Biomedical Engineering and Bioengineering Commons^™

Plasmonically-Enhanced Dna-Rna Hybrid-Based Bioassay For Amplification-Free Quantification Of Sars-Cov-2, Yuxiong Liu

McKelvey School of Engineering Theses & Dissertations

Corona Virus Disease 2019 (COIVD-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly infectious respiratory illness. Within just a few months, it spread around the whole world and became a global pandemic. Real-time reverse-transcription polymerase chain reaction (RT-PCR) works as a gold standard method diagnosing COVID-19 with high sensitivity and specificity. But due to the programs of RT-PCR, it usually takes more than 24 hours to get the results while specialized devices are also required. False-negative results can happen as well using RT-PCR which increase the risk of spreading coronavirus. To promote quicker detection of COVID-19, …

Toward Lignin Valorization: Development Of Rhodococcus Opacus Pd630 As A Chassis For Triacylglycerol (Tag) Production From Recalcitrant Aromatic Feedstocks, Rhiannon R. Carr

McKelvey School of Engineering Theses & Dissertations

The advent of the industrial era was precipitated by the discovery of fossil fuels, and ushered in unprecedented changes for humanity included but not limited to the development of rapid transit and communications, improvements to food distribution and preservation, the mass production of goods, and a radical rearrangement of communities from relatively small enclaves to metropolises. With all the benefits, however, come considerable costs, especially to the global environment. Greenhouse gas emissions, built up over centuries of unregulated combustion, have precipitated a rate of global temperature change unparalleled in the 4.5 billion-year history of this planet. In order to preserve …

Single-Molecule Localization Microscopy Of 3d Orientation And Anisotropic Wobble Using A Polarized Vortex Point Spread Function, Tianben Ding, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Within condensed matter, single fluorophores are sensitive probes of their chemical environments, but it is difficult to use their limited photon budget to image precisely their positions, 3D orientations, and rotational diffusion simultaneously. We demonstrate the polarized vortex point spread function (PSF) for measuring these parameters, including characterizing the anisotropy of a molecule’s wobble, simultaneously from a single image. Even when imaging dim emitters (∼500 photons detected), the polarized vortex PSF can obtain 12 nm localization precision, 4°–8° orientation precision, and 26° wobble precision. We use the vortex PSF to measure the emission anisotropy of fluorescent beads, the wobble dynamics …

Using Computer Vision To Track Anatomical Structures During Cochlear Implant Surgery, Nicholas Bach

McKelvey School of Engineering Theses & Dissertations

There is a steep learning curve for surgeons performing cochlear implant surgeries. We aimed to use computer vision to track anatomical features with the goal of helping surgeons perform cochlear implant surgery without damaging the cochlea. We compared nine algorithms in total, seven object tracking algorithms and two optical flow algorithms utilizing the LucasKanade method, on manually created cochlear implant surgery videos to determine the accuracy associated with each. Compared with eight other algorithms, we observed that an iterative pyramidal implementation of the Lucas-Kanade (IPLK) method, implemented through OpenCV, performed the best. The IPLK method had the lowest error rate …

Towards The Discovery Of Prognostic Biomarkers For Glioblastoma Using Resting-State Functional Connectivity, Andy G. S. Daniel

McKelvey School of Engineering Theses & Dissertations

Gliomas are highly diffusive, primary brain tumors. The most malignant form, glioblastoma, has a dismal survival rate: 14-17 months following the current standard of care, which consists of surgery, radiation, and chemotherapy. Insights into the molecular, cellular, and microenvironmental components of glioblastoma have revealed a vast array of factors utilized to support its proliferation, infiltration, and resistance to treatment. Recent advancements have also identified diagnostic and prognostic biomarkers that are now being used to guide treatment planning. However, survival has improved only marginally, thus emphasizing the continued need for novel biomarkers and treatment strategies. Given its delicate location in the …

Photoacoustic Imaging, Feature Extraction, And Machine Learning Implementation For Ovarian And Colorectal Cancer Diagnosis, Eghbal Amidi

McKelvey School of Engineering Theses & Dissertations

Among all cancers related to women’s reproductive systems, ovarian cancer has the highest mortality rate. Pelvic examination, transvaginal ultrasound (TVUS), and blood testing for cancer antigen 125 (CA-125), are the conventional screening tools for ovarian cancer, but they offer very low specificity. Other tools, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET), also have limitations in detecting small lesions. In the USA, considering men and women separately, colorectal cancer is the third most common cause of death related to cancer; for men and women combined, it is the second leading cause of cancer deaths. …

Quantitative Flow Cytometry-Guided Protein Biomarker Characterization For Translational Proteomics And Precision Medicine, Yingye Fang

McKelvey School of Engineering Theses & Dissertations

Angiogenesis, the growth of blood vessels from pre-existing vasculature, is primarily regulated by vascular endothelial growth factor receptors (VEGFRs). Dysregulated angiogenesis is associated with cancers, obesity, and over 70 vascular diseases. Upregulated VEGFR protein expressions in diseased vasculature are promising biomarkers for predicting clinical outcomes, as indicated by non-quantitative immunohistochemical studies in patients with impaired vascularization or tumor angiogenesis. While the quantitative characterization of VEGFRs is critical in identifying biomarkers for anti-angiogenic therapies, VEGFR biomarker development presents two particular challenges: (1) The invasive tissue biopsy needed limits the amount of VEGFR data that can be collected from both normal and …

Attachment Of Fibrous Materials In Nature And Surgical Repair, Ethan Daniel Hoppe

McKelvey School of Engineering Theses & Dissertations

Mother nature is the ultimate problem solver. Often by brute force and necessity for survival, the organism that has the best solution to a problem is the one to proliferate. One of these problems for which nature provides an elegant solution is the attachment of dissimilar materials. This dissertation explores the strengthening and relaxation of interactions between soft and hard materials, typically with one of the two being fibrous in character, with the goal of identifying strategies for improving the surgical reattachment of tendon to bone. The work begins with a study of the plant Harpagonella palmeri, which the dissertation …

Human Ipsc Tissue-Engineered Cartilage For Disease Modeling Of Skeletal Dysplasia-Causing Trpv4 Mutations, Amanda R. Dicks

McKelvey School of Engineering Theses & Dissertations

Cartilage is essential to joint development and function. However, there is a variety of cartilage diseases, ranging from developmental (e.g., skeletal dysplasias) to degenerative (e.g., arthritis), in which treatments and therapeutics are lacking. For example, specific point mutations in the ion channel transient receptor potential vanilloid 4 (TRPV4) prevent proper joint development, leading to mild brachyolmia and severe, neonatally lethal metatropic dysplasia. Tissue-engineered cartilage offers an opportunity to elucidate the underlying mechanisms of these cartilage diseases for the development of treatments. Human induced pluripotent stem cells (hiPSCs) are an improved cell source option for cartilage tissue engineering given their minimal …

Mechanisms For Osteoblast And Osteocyte Initiation And Sustainment Of Bone Formation In Young-Adult And Aged Mice, Taylor Lynn Harris

McKelvey School of Engineering Theses & Dissertations

The cellular mechanisms for loading-induced bone formation, from osteocyte mechano-sensation to osteoblast-directed bone formation, are not well understood. Elucidating these mechanisms and identifying any processes that are disrupted in aged mice can aide in the development of new anabolic drugs for treating diseases like osteoporosis. This thesis begins by investigating the genes expressed by osteocytes following loading at an early mechanosensitive (4-hr) timepoint, and later at a bone-forming (day 5) timepoint. We demonstrated increases in Ngf and Wnt1 in osteocyte-enriched intracortical bone by laser capture microdissection and microarray analysis. These results were important in demonstrating the presence of Ngf in …

Understanding And Improving Adult Stem Cells For Cartilage Tissue Engineering, Dakota Katz

McKelvey School of Engineering Theses & Dissertations

Articular cartilage allows for near frictionless joint movement; however, when damaged the tissue has very little capacity for self-repair. Tissue engineering can be used to both repair damaged articular cartilage and as an in vitro model for joint disease. Commonly used cell sources for tissue engineering are adipose-derived and bone marrow-derived mesenchymal stem cells (ASCs and MSCs) because they can be patient matched, expand rapidly in culture, and have multipotent differentiation potential. However, donor-to-donor variability of differentiation potential can mask the results of in vitro experiments and ASCs and MSCs only retain their multipotency for a limited number of passages. …

Long-Term Neural Activity Recorders Using Energy-Based Sensing, Compressive Computation And Data Logging, Darshit Mehta

McKelvey School of Engineering Theses & Dissertations

Insects are ideal candidates for developing bio-robotic systems owing to their ability to thrive in almost any environment. For example, neurons in their exquisite olfactory sensory systems can be tapped to create a sensing platform for standoff chemical monitoring. However, for enabling such cyborg systems, it is vital that the neural activity of a freely behaving organism can be measured for long periods of time. The current state-of-the-art neural recording techniques are power-intensive and they either need batteries, which make them too bulky for insects, or they have to maintain a continuous telemetry link to an external power source which …

Developing An Induction Protocol And Generating A Selectable Cell Line To Obtain High-Purity V0v Interneuron Cultures From Mouse Embryonic Stem Cells, Jennifer Pardieck

McKelvey School of Engineering Theses & Dissertations

Spinal cord injury (SCI) leads to loss of motor function among other devastating impairments, with patients having a grim outlook on recovery as currently there are no widely efficacious treatment methods. The native regenerative capacity of the neurons in the central nervous system is limited, thus recovery of the axonal connections between the different components of the complex circuitry that enables motor function is minimal after SCI. Investigators aiming to improve motor function post-SCI approach the problem from different angles, including removing inhibitory elements to axonal regeneration and supporting regeneration through implantation of biomaterials, exposure to pro-regenerative factors, and transplantation …

Injectable Ct/Mri Contrast Agent For Gastrointestinal Tumor Tracking, Luna Zhang

McKelvey School of Engineering Theses & Dissertations

Gastrointestinal cancers remain to be of the most common and deadly cancers worldwide. Early detection and treatments are crucial for reducing mortality and improving patient outcome. Radiation therapy is a non-invasive localized tumor treatment method, and utilizes radiation to kill the cancerous cells and shrink tumors at specific sites. Precise localization at the target tumor site is therefore important before radiation therapy, especially for gastrointestinal tumor sites located in the moving bowel. Currently, invasive endoscopies along with ink tattoos are used for identifying tumor location, which often require sedation and bring much discomfort. Imaging tests, including CT and MRI, play …

Post-Traumatic Elbow Contracture Characterization And Physical Therapy-Based Treatment Strategies In A Preclinical Model, Alex Reiter

McKelvey School of Engineering Theses & Dissertations

The elbow is the most commonly dislocated joint in the pediatric population and second most common in adults. As one of the most congruous joints in the body, slight changes in biomechanics due to injury can lead to drastic reductions in range of motion causing potential quality of life issues. Post-traumatic joint contracture occurs in 12% of patients following elbow dislocation or fracture, and it is characterized by a loss in ROM, joint stiffness, and pain. Preventing joint contracture and functional deficits from occurring is one of the primary goals when managing these injuries. A rat model of joint contracture …

Laminin-Mimetic Peptide-Functionalized Hydrogel Systems For The Phenotypic Modulation Of Cells Of The Nucleus Pulposus, Marcos Nicolas Barcellona

McKelvey School of Engineering Theses & Dissertations

The intervertebral disc (IVD) has been widely observed to undergo significant structural and biochemical changes with age and maturation. As degeneration progresses, changes in extracellular matrix composition and deposition, tissue cellularity, and metabolic activity have been characterized. Although the epidemiology of disc degeneration remains unclear, it is believed that the nucleus pulposus (NP) region of the IVD may be implicated in early degeneration. Specifically, cells of the nucleus pulposus have been observed to undergo a shift from their notochordal-like juvenile phenotype to a more fibroblast-like state in a manner concomitant to degenerative events. Because the disc has inherently little capacity …

Understanding A Role For Synovium In Intra-Articular Drug Clearance: A Computational And Experimental Approach, Young Guang

McKelvey School of Engineering Theses & Dissertations

The synovium is a membranous tissue that governs molecular transport between the intra-articular (IA) joint space and the systemic circulatory system. Drug delivery to the IA space is an attractive option to treat localized joint diseases such as osteoarthritis. However, short residence times due to rapid clearance from the joint diminishes efficacy of IA injected drugs. While many studies exist on the clearance of drugs from the IA space, these studies lack the ability to isolate and characterize trans-synovial transport.The first aim of this dissertation establishes a computational finite element (FE) model of trans-synovial transport using multiphasic mixture theory. The …

Magnetic Resonance-Guided High Intensity Focused Ultrasound (Mrghifu) Induced Hyperthermia (Ht) For Treatment Of Cervical Cancer, Lifei Zhu

McKelvey School of Engineering Theses & Dissertations

Hyperthermia (HT), which refers to increasing the temperature of the tumor tissue to 40–45°C for an extended period of time, has been reported to be one of the most effective sensitizers for radiation therapy (RT) and/or chemotherapy. High intensity focused ultrasound (HIFU) has been developed as a non-invasive and non-ionizing tool to induce localized HT. Magnetic resonance thermometry (MR thermometry) is one of the most reliable methods for non-invasively and precisely measuring the in vivo volumetric temperature in real time. The integration of MR thermometry with HIFU has been implemented in commercially available magnetic resonance guided high intensity focused ultrasound …

Assessment And Diagnosis Of Human Colorectal And Ovarian Cancer Using Optical Imaging And Computer-Aided Diagnosis, Yifeng Zeng

McKelvey School of Engineering Theses & Dissertations

Tissue optical scattering has recently emerged as an important diagnosis parameter associated with early tumor development and progression. To characterize the differences between benign and malignant colorectal tissues, we have created an automated optical scattering coefficient mapping algorithm using an optical coherence tomography (OCT) system. A novel feature called the angular spectrum index quantifies the scattering coefficient distribution. In addition to scattering, subsurface morphological changes are also associated with the development of colorectal cancer. We have observed a specific mucosa structure indicating normal human colorectal tissue, and have developed a real-time pattern recognition neural network to localize this specific structure …

Cortical Organization In Humans And Nonhuman Primates: The Evolution Of Cognitive Areas And Circuits, Chad Joseph Donahue

McKelvey School of Engineering Theses & Dissertations

Similarities in organization of cerebral cortex in humans and nonhuman primates offer the promise of leveraging data from invasive animal studies to better understand the complexities of the human brain, particularly those related to higher cognitive function (e.g. attention, working memory, language). Such comparisons necessitate the identification of convincing cortical homologues (areas or regions presumed to have derived from a common ancestor), requiring an accurate interspecies mapping of cortical areas and features. To this end, I describe (i) a survey of connectivity and its measures across primate species, particularly retrograde tracing and diffusion tractography, (ii) a morphometric analysis of cognitive …

Synthetic Gene Circuits For Self-Regulating And Temporal Delivery Of Anti-Inflammatory Biologic Drugs In Engineered Tissues, Lara Pferdehirt

McKelvey School of Engineering Theses & Dissertations

The recent advances in the fields of synthetic biology and genome engineering open up new possibilities for creating cell-based therapies. We combined these tools to target repair of articular cartilage, a tissue that lacks a natural ability to regenerate, in the presence of arthritic diseases. To this end, we developed cell-based therapies that harness disease pathways and the unique properties of articular cartilage for prescribed, localized, and controlled delivery of biologics, creating the next generation of cell therapies and new classes of synthetic circuits. We created tissue engineered cartilage from murine induced pluripotent stem cells that had the ability to …

Engineering Nucleus Pulposus Cell-Matrix Interactions With Laminin Ligands For Tissue Regeneration, Julie Elizabeth Speer

McKelvey School of Engineering Theses & Dissertations

Low back pain and degenerative conditions of the intervertebral disc (IVD) represent major global socioeconomic and medical burdens. The structures that comprise the IVD including the anulus fibrosis and the nucleus pulposus (NP) work together to stabilize the axial skeleton and distribute mechanical forces. However, the degenerative cascade, which is thought to begin with changes to the NP, results in alterations to the disc that can be seen across length scales including elongated cell shapes, tissue dehydration, and loss of disc height. Patients who present clinically with these changes may also experience altered biomechanics, pain upon motion, impairments to their …

Plasmonically-Enhanced Ultrasensitive Biodetection Technologies, Zheyu Wang

McKelvey School of Engineering Theses & Dissertations

Detection and quantification of biomolecules within biological fluids and tissues is of fundamental importance to biomedical research and clinical diagnostics. It is impossible to fully characterize complex, non-linear, biochemical systems without being able to accurately and quantitatively determine the component molecules. This problem is ubiquitous across all domains of biomedical research, and it is a major barrier to fully understanding health, ageing, and disease. Such bottlenecks are extremely challenging to be solved, especially for proteins and peptides, which do not have amplification schemes such as polymerase chain reaction for nucleic acids, because relevant concentrations of molecules related to diseases such …

Computational Modelling Enables Robust Multidimensional Nanoscopy, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

The following sections are included:

• Present State of Computational Modelling in Fluorescence Nanoscopy

• Recent Contributions to Computational Modelling in Fluorescence Nanoscopy

• Outlook on Computational Modelling in Fluorescence Nanoscopy

• Acknowledgments

• References

Midfoot And Ankle Movement Dysfunction In People With Diabetes Mellitus And Peripheral Neuropathy, Hyo Jung Jeong

Arts & Sciences Electronic Theses and Dissertations

People with diabetes mellitus and peripheral neuropathy (DMPN) have midfoot and ankle musculoskeletal problems, including limited joint mobility and weakness and atrophy of foot intrinsic and calf muscles. Impaired foot structures and function could lead to midfoot and ankle movement dysfunction, measured by a heel rise task. A repeated movement dysfunction during weightbearing tasks (e.g., heel rise, walking) could cause excessive stress on the plantar tissue, which is a leading cause of plantar ulceration in people with DMPN. Understanding heel rise performance and the underlying mechanisms could help prevent the sequence of events associated with plantar ulcer development in people …

Focused Ultrasound-Mediated Drug Delivery To The Brainstem, Dezhuang Ye

McKelvey School of Engineering Theses & Dissertations

Brainstem gliomas are tumors that occur in the brainstem, the brain region that connects the brain to the spinal cord and controls vital body functions. The critical anatomic location of the brainstem precludes surgical intervention and limits the use of invasive therapeutic techniques. Moreover, the frequently intact blood-brain barrier (BBB) of most brainstem gliomas prevents therapeutic agents from reaching the diseased site. The currently available techniques for brain drug delivery are either invasive (e.g., convection-enhanced delivery) or lack targeting to the diseased site (e.g., intranasal brain drug delivery). Novel techniques that can noninvasively overcome the BBB are critically needed for …

Deep Learning For Task-Based Image Quality Assessment In Medical Imaging, Weimin Zhou

McKelvey School of Engineering Theses & Dissertations

It has been advocated to use objective measures of image quality (IQ) for assessing and optimizing medical imaging systems. Objective measures of IQ quantify the performance of an observer at a specific diagnostic task. Binary signal detection tasks and joint signal detection and localization (detection-localization) tasks are commonly considered in medical imaging. When optimizing imaging systems for binary signal detection tasks, the performance of the Bayesian Ideal Observer (IO) has been advocated for use as a figure-of-merit (FOM). The IO maximizes the observer performance that is summarized by the receiver operating characteristic (ROC) curve. When signal detection-localization tasks are considered, …

Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn

McKelvey School of Engineering Theses & Dissertations

During mammalian embryogenesis, the first major lineage segregation occurs when embryonic epiblast, and extraembryonic trophectoderm and hypoblast arise in the blastocyst. In the next fundamental and conserved phase of animal embryogenesis known as gastrulation, extraembryonic cells provide signals to epiblast to instruct embryonic patterning, and epiblast gives rise to germ layers ectoderm, mesoderm, and endoderm, that will establish all embryonic tissues. Proper specification and morphogenesis of germ layers during gastrulation is vital for correct embryonic development. Due to ethical and legal restrictions limiting human embryo studies, human gastrulation is poorly understood. Our knowledge of human gastrulation has largely been derived …

Uncovering The Roles And Evolved Sequence Grammar Of Hypervariable Intrinsically Disordered Proteins In Bacterial Cell Division, Megan Cohan

McKelvey School of Engineering Theses & Dissertations

Across all domains of life, a defining hallmark of the onset of cell division is the formation of a cytokinetic ring at the center of the cell. Cell division is a tightly controlled process that involves various regulatory factors that modulate the assembly of the cytokinetic ring. In rod-shaped bacteria, the ring is termed the Z-ring after the protein FtsZ, which is foundational to ring formation and is the bacterial homolog of tubulin. Like tubulin, FtsZ is an assembling GTPase, where GTP binding promotes the cooperative assembly into FtsZ polymers that laterally associate to form bundles. While the GTPase domain …

Nanoscale Enhancement Of Photosensitized Radionuclide Stimulated Therapy, Daniel Douglas Lane

McKelvey School of Engineering Theses & Dissertations

Photodynamic therapy (PDT) provides efficient tumor killing through the generation of reactive oxygen species (ROS) from the optical excitation of a photosensitizer (PS). Furthermore, this mechanism is highly immune stimulating, providing systemic tumor immunity with a reduction in metastasis. However, these materials had previously been limited by their dependence upon external light sources, allowing treatment of only laser-accessible malignancy. With the recent development of photosensitized radiation stimulated therapy (PRaST) this depth dependence is broken through co-localization of radionuclides and semiconducting photosensitizers. This dissertation focuses on the enhancement of titanium dioxide (TiO2) based PRaST agents through understanding of TiO2 material parameters …