Engineering Commons^™

Exploring Modalities Of Productivity And Critical Quality Attributes In Fed-Batch Chinese Hamster Ovary Cell Cultures, Stephanie Klaubert

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Chinese hamster ovary (CHO) cells are among the most commonly used mammalian cell lines for the production of recombinant therapeutic proteins due to ease of culturing and humanlike post-translational modification capabilities. However, when compared to microbial systems, CHO cell line growth and productivity is relatively low. As the demand for monoclonal antibody (mAb) treatments continues to rise, it is critical to explore modalities for improved growth and productivity in CHO cell cultures, with the goal of increased protein concentrations and maintained product quality. Though some mechanisms for improved productivity, including temperature and cell culture media formulations, are relatively well understood; …

Computationally-Driven Insights Into The Ligand Environments Of Materials For Catalysis And Separations, Stephen Vicchio

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Designing new catalytic and sorption materials is necessary to limit global temperature rise below 1.5 ◦C by 2050, while also meeting global energy demands. Climate change and energy production are not mutually exclusive; global population growth has direct impacts on global energy demands and climate. In both catalysis and adsorption applications, new technologies are needed to address these challenges. Catalysis can provide alternate, low-energy routes for converting low-value gases into higher-value chemical commodities, thus altering our current energy production. Likewise, new sorption materials can capture previously emitted CO₂ from decades of energy production from fossil fuels, thus helping to …

Improving Lignin Recovery From Paper Mill And Biorefinery Waste Streams Via Liquid-Phase Splitting, Carter Fitzgerald

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Lignin is an abundant biopolymer with significant promise due to its aromaticity. It has been targeted as a replacement for a number of petroleum-based products including adhesives, coatings, polyurethane foams, activated carbon, and carbon fibers. However, commercially available bulk lignins are too polydisperse, and contain too many residual metals from the pulping process that are detrimental to the properties of the final product.

The Sequential Liquid-lignin Recovery and Purification (SLRP) process was developed by Michael Lake and John Blackburn, in collaboration with Clemson, with the intention of creating a continuous method for recovering lignin from paper-mill black liquors. Thies and …

Protein A And Multimodal Anion-Exchange Membrane Adsorbers For Downstream Purification Of Therapeutic Biomolecules, Joshua Osuofa

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This dissertation explores development and characterization of membrane chromatography tools for downstream purification of therapeutic biomolecules. Convective technologies, particularly membrane chromatography, are emerging in the field of bioseparations as an alternative to resin chromatography due to their improved throughput capability. On the forefront of emerging membrane technologies are multimodal and Protein A membrane adsorbers. The overarching theme of this dissertation research was to investigate advances in these membrane chromatography tools. The primary objective was to develop and characterize novel Protein A membrane adsorbers. A secondary objective was to characterize newly commercialized Protein A and multimodal anion exchange membrane adsorbers.

Two …

Multiscale Modeling And Gaussian Process Regression For Applications In Composite Materials, Joshua Arp

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An ongoing challenge in advanced materials design is the development of accurate multiscale models that consider uncertainty while establishing a link between knowledge or information about constituent materials to overall composite properties. Successful models can accurately predict composite properties, reducing the high financial and labor costs associated with experimental determination and accelerating material innovation. Whereas early pioneers in micromechanics developed simplistic theoretical models to map these relationships, modern advances in computer technology have enabled detailed simulators capable of accurately predicting complex and multiscale phenomena.

This work advances domain knowledge via two means: firstly, through the development of high-fidelity, physics-based finite …

Characterization Of Lignin And Cellulose Biopolymers Structure – Function Relationships, Zachariah Pittman

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Biomass is vital to ongoing efforts to secure a sustainable future. While many of our efforts focus on finding alternative forms of energy, biomass among them, only biomass has the potential to serve as a sustainable materials feedstock. However, biomass is heterogenous, complicating the upgrading processes needed to manufacture commodity and performance products. For example, plant biomass consists largely of cellulose, a crystalline polysaccharide, and lignin, a highly stable polyaromatic. The specific properties of cellulose and lignin depend greatly on the plant, harvesting conditions, and isolation procedures. Thus, accurate and reliable determination of the fundamental properties of biomass is crucial …

Elucidating The Mechanical And Transport Properties Of Lignin-Based Hydrogel Composites, Nicholas Gregorich

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The use of lignin in the fabrication of soft composites has become an emerging area of research in polymer science and polymer chemistry. These lignin-based materials present numerous benefits, notably, a reduction in the use of petroleum-based precursor, improved structural benefits to otherwise soft host polymers, as well as the inherent antimicrobial and antioxidant properties of lignin, making it suitable for biomaterials. Herein, we present two chemical reaction pathways of incorporating lignin that was fractionated and cleaned using the Aqueous Lignin Purification with Hot Agents (ALPHA) process into poly(vinyl alcohol) (PVA) hydrogel composites for aqueous-based separations. By leveraging the ALPHA …

Fluorescence Multiplexing With Combination Probes For Biological And Diagnostic Applications, Madeline Mccarthy

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Cancer refers to a group of diseases containing more than 200 different subtypes. Cancer is a heterogeneous disease by nature, meaning that there are differences among tumors of the same type in different patients, and there are differences among cancer cells within a single tumor of one patient. Since cancer is not a single disease, nor does it have a single cause, it proves to be incredibly hard to diagnose and treat. The ability to study cellular markers, cell and tissue spatial arrangement, and gene function are all integral parts of cancer diagnostic and treatment efforts.

Here, I first present …

Bridging The Gap Between Phase Behavior And Processing For Renewable And Refinable Carbonaceous Precursors, Graham Tindall

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As a category of materials, engineered carbons, specifically carbon fibers, are first-in-class for properties such as modulus, specific strength, and thermal resilience; however, the inability to directly process atomic carbon necessitates the development and optimization of carbonaceous precursors. Because the structure and properties of carbon are highly dependent on the precursors and requisite processing, numerous materials have been investigated as feedstocks for large-scale production. Although cellulose and rayon were among the first investigated, polyacrylonitrile (PAN) is the current hegemon of carbon fiber precursors. PAN feeds 90% of this market, but it is neither inexpensive nor renewable. Because a significant fraction …

Probing The Structure Of Water On Surfaces: From Water Absorption To Ice Nucleation, Jiarun Zhou

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Water, essential for all life forms, is the most abundant, simple, yet mysterious molecule in the world. This molecule, consisting of only three atoms, behaves in unexpectedly different ways with the change of environment. In the past, studies of water under different conditions (temperature, pressure, on the surfaces, with confinement) have been conducted using experimental and computational methods. However, the influence of a given environment on water properties is yet to be fully understood. This dissertation studies water at complex interfaces (surfaces with various chemistry and physics properties) in both the liquid and crystalline states. Various heterogeneous systems used to …

Carbon Fibers From Bio-Based Precursors Derived From Renewable Sources, Sagar Kanhere

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Carbon fibers have the highest strength and modulus among all known fibers and are used as reinforcements in high-performance composites [1]. Carbon fibers also have a very low density relative to metals. Therefore, carbon fibers possess ultrahigh specific strength and modulus, which make them desirable for high-performance light-weight composites. A vast majority of commercial carbon fibers are produced from PAN precursors that are expensive, which limits the use of PAN-derived carbon fibers to aerospace applications (e.g., airplanes). However, for costsensitive applications, there is a need for low-cost, moderate performance carbon fibers. Lignin is a low-cost by-product of pulping and biorefining …

Elucidation Of Active Site And Mechanism Of Metal Catalysts Supported In Nu-1000, Hafeera Shabbir

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Advances in extraction of shale oil and gas has increased the production of geographically stranded natural gas (primarily consisting of methane (C1) and ethane (C2)) that is burned on site. A potential utilization strategy for shale gas is to convert it into fuel range hydrocarbons by catalytic dehydrogenation followed by oligomerization by direct efficient catalysts. This work focuses on understanding metal cation catalysts supported on metal-organic framework (MOF) NU-1000 that will actively and selectively do this transformation under mild reaction conditions, while remaining stable to deactivation (via metal agglomeration or sintering). I built computational models validated by experimental methods to …

Development Of Enzyme-Responsive Polymersomes As A Drug Delivery System For Gm1 Gangliosidosis, Bipin Chakravarthy Paruchuri

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GM1 gangliosidosis is a lysosomal storage disorder caused by deficiency of β-galactosidase (βgal) and subsequent accumulation of GM1 ganglioside in lysosomes. The rare nature of this disorder presents challenges with prognosis and treatment. Enzyme replacement therapy (ERT) can effectively treat systemic deficiencies, but the intravenously administered enzyme cannot cross the blood-brain barrier (BBB) to treat the central nervous system. A delivery system to encapsulate and deliver the enzyme can facilitate enzyme transport across the BBB with suitable surface modifications. One of the pathological aspects of GM1-affected cells is the upregulation of the lysosomal enzyme hexosaminidase A (HexA). In this dissertation, …

Profiling And Engineering The Unfolded Protein Response In Therapeutic Protein-Producing Cho Cell Lines, Dyllan Rives

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Industrial Chinese hamster ovary (CHO) production of therapeutics requires cell lines with high secretory capacity to avoid an accumulation of improperly folded proteins, or endoplasmic reticulum (ER) stress. This presents a challenging engineering bottleneck. The unfolded protein response (UPR) is initiated to overcome ER stress and reestablish homeostasis. In this dissertation, the impacts of ER stress and the UPR on protein production in mammalian cells are detailed, and both selection- and rational-based strategies for enhancing the ER stress response in productive CHO cell lines are reviewed. This project aims to expand on recent research efforts for engineering ER stress-related responses …

Metabolic Engineering Of Yarrowia Lipolytica For Enhanced Peroxisomal Production Of Polyhydroxyalkanoates, Michael Spagnuolo

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Traditional chemical processes are made inefficient by the generation of side products and reactions that fail to reach completion. Bioprocesses, on the other hand, lose product potential due to the necessity of growing the organism required to produce the desired compounds. The field of metabolic engineering often seeks to alter this balance between product formation and cell growth to generate more product from the same quantity of feed (reagent). In addition to balance, such organisms may also be engineered to produce the desired products from nontraditional substrates, such as waste compounds. In resource-poor environments, the ability to produce a wanted …

Effects Of Continuous In Situ Low-Dose Ionizing Radiation On Microorganisms, Molly E. Wintenberg

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Precise detection and monitoring of nuclear fuel cycle, enrichment, and weapon development activities are critical for supporting warfighter preparation in chemical, biological, radiological, nuclear, and explosives (CBRNE) operations, clandestine activities, and nuclear compliance. A biological sensing system could serve as an alternative to traditional detection methods by using organic material naturally present in the environment to discreetly detect residual trace nuclear material. Microorganisms provide an optimal platform for an alternative sensing system; however, their response to low levels of ionizing radiation is poorly characterized. Combining the power of next-generation sequencing and transcriptomic analysis, this dissertation takes an approach to obtain …

Extractive Membranes For The Detection And Screening Of Waterborne Plutonium, James Foster

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The development of rapid screening tools for special nuclear materials remains a crucial focus for nonproliferation efforts. Traditional approaches for the analysis of trace-level Pu isotopes in water requires tedious and time-consuming sample preparation steps that do not lend well to expeditious screening. Therefore, a novel analytical method that combines both Pu concentration and source preparation into a single detection system would make for an invaluable tool for nuclear security applications. Extractive membranes absorbers can help to fulfill this role as they are capable of concentrating Pu to detectable limits while subsequently serving as alpha spectrometry sample sources. In Chapter …

Reactive Thin Film Polymers And Thin Film Composite Membranes For The Rapid Screening Of Uranium Isotopes, Abenazer W. Darge

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Traditional radiochemistry approaches for the detection of trace-level alpha-emitting radioisotopes in water require lengthy offsite sample preparations and do not lend themselves to rapid quantification. Therefore, a novel platform is needed that combines onsite purification, concentration, and isotopic screening with a fieldable detection system. My dissertation research objective was to develop novel reactive thin polymer films and thin film composite membranes for the selective separation of uranium from environmental water followed by direct isotopic analysis by alpha spectroscopy. Chapter 1 reviews progress made on uranium separation from aqueous matrices and discusses methods used for the determination of isotopic composition.

Chapter …

Towards Understanding Protein Immobilization Rules Through Site-Specific Covalent Immobilization Of T4 Lysozyme, Maxwell Hilbert

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Soluble enzymes have the unique ability to assist the conversion of complex substrates in fewer steps compared to conventional chemical synthesis; however, when immobilized to a surface, the insoluble enzyme's activity and stability can suffer in its new environment. To improve upon future immobilized enzyme efficacy, a fundamental understanding of the interactions across the enzyme, linker, and surface during covalent, site-specific immobilization that can be detrimental to its activity is required. More specifically, using a well-characterized and model enzyme, T4 lysozyme (T4L), 28 different cysteine attachment points' effects on site-specifically immobilized activity are examined. Different combinations of heterobifunctional amine-to-sulfhydryl crosslinkers …

Multi-Scale Assessment Of Binding Geometries And Energetics Of Aqueous Phase Reforming Of Glycerol And Methanol: Towards Realistic, Accurate, And Computationally Tractable Strategies, Tianjun Xie

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No abstract provided.

First Principles-Based Microkinetic Modeling Of Ethanol From Syngas On Bimetallic Co-Pd Catalysts, Anuradha Gundamaraju

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In the future, the availability of reliable alternative fuels will be crucial for any country to become energy independent. One such alternative is ethanol as it can be used both as a fuel and as a fuel additive. Most of the ethanol produced in the world today is derived from biomass. The biomass feedstocks and fermentation broths used in ethanol production both contain high amounts of water and therefore, the energy efficiency of the process is lessened by product separation processes (azeotropic separation of water and ethanol) that are non-trivial and highly inefficient (due to the evaporation of water). An …

Role Of Surface Factors On Heterogeneous Ice Nucleation, Brittany Glatz

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Heterogeneous ice nucleation is the primary pathway for ice formation. However, the detailed molecular mechanisms by which surfaces promote or hinder ice nucleation are not well understood. We present results from extensive molecular dynamics and forward flux sampling (FFS) simulations of ice nucleation near modified surfaces. The surfaces are modified to investigate the effects of different surface factors on the rate and mechanism of ice nucleation. We find that the surface charge distribution has significant effects on ice nucleation. We also investigate the interplay of surface lattice and hydrogen bonding properties in affecting ice nucleation. We find that lattice matching …

Development Of A New Multimodal Membrane Adsorber And Its Application In Chromatographic Bioseparations, Juan Wang

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This dissertation presents work on the design and synthesis of a new membrane chromatography material, the description of its protein binding behavior using a thermodynamic adsorption isotherm model, and the application of the new membrane material in biologics downstream recovery and purification processes. As protein titers continue to increase dramatically in upstream biomanufacturing, innovations in downstream purification are not keeping pace, resulting in manufacturing capacity constraints and high production costs. Chromatography is the key unit operation used in several steps of the downstream purification platform. Traditional resin bead chromatography, while effective and reliable for isolation and purification of proteins, limits …

Low Cost, Carbon-Based Micro- And Nano-Structured Electrodes For High Performance Supercapacitors, Kryssia Pamela Díaz Orellana

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Advances in the development of sustainable, low-cost, and reliable energy storage technologies have become a high priority as the demand for high power, and high energy storage devices has risen with emerging technologies in electronics, transportation, and renewable energy systems. Supercapacitors, due to their relatively high energy density and power density, provide an attractive alternative to bridge the gap between conventional batteries and capacitors. Materials ranging from high surface area, inert carbons to Faradaic metal oxides and conducting polymers have been used to achieve a range of performance properties in supercapacitors. However, the development of new technologies faces many challenges, …

Design And Synthesis Of Polymer, Carbon And Composite Electrodes For High Energy And High Power Supercapacitors, Margarita Arcila-Velez

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Supercapacitors (SCs) are promising energy storage devices because they deliver energy faster than Li-ion batteries and store larger amounts of charge compared to dielectric capacitors. SCs are classified in electrical double layer capacitors (EDLCs) and pseudocapacitors, based on their charge storage mechanism. EDLCs store charge electrostatically, i.e. by physical charge separation. This mechanism limits the storable amount of energy to the available surface area of the electrode, typically made of carbon materials, but grants good cycling stability of the SC device. Pseudocapacitor electrodes, commonly made of conducting polymers or metal oxides, store charge faradaically, i.e. through redox reactions throughout the …

Optimization Of Pyrochlore Catalysts For The Dry Reforming Of Methane, Felipe Polo Garzon

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The conversion of methane into syngas (a mixture of CO and H2), which can be further converted into a variety of chemicals and particularly liquid fuels, is of growing importance given recent increases in methane production world-wide. Furthermore, since using CO2 as the co-feed offers many environmental advantages, dry reforming of methane (DRM, CH4 + CO2 ⇌ 2CO + 2H2) has received renewed attention. In recent years, experimentalists have shown that the Rh-substituted lanthanum zirconate pyrochlore (LRhZ) material is catalytically active for DRM, exhibits long-term thermal stability and resists deactivation; however, previous to this doctoral work, a detailed understanding of …

Investigating Polymer Based Scaffolds For Urinary Bladder Tissue Engineering, Srikanth Sivaraman

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Current surgical treatments for urinary bladder disorders rely on the use of autologous intestinal segments and xenografts such as small intestinal submucosa, which suffer from various complications including mechanical mismatch and graft shrinkage. Despite early promises of bladder tissue engineering, a recent report of unsuccessful clinical trials suggests that the technology needs further improvement and evaluation through animal models of bladder dysfunction. Therefore, the objective of this doctoral dissertation was to characterize a viable bladder tissue scaffold (patch) which mimics the mechanical properties of the bladder, maintains the phenotype of the BSMC seeded in it and finally, tested in vivo …

Thermally Responsive Polymer Electrolytes For Inherently Safe Electrochemical Energy Storage, Jesse Kelly

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Electrochemical double layer capacitors (EDLCs), supercapacitors and Li-ion batteries have emerged as premier candidates to meet the rising demands in energy storage; however, such systems are limited by thermal hazards, thermal runaway, fires and explosions, all of which become increasingly more dangerous in large-format devices. To prevent such scenarios, thermally-responsive polymer electrolytes (RPEs) that alter properties in electrochemical energy storage devices were designed and tested. These RPEs will be used to limit or halt device operation when temperatures increase beyond a predetermined threshold, therefore limiting further heating. The development of these responsive systems will offer an inherent safety mechanism in …

Synthesis And Characterization Of Chemically Functionalized Shape Memory Nanofoams For Unattended Sensing Applications, Anna Paola Soliani

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The work in this dissertation is devoted to the synthesis and characterization of novel materials for off-line unattended sensing: shape-memory grafted nanofoams. The fabrication process and characterization of highly efficient, polymeric nanosensor element with the ability to selectively detect analytes and retain memory of specific exposure events is reported. These shape memory nanofoams could potentially act as efficient and highly sensitive coatings for evanescent waveguide-based optical monitoring systems. On exposure to specific analytes, the polymeric coatings locally change their internal structure irreversibly at the nanolevel, affecting the local optical properties such as refractive index. Currently, enrichment polymer layers (EPLs) are …

High-Productivity Membrane Adsorbers: Polymer Surface-Modification Studies For Ion-Exchange And Affinity Bioseparations, Heather Chenette

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This Dissertation centers on the surface-modification of macroporous membranes to make them selective adsorbers for different proteins, and the analysis of the performance of these membranes relative to existing technology. Traditional chromatographic separations for the isolation and purification of proteins implement a column packed with resin beads or gel media that contain specific binding ligands on their exposed surface area. The productivity of this process is balanced by the effective use of the binding sites within the column and the speed at which the separation can take place, in addition to the need to maintain sufficient protein purity and bioactivity. …