Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2011. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student submitted PDF version of thesis. / Includes bibliographical references (p. 223-230). / A process is proposed to perform separations via crystallization by using multiple tanks and constraining crystal growth to solid surfaces. Multiple tanks allow multiple recrystallizations to improve product purity and to ensure high recovery of the component of interest. Crystal growth on solid surfaces avoids multi-phase flow handling which can cause operational difficulties. A model is developed for this process for solid solution forming systems which is also applied to batch crystallization for comparison. The solid product from the process is found to provide enhanced purity (1-2% increase) at yields approaching the batch yield when a large number of tanks are used; the ratio of incorporation rate constants (?) is significantly less than one; and the surface equilibrium constant (K) is less than order one. The liquid effluent from the process is also a viable product when ?>1 and K is close to or greater than one. The use of a sweep stream entering at a tank up-stream of the feed tank was determined to be undesirable due to diminished yield. Batch experiments performed to validate the proposed model with asparagine as the component of interest and aspartic acid as the impurity in water were found to be inconclusive. Fitting of parameter values to the liquid phase was not successful due to crystal growth on surfaces other than the designated seed. The parameters ? and K fitted to solid phase data were found to be 0.1-3 and 0.4-0.6 respectively which are favorable parameters for use of the semi-continuous process with the solid taken as the product. The presence of crystals on multiple surfaces in the liquid phase indicates that constraint of crystallization to a specific surface was not achieved. The impurity distribution in the solid layer did not match the model prediction throughout the crystal. Non-uniform initial growth behavior or uneven dissolution of the crystal during analysis could cause the observed behavior. Further experiments should be conducted that in-crease the ratio of product to accumulation in the liquid phase and employ solid sampling methods that give more consistent results. / by Nathan M. Aumock. / Ph.D.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1923. / by Khye Hong Oon. / B.S.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Selectivity is a very important consideration when designing cancer treatment. Therefore, targeting cancer-specific isoforms of key metabolic enzymes is a very promising strategy. Elevated glucose consumption and lactate secretion under aerobic conditions is a hallmark of many cancer cells. One of the major contributors to this highly glycolytic phenotype is hexokinase 2 isoform (HK2), which is significantly overexpressed in many tumors but not in normal adult tissue. Several small molecule inhibitors targeting HK have exhibited promising anticancer activity. However, these small molecule inhibitors cannot differentiate between HK isoforms, leading to severe side effects. Elucidating the differences between HK isoforms can guide us in designing isoform-specific inhibitors. Moreover, the complexity and robustness of cellular metabolism and the intricate mechanism underlying cancer development and progression make it very difficult to effectively treat cancer by targeting a single metabolic enzyme. Improved understanding of the metabolic effects of HK to cancer can guide us in identifying selective targets and designing effective combination therapies. We first studied the differential subcellular localizations of HKl and HK2 by selective permeabilization and cell fractionation. We then characterized the metabolic functions of HK for cell growth and proliferation using stable isotope labeling and metabolic flux analysis. Key findings were verified in a hepatocellular carcinoma cell line using low glucose feeding or HK inhibitor. These experiments identified differential HK enzymatic activity in different cell compartments, and discovered key metabolic pathways co-regulated with glycolysis via cellular redox status. These findings may provide guidance in designing cancer-specific inhibitors or combination therapy targeting multiple synergistic metabolic pathways. / by Zhe Zhang. / Ph. D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2014. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Cataloged from student-submitted PDF version of thesis. / Includes bibliographical references (pages 201-223). / For this thesis, several tools for dynamic model development were developed and analyzed. Dynamic models can be used to simulate and optimize the behavior of a great number of natural and engineered systems, from the movement of celestial bodies to projectile motion to biological and chemical reaction networks. This thesis focuses on applications in chemical kinetic systems. Ordinary differential equations (ODEs) are sufficient to model many dynamic systems, such as those listed above. Differential-algebraic equations (DAEs) can be used to model any ODE system and can also contain algebraic equations, such as those for chemical equilibrium. Software was developed for global dynamic optimization, convergence order was analyzed for the underlying global dynamic optimization methods, and methods were developed to design, execute, and analyze time-varying experiments for parameter estimation and chemical kinetic model discrimination in microreactors. The global dynamic optimization and convergence order analysis thereof apply to systems modeled by ODEs; the experimental design work applies to systems modeled by DAEs. When optimizing systems with dynamic models embedded, especially in chemical engineering problems, there are often multiple suboptimal local optima, so local optimization methods frequently fail to find the true (global) optimum. Rigorous global dynamic optimization methods have been developed for the past decade or so. At the outset of this thesis, it was possible to optimize systems with up to about five decision variables and five state variables, but larger and more realistic systems were too computationally intensive. The software package developed herein, called dGDOpt, for deterministic Global Dynamic Optimizer, was able to solve problems with up to nine parameters with five state variables in one case and a single parameter with up to 41 state variables in another case. The improved computational efficiency of the software is due to improved methods developed by previous workers for computing interval bounds and convex relaxations of the solutions of parametric ODEs as well as improved branch-and-bound heuristics developed in the present work. The convergence order and prefactor were analyzed for some of the bounding and relaxation methods implemented in dGDOpt. In the dGDOpt software, we observed that the empirical convergence order for two different methods often differed, even though we suspected that both had the same analytical convergence order. In this thesis, it is proven that the bounds on the solutions of nonlinear ODEs converge linearly and the relaxations of the solutions of nonlinear ODEs converge quadratically for both methods. It is also proven that the convergence prefactor for an improved relaxation method can decrease over time, whereas the convergence prefactor for an earlier relaxation method can only increase over time, with worst-case exponential dependence on time. That is, the improved bounding method can actually shed conservatism from the relaxations as time goes on, whereas the initial method can only gain conservatism with time. Finally, it is shown how the time dependence of the bounds and relaxations explains the difference in empirical convergence order between the two relaxation methods. Finally, a dynamic model for a microreactor system was used to design, execute, and analyze experiments in order to discriminate between models and identify the best parameters with less experimental time and material usage. From a pool of five candidate chemical kinetic models, a single best model was found and optimal chemical kinetic parameters were obtained for that model. / by Spencer Daniel Schaber. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1986. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Vita. / Includes bibliographies. / by Donald Lyle Koch. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995. / Includes bibliographical references (leaf 58). / by Marc Van Dyke. / M.S.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010. / Page 71 blank. Cataloged from PDF version of thesis. / Includes bibliographical references (p. 67-70). / Recombinant proteins produced by different host organisms have been broadly used as therapeutics. Considering the demand for large quantities of protein drugs, methods are needed to increase reactor titers in a timely and cost-effective manner. We used random chemical mutagenesis to modify a wild-type strain of the heterologous protein production host Pichia pastoris, which resulted in overall improvement of the secretion rate of the mutated population. More than 4000 single-cells were simultaneously screened for high secretion of a human Fc fragment using microengraving and the top-producing clones were retrieved. Future characterization of these improved clones by transcript profiling should yield information about networks of genes central in heterologous protein secretion in the yeast P. pastoris. / by Vasiliki Panagiotou. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995. / Includes bibliographical references (v. 2, leaves 421-432). / by Menner A. Tatang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1994. / Includes bibliographical references (leaves [127]-133). / by Tapesh Kumar Yadav. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004. / Includes bibliographical references. / (cont.) With this approach, an upper bound on the yield for OCM was computed. Results showed that even with optimal surface chemistry, strict limits existed on the attainable yield. Surface energetics necessary for superior OCM performance were identified and the origins of these requirements elucidated. The resulting upper bound on OCM yield under conventional, packed-bed, continuous-feed operation was found to be 28%. The catalytic properties of LiCl/sulfated ZrO₂-based catalysts were explored for ODHE. LiCl was shown to strongly interact with the acid sites on sulfated ZrO₂ (SZ), influencing its catalytic behavior. Two approaches were taken to modify the nature/strength of the LiCl-support interaction. Firstly, LiCl/Nd₂O₃-impregnated MoO/ZrO₂ and WOx/ZrO₂ were examined. Unlike SZ, these supports allowed for the tailoring of MoO[sub]x and WO[sub]x surface densities, which in turn drastically altered their ODHE performance. The poor stability of these supports, however, rendered them inferior to SZ. Secondly, the effects of dopant incorporation on the catalytic behavior of LiCI/MO,/SZ were studied. Si-doped ZrO₂-based catalysts synthesized via the sol-gel method were found to exhibit superior activity, selectivity and stability for ODHE. Sulfate decomposition experiments related the ODHE activity of these materials to the influence of the Si dopant on the sulfate binding strength. The sol-gel synthesis conditions were optimized with respect to sol pH, water:alkoxide ratio and silicon precursor, achieving improved catalyst homogeneity and enhanced ODHE performance ... / Within the petrochemical industry, a sizeable economic incentive exists for the upgrading of low-value, light alkanes. For instance, the dehydrogenation of ethane to ethene is of considerable interest due to ethene's use as a polymeric and chemical precursor. Partial oxidation provides an attractive alternative to standard pyrolysis methods for alkane-to-alkene conversion. Unlike pyrolysis, partial oxidative routes are largely unaffected by coke formation and have the added benefit of exothermicity. With the inclusion of oxygen as a reactant, however, numerous additional reaction pathways result. Among these, the presence of parallel and consecutive reaction channels to CO[sub]x products is of major concern. For this reason, previous efforts to create selective partial oxidation catalysts with high activity have typically fallen below economic feasibility requirements. This thesis focuses on the following alkane-to-alkene transformation reactions: Oxidative Coupling of Methane (OCM): 2CH₄ + O₂ <--> C₂H₄ + 2 H₂O Oxidative Dehydrogenation of Ethane (ODHE): C₂H₆ + 1/2 O₂ <--> C₂H₄ + H₂O Oxidative Dehydrogenation of Propane (ODHP): C₃H₈ + 1/2 O₂ <--> C₃H₆ + H₂O. Regarding OCM, an approach was presented for determining an upper bound on the yield of a catalytic process, which allowed for variations in the catalytic chemistry. Scaling and thermodynamic arguments were used to set parameters of an elementary step surface mechanism at values resulting in optimal yields, subjected only to physical constraints. Remaining unknowns were treated as independent variables and varied over a broad range. The result was a set of thermodynamically consistent mechanisms with optimal kinetics that could be incorporated into reactor-transport models. / by Yee San Su. / Ph.D.