Department of Chemical Engineering Graduate Theses

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    Microfluidic platforms to evaluate the effects of drugs on fertility and proteins on cancer progression – a focus on cisplatin, alpha-smooth muscle actin, and glial cell line-derived neurotrophic factor
    (2024-05-06) Bustillo Perez, Bexi; Chemical Engineering; Wells, Laura
    The introduction of in vitro systems that can mimic organ physiology and allow studying the progression of diseases such as cancer is necessary to get reliable information about cell responses and test drug efficacy and toxicity. Classical cell culture systems facilitate a wide range of clinical in vitro studies. These cell culture systems often consist of static and flat platforms that poorly mimic the conditions in living organisms. Microfluidics has emerged as an innovative technology that provides the tools to study cells in dynamic conditions that are present in the cell microenvironment. Two-dimensional (2D) and three-dimensional (3D) microfluidic cell cultures also referred to as organ-on-a-chip (OOC) have proved to have the potential to replace animal models since it is possible to recreate key factors of the organs inside the human body, those factors include gradients of growth factors, oxygen, pH, cycling strain, and shear stress. In the present work, microfluidic platforms have been designed and fabricated to seed and grow bovine oviduct epithelial cells, to measure changes in the cilia beating frequencies (CBFs), when those cells are exposed to cisplatin using an oviduct-on-chip platform. The transparent membrane assembled in this device facilitates observational studies of the cells alive. Establishing an air-liquid interface in the microfluidic chip allowed us to maintain the cell polarization for up to three months. An oviduct fimbriae-on-a-chip was also developed with the previously fabricated microfluidic device, to study some of the early events that occur in the development of ovarian cancer. A third microfluidic platform was fabricated to evaluate cell migration mediated by the Rearranged during transfection (RET) receptor and to evaluate the response of cells to chemotherapy in different collagen-based hydrogels.
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    Supercapacitor-Battery Hybrid Based on Multivalent Vanadium
    (2024-05-03) Lung, Ej Jun; Chemical Engineering; Barz, Dominik
    This thesis is concerned with a hybrid energy storage device that combines the advantages of both a battery and a supercapacitor. The hybrid utilizes two different charge storage mechanisms: electrical double layer formation and Faradic reactions by combination of high-surface area electrode materials and a redox active species in the electrolyte. This hybridization results in a relatively high energy content at low current densities as well as high-power density at high current densities. In this thesis, we investigate different strategies to utilize all four vanadium redox states to further increase the performance of the hybrid. Two strategic approaches are pursued to enable an additional redox reaction utilizing vanadium with a redox state of II: i) tuning the electrolyte composition and ii) adjusting the electrode size. By expanding the voltage window, these novel approaches resulted in devices with a higher specific energy density and specific capacity compared to the previous design. A multitude of characterization methods are utilized in this thesis. Three-electrode and two-electrode cyclic voltammetry is conducted to identify the redox peaks contributing to the faradic reaction during galvanostatic charge and discharge. Electrochemical impedance spectroscopy is carried out to measure the impedance of the coin cells and how different factors, such as the conductivity of the electrolyte, membrane, or current collector material, affect it. In terms of membranes, Neosepta® Cation Exchange Membrane performs best at lower current densities, while NafionTM 212 or a glass fiber filter paper are preferred for higher current densities. A device with 3M vanadyl sulfate in 2 M sulfuric acid showed the highest initial discharge capacity of 1460 mA h g-1 (2.28 mA h cm-2) at 5 A g-1. Additionally, this thesis proposes a novel flexible three-electrode device (F3ED). The design of the F3ED allows for the usage of two different membranes, enabling the device to operate over a wider range of ii current densities. A prototype of the F3ED is produced, and the results successfully demonstrate the feasibility of the design. The concept of a three-electrode design might also work for other (hybrid) systems that face challenges in operating over a wide range of current densities.
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    Co-Delivery of Peptide QK and WKYMVm for Minimally Invasive Therapeutic Angiogenesis in Treating Critical Limb Ischemia
    Pang, Yuan; Chemical Engineering; Brian, Amsden
    Critical Limb Ischemia (CLI) is a leading cause of mortality among vascular diseases. Current surgical treatments often fail due to the ineffective restoration of blood flow in the diseased vasculature, leading to high rates of amputation and mortality. The delivery of therapeutic peptides emerges as a promising alternative, offering the potential to stimulate non-invasive angiogenesis at ischemic sites. However, current delivery platforms still face challenges such as burst release, incomplete delivery, and the potential to generate acidic by-products that deactivate the therapeutics. To address these issues, we propose a manually injectable viscous liquid platform consisting of an aliphatic polycarbonate for the delivery of pro-angiogenic peptides QK and WKYMVm. The polymer bears pendant short-chain fatty acids (SCFAs) that have the potential to polarize M2 macrophages and modulate the immune response. The system is also degradable into non-acidic products through intramolecular cyclization. In this work, we investigated the hydrolytic degradation of copolymers composed of 5-hydroxyl trimethylene carbonate (HT) and 5-butyrate-trimethylene carbonate (BtT), as well as terpolymers containing trimethylene carbonate (T), HT, and BtT or 5-propionate-trimethylene carbonate (PtT), initiated with either 1-octanol or triethylene carbonate (EG3). The terpolymer system achieved a sustained degradation profile with maximum mass loss of 70% in four weeks. An HT content below 75% resulted in incomplete mass loss, as the HT units led to insufficient segmentation into water-insoluble oligomers. Terpolymers initiated with EG3 exhibited a higher degree of mass loss than those initiated with 1-octanol, due to increased chain flexibility, hydrophilicity, and solubility of cleaved oligomers when attached to EG3. The polymer degradation products were non-cytotoxic to 3T3 fibroblasts. Injectable peptide formulations with single or dual loading of QK and WKYMVm were successfully created, achieving sustained release of structurally intact WKYMVm and QK over four weeks, with near-complete release of WKYMVm and 71% of QK. Additionally, we investigated the feasibility of creating solid delivery devices by incorporating UPy motifs into the originally amorphous T-based polymer, enabling a semi-crystalline transition through terminal dimerization induced by quadruple hydrogen bonds.
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    Macromolecular Migration in Microfluidics
    Coombs, Steacy; Chemical Engineering; Giacomin, Alan Jeffrey; Escobedo, Carlos
    One of the great fascinations chemical engineers have with polymeric liquids is their curious behaviour when confined. In this thesis, we use macromolecular theory that relies entirely on flow orientation to explain the rheology of polymeric liquids in confinement. Specifically, we use rigid dumbbell theory to explain the curious effects of polymer confinement: (a) diminishing complex viscosity, and (b) emigration from high-shear. Whereas much is known about the complex viscosity of polymeric liquids, far less is understood about the behaviour of this material function when macromolecules are confined. By confined, we mean that the gap along the velocity gradient is small enough to reorient the polymers. In the first part of this thesis, we examine classical analytical solutions for a confined rigid dumbbell suspension in small-amplitude oscillatory shear flow. We test these analytical solutions against the measured effects of confinement on both parts of the complex viscosity of a Carbopol suspension and three polystyrene solutions. Microfluidic design, fabrication and experiments have developed rapidly, leading to lab-on-chip separation or fractionation. In the second part of this thesis, we design a continuous concentrator for macromolecular solutions. Our design relies on the analytical solutions for orientational diffusion under laminar pressure-driven slot flow through a microchannel. Using rigid dumbbell theory, we provide analytical solutions for the design of our microfluidic macromolecular hydrodynamic chromatography. We arrive at our design through the use of well-known confinement-driven composition profiles. Using a pair of razor-sharp blades, our design separates the slot flow into a symmetric core inner slot (concentrated) between two outer slots (diluted). We discover a minimum dimensionless blade leading edge separation for complete fractionation, and that this decreases with confinement, and also decreases with dimensionless shear rate. In the last part of this thesis, using our earlier analytical rigid dumbbell theory for orientational diffusion under laminar pressure-driven slot flow through a microchannel, we design and fabricate a passive, continuous microfluidic separator. By passive, we mean channel geometry or particle inertia control the migration inside the microchannels. We designed and fabricated (soft lithography) slot-flow and square duct straight microfluidic channels with one inlet and three outlets.
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    Machine Learning-Driven Insights: Rare Disease Drug Discovery and Cancer Patient Stratification
    Li, Xinran; Chemical Engineering; Yang, Laurence
    The computational prowess of machine learning (ML), synergized with the establishment and refinement of diverse databases, emerges as a tool to revolutionize drug discovery and cancer treatment. In this thesis, a pipeline incorporating a novel deep-learning based ML method with traditional molecular docking was developed to accelerate drug screening for leishmaniasis. This thesis then concentrated its analytical lens on the categorization of triple negative breast cancer (TNBC) by applying unsupervised learning algorithms on gene expression data. The resultant subtypes, as delineated by each algorithm, underwent a comparative analysis. Furthermore, these clusters were enriched for gene ontology (GO) terms to unveil the distinct characteristics and prognosis implications of potential new clusters.