Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2012. / Cataloged from PDF version of thesis. / Includes bibliographical references (p. [113]-123). / The synthesis of complex microparticles is an important objective. These particles can find use in a number of applications ranging from tissue engineering to ceramics and assembly. Tuned assembly of anisotropic particles can give rise to macrostructures with complex morphologies. Externally applied fields like electric or magnetic fields are useful ways to tune the assembly of anisotropic particles. This thesis begins with an understanding of the flow conditions in stop-flow lithography (SFL), the technique used for anisotropic microparticle synthesis, followed by the demonstration of the versatility of SFL by synthesizing soft cell-laden microgels, hard ceramic microcomponents and 3D curved microparticles. The thesis ends with the study of the assembly of anisotropic magnetic hydrogels synthesized using SFL. In the first section of the thesis, we introduce SFL and identify optimal conditions for particle synthesis using SFL. We do so by analyzing the dynamic response of a retracting PDMS wall after the removal of an external stress. We realized that for small deformations the problem lends itself to a regular perturbation analysis that is analytically solvable at zeroth-order. We compared the zeroth-order solution to the numerically solved full solution and to trends seen in experiments. In the second section we demonstrate the ability to synthesize complex particles using SFL. We generated anisotropic cell-laden microgels with reasonable cell viability. This work required the use of careful, benign conditions to ensure good cell viability and precise stop of the flow to ensure good resolution of cell-laden hydrogels. We determined an optimal cell density in a mixture of the cell suspension with the oligomer and photoinitiator. Then, we varied the concentrations of the oligomer and photoinitiator in the mixture to achieve reasonable polymerization times while simultaneously ensuring the desired cell viability. In a different work, we demonstrated the ability to make colloidal glass and silicon microcomponents using SFL. We flew a shear thinning colloidal silica suspension mixed with oligomer and photoinitiator through a microchannel and flashed UV light through a photomask to synthesize polymeric microcomponents of desired shape. In order to enhance their structural integrity, these colloidal microgears were transformed into fully dense, glassy silica microparticles by sintering at 1150 'C for 3 - 10 hours. SFL has traditionally been used to synthesize 2D extruded particles. We demonstrated the ability to synthesize 3D curved particles using SFL by introducing curvature in the direction orthogonal to the projection of UV light. We achieved this by co-flowing two streams which we called the polymerization and tuning fluid respectively, through a microchannel. On stopping the fluids, curvature developed at the interface of the fluids to minimize the surface energy. The quiescent fluids were exposed to a flash of UV light through a photomask which resulted in the gelling of the region within the polymerization fluid. The resulting microparticle had a shape in the plane of projection of light dictated by the mask and curvature in the plane orthogonal to the projection of light determined by the surface properties of the fluids used. The chemical programmability of this technique was demonstrated by synthesizing Janus, patched and capped polymeric microparticles. In the final part of this thesis we present a framework for the study of the directed assembly of H-shaped magnetic hydrogels. We synthesized non-Brownian H-shaped microparticles with encapsulated nanometer sized magnetic beads for assembly studies. Directed assembly at low surface coverage involves two time steps: i) rotation to attain an equilibrium orientation, followed by ii) translation to form assembled structures. Hence, as a first step to understanding the assembly of these particles, we studied their rotation. We developed a Finite Element Integration (FEI) method to identify the preferred particle orientation (relative to the applied field) at different values of the geometric parameters defining H shapes and constructed a phase diagram to generalize the results. We validated the theoretical predictions by comparing with experiments performed using magnetic hydrogels synthesized using SFL. These results aided in the choice of H-shaped particles for further assembly studies wherein we demonstrated the ability of these particles to widen chains and induce branching orthogonal to the applied field. / by Priyadarshi Panda. / Ph.D.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1999. / Includes bibliographical references. / A key problem in biomedical engineering today is in understanding the mechanisms which control cellular functions such as cell proliferation, migration and differentiation. The ability to engineer tissue replacements requires understanding of the interactions between the cell and its environment - the surface with which it interfaces and the fluid medium surrounding it. We are interested in designing a biologically inspired substrata which controls mammalian cell migration based on principles of receptor/ligand interactions involved in its regulation. Recent studies have shown that integrin cell surface receptors for the extracellular matrix (ECM) proteins initiate signaling cascades, some of which are in common with those initiated by growth factors. We have quantitatively investigated the potential synergy between growth factors and ECM ligands in governance of cell motility. In initial experiments using a model system of the ECM protein fibronectin and epidermal growth factor (EGF), we found that locomotion speed of a mouse fibroblast cell line is affected by combinations of EGF and fibronectin in diverse ways that can be accounted for by a biophysical model for migration. Following on these finding, we have designed a minimalistic artificial matrix using the linear peptide sequence, arginine-glycine-aspartic acid (ROD), derived from fibronectin as the adhesion ligand, conjugated to a protein resistant poly (ethylene oxide) (PEO) surface. With this system, we have identified a role for the micro-level spatial presentation of the ROD peptide integrin ligand in stimulating migration. In addition, we have investigated the role of presentation of EGF as a soluble ligand in its governance of cell motility. We find that presentation of EGF in an autocrine manner in human mammary epithelial cells, where the cell simultaneously synthesizes the receptor and the ligand, results in the regulation of the directionality of cell motion. Formation of cell surface EGF/EGFR complexes in an autocrine manner causes an increased persistence of cell motion which is abrogated upon addition of EGF into the bulk extracellular media. These studies highlight the importance of quantitative deconstruction of a biological problem and have important ramifications for the rational design of cell receptor/ligand interactions to control cell behavior. / by Gargi Maheshwari. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1993. / Includes bibliographical references (leaves 361-369). / by Fred J. Armellini. / Ph.D.

Thesis (B.S.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1943. / MIT copy bound with: The use of scrap leather for artificial leather soles / Alfred B. Babcock, Jr. and William R. Kittredge. 1943. / Includes bibliographical references (leaves 20-21). / by Stanley B. Roboff. / B.S.

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1999. / "September 1999." / Includes bibliographical references. / It is well known that the method by which a drug is delivered can have a significant effect on the drug's therapeutic efficacy. There exist numerous cases where constant release is not the optimal method of drug delivery; instead, delivery of pulses of drug at variable time intervals is the preferred method. This method is commonly referred to as pulsatile delivery, and it is preferred in some cases because it closely mimics the way in which the human body naturally produces the compounds. The objectives of this thesis were to design, fabricate, and characterize a microchip capable of achieving both pulsatile and continuous release of multiple chemical substances on demand. Each prototype microchip consisted of an array of reservoirs etched into and extending through a silicon wafer. Each reservoir was covered on one end by a thin conductive membrane that served as the anode in an electrochemical reaction. The reservoir was filled with chemicals through the other side of the reservoir and was then sealed. The proposed release mechanism had no moving parts and was based on the electrochemical dissolution of a thin anode membrane covering each reservoir. Each reservoir was independently addressable, and the electric potential was applied to an anode membrane using wires and a potentiostat. Future integration of microelectronic components may allow reservoirs to be opened on demand by a preprogrammed microprocessor, remote control, or by biosensors and biofeedback controllers. Potential advantages of the microchip for the release of drugs and other chemicals may include its small size, low power consumption, and the absence of moving parts. Such microchips may find application in a wide array of fields such as drug delivery, medical diagnostics, chemical detection. industrial process monitoring and control, and micro-scale chemical synthesis. A process was developed for producing prototype microchips using microfabrication methods such as ultraviolet photolithography, chemical vapor deposition (CYD), reactive ion etching (RTE), and electron beam evaporation. An important component of this process was a procedure for making thin ( I 000-3000 [angstroms]), unsupported, metal membrane anodes on silicon. In addition, the fabrication process was designed so that the chemicals to be released would !lever be exposed to solvents, acids, bases, or high temperatures. This was accomplished by completing all device fabrication steps before reservoir filling. This important process feature would be especially useful when dealing with easily denatured molecules such as proteins or DNA. Gold was selected as the model membrane and electrode material for the prototype controlled release microchips primarily due to its unique electrochemical properties. It is easily deposited and patterned, has a low reactivity with other substances, and resists spontaneous corrosion in most aqueous solutions over the entire pH range. However, the presence of a small amount of chloride ion in solution creates an electric potential/pH region that thermodynamically favors the dissolution of gold as water soluble gold chloride complexes. Experiments showed that gold thin films are rapidly corroded in saline solution and that corrosion occurs preferentially in the grain boundaries. Release studies were conducted to demonstrate that single and multiple substances could be released from microchip devices on demand. Sodium fluorescein (a fluorescent dye) and radioactive calcium (in the form, 45CaCI) were chosen as model substances for release due to their simplicity of detection in solution. Prototype devices were filled with one or both substances, sealed, and submerged in either phosphate buffered saline or 0.145 M NaCl solution. A potential of+ 1.04 volts relative to a saturated calomel reference electrode (SCE) was applied between a gold membrane anode covering a filled reservoir and a cathode. Electrochemical dissolution of the gold membrane anode typically occurred within 10-20 seconds of application of the potential. Once the reservoir was opened, the compound in the reservoir was able to diffuse into the surrounding solution and was detected by fluorescence spectroscopy or scintillation counting. This process was repeated to obtain multiple releases from a single device. Disintegration refers to the "falling apart" of a gold membrane over a reservoir resulting from gold corrosion and possibly. applied physical stresses. The visualization of the membrane disintegration process was achieved by videotaping the corrosion of gold membranes through a microscope. The observations from these in situ membrane disintegration experiments were then combined with gold corrosion concepts and data to develop a qualitative mechanism for the disintegration of thin. gold membranes covering chemical reservoirs. Future work should focus on materials science issues, microelectronics fabrication and packaging, and in vivo studies. / by John Thomas Santini, Jr. / 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. / Includes bibliographical references (p. 227-234). / The work presented in this thesis consists of two major parts. In Chapter 2, the theory for sensitivity analysis of oscillatory systems is developed and discussed. Several contributions are made, in particular in the precise definition of phase sensitivities and in the generalization of the theory to all types of autonomous oscillators. All methods rely on the solution of a boundary value problem, which identifies the periodic orbit. The choice of initial condition on the limit cycle has important consequences for phase sensitivity analysis, and its influence is quantified and discussed in detail. The results are exact and efficient to compute compared to existing partial methods. The theory is then applied to different models of the mammalian circadian clock system in the following chapters. First, different types of sensitivities in a pair of smaller models are analyzed. The models have slightly different architectures, with one having an additional negative feedback loop compared to the other. The differences in their behavior with respect to phases, the period and amplitude are discussed in the context of their network architecture. It is found that, contrary to previous assumptions in the literature, the additional negative feedback loop makes the model less "flexible" in at least one sense that was studied here. The theory was also applied to larger, more detailed models of the mammalian circadian clock, based on the original model of Forger and Peskin. Between the original model's publication in 2003 and the present time, several key advances were made in understanding the mechanistic detail of the mammalian circadian clock, and at least one additional clock gene was identified. These advances are incorporated in an extended model, which is then studied using sensitivity analysis. Period sensitivity analysis is performed first and it was found that only one negative feedback loop dominates the setting of the period. / (cont.) This was an interesting one-to-one correlation between one topological feature of the network and a single metric of network performance. This led to the question of whether the network architecture is modular, in the sense that each of the several feedback loops might be responsible for a separate network function. A function of particular interest is the ability to separately track "dawn" and "dusk", which is reported to be present in the circadian clock. The ability of the mammalian circadian clock to modify different relative phases --defined by different molecular events -- independently of the period was analyzed. If the model can maintain a perceived day -- defined by the time difference between two phases -- of different lengths, it can be argued that the model can track dawn and dusk separately. This capability is found in all mammalian clock models that were studied in this work, and furthermore, that a network-wide effort is needed to do so. Unlike in the case of the period sensitivities, relative phase sensitivities are distributed throughout several feedback loops. Interestingly, a small number of "key parameters" could be identified in the detailed models that consistently play important roles in the setting of period, amplitude and phases. It appears that most circadian clock features are under shared control by local parameters and by the more global "key parameters". Lastly, it is shown that sensitivity analysis, in particular period sensitivity analysis, can be very useful in parameter estimation for oscillatory systems biology models. In an approach termed "feature-based parameter fitting", the model's parameter values are selected based on their impact on the "features" of an oscillation (period, phases, amplitudes) rather than concentration data points. It is discussed how this approach changes the cost function during the parameter estimation optimization, and when it can be beneficial. / (cont.) A minimal model system from circadian biology, the Goodwin oscillator, is taken as an example. Overall, in this thesis it is shown that the contributions made to the theoretical understanding of sensitivities in oscillatory systems are relevant and useful in trying to answer questions that are currently open in circadian biology. In some cases, the theory could indicate exactly which experiments or detailed mechanistic studies are needed in order to perform meaningful mathematical analysis of the system as a whole. It is shown that, provided the biologically relevant quantities are analyzed, a network-wide understanding of the interplay between network function and topology can be gained and differences in performance between models of different size or topology can be quantified. / by Anna Katharina Wilkins. / Ph.D.

Thesis (Sc.D.) Massachusetts Institute of Technology. Dept. of Chemical Engineering, 1953. / Vita. / Includes bibliographies. / by Curtis Chandler Williams, III. / Sc.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1986. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Includes bibliographies. / by Louis J. Durlofsky. / I. Flow between finite rotating disks II. Simulation of hydrodynamically interacting particles in stokes flow. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 1989. / GRSN 408655 / Science hard copy bound in 2 v. / Includes bibliographical references (leaves 255-261). / by Thomas Paul Griffin. / Ph.D.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2007. / Includes bibliographical references (p. 214-228). / In this thesis, the unusual physics of rodlike liquid crystals are explored through simulations of rigid-rod kinetic theory discretized by the finite element method. As their name suggests. these substances retain crystalline. anisotropic microstructure but deform as a liquid: the microstructure results from the anisotropic shape and interactions of the constituent molecules. The molecules are modeled as Brownian. interacting, rigid rods in a kinetic theory formulation. A solution of such rods undergoes a phase transition from a disordered (isotropic) state to an ordered (nematic) state as the density of rods is increased: such a solution also exhibits interesting, complex. non-Newtonian rheological behavior. Liquid-crystalline substances are used in a number of high-performance industrial applications because the aligned, liquid-crystalline structure yields superior mechanical properties in the final product. The properties can be compromised by any interfaces or defects present in the system. The processing of these systems is poorly understood, and further progress requires accurate modeling of the coupled evolution of the microstructure and non-Newtonian flow field. The main goal of this thesis is the simulation of liquid-crystalline phenomena featuring sharp nonhomogeneities in structure on the length scale of a single rod. Such critical phenomena include the interfaces and defects that are prevalent in isotropic-nematic coexistence, phase transitions. aligning boundaries such as walls. and nonhomogeneous flows. In order to capture this level of detail, simulations evolve the rod distribution function, which describes the distribution of rod positions and orientations, coupled with the velocity field. The evolution equation for the distribution function is known as the Doi diffusion equation. / Prior studies of rigid rod behavior have typically avoided this level of detail: instead. a series of approximations and assumptions have been used to simplify the diffusion equation and avoid evolving the distribution function since it is a quantity that varies in both spatial dimensions and orientation dimensions. These prior studies evolve the order tensor (the second moment of the distribution function) and invoke closure approximations to obtain a closed form for an evolution equation for this tensor. However, these techniques suffer from inaccuracy, often of unknown magnitude, because of the closure approximations, and they lose the ability to describe phenomena where gradients in structure on the length scale of a single rod are important or where variations in density are important. This thesis avoids these approximations and their attending limitations. A parallel, finite-element method is used to discretize the rod distribution function and the rod interaction potential. However, these simulations differ from traditional finite-element-based simulations of complex fluids because of the coupling between the physical space for rod location and orientation space for rod alignment and because of the difficulty of computing extended rod-rod interactions in a tractable manner. Instead of approximating the rod-rod interaction potential via Taylor expansions as previous studies have done, novel numerical methods are developed to meet these challenges and allow rapid, parallel computation of the full, nonhomogeneous Doi diffusion equation. These methods are applied to the equilibrium phase behavior of solutions of rigid rods in both periodic systems and system bounded by hard walls. Newton's method is used to solve the nonlinear set of equations for extrema of the system free energy, and the properties of the Jacobian matrix describe a local free energy surface. / Simulation results show that periodic, isotropic-nematic coexistence states are stable in a given concentration range; the bulk phase properties and interfacial properties are independent of the average concentration or size of the system if the solution is stable. Results for confined systems show a number of surprising results when hard wall boundary conditions are used; in particular, the phase behavior of an extremely large system bounded by walls does not converge to the phase behavior of a homogeneous system without bounds, because the walls fundamentally alter the free energy surface of the system. Spinodal decomposition, the phase transition from an unstable isotropic state to a stable nematic state, is also studied. Prior studies of this process have been limited to linear stability analyses and have yielded sharp conflicts about the dominant mechanism of the process. The linear stability analysis is re-examined and prior conflicts are resolved by numerically showing that the process mechanism is a strong function of the system concentration and diffusivities for rotational and translational rod motion. A semi-implicit, finite-element-based time stepper is then used for full dynamic simulations of the spinodal decomposition process. These simulations mark the first results for the nonhomogeneous Doi diffusion equation in the spinodal decomposition process, and the results show how restricted rod motion can cause the process to become kinetically trapped in nonhomogeneous intermediate states. The method is also applied to the related problem of coarsening between large nematic domains of aligned rods, and results show the effects of domain misalignment on the final structure. This dynamic method is then extended to simulations of rigid rods in wall-driven, rectilinear shear flow and pressure-driven flow between parallel plates. These simulations mark the first results for the full nonhomogeneous Doi diffusion equation in nonhomogeneous shear flow. / Silmulation results show that the accurate treatment of wall-rod interactions is critically important: aphysical anchoring conditions at walls can suppress out-of-plane instabilities in planar shear flow. Also. simulations of pressure-driven flow show that misaligned domains marked by "'twist" interfaces can spontaneously form as a result in gradients in the shear rate: this concept lends important insight into the formation of domains in macroscopic rheological experiments. Results also show that miisaligned. tumnbling domains are not stable. Phase diagrarns for wall-driven. rectilinear shear flow and pressure-driven. rectilinear shear flow are given for varying shear rate and system size. / by Micah James Green. / Ph.D.