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Ces travaux de thèse traitent de l’étude de glycolipides et plus précisément d’esters de trehalose pour la synthèse de nouveaux polymères bio-sourcés. Des monoesters et diesters de trehalose ont ainsi été synthétisés par estérification des alcools primaires du trehalose avec des acides gras selon deux voies de synthèse. La première utilisant un agent de couplage peptidique ne nécessite pas l’utilisation de groupement protecteur pour estérifier sélectivement les alcools primaires. La deuxième est une estérification sélective catalysée par une lipase. L’auto-assemblage des esters de tréhalose a ensuite été étudié. Les monoesters possèdent des propriétés tensio-actives dans l’eau et le trehalose monoeruçate a la capacité de gélifier l’eau. Les diesters, quant à eux sont de bons gélifiants pour les solvants organiques etles huiles végétales. Par conséquent, des gels ont été préparés dans trois huiles végétales, puis leur morphologie et leur propriété rhéologique ont été étudiées. Ensuite, les diesters ont été fonctionnalisé et polymérisés selon différentes stratégies. Ainsi, des polyuréthanes et des poly(hydroxyuréthane)s ont été synthétisés par polycondensation tandis que des glycopolyesters ont été obtenus par polymérisation par métathèse et addition thiol-ène. Finalement,les propriétés d’auto-assemblage de ces polymères ont été étudiées. Ces derniers peuvent former des nanoparticules par la méthode de déplacement de solvants. / The aim of this thesis was to study glycolipids and particularly trehalose esters for the synthesis of new bio-sourced polymers. Trehalose monoesters and diesters were synthesized by two esterification pathways of the primary alcohol of trehalose with different fatty acids. The first synthetic route is a protective group-free esterification using a peptide coupling agent and the second one is a lipase-catalyzed esterification. The self-assembly properties of the trehalose esters were investigated. Trehalose monoesters showed surfactant properties in water and trehalose monoerucate was even able to form gels in water. The trehalose diesters appeared to be good gelators for organic solvent and vegetable oil. Thus, gels in three vegetable oils were prepared and their morphology and rheological properties were studied. Afterwards, trehalose diesters were functionalized and polymerized with different strategies.Thus, polyurethanes and poly(hydroxyurethane)s were obtained by polycondensation where as glyco-polyesters were synthesized by acyclic diene metathesis (ADMET) and thiol-enepolymerization. Finally, the self-assembly properties of these polymers were investigated. The latter were able to form some nanoparticles by solvent displacement method.

De nouveaux processus de cyclisation d’allènes fonctionnalisés catalysées par des triflates métalliques sont présentés. Deux stratégies ont été développées. Dans un premier temps, une réaction de type carbonyl-ène intramoléculaire à partir de cétones γ-alléniques est développée. Cette réaction se déroule dans des conditions très douces avec une charge catalytique en triflate de bismuth(III) de seulement 1 mol%. Cette stratégie a ensuite été étendue à d’autres dérivés cétones γ-alléniques. Les alcools diéniques résultants ont pu être engagés avec succès dans une réaction de type Diels-Alder menant à la formation de structures polycycliques fonctionnalisées avec de bons rendements et une excellente régio- et diastéréosélectivité. La cyclisation d’éthers d’énol catalysée par les triflates métalliques a été par la suite étudiée. Cette stratégie permet d’obtenir des dérivés cyclopentènes avec de bons rendements en utilisant seulement 0,1 mol% de triflate de bismuth(III). Des dérivés dihydrofuranes peuvent être également formés par cette stratégie. Ces produits résultent de l’attaque nucléophile du carbone central de l’allène sur l’éther d’énol activé. Cette réactivité a pu être inversée en utilisant un complexe d’or(I) comme catalyseur en présence d’un nucléophile externe, donnant ainsi naissance à des produits différents. Dans une dernière partie, des applications dans le domaine de la chimie des arômes et des parfums ont été développées. Des dérivés acétates et alcools alléniques ont été synthétisés et exposés à des tests olfactifs, révélant des tonalités olfactives intéressantes. Des notes fruitées et florales dominantes et des nuances vertes et boisées ont été détectées. / Novel processes of metal triflate-catalyzed cyclizations of functionalized allenes are presented. Two strategies have been developed. In a first part, the intramolecular carbonyl-ene reaction with γ-allenic ketones is described. This reaction proceeds under very mild conditions using only 1 mol% of bismuth(III) triflate. The scope of this reaction was extended to several γ-allenic ketone derivatives, featuring various substitution patterns. The resulting dienols were successfully engaged in a Diels-Alder reaction allowing the formation of polycyclic functionalized frameworks in good yields with excellent regio- and diastereoselectivities. In a second part, the metal triflate-catalyzed cyclization of allenic-enol ethers is described. This reaction gives access to cyclopentene derivatives in good yields using only 0.1 mol% of bismuth(III) triflate. Dihydrofuran derivatives could also be formed using this strategy. This cycloisomerisation reaction proceeds through an initial enol ether activation, followed by the nucleophilic attack of the allene moiety. This reactivity could be inverted using a gold(I) catalyst, in the presence of an exogenous nucleophile, allowing the formation of different products. Within our interest in flavor and fragrance chemistry, allenic acetates and alcohols have been synthesized and subjected to olfactive evaluation, revealing dominant fruity and floral notes. Green and woody undertones have been detected as well.

Indiana University-Purdue University Indianapolis (IUPUI) / As liver disease becomes more prevalent, the development of an in vitro culture system to study disease progression and its repair mechanisms is essential. Typically, 2D cultures are used to investigate liver cell (e.g., hepatocyte) function in vitro; however, hepatocytes lose function rapidly when they were isolated from the liver. This has promoted researchers to develop 3D scaffolds to recreate the natural microenvironment of hepatic cells. For example, gelatin-based hydrogels have been increasingly used to promote cell fate processes in 3D. Most gelatin-based systems require the use of physical gelation or non-specific chemical crosslinking. Both of these methods yield gelatin hydrogels with highly interdependent material properties (e.g., bioactivity and matrix stiffness). The purpose of this thesis research was to prepare modularly crosslinked gelatin-based hydrogels for studying the influence of independent matrix properties on hepatic cell fate in 3D. The first objective was to establish tunable gelatin-based thiol-norbornene hydrogels and to demonstrate that the mechanical and biological properties of gelatin hydrogels can be independently adjusted. Furthermore, norbornene and heparin dual-functionalized gelatin (i.e., GelNB-Hep) was prepared and used to sequester and slowly release hepatocyte growth factor (HGF). The second objective was to investigate the viability and functions of hepatocytes encapsulated in gelatin-based hydrogels. Hepatocellular carcinoma cells, Huh7, were used as a model cell type to demonstrate the cytocompatibility of the system. The properties of GelNB hydrogels were modularly tuned to systematically evaluate the effects of matrix properties on cell viability and functions, including CYP3A4 activity and urea secretion. The last objective was to examine the effect of heparin immobilization on hepatocyte viability and functions. The conjugation of heparin onto GelNB led to suppressed Huh7 cell metabolic activity and improved hepatocellular functions. This hybrid hydrogel system should provide a promising 3D cell culture platform for studying cell fate processes.

Strukturella batterier är multifunktionella; de tillhandahåller lagring av elektrokemisk energi samtidigt som de bidrar med en lastbärande funktion. Tillsammans möjliggör detta att batteriet kan integreras i karossen hos ett elektriskt fordon eller apparat. Denna multifunktionalitet möjliggör således en avsevärd reducering i fordonets vikt. Kompositmaterialet är förstärkt av kolfiberelektroder, innesluten i en elektrolytstruktur. För att förverkliga detta koncept måste batteriets elektrolyt kunna motstå mekanisk belastning, samtidigt som den transporterar joner mellan batteriets elektroder. Denna studie syftar till att bygga vidare på konceptet av fas-separerade polymerelektrolyter, skapade från polymerisationsinducerad fasseparation via termisk härdning, vilket är en teknik utvecklad av Schneider et al. och Ihrner et al. Vidare undersöks effekten av att dels använda en elektrolytlösning baserad på EC:PC, men även att inkorporera tioler till polymernätverket. Tvärbindningsmolekylerna som användes i denna studie inkluderade trimetylolpropan tris(3-merkaptopropionat) (3TMP), pentaerythritol tetrakis(3-merkaptopropionat) (4PER), och dipentaerythritol hexakis-(3-merkaptopropionat) (6DPER). Dessa skiljer sig i antal funktionella tiolgrupper. Konduktivitet, termo-mekanisk prestanda och strukturberoende egenskaper undersöktes genom tre laborativa faser. Den första fasen behandlade inverkan på elektrolytsystemet av ändrat lösningsmedel, tiol-funktionalitet samt tiolgruppförhållandet gentemot allyl gruppen på den primära monomeren. Sampolymeren innehållandes 6DPER uppvisade bäst multifunktionalitet, varpå denna utvecklades vidare i fas två där en optimal sammansättning fastställdes som bestod utav 45 viktprocent jonlösning. I den slutliga fasen konstruerades en halv-cell baserat på den tidigare optimerade elektrolytkompositionen; den uppmätta kapaciteten visar tydlig förbättring jämfört med tidigare forskning. Resultatet som erhölls i denna studie bidrar till förståendet av strukturella batteri-elektrolyter samt den forskning som en dag kan komma att förverkliga strukturella batterier och dess tillämpningskrav. / Structural batteries are multifunctional; providing electrochemical energy storage synergistically with a load-bearing function that enables their integration into the body panels of electric devices and vehicles. Thus, massless energy can be achieved. As a composite material, it is composed of reinforcing carbon fibre electrodes embedded in an electrolyte matrix. To realize this concept, the electrolyte must simultaneously transfer mechanical load and transport ions between electrodes. The following study builds on a phase-separated polymer electrolyte, created using polymerization-induced phase separation via thermal curing, formulated by Schneider et al. and Ihrner et al.. The impact of the incorporation of thiols for copolymerization and as cross-linking agents for the polymer network was researched along with use of an EC:PC-based solvent. The three thiols studied were: trimethylolpropane tris(3-mercaptopropionate) (3TMP), pentaerythritol tetrakis(3-mercaptopropionate) (4PER), and dipentaerythritol hexakis-(3-mercaptopropionate) (6DPER). These differed in regard to the amount of thiol functional groups present. Ionic conductivity, thermo-mechanical performance and structure-property relationships were studied across 3 laboratory phases. The first phase concerned the effect of thiol-functionality, the thiol functional group ratio relative to the allyl group present in the primary monomer, and the solvent interaction. 6DPER was concluded to be the most promising cross-linking agent. During the second phase, the effect of electrolyte content was evaluated with an optimum of 45 weight% determined. The third phase concluded the study, wherein a half-cell was assembled with the optimized electrolyte formulation showing improved capacity relative to previous studies. The results developed here contribute to the understanding of structural battery electrolyte systems and their continued research to meet application demands.

Today, the growing and aging population, and the rise of new global threats on human health puts an increasing demand on the healthcare system and calls for preventive actions. To make existing medical treatments more efficient and widely accessible and to prevent the emergence of new threats such as drug-resistant bacteria, improved diagnostic technologies are needed. Potential solutions to address these medical challenges could come from the development of novel lab-on-chip (LoC) for point-of-care (PoC) diagnostics. At the same time, the increasing demand for sustainable energy calls for the development of novel approaches for energy conversion and storage systems (ECS), to which micro- and nanotechnologies could also contribute. This thesis has for objective to contribute to these developments and presents the results of interdisciplinary research at the crossing of three disciplines of physics and engineering: electrokinetic transport in fluids, manufacturing of micro- and nanofluidic systems, and surface control and modification. By combining knowledge from each of these disciplines, novel solutions and functionalities were developed at the macro-, micro- and nanoscale, towards applications in PoC diagnostics and ECS systems. At the macroscale, electrokinetic transport was applied to the development of a novel PoC sampler for the efficient capture of exhaled breath aerosol onto a microfluidic platform. At the microscale, several methods for polymer micromanufacturing and surface modification were developed. Using direct photolithography in off-stoichiometry thiol-ene (OSTE) polymers, a novel manufacturing method for mold-free rapid prototyping of microfluidic devices was developed. An investigation of the photolithography of OSTE polymers revealed that a novel photopatterning mechanism arises from the off-stoichiometric polymer formulation. Using photografting on OSTE surfaces, a novel surface modification method was developed for the photopatterning of the surface energy. Finally, a novel method was developed for single-step microstructuring and micropatterning of surface energy, using a molecular self-alignment process resulting in spontaneous mimicking, in the replica, of the surface energy of the mold. At the nanoscale, several solutions for the study of electrokinetic transport toward selective biofiltration and energy conversion were developed. A novel, comprehensive model was developed for electrostatic gating of the electrokinetic transport in nanofluidics. A novel method for the manufacturing of electrostatically-gated nanofluidic membranes was developed, using atomic layer deposition (ALD) in deep anodic alumina oxide (AAO) nanopores. Finally, a preliminary investigation of the nanopatterning of OSTE polymers was performed for the manufacturing of polymer nanofluidic devices. / <p>QC 20140509</p> / Rappid / NanoGate / Norosensor

In novel drug delivery system, the encapsulation of therapeutic cells in microparticles has great promises for the treatment of a range of health con- ditions. Therefore, the encapsulation material and technology are of great importance to the validity and efficiency of the advanced medical therapy. Several unsolved challenges in regards to versatile microparticle synthesis ma- terials and methods form the main obstacle for a translation of novel cell therapy concepts from research to clinical practice. Thiol-ene based polymer systems have emerged and gained great popular- ity in material development in general and in biomedical applications specif- ically. The thiol-ene platform is broad and therefore of interest for a variety of applications. At the same time, many aspects of this material platform are largely unexplored, for example material and manufacturing technology developments for microfluidic applications . In this Ph.D. thesis, thiol-ene materials are explored for use in cell encap- sulation. The marriage of these two technology fields breeds the possibility for a novel microfluidic cell encapsulation approach using a novel encapsulation material. To this end, several new manufacturing technologies for thiol-ene and thiol-ene-epoxy droplet microfluidic devices were developed. Moreover, core-shell microparticle synthesis for cell encapsulation based on a novel co- synthesis concept using a thiol-ene based material was developed and inves- tigated. Finally, a thiol-ene-epoxy system was also used for the formation of microwells and microchannels that improve protein analysis on microarrays. The first part of the thesis presents the background and state-of-the-art technologies in regards to cell therapy, microfluidics, and thiol-ene based ma- terials. In the second part of the thesis, a novel manufacturing approach of thiol-ene-epoxy material as well as core-shell particle co-synthesis in micro- fluidics using thiol-ene based material are presented and characterized. The third part of the thesis presents the cell viability studies of encapsulated cells using the novel encapsulation material and method. In the final part of the thesis, two applications of thiol-ene-epoxy gaskets for protein detection mi- croarrays are presented. / Inkapsling av levande celler i mikrokapslar för terapeutiska ändamål är mycket lovande för frmatida behandling av många olika sjukdomar. Emeller- tid är en behandlings effektivitet i hög grad beroende av vilka material som används för inkapsling och vilken teknisk lösning som används för att ska- pa mikrokapslarna. För närvarande återstår det många utmaningar för att omvandla grundforskningresultat till klinisk verklighet, vilken kräver mer än- damålsenliga tillvägagångssätt för att tillverka mikrokapslar i material som är kompatibla med användningsområdena. De senaste åren har tiol-en baserade polymerer har blivit mycket använda för materialutveckling i stort och för biomedicinska tillämpningar i synnerhet. Med tiol-en kemi kan en mycket stor mängd helt olika syntetiska material framställas, vilket gör tiol-ener intressanta för en mängd applikationer. För närvarande är dock mycket inom denna materialklass outforskat, t.ex. inom material och tillverkningmetodik för mikrofluidiktillämpningar. I denna avhandling används tiol-ener för cellinkapsling. Sammanslagning av dessa teknologier möjliggör en ny typ av cellinkapsling med nya materi- alegenskaper. En mängd olika tillverkningssätt där tiol-en eller tiol-en-epoxi används för droplet-mikrofluidiksystem utvecklades. Core-shell mikrokapsel- syntes för cell-inkapsling baserat på en ny metod för samtidig syntes av både core och shell utvecklades och karaktäriserades. Slutligen utvecklades ett tiol- en-epoxi system för enkel integrering med proteinmikroarrayer på objektsglas. I avhandlingens första del presenteras bakgrund och dagens bästa teknolo- gier för terapeutisk cellinkapsling, mikrofluidik och tiol-en baserade material. I avhandlingens andra del presenteras en ny tillverkningsmetod för mikro- strukturerade tiol-en-epoxi artiklar och samtidig syntes av core och shell för mikrokapslar med användande av mikrofluidik. I den tredje delen presenteras cellöverlevandsstudier för de celler som inkapslats med de nya materialen och de nyutvecklade metoderna. I den avslutande delen beskrivs två specifika fall där tiol-en-epoxi komponenter används för proteindetektion och mikroarrayer. / <p>QC 20171122</p>

Indiana University-Purdue University Indianapolis (IUPUI) / Hydrogels prepared from photopolymerization have been used for a variety of tissue engineering and controlled release applications. Polymeric biomaterials with high cytocompatibility, versatile degradation behaviors, and diverse material properties are particularly useful in studying cell fate processes. In recent years, step-growth thiol-ene photochemistry has been utilized to form cytocompatible hydrogels for tissue engineering applications. This radical-mediated gelation scheme utilizes norbornene functionalized multi-arm poly(ethylene glycol) (PEGNB) as the macromer and di-thiol containing molecules as the crosslinkers to form chemically crosslinked hydrogels. While the gelation mechanism was well-described in the literature, the network properties and degradation behaviors of these hydrogels have not been fully characterized. In addition, existing thiol-ene photopolymerizations often used type I photoinitiators in conjunction with an ultraviolet (UV) light source to initiate gelation. The use of cleavage type initiators and UV light often raises biosafety concerns. The first objective of this thesis was to understand the gelation and degradation properties of thiol-ene hydrogels. In this regard, two types of step-growth hydrogels were compared, namely thiol-ene hydrogels and Michael-type addition hydrogels. Between these two step-growth gel systems, it was found that thiol-ene click reactions formed hydrogels with higher crosslinking efficiency. However, thiol-ene hydrogels still contained significant network non-ideality, demonstrated by a high dependency of hydrogel swelling on macromer contents. In addition, the presence of ester bonds within the PEGNB macromer rendered thiol-ene hydrogels hydrolytically degradable. Through validating model predictions with experimental results, it was found that the hydrolytic degradation of thiol-ene hydrogels was not only governed by ester bond hydrolysis, but also affected by the degree of network crosslinking. In an attempt to manipulate network crosslinking and degradation rate of thiol-ene hydrogels, different macromer contents and peptide crosslinkers with different amino acid sequences were used. A chymotrypsin-sensitive peptide was also used as part of the hydrogel crosslinkers to render thiol-ene hydrogels enzymatically degradable. The second objective of this thesis was to develop a visible light-mediated thiol-ene hydrogelation scheme using a type II photoinitiator, eosin-Y, as the only photoinitiator. This approach eliminates the incorporation of potentially cytotoxic co-initiator and co-monomer that are typically used with a type II initiator. In addition to investigating the gelation kinetics and properties of thiol-ene hydrogels formed by this new gelation scheme, it was found that the visible light-mediated thiol-ene hydrogels were highly cytocompatible for human mesenchymal stem cells (hMSCs) and pancreatic MIN6 beta-cells. It was also found that eosin-Y could be repeatedly excited for preparing step-growth hydrogels with multilayer structures. This new gelation chemistry may have great utilities in controlled release of multiple sensitive growth factors and encapsulation of multiple cell types for tissue regeneration.

The research presented in this dissertation is focused on the construction of complex molecular structures on planar gold and silicon dioxide surfaces using a variety of surface modification techniques, along with thorough surface characterization at each modification step. The dissertation is structured into six separate chapters. In Chapter 1, an introduction to the importance and implications of molecular level surface modification, commonly employed surface modification methods, and available surface characterization techniques is presented. Chapter 2 shows applications of novel methodologies for the functionalization of gold surfaces using alkane dithiol self-assembled monolayers and thiol-ene click chemistry. The resulting functionalized gold substrates demonstrate higher chemical stability than alkanethiol self-assembled monolayers alone and allow spatially controlled functionalization of gold surfaces with light. In Chapter 3, work on tunable hydrophobic surfaces is presented. These surfaces are prepared using a combination of organosilane chemistry, layer-by-layer polyelectrolyte deposition, and thiol-ene chemistry. These hydrophobic surfaces demonstrate high mechanical and chemical stability, even at low pH (1.68). The pinning of water droplets could be tuned on them by the extent of their thermal treatment. Comprehensive surface characterization using X-ray photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectrometry (ToF-SIMS), spectroscopic ellipsometry, atomic force microscopy, and water contact angles was carried out on the molecular assemblies prepared on gold and silicon dioxide surfaces. Chapters 4 and 5 are focused on the application, data interpretation, and enhancement in sensitivity of different surface characterization methods. In Chapter 4, XPS, ToF-SIMS, and principal components analysis are used to probe a real world corrosion-type problem. This systemic study showed the destruction of a protective coating composed of a nitrilotris(methylene)triphosphonic acid by a low-intensity fluorine plasma. In Chapter 5, enhancement in ToF-SIMS signals is shown via bismuth metal deposition. These surfaces are also probed by spectroscopic ellipsometry using the interference enhancement method. Finally, Chapter 6 concludes this dissertation by describing possible future work.