, each Chapter is devoted to the study of the dynamics and thermodynamics of systems having a fixed or effective maximum valence $M$. In the last years a lot of effort has been devoted to the study of end-to-end stacking interactions between different strands of nucleic acids, which play an important role in both physical and biological applications of DNA and RNA. In Chapter~1, building on the experimental work of Bellini \textit{et al.}, we make use of a theoretical framework recently developed to tackle the problem of the isotropic--nematic phase coexistence in solutions of short DNA duplexes (DNADs). We compare the parameter-free theoretical predictions with results from large scale numerical simulations on GPUs of a coarse-grained realistic model and find a good quantitative agreement at low concentrations. We then predict the phase boundaries for different DNAD lengths and compare the results with experimental findings. In Chapter~2 we investigate the structural and thermodynamic properties of systems having $M=2$, that is systems that undergo an extensive formation of linear structures as temperature is lowered. We focus on bi-functional patchy particles whose interaction details are chosen to qualitatively mimic the behaviour of the low-density, low-temperature dipolar hard sphere (DHS) model by analysing the outcomes of the simulations carried out in Chapter~3. In particular, we are interested in the interplay between chains and rings in equilibrium polymerization processes in a region of the phase diagram where the formation of the latter is favoured. The very good quantitative agreement found by comparing numerical results with theoretical, parameter-free predictions calls for an extension of the theory with the inclusion of branching, in order to understand how the presence of rings affects the phase separation. Chapter~3 is devoted to the investigation of the phase behaviour of dipolar fluids, i.e. systems interacting mainly through dipole-dipole potentials. For spheres, the lowest-energy configuration is the nose-to-tail contact geometry, and hence the ground state is an infinite chain or ring like in regular $M=2$ systems. For finite temperatures, on the other hand, thermal fluctuations allow for the appearance of defects like dangling ends and chain branching which, in the language of this Thesis, makes for a temperature-dependent valence. This general mechanism, under some specific conditions, can lead to a very peculiar phase separation, driven by a balance between these \textit{topological} defects rather than by the energy/entropy competition usually responsible for regular gas--liquid phase transitions. This topological phase transition has been recently observed in a model system of patchy particles but it is unclear whether such mechanism still holds in dipolar fluids in general and in the DHS model in particular. We focus on the DHS model, whose phase behaviour at low densities and temperatures has been studied for decades but still remains largely unknown. In particular, we look for the gas--liquid critical point by means of state-of-the-art Monte Carlo simulations in a region where it has long been thought to be. We find no evidence of a phase transition and we speculate that this is due to an abundance of rings, providing a remarkable example of phase separation suppressed by self-assembly. In Chapter~4 we study the dynamics of tetravalent patchy particles in the optimal network density region. For this fixed value of density the system is able to form a fully connected random network, i.e. an ideal gel. Indeed, as the temperature is lowered, a percolating network forms and the dynamics slows down. Although the observed dynamical arrest is different from the glass case, where excluded volume interactions are dominant, the decay of the self-- and collective correlation functions of the resulting fluid bears similarities with that observed in glassy systems. Remarkably, comparing the characteristic decay times of density-density correlation functions with the average bond life, we find that only at very low $T$ the decay of the density fluctuations requires the breakage of bonds. In Chapter~5 we introduce DNA as a building block that can be used to rationally design novel, self-assembling materials with tunable properties. In this Chapter, we study the phase behaviour and the dynamics of four-armed DNA constructs at low densities. We use the coarse-grained, realistic DNA model employed in Chapter~1 and state-of-the-art simulation techniques, as presented in Chapter~6, to investigate systems composed of thousands of nucleotides undergoing a two-step self-assembling process and we quantitatively compare the outcome with experimental results obtained for a very similar system. In Chapter~6 we introduce Graphics Processing Units (GPUs) as valuable tools for present day numerical investigations. We outline both the architecture of NVIDIA GPUs and NVIDIA CUDA, the software layer built on top of the hardware required to program these devices. We then present the techniques employed to write an efficient, general Molecular Dynamics code and compare its performances with a regular CPU code. The observed performance boost allows us to tackle the analysis of the dynamics and thermodynamics of very large systems without having to resort to massive CPU clusters (see Chapters~1,~4 and~5). Our work shows that it is possible to predict the location of thermodynamic and dynamic \textit{locii} of very complicated objects by means of numerical simulations. Since the available computational power keeps increasing at a steady pace, it will be soon possible to repeat the pioneering study presented in this Thesis on a more automated basis and for even more complicated system. For example, it will be possible to directly study the isotropic--nematic phase transition of short DNA duplexes investigated in Chapter~1 or design self-assembling DNA strands able to reproduce the behaviour of the patchy colloids or dipolar fluids studied throughout this Thesis. Being able to carefully design the building blocks and then predict beforehand the properties of a compound will greatly simplify the process of synthesising tomorrow's materials.

碩士
國立高雄應用科技大學
化學工程與材料工程系博碩士班
104
As the development of electronic components in the direction of miniaturization, high-power, and high integration, it requires more and higher performance, so the waste heat generated by the operation of components, need to be ruled out quickly, otherwise it will reduce the performance of electronic components. High thermal conductivity polymer composite materials with high thermal conductivity and high-performance are the most widely used in electronic components. This study is using electrospinning method to prepare high thermal conductivity micron network Al2O3-Ag fillers, and applied to enhance thermal conductivity of Al2O3-Ag/epoxy composites. Commonly, to enhance thermal conductivity of polymer matrix composite via a large amount of thermal conductivity powders loading in matrix (ex: AlN). From the images of SEM, indicated the Al2O3-Ag fillers with 1-D micron network structure and high aspect ratio (> 50), and identified as cubic system Ag and rhombohedral system Al2O3 by XRD and TEM. From the spectra of FT-IR, confirmed the material surface grafted with siloxane. By a four-point probe tester detected the volume resistivity value, confirmed the Al2O3-Ag/epoxy composites is non-conductive material. The Al2O3-Ag/epoxy composites using a thermal conductivity meter (Hot-Disk) to detect the heat transfer coefficient, was prepared the Al2O3-Ag fiber and modified Al2O3-Ag fibrous fillers, as 50 wt% addition amount of epoxy composite, the thermal conductivity were 0.77, 0.60 W/mK, respectively. And had 285% and 200% enhancement in thermal conductivity, respectively. This conclusion can be observed the filler which were modified has the better thermal conductivity, by using SEM observe the surface morphology of cross section can be found within the composites material is modified through the addition of materials and organic substrates interface significantly reduced, which can be attributed to the additional material bonded with an epoxy resin. DMA detects storage modulus and glass transition temperature, in addition to silane internal substrate material can effectively inhibit crack growth and storage modulus increases, but because of this situation hinders the crosslinked epoxy resin.

[Italiano] Obiettivo del Progetto di Dottorato, finanziato dalla Nylstar-Italia (azienda produttrice di poliammide), era realizzare fibre ad azione cosmetica per produrre calze, guanti e maglieria intima a nuovo valore aggiunto da introdurre nel mercato dei tessili skin care. Il primo passo dell’attività di ricerca è consistito nell’individuazione dell’agente cosmetico in base alla sua affinità con lo strato cutaneo e alla sua resistenza alla degradazione termica, tenendo conto che la poliammide 6 (PA6) viene processata ad altissima temperatura (240°C). L’analisi termica è stata effettuata su campioni di Vitamina E (tocoferolo con capacità antiossidanti), Myritol (miscela di trigliceridi dell’acido caprilico e capronico, universalmente impiegato in cosmesi) e Olio di Jojoba (estere di cera liquida costituito da acidi grassi e alcoli ad alto peso molecolare). E’ risultato che l’Olio di Jojoba possiede una temperatura di inizio degradazione di circa 327°C e subisce una perdita in peso di circa l’1% se lasciato 15minuti a 290°C in atmosfera di azoto; inoltre la sua costituzione chimica è altamente affine a quella del sebo prodotto dalla pelle, quindi viene facilmente assorbito da essa. Poiché PA6 e Olio di Jojoba hanno diversa natura chimico-fisica, l’additivazione è stata effettuata ricorrendo ad una duplice strategia: la preparazione di microcapsule a guscio poliammidico contenenti l’Olio e la dispersione dello stesso in matrice mediante un vettore nanoparticellare. Le microcapsule sono state sintetizzate mediante policondensazione interfacciale. Per le poliammidi la reazione avviene all’interfaccia tra due fasi: la fase acquosa contenente il monomero idrofilo (una diammina) e la fase organica contenente il monomero idrofobo (il dicloruro di un acido). La procedura di sintesi consta di tre momenti: 1)realizzazione di un’emulsione diretta della fase organica contenente il dicloruro in acqua 2)trattamento con ultrasuoni dell’emulsione delle goccioline 3)aggiunta della fase acquosa contenente la diammina Al fine di ottenere un guscio poliammidico con buone caratteristiche meccaniche, sono state utilizzate ammine e dicloruri di vario tipo nonché due diversi agenti reticolanti da impiegare rispettivamente in fase acquosa o in fase organica. Le microcapsule sono state osservate al SEM per decidere, qualitativamente, quale sistema fosse più idoneo ai nostri scopi. La combinazione esametilendiammina (HMDA)- dicloruro di tereftaloile (DCT)- tricloruro di mesoile (come agente reticolante) fornisce microcapsule di forma sferica, con guscio esterno liscio e compatto e diametro medio 5-10micron. Queste microcapsule sono state introdotte nella matrice polimerica, i risultati dell’analisi al DSC indicano che il guscio politereftalammidico protegge in una certa misura l’Olio dalla degradazione termica. Parallelamente è stato sperimentato come compatibilizzante un vettore nanometrico, in particolare sono stati confrontati un organoclay commerciale (Nanomer®I.28) e il CaCO3 nanoparticellare. Sono state preparate blends a diverso contenuto in peso filler/Olio di Jojoba dalle quali sono poi state ricavate le fibre. Sulle miscele polimeriche sono state eseguite indagini morfologiche ai raggi X e al microscopio elettronico a trasmissione, sulle nano-fibre sono state effettuate prove di caratterizzazione termica e meccanica. Il dato più interessante è relativo all’effetto della struttura geometrica del vettore nanometrico: il nanofiller lamellare intrappola l’Olio di Jojoba tra gli strati e lo protegge dalla degradazione nelle fasi successive della lavorazione, mentre le nanoparticelle di CaCO3 rappresentano solo un substrato su cui l’olio viene adsorbito per essere trasportato nella matrice senza svolgere nessuna azione protettiva. L’analisi FTIR ha consentito di monitorare la presenza del Jojoba nella poliammide mediante l’osservazione del segnale relativo al picco estereo caratteristico a 1740cm-1: a parità di contenuto di nanocarica, i materiali a base di organoclay mostrano una banda più intensa se paragonati a quelli contenenti CaCO3. La proprietà di maggiore interesse ai fini dell’applicazione cosmetotessili delle fibre nanocomposite, riguarda il rilascio dell’agente attivo. Una valutazione preliminare della possibilità di estrarre l’Olio di Jojoba dalla poliammide è stata effettuata ponendo i materiali in isopropanolo. L’analisi FTIR ha mostrato come dopo circa 26 ore a temperatura ambiente, il segnale relativo all’Olio non compare più nello spettro di tutti i campioni. Test di rilascio sono stati eseguiti anche simulando le condizioni di utilizzo delle fibre, nello specifico il trattamento di lavaggio e il contatto con il sebo cutaneo. Nel caso della simulazione di lavaggio dopo due ore in acqua e DASH a 55°C, il picco a 1740cm-1 è rimasto invariato. Il contatto prolungato (48 ore a T=37°C) con una formulazione simulante il sebo cutaneo ha invece provocato una modifica del segnale caratteristico dell’Olio di Jojoba; ulteriori analisi verranno effettuate per comprendere tale meccanismo di rilascio. [Inglese] The textile and clothing industry, normally seen as a traditional industry, needs nowadays to fight increased competition specically from Asia. There is a general recognition that traditional apparel products may be no longer sufficient to sustain a viable business and the EU textile industries have to move towards more innovative and high quality products. New materials and technologies promote development of high-tech textiles, characterized by unprecedented functions and effects. An example of the new way to combine tradition and innovation is represented by fibers having skin care activity, which are able to release on the wearer cosmetics and perfumes agents. Widely spreaded are microcapsules containing active substances grafted on the textile or spinned into the fibers, which can release thei content as a consequence of body heat and friction. Otherwise, the active agent embebbed into the fabric can be transferred thanks to humidity exchange between skin and fibers surface. Specific purpose of this PhD work has been to estimate the possibility of making products having skin care effects by means of Jojoba Oil additivation to nylon fibers. Since polyamide 6 and Jojoba Oil have different physico-chemical nature, the additivation was carried on by means of two different strategies: synthesis of politerephthalamide microcapsules containing Jojoba Oil and direct dispersion of Jojoba Oil into the polyamide matrix using a nanosized filler acting as additive carrier. In this study polyamide microcapsules Jojoba Oil containing having mean diameter of ~5m were synthesized by means of ultrasonic irradiations. A qualitative description of microcapsules characteristics in terms of dependence upon both the formulation and the process conditions has been reported. In summary, the combination of HMDA with TDC and BTC produces the best microcapsule membranes with smooth and dense surfaces and low porosity. The efficiency of using the cross-linking agent in the organic phase instead of in the aqueous phase is also demonstrated by SEM observations. By using aliphatic acid dichloride, even if model microcapsules containing toluene have good aspect, no Jojoba Oil microcapsules can be formed in the same experimental conditions. It means that the system behaviour is strictly dependent on the type of the organic phase: it is reasonable to think that something related to the chemical nature of the acid dichloride in the Jojoba Oil phase (e.g. diffusion rate toward oil/water interface, rate of hydrolysis of COCl groups, etc.) influence the membrane formation mechanism. An interesting outcome of SEM study shows the possibility to reduce microcapsules size from ~15m diameter to ~5m diameter by using ultrasonic irradiations during the dispersion step. Obtained microcapsules were melt extruded with polyamide 6; TGA and DSC analysis and SEM observations of polymer blends confirmed the high thermal and mechanical resistance of polyamide cross-linked shell microcapsules, preventing Jojoba Oil degradation and promoting its combination with nylon 6. The restriction for this research line was the difficulty to get well dry and isolated microcapsules without breaking their shell during the separation step from bulk solution and the availability of injection technology for direct spinning of microcapsules in fibers. On the other side, promising potential applications offered by new nanomaterials led to verify the possibility of using nanofibers in cosmeto textile field. To compare the effect of nanofiller type on the mechanical, thermal and release properties of polyamide 6/Jojoba Oil systems, both commercial organoclay and nanosized CaCO3 were used to prepare polymer blends. A serie of polyamide 6/nanofiller-Jojoba Oil nanocomposites with different filler-Jojoba Oil contents have been prepared by melt compounding and then extruded from a capillary rheometer to obtain fibers useful in cosmetic field. WAXS and TEM analyses show that nanocomposite blends have exfoliated and partially intercalated morphologies. TGAs show that thermal stability of nanofibers is improved by about 30°C when clay loading is 1.5 wt%; higher concentrations lead to a less significant improvement, probably due to the presence of Jojoba Oil which is characterized by a faster degradation mechanism. Tensile tests indicate that mechanicla properties of polyamide 6/organoclay-Jojoba Oil nanofibers at high clay loadings are enhanced compared with neat polyamide 6; on the other hand, when clay concentration is low (less than 5 wt%) the behaviour of cosmeto-nanofibers is overall similar to that of polyamide 6 neat fibers. Such a result seems to be promising for our purpose, since these new cosmeto-nanofibers should have the same range of utilization of traditional nylons. FTIR observations allow to check Jojoba Oil presence in every polymer blend: cosmetic agent degradation is prevented by layers structure of the organoclay and time desorption in solvent of Jojoba Oil was studied by variation of peak intensity at 1740 cm-1. It was found that time release of the cosmetic agent through polyamide 6/organoclay-Jojoba nanocomposites (containing less than 7 wt% clay concentration) is slow and controlled due to the finer dispersion of organoclay within polymer matrix. Concerning systems containing CaCO3, mechanical tests confirmed that these nanoparticles did not vary significantly tensile properties of nylon fibers, even at high nanofiller loading. Nevertheless FTIR analysis show that Jojoba Oil is not protected by degradation during extrusion processes. Simulations of application conditions were carried out and qualitative considerations are as follows: 1)the cosmetic oil content did not vary after nylon fibers washing, allowing regular textile laundery treatments, 2)when nanofibers are in contact with sebum at body temperature, Jojoba Oil characteristic peak is split in two signals indicative of different rates of components release. These results encourage further investigation on release mechanism of the cosmetic agent through the polymer matrix, promoting the interest on potential applications of such nanofibers in cosmetotextile field.

碩士
國立交通大學
應用化學系碩博士班
102
In this study, the reverse microemulsion system, consisting of water, Triton X-100, hexanol and methylcyclohexane was applied for the synthesis of chitosan nanoparticles (CNPs), chitosan-HRP complex nanoparticles (C-HRP-cNPs) and chitosan microcapsules (CMCs). The physical properties such as the morphology and the diameter of these three kinds of chitosan materials were characterized by confocal laser scanning microscope (CLSM), scanning electron microscope (SEM) and dynamic light scattering (DLS). Our study indicated that the size control of CNPs could be achieved by temperature adjustment; while varying chitosan concentration and the ratio of incorporated HRP influenced significantly the morphology and the stability of CNPs and C-HRP-cNPs . To investigate the feasibility of three chitosan-based solid supports for enzyme immobilization, horse radish peroxidase (HRP) was employed as the model enzyme. Surface modified HRP-Chitosan nanoparticles (surHRP-CNPs), C-HRP-cNPs , and Encapsulated-HRP Chitosan nanocapsules (eHRP-CMCs) were prepared, and the total enzyme amounts and the corresponding activity of immobilized HRP were quantified to evaluate the immobilization processes. Different synthetic conditions contributed to varied quantity and stability of immobilized HRP in each type of chitosan nanomaterials. Finally, we employed the HRP-immobilized chitosan nanomaterials as signal generator for the immunoassay applications. The ligand recognition interface and the performance of signal generation in the assay were found to be greatly influenced by the different fabrication procedures of chitosan nanomaterials.