Biomedical Engineering and Bioengineering Commons^™

Device Design Factors For Enhancing The Functionality Of Chronic Intracortical Microelectrodes, Heui Chang Lee

Open Access Dissertations

Intracortical microelectrodes are devices used in brain-computer interfaces (BCI) to help regain lost motor, sensory, and cognitive functions of individuals with neurological disorders. However, the long-term performance of microelectrode arrays is hampered by a series of inflammatory tissue responses. The consequence of the inflammatory response is the formation of a dense astroglial sheath around the vicinity of the electrode, impeding the electrical conduction between the electrode and neurons. Furthermore, due to the cascade of neuroinflammatory events, the number of neurons is significantly reduced near the electrode, manifested by decrease in signal-to-noise ratio (SNR) and the yield of electrodes. Over time, …

Characterizing The Effects Of Repetitive Head Trauma In Female Soccer Athletes For Prevention Of Mild Traumatic Brain Injury, Diana Otero Svaldi

Open Access Dissertations

As participation in women’s soccer continues to grow and the longevity of female athletes’ careers continues to increase, prevention of mTBI in women’s soccer has become a major concern for female athletes as the long-term risks associated with a history of mTBI are well documented. Among women’s sports, soccer exhibits the highest concussion rates, on par with those of men’s football at the collegiate level. Head impact monitoring technology has revealed that “concussive hits” occurring directly before symptomatic injury are not predictive of mTBI, suggesting that the cumulative effect of repetitive head impacts experienced by collision sport athletes should be …

Dynamic Holography In Semiconductors And Biomedical Optics, Hao Sun

Open Access Dissertations

Three-dimensional scanning and display are rapidly-advancing new technologies with important commercial drivers such as 3D printing and remote imaging for big data applications. Holography is a natural approach to recording and displaying three-dimensional information because it uses phase-sensitive interferometry to record interference patterns when a reference beam encounters coherent light arriving from an object. The 3D information is contained in the values of wave optics. Holography is a broad field that goes beyond recording and displaying. For instance, holographic optical elements, which take advantage of holographic imaging principles, perform the functions of lenses, gratings or mirrors. Holographic interferometry is also …

Concurrent Detection And Isolation Of Cellular And Molecular Biomarkers, Wanfeng Huang

Open Access Dissertations

Detection of cancer markers such as protein biomolecules and cancer cells in bodily fluids is of great importance in early diagnosis, prognosis as well as evaluation of therapy efficacy. Numerous devices have been developed for detecting either cellular or molecular targets, however there has not yet been a system that can simultaneously detect both cellular and molecular targets effectively. Molecule and cell-based assays are important because each type of target can tell a different story about the state of the disease and the two types of information can potentially be combined and/or compared for more accurate biological or clinical assessments. …

Laser-Processed Parchment Paper For Fabrication Of Chronic Wound Dressings With Selective Oxygenation, Manuel Ochoa

Open Access Dissertations

Chronic non-healing wounds (e.g., diabetic foot ulcers and bed sores) impact over 6.5 million Americans per year, costs in excess of $25 billion to treat on an annual basis, and are on the rise due to increasing levels of obesity and diabetes compounded by an aging population. A major inhibitor of healing is suboptimal oxygenation of the wound bed. Unlike acute injuries that receive sufficient oxygen via a functional blood vessel network, chronic wounds often suffer from the lack of a proper vascular network; thus being incapable of providing sufficient oxygen for tissue growth. Typical medical treatment of hypoxic chronic …

Optical Dosimetry Tools And Monte Carlo Based Methods For Applications In Image Guided Optical Therapy In The Brain, Akshay N Prabhu Verleker

Open Access Dissertations

Purpose: The long-term goal of this research is to determine the feasibility of using near infra-red light to stimulate drug release in metastatic lesions within the brain. In this work, we focused on developing the tools needed to quantify and verify photon fluence distribution in biological tissue. To accomplish this task, an optical dosimetry probe and Monte Carlo based simulation code were fabricated, calibrated and developed to predict light transport in heterogeneous tissue phantoms of the skull and brain. Empirical model (EM) of photon transport using CT images as input were devised to provide real-time calculations capable of being translated …

The Role Of Mechanical Loading In Chondrocyte Signaling Pathways, Qiaoqiao Wan

Open Access Dissertations

Chondrocytes are a predominant cell type present in articular cartilage, whose integrity is jeopardized in joint degenerative diseases such as osteoarthritis (OA). In the chondrocytes of patients with OA, the elevated levels of inflammatory cytokines such as interleukin 1β (IL1β) and tumor necrosis factor α (TNFα) have been reported. These cytokines contribute to degradation of cartilage matrix by increasing activities of proteolytic enzymes. In addition to their contribution to proteolytic enzymes, these cytokines adversely affect anabolic activity of chondrocytes by inhibiting the production of proteoglycans and type II collagen. Therefore, blocking the action of these cytokines is a potential strategy …

Development Of Orthogonally Crosslinked Thiol-Ene Hydrogels For Encapsulation Of Pancreatic Beta-Cells, Han Shih

Open Access Dissertations

Type I diabetes mellitus (T1DM) is an autoimmune disease caused by auto-reactive T-cell-mediated destruction of insulin-producing β-cells. Effective encapsulation strategies can protect the transplanted islets from direct attack by host immune cells while maintaining insulin secretion. To achieve this goal, I have developed a hydrogel conformal coating using a visible light-mediated interfacial thiol-ene photopolymerization. Unlike conventional chain-growth visible light polymerizations, no additional cytotoxic co-initiator or co-monomer was required in thiol-ene gelation scheme for rapid gelation. More importantly, islets coated with thiol-ene gel maintained their viability and function in vitro. In addition to microencapsulate β-cells, the second objective of my …

Influence Of The 3d Microenvironment On Glioblastoma Migration And Drug Response, Ruth Marisol Herrera Perez

Open Access Dissertations

Glioblastoma (GBM) is a highly invasive brain cancer characterized by poor prognosis. Despite significant efforts by the basic and clinical research community our understanding of GBM progression and recurrence has been incremental. Improvements in therapeutic response have been dismal, and GBM continues to be the deadliest tumor of the central nervous system, with patient average survival rate of 12 months. Synergistic relationships that the tumor cells establish with the brain microenvironment have been proven fundamental for successful tumor progression and maintenance. Yet, many in vitro GBM studies are performed in formats that fail to recapitulate the most essential component of …

Direct Drug Screening And Lipid Profiling Using Ambient Mass Spectrometry, Yuan Su

Open Access Dissertations

Mass spectrometry (MS) stands in an outstanding position in analysis of biological specimens owing to its abundant structural information, high accuracy, incomparable sensitivity, high speed, and the large variety of its applications. The ion source, an instrumental part for converting the analyte into ions, has played an important role in analyzing biological specimens by MS. However, the performance of conventional spray-based ionization methods always suffers from chemical interferences derived from complex biological matrices. A series of sample extraction, purification, and separation steps is required before the ionization, so as to ensure excellent performance of MS analysis. In order to simplify …

Improving The Mechanistic Study Of Neuromuscular Diseases Through The Development Of A Fully Wireless And Implantable Recording Device, Rebecca A. Bercich

Open Access Dissertations

Neuromuscular diseases manifest by a handful of known phenotypes affecting the peripheral nerves, skeletal muscle fibers, and neuromuscular junction. Common signs of these diseases include demyelination, myasthenia, atrophy, and aberrant muscle activity—all of which may be tracked over time using one or more electrophysiological markers. Mice, which are the predominant mammalian model for most human diseases, have been used to study congenital neuromuscular diseases for decades. However, our understanding of the mechanisms underlying these pathologies is still incomplete. This is in part due to the lack of instrumentation available to easily collect longitudinal, in vivo electrophysiological activity from mice. There …

Advancing Multiple Model-Based Control Of Complex Biological Systems: Applications In T Cell Biology, Jeffrey P. Perley

Open Access Dissertations

Activated CD4+ T cells are important regulators of the adaptive immune response against invading pathogens and cancerous host cells. The process of activation is mediated by the T cell receptor and a vast network of intracellular signal transduction pathways, which recognize and interpret antigenic signals to determine the cell's response. The critical role of these early signaling events in normal cell function and the pathogenesis of disease ultimately make them attractive therapeutic targets for numerous autoimmune diseases and cancers.

Scientists increasingly rely on predictive mathematical models and control-theoretic tools to design effective strategies to manipulate cellular processes for the advancement …

Coupled Resonator Based Wireless Power Transfer For Bioelectronics, Henry Mei

Open Access Dissertations

Implantable and wearable bioelectronics provide the ability to monitor and modulate physiological processes. They represent a promising set of technologies that can provide new treatment for patients or new tools for scientific discovery, such as in long-term studies involving small animals. As these technologies advance, two trends are clear, miniaturization and increased sophistication i.e. multiple channels, wireless bi-directional communication, and responsiveness (closed-loop devices). One primary challenge in realizing miniaturized and sophisticated bioelectronics is powering. Integration and development of wireless power transfer (WPT) technology, however, can overcome this challenge.

In this dissertation, I propose the use of coupled resonator WPT for …

Supervised Learning-Based Explicit Nonlinear Model Predictive Control And Unknown Input Estimation In Biomedical Systems, Ankush Chakrabarty

Open Access Dissertations

Application of nonlinear control theory to biomedical systems involves tackling some unique and challenging problems. The mathematical models that describe biomedical systems are typically large and nonlinear. In addition, biological systems exhibit dynamics which are not reflected in the model (so-called 'un-modeled dynamics') and hard constraints on the states and control actions, which exacerbate the difficulties in designing model-based controllers or observers.

This thesis investigates the design of scalable fast explicit nonlinear model predictive controllers (ENMPCs). The design involves (i) the estimation of a feasible region using Lyapunov stability methods and support vector machines; and (ii) within the estimated feasible …

Freezing-Induced Deformation Of Biomaterials In Cryomedicine, Altug Ozcelikkale

Open Access Dissertations

Cryomedicine utilizes low temperature treatments of biological proteins, cells and tissues for cryopreservation, materials processing and cryotherapy. Lack of proper understanding of cryodamage that occurs during these applications remains to be the primary bottleneck for development of successful tissue cryopreservation and cryosurgery procedures. An engineering approach based on a view of biological systems as functional biomaterials can help identify, predict and control the primary cryodamage mechanisms by developing an understanding of underlying freezing-induced biophysical processes. In particular, freezing constitutes the main structural/mechanical origin of cryodamage and results in significant deformation of biomaterials at multiple length scales. Understanding of these freezing-induced …

Optimizing The Neural Response To Electrical Stimulation And Exploring New Applications Of Neurostimulation, Kurt Yuqin Qing

Open Access Dissertations

Electrical stimulation has been successful in treating patients who suffer from neurologic and neuropsychiatric disorders that are resistant to standard treatments. For deep brain stimulation (DBS), its official approved use has been limited to mainly motor disorders, such as Parkinson's disease and essential tremor. Alcohol use disorder, and addictive disorders in general, is a prevalent condition that is difficult to treat long-term. To determine whether DBS can reduce alcohol drinking in animals, voluntary alcohol consumption of alcohol-preferring rats before, during, and after stimulation of the nucleus accumbens shell were compared. Intake levels in the low stimulus intensity group (n=3, 100&mgr;A …

The Role Of Death-Associated Protein Kinase In Endothelial Apoptosis Under Fluid Shear Stress, Keith R. Rennier

Open Access Dissertations

Endothelial cells are the interface between hemodynamic fluid flow and vascular tissue contact. They actively translate physical and chemical stimuli into intracellular signaling cascades which in turn regulate cell function, and endothelial dysfunction leads to inflammation and diseased conditions. For example, atherosclerosis, a chronic vascular disease, favorably develops in regions of disturbed fluid flow and low shear stress. Apoptosis, or programmed cell death, must be properly regulated to maintain homeostasis in the vascular wall. The loss of apoptosis control, as seen in low shear stress regions, is implicated in various diseases such as atherosclerosis and cancer. Death-associated protein kinase, DAPK …

The Pathological Role Of Acrolein In Experimental Autoimmune Encephalomyelitis And Multiple Sclerosis, Melissa A. Tully

Open Access Dissertations

Multiple sclerosis (MS) is an autoimmune demyelinating neuropathy that affects nearly 2.5 million people worldwide. Despite substantial efforts, few treatments are currently available largely due to limited knowledge of pathogenic mechanisms underlying the disease. The immune-inflammatory nature of the pathology has prompted investigation of the role of oxidative stress in disease development and progression; however targeting reactive oxygen species for neutralization has had marginal success therapeutically, suggesting that an alternate oxidative stress-related target would prove beneficial. Recently, our lab has implicated acrolein, a highly reactive aldehyde that is both a byproduct and catalyst of lipid peroxidation, as a potential therapeutic …

Surface Modification Of Traditional And Bioresorbable Metallic Implant Materials For Improved Biocompatibility, Emily Kristine Walker

Open Access Dissertations

Due to their strength, elasticity, and durability, a variety of metal alloys are commonly used in medical implants. Traditionally, corrosion-resistant metals have been preferred. These permanent materials can cause negative systemic and local tissue effects in the long-term. Permanent stenting can lead to late-stent thrombosis and in-stent restenosis. Metallic pins and screws for fracture fixation can corrode and fail, cause loss of bone mass, and contribute to inflammation and pain at the implant site, requiring reintervention. Corrodible metallic implants have the potential to prevent many of these complications by providing transient support to the affected tissue, dissolving at a rate …

A Three Constituent Mixture Theory Model Of Cutaneous And Subcutaneous Tissue In The Context Of Neonatal Pressure Ulcer Etiology And Prevention, Anne Dye Zakrajsek

Open Access Dissertations

Localized ischemia, impaired interstitial fluid flow, and sustained mechanical loading of cells have all been hypothesized as mechanisms of pressure ulcer (PrU) etiology. Time-varying loading has experimentally been shown to increase fluid flow in human skin in vivo. Towards the design of prophylactic protocols and treatment modalities for PrU management there is a need for an analytical model to investigate the local fluid flow characteristics of skin tissue under time-varying loading. In this study, a triphasic mixture theory model with constituents of extracellular matrix, interstitial fluid, and blood was calibrated and validated and used to investigate stress and fluid velocity …

A Novel In Vivo Tumor Oxygen Profiling Assay: Combining Functional And Molecular Imaging With Multivariate Mathematical Modeling, Chung-Wein Lee

Open Access Dissertations

Purpose: The objective of this study is to develop and test a novel high spatio-temporal in vivo assay to quantify tumor oxygenation and hypoxia. The assay implements a biophysical model of oxygen transport to fuse parameters acquired from in vivo functional and molecular imaging modalities. ^ Introduction: Tumor hypoxia plays an important role in carcinogenesis. It triggers pathological angiogenesis to supply more oxygen to the tumor cells and promotes cancer cell metastasis. Preclinical and clinical evidence show that anti-angiogenic treatment is capable of normalizing the tumor vasculature both structurally and functionally. The resulting normalized vasculature provides a more efficient and …

Unveiling The Mechanical Behavior Of The Rod-Like Microstructure In The Radular Teeth Of Cryptochiton Stelleri, Enrique Escobar De Obaldia

Open Access Dissertations

Natural ceramics provided with high volume fractions of mineralized materials that are surrounded by a weak organic interface combine the stiff mechanical behavior of building blocks, like hydroxyapatite or aragonite, and the compliance of the organic surroundings. Unique mechanical properties (e.g. light density and toughness) distinguish bio-composites from common engineering materials. A key example is the highly mineralized shell of the radular teeth of the Crypochiton stelleri. Nature has provided the radular teeth with a highly oriented rod-like microstructure of nano-scale dimensions embedded in a matrix of chitin sheaths. Compared to other biological materials, the external iron oxide layer of …

Wireless Tools For Neuromodulation, Steven T Lee

Open Access Dissertations

Epilepsy is a spectrum of diseases characterized by recurrent seizures. It is estimated that 50 million individuals worldwide are affected and 30% of cases are medically refractory or drug resistant. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are the only FDA approved device based therapies. Neither therapy offers complete seizure freedom in a majority of users. Novel methodologies are needed to better understand mechanisms and chronic nature of epilepsy. Most tools for neuromodulation in rodents are tethered. The few wireless devices use batteries or are inductively powered. The tether restricts movement, limits behavioral tests, and increases the risk …

Instrumentation And Development Of A Mass Spectrometry System For The Study Of Gas-Phase Biomolecular Ion Reactions, Ziqing Lin

Open Access Dissertations

Gas-phase reactions of biomolecular ions are highly relevant to the understanding of structures and functions of the biomolecules. Mass spectrometry is a powerful tool in investigating gas-phase ion chemistry. Various mass spectrometers have been developed to explore ion/molecule reactions, ion/ion reactions, ion/photon reactions, ion/radical reactions etc., both at atmospheric pressure and in vacuum. In-vacuum reactions have an advantage of involving pre-selecting the ions for the reactions using a mass analyzer. Over the decades, a variety of mass analyzers have been employed in the research of ion chemistry. Hybrid configurations, such as quadrupole ion trap with a time-of-flight and or a …

Acrolein As A Novel Therapeutic Target For Spinal Cord Injury Induced Neuropathic Pain, Jonghyuck Park

Open Access Dissertations

Despite years of research, post-spinal cord injury (SCI) chronic neuropathic pain remains refractory to treatment and drastically impairs quality of life for SCI victims beyond paralysis. Although inflammation and free radicals contribute to neuropathic pain in SCI, the mechanism is not completely clear. We have recently demonstrated that acrolein, a product and catalyst of lipid peroxidation, induces a vicious cycle of oxidative stress, amplifying its effects and perpetuating oxidative stress and inflammation. In the current study, we have confirmed that acrolein is elevated significantly at least two weeks post-SCI which coincides with the emergence of hyperalgesia (mechanical, cold and thermal). …

Development Of A Static Bioactive Stent Prototype And Dynamic Aneurysm-On-A-Chip(Tm) Model For The Treatment Of Aneurysms, Lisa M. Reece

Open Access Dissertations

Aneurysms are pockets of blood that collect outside blood vessel walls forming dilatations and leaving arterial walls very prone to rupture. Current treatments include: (1) clipping, and (2) coil embolization, including stent-assisted coiling. While these procedures can be effective, it would be advantageous to design a biologically active stent, modified with magnetic stent coatings, allowing cells to be manipulated to heal the arterial lining. Further, velocity, pressure, and wall shear stresses aid in the disease development of aneurysmal growth, but the shear force mechanisms effecting wound closure is elusive. Due to these factors, there is a definite need to cultivate …

Probabilistic Uncertainty Quantification And Experiment Design For Nonlinear Models: Applications In Systems Biology, Vu Cao Duy Thien Dinh

Open Access Dissertations

Despite the ever-increasing interest in understanding biology at the system level, there are several factors that hinder studies and analyses of biological systems. First, unlike systems from other applied fields whose parameters can be effectively identified, biological systems are usually unidentifiable, even in the ideal case when all possible system outputs are known with high accuracy. Second, the presence of multivariate bifurcations often leads the system to behaviors that are completely different in nature. In such cases, system outputs (as function of parameters/inputs) are usually discontinuous or have sharp transitions across domains with different behaviors. Finally, models from systems biology …

Intranuclear Strain Measured By Iterative Warping In Cells Under Mechanical And Osmotic Stress, Jonathan T Henderson

Open Access Dissertations

The nucleus is a membrane bound organelle and regulation center for gene expression in the cell. Mechanical forces transfer to the nucleus directly and indirectly through specific cellular cytoskeletal structures and pathways. There is increasing evidence that the transferred forces to the nucleus orchestrate gene expression activity. Methods to characterize nuclear mechanics typically study isolated cells or cells embedded in 3D gel matrices. Often report only aspect ratio and volume changes, measures that oversimplify the inherent complexity of internal strain patterns. This presents technical challenges to simultaneously observe small scale nuclear mechanics and gene expression levels inside the nuclei of …

Hierarchical Cell Fluid Extracellular Matrix Interaction In Cell Microenvironment, Soham Ghosh

Open Access Dissertations

Hierarchical structural interactions between components of cell microenvironment, the extracellular matrix (ECM), cytoplasm, nucleus and fluid, are important phenomena that decide cell level physiological process and tissue engineering applications. One of those tissue engineering modalities is freezing of biomaterials, important in a wide variety of biomedical applications including cryopreservation and cryosurgeries. In order to design these applications, freezing-induced changes of the cells and tissues and corresponding biophysical mechanisms need to be well understood. Although the effects of freezing on cells in suspension have been extensively studied, the intracellular mechanics of cells embedded in the extracellular matrix (ECM) during freezing are …

Development Of Planar Patch Clamp With Potentiometric Calcium Ion-Selective Electrode, Kul Inn

Open Access Dissertations

Ion channels are proteins in cell lipid bilayer membranes and act as pores which can adopt closed and open states, thus gating the flow of ions in and out of the cell. Patch clamp technology has been the proven standard for fundamental studies of ion channel activities. However, the technique has some basic limitations: low throughput, time consuming nature of its process, need of highly skilled personnel and inability to identify ionic composition of electrophysiological events. Many different materials and fabrication methods have been introduced to replace traditional patch clamp setup to overcome limitations.^ In this dissertation, a planar patch …