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.

Nanoporous metal-organic frameworks (MOFs) have attracted tremendous interest due to their potential applications in gas-storage, gas separation, gas sensing, and catalysis. MOFs consist of metal-oxygen polyhedera interconnected with a variety of organic linker molecules, resulting in tailored nanoporous materials. With a judicious choice of organic linker groups, it is possible to fine-tune size, shape, and chemical functionality of the cavities and the internal surfaces. This unique structural feature offers unprecedented opportunities in small-molecule separations as well as chiral separations and catalysis. Prototypical iso-reticular metal-organic frameworks (IRMOFs) have been extensively studied among MOFs due to the simplicity of their synthesis and the variety of their potential applications. IRMOFs are a specific series of metal-organic frameworks developed by Yaghi and his coworkers. All IRMOFs are composed of oxygen-centered Zn4O tetrahedra interconnected with dicarboxylate linkers, forming a cubic type three dimensional (3D) porous network with high surface area. Despite a great deal of research in the synthesis and characterization of MOFs, there have been relatively few reports on the development of their applications, such as the fabrication of MOF thin films and membranes for gas separations. This is mainly due to the challenges associated with relatively difficult heterogeneous nucleation (seeding) and growth of MOFs on supports, and crack formation compared to their counterparts. Thin films and membranes of MOFs have great potentials for applications in membranebased gas separations, reactors, chemical sensors, and nonlinear optical devices. In this dissertation, the fabrication of IRMOF-1 membrane using a novel seeding method and its gas diffusion properties has been demonstrated. Introduction of the new seeding method for MOFs using microwaves resulted in well inter-grown IRMOF membranes showing Knudsen type transport of small gases through its pore. The heteroepitaxial growth of one IRMOF on another produced multi-layered IRMOF membranes. In addition, postsynthetic modification (PSM) of IRMOFs created functionalized membranes with enhanced stability against water as well as reduced crack formation during membrane fabrication. Lastly, hierarchical IRMOFs with improved CO2 adsorption properties were synthesized via PSM with cyanuric chloride.

The 105aa lambda S protein is the prototype holin, S accumulates in the cytoplasmic membrane during late gene expression until, at a time programmed into its primary structure, it disrupts the membrane and allows the lambda lysozyme, R, to attack the cell wall. In this study, a zwitterionic detergent Empigen BB, was used to extract and purify the lambda holin S. In Empigen BB, CD analysis on S gave 54% alpha helical content, consistent with 3 TM domains, which has been reported by other in vivo studies. Empigen BB-purified S can be exchanged into a chaotropic solution by dialysis and reconstituted into preformed lipid vesicles for activity assays. When diluted to fluorescein-loaded suspensions of liposomes, different chaotrope-solubilized S alleles caused dye release reflective of their in vivo phenotypes. The problem was the low efficiency of delivery of S to the liposomes. Unfortunately, dye loaded liposomes are highly sensitive to any detergent, making it necessary to find other ways to solubilize S. GroEL, a chaperonin from E. coli, is responsible for folding and refolding globular proteins in vitro. It has also been reported that GroEL improves the ability of a membrane protein synthesized in vitro to insert post-translationally into liposomes. This work will investigate the behavior of GroEL towards membrane proteins. The first of two membrane proteins studied in this respect is Bacteriorhodopsin (BR), a membrane proton pump, from H. halibium. The second is the105aa S protein, a prototype holin from bacteriophage lambda. Holin and BR subjected to detergent removal in the presence of GroEL remained in solution, while in the control sample (without GroEL) S and BR precipitated. "GroELsolubilized" holin still retained its lesion forming activity and solubilized BR maintained its proton pumping ability, detected by using a liposome dye activity assay unique to each protein. This approach may be applicable to other systems requiring detergent- or chaotrope-free preparation of membrane proteins. Finally, these results suggest that GroEL may be involved in the insertion of integral membrane proteins into the lipid bilayer, a role heretofore unsuspected.

Thesis (Ph. D.)--University of Alberta, 2010. / Title from pdf file main screen (viewed on Jan. 18, 2010). A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Biochemistry, University of Alberta. Includes bibliographical references.

Thesis (M.S.)--Brigham Young University. Dept. of Microbiology and Molecular Biology, 2008. / Includes bibliographical references (p. 44-47).

Thesis (Ph. D.)--Hong Kong University of Science and Technology, 2003. / Includes bibliographical references (leaves 130-138). Also available in electronic version. Access restricted to campus users.

Thesis (Ph.D)--Mechanical Engineering, Georgia Institute of Technology, 2009. / Committee Chair: Andrei Fedorov; Committee Member: Srinivas Garimella; Committee Member: Timothy Lieuwen; Committee Member: William Koros; Committee Member: William Wepfer. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Thesis (MTech (Chemical Engineering))--Peninsula Technikon, 2000. / Word processed copy. Summary in English. Includes bibliographical references. Also available online.

published_or_final_version / Chinese Medicine / Doctoral / Doctor of Philosophy