Biomedical Engineering and Bioengineering Commons^™

Plasmonically-Enhanced Ultrasensitive Biodetection Technologies, Zheyu Wang

McKelvey School of Engineering Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

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

McKelvey School of Engineering Graduate Student 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 …

Neural Coding And Organization Principles In The Drosophila Olfactory System, Haoyang Rong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Sensory systems receive and process external stimuli to allow an organism to perceive and react to the environment. How is sensory information subsequently represented, transformed, and interpreted in the neural system? In this dissertation, I have investigated this fundamental question using the fruit fly (Drosophila melanogaster) olfactory system.Chemical cues are transduced into neural signals in the insect antenna by the olfactory receptor neurons (ORNs). The ORNs send their axons to the antennal lobe (AL), with each ORN type innervating a specific neuropil (glomerulus), where they synapse onto excitatory and inhibitory projection neurons (ePNs and iPNs). The ePNs project their axons …

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

McKelvey School of Engineering Graduate Student 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 Graduate Student 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 Graduate Student 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 Graduate Student 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 Graduate Student 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 …

Evaluating The Structural And Functional Consequences Of Traumatic Joint Injury And Their Relation To Nf-Κb In A Non-Invasive Model Of Post-Traumatic Osteoarthritis, Ian Matthew Berke

McKelvey School of Engineering Graduate Student Theses & Dissertations

Post-traumatic osteoarthritis (PTOA) is a painful and debilitating disease of the synovial joint, characterized by degenerative changes to various joint tissues following traumatic joint injury. While several risk factors have been identified in the symptomatic progression of PTOA following injury, inflammation and NF-κB mediated changes are believed to significantly contribute to symptomatic joint dysfunction and pain. However, the temporal presentation of these pro-inflammatory signals following clinically relevant injury and their relationship to the development of symptomatic disease have not been thoroughly investigated. Therefore, there exists a critical need to better understand how these early inflammatory events following injury may contribute …

Theory, Design And Implementation Of Energy-Efficient Biotelemetry Using Ultrasound Imaging, Sri Harsha Kondapalli

McKelvey School of Engineering Graduate Student Theses & Dissertations

This dissertation investigates the fundamental limits of energy dissipation in establishing a communication link with implantable medical devices using ultrasound imaging-based biotelemetry.

Ultrasound imaging technology has undergone a revolution during the last decade due to two primary innovations: advances in ultrasonic transducers that can operate over a broad range of frequencies and progresses in high-speed, high-resolution analog-to-digital converters and signal processors. Existing clinical and FDA approved bench-top ultrasound systems cangenerate real-time high-resolution images at frame rates as high as 10000 frames per second. On the other end of the spectrum, portable and hand-held ultrasound systems can generate high-speed real-time scans, …

Autologous Stem Cell-Derived Β Cells For Diabetes Cell Replacement Therapy, Kristina G. Maxwell

McKelvey School of Engineering Graduate Student Theses & Dissertations

Autologous stem cell therapy is a promising treatment for patients with diabetes worldwide. Previous stem cell-derived β (SC-β) cell protocols were unable to efficiently differentiate multiple patient induced pluripotent stem cells (iPSCs) into stem cell-derived islets (SC-islets), containing insulin-secreting SC-β cells. Recent updates targeting the actin cytoskeleton have enabled the differentiation of 14 diabetic and nondiabetic stem cell lines into SC-islets. We used genetic engineering, specifically CRISPR/Cas9, to correct the diabetes-causing mutation in stem cells from patients with Wolfram Syndrome. The genetically engineered SC-β cells functioned and had a composition similar to nondiabetic SC-β cells, unlike the unedited SC-β cells …

Liposomal Delivery Of Remdesivir For Localized And Targeted Treatment Of Covid-19, Anupama Melam

McKelvey School of Engineering Graduate Student Theses & Dissertations

Liposomal delivery of Remdesivir for localized and targeted treatment of COVID-19

COVID-19 is a serious, and in many cases lethal, disease that is caused by infection of the upper respiratory tract by the novel betacoronavirus, SARS-Cov-2 virus. This disease has a very high mortality rate and has affected the world in a global pandemic. SARS-Cov-2 binds to the ACE2 receptor via the receptor-binding domain (RBD) in the S protein. After this, the virus fuses with the cell membrane by the formation of a six-helix bundle. Thus, the S protein plays a major role in ensuring that the virus attaches to …

The Role Of Gene Transcription And Inflammatory Cytokines In Bone Fracture Repair, Brandon Alan Coates

McKelvey School of Engineering Graduate Student Theses & Dissertations

In most instances, the skeleton has a remarkable capacity for repair following injury. However, in 5 to 10% of patients, fractures fail to properly heal resulting in non-union. A need exists for a more comprehensive understanding of the complex biology of fracture repair, which involves the coordinated work of many cell types including osteoblasts, osteoclasts, and immune cells. Depending on the extent of injury, fractures will heal through either intramembranous bone formation, involving the direct formation of bone callus, or endochondral bone formation, featuring a cartilage intermediary prior to bone callus formation. Both processes begin with inflammation, which sets the …

Quantitative Fluorescence Imaging For Investigation And Treatment Of Disease, Lemoyne Michael Habimana-Griffin

McKelvey School of Engineering Graduate Student Theses & Dissertations

Molecular imaging is a powerful tool that enables interrogation of basic molecular mechanisms, diagnosis of disease, guidance of therapeutic modalities and monitoring of treatment response. Among the various imaging modalities, optical imaging is particularly suited for preclinical molecular imaging owing to its high sensitivity, lack of exposure to ionizing radiation, low cost, portability and scalability of imaging from the microscopic to macroscopic scale. In particular, fluorescence molecular tomography (FMT) provides quantitative 3D reconstructions of fluorescence distributions down to picomole quantities allowing for whole animal molecular imaging. In this work, FMT is applied to detect disease-specific molecular probes, to monitor and …

Application Of Photoacoustic Imaging In Understanding Tissue Remodeling, Yuan Qu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic Imaging (PAI) as an imaging method in biomedical research can provide high spatial resolution, various contrasts, great detection sensitivity, and deep penetration. These advantages are attributed to the combination of optical excitation and acoustic detection, which releases PAI from the ballistic limit faced by other optical imaging technique with high spatial resolution. In this dissertation, we aim to apply this technique to understand the connective tissue remodeling that is a ubiquitous physiological change in various medical complications.Chapter 1 elaborates the mechanism of PAI as well as the motivation of my dissertation.In Chapter 2, I introduce a new contrast mechanism …

Tissue Engineering Of Induced Pluripotent Stem Cells For The Development Of Novel Treatment Strategies For Osteoarthritis, Alison Ross

McKelvey School of Engineering Graduate Student Theses & Dissertations

Osteoarthritis (OA) is a debilitating joint disease that is primarily characterized by the degeneration of articular cartilage, the soft connective tissue that covers articulating bone surfaces in diarthrodial joints. While there are a number of risk factors for developing OA, the progression of this disease is mediated in part by pro-inflammatory cytokines from both the synovium and chondrocytes, the resident cells of articular cartilage. These cytokines, specifically interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α), induce aberrant expression of catabolic and degradative enzymes and inflammatory cytokines in OA, which promotes degradation of engineered tissues as well as native articular …

Ultrasound Guided Diffuse Optical Tomography For Breast Cancer Diagnosis: Algorithm Development, K M Shihab Uddin

McKelvey School of Engineering Graduate Student Theses & Dissertations

According to National Breast Cancer Society, one in every eight women in United States is diagnosed with breast cancer in her lifetime. American Cancer Society recommends a semi-annual breast-cancer screening for every woman which can be heavily facilitated by the availability of low-cost, non-invasive diagnostic method with good sensitivity and penetration depth. Ultrasound (US) guided Diffuse Optical Tomography (US-guided DOT) has been explored as a breast-cancer diagnostic and screening tool over the past two decades. It has demonstrated a great potential for breast-cancer diagnosis, treatment monitoring and chemotherapy-response prediction. In this imaging method, optical measurements of four different wavelengths are …

Exploring Attacks And Defenses In Additive Manufacturing Processes: Implications In Cyber-Physical Security, Nicholas Deily

McKelvey School of Engineering Graduate Student Theses & Dissertations

Many industries are rapidly adopting additive manufacturing (AM) because of the added versatility this technology offers over traditional manufacturing techniques. But with AM, there comes a unique set of security challenges that must be addressed. In particular, the issue of part verification is critically important given the growing reliance of safety-critical systems on 3D printed parts. In this thesis, the current state of part verification technologies will be examined in the con- text of AM-specific geometric-modification attacks, and an automated tool for 3D printed part verification will be presented. This work will cover: 1) the impacts of malicious attacks on …

Ultrasensitive Biodetection Based On Plasmonically-Active Materials, Jingyi Luan

McKelvey School of Engineering Graduate Student Theses & Dissertations

A broad range of biomarkers continue to emerge as potentially important parameters for early detection of many pathological conditions.1 A disease biomarker (e.g. protein, a fragment of a pro-tein, DNA/RNA, or metabolites) is a ‘molecular signature’ of the physiological state of patient at specific time and is therefore extremely important for early and possibly pre-symptomatic diagno-sis and accurate monitoring of therapeutic intervention. Relevant concentrations of biomarkers related to diseases such as cancer, heart disease, inflammation, and neurological disorders can range in many orders of magnitude from μg/ml levels to sub-fg/ml, some of which possibly still remain unidentified due to the …

The Mechanobiology Of Elbow Contracture: Pathogenesis And Prevention, Chelsey Dunham

McKelvey School of Engineering Graduate Student Theses & Dissertations

Post-traumatic elbow contracture is a multi-tissue pathology which develops in up to 50% of patients following elbow trauma (e.g., fracture, dislocation). It is unclear which periarticular soft tissues are driving the functional deficit following injury because it is not possible in clinical settings to isolate each soft tissues’ mechanical and biological contributions to elbow contracture. Therefore, an animal model is needed to identify the primary periarticular soft tissue(s) which contribute to contracture. The first animal models of contracture were developed in the knee; however, these studies are not generalizable to the elbow due to anatomical and functional differences between these …

Toward Controlling Cardiac Tissue Pacing Using Modified Mrna, Yicheng Zhao

McKelvey School of Engineering Graduate Student Theses & Dissertations

Arrhythmia is a common heart disease that happens when the heart is beating too fast, too slow, or irregularly. To study the mechanisms and treatments of this disease, it is important to acutely control the beating rate of the model as it will help distinguish the contribution of different potassium currents and drug-induced action potential in cardiomyocytes. The current method of tissue pacing, electrical pacing, causes contamination and corrosive damage to tissues, thus the tissues fail to be used repeatedly or in future studies. In this study, red-shifted channelrhodopsin (ReaChR) is applied as a non-chemical means to control the beating …

Transcriptomic Analysis Of Cytokine-Treated Tissue-Engineered Cartilage As An In Vitro Model Of Osteoarthritis, Jiehan Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

Osteoarthritis (OA), as the most common form of arthritis and a leading cause of disability worldwide, currently has no disease-modifying drugs. Inflammation plays an important role in cartilage degeneration in OA, and pro-inflammatory cytokines, IL-1β and TNF-α, have been shown to induce degradative changes along with aberrant gene expression in chondrocytes, the only resident cells in cartilage. The goal of this study was to further understand the transcriptomic regulation of tissue-engineered cartilage in response to inflammatory cytokines using an in vitro miPSC model system. We performed RNA sequencing for the IL-1β or TNF-α treated tissue-engineered cartilage derived from murine iPSCs, …

Design And Validation Of A Dynamic Pressure-Based Loading Device And 3d Strain Tracking Protocol For Ventral Hernia Modeling, Griffin Kivitz

McKelvey School of Engineering Graduate Student Theses & Dissertations

It is estimated that 350,000-500,000 ventral hernia repair surgeries are performed each year in the United States. While the long-term recurrence rate of ventral hernia repairs is not yet known, when tissues are exposed to the trauma of surgery, there is always the chance of recurrence. Commonly used ex vivo testing methods for determining the mechanical properties of the abdominal wall and biomaterials for hernia repair consist primarily of uniaxial and biaxial testing, which are not physiologically relevant loading environments. The need for a testing device that can exert physiologically relevant loads ex vivo to an abdominal wall is crucial …

A High Frequency Photoacoustic System For Colorectal Cancer Imaging, Kexin Huang

McKelvey School of Engineering Graduate Student Theses & Dissertations

While colorectal cancer is the second largest cause of cancer-related deaths in the United States, early detection is a key factor in its survival rate. Compared to conventional imaging modalities, photoacoustic imaging offers benefits in providing angiographic images which are valuable for early-stage tumor detection. This thesis presents the design of a 32-channel 80 MHz photoacoustic image system, whose relatively high frequency offers particular advantages. The system comprises several modules, including a laser system, ultrasound probe, AD convertor, microcontroller (FPGA), and a computer. The system requires programs for the FPGA and the data receiver on the computer. The data transportation …

Computational Imaging Methods For Analysis Of Datscan Spect Images, Hae Sol Moon

McKelvey School of Engineering Graduate Student Theses & Dissertations

There is an important need to develop biomarkers to improve the diagnosis and assess the severity of Parkinson’s disease (PD). The potential to derive such biomarkers from quantitative dopamine transporter scan (DaT-Scan) single-photon emission computed tomography (SPECT) imaging, in particular the uptake of DaT in the caudate, putamen, and globus pallidus regions, is highly appealing as imaging is non-invasive and DaTScan is already used in the management of patients with PD. However, reliable quantification requires reliable segmentation of these regions in these images. Reliable segmentation is challenging due to the limited spatial resolution and high image noise in SPECT images …

Development Of High-Speed Photoacoustic Imaging Technology And Its Applications In Biomedical Research, Yun He

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) is a novel imaging modality that combines the fine lateral resolution from optical imaging and the deep penetration from ultrasonic imaging, and provides rich optical-absorption–based images. PAT has been widely used in extracting structural and functional information from both ex vivo tissue samples to in vivo animals and humans with different length scales by imaging various endogenous and exogenous contrasts at the ultraviolet to infrared spectrum. For example, hemoglobin in red blood cells is of particular interest in PAT since it is one of the dominant absorbers in tissue at the visible wavelength.The main focus of …

Rhodococcus Opacus Pd630 Genetic Tool Development To Enable The Conversion Of Biomass, Drew Michael Delorenzo

McKelvey School of Engineering Graduate Student Theses & Dissertations

The discovery of fossil fuels facilitated a new era in human history and allowed many firsts, such as the mass production of goods, the ability to travel and communicate long distances, the formation of population dense cities, and unprecedented improvements in quality of life. Alternative sources of energy and chemicals are needed, however, as hydrocarbon reserves continue to deplete and the effects of burning fossils on the planet become better understood. Lignocellulosic biomass is the most abundant raw material in the world and a viable alternative to petroleum-derived products. The pre-treatment of lignocellulose (e.g., thermocatalytic depolymerization, enzymatic hydrolysis, pyrolysis, etc.) …