Polymers of Intrinsic Microporosity (PIMs) combine the desirable processability of polymers with a significant degree of microporosity generated from the inefficient packing of their rigid and contorted structures. They are attracting attention for a variety of applications including as membrane materials for gas separations. Over the last 30 years, membranes have become an established technology for separating gases and are likely to play key role in reducing the environmental impact and costs of many industrial processes such as O2 or N2 enrichment from air, natural gas upgrading and hydrogen recovery from ammonia production. This thesis describes the synthesis of a series of novel PIMs, primarily PIM-polyimide structures (PIM-PI) and investigates their potential in such applications. In particular, it focuses on the design and synthesis of solution processable PIMs in order to study how structural differences affect the gas permeability. The first section describes the synthesis of a variety of PIM-PIs using large bulky diamines derived from spirobisindane (SBI) and biphenylfluorene (BPF) structures which are useful monomers for achieving high BET (Brunauer-Emmett- Teller) surface areas (> 650 m2 g-1). The second section describes a whole series PIs based on novel and literature based Tröger’s base (TB) diamine monomers. Most of these exhibited good solubility, excellent thermal stability and intrinsic microporosity, with apparent BET surface areas in the range 450-739 m2 g-1. Notably, a polyimide derived from Me2TB and pyromellitic anhydride demonstrates gas permeability data above the 2008 upper bounds for important gas pairs such as O2/N2, H2/N2 and H2/CH4. The third section aims to enforce rigidity within the polymers further by incorporating differently substituted monomers based on rigid ethanoanthracene (EA) units. This includes the formation of a novel EA-EA based PI with an exceptionally rigid polymeric structure, possessing a BET surface area of 694 m2 g-1. In addition to very high permeability, this polymer demonstrates improved gas selectivity due to its enhanced performance as a molecular sieve, placing it amongst some of the highest performing polymers to date. The final section looks at other ways in which rigidity can be enforced including the formation of TB-polymers and thermally rearranged (TR) polymers and assesses their potential for future investigations.

Securing water in the right quantities at the right quality for the right price is a major issue around the world. Membranes are making an increasingly important contribution to meeting this need; however their performance is limited by fouling. This thesis reports on an investigation into the fouling of systems related to water treatment using the Direct Observation Through the Membrane (DOTM). The investigation focused on the measurement of critical flux and observation of particle behaviour under a variety of conditions and for a number of different particles. The range of meanings attributed to critical flux in the literature was analysed and several proposals made for the improved use of the concept. In particular, critical flux determination techniques were classified by whether they measure resistance changes or particle deposition; leading to the definition of Critical Resistance and Critical Deposition Fluxes. In this thesis the deposition definition is used exclusively. The effect of Reynolds number and spacer orientation on critical flux was correlated for spacer-filled channels. The heterogeneous deposition patterns observed with regions of heavy deposition next to areas of little or no deposition. This pattern was related to the local hydrodynamics of spacer cells (a few mm2 in size). The correlations developed for critical flux in spacer-filled channels were adjusted for submicron particle size and incorporated into a SpiralWound Module (SWM) leaf model and then used to simulate the fouling of SWM leaves under a range of operating conditions and operating policies. The Mass Balance technique of critical flux determination was also briefly assessed. The applicability of critical flux criteria to SWM arrays was discussed. Fouling, particle behaviour and critical flux were also investigated in air-sparged systems. The post-cleaning water flux was found to be enhanced when the membrane is fouled in the presence of bubbles. The rate of flux decline was reduced by bubbles. Critical flux increased with air flowrate, and decreased with increased liquid flowrate and concentration. Bubbles caused particles to periodically deposit on the membrane. Particles were observed to stream past the membrane under the influence of back-diffusive forces. Video clips of particulate fouling are provided.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 93-119).

La présence de leucocytes dans les dérivés sanguins à transfuser a été soulignée et rendue responsable de différentes complications graves chez les patients receveurs,et notamment chez certaines catégories de patients plus sensibles tels les immunodéprimés, les nouveau-nés, les candidats aux greffes, et les personnes transfusées à répétition. Le but de ce projet est l'aménagement de membranes de filtration du sang permettant une rétention cellulaire sélective par greffage covalent de ligands spécifiquement reconnus par les intégrines α4β1, α4β7, et β2 exprimées chez les leucocytes Nous avons envisagé l'amélioration des propriétés filtrantes de deux membranes commerciales, de PVDF et de PBT, en y fixant de manière covalente des ligands d'intégrines de leucocytes. Nous avons réalisé la synthèse de divers dérivés des tripeptides LDV et LLG ainsi que d'un composé peptidomimétique. Ces molécules ont été greffées de manière covalente aux membranes, par le biais de bras d'espacement de type polyéthylène glycol, permettant d'exposer les signaux biologiques de façon optimale vis-à-vis de la reconnaissance cellulaire. Nous avons caractérisé les membranes de PVDF et de PBT par SEM (Scanning electron microscopy : étude structurale, compatibilité des solvants, contrôle d'intégrité après traitements), par XPS (X-Ray photoelectron spectroscopy : étude sur les membranes natives, greffages de sondes chlorées ou fluorées) ainsi que par LSC (Liquid scintillation counting : mesures de réactivité de surface vis-à-vis de la lysine tritiée,tests d'activation, mise au point des modes opératoires).Les fonctions accessibles au greffage sont de type acides carboxyliques et alcools pour les membranes de PBT et de type alcools pour celles de PVDF. Diverses méthodes de greffage ont été testées sur ces deux matériaux. La méthode retenue pour le PBT consiste en l'utilisation d'un clip moléculaire muni d'une fonction azoture et d'un ester activé sous forme de N-hydroxysuccinimide, mis au point au laboratoire, greffé par activation photochimique. D'autre part, c'est une activation des fonctions alcools présentes sur le PVDF par le fluorure de cyanuryle qui a retenu notre attention. Ces deux méthodes ont été appliquées à la fixation des ligands d'intérêt synthétisés par nos soins. Les membranes dérivatisées ont finalement été analysées en XPS pour s'assurer de la présence des ligands et utilisées dans des tests de filtration de buffy coat. La qualité de la filtration obtenue a pu être évaluée en cytométrie de flux. Les résultats obtenus sont intéressants puisqu'une nette amélioration de la qualité de la rétention leucocytaire a pu être observée (facteur 100).

Les systèmes d’efflux tripartite de type Resistance, Nodulation and cell-Division (RND) sont essentiels dans le maintien de phénotypes de résistance multidrogues et contre les métaux lourds dans nombreuses bactéries Gram-négatives. Le transport de ces composés toxiques hors de la cellule est permis par l’assemblage d’une protéine de type antiporteur cation/proton (unité RND) insérée dans la membrane interne, connectée à une protéine insérée dans la membrane externe, pour former un canal de sorti qui traverse l’entièreté de l’enveloppe cellulaire. Le troisième composant du système, la protéine de type membrane fusion protein (MFP) qui est aussi appelée periplasmic adaptor protein (PAP), est requis pour permettre l’assemblage de tout ce complexe à trois composants. Cependant, les MFPs sont supposées jouer un rôle important et actif dans le mécanisme d’efflux du substrat. Pour mieux comprendre le rôle des MFPs au sein des systèmes d’efflux de type RND, nous avons étudié les protéines ZneB (précédemment appelée HmxB) et SilB, les composants périplasmiques des systèmes ZneCBA et SilABC responsables de la résistance aux métaux lourds chez Cupriavidus metallidurans CH34. Nous avons identifié la spécificité de liaison au substrat de ces protéines, montrant leur capacité à fixer le zinc (ZneB), ou le cuivre et l’argent (SilB). De plus, nous avons résolu la structure cristalline de ZneB à une résolution de 2.8 Å dans la forme apo- et avec un ion zinc fixé. La structure de ZneB possède une architecture générale composée de quatre domaines caractéristiques des MFPs, et la présence du site de coordination au zinc dans une région très flexible à l’interface des domaines β-barrel et membrane proximal. Les modifications structurales que la protéine subit lors de la fixation du zinc on été observée dans le cristal mais aussi en solution, ce qui suggère un rôle actif des MFPs dans le mécanisme d’efflux des métaux, vraisemblablement via la fixation et le relargage de l’ion à l’antiporteur. Les études de sélectivité de transport des antiporteurs ZneA et SilA montre que ces dernières et leurs protéines périplasmiques respectives ont des affinités similaires pour les métaux lourds. De plus, les études de transport ont apportés des arguments en faveur de l’hypothèse de capture cytoplasmique du substrat par l’antiporteur, tandis que la capacité des protéines périplasmiques à fixer les métaux lourds a apporté des arguments en faveur de l’hypothèse de capture périplasmique du substrat par l’antiporteur. Les deux modes de capture pourraient en réalité coexister ; cependant, le débat autour du compartiment cellulaire de capture du substrat par l’antiporteur est complexe et requiert de plus amples efforts afin d’être cerné. / Tripartite resistance nodulation cell division (RND)-based efflux complexes are paramount for multidrug and heavy metal resistance in numerous Gram-negative bacteria. The transport of these toxic compounds out of the cell is driven by the inner membrane proton/substrate antiporter (RND protein) connected to an outer membrane protein to form an exit duct that spans the entire cell envelope. The third component, a membrane fusion protein (MFP) also called periplasmic adaptor protein, is required for the assembly of this complex. However, MFPs are also proposed to play an important active role in substrate efflux. To better understand the role of MFPs in RND-driven efflux systems, we studied ZneB (formerly HmxB) and SilB, the MFP components of the ZneCAB and SilABC heavy metal RND-driven efflux complexes from Cupriavidus metallidurans CH34. We have identified the substrate binding specificity of the proteins, showing their ability to selectively bind zinc (ZneB), or copper and silver cations (SilB). Moreover, we have solved the crystal structure of the apo- and the metal-bound forms of ZneB to 2.8 Å resolution. The structure of ZneB displays a general architecture composed of four domains characteristic of MFPs, and it reveals the metal coordination site at the very flexible interface between the β-barrel and the membrane proximal domains. Structural modifications of the protein upon zinc binding were observed in both the crystal structure and in solution, suggesting an active role of MFPs in substrate efflux possibly through binding and release. The selectivity assays of the antiporter proteins ZneA and SilA demonstrated similar specificities in relation to their cognate MFPs toward heavy metal cations. Moreover, antiporter transport assays provide evidence for cytoplasmic substrate capture by this protein, whereas MFP substrate binding provides evidence for periplasmic substrate capture. Therefore, both modes of capture might co-exist; nevertheless, the substrate capture issue is a complex topic still needing consequent efforts to understand it.

Cholesterol is an important component in maintaining the structure and dynamics of cell membranes. Dysregulation of cholesterol results in detrimental changes including decreased fluidity of the membrane and changes in membrane permeability. Because cholesterol is synthesized and regulated in the liver, many liver diseases are accompanied by dysregulation of cholesterol. And this dysregulation could alter transportation of small molecules through the cell membrane of such diseased cells. This study will focus on the diffusion of three small-molecule drugs through liver cell membranes with varying cholesterol concentration using a molecular dynamics approach. Results from this study could provide more detail about cholesterol’s effect on liver cell membrane permeability.

In this thesis, a new model is formulated for a piezoelectric membrane and fluid motion in a microchannel heat engine. A new slug flow model is developed for droplet motion in a circular cross-section channel. The model includes friction, pressure, viscous and thermocapillary forces on the droplet. This thesis examines the concept of a piezoelectric device at one end of the channel to generate electricity from thermocapillary pumping of the droplet within the microchannel. The slug flow model is used to predict the flow energy needed to convert the thermocapillary pumping into electrical energy. A thin membrane design of a piezoelectric device is developed and modelled with the slug flow approximation. The deformation of the piezoelectric membrane is analyzed. The deformation is found to be a function of the air pressure in the closed microchannel and the displacement of the droplet along the microchannel. This was formulated based on the bending of a thin plate (representing the membrane). The displacement relates to the final output voltage of the design. The direct piezoelectric effect was also examined to determine a relationship between the output voltage and induced stress on the membrane by the force of air. Results are presented for a micro heat engine configuration containing a single membrane on one side of the droplet. It was found that the deformation of the membrane and the output voltage were directly proportional to the displacement of the droplet. A relatively small output voltage was gained from a complete cycle of the droplet. A sensitivity study was performed by varying the channel dimensions along with the dimensions of the piezoelectric membrane. The coupling factor of the piezoelectric membrane was varied to examine its effect on the output voltage. It was found that a larger channel and thinner membrane resulted in a larger output voltage. Materials with a large piezoelectric constant were found to have the largest output voltage, as opposed to those with a lower dielectric constant. / UOIT

This thesis investigates the fouling of a microfiltration membrane by biological solutions. Membrane fouling is recognized as a major drawback for the application of microfiltration in the purification of biotechnology products. Membrane fouling was analyzed and compared for filtrations performed with a hollow fiber microfiltration module operated at constant permeate flux using bovine serum albumin (BSA) solutions or Chinese hamster ovary (CHO) cell culture broths as feed solutions. A mechanistic model was developed to represent the fouling of a cross-flow microfiltration membrane operated at constant permeate flux. Fouling was observed as an increase in the transmembrane pressure (TMP) and assumed to occur first by pore blockage followed by cake formation over the blocked pores. The effect of the cross-flow action was described by the removal of deposits from the membrane surface thereby reducing the pore blockage and the mass of the cake. The model was fitted to the TMP profiles obtained during the filtration of BSA solutions and Chinese hamster ovary (CHO) cell culture broths with a 0.45 µm polysulfone hollow fiber membrane. According to the fitted model, pores blocked faster and more cake was formed with increasing BSA concentration. In the case of CHO cell culture broth, increasing the wall shear rate (proportional to cross-flow velocity) seemed to lead to the formation of a less pronounced cake but more pore blockage. The cross-flow mechanistic model was applied to the microfiltration of CHO cell culture supernatants harvested at different days of the fermentation process. The filtrations were performed at two different shear rates and with two different membrane pore sizes. The cell culture supernatant caused membrane fouling observed as an increase in both the TMP and the membrane hydraulic resistance estimated from water flux measurements at the end of the filtrations. The highest TMP increase was observed for the filtrations with the smaller membrane pore size (0.2 µm) and the higher shear rate (8000 s-1). The hydraulic resistance estimates of the fouled membrane also revealed a higher irreversible fouling for the smaller (0.2 µm) membrane pore size while the model analysis indicates that more fouling occurred at the entrance of the membrane pores. The shear rate was found to strongly influence the contribution of the reversible fouling to the total hydraulic resistance of the membrane. The cross-flow mechanistic model indicates a higher pore blockage for the most severe membrane fouling observed experimentally for the smaller membrane pore size and the higher shear rate. At the same time, a smaller cake deposit was predicted for the higher shear rate. The different cell culture harvest time investigated in this study did not reveal any differences in membrane fouling. BSA solutions were used to evaluate the contribution of BSA aggregates, fresh cell culture medium and the non-ionic surfactant Pluronic F-68 to membrane fouling. A simple empirical model was developed to represent the TMP increase and to derive the initial fouling rate. The initial fouling rate, the normalized TMP and the irreversible membrane resistance at the end of the filtration were analyzed to determine the effect of BSA solution characteristics on membrane fouling. The initial fouling rate increased with increasing BSA aggregate content consistent with a two-step fouling mechanism that was proposed for membrane fouling by BSA. Increased BSA concentration and the use of fresh cell culture medium compared to potassium phosphate buffer resulted in an increase in initial fouling rate, TMP and irreversible membrane fouling. The addition of the non-ionic surfactant Pluronic-F68 to the BSA solutions decreased the long-term fouling and the irreversible fouling but did not affect the initial fouling rate.

We theoretically study the adhesion and membrane-mediated interaction of cylindrical colloids to a flat fluid membrane. There are two ways to approach this problem. The first way, based on energy, requires finding the equilibrium shape of the membrane given the placement of the particle(s). In order to do so, we need to know how the energy of the surface depends on its shape (i.e. the surface Hamiltonian), as well as how the adhered colloid deforms the membrane. The second way to approach this class of problems is “geometrical”, where forces between the membrane-adhered particles are related directly to the geometry of the deformed membrane via the surface stress tensor. The surface Hamiltonian allows finding the stress at any point on the membrane in terms of local geometry. The force acting on the colloid can then be found by integrating this surface stress tensor along any contour enclosing the colloid. In this thesis, using the approach based on free energy calculations, we look into the problem of cylindrical colloids adhering to a membrane with fixed constant adhesion energy between the membrane and the colloids. Angle-arclength parameterization is used in order to treat the problem beyond small gradient approximation. We present three different cases here: single cylinder adhering on a membrane, two cylinders adhering on the same side of the membrane, and two cylinders adhering on different sides of the membrane. For the single cylinder case we present a structural phase diagram to separate no wrapping, partial wrapping and closure states and we compare it to the phase diagram obtained for a related system of spherical colloids. For two cylinders adhered on the same side of the membrane we obtain repulsive interaction and transition from shallow to deep wrapping as the cylinders move apart from each other. We also look into a phase where two cylinders are vertically stacked and discuss its energetics. For two cylinders adhering to the opposite sides of the membrane, attractive interaction is obtained in accordance with previous results and we further show that in that case two cylinders are generally in contact and a first-order transition from shallow to full wrapping is possible. In the last section, we put a framework for the class of problems where the particle is between the membrane and the supporting interface, where adhesion is assumed between the interface and the membrane.

The norepinephrine transporter (NET) clears norepinephrine (NE) from the synapse after vesicular release. NET is a target of the psychostimulant amphetamine (AMPH). We have recently shown that AMPH alters trafficking of the transporter, causing a net decrease in surface NET in the monoaminergic CAD cell line. In this study we demonstrate, by confocal imaging of immunostained superior cervical ganglion (SCG) neurons, that AMPH causes an increase in NET levels inside terminal boutons. Further, the intracellular compartment in which NET accumulates upon AMPH exposure is not known; such information would inform investigation of the mechanism by which the drug affects NETs cellular distribution. We show that after AMPH treatment, NET co-fractionates with both Rab4 and Rab11, and that AMPH increases co-localization of NET with these endosomal markers as indicated by the intensity correlation quotient (ICQ). Finally, we show that the functions of both GTPases are involved in AMPH-regulated NET trafficking by transfection of dominant negative (DN) constructs followed by cell-surface biotinylation. Our results support the conclusion that AMPH-regulated NET trafficking occurs through endosomes.