Chemical and Biomolecular Engineering Theses and Dissertations

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Expression and Purification of the Cell-Penetrating Peptide MAP Fused to Protein Cargo
(2024) CHUNG, REN-JHE; Karlsson, Amy J; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Candida albicans is a common fungal pathogen that presents a significant public health issue due to its resistance to traditional antifungal small molecule medications. While large therapeutics offer potential as alternative treatments with novel mechanisms of action, their efficacy is hindered by low cellular uptake and limited accessibility to intracellular targets. Cell-penetrating peptides (CPPs) are promising vehicles for facilitating the intracellular delivery of large biomolecules. CPPs are short protein peptides capable of crossing various membrane barriers, even when conjugated to cargo molecules. However, producing CPP fusion proteins can be challenging due to their higher toxicity to host cells. To enhance expression, we studied and optimized several contributing factors, including expression partners, host cell strains, sequential order of CPP and cargo, and induction conditions, for the fusion of CPP MAP to the cargo monomeric enhanced green fluorescent protein (meGFP). Our findings indicated that the expression partner, combined with positioning MAP at the N-terminus of the cargo, resulted in relatively high expression levels. The highest expression level was achieved in the BL21(DE3) Escherichia coli strain, with induction at 20°C for 24 hours. These results support further research on the application of MAP recombinant proteins and lay the foundation for the generalization of CPP recombinant protein expression.
INTEGRATED PROCESS MODELING AND EXPERIMENTAL ANALYSIS FOR OPTIMIZING CONTINUOUS MANUFACTURE OF DRUG SUBSTANCE CARBAMAZEPINE
(2024) Kraus, Harrison; Choi, Kyu Yong; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
This dissertation presents a comprehensive study on the continuous manufacture (CM) of the drug substance (DS) carbamazepine (CBZ), a widely used anti-epileptic medication, aimed at enhancing process efficiency and product quality. The research progresses through a series of investigations, beginning with the development of kinetic models for CBZ synthesis from iminostilbene via two different synthetic routes using urea and potassium cyanate across various reactor setups, including batch and continuous flow systems. Discrepancies between batch and continuous models, particularly in yield prediction and impurity formation, are thoroughly examined and addressed through adjustments in reactant addition methods and system designs. This demonstrates the value of mechanistic modeling, a tool that has been undervalued in recent research particularly for its ability to compare between batch and continuous systems. Subsequently, the research delves into the crystallization processes, employing a population balance model (PBM) to study CBZ polymorph form III crystal formation, highlighting the influence of seed crystal size distribution on product crystal quality. It also provides novel strategies for modeling the evolution of crystal size distribution (CSD) due to nucleation and growth and evaluates the robustness of these strategies as seed CSD varies. Lastly, the scope is expanded to a holistic view of the integrated synthesis and crystallization process presenting one of the first studies of a complete DS CM system and emphasizing the development of a robust Quality-by-Control (QbC) framework. This includes the implementation of in-line Raman spectroscopy for real-time concentration monitoring, an active feedback level control system, dynamic modeling of impurity partitioning for enhancing disturbance mitigation across the CM process, and a retrograde design strategy that optimizes the upstream synthesis based on downstream purification capabilities/limitations. Through all these contributions, the dissertation aims to advance the modernization of continuous manufacturing practices in the pharmaceutical industry and promotes a shift towards more adaptive and controlled production environments.
Sutureless Anastomosis: Electroadhering a Hydrogel Sleeve Over Cut Pieces of Tubular Tissue
(2024) Grasso, Samantha Marie; Raghavan, Srinivasa R; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Recently, our lab demonstrated that cationic gels could be adhered to animal tissues by applying an electric field (10 V DC, for ~ 20 s). This phenomenon, termed electroadhesion (EA), could potentially be used to repair injured tissues without sutures. An extreme injury is when a tube in the body (e.g., a blood vessel or an intestine) is cut into two segments. The surgical process of joining the segments is termed anastomosis, and thus far has only been done clinically with sutures. Here, we explore the use of EA for performing sutureless anastomoses in vitro with bovine aorta and chicken intestine. For this purpose, we make a strong and stretchable cationic gel in the form of a sleeve (i.e., a hollow tube). By using a custom plastic mold, we control both the sleeve diameter and wall thickness. A sleeve with a diameter matching that of the tubular tissue is slipped over the cut segments of the tube, followed by application of the DC electric field. Thereby, the sleeve becomes strongly adhered by EA to the underlying tube. Water or blood is then flowed through the repaired tube, and we record the burst pressure Pburst of the tube. We find that Pburst is > 80 mm Hg and close to the Pburst of an intact (uncut) tube. In comparison to the sleeve, a long strip of the gel attached around the cut tubular pieces allows a much lower Pburst. Thus, our study shows that gel-sleeves adhered by EA could enable anastomoses to be performed in the clinic without the need for sutures.
Slow and Sustained Release of Hydrophilic Solutes from Capsules
(2024) Cho, Hannah Yeonhee; Raghavan, Srinivasa R; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Capsules can be used to deliver solutes encapsulated in their aqueous core, including drugs. However, small, hydrophilic solutes tend to leak out of typical capsules in a matter of minutes. Solute release can be completely prevented if the capsule shell is made of a hydrophobic solid like paraffin wax. The goal of this study is to achieve release profiles between these extremes 3⁄4 i.e., release of solutes in a slow and sustained manner over a period of days. For this, we modify the wax-shell design above and include a nonionic surfactant (from the Brij series) along with the wax. Most of our studies have been done with Brij-C10, which has a polyethylene glycol (PEG) head and a hexadecyl (C16) tail. We show that capsules with a shell of 80/20 wax/Brij can release model dyes from the aqueous core over 20+ days. Such slow release has not been reported previously. The release rate can be tuned via the concentration of Brij in the shell (the higher the Brij, the faster the release) as well as the chemistry of the Brij (i.e., the size of the surfactant head or tail). The sustained release occurs because the Brij-bearing shell has microchannels through which the solute can permeate. Our approach can be used to slowly release many solutes, including dyes, drugs, and reactive reagents (such as H2O2). The simplicity and versatility of this approach make it highly suitable for controlled release applications across the pharmaceutical, agrochemical, and cosmetics industries.
Chemically Fueled Transient Porous Hydrogels as Autonomous Soft Actuators
(2024) Battumur, Sarangua; Woehl, Taylor J.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Biomimetic materials take inspiration from biological systems to develop transformativereconfigurable synthetic materials. One example of a biological system is the contraction of muscle fibers driven by biochemical reactions. Actin filaments are crucial to cellular functions, facilitating movement, division, and structural integrity through ATP-driven polymerization and depolymerization. This ability to self-assemble and disassemble in response to biochemical signals provides a model for creating materials that mimic the sophisticated control found in biological systems. This thesis describes the use of a chemical reaction network to rapidly and autonomouslyreconfigure the size of a porous polymer hydrogels within tens of minutes. This hydrogel, composed of acrylic acid and acrylamide monomers, exhibits exceptional microporosity and an ability to expand approximately 150 times its original size within 15 seconds when exposed to water. The chemical reaction network utilizes a carbodiimide molecule, which transiently converts carboxylic acid moieties to anhydride bonds, causing transient shrinking of the hydrogel. The hydrogel spontaneously swelled due to hydrolysis of the anhydride bonds. We enhance the swelling rate of the porous hydrogels by adding polymer beads loaded with formaldehyde and sulfite buffer to the reaction vessel, which generate a time delayed pH increase that accelerates the hydrolysis of the anhydride bonds. This multi-reaction network forms porous hydrogels that contract and reswell autonomously in less than 10 minutes,compared to about 1 hour without the delayed pH change. This approach not only enables a faster reconfiguration of the porous gel induced by EDC through the hydrolysis of the anhydride due to a transient pH change, but also integrates this external stimulus into a single-step, autonomous process. This work also deepens our understanding of natural and synthetic actuation systems and how to couple different reactions to enhance their response. By harnessing the principles of bioinspired actuation, our work bridges the gap between the orchestrated movements of biological systems and the engineered behavior of synthetic materials, infusing our constructs with a level of adaptability and responsiveness that mirrors the natural world.
HISTATIN 5 MODIFICATIONS IMPACT PROTEOLYTIC STABILITY IN THE PRESENCE OF FUNGAL AND SALIVARY PROTEASES
(2024) Makambi, Wright Kingi; Karlsson, Amy J; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Candida albicans, found in the oral cavities of 30-50% of the global population, can lead to oral candidiasis, particularly in immunocompromised individuals like those with HIV or diabetes. The current treatments, small-molecule antifungals, often fall short due to drug resistance and toxicity. To address these challenges, histatin 5 (Hst5), a 24-amino-acid peptide naturally present in human saliva, has been studied as a potential antifungal therapy. Hst5, however, is susceptible to degradation by secreted aspartyl proteases (Saps) produced by C. albicans and salivary enzymes, limiting its potential efficacy as a therapeutic. We have engineered Hst5 variants utilizing rational design in order to understand the interactions with Saps and Saliva. We have also made advancements in developing a novel screening method utilizing the directed evolution technique yeast surface display. Our study employed rational design to modify Hst5, at its lysine residues (K5, K11, K13, and K17), substituting them with leucine or arginine to examine their influence on interactions with Saps (Sap1, Sap2, Sap3, Sap5, Sap6, Sap9, and Sap10). Sap5, Sap6, and Sap10 did not degrade Hst5 at the tested conditions, while Sap1, Sap2, Sap3, and Sap9 did. Some modifications, such as K13L, are particularly susceptible to proteolysis by Sap1, Sap2, Sap3, and Sap9. In contrast, K17L substantially increases the stability and antifungal activity of Hst5 in the presence of Saps. Additionally, although the K11RK17L variant was degraded more than the K17L variant, their antifungal activities were largely similar. The proteolysis products of were also identified by mass spectrometry identifying the [4-24], [1-17], and [14-24] Sap proteolysis products. We also evaluated the proteolytic stability of these variants in saliva. Both K17L and K5R showed improved stability; however, the enhancements were modest, suggesting that further engineering is required to achieve significant improvements. Further experiments evaluated how additional amino acid substitutions at K13 and K17 affect the peptide’s proteolytic stability in the presence of Saps (with and without zinc). Our findings suggest that the positive charge at K13 is important for the proteolytic stability of Hst5, as all other variants tested except K13R reduce overall proteolytic stability. Furthermore, many substitutions at K17, including tryptophan, significantly enhance proteolytic resistance and antifungal activity following incubation with Saps. The K17W variant showed improved stability and antifungal efficacy, maintaining its function even in the presence of zinc and exhibiting stronger antibiofilm activity than the parent Hst5. In addition to the rational design work, we have advanced the development of a directed evolution yeast surface display platform for screening peptides for proteolytic stability. This would allow for the expression of large peptide libraries on the surface of Saccharomyces cerevisiae. Through optimization of expression and display conditions, we determined an induction media at 30°C with a pH of 3.5 and devoid of glucose improved the expression and display of Hst5 peptides on the surface of S. cerevisiae. We also optimized the degradation conditions for Sap2 37°C, a pH not exceeding 7.4, and a Sap2 concentration of 0.78 µg/mL led to the best discrepancy between proteolytically stable variants. Additionally, we found that a 40 amino acid linker between the peptide and the yeast surface provided the best observing proteolytic degradation. Using the optimized system, we showed that yeast surface display can be used to discriminate between peptide variants with different levels of proteolytic stability. This lays the foundation for future work to screen large libraries of peptides for proteolytic stability. From these results, we have gained a deeper understanding of the interactions between Hst5 and Saps, showing that modification at different lysine residues greatly impacts the proteolytic stability of Hst5. Furthermore, we have shown that the yeast surface display platform can be used to screen the proteolytic stability of peptides. Looking forward, this peptide should be engineered for proteolytic stability in saliva. Furthermore, mock screens should be made before screening a library of peptides using the yeast surface display platform.
EXPERIMENTAL INVESTIGATION OF THE LIPID-BINDING MECHANISM OF OSH4 PROTEIN
(2024) Konakbayeva, Dinara; Karlsson, Amy; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Recent findings show that intracellular lipid traffic between organelles primarily occurs through a non-vesicular pathway involving lipid transport proteins (LTPs) and is facilitated by areas of close apposition between two organelles so called membrane contact sites (MCS). Oxysterol-binding homologue (Osh) proteins in the yeast Saccharomyces cerevisiae serve as examples of LTPs. Osh proteins are crucial for transporting signaling lipids and are believed to form MCSs. In this study, we examined the binding mechanism of the Osh4 protein, aiming to gain a better understanding of its explicit membrane-binding mechanism.The Osh4 protein possesses an α-helical binding domain known as the amphipathic lipid-packing sensor (ALPS)-like motif. Our approach involved utilizing experimental methods to examine the biophysical interactions of both the ALPS peptide and the full-length Osh4 protein. To investigate the binding interactions of ALPS with membranes of different lipid compositions, we examined its interactions with three different mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC; has a zwitterionic head group) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS; has a negatively charged head group)—1:1 POPC-POPS, 4:1 POPC-POPS, and 9:1 POPC-POPS—as well as pure POPC. To understand the structural changes in ALPS and model membranes during peptide-membrane interactions, we performed a series of experimental studies. Circular dichroism (CD) was used to study the changes in the secondary structure of ALPS in different environments. The CD data indicated that the α-helical conformation of the ALPS peptide was more pronounced in the presence of POPC-POPS liposomes, especially with a higher content of POPS lipid, compared to liposomes composed entirely of POPC. This observation underscores the significant influence of anionic lipids in the facilitation of peptide folding at the membrane-water interface. X-ray diffraction was utilized to study the changes in membrane structure upon ALPS binds to it. The X-ray diffraction results showed that the ALPS peptide caused thinning of the multilayer with an increased POPS lipid ratio. This could be due to the electrostatic interaction of the positively charged Lys residue in the ALPS sequence with the anionic POPS lipid. We also studied the binding of the peptide to membranes by observing changes in the Trp fluorescence emission spectrum of ALPS upon the addition of liposomes. We observed a blue shift in the fluorescence emission maximum of Trp with higher POPS content. This suggests that the ALPS peptide was experiencing a more hydrophobic and less polar environment in the presence of the liposomes, indicating possible penetration of the peptide into the hydrocarbon region of the bilayer. The blue shifts of Trp emission in the presence of POPS liposomes were higher than those observed with POPC liposomes and suggest that the ALPS peptide binds better to charged POPS lipids, which is consistent with the X-ray diffraction data. We also conducted Trp fluorescence titration and ITC experiments to gain deeper insights into the binding affinity of the ALPS peptide to a model membrane. Using fluorescence data, we estimated the binding constant for the binding of ALPS to liposomes by performing titration measurements of vesicles with the ALPS peptide. Our analysis demonstrated that ALPS binding to 4:1 POPC-POPS lipid membranes had a Kd of 1.88 ± 0.47 μM, which corresponds to a free energy change (ΔG) of -7.82 ± 0.15 kcal/mol. Additionally, the ITC experiments performed with the same vesicles yielded a ΔG of -4.41± 0.04 kcal/mol. This result is slightly less than the ΔG value of -7.82 ± 0.15 kcal/mol obtained from fluorescence spectroscopy titration. The observed discrepancy of -3.41 kcal/mol may indicate the energy associated with the folding of the ALPS peptide. In order to understand how Osh4 forms MCSs between two membranes, we need to examine how the membranes interact with the full-length protein. The first step to achieve this is to produce the protein through recombinant protein production methods. After evaluating two different fusion tags, glutathione S-transferase (GST) and small ubiquitin-related modifier (SUMO), it was found that the SUMO tag resulted in higher protein yield and greater protein purity. Our work lays the foundation for future experiments with the full-length Osh4 protein to improve our understanding of the mechanisms of lipid transport between membranes. Our results emphasize the ALPS peptide’s selectivity for specific lipid environments, particularly its affinity for anionic lipids. We demonstrated that the presence of anionic lipids is crucial for the motif's ability to induce conformational changes upon binding to a membrane, and these conformational changes likely play a critical role in intracellular lipid trafficking and membrane organization.
Study of Membrane Binding Proteins and Related Signaling Molecules
(2023) Allsopp, Robert James; Klauda, Jeffery B; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
The membrane contact site theory is a critical theory to understanding lipid transport. The Osh protein is a yeast lipid transport protein theorized to form membrane contact sites. We investigated the contact site theory by identifying a second binding domain and studying the Osh Amphipathic Lipid Packing Sensor (ALPS) to explain better why each protein might target different organelles. The α6- α7 domain appears more charged and prefers lipids with oppositely charged inositol sugars, making it ideal for binding to the Trans Golgi Network (TGN) and the plasma membrane. The ALPS peptide is another dedicated binding domain bound in several membrane types with varied Phosphatidylcholines (PC) tails to vary the lipid packing. If the force field was valid, the results indicate that Osh4 ALPS prefers the loose packing of POPC, and Osh5 ALPS prefers the tighter packing of DMPC. More input from the wet lab is needed before researchers can make predictions from the force field. Another vital area of research is antimicrobial peptides (AMPs) that disrupt the membrane. Part of the dissertation focused on determining the dual placement of the AMPs on the surface and inserted into the membrane. For the first time, the membrane properties of bilayers with AMPs were studied, using the combination of all-atom simulation informed by x-ray scattering. The surface tension was a critical parameter that enabled us to compare the simulation to the wet lab results and became vital in allowing the peptide to be inserted into the membrane and remain stable. The 5-HT3A project simulated predicted structures of toxins with computational tools. Our work simulated these toxins for the first time, and we observed the unbiased binding of σ-GVIIIA conotoxin to the allosteric binding pocket. In the first trajectories, the ion channel pore remained closed, similar enough to the native apo crystal structure that water could form a partially water-filled channel for a few microseconds. In one example, the 5-HT3A had serotonin in all of the binding pockets for close to 1 µs. The long simulation of the conotoxin showed that the extracellular domain (ECD) was deformed by more than a nanometer compared to a control. This deformation was the first indication that such a conformation is possible and might be related to the presence of the toxin. Finally, traumatic brain injury was studied by identifying new molecules that activate fibroblast growth factor (FGF) and toll-like receptor (TLR) proteins. The focus on FGF resulted in identifying a critical conformational change and potential new binding sites (previously unknown) that activate FGF without activating damaging inflammatory TLR responses.
LITHIUM ANODE INTERFACE DESIGN FOR ALL-SOLID-STATE LITHIUM-METAL BATTERIES
(2023) Wang, Zeyi; Wang, Chunsheng; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
All-solid-state lithium-metal batteries (ASSLBs) have attracted intense interest as the next generation of energy storage devices due to their high energy density and safety. However, the Li dendrite growth and high interface resistance remain challenges due to the lack of understanding of the mechanism. Inserting a solid-electrolyte interlayer/interphase (SEI) with high lithiophobicity, high ionic conductivity, and low electronic conductivity at the Li/SSE interface can solve these problems. However, how lithiophobicity, ionic conductivity, and electronic conductivity of the interlayers affect the lithium dendrite suppression capability of the SEI has not been systematically investigated yet but is critical for ASSLBs. The main goal of this dissertation is to propose a comprehensive interface design principle/frame by considering the impacts of interlayer lithiophobicity, electronic/ionic conductivity, and porosity to Li striping/plating behavior. A combination of modeling and experiments was used to validate the design principle. The developed principle could help to resolve the electrolyte reduction and void formation issues in all-solid-state batteries. The design principle can be applied to different solid electrolytes that have different reactivity against Li, which was presented in the 3rd-6th Chapters for detail. The interlayer design principle opens opportunities to develop safe and high-energy ASSLBs.In the 3rd chapter, we investigated the correlation among ionic and electronic conductivities, lithiophobicity, and Li plating stability in the Li7N2I-Carbon Nanotube (LNI-CNT) interlayer. LNI solid electrolyte has a high ionic conductivity of 3.1 × 10–4 S cm–1 and a low electronic conductivity, high lithiophobicity, and high electrochemical stability against Li, while CNT has a high lithiophobicity, high electronic conductivity, and low tap density. Therefore, mixing LNI with CNT at different ratios can form porous lithiophobic interlayers with variable ionic and electronic conductivity. The 90 μm LNI-5% CNT interlayer enabled Li to plate on the Li/LNI-CNT interface (rather than the SSE/LNI-CNT interface) and then reversibly penetrate into/extract from the porous LNI-CNT interlayer during Li plating/stripping. The 3-dimensional Li/LNI-5% CNT interlayer contact achieved by well-controlled Li nucleation and growth enabled Li/LNI/Li cell to charge/discharge at a high current density of 4.0 mA cm-2 and a high capacity of 4.0 mAh cm-2 for > 600 hours. We also reported that a stable Li plating/stripping cycle can be achieved if the Li nucleation region in the interlayer is smaller or equal to the Li growth region in the interlayer (from the Li anode). This study represents a comprehensive interlayer design for ASSLBs with a significantly improved dendrite suppression capability and reversibility. In the 4th chapter, we develop an LNI-Mg interlayer to increase the Li dendrite suppression capability of Li//Li cells with Li6PS5Cl solid electrolyte. LNI-25%Mg interlayer can form gradient electronic conductivity inside the interlayer due to Mg migrating from the interlayer to the Li anode during activation, which can reduce the interlayer thickness and enhance the Li dendrite suppression capability. The migration of Mg was attributed to the formation of LiMg solid solution. It was found that the gradient electronic conductive LNI-Mg interlayer has better Li dendrite suppression capability than the homogeneous electronic conductive LNI-CNT interlayer due to more constrained Li plating region and mitigated electrolyte reduction. As a result, 18.5 µm LNI-25%Mg interlayer enables Li4SiO4@NMC811/LPSC/Li full cells with an areal capacity of 2.2 mAh cm-2 to be charged/discharged for 350 cycles at 60 oC with capacity retention of 82.4%. This study promotes the development of ASSLBs with higher energy density. In the 5th chapter, we combined experimental techniques and simulation methods to investigate the relationship between the interlayer’s ionic/electronic conductivity ratio, lithiophobicity, and Li plating/striping behavior in carbon-based interlayers. Firstly, we screen the carbon materials based on their ionic/electronic conductivity ratio and lithiophobicity. Li stripping/plating mechanisms were identified in different carbon materials from simulations. Secondly, we predict the critical current density of the interlayer based on the boundary condition of avoiding Li nucleation during Li plating and void formation during striping. Finally, guided by the theoretical prediction, we optimized the ionic/electronic conductivity and lithiophobicity of the carbon-based interlayer by dopping with CuO. The CuO-CNF-M (M= Mg or Ag) interlayer in situ converts to Cu-Li2O-CNF SEI/LiM structure during Li plating. The optimized SEI with ionic conductivity of 0.41 S/m and electronic conductivity of 3.3×10-3 S/m coupling with LiM anode (in-situ formed during Li plating) enables lithium-free NMC811||Cu cell to achieve long cycle life. This work represents a valuable attempt to promote the development of high-performance Li anode interlayer with a joint effort of simulations and experiments. In the 6th chapter, we design a P and I rich SEI for halide electrolytes. Halide electrolytes have the advantage of matching with high-voltage cathodes due to the high thermodynamic oxidation potential. However, they are unstable against Li anode due to their strong reactivity with Li and the formation of electronic conductive metal. In this chapter, we propose and verify critical overpotential as a criterion for Li dendrite growth. By tuning the composition of the SEI, we reduce the overpotential to lower than critical overpotential using P and I containing SEI. The P and I containing SEI with a high ionic/electronic conductivity ratio of the SEI enable Li/LYbC/Li cells to cycle at the current density of 0.1 mA cm-2 with a capacity of 0.05 mA cm-2 for more than 220 hours without a short circuit. This work represents a valuable attempt to achieve Li-stable halide electrolyte.
HYDROGEN SEPARATION AND CARBON CAPTURE BY CARBON MOLECULAR SIEVE MEMBRANES DERIVED FROM INTERFACIALLY POLYMERIZED POLYARAMIDS
(2023) IYER, GAURAV MURALI; Zhang, Chen; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Due to its high energy density and zero-emission combustion, hydrogen (H2) has emerged as a clean fuel for energy generation and transportation. Also, H2 is an important chemical used in petrochemical refining, metal production, and fertilizer manufacture. In the United States, more than 10 million metric tons of H2 is produced each year by steam methane reforming, which gives 100 million metric tons of carbon dioxide (CO2) by-product. Downstream H2/CO2 separation is therefore needed to produce high-purity H2 product while simultaneously capturing the CO2 by-product. State-of-the-art separation technologies such as pressure-swing adsorption (PSA) and amine absorption are energy intensive with large footprints. Membrane-based H2/CO2 separation provides an energy-efficient alternative with smaller footprints. Commercial implementation of membrane-based H2/CO2 separation requires scalable membranes with high H2/CO2 selectivity to produce high-purity H2 product.The overarching goal of this PhD dissertation is to understand the formation and pore structure-transport property relationships in novel carbon molecular sieve (CMS) membranes derived from interfacially polymerized aromatic polyamides (polyaramids) for H2/CO2 separation. Polyaramid precursor hollow fiber membranes were fabricated by solution spinning of an uncrosslinked polyaramid precursor synthesized by stirred interfacial polymerization, which gave polyaramid-derived CMS membranes following pyrolysis. The formation, pore structure, and transport properties of the novel polyaramid-derived CMS membranes were systematically investigated. The polyaramid-derived CMS membrane pyrolyzed at 925 °C showed unprecedented H2/CO2 separation performance under single-gas permeation. Further increasing the pyrolysis temperature to 1050 °C dramatically enhanced the mixed-gas H2/CO2 separation factor to more than one order of magnitude higher than the most selective CMS membrane reported in literature. Modeling further demonstrates the attractiveness of the polyaramid-derived CMS membrane for enrichment of highly-pure H2 from the reaction product of steam methane reforming. Finally, the effect of precursor amide moiety on CMS membrane pore structure and transport properties was studied by comparing the polyaramid-derived CMS membrane with CMS membranes derived from a polyimide precursor and a polyamide-imide copolymer precursor under identical pyrolysis conditions. The results show that introducing precursor amide moiety is a powerful tool to tailor the H2/CO2 transport properties of CMS membranes via controlling the precursor hydrogen bonding and CMS membrane pore structure.
Battery Studies with Particular Reference to Organic Depolarizers
(1955) Monson, William L.; Huff, W. J.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, MD)
Since Volta's invention of the first primary cell, using silver and zinc, numerous other cell combinations have been studied, covering a wide variety of anode and cathode materials. The latter have included both inorganic and organic substances capable of electrochemical reduction, although, historically, organic cathode materials have received very much less attention than the inorganic. It was the purpose of this investigation to study the actual behavior of a selected number of quinones as depolarizers in primary cells. Performance of experimental cells was compared with cells of the usual dry cell composition but of the same size and construction as cells of experimental composition. The results show that certain substituted anthraquinones possess good depolarizing ability as measured by discharge voltage and coulombic capacity. Energy output in some cases was higher than that of the manganese dioxide control cells (zinc anodes in all cases) because of higher effective coulombic capacities. A qualitative study of the effect of substituents on the discharge voltages of various quinones showed that cell working voltages were much more sensitive to quinone substitution than were the calculated reversible potentials. Also, in the case of nitro-substituted anthraquinones more coulombic capacity was obtained than could be accounted for by the simple reduction to the corresponding hydroquinone. The possibility of a reduction of the nitro-group of this compound was considered. Substances investigated were benzoquinone, naphthoquinone, anthraquinone, and certain of their derivatives, using various electrolytes. The size of the experimental cells was such that about 0.2 gram of the various depolarizers could be studied conveniently.
ADVANCED REACTION ENGINEERING FOR THE NONOXIDATIVE VALORIZATION OF METHANE
(2023) Cheng, Sichao; Liu, Dongxia; Zhang, Chen; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Non-oxidative methane conversion (NMC) represents a promising pathway that directly transforms methane into higher hydrocarbons such as ethane, ethylene, acetylene, aromatics, and hydrogen in a single-step synthesis. This process holds particular appeal due to its potential for remote operation and its status as a carbon-neutral process, given that it does not produce carbon dioxide in the product effluent. As such, NMC could serve as a viable alternative to existing multi-step, energy-intensive processes like the Fischer-Tropsch synthesis and liquid petroleum gas production. Despite its potential, NMC faces significant challenges. The thermodynamic stability of methane, attributed to its strong C-H bonds, poses a considerable obstacle. Other challenges include low selectivity towards desired products, rapid catalyst deactivation, and kinetic hindrance, all of which complicate the process. As of now, these challenges have prevented the development of a commercially viable NMC process. This dissertation aims at overcoming these hurdles to unlock the full potential of NMC, paving the way for a more efficient and sustainable method of methane conversion from the perspective of both catalyst design and reaction engineering. The impact of hydrogen activation on NMC using a hydrogen-permeable SrCe0.8Zr0.2O3-δ (SCZO) perovskite oxide material over the iron/silica catalyst was explored. The SCZO oxide, with its mixed ionic and electronic conductivity, facilitates H2 activation into protons and electrons. The SCZO's ability to absorb H2 in-situ lowers its local concentration, promoted the improvement of NMC reaction thanks to the Le Chaterlie’s principle. To further improve the NMC reaction performance, an innovative autothermal catalytic wall reactor (ACWR) designed for self-sustaining NMC with high hydrocarbon product yield (>21% C2 & >27% Aromatics) and minimal coke formation. The system, potentially powered by combusting the sole co-product H2, offers a self-sustained and negative neutral operation of NMC. Further operando studies via Spatial Resolved Capillary Inlet Mass Spectrometry (SpaciMS) have demonstrated that the increased local concentration and the volcanic axial concentration profile of ethylene within the ACWR highlight its effectiveness in comparison to traditional reactor designs. With the detection of a higher ethylene concentration near the reactor wall, SpaciMS studies have also provided experimental evidence that ethylene is a surface product of the Fe/SiO2 catalyst. A novel Pulsed Heating and Quenching (PHQ) thermochemical synthesis technique was applied to methane pyrolysis to demonstrate high selectivity to valuable C2 products. The technique's salient features include rapid activation of reactants at high temperatures for increased rates and conversions, and precise control over the heating process, enhancing the selectivity of desired products.
Journey Through Aerosol Science: Unraveling Kidney Stone Formation, Advancing Visualization, and Particle Capture Technologies
(2023) Rastogi, Dewansh; Asa-Awuku, Akua; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Aerosols are solid or liquid particles that are suspended in air or gas and are present throughout the Earth’s atmosphere due to a variety of anthropogenic and biogenic sources. These aerosol particles play an indispensable role in maintaining the planet's temperature, facilitating the dispersion of airborne pathogens, and enabling targeted pulmonary drug delivery. Our present comprehension of aerosol physics has been instrumental in elucidating the intricate processes of particle formation and their interactions with their immediate surroundings. Depending on their chemical composition and physical properties, these particles exhibit a range of effects on human existence. A profound understanding of the physics governing particle formation not only equips us to engineer aerosols for specific applications, such as nanoparticle synthesis, affording precise control over particle morphology and phase, but also empowers us to delve into the realm of aerosol interactions, unraveling the intricate interplay between particles and the environmental contexts they inhabit. This knowledge base in aerosol science, in turn, enables the development of advanced tools for the capture and analysis of these microscopic particles, thereby advancing our collective comprehension of the field of aerosol science. Furthermore, the physics governing aerosol interactions enables the exploration of particle-environment interactions within contexts of interest. This foundational knowledge base in aerosol science empowers the development of advanced tools for the capture and examination of these diminutive particles, furthering our collective understanding of aerosol science. Consequently, this thesis embarks on an exploration of the principles of aerosol science in multidisciplinary research and the development of new tools for the visualization and capture of aerosols.
CARBON MOLECULAR SIEVE HOLLOW FIBER MEMBRANE REACTORS FOR PROPANE DEHYDROGENATION
(2023) Liu, Lu; Zhang, Chen; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Propylene (C3H6) is a crucial petrochemical feedstock for a number of bulk chemicals and polymers. While steam cracking currently dominates C3H6 production, propane (C3H8) dehydrogenation (PDH) has been increasingly practiced addressing the gap between C3H6 demand and production. The C3H8 conversion of PDH reaction is challenged by thermodynamic limitation and catalyst deactivation at elevated reaction temperature. Membrane reactors can address both challenges and hence enhance the energy efficiency of PDH by achieving attractive and stable C3H8 conversion at low reaction temperature via selective removal of the hydrogen (H2) product to shift the reaction equilibrium. Large-scale practice of PDH membrane reactors has not occurred due to the lack of scalable membranes that can provide attractive H2/C3H8 separation performance at PDH conditions. Carbon molecular sieve (CMS) hollow fiber membranes are a class of tunable and scalable inorganic membranes that are stable under non-oxidative high-temperature conditions, and therefore are potentially promising for PDH membrane reactors.This PhD dissertation aims to investigate low-temperature propane dehydrogenation in novel membrane reactors comprising asymmetric CMS hollow fiber membranes. First, asymmetric polyimide-derived CMS hollow fiber membranes were fabricated and their high-temperature H2/C3H8 performance was assessed. The roles of membrane pyrolysis temperature, permeation temperature, and feed composition on high-temperature H2/C3H8 separation performance were systematically investigated. The effects of high-temperature H2 and C3H6 exposure on CMS pore structure and transport properties were also examined. Under a continuous permeation test (~130 hours) of H2/C3H8 feed mixture at 600 oC, the asymmetric CMS hollow fiber membranes showed stable separation performance with outstanding H2 permeance of 430 GPU and H2/C3H8 separation factor of 511 exceeding those of microporous oxide membranes. H2-permeable CMS hollow fiber membrane reactors were created using the asymmetric CMS hollow fiber membranes and platinum-based catalysts. The effects of reactor operating conditions (i.e., reaction temperature, feed space velocity, sweep flow rate, C3H8 partial pressure, number of CMS hollow fibers) on PDH performance of the CMS hollow fiber membrane reactor were studied. Due to selective removal of H2 product, the H2-permeable CMS hollow fiber membrane reactor showed up to 300% higher C3H8 conversion than equilibrium conversion. Stable performance with commercially attractive C3H8 conversion (above 30%) and high C3H6 selectivity (above 98%) were obtained in the CMS hollow fiber membrane reactor at 450 °C for over 110 hours. The CMS hollow fiber membrane reactors developed in this dissertation outperform PDH membrane reactors reported in literature by having higher conversion enhancement, lower reaction temperature, and the lowest deactivation rate. These experimental results demonstrated the attractiveness of the novel CMS hollow fiber membrane reactors for energy efficient C3H6 production. One-dimensional isothermal models were further developed by material balance to understand the cooperative reaction and separation in the CMS hollow fiber membrane reactors. The modeling results of H2-permeable CMS hollow fiber membrane reactor showed overall good agreement with experimental results. The models also demonstrated the viability of C3H6-permeable CMS hollow fiber membrane reactor and catalytic CMS hollow fiber membrane reactor, which provide valuable guidance to future development of CMS hollow fiber membrane reactors following this PhD research.
VISUALIZING DYNAMICS DURING CHEMICAL REACTION DRIVEN NON – EQUILIBRIUM COLLOIDAL AND NANOPARTICLE ASSEMBLY
(2023) Dissanayake Appuhamillage, Thilini Umesha; Woehl, Taylor; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Biological nano and microstructures exist far from thermodynamic equilibrium by continuous consumption of energy that allows them to reconfigure or adapt to changes in the local environment. Utilization of these non-equilibrium structure formation processes in synthetic colloidal particle and nanoparticle (NP) systems is expected to enable unprecedented control over the dynamics of synthetic active soft materials and systems that are beyond the reach of equilibrium self – assembly. In this work we adapted two non – equilibrium structure formation processes observed in biological systems, dissipative assembly and reaction diffusion instability, to generate dynamic colloidal assemblies and self-organized patterns of nanoparticles. First, we investigated how the surface chemistry and interparticle interactions between colloids changed during chemical reaction driven dissipative assembly of polystyrene colloids. A key result was the first, time dependent measurements of the dynamic colloid surface chemistry (surface charge and hydrophobicity) during dissipative assembly. Importantly, we demonstrated that thermodynamic interparticle interaction models typically used for equilibrium self-assembly are effective in describing fuel driven colloid assembly far from equilibrium. The interparticle interaction models demonstrated that electrostatic interactions controlled the concentration of particle aggregates while the strength of hydrophobic interactions determined whether colloids underwent irreversible aggregation or dissipative assembly. Next, using a correlative fluorescence microscopy and liquid phase transmission electron microscopy (LPTEM) method, we demonstrated that aminated polymer capping ligands on metal NPs undergo crosslinking and chain scission reactions as a result of formation of hydroxyl and hydrogen radicals due to electron beam induced radiolysis of water. We demonstrated that a hydroxyl radical scavenger can minimize the electron beam induced reactions in the polymers. Based on this fundamental knowledge, we introduced an instability to an initially homogenous gold NP decorated aminopolysiloxane thin film immersed in water by scanning TEM beam. Radiolysis driven polymer radical reactions of polysiloxane coupled with diffusion of radicals, polymers, and NPs caused the polymer and NP to self-organize into repeating spatial patterns, i.e., Turing patterns, with no template or specific interparticle interactions. Spots, strings and labyrinth patterns that closely resembled Turing skin pigmentation patterns on various animals were obtained by tuning the chemistry of the system. A series of systematic experiments identified that hydroxyl radicals and NPs as critical species driving the formation of the NP patterns. We expect this work could be used as a model system in establishing design rules for nanoscale pattern formation by reaction – diffusion instability.
Atomic Layer Deposition for Engineering Carbon Hollow Fiber Membrane Pore Structure
(2023) Whitmore, Joseph; Adomaitis, Raymond; Zhang, Chen; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Alumina (Al2O3) films, fabricated using atomic layer deposition (ALD) are useful components of composite materials, providing corrosion resistance, transport barriers, or dielectric properties. The process dynamics of alumina ALD in and around pores are examined in order to support the fabrication of membranes with planar and hollow-fiber geometries. In this study carbon molecular sieve (CMS) membranes are created from pyrolysis of polymer precursors which have properties based on the geometry of and pretreatment applied to the precursor before inert-gas pyrolysis. Modeling and simulation are performed for gaseous reactant transport inside arbitrarily porous networks common to such membranes using analytic and numerical methods to identify potential mass transfer limitations. Associated experimental work used two ALD reactor systems to deposit alumina on the precursor fibers and completed membranes. When the requisite ALD parameters fell outside of the operating conditions of the commercial system, a second system was designed and constructed to support long exposures and simplify masking of undesired deposition surfaces. Characterization of the coated precursors and final CMS membranes was conducted using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and several performance metrics including constant-pressure permeation and pure water flux measurements. This research details study is the successful fabrication of several desirable membrane geometries using ALD, along with transport insight and a proposed reaction mechanism for coating nucleation on the polymer surface.
ENGINEERING THE B1 DOMAIN OF STREPTOCOCCAL PROTEIN G: STRUCTURAL INVESTIGATIONS BY MULTlDIMENSIONAL HETERONUCLEAR NMR
(2000) Frank, Mary Kirsten; Thirumalai, Devarajan; Institute for Physical Science and Technology; Digital Repository at the University of Maryland; University of Maryland (College Park, MD)
The B1 domain of streptococcal protein G provides a well-characterized system for structural investigations of proteins. In this thesis, the urea-unfolded state has been characterized, the tolerance towards hydrophobic substitutions in the core has been surveyed, the hydrogen exchange behavior of the backbone amides has been elucidated, and structural information on a tetrameric mutant of this domain has been gathered. The chemical shifts of the urea-unfolded state were assigned. The secondary chemical shifts, the 3JHNa coupling constants and the short-range NOEs gave no indication of residual structure. Measurement of the backbone 15N relaxation parameters revealed a region of restricted motion in the β3- β4 turn of the native protein. Motion in the rest of the protein was uniform, with the exception of 3-4 residues at either end of the chain. A series of hydrophobic substitutions were made in the hydrophobic core. The resulting mutants were assayed for stability and overall fold . The core of the protein is particularly sensitive to substitutions at position 26. One of the mutants was unable to adopt the GB1 fold and optimized its stability by adopting a homotetrameric form. Hydrogen exchange in the backbone amides was measured at 25 °C. Rates of hydrogen exchange were inversely correlated with burial of the amide nitrogen. The slow-exchanging backbone amides did not correlate with the hydrogen bonds formed early in protein folding. Hydrogen exchange rates from NH to ND and from ND to NH were similar. The ratio between these two rates does not correlate with any obvious physical parameters of the hydrogen bonds. Chemical shifts for the tetrameric mutant (HS#124) were determined using three-dimensional heteronuclear NMR techniques. Measurement of the backbone dynamics revealed a highly flexible region between positions 8 and 22. The secondary structure and β-sheet interactions of this mutant were characterized. The β-sheet interactions were intermolecular and only one of the three β-strand pairings was similar to the β-strand pairings found in wild type GB1 . The novel pairing is between β1 of one monomer and β1 of another monomer and a shift in register is observed for the β3-β4 pairing.
CFD INVESTIGATION OF A PULSE JET MIXED VESSEL WITH RANS, LES, AND LBM SIMULATION MODELS
(2023) Kim, Jung; Calabrese, Richard V.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Pulse Jet Mixed (PJM) vessels are used to process nuclear waste due to their maintenance free operation. In this study we model the turbulent velocity field in water during normal PJM operation to gain insight into vessel operations and to evolve a modeling strategy for process design and operator training. Three transient simulation models, developed using Large Eddy Simulation (LES), unsteady Reynolds-Averaged Navier-Stokes (RANS), and Lattice Boltzmann Method (LBM) techniques, are compared to velocity measurements acquired for 3 test scenarios at 3 locations in a pilot scale vessel at the US DOE National Energy Technology Laboratory (NETL). The LES and RANS simulations are performed in ANSYS Fluent, and the LBM simulations in M-STAR.The LES model well predicts the experimental data provided that the operational pressure profile within the individual pulse tubes is considered. While the RANS model failed to predict the data and exhibited significant differences from LES with respect to turbulence quantities, it is a useful comparison tool that can quickly predict averaged flow parameters. The LBM model’s rigid grid system is deemed unsuitable, as currently configured, for the NETL PJM vessel’s wide range of length scales and curved boundaries, resulting in the longest simulation time and least accurate velocity predictions. Predicted velocity and turbulence metrics are explored to better understand the strengths and failures of the three models. Because the LES model produced the most accurate predictions, it is exploited to generate animations and still images on various 2D planes that depict extremely complex flow patterns throughout the vessel with numerous local jets and mixing layer vortices The study concludes with recommendations for future research to improve the model development and validation strategy.
ATMOSPHERIC ORGANIC AEROSOLS: THE EFFECT OF PHYSIOCHEMICAL PROPERTIES ON HYGROSCOPICITY
(2023) Malek, Kotiba; Asa-Awuku, Akua; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Aerosols, tiny solid or liquid particles, are ubiquitous in the atmosphere yet their impact on climate remains poorly understood. One prominent way aerosols are able to impact the climate is through their ability to uptake water and form clouds. The chemical diversity and aerosol interactions in the atmosphere can greatly complicate the investigation of aerosol-cloud interactions. This complexity is expressed with a large uncertainty associated with aerosols’ role on climate change. This dissertation investigates the aerosol-cloud interaction by measuring the water uptake of atmospherically relevant aerosols. Our results highlight the importance of accounting for various physiochemical properties when exploring the water uptake of atmospheric aerosols. One such property is liquid-liquid phase separation (LLPS) in ternary mixtures. Our work offers new evidence, insight, and a paradigm shift to the contribution of LLPS to supersaturated droplet activation. We complemented this finding with a theoretical model, that incorporates solubility, O:C ratio, and LLPS, for predicting κ-hygroscopicity of ternary mixtures. Another physiochemical property that was shown to play a key role in droplet activation of polymeric aerosols is chemical structure. Our study shows that polycatechol is more hygroscopic than polyguaiacol and the difference in hygroscopicity is attributed to the density of hydroxyl groups in both structures. Polycatechol has a higher density of hydroxyl groups than polyguaiacol, resulting in polycatechol having stronger water uptake affinity than polyguaiacol. When maintaining the same structural makeup by investigating the water uptake of two isomeric compounds, we discovered that solubility was the driving force in water uptake. The more soluble isomer o-aminophenol was more hygroscopic than p-aminophenol. Hence, a small change in the position of functional groups can impact solubility which in turn influence hygroscopicity. Lastly, we explored the presence of gas-phase organics on the water uptake of isomers with a wide range of solubilities. Our work highlights that gas-phase organics, specifically ethanol, can influence the water uptake of aerosols. Ethanol was shown to increase water uptake efficiencies based on solubility, with the least soluble compound showing stronger affinity to water uptake. Overall, this thesis advances our knowledge and understanding of aerosol-cloud interactions and its implications on climate change.
Delayed Release of Hydrophilic Solutes from Capsules
(2023) Utlu, Eylul; Raghavan, Srinivasa R.; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
Hydrophilic small-molecule solutes (e.g., drugs) can be loaded into hydrogels, but the solutes leak out rapidly (in minutes) when the gels are placed in water. Solute release can be completely stopped if the gel is covered by a thin shell of paraffin wax (melting point Tm ~ 57°C); in such ‘capsules’, the wax shell is a hydrophobic solid. Here, we vary the design of our capsules to achieve ‘delayed release’ of solutes into water: i.e., no release for a delay period (6 to 72 h) followed by a slow and sustained release thereafter. The key is to include an additive in the shell that is miscible with the wax but is weakly hydrophilic and has a lower Tm. Examples are fatty acid esters, notably isopropyl palmitate (IPP, Tm ~ 11°C). For example, when a solute-loaded gel is covered by a 80/20 wax/IPP shell, we find a 3-day delay at 25°C before any release, followed by a near-constant release rate (i.e., ‘zero-order’ release) for the next 20 h. The time delay and release rate can be tuned via the concentration and type of additive in the shell. The delayed release occurs because the wax/IPP shell is an inhomogeneous crystal (as wax and IPP are only partially miscible). Our approach can be used to delay the release of dyes, drugs (e.g., diclofenac), and reactive agents (e.g., H2O2) out of the core gel. The simplicity and generality of our approach should make it useful for controlled release applications in the pharmaceutical, agrochemical, and cosmetics industries.

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