Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005. / Includes bibliographical references (p. 42-44). / (cont.) produced normal growth curves in the presence of particles. However, the particles do still exhibit some toxicity towards the cells, as the maximum cell density of cells cultured with particles does not reach that of control cultures. Both particles were found to increase the oxygen transfer in an aqueous solution. A 1.5% solution of particle A enhanced the oxygen transfer 41.8% over the control, water, while 1.4% particle B enhanced 15.9% over the control. While particle A has a better effect on oxygen transfer, this particle is not suitable to be used with mammalian cell cultures as it is highly toxic. / This thesis focuses on the compatibility of polymer-coated magnetic nanoparticles with mammalian systems. The magnetic particles are designed to increase oxygen transfer in mammalian cell bioreactors. Magnetic nanoparticle A consists of a magnetite core attached to a layer of oleic acid, in which oxygen is four times as soluble as it is in water. The entire particle is coated with an attached layer of a surfactant, hitenol, to stabilize the particle against agglomeration. The entire particle has a diameter of approximately 20 nm. However, particle A was found to be extremely toxic to both [gamma]-CHO and hybridoma cells, causing complete cell death within four hours. This is most likely due to the surface surfactant, hitenol. A more biocompatible nanoparticle, particle B, was created. This particle is synthesized with a brush copolymer consisting of octadecylamine (ODA) and poly(ethylene oxide) (PEO) attached to a poly(acrylic acid) backbone. Once attached to the magnetite core, the ODA forms the inner layer that solubilizes oxygen, while PEO forms the stabilizing coating. Particle B forms nanoclusters about 100 nm in diameter. Thoroughly cleaning the nanoparticles is very important, as mammalian cells are very sensitive to foreign chemicals. Particles cleaned with dialysis did not remove all impurities, as all [gamma]-CHO cells in the presences of these particles were killed within 24 hours. High gradient magnetic separation (HGMS) was used to clean particles, and was found to be a much more effective method. However, sufficient amounts of washing fluid, about sixty column volumes, were needed to ensure proper cleaning. Once properly cleaned, the particles were found to be much less toxic towards the cells. Both [gamma]-CHO and hybridoma cells / by Kelly M. Kral. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995. / Includes bibliographical references (leaves 180-187). / by Randy Stewart Lewis. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1943. / Includes bibliographical references (leaves 54-55). / by Muslihittin Asim Tunca. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 141-161). / The ability to accurately detect and quantify biological molecules in complex mixtures is crucial in basic research as well as in clinical settings. Advancements in genetic analysis, molecular diagnostics, and patient-tailored medicine require robust detection technologies that can obtain high-density information from a range of physiological samples in a rapid and cost-effective manner. Compared to conventional microarrays and methods based on polymerase chain reaction (PCR), suspension (particle-based) arrays offer several advantages in the multiplexed detection of biomolecules, including higher rates of sample processing, reduced consumption of sample and reagent, and rapid probe-set modification for customizable assays. This thesis expands the utility of a novel hydrogel-based microparticle array through (1) the creation of a microfluidic, flow-through fluorescence scanner for high-throughput particle analysis, (2) the development of a suite of techniques for the highly sensitive and specific detection of microRNA (miRNA) biomarkers, and (3) the investigation of new methods for directly measuring biomolecules at the single-cell level. Graphically-encoded hydrogel microparticles synthesized from non-fouling, bioinert poly(ethylene glycol) (PEG) and functionalized with biomolecule probes offer great promise in the development of high-performance, multiplexed bioassays. To extend this platform to applications in high-throughput analysis, particle design was optimized to ensure mechanical stability in high-velocity flow systems, and a single-color microfluidic scanner was constructed for the rapid fluorescence interrogation of each particle's spatially-segregated "code" and "probe" regions. The detection advantages of three-dimensional, probe-laden hydrogel scaffolds and the operational efficiencies of suspension array technology were then leveraged for the rapid multiplexed expression profiling of miRNA. The graphical encoding method and ligationbased labeling scheme implemented here allowed for scalable multiplexing with a simple workflow and an unprecedented combination of sensitivity, flexibility, and throughput. Through the rolling circle amplification of a labeling oligonucleotide, it was possible to further enhance the system's sensitivity and resolve single-molecule miRNA binding events on particle surfaces, enabling the first direct detection of low-abundance miRNA in human serum without the need for RNA extraction or target amplification. Finally, by arraying cells and gel particles in polydimethylsiloxane (PDMS) microwells, it was possible to dramatically improve the particles' target capture efficiency and thereby move closer to a regime in which miRNAs and other biological molecules may be directly detected without target amplification from single cells. / by Stephen Clifford Chapin. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1998. / Includes bibliographical references (leaf 18). / by Michael J. Marsh. / M.S.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1971. / Bibliography: leaves 80-82. / by Ronald S. Eisinger. / M.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2004. / Includes bibliographical references (p. 269-283). / This thesis developed and applied tools to bridge the gap between available data and action for urban air quality management, focusing on strategies to reduce particle concentrations. One of the principal thesis contributions is a Bayesian method to exploit the asymmetry between the rich aerosol dataset and the relatively poor dataset on gas-phase precursors. A Markov Chain Monte Carlo algorithm was combined with the equilibrium inorganic aerosol model ISORROPIA to produce a powerful tool to analyze aerosol data and predict gas phase concentrations where these are unavailable. The method directly incorporates measurement uncertainty, prior knowledge, and provides for a formal framework to combine measurements of different quality. Applying the method to data from Mexico City, evidence for stable and metastable aerosols was found. Gas phase concentrations were estimated including, for the first time in Mexico City, hydrochloric acid. The MIT Inorganic Aerosol Model was developed based on the work of Resch (1995). The equilibrium treatment of ammonia and nitric acid is included in the model, as is the partial dissociation of bisulfate. Model predictions were critically compared with available models and data, and the role of complexes and hydrates investigated. For the first time, a model that includes complexes and hydrates was applied to an urban environment. Based on 1997 data from Mexico City, it was found that complexes and hydrates are predicted to form in a majority of cases. / (cont.) Despite their frequent formation, their effect on model predictions is small given the uncertainties in thermodynamic parameters and field observations. Reductions in ammonia concentrations are likely to be less effective at reducing PM2.5 in Mexico City than expected, while reductions in nitrate and sulfate are expected to be effective. This conclusion is robust including or excluding complexes and hydrates and assuming stable or metastable aerosols, although the best model performance is achieved assuming efflorescence. An inverse technique to estimate the emission rate of a point source using field observations was developed. The relatively simple model minimizes data requirements and is broadly applicable. By incorporating the uncertainty in wind direction, the emissions rate of a tracer was recovered within measurement uncertainty. / y Federico M. San Martini. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 111-122). / Chemoattractant gradients play important roles in the normal function of immune system, from lymphocyte homeostasis to mounting efficient immune responses against infection. Improved fundamental knowledge about the role of chemoattractant gradients developed around single source cells in controlling chemotaxis of "receiving" cells would not only greatly advance our understanding of the basic mechanisms of cell chemotaxis but also would inform strategies for modulating chemoattractant gradients in therapeutic applications, such as adjuvant materials for vaccines and cancer immunotherapy recruiting immune cells of interest. In this thesis, we first applied mathematical modeling to understand the key characteristics of chemoattractant gradients secreted from single source cells at physiological rates. During the transport of chemoattractants, we considered the diffusion of soluble attractants, binding to matrix and degradation by proteolytic enzymes. From the calculated chemoattractant concentration gradients, we predicted the characteristics of attractant receptor engagement on responding cells, and estimated the maximum stimulation distance effectively triggering chemotaxis of responding cells based on the threshold for receptor engagement gradients, a difference of ~10 ligand-engaged receptors between the front and back of responding cells. This characteristic maximum stimulation distance is a function of multiple parameters including secretion rate of the source cell, diffusion constant of the chemoattractant, interaction with matrix, degradation or clearance of chemoattractant in the tissues, and the density of source cells. In addition, chemokine receptor desensitization induced by chemoattractants could shorten the maximum stimulation distance. We then developed Artificial Secreting Cells (ASCs) to mimic real chemoattractant secreting cells using cell-sized polysaccharide-based hydrogel microspheres releasing chemoattractant in a controlled manner. These alginate hydrogel microspheres, ~30 [mu]m in size, were crosslinked with Ca2+ between gluronic acid units on alginate backbones and provided a natural and bioactive environment for chemokines. The chemokines could be loaded into these alginate microspheres by soaking them in concentrated chemokine solutions and released in a reversible manner. This approach was shown as a general strategy for several chemokines, such as CCL21, CCL19, CXCL10 and CXCL12. The loading and release properties of individual chemokines were highly correlated with the average charge density on protein surface. We have also demonstrated that the controlled gradients created by ASCs were similar to the modeled gradients developed around single source cells. Further we used 3D collagen hydrogels embedded with ASCs as an in vitro model to investigate single human T-cell and dendritic cell migration dynamics to CCL21 and CCL19 chemokine gradients. Individual T-cells exhibited a binary response to isolated attractant sources, migrating highly directionally or ignoring the gradient completely; the fraction of responding cells correlated with chemokine receptor occupancy induced by the gradient. In sustained gradients eliciting low receptor desensitization, attracted T-cells or dendritic cells swarmed around isolated ASCs for hours. With increasing ASC density, overlapping gradients and high attractant concentrations caused a transition from local swarming to transient "hopping" of cells bead to bead. Thus, diverse migration responses observed in vivo may be determined by chemoattractant source density and secretion rate, which govern receptor occupancy patterns in nearby cells. / by Yana Wang. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 169-186). / Chemical kinetic modeling plays an important role in the study of reactive chemical systems. Thus, an automated means of constructing chemical kinetic models forms a useful tool in the engineering and science surrounding such systems. This document describes work to further develop one such tool, known as RMG (Reaction Mechanism Generator). Focus is placed on improving the accuracy of parameter estimation in the mechanism generation process and expanding the scope of applicability of the tool. In particular, effort has targeted the generation and use of explicit three-dimensional molecular structures for chemical species considered during reaction mechanism generation. This work has resulted in the generation of a software system integrated with RMG that can automatically generate and use such structures with quantum chemistry or force field codes to obtain more reliable thermochemistry estimates for cyclic structures without human intervention. Ultimately, the result of these updates is improved usefulness and reliability of the software system as a predictive tool. An application of the tool to the high temperature oxidation of JP-10, a jet fuel often used in military applications, is described. Using the newly refined RMG system, a detailed chemical kinetic model was constructed for this system. The resulting model represents a significant improvement upon existing work for JP- 10 oxidation by capturing detailed chemistry for this system. Simulations with this model have been found to produce results for ignition delay and product distribution that compare favorably with experimental results. The successful application of the refined RMG software system to this system demonstrates the practical utility of these updates. / by Gregory Russell Magoon. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references. / When an aqueous surfactant solution is exposed to a clean water/air surface, it takes a finite time for the surfactant molecules to physically transport from the bulk aqueous solution to the surface in order to adsorb and reduce the surface tension. The time scales associated with the reduction in surface tension can vary between milliseconds to hours depending on the surfactant type and its concentration. Accordingly, development of a fundamental understanding of the underlying physical phenomena involved in the kinetics of surfactant adsorption will help to: (i) understand the observed Dynamic Surface Tension (DST) behavior of surfactants, and (ii) design optimal surfactant formulations for applications in which the surfactant adsorption kinetics plays a significant role in determining the effectiveness of the formulation. This thesis deals with modeling the adsorption kinetics of nonionic surfactants at prernicellar surfactant concentrations. Traditionally, the adsorption kinetics of nonionic surfactants at premicellar surfactant concentrations has been understood in the context of two models: (1) the diffusion-controlled model, which assumes that diffusion of surfactant molecules from the bulk solution to the surface is the rate-limiting step, and (2) the mixed diffusion-barrier controlled model, which hypothesizes the existence of an energy barrier for surfactant adsorption from the bulk solution to the surface, and assumes that both diffusion and the energy barrier determine the overall rate of surfactant adsorption. Although the existence of the energy barrier was hypothesized more than 50 years ago, the physical basis underlying the existence of the energy barrier has not yet been elucidated. / (cont.) The first major contribution of this thesis was demonstrating that the energy barrier is associated with the adsorption of a single surfactant molecule onto a clean surface, contrary to the broadly-held view that the energy barrier is associated with collective interactions between the adsorbed surfactant molecules. This was demonstrated by developing a generalized mixed diffusion-barrier controlled model and deriving a short-time adsorption kinetics formalism for this generalized model. The short-time formalism revealed that, when adsorption takes place onto an initially clean surface, the adsorption kinetics is independent of the specific interactions between the adsorbed surfactant molecules, and is solely controlled by the energy barrier at asymptotic short times. This observation led to the important conclusion that the energy barrier is related to the adsorption of a single surfactant molecule onto a clean surface. One of the major drawbacks with the traditional procedure to determine the adsorption kinetics rate-limiting mechanism (diffusion-controlled vs. mixed diffusion-barrier controlled), including the values of the relevant adsorption kinetics parameters, from experimental DST data is that it requires a specific model for the equilibrium adsorption behavior of the surfactant, where the deduced results were found to be extremely sensitive to the accuracy of the specific equilibrium model used. As a result, it has not been possible to elucidate the underlying physical basis of the energy barrier by analyzing the experimental DST data of nonionic surfactants. / (cont.) With this limitation in mind, the second major contribution of this thesis was the development of a new methodology to determine the adsorption kinetics rate-limiting mechanism, including the values of the relevant adsorption kinetics parameters, from the experimental DST data without using any model for the equilibrium surfactant adsorption behavior. The new methodology was implemented to analyze the experimental DST behavior of several alkyl poly(ethylene) oxide, CiEj, nonionic surfactants, and revealed that the energy barrier may be related to the hydrophobic effect. The third major contribution of this thesis was the development of a novel approach to determine the equilibrium adsorption properties of nonionic surfactants from experimental dynamic surface tension data, a novel concept which has never been explored in the surface tension literature. Motivated by the observed high sensitivity of the predicted DST profiles to the accuracy of the model used to describe the equilibrium surfactant adsorption behavior, a new methodology was developed to determine the Equilibrium Surface Tension versus surfactant bulk solution Concentration (ESTC) behavior of nonionic surfactants from experimental DST data when the adsorption kinetics rate-limiting mechanism is diffusion-controlled. The new methodology requires: (1) experimental DST data measured at a single surfactant bulk solution concentration, Cb, (2) the diffusion coefficient of the surfactant molecule, and (3) one equilibrium surface tension value measured at a single surfactant bulk solution concentration, to determine the entire ESTC curve corresponding to surfactant bulk solution concentrations which are less than, or equal to, Cb. The new methodology was implemented to analyze the experimental pendant-bubble DST data of C12E4 and C12E6. / (cont.) For this purpose, the time scale associated with the validity of the assumption involving diffusive transport of surfactant molecules in the bulk solution in a pendant-bubble DST measurement was first determined, and the experimental DST data at those time scales was analyzed using the new methodology to predict the ESTC curves of C12E4 and C12E6. In both cases, the predicted ESTC behavior compared very well with the appropriate experimental DST results reported in the literature. The final major contribution of this thesis was the development of a novel theoretical framework to design optimal surfactant formulations that meet specific adsorption kinetics requirements, which circumvents the more widely used and time consuming experimental trail-and-error surfactant selection approach. Specifically, the new theoretical framework involves using predictive DST models in conjunction with optimization techniques to identify the most efficient surfactant formulation that meets a specific surfactant adsorption kinetics requirement. The technical feasibility of the new theoretical framework and its effectiveness was demonstrated in the context of the adsorption kinetics of nonionic surfactants. Overall, the results obtained in this thesis contribute to: (1) the development of a fundamental physical understanding of the energy barrier, (2) the development of efficient and reliable methodologies to more accurately analyze experimental DST data, and (3) the design of optimal surfactant formulations in industrial applications. / by Srinivas Nageswaran Moorkanikkara. / Ph.D.