Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 82-83). / The operational parameters of the automated Spray-LbL technique for thin film deposition have been investigated in order to-identify their effects on film thickness and roughness. We use the automated Spray-LbL system developed at MIT by the Hammond lab to build 25 bilayer films of poly (ally amine hydrochloride) (PAH) and poly (acrylic acid) (PAA). Each of the 10 operational parameters of this system are explored individually to isolate each parameter's effect on film thickness and roughness. The parameter effects are analyzed for apparent trends to determine the parameters best suited for adjusting film thickness and roughness. The optimal parameters for thickness adjustment are polyelectrolyte solution concentration, polyelectrolyte spray time, spraying distance, air pressure and polyelectrolyte charge density. These parameters are independent of the type of species used to construct the film, and thus the trends should apply to any species used to construct thin films. The effect of each of the 10 operational parameters is examined in detail. While researching the parameter effects, polyelectrolyte interdiffusion in the films was observed. This interdiffusion is investigated using both the conventional dipped LbL and Spray-LbL deposition techniques. Interdiffusion is shown to be dependent on 3 factors, the charge density of the polyelectrolytes, the molecular weight of the polyelectrolytes, and the contact time between the polyelectrolyte solutions and the surface of the film. Interdiffusion is observed when the PAH is partially charged, the polyelectrolytes chains have a low molecular weight, and the contact time is sufficiently long enough to allow for interdiffusion. The significantly reduced contact time during the automated Spray-LbL process not only speeds up the film deposition time, but also significantly hinders the interdiffusion of PAH resulting in much thinner films than what is possible from dipping. Finally, the uniformity of the films produced using the automated Spray-LbL system is investigated. Films deposited on substrates greater than 1 in diameter area exhibit more than 20% variance in thickness. Adjustments were made to the setup of the system in an effort to expand this area of film thickness uniformity. However, it is determined that the design of this automated Spray-LbL system limits the film uniformity to an area of 1 in diameter. / by James Hart Gifford. / S.M.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 189-203). / The heterogeneous molecular interactions that operate at material interfaces control the efficiency of chemical engineering processes as diverse as adsorption, emulsification, heat exchange, and froth flotation. In particular, the process of colloidal self-assembly harnesses the rich tapestry of interactions that operate at several length scales, including van der Waals and electrostatic interactions, the hydrophobic effect, and entropic considerations, to drive the autonomous aggregation of simple building blocks into intricate architectures. This bottom-up approach has increasingly become the mainstay of the colloids community in its quest to design and fabricate increasingly complex soft-matter assemblies for pharmaceutical, catalytic, optical, or environmental applications. Accurately modeling and manipulating interfacial interactions across many different length scales is vital to optimizing the self-assembly and stability of colloidal suspensions. With the above background in mind, in this thesis, I illustrate the modeling of interfacial phenomena at a range of length scales, with a particular focus on utilizing a combination of computer simulations and molecular-thermodynamic theories to evaluate the free energies associated with the formation and reconfiguration of revolutionary colloidal systems, including dynamically-responsive colloids and two-dimensional nanomaterial suspensions. First, I examine the interplay between interfacial tensions during the one-step fabrication, and stimuli-responsive dynamic reconfiguration, of three-phase and four-phase complex emulsions. This fabrication makes use of the temperature-sensitive miscibility of hydrocarbon, silicone, and fluorocarbon liquids and is applied to both microfluidic and scalable batch production of complex droplets. I demonstrate that droplet geometries can be alternated between encapsulated and Janus configurations by judicious variations in interfacial tensions, as controlled via conventional hydrocarbon and fluorinated surfactants, as well as by stimuli-responsive and cleavable surfactants. Subsequently, I examine the molecular origins of the ability of surfactants to modulate the interfacial tensions at fluid-fluid interfaces, including developing a computer simulation-aided molecular- thermodynamic framework to predict the adsorption isotherms of non-ionic surfactants at the air-water interface. The use of computer simulations to evaluate free-energy changes is implemented to model a surfactant molecule possessing tumor-selective cytotoxicity. Utilizing potential of mean force calculations, I shed light on the preference of this anti-cancer drug for certain types of lipid bilayers, including advancing a hypothesis for the mechanism through which this drug induces apoptosis. I then utilize potential of mean force calculations to evaluate the formation of colloidal suspensions of two novel two-dimensional materials: phosphorene and molybdenum disulfide (MoS2). I focus on the correlations between the structural features of commonly-used solvents and: (1) their ability to intercalate between nanomaterial sheets and induce exfoliation, and (2) their effect on the energy barrier hindering the aggregation of the phosphorene and MoS2 sheets. The combination of simulation-based computation of the potential of mean force (PMF) between pairs of nanomaterial sheets, as well as the application of theories of colloid aggregation, offers a detailed picture of the mechanics underlying the liquid-phase exfoliation and the subsequent colloidal stability of phosphorene and MOS2 sheets in the commonly-used solvents considered. The agreement between the predicted and the experimentally-observed solvent efficacies provides a molecular context to rationalize the currently prevailing solubility-parameter-based theories, and for deriving design principles to identify effective nanomaterial exfoliation media. / by Vishnu Sresht. / Ph. D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1993. / Includes bibliographical references (leaves [193]-201). / by Jerry Christopher Meyer. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013. / 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. 133-151). / Cell-to-cell variability in clonal populations is reflected in a distribution of mRNA and protein levels among individual cells, including those of key transcription factors governing embryonic stem cell (ESC) pluripotency and differentiation. This may be a source of heterogeneity resulting in mixtures of cell types in differentiated populations despite efforts to control the differentiation conditions and the use of a clonal starting population. In addition, this distribution may be affected by the cell microenvironment during self-renewal. Prior studies on self-renewal culture of ESC, however, focused on long term proliferation and pluripotency. The effects of culture conditions during self-renewal on the effectiveness of subsequent differentiation protocols remains understudied. Using a mouse ESC line harboring a GFP reporter, we examined cell-to-cell variability in clonal undifferentiated populations and how such variability affects subsequent differentiation. Subpopulations sorted according to their levels of Oct4-GFP expression displayed distinctly different expression levels of pluripotency and early differentiation markers and differentiated into cardiomyocytes at different efficiencies. However, when allowed to self-renew after sorting, the subpopulations regenerated the parental distributions of Oct4-GFP and subsequent differentiation after regeneration did not show differences. In addition to differences between cells in a clonal population, self-renewal conditions affecting Oct4 expression on the population-level were examined. Changes in culture conditions during self-renewal by low oxygen culture or small molecule dual inhibition (2i) of mitogen-activated protein kinase and glycogen synthase kinase reversibly affected levels of Oct4 expression in cells that were otherwise pluripotent. Effects of different self-renewal conditions immediately preceding differentiation are manifested by changes in subsequent differentiation to cardiomyocytes. This study demonstrates that manipulation of self-renewal culture conditions can lead to changes in the outcomes of defined differentiation protocols, a novel dimension to explore for directed differentiation of pluripotent stem cells. / by Jit Hin Tan. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1999. / Includes bibliographical references. / While the synthesis of continuous processes has been advanced to significant levels of effectiveness, through pure or hybrid implementations of rigorous optimization-based and heuristic approaches, corresponding progress in the synthesis of batch processing schemes has been lagging behind. Most of the research in the batch area has focused on the design of multipurpose or dedicated batch plants, and the optimal planning and scheduling of batch operations in multipurpose plant configurations. Unlike a continuous plant, which is composed of a well-defined network of (mostly) sing!e-function unit operations, a batch process is deployed through a series of batch-operating vessels, which accommodate varying sets of physico-chemical transformations of processing materials. As a result, while the synthesis of a continuous plant leads to a structured flow sheet of unit operations, the synthesis of a batch processing scheme leads to a structured sequence of operating steps. Consequently, we have approached the synthesis of batch processing schemes as a problem of synthesis of operating procedures. Such an operations-centered synthesis decouples the selection of equipment and allows efficient solution of a rather cumbersome combinatorial optimization problem, while allowing the synthesis of novel processes through the grouping of varying sets of operations in the same equipment. The methodology we have developed for selecting and ordering the operations to be performed is based on a combination of Means-Ends Analysis (MEA) and NonMonotonic Planning (NMP). This approach uses means-ends analysis to detect differences between the current process state and the desired product state. When a difference is detected, we apply a non-monotonic planning methodology, which incorporates a combination of heuristic and quantitative methods to construct a plan consisting of operations capable of resolving the difference. The first step is to determine a set of feasible operations that will eliminate the difference. This set of operations is known a,;; the Task Category. The operations are grouped into Task Categories based on the attributes of the tasks they perform. These Task Categories allow us to narrow the number of alternatives that need to be examined. From within the Task Category, a single operation is chosen to be incorporated into the design while all other operations in the set are retained as possible alternatives. In order to determine the applicability of the operation, the preconditions of the operation are assessed against the current process state. If any of the preconditions is violated, operations called "White Knights" are selected and applied before the current operation to alter the current state and remove the precondition violation. The elimination of the precondition violations through the nonmonotonic planning routine leads to a feasible ordering of operational steps which describe aspects of the evolving processing scheme. After all the precondition violations have been removed, the sequence of operations that has been generated is applied and a new current process state is generated. The Means-Ends Analysis with Nonmonotonic Planning (MEA-NMP) methodology is iteratively applied to resolve remaining differences between the new current states and the final product state. The MEA-NMP approach provides us with base case design, as well as, the search space of feasible alternatives by linking the Task Categories together to form the process superstructure. Since the alternatives have been maintained through the identification of the Task Categories, the problem can be formulated as a MINLP and a common MINLP solution strategy can be applied to determine the optimal design. This thesis describes both the MEA-NMP strategy, as well as, its methodological details. We will discuss how the combinatorial optimization problem, defining the synthesis of batch processing schemes, is decomposed into (a) a logic-based component, defining the feasible processing alternatives, and implemented through c:he MEA-NMP strategy, and (b) a reduced MINLP formulation whose solution identifies the optimal processing scheme. In addition, we will discuss the detailed mathematical formulation of the batch process synthesis problem using the finite automaton and the State Task Network, the models employed for the representation of Tasks, the logic that guides the selection of White Knights, and the metrics used for the evaluation of processing alternatives. In the thesis we also outline the computer-aided elements which implement the above ideas within the framework of the BatchDesign-Kit, and will illustrate the application for the MEA-NMP strategy on realistic case studies pertaining to the synthesis of processing schemes for the manufacturing of pharmaceuticals. Finally, we discuss the conclusions and contributions attributed to this work and possible directions for future research that have been brought to our attention during the development of this thesis. / by Shahin A. Ali. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1993. / Includes bibliographical references (p. 207-213). / by Joanne Liu. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013. / Title as it appears in MIT Commencement Exercises program, June 2013: Generation of phenotypic diversity in yeast using promoter inversion through Cre-lox recombination. Page 84 blank. Cataloged from PDF version of thesis. / Includes bibliographical references. / Modifying the expression of multiple genes enables both deeper understanding of their function and the engineering of complex multigenic cellular phenotypes. However, deletion or overexpression of multiple genes is typically laborious and involves multiple sequential genetic modifications. Here we describe a strategy to randomize the expression state of multiple genes in S. cerevisiae using Cre-loxP recombination. By inserting promoters flanked by inverted loxP sites in front of a gene of interest we can randomly alter its expression by turning it OFF or ON, or between 4 distinct expression states. We show at least 6 genes can be randomized independently and argue that using orthogonal loxP sites and an additional recombinase should increase this number to at least 30. Finally, we show how combining this strategy with mating allows easy introduction of native regulation as an additional expression state and use this to probe the role of 4 different enzymes involved in base excision repair in tolerance to methyl methane sulfonate (MMS), a genotoxic DNA alkylating agent. The set of vectors developed here can be used to randomize the expression of both heterologous genes and endogenous genes, and could immediately prove useful for metabolic engineering in yeast. Because Cre-loxP recombination works in many organisms, this strategy should be readily extendable. / by Bradley Niesner. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 79-85). / Flow chemistry is becoming an accepted method of continuous synthesis with its considerable advantages over batch chemistry, such as smaller infrastructure, faster production, and safer operation for aggressive reactions or extreme conditions. However, to realize the full benefits of flow chemistry in multi-step reactions, continuous work-up techniques are needed. They will eliminate intermediate batch work-up steps that are often inefficient and time-consuming. This thesis describes the development of continuous liquid-liquid extraction and evaporation techniques along with their integration in multistep reaction sequences and purification on the mL/min scale. Fully-integrated syntheses for active pharmaceutical ingredients (APIs), lidocaine and fluoxetine, were studied in detail. These two examples represent two different strategies for integrating multistep reactions. Sequential reactive steps in the lidocaine synthesis were designed to be compatible without any separation, while in-line purification, liquid-liquid extraction, was required for the fluoxetine synthesis. The key outcome of this work was the construction of a compact, reconfigurable system for manufacturing four different APIs, at throughput of hundreds to thousands dosages per day. The system represents a significant advance in continuous manufacturing by demonstrating feasibility of facility decentralization and on-demand production. Another significant accomplishment of this thesis is the development of multistage liquid-liquid extraction using liquid-liquid membrane-based separators that enable highly efficient continuous extraction. While previous efforts have demonstrated a single stage or, at most, a few stages in crosscurrent configuration, the objective was to build a countercurrent extraction setup in the context of laboratory scale (i.e. mL/min). The setup was made possible with an integrated pressure control element, allowing non-precise interstage pumping to be employed. This setup was found effective for a wide range of industrially-relevant applications, from multicomponent solvent recovery to in-line removal of phase transfer catalysts. The thesis provides opportunities for future directions. For example, improvement in unit operations, such as pumping, solid handling, evaporation, and process control, will be needed to reach the potential of flow synthesis. The countercurrent extraction setup can be automated for faster screening and optimization of extraction conditions as well as be applied to complex processes, such as reactive extraction and enantioseparation. / by Nopphon Weeranoppanant. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1988. / Includes bibliographical references. / by Frank T. Gentile. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005. / Includes bibliographical references. / With the rapid advances in kinetic modeling, building elementary surface mechanisms have become vital to understand the complex chemistry for catalytic partial oxidation systems. Given that there is selected experimental knowledge on surface species and a large number of unknown thermochemical, rate parameters, the challenge is to integrate the knowledge to identify all the important species and accurately estimate the parameters to build a detailed surface mechanism. This thesis presents computational methodology for quickly calculating thermodynamically consistent temperature/coverage-dependent heats of formation, heat capacities and entropies, correction approach for improving accuracy in heats of formation predicted by composite G3- based quantum chemistry methods, and detailed surface mechanism for explaining selectivity in ethylene epoxidation. Basis of the computational methodology is the Unity Bond Index- Quadratic Exponential Potential (UBI-QEP) approach, which applies quadratic exponential potential to model interaction energies between atoms and additive pairwise energies to compute total energy of an adsorbed molecule. By minimizing the total energy subject to bond order constraint, formulas for chemisorption enthalpies have been derived for surface species bound to on-top, hollow and bridge coordination sites with symmetric, asymmetric and chelating coordination structures on transition metal catalysts. The UBI-QEP theory for diatomics has been extended for polyatomic adsorbates with empirical modifications to the theory. / (cont.) Formulas for activation energies have been derived for generic reaction types, including simple adsorption, dissociation-recombination, and disproportionation reactions. Basis of the correction approach is the Bond Additivity Correction (BAC) procedures, which apply atomic, molecular and bond- wise modifications to enthalpies of molecules predicted by G3B3 and G3MP2B3 composite quantum chemistry methods available in Gaussian® suite of programs. The new procedures have improved the accuracy of thermochemical properties for open and closed shell molecules containing various chemical moieties, multireference configurations, isomers and degrees of saturation involving elements from first 3 rows of the periodic table. The detailed mechanism explains the selectivity to ethylene oxide based on the parallel branching reactions of surface oxametallacycle to epoxide and acetaldehyde. Using Decomposition Tree Approach, surface reactions and species have been generated to develop a comprehensive mechanism for epoxidation. As a result of these developments in the thesis, chemisorption enthalpies can now be estimated within 3 kcal/mol of experimental values for transition metal catalysts and enthalpies predicted by G3B3 and G3MP2B3 Gaussian methods can be corrected within 0.5 kcal/mol. Examples of heterogeneous reaction systems involving silver-catalyzed ethylene epoxidation demonstrate the effectiveness of the methodologies developed in this work. / by Bharthwaj Anantharaman. / Ph.D.