Nous étudions la déformation d'une capsule dans un canal microftuidique expérimentalement et numériquement. L'écoulement des rnicrocapsules est d'abord étudié numériquement dans un canal droit à section carrée. L'objectif est de développer une méthode de caractérisation des propriétés mécaniques de la membrane des capsules, à partir de leur déformation dans le canal. Nous avons mis en place une méthode d’identification afin de comparer la déformation des capsules observée expérimentalement et celle prédite par un modèle numérique tridimensionnel correspondant. La précision et la robustesse de l'algorithme d'analyse inverse ont été étudiées en faisant varier légèrement la géométrie des canaux. Finalement, la méthode a été utilisée afin de déterminer les propriétés mécaniques de rnicrocapsules dont la membrane est faite d’albumine réticulée. Nous avons ensuite appliqué une méthode de décomposition orthogonale aux valeurs propres (POD) aux formes prises par les capsules lors de leur passage dans un canal droit ou bifurqué. Des données numériques ont d 'abord été utilisées afin de déterminer la dimension de la variété des formes prises par une capsule dans un canal droit. La base POD ainsi construite a été utilisée pour interpoler les formes et obtenir la déformation d'une capsule à tous les temps, et pour tout paramètre d’écoulement. Nous avons également étudié expérimentalement les microcapsules lors de leur déformation dans un canal bifurqué. Nous avons ainsi obtenu les premiers résultats qualitatifs pour cette configuration. Nous avons développé un programme de détection de contour semi-automatique afin de faciliter le traitement d’image. Enfin, nous avons appliqué la méthode POD sur ces contours 2D réalistes et ainsi démontré la faisabilité d'utiliser une base réduite POD pour décrire la déformation de capsules clans un canal bifurqué. / The motion and deformation of a liquid-filled classic microcapsule flowing in microchannels is investigated bath experimentally and numerically. The flow of capsules into a straight microfluidic channel with a square cross-section is firstly studied. The objective is to develop a method to determine the mechanical properties of the capsule membrane from its hydrodynamic deformation. A method of identification has been devised to compare the particle deformed shape measured experimentally in the microchannels to the ones predicted by a three-dimensional numerical model for the same configuration. The precision and robustness of the inverse analysis algorithm have been tested when the microfluidic channels slightly depart from pure squareness. We have finally applied the method on microcapsules with a membrane made of reticulated albumin and determined their rnechanical properties. A Proper Orthogonal Decomposition (POD) has then been applied to the shapes assumed by the capsules while flowing in either a straight or bi­ furcated channel. Using numerical data in a straight channel, we have determined the dimension of the capsule shape variety. We have then interpolated the coefficients resulting from the POD analysis to compute the capsule deformed shape at any time for any flow parameter. Capsules have finally been investigated flowing in a bifurcated microchannel. Qualitative results of the motion and deformation of capsules in such channel have been obtained. A semi-automatic contour detection program has been developed to improve the image analysis. The POD method has been applied to the experimental results, thus proving the feasibility of building a reduced-order model of the phenomenon by using a POD reduced basis.

En vue de vectoriser de façon ciblée des microcapsules de parfum vers un substrat textile pour des applications lessivielles, ce travail de thèse s’est consacré à la modification chimique de la surface de ces microcapsules en milieu aqueux par des polysaccharides ayant des affinités particulières pour les substrats de cellulose (agent d’aide au dépôt). Pour ce faire, une approche mettant en jeu des fonctionnalités époxy a été développée en deux étapes : fonctionnalisation de la surface des microcapsules par des molécules relais, puis greffage covalent d’un polysaccharide via la fonctionnalité époxy. Après chaque étape de greffage covalent en surface des microcapsules, différentes stratégies de caractérisations ont été mises en place (spectroscopies infrarouge, RAMAN, RMN du solide, XPS, ATG, mesure du potentiel zêta, gravimétrie, microscopie optique et fluorescente). Des expériences témoins ont également été réalisées pour prouver la non-adsorption des greffons de surface sur les microcapsules. La synthèse et le greffage de polysaccharides marqués avec des sondes fluorescente, alcyne et méthacrylate nous ont également permis d’appuyer nos conclusions. Afin d’envisager des modifications chimiques en milieu aqueux, la stabilité des composés époxy dans l’eau a dû être étudiée de façon précise par spectroscopie RMN en solution et nous avons abouti avec succès à une meilleure compréhension des phénomènes réactionnels époxy-amine et époxy-hydroxyle en milieu aqueux.Enfin, une enzyme (la lipase) a également pu être greffée de façon covalente via la fonctionnalisation époxy tout en conservant son activité catalytique. / Colloidal suspensions are of paramount significance in industrial applications. They are employed in various domains like paintings, inks, pigments, pharmacology, cosmetics, food,textile, composite materials or waste water treatment. Properties of colloids strongly depend on parameters such as the chemical composition, dimensions or morphology. To confer additional features to the colloids, i.e. stability, compatibilization, targeting, stealth properties and so on, it is also crucial to tailor their surface functionalization. In this work, we intend to develop a methodology allowing for tuning the surface properties of highly cross-linked fragrance microcapsules to graft polysaccharides. To do so, the first objective of this work is to identify functionalities at the surface (of the colloids) amenable to post-modifications. Based on this crucial insight, suitable surface chemistries are further explored to impart new properties to the colloids. Thus the presence of amine functions is highlighted by ninhydrine tests and then exploited to incorporate new functionalities at the surface of colloids.Incorporation of fluorescent tags (such as  Rhodamine Isothiocyanate, RITC), intermediate polymer epoxy chains (α,ω-epoxy functionalized polyethylene glycol or PGMA) are performed. Depending on the nature of the moieties to be grafted, the resulting colloids are subsequently characterized by Confocal Laser Scanning Microscopy (CLSM), FTIR, XPS, and RAMAN Spectroscopy. After this first step of functionnalization, epoxy rings at the surface are used to postgraft polysaccharides.

Probiotics are marketed throughout the world to promote the health of the consumer by improving the microorganisms that normally occur in the intestinal tract (Tannock, 1997). It has also been suggested that probiotics can prevent pathogen infections by adhering to the intestinal mucosa (Lee, Lim, Teng, Ouwehand, Tuomola, & Salminen, 2000). While probiotics can be delivered to the infected areas in multiple fashions, microencapsulation is a newer form of delivering probiotics straight to the infected area. A whey protein microcapsule is thought to protect the probiotics from stomach acid and delivers the treatment to the affected area. To ensure this microencapsulation treatment is affective, the microcapsules will be stained and imaged to see if the microcapsules are constructed in a way which is consistent with the theory: a whey protein microcapsule surrounding bacteria and fat droplets. Through these experiments, it was shown that the microcapsule was not constructed as previously thought. Instead of a thin layer of protein surrounding the bacteria, it more closely resembled a solid ball of protein with bacteria and fat trapped inside. The bacteria are able to survive stomach like conditions (0.1M HCl for 8 hours) due to other forms of microencapsulation.

La technologie de la microencapsulation comprend généralement deux procédés : les procédés de production de microgouttes/microémulsions et les procédés de leur encapsulation. A cause de difficultés de calibrer la taille de microgouttes, des microcapsules ont souvent une grande dispersion sur leur taille. La technologie microfluidique permet d'améliorer la monodispersité de microcapsules.<br />Cette thèse a pour objet la conception et la réalisation d'un système microfluidique pour la production de gouttes calibrées et leur encapsulation. La contribution de cette thèse consiste en trois aspects : le premier concerne les effets géométriques sur la formation de goutte ; le deuxième concerne la dynamique des écoulements, le comportement d'écoulement laminaire, les propriétés physico-chimiques des couples diphasiques sur la taille de gouttes, les lois corrélant la taille de gouttes. Troisièmement, un système microfluidique est conçu dans lequel le procédé complet de la microencapsulation est réalisé pour la fabrication de microcapsules monodisperses. Les perspectives d'applications sont nombreuses.

The mechanical properties of biomaterials play important roles in performing their specialized functions: synthesizing, storing, and transporting biomolecules; maintaining internal structures; and responding to external environments. Besides biological cells, there are also many other biomaterials that are highly deformable and have a diameter between 1μm and 100μm, comparable to that of most biological cells. For example, many polymeric microcapsules for drug delivery use are spherical particles of micrometers size. In order to mechanically characterize individual micrometer-sized biomaterials, the capability of capturing high-resolution and low-magnitude force feedback is required. This research focuses on the development of micro devices and experimental techniques for quantifying the mechanical properties of alginate-chitosan microcapsules. The micro devices include microelectromechanical systems (MEMS) capacitive force sensors and force-feedback microgrippers, capable of measuring sub-μN forces. Employing the MEMS devices, systems were constructed to perform the micro-scale compression testing of microcapsules. The force sensors are capable of resolving forces up to 110μN with a resolution of 33.2nN along two independent axes. The force sensors were applied to characterizing the mechanical properties of hydrogel microparticles without assembling additional end-effectors. The microcapsules were immobilized by a PDMS holding device and compressed between the sensor probe and holding device. Young's modulus values of individual microcapsules with 1%, 2%, and 3% chitosan coating were determined through the micro-scale compression testing in both distilled deionized (DDI) water and pH 7.4 phosphate buffered saline (PBS). The Young's modulus values were also correlated to protein release rates. Instead of compressing the microcapsule against the wall of the holding device, a force-feedback MEMS microgripper with the capability of directly compressing the microcapsule between two gripping arms has been used for characterizing both the elastic and viscoelastic properties of the microcapsules during micromanipulation. The single-chip microgripper integrates an electrothermal microactuator and two capacitive force sensors, one for contact detection (force resolution: 38.5nN) and the other for gripping force measurements (force resolution: 19.9nN). Through nanoNewton force measurements, closed-loop force control, and visual tracking, the system quantified the Young's modulus values and viscoelastic parameters of alginate microcapsules, demonstrating an easy-to-operate, accurate compression testing technique for characterizing soft, micrometer-sized biomaterials.

The mechanical properties of biomaterials play important roles in performing their specialized functions: synthesizing, storing, and transporting biomolecules; maintaining internal structures; and responding to external environments. Besides biological cells, there are also many other biomaterials that are highly deformable and have a diameter between 1μm and 100μm, comparable to that of most biological cells. For example, many polymeric microcapsules for drug delivery use are spherical particles of micrometers size. In order to mechanically characterize individual micrometer-sized biomaterials, the capability of capturing high-resolution and low-magnitude force feedback is required. This research focuses on the development of micro devices and experimental techniques for quantifying the mechanical properties of alginate-chitosan microcapsules. The micro devices include microelectromechanical systems (MEMS) capacitive force sensors and force-feedback microgrippers, capable of measuring sub-μN forces. Employing the MEMS devices, systems were constructed to perform the micro-scale compression testing of microcapsules. The force sensors are capable of resolving forces up to 110μN with a resolution of 33.2nN along two independent axes. The force sensors were applied to characterizing the mechanical properties of hydrogel microparticles without assembling additional end-effectors. The microcapsules were immobilized by a PDMS holding device and compressed between the sensor probe and holding device. Young's modulus values of individual microcapsules with 1%, 2%, and 3% chitosan coating were determined through the micro-scale compression testing in both distilled deionized (DDI) water and pH 7.4 phosphate buffered saline (PBS). The Young's modulus values were also correlated to protein release rates. Instead of compressing the microcapsule against the wall of the holding device, a force-feedback MEMS microgripper with the capability of directly compressing the microcapsule between two gripping arms has been used for characterizing both the elastic and viscoelastic properties of the microcapsules during micromanipulation. The single-chip microgripper integrates an electrothermal microactuator and two capacitive force sensors, one for contact detection (force resolution: 38.5nN) and the other for gripping force measurements (force resolution: 19.9nN). Through nanoNewton force measurements, closed-loop force control, and visual tracking, the system quantified the Young's modulus values and viscoelastic parameters of alginate microcapsules, demonstrating an easy-to-operate, accurate compression testing technique for characterizing soft, micrometer-sized biomaterials.

L'acide hyaluronique est un polysaccharide fortement hydraté. Grâce à sa présence naturelle dans le corps humain et aux nombreuses possibilités de modifications chimiques de ce polysaccharide, l'acide hyaluronique est un bon candidat pour la conception de transporteurs de principes actifs. Dans cette thèse, nous avons synthétisé différents types de dérivés du HA en milieu aqueux. Ceux-ci comprennent les dérivés alkylés du HA, HA-cyclodextrine conjugués et des copolymères "hybrides" composés de HA et d'un copolymère thermosensible de l'éthylène glycol.Basé sur la capacité d'accueillir des molécules hydrophobes paclitaxel dans leurs hydrophobes "nanocavités", nous avons ensuite montré la formation de multicouches de polyélectrolytes de capsules à partir de ces dérivés du HA. L'insertion des molécules paclitaxel dans la paroi des capsules a été réalisée par pré-complexation avec les dérivés du HA en solution, et ensuite déposition ces PTX-polyélectrolytes avec le poly(L-lysine) selon la technique de couche par couche.Dans les deux cas, les capsules chargées de PTX ont été trouvés qu'elles permettent de réduire la viabilité et la prolifération des cellules cancéreuses. Ces multicouches ouvrent de nouvelles voies vers des applications en nanomédecine, comme systèmes transporteurs de médicaments hydrophobes. L'acide hyaluronique modifié par maleimide a été réagit avec poly(diethyleneglycolmethacrylate - oligoethyleneglycolmethacrylate (poly(DEGMA-co-OEGMA)) modifié par thiol afin d'obtenir le copolymère "hybrides" thermosensible. La valeur de la LCST de ce copolymère de HA est autour de 35 °C en déterminant par les mesures du point de trouble des solutions. Au-dessus de cette température, le HA-poly(DEGMA-co-OEGMA) conduit à la formation des nanogels avec la capacité d'encapsuler des molécules hydrophobes dans leur domaine hydrophobe.Les nanogels chargés en PTX ont montré une cytotoxicité plus élevée avec des cellules du cancer surexprimant le récepteur CD44. Ces résultats suggèrent que ces nanogels thermosensible pourraient s'avérer être des candidats intéressants pour la libration thérapeutique dans le traitement de cancer.

[pt] Devido à diminuição do número de descobertas de novas reservas de óleo e gás nas últimas décadas, as companhias de petróleo têm demonstrado um interesse cada vez maior em melhorar a eficiência dos processos de recuperação de óleo. Geralmente, após as fases de recuperação primário e secundário, uma grande quantidade de óleo permanece dentro do reservatório, pois a extração se torna não rentável. Assim, cresce o número de estudos voltados para a recuperação avançada de petróleo, com o objetivo de obter uma melhor fração de recuperação. O foco deste trabalho é estudar os fundamentos do deslocamento de óleo em meios porosos usando um microscópio confocal de varredura a laser, que possibilita visualizações 3D com boa resolução. A análise foi no deslocamento de óleo resultante da injeção de uma suspensão de capsulas de goma gelana em água após a injeção de água. Estas capsulas, movendo com a água, bloqueiam alguns dos caminhos preferenciais e forçam a água a deslocar uma parte do óleo preso. O resultado alcançado foi uma coleção de imagens 3D de meios porosos artificiais, nas quais foi possível distinguir a distribuição das fases (microcápsulas, fase aquosa e oleosa) dentro dos meios porosos, antes e após a injeção das microcápsulas. Essas imagens mostraram que as microcápsulas de goma gelana bloqueiam os caminhos preferenciais da água e que, após o bloqueio, alguns gânglios de óleo foram deslocados de suas posições originais. Esta tese aplica técnicas modernas de microscopia para examinar o conceito por trás da recuperação avançada de óleo usando microcápsulas. / [en] Thanks to decay of new discoveries of oil and gas reserves in the past decades, oil companies have a growing interest in the increase of oil recovery efficiency. Commonly, after primary and secondary recovery phases, a largeamount of oil remains inside the reservoir, as it becomes unprofitable to continue the extraction. Thus, the number of studies focused on enhanced oil recovery is growing, aiming to obtain a better recovery fraction. The focus of this work is to study the fundamentals of oil displacement in porous media using a confocal laser scanning microscope, which enables 3D visualization with a good resolution. The analysis was on oil displacement that results from the use of a suspension of gellan gum microcapsules in water injected after water injection. These microcapsules, moving along with the water, blocked some of the preferential paths and forced the water to displaces parcels of the trapped oil. The result achieved was a collection of 3D images from artificial porous media, in which it was possible to distinguish the distribution of phases (microcapsules, oil, and aqueous phases) inside the porous media, before and after the microcapsules injection. These images showed that indeed the gellan gum microcapsules blocked preferential water paths and that, after the blockage, some oil ganglia were displaced from their original positions. This thesis applies modern techniques of microscopy to investigate the concept behind enhanced oil recovery using microcapsules.

The development of a bioartificial pancreas (BAP) has the potential to substantially improve the treatment of insulin-dependent diabetes. Composed of insulin-secreting cells encapsulated in a hydrogel material, a BAP may provide superior glycemic regulation compared with conventional exogenous insulin-delivery therapies. Towards this goal, β- cells or islets encapsulated in alginate microcapsules remain a promising approach. Due to the limited supply of human islets, alternative cell sources are under investigation for incorporation into a BAP, including porcine islets and β- cell lines. Several challenges remain to clinical implementation, including loss of islet or β- cell function and viability following transplantation and host response to the transplanted microcapsules. The objective of this work was to evaluate strategies to improve a BAP by supporting the function and survival of encapsulated islets and β -cells. Towards this goal, two areas were explored: 1) the provision of pro-survival and insulinotropic factors, namely, CXCL12 and GLP-1 (or a GLP-1 analog, Exendin-4), to encapsulated islets and β-cells and 2) modification of the alginate microcapsule to confer long-term resistance to host cell adhesion. To achieve the first objective, methods to deliver both pro-survival and insulinotropic factors to a BAP were developed and their effects on encapsulated β-cells and porcine islets were studied, both in vitro and in vivo. Results demonstrate that delivery of pro-survival and insulinotropic factors is a promising strategy to prolong the survival and function of a BAP. To reduce host cell adhesion to the microcapsule, we employed covalent conjugation of PEG to the surface of alginate-PLL capsules to replace the un-crosslinked layer of alginate used in traditional alginate-PLL-alginate (APA) microcapsules. Results demonstrate that while PEGylation of alginate-PLL microcapsules initially reduced host cell adhesion over 2 weeks in vivo compared with APA capsules, the PEG coating did not provide long-term protection over 3 months. Taken together, these studies represent a multipronged approach towards improving the duration of BAP function, with the ultimate goal of advancing this technology to the clinic.

No description available.