Biomedical Engineering and Bioengineering Commons^™

Design Of Human Serum Albumin And Adenovirus Conjugation Via Catcher/Tag Molecular Glue, Peijie Zhao

McKelvey School of Engineering Theses & Dissertations

Adenovirus (Ad) has been the ideal cargo delivery mechanism, and its moderate immunological response makes it ideal for in vivo gene therapies since its discovery in 1953. However, the robust immunogenicity of the Ad capsid and low vaccine absorption via mucous membranes and epithelium put a limit on the process of developing intranasal vaccines. Efforts are being made to enhance the effectiveness of Ad vectors and numerous studies have demonstrated the remarkable capacity of human serum albumin (HSA) to extend plasma half-life and facilitate targeted intranasal delivery. In this study, we devised an innovative method for employing the Catcher/Tag molecular …

Improving And Integrating Quantitative Single Cell Spatial Biology For Theranostic Medicine, Peng Lu

McKelvey School of Engineering Theses & Dissertations

Disease states are the result of a complex interplay of many different cell types interacting in close proximity in the context of often heterogeneous tissues. Alpha particles are drawing intense research and clinical interest because of their potent cytotoxic effects and their short path lengths. Analyzing the dose distribution and tissue micro-environment for alpha therapy plays a key role in predicting the efficacy of this targeted radiotherapy. However, to date there have been no direct on-tissue analytical methods for alpha dose distributions and the corresponding tissue microenvironments.

Therefore, we have developed a pipeline to overcome this limitation by utilizing quantitative …

Automatic Cardiac Mri Image Segmentation And Mesh Generation, Ziyuan Li

McKelvey School of Engineering Theses & Dissertations

Segmenting and reconstructing cardiac anatomical structures from magnetic resonance (MR) images is essential for the quantitative measurement and automatic diagnosis of cardiovascular diseases [1]. However, manual evaluation of the time-series cardiac MRI (CMRI) obtained during routine clinical care are laborious, inefficient, and tends to produce biased and non-reproducible results [2]. This thesis proposes an end-to-end pipeline for automatically segmenting short-axis (SAX) CMRI images and generating high-quality 2D and 3D meshes suitable for finite element analysis. The main advantage of our approach is that it can not only work as a stand-alone pipeline for the automatic CMR image segmentation and mesh …

Calculating The Difference In Stiffness Of Living T Cells Through Micropipette Aspiration, Minju Lee

McKelvey School of Engineering Theses & Dissertations

Cardiovascular disease (CVD) accounted for 17.9 million deaths in 2019, with fibrosis contributing to nearly a quarter of these fatalities [1,2]. Fibrosis, characterized by excessive connective tissue formation, has been strongly linked to T cells, essential components of the immune system. This study explores the mechanisms of T cell activation and the subsequent changes in biophysical properties like diameter, stiffness, and elasticity, aiming to develop therapeutic strategies for fibrosis-related diseases, including CVD. Utilizing the micropipette aspiration technique, we accurately assessed T cell stiffness and observed a change in bulk cell stiffness upon activation. The results demonstrated increased fluid-like behavior in …

The Effect Of Spinal Cord Stimulation And Video Games Training On Body-Machine Interface Control, Jie Fei

McKelvey School of Engineering Theses & Dissertations

Damage to the spinal cord causes long-lasting loss of motor and sensory function, and currently, there is no ‘cure’ for paralysis. However, even people with severe spinal cord injuries (SCI) have some residual mobility. Studies have shown that transcutaneous electrical spinal cord stimulation (tSCS) combined with functional training targeting residual mobility can further improve the motor function of individuals with SCI. In this study, we present a technical framework that aims to enhance rehabilitation outcomes by targeting residual mobility through a motor training-based approach. Our technical framework centers around a non-invasive body-machine interface (BoMI) that relies on the use of …

Novel Microfluidic Devices To Model The Interactions Between Lymphatics And Breast Cancer, Jade Weber

McKelvey School of Engineering Theses & Dissertations

The lymphatic system is responsible for immune circulation and fluid balance in the body. It accomplishes this by draining interstitial fluid from local tissue and transferring it to lymph nodes and back into blood circulation. However, this process is implicated in many pathologies, one of the most dangerous being breast cancer metastasis to the lymph nodes. The largest factor in breast cancer patient mortality is metastasis. Lymphangiogenesis, the growth of new lymphatic vessels, has been thought to play a dynamic role in aiding breast cancer metastasis. Breast cancer tumor cells have been shown to remodel the functionality of local lymph …

Optical Perturbation Of Protein Kinase A Activity Via Photoactivatable Inhibitor Peptides, Peter Chen

McKelvey School of Engineering Theses & Dissertations

Protein Kinase A (PKA) plays important roles in diverse biological processes such as sleep, long term memory, and synaptic plasticity. In addition, PKA also acts as an integrator of neuromodulator signaling though G protein-coupled receptor activation. However, despite genetic knockout and pharmacological inhibition experiments that demonstrate the importance of PKA, it is unclear where, when, or how PKA plays these roles in cellular physiology and behavior. In order to better understand the function of PKA in these processes, and how neuromodulator signaling drives complex behavioral changes, there exists a need for a method to selectively activate/inactivate PKA with high spatial …

A General-Purpose Software Platform For Closed-Loop Neuromodulation, William Engelhardt

McKelvey School of Engineering Theses & Dissertations

Implementing closed-loop neuromodulation therapies is a challenging and expensive endeavor. It requires developing software capable of acquiring signals from a bio-signal amplifier, analysis of these signals, and initiation of precisely timed stimulation, all of which need to be accomplished in real-time with very low latency. Developing this software is difficult, as it requires a wide range of expertise ranging from interfacing with hardware to real-time signal processing. Even when successfully implementing such a system for one set of hardware, it often then only works within the laboratory that conceived it. This is because of the inherent heterogeneity in the devices …

Single-Molecule Super-Resolution Imaging Of Geobacter Sulfurreducens Under Anaerobic Conditions, Ziyi Hu

McKelvey School of Engineering Theses & Dissertations

Geobacter sulfurreducens are anaerobic bacteria capable of making electrical contacts with other organisms and extracellular electron acceptors. The challenge of imaging live Geobacter bacteria is maintaining anaerobic conditions during the imaging process. In this thesis, we augment a single-molecule localization microscope (SMLM) with a home-built anaerobic imaging chamber and use constant argon bubbling to maintain oxygen-free imaging conditions. To validate the imaging protocol, we use the transient binding of Nile red to resolve the spherical morphology of lipid-coated glass spheres with nanoscale resolution. However, when imaging Geobacter, the distribution of Nile red localizations is non-uniform, both between different cells …

Development Of A Multispectral Vis-Swir Imaging Modality For Cutaneous Water Assessment, Quinlan Mcgrath

McKelvey School of Engineering Theses & Dissertations

Inflammatory skin diseases are estimated to impact 20% of the global population and are the fourth leading cause of nonfatal disability worldwide. Diagnosis and management are predominantly based on clinician visual assessment of disease related changes in skin morphology. The qualitative nature of this method can result in misdiagnosis and underdiagnoses of treatable diseases. There persists systematic undertreatment of skin of color patients given the more subtle presentation of erythema against pigmented skin. There exists a clinical need for a quantitative and objective inflammation assessment tool that meets the needs of a diverse patient population. The accumulation of interstitial fluid …

A Novel Mrna Delivery Strategy Employing Adenovirus Piggyback Mrna Binders Via Catcher/Tag Molecular Glue, Kexin Geng

McKelvey School of Engineering Theses & Dissertations

mRNA-based therapeutics open a new era for the prevention and treatment of a wide range of diseases. However, existing mRNA delivery vehicles have limited repertoires for dendritic cell targeting and intranasal administration which are two paramount delivery pathways of significant advantages for treating cancer and infectious respiratory diseases. Adenovirus (Ad) with well-deciphered viral genomes and intensive-studied structure biology has been developed for DCs-targeted cancer vaccines and intranasal COVID vaccines. In light of these virtues, Ad presents as the “off-the-shelf” tool possessing well-defined manufacturable capabilities and translatable feasibility that perfectly complements the current limitations of mRNA delivery. In this study, we …

3-Dimensional Visualization Of Cardiac Plaque Mapping Data, Phan Ly Vy Nguyen

McKelvey School of Engineering Theses & Dissertations

Atrial Fibrillation (AF) of one of the most prevalent cardiac arrythmia in humans, and also the most studied arrythmias due to its high association with cardiovascular morbidity and mortality. Diagnosis of AF, which is highly dependent on the observation of the irregular signal in the atria, is often challenging since AF is often asymptomatic at the onset. There has been a lot of effort in exploring different cardiac mapping techniques to understand the dynamics of AF for better intervention. This study aims at developing a MATLAB interface that assists the development of a cardiac plaque mapping data acquisition system in …

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

Dual Color Optogenetic Control For Analyzing Cardiac Function In Drosophila, Jiantao Zhu

McKelvey School of Engineering Theses & Dissertations

Prolonged consumption of carbohydrate-rich diets and immobile lifestyles frequently cause metabolic disorders and obesity and, as a result, may lead to progressive heart dysfunction among broad social groups of the population. Drosophila melanogaster serves as an essential model organism in cardiovascular disease research due to conserved physiological and genomic traits shared with humans, its genetic and molecular toolbox versatility, and cost-effective maintenance. Here, we combine optogenetics and optical coherence tomography to study cardiovascular function in D. melanogaster. A new optogenetic pacing system has been developed, employing a transgenic line carrying two opsins: ChR2 and NpHR2.0. A custom-built hardware setup …

Development Of Methods To Enhance Stem Cell Derived Islet Survival, Aining Fan

McKelvey School of Engineering Theses & Dissertations

No abstract provided.

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …

Comparison Of In-Vitro 3d Human Embryoids With Current Models For Gastrulation, Jin Park

McKelvey School of Engineering Theses & Dissertations

Gastrulation is an early morphogenetic process that is conserved across most metazoans and lays out the future body plan through the formation and shaping of the three germ layers: endoderm, mesoderm, and ectoderm. Despite its importance, not much is known about the events surrounding human gastrulation that occurs in utero due to ethical and technical limitations on studying human embryos. Therefore, many researchers have devised protocols for creating in vitro models of gastrulation using embryonic stem cells. Initially starting with mouse embryonic stem cells, the field of in vitro embryo models has advanced rapidly, with protocols using human embryonic stem …