A range of microgels with two different functionalities were synthesized, and their utility in novel bioapplications was examined. Cationic microgels with varying properties were developed by tuning synthesis conditions. Their size and primary amine content was analyzed, and one microgel system was selected as a model construct. Its primary amine groups were conjugated to two dyes with properties favorable for utilization as contrast agents in photoacoustic imaging. The concentration of contrast agent in single particles was determined. The implications of a high local dye concentration in the generation of high intensity photoacoustic signals, are discussed. The second bioapplication involved the targeted delivery of fibrinolytics to fibrin clots, in order to bring about dissolution of abnormal thrombi. For this purpose, core/shell microgels with carboxylic acid groups in their shells were synthesized in three size ranges. Following this, their dimension based differential localization in and around porous fibrin clots was examined. Fibrin-specific peptides were then conjugated onto the shells of these particles and the conjugates were shown to demonstrate strong interactions with the fibrin clots. The microgels conjugated to the peptide with the highest binding affinity to fibrin, were observed to bring about disruption of fibrin clots, merely through interference in the dynamic interactions among clot fibers, due to the equilibrium nature of the fibrin polymer. The implications of these novel results and future studies required to facilitate a better understanding of the phenomena involved, are discussed.

Le traitement du diabète de type 1 en boucle fermée représente un enjeu majeur tant sur le plan sociétal que thérapeutique. L’une des solutions consiste en une formulation thérapeutique basée sur des microvéhicules capables de délivrer la bonne dose d’insuline selon une cinétique adaptée aux variations de la glycémie. Les microgels sont des particules de polymère réticulé formant des édifices submicrométriques tridimensionnels gonflés par un solvant, dont le taux de gonflement dépend des conditions environnementales. Leur porosité permet à la fois l’encapsulation d’espèces et leur libération à une vitesse dépendant de leur diffusion à travers le réseau. Nous avons synthétisé des microgels à base de poly(N-alkylacrylamide) fonctionnalisés par des récepteurs du glucose dérivés de l’acide phénylboronique. Ces microgels, à la base thermosensibles, présentent la propriété de changer de volume en fonction de la concentration en glucose et se présentent comme d’excellents candidats pour la délivrance auto-régulée d’insuline dans le cadre du traitement du diabète. Ils permettent la délivrance répétée de doses d’insuline modulée par la glycémie. La quantité d’insuline encapsulée a pu être améliorée en structurant les microgels en architecture cœur-écorce ou capsule.En outre, nous avons utilisé ces microgels pour développer des capteurs au glucose, sélectifs vis-à-vis des autres saccharides et quelques études de cytotoxicité ont été amorcées et ont permis d’établir avec satisfaction que certains de nos objets n’étaient pas toxiques.Les résultats obtenus ont donc permis d’affirmer que la technologie des microgels sensibles au glucose peut répondre de manière conceptuelle aux attentes des patients diabétiques pour permettre la délivrance d’insuline en boucle fermée. / Bioresponsive hydrogels can change many of their physical properties in response to the recognition of a target in the solution. In particular, changes in hydrogel swelling lead in turn to controllable changes in shape, volume, pore size, mechanical and optical properties. We focus our research on the development of glucose-responsive microgels which hold promising interest in the field of both sensing and drug delivery. These cross-linked polymer particles, made of highly swollen networks, can swell proportionally to the concentration of glucose in the surrounding medium. Since they are porous, they can entrap a drug and release it a rate dependent on their swelling degree, which is of particular interest in the case of insulin as a drug. Such systems could be used as self-regulated insulin delivery systems for diabetes treatment. With that aim, we have designed microgels able to sense glucose concentrations in the patho-physiological range, under physiological conditions. Insulin was successfully loaded into the nanogels and was shown to be released at a rate dependent on glucose concentration. Furthermore, microgels with a controlled internal structure were synthesized, such as core-shell microgels and capsules. These latter developments led to improvements in terms of insulin encapsulation efficiency and glucose-triggered delivery. Besides, other nanogel formulations were investigated, in order to improve both their biocompatibility as well as the selectivity of their response to glucose compared to other saccharides.

This dissertation describes the development of temperature and pH-responsive interfaces, where the emphasis is placed on tuning the responsivities within a physiological temperature range. This tuning is achieved through the utilization of polymeric building blocks, where each component is specifically synthesized to have a unique responsivity. The assembly of these components onto surfaces permits the fabrication of stimuli-responsive interfaces. In addition, this dissertation explores the use of a self-assembling peptide as a modular building block to modify the interface of hydrogel microparticles, resulting in the formation of a new biosynthetic construct. Hydrogels are three-dimensional, crosslinked polymer networks that swell in water. Over the years, hydrogels have been extensively explored as biomaterials due to their high water content, tunable mechanics, and chemical versatility. Two areas where hydrogels have received considerable interest are drug delivery and extracellular matrices. Unfortunately, developing structurally and functionally complex hydrogels from the top down is challenging because many parameters cannot be independently tuned in a bulk material. An alternative route would be to develop a library of building blocks, where each is tailored for a given function, and assemble these components into composite structures. The building block synthesized and utilized in this dissertation is a microgel. Microgels are a colloidal dispersion of hydrogel microparticles, ranging in size from 100 to 1000 nm in diameter. The microgels were prepared from environmentally responsive polymers, sensitive to both temperature and pH. Microgels have been used in the fabrication of polyelectrolyte layer-by-layer films, where the microgel serves as the polyanion and a linear polycation is used to “stitch” the particles together. In Chapters 3 and 4, stimuli-responsive interfaces are prepared from environmentally responsive microgel building blocks. In particular, Chapter 3 demonstrates tuning of the film response temperature by preparing several different microgels with differing ratios of two thermoresponsive polymers. Chapter 4 evaluates the influence of the pH environment on the thermoresponsivity of microgel films. While the pH environment was found to substantially affect some films, it is possible to prepare microgel films that behave independently of pH. The swelling/de-swelling of the films was also investigated by atomic force microscopy (AFM) as a function of both pH and temperature. It was determined that the AFM imaging parameters can drastically affect the measured film thicknesses (Appendix A) due to the soft, deformable nature of microgel films. The studies in these chapters illustrate the advantages of preparing composite structures from discrete components, where the functionality of the composite is dictated by the constituent particles. In Chapter 5, attention is placed on modifying the surface of microgel particles. Many of the traditional routes used to modify microgels involve the incorporation of co-monomers into the network or the addition of polymer shells. However, a new core/shell construct is presented, where a microgel core is coated with a self-assembling peptide shell. In this scenario, the peptide shell serves as a modular scaffold, where surface-localized functional groups can participate in reactions. Although there are still a number of questions remaining in regard to the assembly process and stability of the construct, initial experiments suggests that this is an interesting and promising structure to study. Finally, a discussion of future directions and possible experiments is provided in Chapter 6. Hopefully, this will serve as a guide for further exploration of the research presented herein. Microgels remain a rich class of materials to study and employ. While their synthesis is rather straightforward, their use often results in complex behavior and interesting phenomena. Understanding their behavior is a crucial step in realizing their full potential.

L’utilisation de nanovecteurs pour la livraison contrôlée de principes actifs est un concept commun de nous jours. Les systèmes de livraison actuels présentent encore cependant des limites au niveau du taux de relargage des principes actifs ainsi que de la stabilité des transporteurs. Les systèmes composés à la fois de nanovecteurs (liposomes, microgels et nanogels) et d’hydrogels peuvent cependant permettre de résoudre ces problèmes. Dans cette étude, nous avons développé un système de livraison contrôlé se basant sur l’incorporation d’un nanovecteur dans une matrice hydrogel dans le but de combler les lacunes des systèmes se basant sur un vecteur uniquement. Une telle combinaison pourrait permettre un contrôle accru du relargage par stabilisation réciproque. Plus spécifiquement, nous avons développé un hydrogel structuré intégrant des liposomes, microgels et nanogels séparément chargés en principes actifs modèles potentiellement relargués de manière contrôlé. Ce contrôle a été obtenu par la modification de différents paramètres tels que la température ainsi que la composition et la concentration en nanovecteurs. Nous avons comparé la capacité de chargement et la cinétique de relargage de la sulforhodamine B et de la rhodamine 6G en utilisant des liposomes de DOPC et DPPC à différents ratios, des nanogels de chitosan/acide hyaluronique et des microgels de N-isopropylacrylamide (NIPAM) à différents ratios d’acide méthacrylique, incorporés dans un hydrogel modèle d’acrylamide. Les liposomes présentaient des capacités de chargement modérés avec un relargage prolongé sur plus de dix jours alors que les nanogels présentaient des capacités de chargement plus élevées mais une cinétique de relargage plus rapide avec un épuisement de la cargaison en deux jours. Comparativement, les microgels relarguaient complétement leur contenu en un jour. Malgré une cinétique de relargage plus rapide, les microgels ont démontré la possibilité de contrôler finement le chargement en principe actif. Ce contrôle peut être atteint par la modification des propriétés structurelles ou en changeant le milieu d’incubation, comme l’a montré la corrélation avec les isothermes de Langmuir. Chaque système développé a démontré un potentiel contrôle du taux de relargage, ce qui en fait des candidats pour des investigations futures. / Controlled delivery of active compounds using nanoscale carriers is nowadays a common concept, but there are still limitations in current delivery systems related to active compound release rate and nanocarriers stability. To address these limitations, delivery systems can be made to incorporate both nanocarriers (liposomes, microgels and nanogels) and hydrogels. In this study, we have developed controlled delivery systems by combining different carriers in order to overcome deficiencies observed in systems using only one type of carrier. Such a combination could lead to an enhanced controlled release delivery system through synergistic stabilization. More specifically, we created a structured hydrogel embedded with either liposomes, microgels, or nanogels, each loaded with model active compounds that would be released in a controlled fashion by manipulating the temperature of release medium and nanocarriers composition and concentration. We compared drug loading and release kinetics of sulforhodamine B from liposomes (composed of DOPC and DPPC at different ratios) and nanogels (chitosan/hyaluronic acid) embedded in acrylamide hydrogels. We also compared drug loading and release kinetics of rhodamine 6G from microgels of N-isopropylacrylamide (NIPAM) with different ratios of methacrylic acid embedded in acrylamide hydrogel. Liposomes demonstrated a moderate drug loading capacity with sustained release for over ten days, while nanogels showed high drug loading but faster release kinetics, exhausting their contents within two days. Comparatively, microgels completely released their content within a day. Despite their faster release kinetics, microgels have shown the capacity to be finely tuned for efficient drug loading. The Langmuir isotherms indicated that it can be achieved by altering their structural properties or by changing their incubation medium. Each developed system has demonstrated a potential in controlling the release rate, which makes them candidates for further investigations in the future.

A parte inicial deste estudo consistiu da síntese de HMSPP (Polipropileno com Alta Resistência do Fundido) também chamado polipropileno modificado por irradiação gama, a partir de iPP (polipropileno isotático) em presença de acetileno sob pressão de 110 kPa e irradiado com &gamma; (gama) de fonte de 60Co nas doses de 5; 12,5 e 20 kGy. A fração gel das amostras foi determinada pela extração de componentes solúveis em xileno. A parte solúvel das amostras foi decantada com deposição do gel em lâminas de vidro, até total volatilização do xileno à temperatura ambiente de 25 °C. À parte solúvel da amostra com 12,5 kGy adicionaram-se nanopartículas de prata (NPsAg) nas proporções de: 0,25; 0,5; 1,0; 2,0 e 4,0% em massa. Estas amostras foram caracterizadas por: microscopia eletrônica de varredura e espectroscopia de energia dispersiva (MEV/EDS), espectroscopia no infravermelho (FTIR), microscopia eletrônica de varredura com emissão de campo (MEV-EC), microscopia de força atômica (MFA), calorimetria exploratória diferencial (DSC), difração de raios X (DRX), redução da unidade formadora de colônias (UFC) (%) e teste de citotoxicidade. Neste estudo da morfologia, observou-se a formação de microgéis de polipropileno na ordem crescente PP 5 kGy < PP 12,5 kGy < 20 kGy. Constatou-se a existência de estruturas nanométricas de géis de polipropileno (nanogéis e nanofibras) nas amostras de PP 12,5 kGy e PP 20 kGy. Os nanogéis são formações reticuladas, ramificadas, e emaranhadas, nucleadas em regiões de incidência de alta concentração de energia (spurs) em uma amostra irradiada. Nos testes de avaliação da atividade bactericida dos géis com NPsAg observou-se eficiência biocida para E. coli e S. aureus a partir de 1% de NPsAg e no teste de citotoxicidade as amostras foram caracterizadas como não citotóxicas para células de mamíferos. Em uma segunda etapa deste trabalho foram produzidos filmes da blenda de iPP e PP modificado (50/50) em uma extrusora de dupla rosca. Adicionou-se ao processamento NPsAg nas proporções de: 0,1; 0,25; 0,5; 1,0; 1,0 PVP; 2,0 e 4,0% em massa. Os filmes foram caracterizados por: calorimetria exploratória diferencial (DSC), análise de termogravimetria (TGA), difração de raios X (DRX), microscopia eletrônica de varredura (MEV), espectroscopia de energia dispersiva (EDS), espectroscopia de ultravioleta-visível (UV-Vis), microscopia eletrônica de transmissão (MET), redução da unidade formadora de colônias (UFC) (%), teste de sensibilidade a antimicrobianos por disco de difusão e teste de citotoxicidade. Os filmes analisados apresentaram pontos de aglomeração de prata e regiões com distribuição homogênea das partículas. O efeito bactericida com a interação entre a prata, e E. coli, P. aeruginosa e S. aureus foi constatado para o filme de PP 1%NPsAg PVP Poli(N-vinil-2-pirrolidona). No teste de difusão o resultado obtido para PP 1% NPsAg PVP foi 100% positivo com essas bactérias. Os filmes não são considerados citotóxicos para células de mamíferos. / The study consists of the synthesis of HMSPP (polypropylene with high melt strength), also called polypropylene modified by gamma irradiation from iPP (isotactic polypropylene) in presence of acetylene at 110 kPa pressure and irradiated with &gamma; of 60Co source at doses of 5, 12.5 and 20 kGy. The gel fraction of the samples was determined by extracting in xylene. The soluble portion of the samples was decanted to deposition on glass substrate until complete volatilization of xylene at room temperature of 25 °C. On the soluble portion of 12.5 kGy irradiated sample were added silver nanoparticles (AgNPs) in proportions of 0.25, 0.5, 1.0, 2.0 and 4.0 wt%. These gel samples were characterized by: scanning electron microscopy/energy dispersive spectroscopy (SEM / EDS), infrared spectroscopy (FTIR), scanning electron microscopy with field emission (FE-SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), reduction of colony forming unit (CFU) (%) and cytotoxicity assay. In this study of the morphology, it has been observed the formation of microgels in polypropylene increasing with the dose PP 5 kGy < PP 12.5 kGy < 20 kGy. Nanoscale structures of gels polypropylene (nanogels and nanofibers) were found in samples of PP 12.5 kGy and 20 kGy. The nanogels are formation of crosslinking, branching and entanglement that are nucleated in regions of high energy concentration (spurs) of one irradiated sample. Efficiency in tests of bactericide activity of the gels with AgNPs was observed versus E. coli and S. aureus from 1% AgNPs and non cytotoxicity were characterized in those samples for mammalian cells. In a second stage of this work films of the blend of PP and modified PP (50/50) were produced in a twin screw extruder. AgNPs were added to the extrusion processing in proportions of 0.1; 0.25; 0.5; 1.0; 1.0 PVP; 2.0 and 4.0 wt%. The films obtained were characterized by differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), reduction of colony forming unit (CFU) (%), antimicrobial susceptibility testing by disk diffusion and cytotoxicity assay. The films analyzed showed agglomeration of silver points and regions with homogeneous distribution of the particles. The bactericide effect with the interaction between silver and E. coli, P. aeruginosa and S. aureus was found for PP film 1% NPsAg Polyvinylpyrrolidone (PVP). In the diffusion test for PP 1% AgNPs (PVP) was obtained 100%positive result for those bacteria. The films were not cytotoxic to mammalian cells.

Les nanogels sont des macromolécules ramifiées solubles possédant une structure en réseau et de dimensions inférieures à 100 nm. La méthodologie récente de la copolymérisation radicalaire réticulante contrôlée permet d'accéder à de telles architectures polymères tout en contrôlant finement leur structure interne. Nous présentons dans ce travail: (i) l'étude préalable de systèmes modèles, permettant de dégager les conditions nécessaires à la synthèse de nanogels; (ii) l'application à la synthèse de nanogels hydrophiles valorisables de poly(alcool vinylique) et de poly(N-vinylpyrrolidone); (iii) une modélisation cinétique permettant de rendre compte des tendances observées expérimentalement et de prévoir les grandeurs caractéristiques de produits synthétisés par cette méthodologie. / Abstract

A parte inicial deste estudo consistiu da síntese de HMSPP (Polipropileno com Alta Resistência do Fundido) também chamado polipropileno modificado por irradiação gama, a partir de iPP (polipropileno isotático) em presença de acetileno sob pressão de 110 kPa e irradiado com &gamma; (gama) de fonte de 60Co nas doses de 5; 12,5 e 20 kGy. A fração gel das amostras foi determinada pela extração de componentes solúveis em xileno. A parte solúvel das amostras foi decantada com deposição do gel em lâminas de vidro, até total volatilização do xileno à temperatura ambiente de 25 °C. À parte solúvel da amostra com 12,5 kGy adicionaram-se nanopartículas de prata (NPsAg) nas proporções de: 0,25; 0,5; 1,0; 2,0 e 4,0% em massa. Estas amostras foram caracterizadas por: microscopia eletrônica de varredura e espectroscopia de energia dispersiva (MEV/EDS), espectroscopia no infravermelho (FTIR), microscopia eletrônica de varredura com emissão de campo (MEV-EC), microscopia de força atômica (MFA), calorimetria exploratória diferencial (DSC), difração de raios X (DRX), redução da unidade formadora de colônias (UFC) (%) e teste de citotoxicidade. Neste estudo da morfologia, observou-se a formação de microgéis de polipropileno na ordem crescente PP 5 kGy < PP 12,5 kGy < 20 kGy. Constatou-se a existência de estruturas nanométricas de géis de polipropileno (nanogéis e nanofibras) nas amostras de PP 12,5 kGy e PP 20 kGy. Os nanogéis são formações reticuladas, ramificadas, e emaranhadas, nucleadas em regiões de incidência de alta concentração de energia (spurs) em uma amostra irradiada. Nos testes de avaliação da atividade bactericida dos géis com NPsAg observou-se eficiência biocida para E. coli e S. aureus a partir de 1% de NPsAg e no teste de citotoxicidade as amostras foram caracterizadas como não citotóxicas para células de mamíferos. Em uma segunda etapa deste trabalho foram produzidos filmes da blenda de iPP e PP modificado (50/50) em uma extrusora de dupla rosca. Adicionou-se ao processamento NPsAg nas proporções de: 0,1; 0,25; 0,5; 1,0; 1,0 PVP; 2,0 e 4,0% em massa. Os filmes foram caracterizados por: calorimetria exploratória diferencial (DSC), análise de termogravimetria (TGA), difração de raios X (DRX), microscopia eletrônica de varredura (MEV), espectroscopia de energia dispersiva (EDS), espectroscopia de ultravioleta-visível (UV-Vis), microscopia eletrônica de transmissão (MET), redução da unidade formadora de colônias (UFC) (%), teste de sensibilidade a antimicrobianos por disco de difusão e teste de citotoxicidade. Os filmes analisados apresentaram pontos de aglomeração de prata e regiões com distribuição homogênea das partículas. O efeito bactericida com a interação entre a prata, e E. coli, P. aeruginosa e S. aureus foi constatado para o filme de PP 1%NPsAg PVP Poli(N-vinil-2-pirrolidona). No teste de difusão o resultado obtido para PP 1% NPsAg PVP foi 100% positivo com essas bactérias. Os filmes não são considerados citotóxicos para células de mamíferos. / The study consists of the synthesis of HMSPP (polypropylene with high melt strength), also called polypropylene modified by gamma irradiation from iPP (isotactic polypropylene) in presence of acetylene at 110 kPa pressure and irradiated with &gamma; of 60Co source at doses of 5, 12.5 and 20 kGy. The gel fraction of the samples was determined by extracting in xylene. The soluble portion of the samples was decanted to deposition on glass substrate until complete volatilization of xylene at room temperature of 25 °C. On the soluble portion of 12.5 kGy irradiated sample were added silver nanoparticles (AgNPs) in proportions of 0.25, 0.5, 1.0, 2.0 and 4.0 wt%. These gel samples were characterized by: scanning electron microscopy/energy dispersive spectroscopy (SEM / EDS), infrared spectroscopy (FTIR), scanning electron microscopy with field emission (FE-SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), reduction of colony forming unit (CFU) (%) and cytotoxicity assay. In this study of the morphology, it has been observed the formation of microgels in polypropylene increasing with the dose PP 5 kGy < PP 12.5 kGy < 20 kGy. Nanoscale structures of gels polypropylene (nanogels and nanofibers) were found in samples of PP 12.5 kGy and 20 kGy. The nanogels are formation of crosslinking, branching and entanglement that are nucleated in regions of high energy concentration (spurs) of one irradiated sample. Efficiency in tests of bactericide activity of the gels with AgNPs was observed versus E. coli and S. aureus from 1% AgNPs and non cytotoxicity were characterized in those samples for mammalian cells. In a second stage of this work films of the blend of PP and modified PP (50/50) were produced in a twin screw extruder. AgNPs were added to the extrusion processing in proportions of 0.1; 0.25; 0.5; 1.0; 1.0 PVP; 2.0 and 4.0 wt%. The films obtained were characterized by differential scanning calorimetry (DSC), thermogravimetry analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), ultraviolet-visible spectroscopy (UV-Vis), transmission electron microscopy (TEM), reduction of colony forming unit (CFU) (%), antimicrobial susceptibility testing by disk diffusion and cytotoxicity assay. The films analyzed showed agglomeration of silver points and regions with homogeneous distribution of the particles. The bactericide effect with the interaction between silver and E. coli, P. aeruginosa and S. aureus was found for PP film 1% NPsAg Polyvinylpyrrolidone (PVP). In the diffusion test for PP 1% AgNPs (PVP) was obtained 100%positive result for those bacteria. The films were not cytotoxic to mammalian cells.

This thesis reports on interactions between microgels and oppositely charged proteins. Two types of negatively charged microgels are investigated: poly(acrylic acid) microgels of 60-80 µm in diameter, and colloidal poly(NIPAM-co-acrylic acid) microgels of around 1 µm in diameter. The proteins used are lysozyme and cytochrome c, which both have positive net charge. The experimental techniques used in the studies of the larger microgels are mainly micromanipulator-assisted microscopy and confocal microscopy, while the smaller microgels are studied mainly with dynamic light scattering. It is observed that large amounts of protein are absorbed by the microgels, and that the uptake involves a substantial deswelling of the microgel. The uptake generally decreases as the ionic strength is increased, which is characteristic of electrostatic interactions. An ionic strength optimum is however observed in the case of lysozyme and poly(acrylic acid) microgels, where the highest uptake (10 gram lysozyme / gram microgel) is observed at ionic strength 40 mM. Cytochrome c uptake in poly(acrylic acid) microgels results in homogenous cytochrome c distribution throughout the microgel, whereas lysozyme uptake results in core-shell formation; the lysozyme concentration becomes much higher in the shell (outer part of the microgel) than in the core (inner part of the microgel). The shell constitutes a stress-bearing network which is sufficiently porous to allow protein diffusion through the shell. The different protein distributions are associated with different protein-protein interactions; strong protein-protein attraction promotes shell formation. In the case of colloidal microgels, lysozyme uptake decreases the electrophoretic mobility and the colloidal stability of the microgels. The microgels flocculate as the uptake reaches charge ratio 0.6-0.7 (positive lysozyme charges/negative microgel charges), largely independent of ionic strength. Initial experiments on the combination of cytochrome c and colloidal microgels show that colloidal stability is maintained at a range of conditions (ionic strength, protein concentration) where flocculation occurred in the case of lysozyme.

We present the phase behavior of soft sphere colloidal dispersions. The pH responsive and thermoresponsive microgels, poly(N-isopropylacrylamide-co-acrylic acid) (pNIPAm-co-AAc), were used as a new building block of colloidal crystals. The phase behavior of microgel dispersions was studied by different methods such as optical microscopy, particle trajectories, mean squared displacement (MSD) vs. lag time plots and radial distribution function. The results show that the phase of the sample relies on the particle concentration for dispersions of the same pH. As the pH approaches the pKa of microgels, the microgel dispersions show unusual crystalline phase at lower effective volume fraction than hard sphere melting transition. Also, at this pH regime, the microgel dispersions undergo slow and spatially heterogeneous crystal growth. The cooperative multi-body type attractive forces were proposed to explain the unusual stability at low effective volume fraction. Ion-dipole interactions were proposed to be the origin of the attractive forces. The melting point of bulk crystals at this pH regime is much higher than the volume phase transition temperature of the building block. These results are supportive of the attractive forces hypothesis.

The studies of the dynamics, phase behavior, interparticle interactions, and hydrodynamics of stimuli-responsive pNIPAm-co-AAc microgels were described in this thesis. Due to their responsiveness to external stimuli, these colloidal particles serve as excellent model systems to probe the relationship between colloidal interactions and phase behavior. As a first step, we established our core experimental methodology, by demonstrating that particle tracking video microscopy is an effective technique to quantify various parameters in colloidal systems. Then we used the technique in combination with a microfluidic device that provides in situ control over sample pH to probe the phase behavior of pNIPAm-co-AAc microgel suspensions. In essence, the experimental set-up enables changes in effective particle volume fractions by changing pH, which can be used to construct the phase diagram. In order to explain the unique features of the microgel phase diagram, we measured the underlying pairwise interparticle potential of pNIPAm-co-AAc microgels directly in quasi-2D suspension and proved that the interactions are pH dependent and can range from weakly attractive to soft repulsive. Finally, the hindered Brownian diffusion due of colloidal particles confined by hard walls was investigated systematically and striking differences between hard sphere and soft sphere were found, with soft pNIPAm-co-AAc microgels showing surprising mobility even under strong confinement.