Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1960. / MIT copy bound with: Evaluation of a technique for the fusion bonding of thermoplastics / by Neil P. Fitzpatrick, Mark R. Pratt [1960] / Includes bibliographical references (leaf 64). / by Robert N. Gunitz, Gerald M. Litton. / B.S.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1986. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE / Bibliography: v.2, leaves 200-208. / by Athanassios Z. Panagiotopoulos. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1985. / Includes bibliographical references. / by Reed Erik Spjut. / Ph.D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1968. / Bibliography: leaves 54-55. / M.S.

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references (leaves 81-83). / P(neopentyl methacrylate-co-ethylene glycol dimethacrylate) copolymer, abbreviated as P(npMAco-EGDA), was selected as the potential air-gap sacrificial material among possible combination of twenty monomers and four crosslinkers. P(npMA-co-EGDA) was deposited onto substrates using initiated chemical vapor deposition (iCVD) technique. Spectroscopic data showed the effective incorporation of both components in the copolymer and the integrity of repeating units were retained. The onset temperature of decomposition of P(npMA-co-EGDA) copolymer could be tuned between 290-3500C by varying the composition of the copolymer. The removal rate of polymer was calculated based on interferometry signal-time curve. The activation energy was determined by fitting the rate of decomposition with logistic model and found to be 162.7+8kJ/mole, which was similar to published data. Flash pyrolysis gas chromatography mass spectroscopy analysis showed that the products of thermal decomposition are monomers, rearranged small molecules and low oligomers. The modulus and the hardness were in the range of 3.9 to 5.5 GPa and 0.38 to 0.75 GPa, respectively, and were higher than those of linear poly(methyl methacrylate) (PMMA). Air-gap structures were constructed in the following scheme: P(npMA-co-EGDA) was deposited on the substrate by iCVD, followed by spincasting PMMA electron beam resist and scanning electron beam lithography to implement patterns on the resist. Reactive ion etching (RIE) was then applied to simultaneously etch the PMMA resist and P(npMA-co-EGDA) sacrificial material away in a controlled manner, leaving the patterned sacrificial material on the substrate. / (cont.) A layer of porous silica was deposited to cover the substrate and the patterned sacrificial material by plasma-enhanced chemical vapor deposition (PECVD) at 2500C and the sample was thermally annealed to allow the decomposed fragments to diffuse through the overlayer of silica. Using the scheme described above, it was possible to construct air-gap structures with feature size of 200nm and feature height of 1 00nm. / by Long Hua Lee. / S.M.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1990. / Includes bibliographical references. / by Keith Evan Dionne. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005. / Includes bibliographical references. / Catalytic processing of fuels was explored in this thesis for both low-temperature polymer electrolyte membrane (PEM) fuel cell as well as high-temperature solid oxide fuel cell (SOFC) applications. Novel catalysts were developed to generate hydrogen for PEM applications from the oxidative steam reforming of methanol. The activity of lanthanum nickel perovskite (LaNiO3) was examined in both dilute fuel and full fuel conditions. Autothermal operation was successfully achieved with higher hydrogen selectivity than conventional Pd-based catalysts. The selected complex oxide catalyst was applied as a thin film onto a 0.2 [mu]m-thick Pd membrane. Pure hydrogen effluent was obtained from the resulting microreactor as desired for PEM applications. SOFC systems would be of interest for portable power generation if the thermal cycling and slow start-up issues could be addressed. One potential solution is the development of Si-supported ultrathin electrolyte structures (~100 nm-thick) of low thermal mass. Due to the low maximum fabrication temperature (< 600°C), electrodes cannot be applied by traditional ceramic processing techniques. Alternative wet-chemical approaches were explored for the electrode deposition. In particular, ceria sol-gel and yttria-stabilized zirconia (YSZ) colloid were developed as inorganic binders for cathode application at temperatures below 600°C. The YSZ sol provided adhesion strength for La0.8Sr0.2Fe0.8Co0.2O3 (LSCF) in excess of 1000 psi. However, the low-temperature calcination process did not provide the LSCF cathode with sufficiently high electrical conductivity. As an alternative, porous Pt thin films with excellent conductivity were developed as the cathode for micro-SOFC applications. To reduce the stack cost, improve the lifetime, and minimize the coking problem of hydrocarbon-based SOFC systems, it is important to reduce the operating temperature from 1000°C to 800°C. Novel anode systems were examined for their ability to process dry methane at the lower operating temperature. Specifically, three different anode formulations were developed for anode-supported SOFC architectures with 10-40 [mu]m-thick YSZ electrolytes. These included ceramic nanocomposite anodes, CeO2/LaCrO3 and Sm-CeO2/La-CaTiO 3. The former gave rise to Cr(VI) formation due to the intimate mixing of the different ceramic nanoparticles. The latter was limited in applicability due to its low electrical conductivity. Thus, 2 a novel cermet system, Ni-Sn/YSZ, was investigated as the anode. Unlike Ni/YSZ, it did not lead to the formation of crystalline carbon, and successfully sustained 1.5 h of methane exposure at 800°C without mechanical damage to the YSZ electrolyte. Power densities comparable to the best existing direct hydrocarbon SOFC systems were achieved by the Ni-Sn/YSZ cermet. / by Steven E. Weiss. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005. / Includes bibliographical references. / We have conceptualized a new class of polymer-linker-drug conjugates to achieve targeted drug delivery for the systemic treatment of cancer and other inflammatory diseases. The physiochemical properties of the polymer allow the conjugate to circulate longer in the body by minimizing renal and hepatic clearance, thereby improving the pharmacokinetics of the attached drugs. Traditionally, linkers are degraded by acidity or by some ubiquitous intracellular enzymes. We incorporate linkers that are sensitive to a specific extracellular enzyme whose overexpression is co-localized with the diseased tissue. The drug molecules remain inactive when attached to the polymer, thus preventing normal tissues from harmful side effects. When the conjugate is transported to the diseased area where there is a high level of the target enzyme, the linkers are cleaved to release the drugs at the specific site. As an example, we designed and synthesized two generations of novel polymer-peptide-drug conjugates for the tumor-targeted delivery of chemotherapeutics. To allow for passive targeting and enhanced permeation and retention (EPR), dextran with a size greater than 6 nm was selected as the polymeric carrier. This biocompatible and biodegradable carrier was chemically modified to allow for conjugation with doxorubicin and methotrexate, two common chemotherapeutics with undesirable side effects. / (cont.) Since matrix-metalloproteinases (MMPs) are associated with a number of types of cancer and their functions are essential to disease progression, including degrading extracellular matrix, releasing angiogenic factors and activating growth factors, we explored the possibility of MMP-mediated drug release. The synthesis procedures combined solid phase and solution phase techniques to enable flexibility in the linker design and in the charge modification of the polymer. This scaleable and robust process produced new conjugates that demonstrated excellent stability under physiological conditions and optimized sensitivity to enzymatic cleavage by MMP-2 and MMP-9. The new conjugate, dextran-peptide-methotrexate, was assessed for its in vivo anti-tumor efficacy and systemic side effects. It was compared to free methotrexate and a similar conjugate, differing by an MMP-insensitive linker, at equivalent intraperitoneal dosages administered weekly. The MMP-sensitive conjugate resulted in effective inhibition of in vivo tumor growth in each of the two separate tumor models that overexpress MMP-2 and MMP-9 (HT-1080 and U- 87). In contrast, free methotrexate resulted in no significant tumor reduction in the same models. Neither free methotrexate nor the conjugate caused any tumor inhibition in mice bearing RT- 112, a slower-growing model which expresses significantly less MMP than HT-1080 and U-87 . The anti-proliferative effect of the drug contributed to the inhibition of tumor growth. Systemic side effects caused by the MMP-sensitive conjugates were tolerable. / (cont.) MMP-insensitive conjugates, though able to inhibit tumor growth, caused toxicity in the small intestine and bone marrow and the experiment was terminated after one injection. We conducted a biodistribution study in HT-1080 bearing mice to investigate the targeting mechanism of the new conjugate. Independent of the linker sequence, passive targeting was evidenced by the prolonged plasma circulation and higher tissue accumulations of the conjugates in comparison with free methotrexate. The ratios of drug accumulation at the tumor versus the major site of side effects (small intestine) for both conjugates were enhanced by the EPR effects. The difference in the drug accumulation at the tumor site was insignificant between conjugates with MMP-sensitive and MMP-insensitive linkers. We concluded that the tumor targeting effect of the dextran-peptide-methotrexate conjugate was dominantly due to passive targeting and EPR. The difference in the systemic side effects observed for the conjugates with different linkers was attributed to their varying susceptibility towards enzymes in normal tissues. / by Ying Chau. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2008. / This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections. / Vita. / Includes bibliographical references. / Epidermal growth factor receptor (EGFR) signaling leads to cellular proliferation and migration, and thus EGFR dysregulation can significantly contribute to the survival of tumor cells. Aberrant EGFR signaling due to receptor overexpression, mutation, or autocrine ligand has been observed in a wide variety of malignancies, and antibody drugs which inhibit EGFR signaling have been developed. However, the epitopes of most EGFR antibodies have not been characterized, and the marginal efficacies of current antibodies underscore the need for improved therapeutics. In this thesis work, we have created a novel method of epitope mapping, which is the determination of antigen residues responsible for mediating an antibody-antigen interaction. In our technique, a library of random mutants of the EGFR antigen is displayed on the surface of yeast, and the library is combinatorially selected for loss of binding to the antibody being mapped. If a mutant shows loss of binding to an antibody, then that residue is a potential contact residue. In addition, we found that many mutants caused a global misfolding of the antigen, requiring the use of high-throughput sorting to remove the misfolded mutants. The development of our epitope mapping method using random mutagenesis and yeast surface display enabled the successful mapping of four different antibodies and three designed ankyrin repeat proteins binding to EGFR. In addition, we continued work on engineering novel antibodies against EGFR domains II and IV. Antibodies against these domains are hypothesized to directly inhibit receptor dimerization and subsequent activation, as opposed to traditional anti-EGFR antibodies which block ligand binding. To accomplish this, peptide mimics of EGFR loops were used as antigens; however, antibodies generated using both yeast surface display and rabbit monoclonal technology were peptide-specific, but did not bind to EGFR protein. / (cont) Finally, we developed a mathematical model to describe equilibrium EGFR ligand binding and dimerization. Based on observations that polyclonal antibodies against EGFR domain II or IV eliminate high affinity EGF binding normally observed on the surface of cells, we hypothesized that preformed inactive dimers were the high affinity component. Our model incorporating this hypothesis successfully reproduced experimental data, resulting in characteristic concave-up Scatchard plots. / by Ginger Chao. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 118-126). / Reactive oxygen species (ROS) have emerged as biological signaling molecules, participating in newly discovered cascades that govern cell proliferation, migration, and pathogenesis. A major challenge in understanding these pathways is the lack of detection technologies that allow for spatial and temporal resolution of specific ROS at the cellular level. The goal of this thesis is to design a nanotube sensor platform able to detect and study H2 0 2 signaling fluxes at the cellular level in order to elucidate their role in biological processes. Understanding this role may lead to new therapeutic targets, and improve understanding of biological signaling. Single-walled carbon nanotubes (SWNT) are rolled sheets of graphene and can be either semiconducting or metallic depending on the angle of rolling and the diameter of the tube. Semi-conducting SWNT are one of only a few types of molecules that exhibit band gap photoluminescence (PL) in the near infrared (nIR), making them ideal for detection in biologically relevant media since it avoids biological auto-fluorescence. SWNT are also completely photostable even at high fluence, unlike conventional fluorophores and quantum dot systems, allowing them to serve as nIR single molecule optical sensors capable of long term and stable operations in vitro and in vivo. In this thesis, we show that the 1D quantum confinement of photogenerated excitons in SWNT can amplify the detection of molecular adsorption to where single-molecule discrimination is realizable, even from within living cells and tissues. / (cont.) We have developed a type I collagen film, similar to those used as 3D cell scaffolds for tissue engineering, containing embedded SWNT capable of reporting single-molecule adsorption of quenching molecules such as H₂0₂ . A Hidden Markov Modeling algorithm is utilized to link single-molecule adsorption events detected on the nanotube to forward and reverse kinetic rate constants for many different analytes. The collagen matrix is shown to impart selectivity to H₂0₂ over other ROS and common interferents. We utilized these new single-molecule sensors to study the fluxes of H₂0₂ from A431 human skin carcinoma cells and particularly the local generation rate from Epidermal Growth Factor Receptor (EGFR), a membrane protein and tyrosine kinase that controls cell proliferation among other functions. We show that an array of nIR fluorescent SWNT is capable of recording the discrete, stochastic quenching events that occur as H₂0₂ molecules are emitted from individual A431 and murine 3T3 fibroblasts cells in response to epidermal growth factor (EGF). We also show mathematically that such single molecule detection arrays have the unique property of distinguishing between "near field" and "far field" molecular generation, allowing one to isolate the flux originating from only the membrane protein. Corresponding inhibition experiments suggest a mechanism whereby water oxidizes singlet oxygen at a catalytic site on the receptor itself, generating H₂0₂ in response to receptor binding. An EGFR-mediated H₂0₂ generation pathway that is consistent with all current and previous literature findings has been proposed for the first time and numerically tested for consistency. / (cont.) In an effort to extend this detection to in vivo systems, we investigated how SWNT are uptaken and localized within living cells and as well as their potential cytotoxicity. To this end, we have developed a novel method of studying this problem by tracking the non-photobleaching SWNT in real time by using a single particle tracking method. Over 10,000 individual trajectories of SWNT were tracked as they are incorporated into and expelled from NIH-3T3 cells in real time on a perfusion microscope stage. An analysis of mean square displacement allows the complete construction of the mechanistic steps involved from single duration experiments. We observe the first conclusive evidence of SWNT exocytosis and show that the rate closely matches the endocytosis rate with negligible temporal offset, thus explains why SWNT are non-cytotoxic for various cell types at a concentration up to 5 mg/L, as observed from our live-dead assay experimental results. Further, we studied the cellular uptake and expulsion rates of length-fractionated SWNT from 130 to 660 nm in NIH-3T3 cells using this method. We developed a quantitative model to correlate endocytosis rate with nanoparticle geometry that accurately describes our data set and also literature results for Au nanoparticles. The model asserts that nanoparticles cluster on the cell membrane to form a size sufficient to generate a large enough enthalpic contribution via receptor ligand interations to overcome the elastic energy and entropic barriers associated with vesicle formation. / (cont.) The total uptake of both SWNT and Au nanoparticles is maximal at a common radius of 25 nm when scaled using an effective capture dimension for membrane diffusion. The ability to understand and predict the cellular uptake of nanoparticles quantitatively should find utility in designing nanosystems with controlled toxicity, efficacy and functionality. The development of such single molecule detection technologies for ROS motivates their application to many other unexplored signaling pathways both in vitro and in vivo. / by Hong Jin. / Ph.D.