Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1929. / Includes bibliographical references (leaves 65-66). / by Eugene C. Koo, Suresh C. Bose. / B.S.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Continuous manufacturing has gained significant interest in recent years as the ultra-lean mode of pharmaceutical production. Albeit the increasing number of studies on the process dynamics in continuous crystallization, in particular in yield improvement and impurity separation, the research community lacks the systematic understanding of the control of polymorphism in continuous crystallization. Variations in the polymorphism of the active pharmaceutical ingredient can undermine the bioavailability and the downstream processability of the drug substance. Thus, precise control of the drug polymorphism is pivotal for delivering quality drug products to the patients. In this thesis work, we aimed to develop a series of steps forward in understanding the polymorph dynamics in continuous crystallization, notably in mixed-suspension, mixed-product removal (MSMPR) crystallization. We first elucidated the major intrinsic and extrinsic factors which govern the process polymorphism in both monotropic and enantiotropic polymorphic compounds. Using the monotropic L-glutamic acid as the model compound, two temperature regimes each with distinctive kinetic and thermodynamic characteristics were identified. It is found that at high temperatures, the polymorph dynamics is mediated by the relative thermodynamics of the polymorphs. The most stable form is likely to be the dominant form at steady state. On the other hand, at low temperatures, the interplay of the crystal growth and nucleation kinetics is found to play an important role in determining the final polymorphism. Similar results were identified in the enantiotropic p-aminobenzoic acid system where three temperature regimes were identified. The additional regime is located near to the transition temperature where the chemical potential of the two polymorphs are identical. The steady state polymorphism is thereby determined by the kinetic energy barriers for the crystallization of the polymorphs. The study of polymorphism was also conducted in cooling-antisolvent crystallization and the effect of solvent composition on the polymorph dynamics was studied. In addition, the dynamic pathways connecting the startup states to the metastable steady states and the stable steady states were determined. The polymorphic transition between these steady states was observed and analyzed. The fundamental understanding of the kinetic competition and the governing dynamics in polymorphic crystallization forms the backbone for developing the polymorph control strategies in this thesis. Based on the polymorph dynamic studies, we designed MSMPR cascade systems to control the process polymorphism. In addition, systematic procedures are established to facilitate the design and optimization of continuous crystallization with the objectives to control polymorphism, optimize process yield and achieve the target crystal size distribution. The operational window is determined within which these control objectives are achieved. As there are increasing interests in transitioning pharmaceutical manufacturing from batch to continuous processing, the results in this thesis should develop a substantial position in the body of scientific literature. / by Tsai-Ta Christopher Lai. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1986. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 360-367. / by Kathleen Anne Dennison. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 89-93). / Bacterial biofilms consist of surface adherent bacteria that surround themselves with a polymer matrix which provides environmental protection and antibiotic resistance. Biofilms can grow on most implanted medical devices, on heart valves, and in the lungs of patients with cystic fibrosis, resulting in difficult to treat infections that can become blood-borne and spread throughout the body. They also pose problems in industry by growing in pipes, on membrane reactors and on ship hulls. Understanding the physical properties and dynamics of biofilms is therefore of interest as such insight may lead to methods for their disruption and removal. Biofilms have been characterized biochemically, as the general composition of the matrix is known, as are the specific polysaccharides forming the bulk of the matrix for some species. Insight into physical properties of biofilms, such as elasticity and deformability, has been limited to macroscale techniques that assess averaged values. These techniques do not provide details on the spatial gradients of physical properties within a biofilm nor do they allow for evaluation of properties over time. In addition, while some methods have been used to understand the adhesive forces of bacteria leading to biofilm formation, little effort has been put forth to understand how bacteria that are natively non-motile can reach a surface to which they adhere. Particle tracking is a technique in which probe particles are placed in a material and observed using microscopy. The observed trajectories can be analyzed in various ways, for example to determine physical properties and structure of the material they are embedded in. Trajectories can also be analyzed to better understand motion patterns of motile probes or to assess for diffusive behavior. In this work, particle tracking was used in different contexts to assess various biofilm systems. The overall goal was to gain an understanding of the structure, physical properties and dynamics of biofilms. We first developed a method by which we performed single particle tracking in biofilms with beads of varying surface functionalization. With a combination of single particle tracking and microrheological concepts, it was found that Escherichia coli biofilms display height dependent charge density that evolves over time. Statistical analyses of bead trajectories and confocal microscopy showed inter-connecting micron scale channels that penetrate throughout the biofilm, which may be important for nutrient transfer through the system. This methodology provides significant insight into a particular biofilm system and can be applied to many others to provide comparisons of biofilm structure. The elucidation of structure provides evidence for the permeability of biofilms to microscale objects, and the ability of a biofilm to mature and change properties over time. Second, we applied particle tracking to elucidate the motions of non-motile bacteria in the presence of a motile species. In static co-culture, Pseudomonas aeruginosa and Staphylococcus aureus formed multispecies biofilms at an air-liquid interface, while monocultures of S. aureus were not capable of forming a biofilm at the interfacial region. Based on these observations, we tested if P. aeruginosa could facilitate the transport of S. aureus to the air-liquid interface by a motility-based mechanism. Using a cell tracking method, we compared the motion behavior of S. aureus in the presence or absence of P. aeruginosa. Our data revealed a shift in S. aureus motility, which changed from random motion in monoculture to directed horizontal and vertical migration when cultured with P. aeruginosa. Additionally, we observed a similar behavior between P. aeruginosa / S. epidermidis and E. coli/S. aureus co-cultures. Our results suggest that non-motile bacteria perhaps leverage motility from other species to promote exploration of new ecological niches. We envision that this observed behavior perhaps has significant implications during the establishment and dissemination of polymicrobial infections in the host organism. By using multiple techniques to assess trajectories of either bead or bacteria probes, we were able to improve understanding of biofilm dynamics. The first technique can be applied to other biofilm systems, such as those formed by genetically modified bacteria, to promote a comparison of biofilm structure and properties. The second can allow for further assessment of interspecies interactions, perhaps to probe the specific mechanisms by which bacteria can attach to one another to improve motility. / by Alona Birjiniuk. / Ph. D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2016. / Cataloged from PDF version of thesis. Vita. / Includes bibliographical references. / The development of carbon efficient and economically viable biomass conversion technologies is crucial for the sustainable production of fuels and chemicals. Catalytic upgrading processes must remove oxygen and add hydrogen while targeting oxygen-containing functional groups. Catalysts must be water-tolerant, stable under hydrothermal conditions, and accessible for large organics. Zeolites are active and selective heterogeneous catalysts used in many industrial processes. Their microporous crystalline frameworks composed of tetrahedral silicate offer shape selectivity and high stability. Heteroatoms such as Sn or A1 can be incorporated into these frameworks to create isolated Lewis and Brønsted acid sites. This thesis uses synthesis, characterization, and reactivity studies to develop novel zeolite acid catalysts for upgrading biomass platform molecules. The first section focuses on designing hierarchical Brønsted acid zeolites to catalyze bulky molecules. A1-containing zeolite nanosheets of single-unit-cell thickness are synthesized using diquarternary ammonium surfactants. Characterization reveals high external surface area and mesoporosity and strong external acid sites. MFI nanosheets have higher stability and selectivity to larger olefins and aromatics in the conversion of propanal to hydrocarbons due to shorter diffusion path lengths compared to bulk MFI zeolite. MWW nanosheets have a three-fold increase in catalytic activity for the alkylation of benzene with benzyl alcohol compared to bulk MWW zeolite. Sn-containing MFI nanosheets are synthesized for the first time and are shown to have higher activity for the Baeyer-Villiger oxidation of bulky ketones than bulk Sn-MFI zeolite, and higher stability than mesoporous, amorphous Sn silicates. The second section focuses on studying and characterizing hydrophobic, water-tolerant Lewis acid zeolites. A detailed kinetics study compares transfer hydrogenation activity of Ti-, Sn-, Zr-, Hf-containing BEA zeolites with different hydrogen donors. A new characterization method using trimethylphosphine oxide probes and NMR is created to deduce structure-activity relationships. Finally, an integrated catalytic process is developed for the efficient production of [gamma]-valerolactone from furfural through sequential transfer hydrogenation and hydrolysis reactions catalyzed by a mixture of Brønsted acid zeolite nanosheets and hydrophobic Lewis acid zeolites. Overall, this thesis demonstrates that a detailed understanding of the structure and active sites in zeolite acid catalysts can allow us to design more efficient catalytic processes. / by Helen Yu Luo. / Ph. D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2017. / Cataloged from PDF version of thesis. / Includes bibliographical references. / The concept of self-powered wearable electronic system has been emerging. Such a system consists of three units: an intelligent end-user electronic device for exporting functions, an energy generation/conversion device responsible for harvesting/scavenging renewable energy, and additionally an energy storage device to ensure non-intermittent operation. The three units should be matched up in terms of energy and power, which demands substantial efforts in research for advancing all the components - the power consumptions of the electronics need to be reduced, the efficiencies of the energy scavenging devices ought to be improved, and the capacities of the energy storage devices are desired to be enhanced. An additional requirement is that the three units should all be made "human-friendly", namely lightweight, flexible and wearable. This necessitates the fabrication of all to be compatible with the unconventional substrates, such as papers and plastics. Along the way to these goals, tremendous opportunities and challenges with regards to materials and device designs are present. This thesis focuses on the development of mechanically flexible thin-film materials for electrochemical devices, towards the achievement of self-powered wearable electronic systems. Initiated chemical vapor deposition (iCVD) and oxidative chemical vapor deposition (oCVD), which are non-destructive to fragile substrates, have been employed for the synthesis of the polymeric thin films. As an effort to enhance the functional end-users, pinhole-free ionic liquid gels with thickness down to 20 nm have been prepared for the first time via iCVD. They show great promise as soft gate insulators for low-power high-speed thin film transistors, which are central to a variety of wearable electronics. To improve the energy storage unit, supercapacitors, a promising energy storage device for low-power devices, have been vapor-printed via oCVD onto flexible low-cost substrates, papers and nylon membranes. Additionally, an ultrathin gel electrolyte coating has been developed to boost the performance stability of polymeric capacitive materials. / by Andong Liu. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995. / Includes bibliographical references (leaves 214-228). / by Gautam Nayar. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, February 2018. / Cataloged from PDF version of thesis. "February 2017." Handwritten on title page "February 2018." / Includes bibliographical references. / It is both uncontroversial and unassailable to assert that small things can often go where big things cannot. It is similarly prosaic to note that at smaller length scales, matter behaves differently than at larger length scales. This thesis exploits these intuitive and simple axioms to yield advances in three independent lines of enquiry: (i) robust and practically accessible encoding of information within microparticles, (ii) rapid, quantitative sensing of hydrophobic colloids and (iii) immunologically-focused drug delivery. Specifically, upconversion nanocrystals are used as the foundation of a novel spatial-spectral patterning motif to produce polymer microparticles with unique, decodable identities. With large single-particle encoding capacities (>10-⁶), an ultralow decoding false alarm rate (<10-⁹), and pronounced insensitivity to both particle chemistry and harsh processing conditions, this architecture enables practical deployment of encoded microparticles in applications with orthogonal requirements, including multiplexed bioassays and covert labeling of objects and packaging for anti-counterfeiting. Next, the large specific surface area of nanoscale objects is exploited by a family of zwitterionic, surfactant-like molecular rotors to develop a broadly applicable tool for sensitive, quantitative, and accessible nanoscale metrology. This tool is shown to address multiple challenges in nanometrology of self-assembled structures, including (i) quantification of surfactant adsorption isotherms on metal oxide surfaces, (ii) determination of self-assembly onset concentration, and (iii) high-throughput readout of drug delivery nanoparticle mass concentration. Finally, the combination of small size and large interfacial area was exploited to design nanoscale formulations for (i) ex vivo delivery to human neutrophils, a significant element of the innate immune system and (ii) targeted delivery of therapeutics to the asthmatic lung. / by Paul W. Bisso. / Ph. D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references (p. 262-274). / Islet transplantation has become a promising treatment for type I diabetes mellitus due to recent success since the development of the Edmonton Protocol. Islet culture prior to transplantation is standard practice in most clinical islet programs. Conventional culture conducted on polystyrene vessels can impose oxygen limitations even at relatively low tissue surface densities. High density islet culture is desirable because it reduces space and handling requirements during culture, but it exacerbates oxygen (02) limitations, causing a reduction in islet viability. The overall objective of this thesis was to maintain islet quality during static culture. As a chemical engineer, I focused on addressing transport limitations present in conventional culture techniques. After demonstrating culture in the absence of 02 transport limitations resulted in nearly 100% recovery of the original viable tissue placed into culture when the combined non-adherent and adherent tissue were considered, I examined the effect of tissue surface density on the recovery of islet tissue, its viability, and its purity for conventional normoxic culture on a polystyrene dish. With conventional culture, the fractional recovery of viable tissue decreased sharply as viable tissue density increased. / (cont.) To improve islet quality in high density culture, I investigated use of elevated ambient 02, reduced culture temperature, and culture on an oxygen-permeable silicone rubber membrane. By applying a theoretical 02 transport model, I investigated how 02 transport changes for each culture condition and compared predictions to the experimental data to determine whether 02 is limiting during high density culture using these new techniques. At high tissue surface densities, the fractional recovery of viable tissue was higher with culture on polystyrene in elevated (56%) 02 or culture at reduced temperature (24'C), and even higher with normoxic culture on a silicone rubber membrane. Theoretical predictions based on 02 transport were qualitatively similar to experimental results but in general overpredicted the amount of viable tissue recovered. Additional theoretical calculations indicated simplifications made when modeling oxygen along with glucose and pH changes during culture could account for the slight overprediction. In conclusion, in high density culture, recovery of viable tissue (1) decreases as culture density increases on a polystyrene surface; (2) increases with increasing external 02; and (3) increases substantially with culture on silicone rubber by removing 02 limitations. / (cont.) The techniques examined significantly improve tissue oxygenation compared to conventional culture, and allow tissue to be cultured at higher densities without a reduction in viability. These methods can be easily implemented, which would enable clinical centers to reduce space and handling requirements during culture prior to transplantation without the reduction in islet viability that can occur with conventional methods, and thereby maximize the use of limited islet resources. / by Michael James Rappel. / Ph.D.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1936. / MIT copy bound with: Hysteresis of nitrocellulos films / by Thomas Alexander Terry, Jr. [1936] / Includes bibliographical references (leaf 18). / by Jean Irwin Wagner. / B.S.