Master of Science, The Ohio State University, 2024, Microbiology

The human gut microbiome is the collection of the microbiota that reside in the human intestinal tract. Imbalances in the gut microbiome are associated with multiple diseases, so studying this is important for preventing and treating these conditions. These imbalances can have multiple causes, such as changes in core temperature. Previous work has indicated that the gut microbiome could play a role in mitigating negative effects of temperature on epithelial tissues, which could have profound effects on human health. Research into the human gut is normally performed by way of animal models, or by using a synthetic model involving the use of human cells on transwells. The goal of this study was to collect preliminary data to determine if gene expression in gut epithelial cells is influenced by the presence of a fecal sample at hypoxic, hyperthermic conditions. An experiment was performed on 36 gut-on-a-chips over the course of 48 hours at three different temperature levels: 30°C, 37°C, and 42°C. Next-Generation Sequencing (NGS) was performed to determine gene expression in the human epithelial cells when comparing the introduction of a fecal sample to the chip in low-oxygen conditions at 42°C. Most genes in the host cells were upregulated when exposed to the fecal sample, with the majority being involved in immune system responses, as well as cell growth and differentiation, host metabolism, and enzymatic activity, which is consistent with what would be expected when the gut bacteria are present. The gut-on-a-chip can be used to study temperature effects on the human epithelial cells, as well as test ways to counteract any negative effects that come with this shift. Future studies can elucidate the role that the gut microbiome may play in the response of the human body to changes in core temperature.

Committee: Karen Dannemiller (Committee Chair); Joshua Hagen (Committee Member); Justin North (Committee Member) Subjects: Biology

Master of Science (M.S.), University of Dayton, 2024, Bioengineering

Electrospun nanofiber (ESNF) membranes have attracted widespread interest in many applications due to their advantages in high specific surface area, high porosity, and structural controllability. This study combines gap electrospinning and electrolyte-assisted electrospinning techniques to develop a novel electrospinning approach for producing nanofiber mats of arbitrary geometry. A 3D printed conductive gelatin-based polymer electrolyte (GPE) solution is used as a geometric collector to focus the deposition of electrospun mats. The method utilizes syringe extrusion 3D printing of the GPE solution to produce a shape upon which ESNF are focused. The printable GPE ink is formulated to ensure it possesses the necessary conductivity, shear-thinning, and thixotropic properties. We have developed a gelatin-based GPE ink, enhanced with Laponite to improve shear-thinning properties and salts to increase conductivity. The 3D printing equipment then extrudes the GPE solution on the surface of the target device according to the pre-designed pattern. The optimized GPE solution formulation contained 8% w/v gelatin, 0.2% w/v Laponite, 2 mol/L sodium chloride, and 14.3% v/v glycerol, which was shown to meet the dual requirements of 3D printing and assisting electrospinning. The ink's conductivity was 8.02 S/m measured using a custom developed four-point probe system for gels. Rheological analysis demonstrated that the ink exhibits shear thinning (fluid behavior index n=0.223), which allows GPE ink to maintain a balance between easy extrusion and structural stability. We tested the electrospinning solution used during the experiment and investigated and characterized electrospinning operating parameters to explore several relationships between unrestricted mat diameter (UMD) and electrospinning operating parameters and GPE patterning threshold. The performance of the GPE ink was thoroughly examined experimentally: under the conditions of 25°C and 26% relative humidity, the (open full item for complete abstract)

Committee: Russell Pirlo (Committee Chair); Donald Klosterman (Committee Member); Erick Vasquez (Committee Member); Li Cao (Committee Member) Subjects: Biomedical Engineering; Biomedical Research

Master of Science (M.S.), University of Dayton, 2022, Chemical Engineering

Microfluidic lab-on-chip and organ-on-chip devices have revolutionized the research, development, and analysis of chemical and biological systems. On-chip devices can be customized for many applications by integrating functional components such as ports, valves, and sensors to control and perform laboratory functions, including reactions and analysis. The most common technique used to fabricate these devices is soft lithography, which requires multiple manual processing and subsequent alignment and assembly steps. However, additive manufacturing is becoming the dominant technique as it allows for the rapid prototyping of different chip designs with fewer steps and materials. Fused filament fabrication (FFF) is one of the several additive manufacturing technologies used to fabricate microfluidic devices. This method enables the addition of functional components such as valves, ports, and sensors via a print-pause-print approach. In addition, FFF allows for small-batch iteration and customization of chip designs. Furthermore, the layer-by-layer 3D printing process registration is fully automated, allowing for advanced 3D designs to be manufactured with no human intervention. Essential functional components of on-chip include ports, valves, channels, and windows. Transparent windows enable monitoring and analysis via microscopy, fluorometric and colorimetric assays, and non-contact optical sensing/actuating techniques. Fused filament fabrication has an inherent drawback in its application to fabricate transparent windows due to the inter-filament seams resulting from the fusion of adjacent filaments. While these seams hold the printed construct together and play a role in the device's mechanical properties, including its resistance to leakage under pressure, they also create imaging artifacts that absorb light. Previous approaches to bypass this limitation have been demonstrated using polystyrene, polymethylmethacrylate, and thermoplastic polyurethane filaments. How (open full item for complete abstract)

Committee: Russell Pirlo (Advisor); Kevin Myers (Committee Member); Li Cao (Committee Member) Subjects: Chemical Engineering

Master of Science, Miami University, 2017, Chemical, Paper and Biomedical Engineering

Engineered nanoparticles show great promise as a future medium for drug delivery due to their ability to transport great distances within the human body. Recent studies have shown that some nanoparticles may have the ability to diffuse to the central nervous system by means of the olfactory region of the nasal cavity. Although animal models and human simulations are available, the information they can provide is limited. In order to better test nanoparticles on this possible pathway, this study has created a more advanced respiratory device that incorporates a microfluidic device in a nasal cavity model to mimic the olfactory region through 3D modeling and printing. The unique geometry of the nasal cavity allows for the gathering of more realistic results. This unique respiratory device, in conjunction with an artificial lung apparatus, is able to accurately simulate a breathing human nasal cavity. During this study, the artificial nasal cavity was exposed to particles of varying sizes to determine the dosage reaching the olfactory region, which in turn can be used to determine which types of particles are most likely to travel this pathway. Results show similar trends to that of past studies: smaller nanoparticles are more effective at transporting to the olfactory region. While preliminary results are promising, further modifications to the setup are discussed that might better simulate an actual nasal cavity as well as to incorporate cell culture into the design.

Committee: Lei Kerr PhD (Advisor); Shashi Lalvani PhD (Committee Member); Douglas Coffin PhD (Committee Member) Subjects: Biomedical Engineering; Chemical Engineering