Chemical & Biomolecular Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/2219
Formerly known as the Department of Chemical Engineering.
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Item Dynamic Modeling for the Design and Cyclic Operation of an Atomic Layer Deposition (ALD) Reactor(MDPI, 2013-08-19) Travis, Curtisha D.; Adomaitis, Raymond A.A laboratory-scale atomic layer deposition (ALD) reactor system model is derived for alumina deposition using trimethylaluminum and water as precursors. Model components describing the precursor thermophysical properties, reactor-scale gas-phase dynamics and surface reaction kinetics derived from absolute reaction rate theory are integrated to simulate the complete reactor system. Limit-cycle solutions defining continuous cyclic ALD reactor operation are computed with a fixed point algorithm based on collocation discretization in time, resulting in an unambiguous definition of film growth-per-cycle (𝑔𝑝𝑐). A key finding of this study is that unintended chemical vapor deposition conditions can mask regions of operation that would otherwise correspond to ideal saturating ALD operation. The use of the simulator for assisting in process design decisions is presented.Item Shape-Changing Tubular Hydrogels(MDPI, 2018-02-22) Raghavan, Srinivasa R.; Fernandes, Neville J.; Cipriano, Bani H.We describe the creation of hollow tubular hydrogels in which different zones along the length of the tube are composed of different gels. Our method to create these gels is adapted from a technique developed previously in our lab for creating solid hybrid hydrogels. The zones of our tubular gel are covalently bonded at the interfaces; as a result, these interfaces are highly robust. Consequently, the tube can be picked up, manipulated and stretched without suffering any damage. The hollow nature of these gels allows them to respond 2–30-fold faster to external stimuli compared to a solid gel of identical composition. We study the case where one zone of the hybrid tube is responsive to pH (due to the incorporation of an ionic monomer) while the other zones are not. Initially, the entire tube has the same diameter, but when pH is changed, the diameter of the pH-responsive zone alone increases (i.e., this zone bulges outward) while the other zones maintain their original diameter. The net result is a drastic change in the shape of the gel, and this can be reversed by reverting the pH to its original value. Similar localized changes in gel shape are shown for two other stimuli: temperature and solvent composition. Our study points the way for researchers to design three-dimensional soft objects that can reversibly change their shape in response to stimuli.Item Effect of a Cationic Surfactant on Microemulsion Globules and Drug Release from Hydrogel Contact Lenses(MDPI, 2019-06-06) Torres-Luna, Cesar; Hu, Naiping; Koolivand, Abdollah; Fan, Xin; Zhu, Yuli; Domszy, Roman; Yang, Jeff; Yang, Arthur; Wang, Nam SunThe present study evaluates the in vitro release of diclofenac sodium (DFNa) from contact lenses based on poly-2-hydroxyethyl methacrylate (pHEMA) hydrogels containing an embedded microemulsion to extend release duration. The oil (ethyl butyrate)-in-water microemulsion systems are prepared with two non-ionic surfactants, Brij 97 or Tween 80, together with a long-alkyl chain cationic surfactant, cetalkonium chloride (CKC). Without CKC, Brij 97 or Tween 80-based microemulsions showed average droplet sizes of 12 nm and 18 nm, respectively. The addition of CKC decreased the average droplet sizes to 2–5 nm for both non-ionic surfactants. Such significant reduction in the average droplet size corresponds to an increase in the DFNa release duration as revealed by the in vitro experiments. Contact lens characterization showed that important properties such as optical transparency and water content of Brij 97-based contact lenses with cationic microemulsions was excellent. However, the optical transparency of the corresponding Tween 80 based contact lenses was unsatisfactory. The results indicate that cationic microemulsion-laden contact lenses can benefit from combinatory effects of microemulsions and cationic surfactant at low CKC weight percentage, e.g., with the release of 70% of the drug in 45, 10, and 7 h for B97-CKC-0.45%, CKC-0.45%, and control lenses, respectively. However, the microemulsion effect on extending DFNa release became negligible at the highest CKC weight percentage (1.8%).Item Formation of Drug-Participating Catanionic Aggregates for Extended Delivery of Non-Steroidal Anti-Inflammatory Drugs from Contact Lenses(MDPI, 2019-10-10) Torres-Luna, Cesar; Koolivand, Abdollah; Fan, Xin; Agrawal, Niti R.; Hu, Naiping; Zhu, Yuli; Domszy, Roman; Briber, Robert M.; Wang, Nam Sun; Yang, ArthurThis paper focuses on extending drug release duration from contact lenses by incorporating catanionic aggregates. The aggregates consist of a long-chain cationic surfactant, i.e., cetalkonium chloride (CKC), and an oppositely charged anti-inflammatory amphiphilic drug. We studied three non-steroidal anti-inflammatory (NSAID) drugs with different octanol–water partition coefficients; diclofenac sodium (DFNa), flurbiprofen sodium (FBNa), and naproxen sodium (NPNa). Confirmation of catanionic aggregate formation in solution was determined by steady and dynamic shear rheology measurements. We observed the increased viscosity, shear thinning, and viscoelastic behavior characteristic of wormlike micelles; the rheological data are reasonably well described using a Maxwellian fluid model with a single relaxation time. In vitro release experiments demonstrated that the extension in the drug release time is dependent on the ability of a drug to form viscoelastic catanionic aggregates. Such aggregates retard the diffusive transport of drug molecules from the contact lenses. Our study revealed that the release kinetics depends on the CKC concentration and the alkyl chain length of the cationic surfactant. We demonstrated that more hydrophobic drugs such as diclofenac sodium show a more extended release than less hydrophobic drugs such as naproxen sodium.Item 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.Item Dynamics of Elastic Capsules in Cross-Junction and T-Junction Microfluidic Channels(2017) Mputu udipabu, Pompon; Dimitrakopoulos, Panagiotis; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this dissertation, we investigate via numerical computations the dynamicsof elastic capsules (made from a thin strain-hardening elastic membrane) in two microfluidic channels of cross-junction and T-junction geometries. For the cross-junction microfluidic channel, we consider an initially spherical capsule with a size smaller than the cross-section of the square channels comprising the cross-junction, and investigate the effects of the capsule size, flow rate, and lateral flow rates on the transient dynamics and deformation of low-viscosity and equiviscous capsules. In addition, we also study the effects of viscosity ratio on the transient capsule dynamics and deformation. Our investigation shows that the intersecting lateral flows at the cross-junction act like a constriction. Larger capsules, higher flow rates and higher intersecting lateral flows result in stronger hydrodynamic forces that cause a significant capsule deformation, i.e., the capsule’s length increases while its height decreases significantly. The capsule obtains different dynamic shape transitions due to the asymmetric shape of the cross-junction. Larger capsules take more time to pass through the cross-junction owning to the higher flow blocking. As the viscosity ratio decreases, the capsule’s transient deformation increases and tail formation develops transiently, especially for low-viscosity capsules owing to the normal-stress effects of the surrounding fluid on the capsule’s interface. However, the viscosity ratio does not affect much the capsule velocity due to a weak inner circulation. Our findings suggest that the tail formation of low-viscosity capsule may promote membrane breaking and thus drug release of pharmaceutical capsules in the microcirculation. Furthermore, we investigate via numerical computations the motion of an elastic capsule (made from an elastic membrane obeying the strain-hardening Skalak law) flowing inside a microfluidic T-junction device. In particular, we consider the effects of the capsule size, flow rate, lateral flow rate, and fluid viscosity ratio on the motion of the capsule in the T-junction micro-channel. As the capsule’s initial lateral position increases, the capsule moves faster and reaches different final lateral positions. As the capsule size increases, the gap between the capsule’s surface and the channel wall decreases. This results in the development of stronger hydrodynamic forces and a decrease in the capsule velocity due to flow blocking. As the capsule size increases, there is a small lateral migration towards the micro-channel centerline, which is the low-shear region of the T-junction micro-channel. This migration is in agreement with experimental and numerical studies on non-inertial lateral migration of vesicles in bounded Poiseuille flow by Coupier et al. [13] who showed that the combined effects of the walls and of the curvature of the velocity profile induce a lateral migration toward the centerline of the channel. As the capillary number Ca increases, the stronger hydrodynamic forces cause the capsule to extend along the flow direction (i.e., the capsule’s length Lx increases as the capsule enters the T-junctions and decreases as the capsule exits the T-junction). There is a small lateral migration away from the micro-channel centerline as the flow rate Ca increases. The capsule lateral position zc, main-flow velocity Ux and migration velocity Uz are practically not affected by the fluids viscosity ratio λ. As the channel’s lateral flow rate increases, the capsule migrates downwards towards the bottom of the device. Our findings on the lateral migration in the T-junction micro-channel suggest that there is a great potential for designing a T-junction microfluidic device that can be used to manipulate artificial and biological capsules.Item RNA Interference mediated knockdown of genes in order to increase protein production using the baculovirus expression system(Springer Nature, 2006-10-10) Hebert, Colin; Kim, Eun Jeong; Kramer, Shannon F; Valdes, James J; Bentley, William EItem Microbial nar-GFP cell sensors reveal oxygen limitations in highly agitated and aerated laboratory-scale fermentors(Springer Nature, 2009-01-15) Garcia, Jose R; Cha, Hyung J; Rao, Govind; Marten, Mark R; Bentley, William ESmall-scale microbial fermentations are often assumed to be homogeneous, and oxygen limitation due to inadequate micromixing is often overlooked as a potential problem. To assess the relative degree of micromixing, and hence propensity for oxygen limitation, a new cellular oxygen sensor has been developed. The oxygen responsive E. coli nitrate reductase (nar) promoter was used to construct an oxygen reporter plasmid (pNar-GFPuv) which allows cell-based reporting of oxygen limitation. Because there are greater than 109 cells in a fermentor, one can outfit a vessel with more than 109 sensors. Our concept was tested in high density, lab-scale (5 L), fed-batch, E. coli fermentations operated with varied mixing efficiency – one verses four impellers. In both cases, bioreactors were maintained identically at greater than 80% dissolved oxygen (DO) during batch phase and at approximately 20% DO during fed-batch phase. Trends for glucose consumption, biomass and DO showed nearly identical behavior. However, fermentations with only one impeller showed significantly higher GFPuv expression than those with four, indicating a higher degree of fluid segregation sufficient for cellular oxygen deprivation. As the characteristic time for GFPuv expression (approx 90 min.) is much larger than that for mixing (approx 10 s), increased specific fluorescence represents an averaged effect of oxygen limitation over time and by natural extension, over space. Thus, the pNar-GFPuv plasmid enabled bioreactor-wide oxygen sensing in that bacterial cells served as individual recirculating sensors integrating their responses over space and time. We envision cell-based oxygen sensors may find utility in a wide variety of bioprocessing applications.Item A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei(Springer Nature, 2013-07-12) Gilbreath, Jeremy J; Semino-Mora, Cristina; Friedline, Christopher J; Liu, Hui; Bodi, Kip L; McAvoy, Thomas J; Francis, Jennifer; Nieroda, Carol; Sardi, Armando; Dubois, Andre; Lazinski, David W; Camilli, Andrew; Testerman, Traci L; Merrell, D ScottPseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease. To more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome. We determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients. Using 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival.Item Experimental evidence and isotopomer analysis of mixotrophic glucose metabolism in the marine diatom Phaeodactylum tricornutum(Springer Nature, 2013-11-14) Zheng, Yuting; Quinn, Andrew H; Sriram, GaneshHeterotrophic fermentation using simple sugars such as glucose is an established and cost-effective method for synthesizing bioproducts from bacteria, yeast and algae. Organisms incapable of metabolizing glucose have limited applications as cell factories, often despite many other advantageous characteristics. Therefore, there is a clear need to investigate glucose metabolism in potential cell factories. One such organism, with a unique metabolic network and a propensity to synthesize highly reduced compounds as a large fraction of its biomass, is the marine diatom Phaeodactylum tricornutum (Pt). Although Pt has been engineered to metabolize glucose, conflicting lines of evidence leave it unresolved whether Pt can natively consume glucose. Isotope labeling experiments in which Pt was mixotrophically grown under light on 100% U-13C glucose and naturally abundant (~99% 12C) dissolved inorganic carbon resulted in proteinogenic amino acids with an average 13C-enrichment of 88%, thus providing convincing evidence of glucose uptake and metabolism. The dissolved inorganic carbon was largely incorporated through anaplerotic rather than photosynthetic fixation. Furthermore, an isotope labeling experiment utilizing 1-13C glucose and subsequent metabolic pathway analysis indicated that (i) the alternative Entner-Doudoroff and Phosphoketolase glycolytic pathways are active during glucose metabolism, and (ii) during mixotrophic growth, serine and glycine are largely synthesized from glyoxylate through photorespiratory reactions rather than from 3-phosphoglycerate. We validated the latter result for mixotrophic growth on glycerol by performing a 2-13C glycerol isotope labeling experiment. Additionally, gene expression assays showed that known, native glucose transporters in Pt are largely insensitive to glucose or light, whereas the gene encoding cytosolic fructose bisphosphate aldolase 3, an important glycolytic enzyme, is overexpressed in light but insensitive to glucose. We have shown that Pt can use glucose as a primary carbon source when grown in light, but cannot use glucose to sustain growth in the dark. We further analyzed the metabolic mechanisms underlying the mixotrophic metabolism of glucose and found isotopic evidence for unusual pathways active in Pt. These insights expand the envelope of Pt cultivation methods using organic substrates. We anticipate that they will guide further engineering of Pt towards sustainable production of fuels, pharmaceuticals, and platform chemicals.