Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references. / In current tablet manufacturing processes, there is a knowledge gap concerning material transformation and the subsequent impact on tablet properties; this gap presents a barrier to rational formulation / process design. In this study, it was hypothesized that the understanding of tablet microstructure is pivotal in bridging our knowledge about the materials, the manufacturing process, and the tablet properties. A series of X-ray micro computed tomography (microCT) characterization methods were developed to untangle material interactions during tablet manufacturing process, leading to an interpretation of tablet compaction mechanisms through 3-D representation of microstructural features. Numerical simulation of liquid intrusion based on microCT data was utilized in calculating tablet microstructure permeability, introducing a novel parameter for characterization of tablet dissolution properties. A tablet holder was designed and used in combination with paddle dissolution test to investigate tablet dissolution process, enabling the classification of dissolution mechanisms and identification of correspondent formulation design strategies. When incorporated with permeability results, a quantitative dissolution model capable of separating the contributions from disintegration and surface dissolution was derived. The dissection of the dissolution process provides a scientific framework supporting the Quality by Design paradigm for product and process development. . This work provides a strategy for building an integrated formulation design and characterization system incorporating microstructural analysis. It opens up an approach in which microstructure becomes a critical target for design and optimization. / by Kangyi Mao. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 205-209). / Technology selection is a complex decision problem that is often faced in process engineering. This has been a particularly important problem recently in the energy field, in which many new technologies have been proposed. Typically only point estimates of the chosen metrics are used in the evaluation, with uncertainty often overlooked. However, uncertainty can have a significant effect on the conclusions and decisions to be made. This work investigates the issues surrounding the uncertainty in process engineering models. Model complexity, selection bias and information gain are examined. Existing model selection methods, including Information Criteria Methods and Hypothesis Testing are analyzed, with an emphasis on how they address issues surrounding uncertainty in models. Bayes' methods are investigated in detail because they offer a mathematically sound and very flexible alternative to traditional techniques. A framework is proposed for evaluating the information difference between competing process engineering models involving uncertainties. This framework can be applied when there are competing processes (e.g. a technology selection problem) or when there are competing models for the one process (e.g. several models of the one process with different levels of complexity). The framework uses the Deterministically Equivalent Modeling Method (DEMM) and Bayes' model selection methods and consequently can be applied to black box models. The methods chosen allow assumptions required in other methods to be relaxed, while keeping computation time minimal. In particular, assumptions about output distributions are relaxed, which is important in process engineering models because equilibrium and theoretical limits can cause output distributions to be highly irregular. A major challenge has been applying Bayes' model selection methods to cases where experimental output data does not exist, which occurs when assessing new technologies. Modifications to existing model selection have been developed to address these cases. Applying this framework will give the information difference between models, and identify which parameters are driving the overall. These results can be used in a sequential decision making process, facilitating decisions over the best use of resources. This may include helping to shape experimental programs or further refinement of the models. The framework has been applied to three case studies. The first involves competing hydrogen producing thermochemical cycles. It was found that the best use of resources was to further investigate the separations involved, rather than the reactions. The second involved two versions of a refinery process. The overall uncertainty was driven by uncertainty in the fitted parameters, and consequently if a difference is to be observed then the uncertainty in these fitted parameters need to be reduced. The third case study involved competing technologies for warm syngas cleanup. The excel-based tool has been constructed so that this framework can be applied by others in the future. This tool calls Matlab to complete the required calculations, but only requires the user to enter the required inputs in Excel, making it easy for the user. / by Ingrid Berkelmans. / Ph.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1962. / Vita. Appendix contains numerous pamphlets. / Includes bibliographical references (leaves 274-277). / by Wayne D. Erickson. / Sc.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008. / Includes bibliographical references. / Line edge roughness (LER) on the sidewalls of gate electrodes in metal oxide semiconductor transistors is one of the most important issues in the manufacturing of modem integrated circuits (IC). The significance of LER increases tremendously as desired features miniaturize because the dimensions of the edge roughness become comparable to those of the features. A fundamental understanding of the origins of the surface roughness and LER formation during plasma etching process is thus necessary to optimize the IC manufacturing process and prevent device failure. To meet this challenge, a 3-D Monte Carlo simulator was developed to model the roughening of a surface as well as follow the macroscopic evolution of its profile during plasma etching. The simulator employs a cellular representation of the surface with Monte Carlo modeling of the mass transport and reaction kinetics. The local geometric properties of surface features were computed by fitting to a polynomial surface, which allowed for a more accurate description of the surface normal and local curvature. This numerical algorithm for simulating etching and deposition was validated by comparing with the theoretical advancement of a surface for the case of isotropic and anisotropic etching. The simulator was used to explore surface roughening during the physical sputtering of a blanket silicon surface by argon ion bombardment. The results showed that there is a significant change in its morphology with different off-normal angles of incidence. When the surface is etched at normal incidence, the surface becomes roughened with no preferred orientation. When etched with an off-normal ion incidence below 500, the surface develops ripples that are oriented perpendicular to the ion beam direction. For off-normal angles between 500 and 600, the surface remains smooth independent of the etch time. / (cont.) The surface is again roughened for angles of incidence above 600, forming patterns that are aligned with the ion beam direction. These trends match qualitatively with those observed in experimental measurements. The simulation results further showed that these transitions of surface morphology with increasing off-normal angles of ion incidence are related to the angular dependence of the etching yield. The effects of other factors, including the angular distribution of scattered ions, the non-uniformity of the film density, the initial roughness of the surface and the re-deposition of sputtered materials were also investigated using our simulator. The roughening of the sidewalls of patterned polysilicon etched with Cl2 was also explored via simulation. The simulation results showed that the primary cause of sidewall roughness is due to the transfer of roughness on the photoresist and anti-reflective coating (ARC) sidewall to the underlying polysilicon sidewall during etching. The root-mean-square (RMS) roughness of the sidewalls due to the features that result from the etching is highest at the photoresist layer and decreases with depth. This trend is consistent with experimental observations. The simulation also showed that the re-deposition of sputtered photoresist particles onto the sidewalls during etching enhances sidewall roughening. / by Hiroyo Kawai. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Magnetic particles have been used for many applications demanding a broad range of particles morphologies and chemistries. Superparamagnetism is advantageous over ferromagnetism because it enables us to control and recover magnetic nanoparticles during and after chemical processing. Superparamagnetic particles have an oriented magnetic moment under a magnetic field but lose this behavior in the absence of a field. Ferromagnetic materials can be superparamagnetic when they consist of a single size domain, which is on the order of 10s of nanometers. However, since the magnetic force is proportional to the volume of the particle, one needs to apply higher gradient of magnetic field to recover smaller particles. Therefore, large particles are preferred for easy manipulation using external forces. For this reason, the synthesis of large, superparamagnetic particles is very important and is desirable for future applications. The purpose of this work is (1) to examine the three synthesis methods of superparamagnetic units, (2) to understand the behavior of particles created using these methods as well as the synthesis mechanisms, and (3) to investigate the potential applications of these particles. Large paramagnetic particles can be made by assembling superparamagnetic nanoparticles. We developed a method for the process-dependent clustering of monodisperse magnetic nanoparticles using a solvent evaporation method from solid-in-oilin- water (S/O/W) type emulsions. When polymers that are incompatible with the nanoparticle coatings were included in the emulsion formulation, monolayer- and multilayer-coated polymer beads and partially coated Janus beads were prepared. The precise number of nanoparticle layers depended on the polymer/magnetic nanoparticle ratio in the oil droplet phase parent emulsion. The magnetic nanoparticle superstructures responded to the application of a modest magnetic field by forming regular chains with alignment of nonuniform structures (e.g., toroids and Janus beads) in accordance with theoretical predictions and with observations in other systems. In addition, we synthesized non-spherical magnetic microparticles with multiple functionalities, shapes and chemistries. Particle synthesis is performed in two steps; polymeric microparticles homogenously functionalized with carboxyl groups were generated AA % using stop-flow lithography, and then in situ co-precipitation was used to grow magnetic nanoparticle at these carboxyl sites. With successive growth of magnetic nanoparticles, we obtained polymeric particles with saturations magnetization up to 42 emu per gram of microparticle, which is significantly greater than what can be obtained commercially. We also investigated the physical properties of magnetic nanoparticles grown in polymeric microparticles, and provide an explanation of the properties. Lastly, we used experimentation and modeling to investigate the synthesis of opaque microparticles made via stop-flow lithography. Opaque magnetic beads incorporated into hydrogel microparticles during synthesis changed the height and the degree of cross-linking of the polymer matrices formed. The effect of the concentration of the opaque material on the particle height was determined experimentally, and agreed well with model predictions based on the photopolymerization process over a wide range of UV absorbance. We also created particles with two independent anisotropies, magnetic and geometric, by applying magnetic fields during particle synthesis. Our work provides a platform for rational design of lithographic patterned opaque particles and also a new class of structured magnetic microparticles. Overall, this work demonstrates three strategies for creating magnetic substrates containing superparamagnetic nanoparticles and characterization of their resulting properties. / by Su Kyung Suh. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2013. / "June 2016." Cataloged from PDF version of thesis. / Includes bibliographical references (p. 158-165). / Intracellular delivery of material is a long-standing challenge for both therapeutic and research applications. Existing technologies rely on a variety of mechanisms to facilitate delivery. Vector-based methods, such as polymeric nanoparticles and liposomes, form complexes with the target material and subsequently facilitate its uptake by the cell of interest, often through endocytosis. Although effective in some applications, these methods have had difficulty translating to patient-derived primary cells, especially stem cells and immune cells. Moreover, these vectors are often limited in the range of target materials they can deliver and leave much material trapped in endocytotic vesicles. Physical methods, such as electroporation and sonoporation, have been able to address some of the challenges with vector-based methods by providing a platform for physical disruption of the cell membrane. By eliminating the need for vector materials and circumventing the endocytotic pathway, these methods have shown an advantage in some applications, especially those involving primary cells that are recalcitrant to vector-based methods. However, both electroporation and sonoporation suffer from high cell toxicity and have had limited success in delivering materials such as proteins and nanomaterials. Electroporation in particular has been shown to damage certain target materials, such as quantum dots. Microinjection, an alternative method in which cells are punctured by a microneedle, can address a variety of target materials and cell types however its low throughput has hindered its adoption for most applications. There is thus a need for more effective intracellular delivery methods. This dissertation describes a microfluidic approach to intracellular delivery that seeks to embody the advantages of a physical method, while mitigating issues related to toxicity and damage to the target material. In our method, the cells of interest are prepared in suspension with the target delivery material and flown through a parallel network of microfluidic channels. Each channel contains a constriction point where the cells are rapidly deformed, or squeezed, as they pass through. This process induces temporary disruption of the cell membrane thereby enabling diffusive transport of material from the surrounding buffer into the cell cytosol. These disruptions persist for less than 5min before membrane integrity is fully restored. This method has thus far been demonstrated in over 15 cell types and has been able to deliver a variety of functional materials including, DNA, RNA, proteins, quantum dots, carbon nanotubes, and small molecules. Our cell squeezing technology has further illustrated its enabling potential in a number of applications detailed herein. Quantum dots are a promising alternative to organic fluorescent dyes due to their superior spectral properties and stability. These nanoparticles have much potential as imaging agents in vitro and in vivo. Delivery of undamaged quantum dots to the cell cytoplasm has been a challenge with existing techniques. Vector-based methods have resulted in aggregation and endosomal sequestration of quantum dots while electroporation can damage the semi-conducting particles and aggregate delivered dots in the cytosol. In our work, we demonstrated efficient cytosolic delivery of quantum dots without inducing aggregation, trapping material in endosomes, or significant loss of cell viability. Moreover, we have shown that individual quantum dots delivered by this approach are detectable in the cell cytosol, thus illustrating the potential of this technique for single molecule tracking studies. These results indicate that our method could potentially be implemented as a robust platform for quantum dot based imaging in a variety of applications. The reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has much potential in its ability to address existing challenges in regenerative medicine by providing a patient-specific source of pluripotent stem cells to generate new tissue. The mechanism of this reprogramming process, however, is still poorly understood and existing technologies suffer from chronically low reprogramming efficiencies (<4%). Moreover, many existing approaches to reprogramming rely on viral vectors to facilitate the delivery of the target transcription factors - these vectors are considered inappropriate for clinical applications due to safety concerns. Cytosolic delivery of protein transcription factors is a possible alternative to viral and plasmidbased reprogramming techniques. Direct protein delivery would negate the current safety concerns with viral and plasmid-based methods as it could not cause potentially tumorigenic changes in the genome. In our work, we implemented the cell squeezing technology as a method to deliver protein transcription factors to the cytosol of primary human fibroblasts. These studies yielded colonies of pluripotent stem cells that appeared to be fully functional. Moreover, the efficiency of this procedure was 10-100x higher than the current state-of-the-art protein reprogramming methods. The versatility of our delivery technology thus provides a promising platform for further study of the reprogramming process and the development of more efficient, clinically applicable, reprogramming procedures. Finally, the technology described herein has been implemented in cancer vaccine applications. Some recent immunotherapies against cancer have focused on the use of dendritic cells as antigen presenting cells. These cells are capable of presenting cancer antigens to other immune cell subsets and prompting a powerful immune response against the target cell type. A significant challenge for these therapies, however, is that current methods to induce antigen presentation in dendritic cells are often inefficient and can potentially induce a parallel regulatory response that reduces treatment efficacy. In our work, we have implemented the device as a platform for direct cytosolic delivery of the target antigen to dendritic cells. This approach could enable effective presentation of the target antigen while minimizing the development of a regulatory response. Our results indicate that this approach can produce effective antigen presentation in vitro, as measured by CD8 T cell coculture assays. Moreover, we have demonstrated effective antigen presentation in B cells, a more desirable clinical alternative to dendritic cells. These results thus illustrate the potential of this technology to be implemented as an enabling, patient-specific vaccination platform with minimal side-effects. In summary, we have developed a robust, high-throughput approach to intracellular delivery. In the described technique, cytosolic delivery is facilitated by the temporary disruption of the cell membrane in response to rapid mechanical deformation of the cell in a microfluidic channel. This technology seeks to addresses some of the challenges of existing vector-based and physical poration methods, such as endocytosis, translation to primary cells, and cell toxicity. Our results in quantum dot, cell reprogramming, and cancer vaccine applications illustrate the strengths of this system. Although in its infancy, this technology has demonstrated the potential to enable a range of clinical and research applications. In the future, better understanding of the underlying mechanism and improvements to the system could produce substantial gains in performance and allow this technique to be widely adopted by researchers and clinicians. / by Armon R. Sharei. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2014. / Cataloged from PDF version of thesis. / Includes bibliographical references. / Biofouling, the undesirable settlement and growth of organisms, occurs immediately when a clean surface is immersed in natural seawater. It is a universal problem and the bottleneck for seawater desalination, which reduces both the yield and the quality of desalted water. Mitigation of fouling in a desalination operation is an on-going challenge due to the delicate nature of desalination membranes, the vast diversity of fouling organisms, and the additional cross-membrane transport resistance exerted by an extra layer of coating. This thesis focuses on benign interface engineering methods and ultra-thin zwitterionic coating synthesis to bridge this gap in surface modification strategies. The direct application of ultra-thin coatings on commercial membranes with intact membrane performance has been enabled by a room-temperature vapor treatment called initiated chemical vapor deposition (iCVD). Diffusion-limited reaction conditions have shown to significantly improve the surface concentration of the antifouling zwitterionic moieties, which is crucial to the fouling resistance of modified membranes. Robustness of the ultra-thin coating is enhanced through cross-linking and covalent attachment between the membrane and the film. The resulting durability of the antifouling coating and its resistance to oxidative reagents lead to an unprecedented synergistic effect that is critical to longterm fouling resistance, which provides unique insight into the adhesion of microbial foulant and promises to lower the price of freshwater in water-scarce countries, where desalination may serve as the only viable means to provide the water supply necessary to sustain agriculture, support personal consumption, and promote economic development. / by Rong Yang. / Ph. D.

Massachusetts Institute of Technology. Dept. of Chemical Engineering. Thesis. 1965. Ph.D. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1990. / Includes bibliographical references (leaves 274-287). / by Evangelos Gogolides. / Ph.D.

Thesis (Sc. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1988. / Bibliography: leaves 251-257. / by Vita LaVopa. / Sc.D.