Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1998. / Includes bibliographical references (p. 381-391). / by William Francis Feehery. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references. / Plasma etching processes often roughen the feature sidewalls forming anisotropic striations. A clear understanding of the origin and control of sidewall roughening is extremely desirable, particularly at the gate level where variations in line width can adversely impact the electrical performance of the device. In addition, at the back end, feature sidewall roughness of the dielectric materials might degrade the resolution of contacts, interfere with the deposition of conformal liner materials, and make the process integration challengeable. In an inductively coupled plasma apparatus, the etching behavior on real feature sidewalls was simulated by etching blank films at grazing ion bombardment angles. The angular etching yields of polysilicon and dielectric materials in Ar, C12/Ar, and C4F8/Ar plasma beams were studied as a function of ion bombardment energy, ion bombardment angle, etching time, plasma pressure, and plasma composition. Interestingly, the effective neutral-to-ion flux ratio was the primary factor influencing the etching yield. A typical sputtering angular yield curve, with a peak around 600 off-normal angle, was formed at non-saturated etching regime, while an ion-enhanced-etching angular yield curve peaked around 650 was observed in the saturated etching regime. / (cont.) In Ar plasma, various films remained smooth after etching at normal angle but became rougher at grazing angles. Specifically, the striation structure formed at grazing angles could be either parallel or transverse to the beam impingement direction. Encouragingly, the sputtering caused roughening at different off-normal angles could be qualitatively explained by the corresponding angular dependent etching yield curve. In fluorocarbon plasmas, the roughening of thermal silicon dioxide and low-k coral films at grazing ion bombardment angles depended on both the etching kinetics and the etching chemistry. In particular, the surface roughened when the etching process was physical-sputtering like (at low neutral-to-ion flux ratios), even though the polymer deposition effect was trivial; when the etching kinetics was dominated by ion-enhanced etching (at high neutral-to-ion flux ratios), the roughening was mainly caused by the local polymer deposition effects. Moreover, surfaces could be etched without roughening at intermediate neutral-to-ion flux ratios and/or with the addition of oxygen to the discharge. The oxygen addition broadened the region over which etching without roughening can be performed. / (cont.) Additionally, the local-polymer-deposition effect can be used to explain the surface roughening of porous low-k films in fluorocarbon plasmas. Last, it was shown that RMS roughness is not adequate to represent the surface roughness on etched surfaces, especially when anisotropic striations exist. Instead, statistical methods such as the power spectral density and geostatistical analysis are capable of measuring the surface roughening in both vertical and lateral dimensions. In this way, the spatial variation of the streaks formed during plasma etching can be characterized quantitatively. / by Yunpeng Yin. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2003. / Includes bibliographical references (p. 139-145). / This thesis focuses on micro devices aimed at rapid analysis of cells and subcellular organelles. These devices take advantage of microfabrication techniques to create environment suitable for biomechanical and biochemical stimulation of cells, to break cell membranes to extract the intracellular materials, and to separate or concentrate organelles and proteins of interest. These procedures greatly reduce the amounts of samples and reagents necessary and the process time required from their macro counterparts. Moreover, they demonstrate operational advantages, such as lower voltages, less heating, and no significant gas formation in electrolysis, over their macroscopic counterparts. First in line of the process stream are a series of microfluidic devices developed for the purpose of studying cell adhesion on biomaterials. Numerical models are developed to aid the quantitative analysis of fluid shear stresses on cells in these devices. The experimental results demonstrate that these devices are capable of capturing ligand-density-dependent, shear-dependent, and growth-factor-dependent adhesion behavior of cell cultures. Next, two electrical microfluidic devices are developed for the purpose of cell lysis and organelle separation. Both devices are fabricated using electroplating techniques to create three-dimensional electrodes, and lithography to accommodate flexible designs in the fluid channels. Simple electrical models for cells and organelles are used to guide the design and operation of the miniaturized electroporation device that can successfully break open cells and release their content. / (cont.) To study the isoelectric focusing field flow fractionation phenomena, another model combining flow calculation and reactive transport of amphoteric particles is used. The experimental results of organelle separation are in good agreement with predicted focusing behavior in the model. This technique is able to separate or concentrate organelles such as mitochondria and peroxisomes in a few minutes, which is greatly reduced from conventional techniques. Experiments demonstrate the separation of nuclei and whole cells from mitochondria. Additionally, the devices are used to distinguish mitochondria with intact membrane potential from those that have lost transmembrane potential. This ability to distinguish the mitochondria populations could potentially be used to assay whether cells have committed apoptosis via the mitochondrial pathway. The modules developed in this thesis demonstrate advantages of scaling down bioanalytical processes. Further developing and combining the technologies demonstrated in this thesis will enable a platform for parallel, fast, and automated cell dynamics and proteomics studies for systems biology. / by Hang Lu. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2002. / Includes bibliographical references. / Microfabrication technology presents the opportunity to create highly instrumented, micro-scale chemical reactors that bring with them the potential for new analytical capabilities, point-of-use synthesis, and highly parallel screening methods. However, the use of integrated circuit-like reaction devices, such as the MIT thin-film microreactor, also gives rise to a spectrum of new engineering challenges with respect to reactor system integration and scale-up schemes. This work demonstrates the integration of multiple microreactors operating in parallel within a system that includes gas flow control components and the associated electronic circuitry. The system built is equivalent to a conventional laboratory reactor system but in 1/10th of the space. Fluidic and electronic interfaces, thermal management, and operational safety are all considerations in microreactor packaging. A standard microchip socket from Texas Instruments was selected as the first level packaging. The sockets have mechanical attributes that lend them to, with minor reworking, simultaneous fluidic and electronic connection. This selection makes PC board mounting of the reactor devices straightforward. Shut-off microvalves and proportional microvalves from Redwood Microsystems, with their control electronics, have also been mounted on PC boards to control the gas flow in the system. This allows the entire system: reactors, device electronics, and gas distribution manifold to be mounted on standard CompactPCI cards and housed in a commercially available chassis. A Kaparel CompactPCI chassis is used to house the microreactor system. / Electrical connections between the boards are achieved through a standard backplane and custom-built rear I/O PC boards. The system is comprised of a temperature controller card that regulates temperature for auxiliary heaters in the system; a gas mixing board that mixes the feed gas for the microreactors; two microreactor boards that each contain two microreactors with their feed flow controllers; and two heater circuit boards that provide power to the microreactor heaters. A National Instruments embedded real time processor is used to provide closed-loop control and monitor system alarms. A host PC, running LabVIEW 6, is used as the human machine interface for operator interaction and historical data logging. / by David J. Quiram. / Ph.D.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1943. / MIT copy bound with: The use of scrap leather for artificial leather soles / Alfred B. Babcock, Jr. and William R. Kittredge. 1943. / Includes bibliographical references (leaves 20-21). / by Clinton C. Kemp. / B.S.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1954. / Includes bibliographical references (leaf 48). / by Samuel W. Ing, Jr. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008. / MIT Science Library copy printed in leaves. / Includes bibliographical references (p. 281-299). / Human societies face diverse health challenges including a rapidly aging population, rising incidence of metabolic disease, and increasing antibiotic resistance. These problems involve complex interactions between genes and environment and are often not well understood. To address these challenges, high-throughput and reproducible advances in genome sequencing, transcript measurement, and protein measurement have been developed; the information resulting from these techniques has led to an increased understanding of cellular function and the identification of number of novel biomarkers for a variety of diseases.In recent years, the monitoring of such systems-level cellular behavior has naturally extended to the metabolite level, leading to the study of metabolomics. The rise of metabolomics corresponds hand in hand with the desire to address some of the phenotypic informational gaps left behind from genomics, transcriptomics, and proteomics. The study of metabolites carries several advantages. First, the number of metabolites in the human "metabolome," estimated at 2500 metabolites, remains a tractable number for analysis as compared to the 35,000 genes and 100,000-1,000,000 proteins. Metabolites also reliably provide an instantaneous "downstream" biochemical snapshot of a cell, and the typical metabolomics analysis is carried out on relatively noninvasive patient fluids such as urine or plasma.The goal of this thesis is to design, develop, and apply methods for the metabolomic analysis of blood via gas chromatography-mass spectrometry (GC-MS) instrumentation. Despite initial successes, methods in metabolomics vary widely and have not been standardized. This was first addressed via the optimization of the instrumentation itself, a topic rarely addressed in the literature but crucial toward the reliable identification of biomarkers. / (cont) We investigated the different GC-MS parameters found to have the largest impact on data quality and employed D-optimal design to pare down the search space to a feasible number of experiments. These parameters were then optimized via response surface estimation to ensure maximum reproducibility and sensitivity of the entire metabolite mixture. The results from this optimization constitute a significant improvement upon existing methods in the literature.Next, methods were developed for the bioinformatics analysis of raw GC-MS data. Current techniques for metabolite tracking are non-systematic and typically require the laborious use of reference libraries. We developed a method to track conserved metabolites across GC-MS replicates and conditions with the optional use of reference libraries and validated it an E. coli dataset and the differential detection of metabolites in a spiked mixture. In addition, we investigated the best methods for the imputation of missing data as applied to three different metabolomics datasets; to this date, missing data imputation has not been comprehensively addressed in the metabolomics literature, and many methods currently used are needlessly inaccurate. After investigating eight different imputation methods via three deletion methods, it was concluded that k-nearest neighbor algorithms were the best and most accurate method for data imputation.Finally, the instrumental parameter optimization and metabolite tracking methods were applied to the problem of predicting patient mortality in end-stage renal disease (ESRD). Although ESRD is a complex and well-studied disease, known risk factors only account for 50% of patient deaths, and prediction accuracies for the disease remain relatively low; in addition, mortality rates in the first 90 days of dialysis treatment are double that after 90 days. / (cont.) We sought to investigate whether the addition of metabolomic information would result in increased accuracy of mortality prediction. One hundred twenty patient samples were obtained from a national dialysis study (equally representing death and survival within 90 days of starting dialysis) and analyzed according to our protocol. Two feature selection algorithms were applied to identify significant metabolites distinguishing death and survival, and the corresponding models resulted in improved receiver-operating characteristic (ROC) curve areas of 0.85 and 0.93. This result constitutes a significant improvement from existing clinical models, which at best result in ROC curve areas of 0.80. Based on this work, we hypothesize that our observed differential fatty acid concentrations are indicative of impaired fatty acid oxidation, leading to insulin resistance in ESRD patients (regardless of Type II diabetes status) and eventually, patient mortality. / by Lily Victoria Tong. / Ph.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1941. / Vita. / Includes bibliographical references (leaves 233-[234]). / by Robert B. Egbert. / Sc.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1938. / Vita. / Includes bibliographical references (leaves 140-146). / by William Burns Tucker. / Sc.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004. / Includes bibliographical references (leaves 231-240). / As part of the non-specific immune response to infection, activated macrophages synthesize nitric oxide (NO) at relatively high rates, thereby creating local concentrations of NO that are toxic to the invading microorganisms. However, high rates of NO synthesis can also damage host tissues, especially if prolonged (as in chronic inflammations). Although NO can act directly, much of its cytotoxicity and genotoxicity may be due to peroxynitrite (ONOO-), formed by the rapid reaction of NO with superoxide (02-)- Superoxide is a byproduct of mitochondrial respiration and of certain cytosolic reactions, and it is present in virtually all cells. Thus, intracellular ONOO- formation is inevitable when cells are exposed to NO, which diffuses readily across cell membranes. Superoxide is generated also by an NADPH oxidase on the external membrane surface of macrophages, thereby delivering it to the extracellular fluid at significant rates. The research in this thesis aimed to determine the concentration profiles of NO and related species in cell cultures and tissues. Toward that end, the diffusion and reactions of NO, 02, and 02- were studied by mathematical modeling and by experimental work with macrophage cultures. The results obtained will be useful in designing NO toxicity experiments and in determining potentially toxic conditions in body tissues. A mathematical model was developed to predict the intracellular concentrations of NO, 02-, and ONOO- in suspension cell cultures exposed to NO and/or peroxynitrite. Steady-state concentrations were computed as a function of radial position within an idealized spherical cell, with a distinction being made between cytosolic and mitochondrial values. / (cont.) Potential sources of peroxynitrite include intracellular generation in mitochondria and cytosol and (depending on the type of experiment) diffusion of extracellular peroxynitrite into the cell. The relative importance of extracellular and intracellular sources was estimated for a wide variety of conditions. The calculated mitochondrial concentrations were generally 5-10 times higher than the cytosolic values. For the baseline conditions, including an NO concentration of 1 [mu]M and no peroxynitrite in the medium, the cytosolic peroxynitrite concentration was estimated as [approx.] 2 nM. The extracellular peroxynitrite concentration required to double the cytosolic level was [approx.] 25 nM, and an extracellular concentration of -100 nM was needed to effect a five-fold increase. Another approach for studying NO and ONOO- toxicity involves the co-culture of activated macrophages (producers of NO and 02-) with "target cells" (which make 02- but not NO). Because peroxynitrite concentrations in such experiments are too small and localized to measure, reaction-diffusion models were developed for situations ranging from isolated cells to many cells randomly distributed on a plate. The average concentration inside randomly distributed target cells increased with increasing macrophage number density, as entry of extracellular peroxynitrite grew in importance relative to intracellular formation. For high cell densities, large peroxynitrite membrane permeabilities, and low rates of intracellular synthesis, the surrounding macrophages were calculated to double or triple the peroxynitrite concentration in an average target cell ... / by Nitesh Nalwaya. / Ph.D.