Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2009. / Includes bibliographical references (p. 117-120). / There are many potential clinical applications for localized drug delivery and sensing systems, such as cancer, vaccinations, pain management, and hormone therapy. Localized drug delivery systems reduce the amount of drug required for a therapeutic effect and the severity of side effects. Delivery of multiple chemicals has been demonstrated previously from a polymeric microreservoir device. This dime-sized device contains small reservoirs loaded with drug and separated from the outside environment by a degradable polymer membrane. This device was modified to allow minimally invasive implantation with a large-bore needle and has demonstrated in vitro pulsatile release of a model compound after a mock implantation step. A biodegradable sealing method was developed for the polymeric microreservoir device, which makes the device completely resorbable and eliminates the surgical removal step needed with a non-resorbable device. Localized sensing systems will allow early detection of diseases and provide a tool for developing personalized treatment programs. The polymer microchip platform has been combined with magnetic relaxation switch (MRSw) nanoparticle sensors to create an in vivo sensing device. MRSw are magnetic nanoparticles (iron oxide core, crosslinked dextran shell) that can detect a variety of analytes. MRSw are kept in the device by a molecular weight cut-off (MWCO) membrane which allows analytes free access to the nanoparticle sensors. / (cont.) The MRSw aggregate in the presence of the analyte they were designed to detect and this aggregation causes a decrease in the transverse relaxation time (T2), which can be detected with magnetic resonance imaging (MRI) or nuclear magnetic resonance relaxometry. In vitro sensing experiments were used to optimize the device design and characterize its performance. In vivo device-based sensing of hCG, a soluble biomarker that is elevated in testicular and ovarian cancer, has been demonstrated. Cell lines secreting hCG were used to produce ectopic tumors in nude mice. The sensing device was implanted and magnetic resonance imaging (MRI) quantified a T2 decrease in mice with tumors compared to control mice (no tumors). This device may be the first continuous monitoring device for cancer that can be implanted at the tumor site and demonstrates feasibility of MRSw measurements in vivo. / by Karen D. Daniel. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 173-181). / Synthetic biology is an evolving field that emphasizes synthesis more than observation which has been and is the scientific method for traditional biology. With powerful synthetic tools, synthetic biologists seek to reproduce natural behaviors (and eventually to create artificial life) from unnatural molecules or try to construct unnatural systems from interchangeable parts. Accompanied with this recent movement, metabolic engineers started to utilize these interchangeable parts (enzymes in this case) to create novel pathways. In addition, engineering biological parts including enzymes, promoters, and protein-protein interaction domains has led to productivity improvement. However, understanding behaviors of a synthetic pathway in an engineered chassis is still a daunting task, requiring global optimization. As the first step to understand pathway design rules and behaviors of synthetic pathways, a synthetic pathway for the production of D-glucaric acid has been designed and constructed in E. coli. To this end, three disparate enzymes were recruited from three different organisms, and the system perturbed by this introduction of heterologous genes was analyzed. Limiting flux through the pathway is the second recombinant step, catalyzed by myo-inositol oxygenase (MIOX), whose activity is strongly influenced by the concentration of the myo-inositol substrate. To increase the effective concentration of myo-inositol, synthetic scaffold devices were built from protein-protein interaction domains to co-recruit all three pathway enzymes in a designable complex. / (cont.) This colocalization led to enhancement of MIOX activity with concomitant productivity improvement, achieving 2.7 g/L of D-glucaric acid production from 10 g/L of D-glucose input. Secondly, retrobiosynthetic approach, a product-targeted design of biological pathways, has been proposed as an alternative strategy to exploit the diversity of enzymecatalyzed reactions. The first step in a glucaric acid pathway designed retrosynthetically involves oxidation of the C-6 hydroxyl group on glucose, but no glucose oxidase in nature has been found to act on this hydroxyl group on glucose. To create glucose 6- oxidase, a computational design and experimental selection was combined with the help of DNA synthesis technology. To this end, the sequence space of candidate mutations was computationally searched, the selected sequences were combinatorially assembled, and the created library was experimentally screened and characterized. Furthermore, the structure-activity relationship of the newly created glucose oxidases was elucidated, and the kinetic model mechanism for these mutants was proposed and analyzed. Collectively, parts, devices, and chassis engineering were applied to a synthetic pathway for the production of D-glucaric acid, and this synthetic biology approach was proven to be effective for new pathway design and improvement. / by Tae Seok Moon. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1992. / Includes bibliographical references (p. 353-374). / by Dimitrios Maroudas. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2011. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / "February 2011." Cataloged from student submitted PDF version of thesis. / Includes bibliographical references (p. 224-237). / The global consumer demand for portable electronic devices is increasing. The emphasis on reducing size and weight has put increased pressure on the power density of available power storage and generation options, which have been dominated by batteries. The energy densities of many hydrocarbon fuels exceed those of conventional batteries by several orders of magnitude, and this gap motivates research efforts into alternative portable power generation devices based on hydrocarbon fuels. Combustion-based power generation strategies have the potential to achieve significant advances in the energy density of a generator, and thermoelectric power generation is particularly attractive due to the moderate temperatures which are required. In this work, a portable-scale thermoelectric power generator was designed, fabricated, and tested. The basis of the system was a mesoscale silicon reactor for the combustion of butane over an alumina-supported platinum catalyst. The system was integrated with commercial bismuth telluride thermoelectric modules to produce 5.8 W of electrical power with a chemical-to-electrical conversion efficiency of 2.5% (based on lower heating value). The energy and power densities of the demonstrated system were 321 Wh/kg and 17 W/kg, respectively. The pressure drop through the system was 258 Pa for a flow of 15 liters per minute of air, and so the parasitic power requirement for air-pressurization was very low. The demonstration represents an order-of-magnitude improvement in portable-scale electrical power from thermoelectrics and hydrocarbon fuels, and a notable increase in the conversion efficiency compared with other published works. The system was also integrated with thermoelectric-mimicking heat sinks, which imitated the performance of high-heat-flux modules. The combustor provided a heat source of 206 to 362 W to the heat sinks at conditions suitable for a portable, air-breathing TE power generator. The combustor efficiency when integrated with the heat sinks was as high as 76%. Assuming a TE power conversion efficiency of 5%, the design point operation would result in thermoelectric power generation of 14 W, with an overall chemical-to-electrical conversion efficiency of 3.8%. / by Christopher Henry Marton. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 140-150). / The electron confinement in carbon nanomaterials provides them with many interesting electronic, mechanical and optical properties, thus making them one of the best suited materials for electronic and sensor applications. However, at present practical realization of nano-scale electronics faces two major challenges: their assembly into functional electronic circuits, and precise engineering of these building blocks. New methods of physical and chemical manipulation are needed to address these challenges. The work presented in this thesis aims to understand and design physical and chemical manipulation methods for carbon nanostructures. More specifically, this thesis is concerned with two main topics on manipulation of carbon nanomaterials: First, the problem of the top-down, parallel placement of anisotropic nanoparticles and secondly, chemical manipulation via controlled chemical functionalization. Physical manipulation of nanostructures has been achieved by designing a method for creating high aspect ratio cylindrical droplets with nano-to-micro scale diameters on a wafer by engineering the substrate surface chemistry, liquid surface tension and liquid film thickness. The substrate surface is manipulated by chemisorption of monolayers of hydrophobic and hydrophilic molecules in form of alternating rectangular strips. The cylindrical droplets selectively form on the hydrophilic strips. The hydrodynamic flow patterns that evolve within the droplets during evaporation are able to orient and position the entrained carbon nanotubes with parallel alignment with nanometer precision. With respect to chemical manipulation, this thesis work focuses on graphene and graphene nanoribbons (GNR). In this work first detailed structure-reactivity relationships for electron-transfer chemistries of graphene and GNR are developed. For GNR, these relationships demonstrate the dependence of the ribbon reactivity on width and orientation of carbon atoms along the edges. Large variations in reactivity are predicted for ribbons of different widths and family type suggesting selective chemistries may be developed to sort or preferentially modify the GNRs. For graphene these structure reactivity relationships include regio-selective chemistry and reactivity dependence on the number of graphene layers on chip. This work demonstrates high reactivity of graphene edges and reports a spectroscopic method to analyze the edge reactivity. This study should aid studies to control the disordered edge structure of GNR by edge selective chemical functionalization and chemically modify graphene depending on the number of layers stacked. The electron transfer chemistries developed in this work have also been used to understand the role of covalent defects on graphene electron conduction. This work may be used in future to assemble graphene sheets in three dimensions to fabricate supermolecular structures (i.e. graphene super lattices). / by Richa Sharma. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Solid tumors have low oxygen tension - hypoxia - that fuels disease progression and treatment resistance. Thus, strategies for alleviating hypoxia are needed. Two factors affect tissue oxygen levels: oxygen supply via blood vessels and oxygen consumption by cells. I focused on improving supply to combat hypoxia. Two vessel abnormalities limit supply. Compression decreases the density of perfused vessels supplying tumors. Excessive leakiness slows blood flow partly by reducing the intravascular pressure drop. Strategies to repair leakiness towards decreasing hypoxia exist, so I developed approaches for overcoming compression. In order to understand the origin of vessel compression, we developed the first ex vivo technique to estimate compressive solid stresses held in tumors. We made measurements of this residual solid stress in numerous tumor types from patients and mice to confirm that elevated stress is conserved across tumors. We then identified structural components within tumors that contribute to stress. Since cancer cells were known to compress vessels, we found that depleting them reduced stress, as did depleting fibroblasts, collagen, and hyaluronan. Depleting these components decompressed blood and lymphatic vessels. After identifying targets to reduce stress, we sought to decrease stress therapeutically to improve treatment outcomes. First, we demonstrated that losartan, an FDA-approved therapy indicated for hypertension, decreases the activation of fibroblasts and the production and maintenance of collagen and hyaluronan. As a result, losartan decompressed vessels, restored perfusion, decreased hypoxia, and potentiated chemotherapy. These results provide a rationale for retrospective analyses demonstrating losartan's benefit and for future clinical trials, one of which is currently underway (NCT01821729). To understand how reversing compression modulates both individual vessels and the vascular network to improve oxygen delivery, we developed a technique using multiphoton phosphorescence quenching microscopy to map oxygenation to perfused blood vessels in live tissues. This technique allowed us to compare the effects of reversing compression to the effects of repairing leakiness on individual vessels and vascular network geometry. In comparing and contrasting these two strategies, we showed how each of these strategies could be improved to increase oxygen delivery. This work also has implications for optimally combining both treatment strategies to increase oxygen delivery to tumors. / by John Daniel Martin. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1998. / Includes bibliographical references (p. 155-160). / by Steven J. Meier. / Ph.D.

Thesis (M.S.) Massachusetts Institute of Technology. Dept. of Chemical Engineering, 1951. / Bibliography: leaves 111-112. / by Oscar C. Eubank, William S. Proctor. / M.S.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Cost effective production of biofuels depends critically on feedstock cost and availability. As such, volatile fatty acids (VFAs) can play an important role in advancing sustainable biofuel production since they can be derived from low cost feedstock including gases and municipal solid waste. To this end, we studied fermentations of the oleaginous microbe Yarrowia lipolytica engineered for lipid overproduction. With acetate as sole carbon source, we conducted fed batch fermentations of Y. lipolytica in which acetic acid was maintained at low, non-inhibitory levels yielding high lipid titer of 50 g/L and productivity of 0.25 g/L/h, along with a lipid content of 60%. We also conducted fed batch fermentations with cell recycle to utilize dilute steams of acetic acid that essentially replicated the results of the fed batch process. Carbon balances were satisfied and no excess carbon dioxide production was detected beyond the amounts associated with biomass formation and product synthesis. Acetate is one member of the entire range of VFAs produced from municipal solid waste (MSW) via anaerobic digestion; thus, facilitating the use of MSW as a primary feedstock would be contingent on the ability of the above strain to grow on a mixture of VFAs. Given the insufficient literature examining microbial growth on VFAs, one of the goals of this project was to explore individual as well as mixed VFAs as a feedstock for Y.lipolytica. Dilute stream of mixed VFAs were successfully used as feed in bioreactor studies to obtain high cell density cultures. Similar results with respect to lipid production were obtained in comparison to the study on acetate. In addition, the microbe could tolerate perturbations in the feed composition and grow to similar cell densities. The success in establishing VFAs as a potential substrate for lipid accumulation in Yarrowia lipolytica raises the possibility of a two-stage commercial bioprocess enabling biodiesel production from MSW. / by Sagar Chakraborty. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1993. / Includes bibliographical references (p. 225-239). / by Craig Allen Zupke. / Ph.D.