acase@tulane.edu

The goal of this research is to study the neutralization of sulfuric acid by engine oils, and more specifically study how the presence of different oil additives affects the acid-neutralizing performance of engine oils by using capillary videomicroscopy. Nowadays the formulation of engine oils has been changing due to a trend of different regulations around the world that seek to diminish the emission of atmospheric pollution from all types of vehicles driven by internal combustion engines. In the particular case of large marine ships powered by low-speed two-stroke diesel engines, pollutant emissions are high given that the marine fuel they use can contain up to 4.5 wt. % of sulfur. But this sulfur content cap in marine fuel is bound to diminish dramatically during the ongoing decades due to regulations and therefore, the industry is coming up with new engine oil formulations accordingly as to comply with these changes. Here a technique called capillary videomicroscopy was used to study new changes to engine oil formulations. The reaction and dispersion of a sulfuric acid micro-droplet into formulations of marine cylinder lubricants (MCL) was studied by microscopically observing and measuring the shrinking of a micropipette-produced droplet in real time. It was found that MCL formulations having a base number (BN) of 40 had an acid-neutralizing performance comparable to those of having BN 70. On the other hand, the addition of fatty alcohols as final additives to MCL formulations so as to boost the MCL’s acid neutralization performance was found to be slightly effective although phase separation due to alcohol insolubility in MCL at room temperatures and other resilient phases formed upon reaction can be detrimental, hence the use of fatty alcohols for boosting any MCL formulation cannot be generalized and should be studied for each formulation. In the case of passenger car motor oils (PCMO), substitution of traditional oil additives by new sulfur-free additive species is driven by the need to prevent the catalytic converter's poisoning by eliminating any sulfur present in the exhaust gas. The effect of the polymeric dispersant on the acid neutralization performance was also studied. The formation of clear, thin and resilient shells surrounding sulfuric acid droplets upon reaction with some MCLs was noticed to be a detrimental aspect towards their acid neutralization performance and more importantly, due to the formation of potential precursors for cylinder liner engine deposits. Finally it is shown a modification of the capillary videomicroscopy technique that allowed long-term monitoring of the fate of microscopic particles while reacting or dissolving under flow, by suspending them using a balance between buoyancy and drag force from creep flow. / acase@tulane.edu

Synthesis and characterization of anisotropic micro- and nanoparticles, either in suspension or localized on a surface, are current areas of intense scientific interest because of their shape-tunable material properties with potential applications in catalysis, microelectronics, data storage and pharmaceutics. Electrochemical deposition represents a facile and versatile route to fabricate anisotropic particles since it offers a high degree of freedom in monitoring and manipulating particle growth processes. The first part of my dissertation presents an additive-mediated electrochemical approach to fabricate anisotropic copper micro- and nanoparticles. This work explores the possibility of using anisotropic copper particles as novel non-noble metal alternatives to expensive anode electrocatalysts (platinum and palladium) used in direct methanol fuel cells (DMFCs). Characterization using SEM, EDS, XRD and TEM confirms the anisotropic morphology and crystal structure of synthesized copper particles. A possible mechanism for anisotropic crystal growth is proposed based on preferential adsorption of additive ions onto selective crystal faces. Methanol oxidation is chosen as model experiment to test the electrocatalytic property of copper particles towards DMFC applications. Characterization using cyclic voltammetry demonstrates shape dependent enhancement in electrocatalytic activity of anisotropic copper particles for methanol oxidation. Chronoamperometry and thermal stability measurements indicate good catalyst stability and durability under steady-state conditions. The second part of my dissertation presents a novel electrochemical fabrication route to generate randomly rough surfaces over large areas. Surface roughness directly affects a material's performance at its functional interface. This work shows that by simple tuning of electrochemical deposition potential for a metal onto an electrode, island nucleation density can be systematically varied. Changes in nucleation density results in generation of thin films with different nanoscale surface roughness. Characterization using AFM illustrates the change in surface topography with applied potential. The fabricated roughness is successfully replicated onto other moldable soft materials (polystyrene and polyurethane) through an embossing and curing step. Roughness gradients were also generated by introducing a controlled mechanical retraction step to the process. Gradient surfaces serve as an effective probing tool for investigating a range of surface parameters in quick time using single experiment, enabling a cost-effective and high-throughput screening method. / acase@tulane.edu

This research is aimed at studying the ionic liquid/n-pentanol interface via video-microscopy and molecular dynamic simulations. Understanding the interfacial phenomena and interfacial transport between ionic liquids and other liquids is of interest to the development and application of ionic liquids in a number of areas. One such area is the biphasic hydroformylation of alkenes to obtain alcohol and aldehyde, in which case ionic liquid is the reaction medium where a catalyst resides. The dissolution of an ionic liquid into an alcohol was studied by microscopically observing and measuring the shrinking of a micropipette-produced droplet in real time. Although microscopic investigation of droplet dissolution has been studied before, no attempt had been made to measure the di↵usion coefficient D of the droplet species in the surrounding medium. A key finding of this work is that the Epstein-Plesset mathematical model, which describes the dissolution of a droplet/bubble in another fluid medium, can be used to measure D. Other experimental studies of the ionic liquid/alcohol system include electrical conductivity and UV-visible spectroscopy measurements of solutions of 1-hexyl-3-methylimidazolium tetrafluoroborate in n-pentanol. Those experiments were done in order to understand the molecular state of the particular ionic liquid in n-pentanol, as well as obtaining the dissociation constant K of such weak electrolyte solution. The experimental results provide an entry to the assessment of ionic liquid interaction with n-pentanol at molecular scale. Subsequently, molecular dynamics simulation was implemented for the investigation of such interaction. The computation started with simulation of the bulk phase of 1-butyl-3-methylimidazolium tetrafluoroborate, an affine ionic liquid on which molecular simulations had already been reported. A generalized probability based on Fuoss approximation for the closest ion to a distinguished countercharge ion was developed. In addition to 1-butyl-3- methylimidazolium tetrafluoroborate, the generalization was tested also on tetraethyl ammonium tetrafluoroborate in propylene carbonate from low to high concentrations, and on the corresponding primitive model. Such generalization helps us understand paring of ions in electrolyte solution, especially for elevated concentrations. Two cases of 1-hexyl-3-methylimidazolium tetrafluoroborate ionic liquid/npentanol system were studied, which are (i) liquid-liquid interface; and (ii) solution of the former in the latter. Computation of biphasic interface revealed interaction at the liquid-liquid junction, e.g., the transport of molecules from one phase to another, and lead to evaluation of di↵usion coefficient that has good agreement with experimental measurement. The simulation of dilute electrolyte solution, i.e., an ionic liquid pair in n-pentanol, gives free energy change as a function of ion separation distance. The dissociation constant K was evaluated and found to be closed to experimental value that was obtained from solution conductivity measurement. The investigation of ion dynamics, especially the memory function transformed from velocity autocorrelation function, lead to the finding of dielectric friction in the system. Furthermore, precise evaluation of D gives satisfied agreement with experimental measurement from micropipette technique. / acase@tulane.edu

The objective of this project is to develop novel treatments, using expression-targeted gene therapy and minicell technology, to replace current methodologies used in the clinic for the treatment of carcinomas, especially transitional cell carcinoma of the bladder. The expression-targeted gene therapy procedure involves cancer-specific DNA elements (promoters) to drive the expression of engineered suicide genes to induce apoptosis in cancer cells. Minicells, a kind of bacterial derivative , prevent tumor recurrence and growth through targeted toxicity and an induced immune response that is similar to that induced by Bacille Calmette-Guerin (BCG), but without the risk of infection due to lack of chromosomes. The osteopontin promoter (popn) was selected via currently accepted methods by comparing endogenous gene expression between normal and cancerous cells. The opn gene is expressed in far greater amounts in cancer cells, so it was reasoned that the opn promoter would be more active in cancer cells as well. Reporter constructs using popn were transfected into both cancerous and normal cell types, with maximum Popn-driven reporter intensity in the cancer cells showing up as strong (102.7%) compared to Pcmv-driven positive controls. Popn-driven reporter intensity was reduced by ~90% in the non-cancer cells. Further enhancements to targeting and expression were obtained through the incorporation of single-nucleotide polymorphisms (SNPs) in the promoter sequence. Further investigations to confirm a correlation between endogenous opn mRNA levels and Popn-driven reporter expression produced a surprising lack of correlation (R2=0.24). However, taking into account opn mRNA splicing variants, a strong negative correlation was determined between mRNA levels of the variant opn-a and Popn-driven transgene activity (R2=0.95). Three novel cancer-specific promoter pran, pbrms1 and pmcm5 were identified through a new screening logic. The activities of those promoters were verified to be much higher in the tested cancer cell lines than the current gold standard used to target gene expression to cancer cells: the promoter of human telomerase reverse transcriptase (phTERT). A constitutively active, apoptosis-inducing analog of caspase 3, referred to as Reverse Caspase3 (RevCasp3), was engineered via gene recombination and cloned into expression-targeted plasmid constructs. These constructs showed excellent activity in inducing apoptosis within the cancer cells tested. Moreover, Pran-RevCasp3 constructs were shown to have significant, cancer-specific killing action within both human and murine cell in vitro. The therapeutic effects of minicell constructs known as VAX-IP were tested within our orthotopic, murine model of transitional cell carcinoma of the bladder. In trials focused on the prevention of tumor growth and tumor implantation, bell-shaped curves were produced by data reflecting the relation between drug dose and tumor burden. The median and average bladder weights, used as a surrogate for tumor burden, decreased with increasing doses of VAX-IP minicells administered via intravesical, transurethral delivery. Activity was lost at high doses of VAX-IP minicells. Compared with the sham-treated group, 1x108 VAX-IP minicells, delivered at 24 hours post-surgery with repeated administrations every 7 days for a total of four treatments, yielded a significant survival advantage to the treated animals (P=0.03). / acase@tulane.edu

The breath figure method is a versatile and facile approach of generating ordered micro and nanoporous structures in polymeric materials. When a polymer solution (dissolved in a high vapor pressure organic solvent) is evaporated out in the presence of a moist air stream, the evaporative cooling effect causes the condensation and nucleation of water droplets onto the polymer solution surface. This leads to the formation of an imprinted porous structure upon removal of the residual solvent and water. The facile removal of the water droplet template leaving its structural imprint is a specifically appealing aspect of the breath figure film technology. The first part of the dissertation work involves the fabrication of drug loaded breath figure thin films and its utilization as a controlled drug release carrier and biomaterial scaffold. In a single fabrication step, single layer/multilayer porous thin films were designed and developed by combining the breath figure process and a modified spin or dip coating technique. Using biodegradable polymers such as poly (lactic-co-glycolic acid) (PLGA) and poly (ethylene glycol) (PEG), drug loaded films were fabricated onto FDA approved medical devices (the Glaucoma drainage device and the Surgical hernia mesh). The porosity of the films is in the range of 2-4 µm as characterized by scanning electron microscope. The drug coated medical implants were characterized for their surface and bulk morphology, the degradation rate of the film, drug release rate and cell cytotoxicity. The results suggest that the use of breath figure morphologies in biodegradable polymer films adds an additional level of control to drug release. In comparison to non-porous films, the breath figure films showed an increased degradation and enhanced drug release. Furthermore, the porous nature of the film was investigated as a biomaterial scaffold to construct three dimensional in vitro tissue model systems. The breath figure film with interconnected pores facilitates cell infiltration and tissue remodelling in vitro, suggesting its high potential in regenerative medicine and tissue engineering applications. In the second part of the dissertation, the versatility of breath figure polymers was explored as a reverse template to create micropatterned soft materials. Unlike traditional lithographic masters, the breath figure assembly is a simple and cost-effective approach to create micro/nano sized “bead†like uniform patterns on the surface of hydrogels and biopolymers. By incorporating iron nanoparticles into the pores, this technique was extended to form hydrogels decorated with nanoparticles specifically in the pattern. The morphology features and the functional characteristics were demonstrated through scanning electron microscopy. The potential applications of these micro-fabricated materials in biosensors and cell culture substrates are outlined. / acase@tulane.edu