Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2011. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. 153-166). / Uncontrolled bleeding and infection are leading causes of patient morbidity and mortality following traumatic injury. Traditional pressure based methods of hemorrhage management are not suitable for incompressible or complex wounds. There is increasing interest in non-pressure based hemostatic dressings; however, many of these existing dressings are not amenable for use in complex sites and are often accompanied by adverse side effects. Additionally, patients are typically administered broad-spectrum antibiotics to prevent and eliminate existing infection. The systemic overuse of antibiotics has led to a worldwide increase in drug-resistant bacteria. As an alternative to these conventional treatments, local therapeutic delivery has the potential to effectively treat cellular dysfunction while avoiding drug toxicity. This thesis focuses on developing degradable layer-by-layer (LbL) assembled multilayer films as local delivery coatings to address infection, inflammation, and bleeding. These films were engineered to deliver potent antibiotics such as vancomycin and exploratory drugs such as antimicrobial peptides, which prevent the development of drug resistant bacteria. Active films with large drug loadings and a range of drug release profiles were developed by taking advantage of film architectures, assembly techniques (spray versus dip LbL), and film component interactions. Due to the prevalence of infection and inflammation, degradable coatings for the concurrent release of antibiotics and anti-inflammatory therapeutics were also designed. These films have the potential to address a wide range of infection and inflammation requirements, from short term infection and inflammation eradication for trauma relief to infection prevention and long term inflammation mitigation from biomedical implants. All films were successfully applied to medically relevant substrates, including bandages and sutures, and were shown to be active in vitro against Staphylococcus aureus and cyclooxygenase. To address current complications with bleeding control, multilayer films were developed based on hydrogen bonding interactions found to occur between a polyphenol, tannic acid, and an essential clotting factor, thrombin. These thin films were used to coat a common clinically applied absorbent and porous gelatin sponge without reducing its liquid absorption capabilities. Coated sponges were shown to be highly effective in promoting hemostasis in a porcine spleen injury model. The therapeutic films developed in this thesis have the potential to be applied to any clinical substrate. Additionally, drug loading and release can be tuned based on the desired application. / by Anita Shukla. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995. / Includes bibliographical references (v. 2, 566-575). / by Eddie Koury. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2010. / Cataloged from PDF version of thesis. / Includes bibliographical references. / All-multiwall carbon nanotube (MWNT) thin films are created by layer-by-layer (LbL) assembly of surface functionalized MWNTs. Negatively and positively charged MWNTs were prepared by surface functionalization, allowing the incorporation of MWNTs into highly tunable thin films via the LbL technique. The pH dependent surface charge on the MWNTs gives this system the unique characteristics of LbL assembly of weak polyelectrolytes, controlling thickness and morphology with assembly pH conditions. We demonstrate that these MWNT thin films have randomly oriented interpenetrating network structure with well developed nanopores using SEM, which is an ideal structure of functional materials for various applications. LbL-MWNT electrodes show high electronic conductivity in comparison with polymer composites with single wall nanotubes, and high capacitive behavior in aqueous electrolyte with precise control of capacity. Of significance, additive-free LbL-MWNT electrodes with thicknesses of several microns can deliver high energy density (200 Wh/kg) at an exceptionally high power of 100 kW/kg in lithium nonaqueous cells. Utilizing the redox reactions on the surface functional groups in a wide voltage window (1.5 - 4.5 V vs. lithium) in nonaqueous electrolytes, asymmetric electrochemical capacitors consisting of LbL-MWNT and either lithium or a lithium titanium oxide negative electrode exhibit gravimetric energy density -5 times higher than conventional electrochemical capacitors with comparable gravimetric power and cycle life. Thin-film LbL-MWNT electrodes could potentially lead to breakthrough power sources for microsystems and flexible electronic devices such as smart cards and ebook readers, while thicker LbL-MWNT electrodes could expand the application of electrochemical capacitors into heavy vehicle and industrial systems, where the ability to deliver high energy at high power will be an enabling technological development. Furthermore, nanoscale pseuduocapactive oxides and electrocatalysts were incorporated into LbL-MWNT electrodes for energy storage and conversion. Inorganic oxides such as MnO2 and RuO2 are incorporated to increase volumetric capacitance in LbLMWNT electrodes using electroless deposition and square wave pulse potential deposition methods. Preliminary results show that we can increase volumetric capacitance of LbLMWNT/ MnO2 and LbL-MWNT/RuO2 composite up to 1000 F/cm3 in aqueous electrolytes. In addition, Pt and Pt/Ru alloy electrocatalysts are introduced into LbL-MWNT electrodes using square wave pulse potential deposition, which show higher CO and methanol oxidation activities. Tailored incorporation of metal and oxide nanoparticles into LbLMWNT electrodes by square wave pulse potential opens a new strategy for novel energy storage and conversion electrodes with superior electrochemical properties. / by Seung Woo Lee. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1998. / Includes bibliographical references. / by David V. Schaffer. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references (p. 248-268). / With the spread of drug-resistant bacteria, existing antibiotics are losing their potency. Antimicrobial peptides (AmPs) represent an exciting class of drug candidates, particularly because their mechanism of action is unlikely to induce drug resistance. If resistance to AmPs were also slower to emerge in the clinic, they would have longer useful lifetimes than existing antibiotics. Nevertheless, a number of limitations exist for AmPs in the clinic. The high cost of peptide manufacture requires that highly potent sequences are created. Additionally, AmP selectivity must be improved if effective systemic doses are to be given without hemolytic activity or other toxicity. Improved high-throughput methods for AmP design or discovery could enable the achievement of both of these goals. To this end, we developed an approach based on the discovery of semi-conserved motifs across natural AmPs, which we demonstrated are associated with antimicrobial activity. Additionally, we created novel AmP formulations that may bypass some of these clinical limitations. In order to evaluate AmP design approaches, a high-throughput production and assay platform was created using in vitro translation. This technology may produce peptides that would be toxic to recombinant hosts and synthesize peptides of arbitrary length. / (cont.) The cost per peptide was minimized through a series of process improvements. First, we created methods to construct oligonucleotides that mimicked our motif-based design of AmPs. This approach allowed the reuse of primers for many peptides, reducing cost and enabling the study of pattern synergy. Additionally, we found peptide translation was enhanced by co-translating a fusion partner in frame with the AmP. The AmP could be freed from the fusion partner after translation using enterokinase digestion. Further, we increased yield 3-fold by optimizing the length of fusion partner. The partner was made as short as possible to limit the translational resources required to synthesize the fusion partner, while being long enough to ensure stability from proteases. The solubility of the fusion partner-AmP construct was also improved through the selection of a highly soluble partner of the optimal length. Finally, we developed a purification scheme to ensure that the in vitro translation extract would not impact measurement of antimicrobial activity. We also developed and evaluated the design of AmPs using semi-conserved motifs. We used a database of over 500 natural AmPs as a training set for pattern discovery. / (cont.) The resulting motifs were exhaustively recombined to create all 20 amino acid sequences that were entirely covered by these patterns. These sequences were clustered, and 42 diverse members selected for characterization using representative Gram negative and Gram positive bacteria. Approximately 50% of the designed AmPs were active against at least one of the bacteria at 256 ug/ml. Control peptides were created in which the amino acids in the designed peptides were rearranged such that they were not homologous to any antimicrobial motifs. Thus, these controls had the same bulk physiochemical properties frequently associated with antimicrobial activity as the designed sequences, but we hypothesized they would not be active because they did not match the antimicrobial motifs. In fact, only 5% of the control sequences had activity at 256 ug/ml, indicating that the antimicrobial motifs give a 10-fold enrichment in activity. Further, two highly active designed peptides had MICs of 16 ug/ml against Bacillus cereus and 64 ug/ml against Escherichia coli. Additionally, AmPs active against B. cereus were all active against the hospital pathogen Staphylococcus aureus, and the bioterror agent, Bacillus anthracis. / (cont.) Our motif-based design may be most effective as the first stage of a two-stage design tool. In the first stage, highly diverse leads with novel profiles are created and evaluated. Promising leads could then be optimized using a variety of techniques. By creating just 44 variants of one lead, we designed an AmP with broad spectrum activity that had MICs of 16 ug/ml against E. coli and 8 ug/ml against B. cereus and 4 ug/ml against S. aureus. Another approach to build on our design tool would be to incorporate activity and toxicity characteristics of members of the training set into the design or scoring of new sequences. In order to begin assembling this data using a standardized method, a representative set of 100 natural, linear AmPs was chosen through clustering. Their antimicrobial activity against E. coli, S. epidermidis, and S. aureus were evaluated, along with hemolytic activity. When further supplemented, this information may enable an improved scoring metric to be created. Additionally, we systematically demonstrated that amidating the c-terminus of natural AmPs improves both antimicrobial activity and therapeutic index. Finally, we recognized that AmP's mechanism of action would allow activity to be retained when they are permanently tethered to medical device surfaces. / (cont.) Unlike existing coatings which rely on the slow release of silver or other antibiotics, a permanently tethered approach could have a longer lifetime and reduced systemic toxicity concerns. A versatile chemistry was developed to create immobilized AmP coatings. These formulations had broad spectrum antimicrobial activity without significant hemolytic activity. Further, the coatings were effective through multiple bacterial challenges. The combination of the AmP design tool along with localized formulations represent a significant advance in the process of moving AmPs to the clinic to combat drug-resistant infections. / by Christopher Loose. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, February 2016. / Cataloged from PDF version of thesis. / Includes bibliographical references. / The self-assembly of globular protein-polymer diblock copolymers represents a promising technology for protein nanopatterning. The self-assembled materials have a high density of proteins and internal nanostructures that serve as continuous transport pathways for substrates, products, cofactors, and/or charges. The polymer block can act as a protective matrix for the protein, improving its stability and longevity in materials. The self-assembly of protein-polymer diblock copolymers is substantially different from that of traditional synthetic diblock copolymers due to the globular and rigid shape, heterogeneous composition, and anisotropic interactions of proteins. This thesis focuses on the control of nanostructures in self-assembled materials with a goal to gain a better understanding of the governing principles in self-assembly. This thesis presents experimental studies on the effect of modulated interactions between protein and polymers on the self-assembly of globular protein-polymer block copolymers. Bioconjugates composed of a model red fluorescent protein, mCherry, and a synthetic homopolymer with different chemical moieties are synthesized. Modulated interactions between protein and polymer by introducing polymer blocks with different hydrogen bonding capabilities change order-disorder transition concentrations in solution and the type of nanostructures formed. Bioconjugates with a weakly segregating polymer block are found to form a double gyroid structure with Ia3d symmetry, as opposed to perforated lamellae of bioconjugates with a strongly segregating polymer block. Common phase behaviors are also revealed, including the order of lyotropic order-order transitions and a re-entrant disordering behavior at high concentrations. Birefringence of the disordered solutions with increasing protein fraction suggests the formation of a nematic liquid crystalline phase arising from protein interactions. Self-assembly of proteinzwitterionic polymer bioconjugates shows that electrostatic segregation of mCherry constitutes one of the major driving forces for microphase separation. Nanostructures of the conjugates are further controlled by changing solvent selectivity. Important considerations in preparing bioconjugate thin films are also presented and discussed. Surface effects as well as kinetics such as solvent evaporation rate and film coating speed are shown to have a large impact on the long-range order of self-assembled nanostructures. / by Dongsook Chang. / Ph. D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 2015. / Cataloged from PDF version of thesis. / Includes bibliographical references (pages 251-278). / Non-wetting surfaces are characterized by the presence of stable pockets of vapor trapped within the asperities of the surface morphology. The utility of these surfaces in reducing skin friction in viscous laminar and turbulent flows is experimentally and theoretically investigated and is the main focus of this thesis. The development of a surface coating that reduces fluid drag can potentially lead to a number of practical applications such as fuel savings in marine vehicles and energy savings in pipe flows. First, a single-step, scalable spray coating technique to fabricate liquid-repellent micro-textured surfaces by depositing a blend of poly(methyl methacrylate) (PMMA) and the low surface energy molecule 1H,1H,2H,2H-heptadecafluorodecyl polyhedral oligomeric silsesquioxane (fluorodecyl POSS, [gamma]sv ~~ 10 mN/m) is presented. The surface morphology of the polymer coating was studied systematically and can be varied from a corpuscular or spherical microstructure to a beads-on-string structure and finally to bundled fibers by controlling the solution concentration c and molecular weight M of the sprayed polymer solution. A scaling law is proposed that relates the minimum necessary concentration of a polymer required to produce fibers cspf to its molecular weight M and the quality of the solvent (through the excluded volume exponent v) of the form cspi ~ M-(v+l). These POSS/PMMA coatings are shown to exhibit both superhydrophobic and superoleophobic properties due to the presence of a film of trapped air (or 'plastron') within the surface microtextures upon contact with a liquid. A combination of texture and surface chemistry is also important in the design of various biomimetic interfaces. Many species of aquatic birds dive tens of meters into water to prey on fish while entraining a 'plastron film' within the complex microstructures of their feathers, which is often thought to confer water repellency to the bird. By combining electron microscopy with contact angle measurements on specially dip-coated feathers, it is demonstrated that in fact the bird feathers are expected to be fully wetted in a typical deep dive. However, surface energy calculations and a stability analysis reveals that, depending on the geometric spacing of the barbules and hydrophobicity of the natural waxy coating, these feathers will spontaneously de-wet once the bird emerges out of water. Conversely, oils and low surface tension liquids wet the feather microstructure irreversibly. The results of this analysis can be used to design thermodynamically 'robust' coatings and fabrics that can spontaneously de-wet and recover their non-wetting properties. The vapor layer entrapped adjacent to the solid wall by the superhydrophobic coating serves to lubricate fluid flow and can potentially reduce skin friction drag. At small Reynolds numbers Re << 1, the effective Navier slip length is evaluated using torque measurements in a parallel plate rheometer resulting in a measured Navier slip length in laminar flow of b ~~ 39 [mu]m, comparable to the mean periodicity of the microstructure evaluated from confocal fluorescence microscopy. To investigate the behavior in turbulent flows (at Re >/- 10⁴), a wide gap Taylor-Couette (TC) cell was constructed. A series of global torque measurements with a spray-coated superhydrophobic inner rotor is used to establish a friction reduction varying from 6% at Re ~ 2 x 10⁴ to a maximum of 22% at Re ~ 8 x 10⁴. By applying a boundary layer theory, a modified Prandtl-von Karman type relationship of the form (Cf /2)-¹/² = Mln Re(Cf /2)¹/² + N + (b/[delta]r)Re(Cf /2)¹/² is derived, from which we extract an effective slip length of b ~ 19 m. In this manner, the presence of a finite microscopic slip length is shown to dramatically affect the bulk skin friction reduction. This result also highlights the remarkable steady enhancement in the drag reduction with increasing Re. By coupling the effective Navier slip length b (i.e., a material property characteristic of the textured surface chemistry and physics) to the hydrodynamic viscous length scale [delta]v = v/u[tau] in near-wall turbulent flows, it is established that it is the dimensionless slip length b+ = b/[delta]v which is the key parameter governing the drag reduction; we find that b+ ~ Re¹/² in the limit of high Reynolds number. The results of the experimental analysis, in combination with the theoretical framework that is developed, allows for the rational design of micro-structured surface coatings that can be applied to reduce macroscopic skin friction drag in turbulent flows. / by Siddarth Srinivasan. / Ph. D.

Massachusetts Institute of Technology. Dept. of Chemical Engineering. Thesis. 1969. Ph.D. / Errata page inserted between p. [i] and ii: Pages 653-666 bound in reverse order. Vita. / Includes bibliographies. / Ph.D.

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Chemical Engineering, September 2014. / Cataloged from PDF version of thesis. "June 2014." / Includes bibliographical references (pages 100-107). / Solid oxide fuel cell (SOFC) is a promising alternative energy source, with its advantages of high operating efficiency, fuel flexibility, low emissions and relatively low cost. However, there are several challenges concerning the SOFC research. Little is known about the complex interfacial electrochemistry and thermochemistry, and it is also difficult to diagnose problems and optimize cell performance. Therefore, physics-based models are needed to better understand the underlying mechanisms of SOFCs. This research work addressed two important aspects of the numerical modeling of SOFCs: the multicomponent gas diffusion in porous electrode at the anode and the heterogeneous electrocatalysis of oxygen reduction reaction (ORR) at the cathode. First, anode was diagnosed to be mainly controlled by multicomponent gas diffusion inside the anode bulk (supporting) layer, and the Dusty Gas model is identified as an appropriate model to describe the gas diffusion resistance extracted from no bias AC impedance. Anode-supported SOFCs with Ni-yttria-stabilized zirconia (YSZ) anode were used to study the multicomponent gas transport in porous electrodes. A fuel gas mixture of H₂-H₂O-N₂ was fed to the anode and AC impedance data were measured at 800°C by varying hydrogen partial pressure at both no bias and a current of 300 mA. Impedance data were also collected at no bias at three different temperatures (800°C, 850°C and 900°C). For the first time, three models were used to analytically derive the diffusion resistance (Rb), which was then compared to the values extracted from experimental impedance data. The Dusty Gas model yields the best predictions and the tortuosity values derived from Dusty Gas model are found to be independent of feeding gas composition, operating current and temperatures, which is consistent with the fundamental or underlying physics. Moreover, with the anode porosity known to be approximately 46%, the tortuosity derived from the Dusty Gas model is 2.3~3.3, which matches both theoretical expectations and experimental measurements. This gas diffusion resistance analysis using AC impedance greatly improves the way to study the multicomponent gas diffusion within porous electrodes. Secondly, electrocatalysis at the SOFC cathode was studied using symmetric cathode cells, whose no bias AC impedance was investigated and modeled using a physics-based electrocatalysis model, describing the coupled dissociative adsorption of oxygen molecules onto the catalytic lanthanum strontium manganite (LSM) particles and surface diffusion of adsorbed species, assuming the charge transfer reaction is relatively fast and at equilibrium. A Gerischer type impedance response with a reflecting boundary condition was theoretically derived assuming the oxygen adsorption follows Langmuir type kinetics. This cathode electrocatalysis model not only captures the frequency dependence of the no bias AC impedance, it also well represents the oxygen partial pressure (pO₂) dependence. Four different impedance curves at pO₂ 2 of 21%, 15%, 10% and 5% were fitted at the same time, and the model was able to well describe them using one set of physically meaningful fitting parameters. Microstructure of the cathode functional layer (CFL) was also studied using this electrocatalysis model. It was found that the diffusion length Ls, is a critical parameter, whose ratio with respect to the characteristic boundary layer length l[delta], (the Thiele modulus) critically controls the effectiveness of the catalytic activity of the cathode functional layer. These understandings of the anode gas diffusion and cathode electrocatalytic process was used to propose an equivalent circuit for the full solid oxide fuel cell, which captures all important resistances in the SOFC, but is still as simple as possible, in order to minimize the number of fitting parameters. This full cell model greatly helps to break down the AC impedance which has overlapped responses from several processes. The analysis identified the rate limiting step of the full Saint-Gobain button cell to be the cathode electrocatalytic process, which indicates that in order to improve the cell performance, research should be focused on improving the cathode functional layer, by either improving the surface catalytic activity of the LSM particles, or changing the microstructure of the cathode functional layer. / by Yeqing Fu. / Ph. D.

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1995. / Includes bibliographical references (p. 267-271). / by Andrew J. Green. / M.S.