Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1973. / Bibliography: leaves 221-225. / by Steven S. Emmer. / M.S.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, February 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references. / The ability to introduce therapeutic at a specified location and time to a healing traumatic wound deep within the body by external non-invasive stimulus could provide great long-term benefit to patients. In this work, we have examined systems consisting of or including amphiphilic copolymers towards deep-tissue externally triggered localized therapeutic delivery applications. First, we probed a polyelectrolyte multilayer incorporating poly(L-glutamic acidtriethylene glycol-diclofenac) copolymer micellar aggregates for near-infrared responsive enhanced therapeutic delivery. It was discovered that the films released small-molecule non-steroidal anti-inflammatory drug diclofenac up to five-fold faster during remote irradiation with near-infrared. The near-infrared source was effective at generating more-rapid release from films with tissue mimic penetration depths of at least twelve centimeters. Irradiations in immediate succession produced diminishing rates of release. The highly near-infrared responsive behavior was attributed to a delayed-elution mechanism. In this mechanism, the diclofenac was first hydrolytically cleaved from unimers in the film and then resided within the hydrophobic cores of micellar aggregates until freed by energy imparted by the near-infrared irradiation. Gold nanorods were incorporated into the films to enhance the response of the films to near infrared above controls. Due to non-covalent suspension of the nanorods, aggregation led to a kinetically dependent enhancement of performance. Next, we improved the synthesis of a copolymer of 2-(dimethylamino)ethyl methacrylate with a spiropyran methacrylate by atom transfer radical polymerization for increased kinetic control. From there, we optimized the composition of this multiresponsive copolymer such that isomerization of the spiropyran moiety brought about a solubility transition surrounding 37°C. This property of the copolymer was designed such that the solubility shift by remote photo-trigger would bring about therapeutic release in a polymer multilayer system analogous to the diclofenac system. Overall, this work demonstrates the utility of engineering amphiphilic copolymers as a powerful approach to impart remotely triggerable therapeutic release properties for use with implants deeply located within the body. / by Samantha Caitlin Collins. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2009. / Includes bibliographical references. / It is critical to decontaminate organophosphate compounds in large scale economically, including OP pesticides in groundwater system and chemical nerve agents on the battle field. Homogeneous or micellar decomposition systems with various nucleophiles improve reaction rates significantly without affording the recovery and reuse of the nucleophiles. This research focuses on developing functional magnetic particles to carry strong [alpha]--nucleophilic groups, which are able to catalyze the decomposition reaction and can be recycled and reused.The amidoxime modified magnetic particles were prepared first. The original particles were synthesized with the two-step procedure to obtain average particle size of around 80nm for effective capture by high gradient magnetic separation (HGMS). The precursor molecule cyanoacetohydrazide reacted with the free carboxyl groups on the particle surfaces and subsequently the nitrile groups were transformed into amidoxime groups. The modified particles were of similar average hydrodynamic diameter as the original ones and colloidally stable over a wide range of solutin pH. The amidoxime-modified particles accelerated the hydrolysis reaction of p-nitrophenyl acetate (PNPA). They were easily recycled by HGMS without loss of reactivity. Higher reactivity of the particle system than homogenous amidoxime systems was attributed to the increased concentration of the substrate on the particle surface due to the presence of hydrophobic centers using pseudo-phase exchange model.Stronger nucleophilic groups, hydroxamic acid, were then attached on the particle surfaces. Original particles were prepared with unsaturated carboxylic acid as the second coating in the two-step procedure. The acrylamide monomers were copolymerized with the second coating and the attached amide groups were converted into the hydroxamic acid groups. / (cont.) The reaction was very efficient. Crosslinking increased the particle size to 200nm and therefore the particles were effectively captured by HGMS. The modified particles significantly accelerated the hydrolysis reaction of PNPA. They were five times more reactive than the amidoxime modified particles based on the same weight of materials. The acetylated particles were only partially regenerated due to the Lossen rearrangement of the acetylated hydroxamic acid groups.During the hydrolysis of OP substrates, including diisopropyl fluorophosphate, methylparaoxon and ethyl-paraoxon, the added a-nucleophiles, 2-PAM and acetohydroxamic acid, only attacked the phosphorus atom to substitute the p-nitrophenol groups in methyland ethyl- paraoxon and the fluoride ions in DFP through second order nucleophilic substitution. Reactions between all three substrates and both nucleophiles yielded the same hydrolysis products as the spontaneous hydrolysis with no detected intermediates, indicating the unstable nature of any intermediates that may be formed. The hydroxamic acid modified particles accelerated the hydrolysis of methyl- and ethyl- paraoxon with relatively modest reactivity. Similar to polyhydroxamic acid, the reactivity was much lower than that of monomeric hydroxamic acid due to the steric hindrance from the polymer chains. The particles lost their reactivity after the reaction due to Lossen rearrangement of the phosphoryl hydroxamic acid. / by Huan Zhang. / Ph.D.

Thesis: Sc. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 123-132). / Methylation at the 5 position of the cytosine base, when followed by guanine (CpG) in the promoter region of a protein-coding gene, is an epigenetic modification that has been shown to be involved in gene silencing. While important for regulating many normal, cellular processes, aberrant DNA methylation has been implicated in the development of human diseases such as cancer. Medical research has begun to identify hypermethylated gene promoters that can be used as predictive, prognostic, and diagnostic biomarkers. Current technologies for DNA methylation detection, however, rely on sodium bisulfite conversion of unmethylated cytosine bases to urasil in the target DNA. Bisulfite treatment is time consuming to perform, degrades >90% of the DNA, and is susceptible to incomplete conversion which can lead to false results. As such, a method that eliminates both chemical conversion and PCR amplification of DNA would enable significantly lower-cost and rapid DNA methylation analysis in the clinic. Methyl binding domain (MBD) family proteins specifically bind double-stranded, methylated DNA which makes them excellent transducers for DNA methylation in biosensing applications. I displayed three of the core members MBD1, MBD2, and MBD4 on the surface of Saccharomyces cerevisiae yeast cells. Using the yeast display platform, I determined the equilibrium dissociation constant of human MBD2 (hMBD2) to be 5.9+/-1.3 nM for binding to singly methylated DNA. I further used the yeast display platform to evolve the hMBD2 protein for improved binding affinity. Affecting five amino acid substitutions doubled the affinity of the wildtype protein to 3.1+/-1.0 nM. Further, concatenating the high-affinity MBD variant from 1x to 3x and expressing it in Escherichia coli as a green fluorescent protein (GFP) fusion improved affinity 6-fold for interfacial binding. After optimizing the expression and purification of engineered MBD-GFP proteins in E. coli, I developed a simple method for detecting methylated DNA fragments from the MGMT gene promoter. A defining feature is that target oligonucleotides from the test sample hybridize directly to capture probes printed in 300 pm diameter spots on an inexpensive biochip without requiring bisulfite conversion. Sub-nanomolar concentrations (0.3 nM) of methylated DNA duplexes are detected using an MBD-GFP protein to transduce binding to either a fluorescent or colorimetric (visible hydrogel) signal formed by photopolymerization with short (<2 min) reaction times. / by Brandon Walter Heimer. / Sc. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 183-204). / Nitric oxide is a biological messenger which is synthesized enzymatically throughout the body and which has numerous physiological functions, including roles in blood pressure control, regulation of clotting, and neurotransmission. It is produced also by macrophages as part of the non-specific immune response, and has been shown to be toxic to invasive microorganisms. However, sustained overproduction of NO, as observed with chronic inflammation or infection, may damage the host tissue and has been linked to increased risk for cancer. Nitric oxide may facilitate tumorigenesis or metastasis by influencing tumor-cell proliferation, angiogenesis, or lymphangiogenesis. However, the concentrations of NO in inflamed tissues or during carcinogenesis are largely unknown. The objective of the research in this thesis was to predict NO concentrations in an inflamed colon and a cutaneous metastatic melanoma, two areas where NO has been implicated in the development or progression of disease. Nitric oxide production in the colon has been linked to inflammatory bowel disease (IBD) and increased risk for colon cancer. However, measurements of NO concentration in the inflamed colon have not been available and it is not known what levels of NO are pathophysiological. A computational model, based on anatomical length scales and rates of NO production measured in cell cultures, was developed to predict spatially varying NO concentrations within a colonic crypt under inflammatory conditions. A variety of scenarios were considered, including different spatial distributions of macrophages and a range of possible macrophage and epithelial synthesis rates for NO. / (cont.) The results were used to predict the range of NO concentrations (<0.3 tM) and cumulative NO dose (560 [mu]M * min) experienced by a given epithelial cell migrating from the base to the top of the crypt. This first set of predictions was based on literature data on the cellular synthesis and consumption of NO. Knowledge of the rates at which macrophages and epithelial cells synthesize NO is critical for predicting the concentrations of NO and other reactive nitrogen species in colonic crypts during inflammation, and elucidating the linkage between inflammatory bowel disease, NO, and cancer. Macrophage-like RAW264.7 cells, primary bone marrow-derived macrophages (BMDM), and HCT116 colonic epithelial cells were subjected to simulated inflammatory conditions, and rates of formation and consumption were determined for NO, O2, and 02-. Production rates of NO were determined in either of two ways: continuous monitoring of NO concentrations in a closed chamber, with corrections for autoxidation; or NO2- accumulation measurements in an open system, with corrections for diffusional losses of NO. The results obtained using the two methods were in excellent agreement. Rates of NO synthesis (2.3 + 0.6 pmol s-1 106 cells-), NO consumption (1.3 ± 0.3 s-1), and 02 consumption (58.8 ± 17 pmol/s/10 6 cells) for activated BMDM were indistinguishable from those of activated RAW264.7 cells. NO production rates calculated from NO2- accumulation data for HCT1 16 cells infected with Helicobacter cinaedi (3.9 ± 0.1 pmol/s/106 cells) were somewhat greater than those of RAW264.7 macrophages infected under similar conditions (2.6 ± 0.1 pmol/s/106 cells). / (cont.) Thus, RAW264.7 cells have nearly identical NO kinetics to primary macrophages, and stimulated epithelial cells are capable of synthesizing NO at rates comparable to macrophages. Using this new cellular data to refine the predictions of the colon model, simulations of NO diffusion and reaction in a crypt during inflammation gave maximum NO concentrations of about 0.2 [mu]M. The presence of iNOS and nitrotyrosine in human metastatic melanoma tumors suggest that NO plays a role in the pathophysiology of metastatic melanomas. However, the concentrations of NO that melanoma cells are exposed to in vivo remains unknown. Cellular rates of NO synthesis and consumption were experimentally determined and used in a reactiondiffusion model to predict NO concentrations in a cutaneous melanoma. NO synthesis by A375 melanoma cells was undetectable using Griess assays. The rate constant for intracellular NO consumption by A375 cells (7.1 ± 1.1 s-1), was determined by monitoring NO concentrations in a closed chamber with corrections for autoxidation and consumption from media-generated 02-. Incorporating NO kinetic data from A375 cells and macrophages into a reaction-diffusion model, NO was found to be localized to the periphery of the melanoma; roughly 90% of the NO synthesized by macrophages is consumed within 30 [mu]m of the tumor edge. Several additional scenarios were modeled, including the effects of varying the volume fraction of macrophages surrounding a melanoma tumor and intratumoral NO synthesis by melanoma cells. As such, a range of NO concentrations were predicted (< 0.2 VM) for the edge of the tumor. / (cont.) Our model may offer some insight into the role NO plays in the metastasis of cutaneous melanomas, which occurs primarily through lymphatic spread. At the melanoma edge, NO may inhibit melanoma cell apoptosis, contributing to abnormal tumor growth and invasion of local lymph vessels or NO may act as a lymphangiogenic factor. The colonic crypt model and the cutaneous melanoma model developed in this work provide the first NO concentration predictions for tissues during inflammation. Despite the different geometries and different cell types involved, the maximum values estimated in both cases were - 0.2 [mu]M. The results from this work can be used for predicting intracellular levels of other reactive nitrogen species, and should help guide further studies to understand the mechanisms by which NO contributes to carcinogenesis in IBD and in cutaneous melanomas. / by Melanie Pei-Heng Chin. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004. / Page 172 blank. / Includes bibliographical references. / (cont.) curve is explained mechanistically by the results of the first study. In a final study, we investigated the phenomenological structure of CHO-EGFR cell paths using turn angle distribution and time series analyses. Increased local cell speed correlated with increased likelihood of local directional persistence, a result independent of biochemical modulation of overall cell motility. Time-based directional autocorrelations were observed that indicate an unusual non-Markov behavior in CHO migration. Overall, these studies demonstrate how biophysical analysis is an effective tool for gaining insight into the quantitative regulation of motility by intracellular signaling. / The physiological importance of cell motility has resulted in intense efforts dedicated towards deconstructing its molecular control mechanisms. Most research employs qualitative approaches, yet quantitative understanding of how altering the function of genes or proteins changes migration responses is critical for engineering therapies targeting pathological cell motility. In this work, we deconstruct hierarchical quantitative relationships between biochemical, biophysical, and phenomenological descriptions of cell motility. Specifically, this thesis establishes quantitative correlations between the activation of key intracellular signaling proteins by extracellular motility cues and the effects of these signals on both the biophysical processes comprising motility and parameters describing the overall paths of translocating cells. Our model system consisted of Chinese Hamster Ovary (CHO) cells transfected with the epidermal growth factor (EGF) receptor. In initial experiments employing EGF and fibronectin (Fn) as extracellular cues, we found that adhesion-mediated stabilization of lamellipodial protrusions governed the magnitude of directional persistence in cell paths. To connect this biophysical control of persistence to intracellular signaling, a second study examined the role of extracellular signal-related kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) signaling in EGF-induced migration. Both molecules controlled directional persistence biphasically, with maximal persistence at intermediate signal strength. Studies of lamellipodial protrusion, in concert with experiments using soluble anti-adhesion peptides to modulate persistence, indicated that the ERK, but not the PI3K, biphasic / by Brian David Harms. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2000. / Includes bibliographical references (leaves 195-207). / Supercritical water oxidation (SCWO) is a process which runs at 250 bar and 400- 6000 C to effect rapid and complete destruction of aqueous organics. The SCWO process streams are very corrosive and pose a materials performance challenge to even noble metals and the most advanced alloys. Corrosion in chlorinated, acidic streams at transitional temperatures (100-400° C) in a Hastelloy C-276 tube is examined through post-failure analysis and controlled exposure experiments. Dealloying and intergranular corrosion were observed. Dealloying rate was found to be strongly correlated with temperature and dielectric constant. Intergranular corrosion behavior was found to be affected by the alloy hardness. In order to understand the fundamental chemistry of localized chloride-assisted corrosion initiation, a density-functional calculation of Cr20 3 was performed and validated against experimental data. The (0001) surface of a-Cr20 3 was computed and found to experience strong relaxations in the terminal oxygens. The surface was found to be susceptible to attack by electron-rich species; this might be defeated by p-doping the oxide. Further, the chemically relevant states at the surface assumed a ferromagnetic order. Effects of a variable dielectric medium upon the chemistry of the surface were assessed for the bare surface and adsorption of H and Cl. / by Jason Alexander Cline. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references. / Initiated chemical vapor deposition (iCVD) is a one-step, soventless process that can be used to produce polymeric thin films. The iCVD technique has been used to polymerize a wide variety of vinyl monomers such as glycidyl methacrylate (adhesive) and 2-hydroxyethyl methacrylate (hydrophilic). The proposed polymerization mechanism is the classical free radical polymerization mechanism of vinyl monomers. Monomer and initiator gases are fed into a vacuum chamber where resistively heated wires are used to thermally decompose the initiator molecules into free radicals. The free radicals then attack the vinyl bonds of the monomer molecules. Propagation occurs on the surface of a cooled substrate. This thesis presents an in-depth mechanistic study of the iCVD deposition of low surface energy poly(1H,1H,2H,2H-perfluorodecyl acrylate) (PPFDA) thin films. PPFDA films have many uses due to their hydrophobic and oleophobic properties. Fourier transform infrared spectroscopy and x-ray photoelectron spectroscopy of the iCVD PPFDA films showed complete retention of the fluorine moieties. Deposition rates as high as 375 nm/min were achieved. It was found that the deposition rate and molecular weight increases with decreasing substrate temperature and increasing monomer partial pressure. / (cont.) Quartz crystal microbalance measurements showed that these effects correlated with an increased monomer concentration at the surface. Dimensionless analysis was used to scale up this iCVD polymerization to a custom modified roll-to-roll reactor. The roll-to-roll process allows for the fast production of realistic size samples. The use of liquid solvents in membrane coating processes often creates a blanket coating in which the pores are clogged due to surface tension problems and wettability. These problems do not exist for solventless processes such as iCVD. This thesis presents the use of the iCVD technique to functionalize electrospun fiber mats and polymeric capillary pore membranes in order to make water-repellent, self-cleaning membranes. X-ray photoelectron microscopy data confirmed the presence of the PPFDA coating on the topside and the backside of the membranes and electron microprobe analysis confirmed the presence of the coating along the pore wall. It was found that the iCVD process can be used to functionalize membranes with very high aspect ratio (-80:1) pores. / by Malancha Gupta. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2009. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 161-169). / Recently, there has been an increasing interest in improving the efficiency and lowering the emissions from operating combustors, e.g. internal combustion (IC) engines and gas turbines. Different fuels, additives etc. are used in these combustors to try to find the optimal operating conditions and fuel combination which gives the best results. This process is ad-hoc and costly, and the expertise gained on one system cannot easily be transfered to other situations. To improve this process a more fundamental understanding of chemistry and physical processes is required. The fundamental constants like rate coefficients of elementary reactions are readily transferable enabling us to use results from one set of experiments or calculations in a different situation. In our group we have taken this approach and developed the software Reaction Mechanism Generator (RMG), which generates chemical mechanism for oxidation and pyrolysis of a given fuel under a set of user-defined physical conditions. RMG uses group additivity values to generate thermochemistry of molecules and has a database of rate coefficients of elementary reactions. These two sets of data are used to generate chemical kinetic mechanism in a systematic manner. The reaction mechanisms generated by RMG are purely predictive and elementary rate coefficient from any reliable source can be added to RMG database to improve the quality of its predictions. The goal of my thesis was two fold, first to extend the capabilities and database of RMG and to release it as an open source software for the chemical kinetic community to use. / (cont.) The second was to take a practical system of interest and use RMG to generate the chemical mechanism and thereby demonstrate the utility of RMG in generating predictive chemical mechanisms for practical situations. As a part of the second step our hope was to generate new chemical insights into soot formation processes which are of great interest. The three most important contributions of the thesis are listed below. 1. My work with RMG has resulted in order of magnitude improvements in the cpu and memory usage of RMG and it has added many useful features to RMG like ac- curate sensitivity analysis for better interpreting the final mechanism. I have also worked on extending the database of RMG, by adding thermochemistry of ringed species that cannot be treated adequately by group additivity. Also kinetic rate rules for intramolecular-H-migration reactions in OOQOOH molecules were added to RMG database, which are important in predicting the low temperature oxidation of alkanes. 2. Recently there have been considerable advances in the methodology for rate coefficient calculations for loose transition states, i.e transition states that are not saddle points. These type of transition states are encountered often in radical-radical reactions. In addition to these advances there has been significant progress in accurate calculation of the pressure dependent rate coefficients for complicated potential energy surfaces with multiple wells and multiple product channels. The method is based on the master equation formulation of the problem. These detailed equations are then appropriately coarse-grained to calculate the phenomenological rate coefficients. / (cont.) I have used these state of the art techniques to calculate the rate coefficients for the formation of various aromatic species like benzene and styrene. The rate coefficients predicted by these methods were tested under certain conditions and are in good agreement with experimental data. 3. Finally to model a two-dimensional diffusion flame we have developed a solver that is able to solve a complicated set of highly coupled differential equations in an efficient manner to give accurate results. The solver in conjunction with chemistry that is developed using techniques mentioned in the last two points is used to solve the mole fraction profiles in the diffusion flame. The results of the simulations are compared to the experimental measurements and this process gives us insight into soot formation in diffusion flames. / by Sandeep Sharma. / Ph.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1968. / Vita. / Bibliography: leaves 213-217. / by Alvin E. Witt. / Sc.D.