Biomedical Engineering and Bioengineering Commons^™

Dynamic Behavior And Interactions Of Ferrofluid Droplets Under Magnetic Fields In Low Reynolds Number Flows, Md Rifat Hassan

Doctoral Dissertations

Digital microfluidics in combination with emulsion microfluidics are crucial building blocks of droplet-based microfluidics, which are prevalent in a wide variety of industrial and biomedical applications, including polymer processing, food production, drug delivery, inkjet printing, and cell-based assays. Therefore, understanding the dynamics and interactions of droplets as well as the interactions between the droplets and solid surfaces are of great importance in order to improve the performance or product in these applications.

Recently, several studies in the literature have demonstrated the potential of magnetic fields in controlling the behavior of droplets in microscale; however, the fundamental mechanism behind the interesting …

Engineering Stimuli-Responsive Polymeric Nanoassemblies: Rational Designs For Intracellular Delivery Of Biologics, Kingshuk Dutta

Doctoral Dissertations

Biologic drugs have gained enormous research attention in recent years as reflected by the development of multiple candidates to the clinical pipelines and an increased percentage of FDA approval. This is reasoned by the fact that biologics have been proven to deliver more predictive and promising benefits for many hard-to-cure diseases by ‘drugging the undruggable’ targets. However, the challenges associated with biologic drug development are multi-fold, viz, poor encapsulation efficacy, systemic instability, low cellular internalization and endosomal escape capability. Thus, it is essential to develop new molecular strategies that can not only address the associated drug delivery challenges, but also …

Controlled Membrane Remodeling By Nanospheres And Nanorods: Experiments Targeting The Design Principles For Membrane-Based Materials, Sarah Zuraw-Weston

Doctoral Dissertations

In this thesis we explore two experimental systems probing the interactions of nanoparticles with lipid bilayer membranes. Inspired by the ability of cell membranes to alter their shape in response to bound particles, we report two experimental studies: one of nanospheres the other of long, slender nano-rods binding to lipid bilayer vesicles and altering the membrane shape. Our work illuminates the role of particle geometry, particle concentration, adhesion strength and membrane tension in how membrane morphology is determined. We combine giant unilamellar vesicles with oppositely charged nanoparticles, carefully tuning adhesion strength, membrane tension and particle concentration. In the case of …

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …

Engineering Mesothelin-Binding Proteins As Targeted Cancer Diagnostics And Therapeutics, Allison Rita Sirois

Doctoral Dissertations

Cancer is a significant global health concern; and traditional therapies, including chemotherapeutics, are often simultaneously toxic yet ineffective. There is a critical need to develop targeted cancer therapeutics which specifically inhibit molecules or molecular pathways essential for tumor growth and maintenance. Furthermore, a targeted therapy is only effective when a patient's tumor expresses the molecular target; therefore, companion diagnostics, including molecular imaging agents, are a necessary counterpart of targeted therapies. Mesothelin (MSLN) is a cell surface protein overexpressed in numerous cancers, including triple-negative breast, pancreatic, ovarian, liver, and lung, with limited expression in normal tissues. Aberrant MSLN expression promotes tumor …

Approaches To Studying Bacterial Biofilms In The Bioeconomy With Nanofabrication Techniques And Engineered Platforms., Michelle Caroline Halsted

Doctoral Dissertations

Studies that estimate more than 90% of bacteria subsist in a biofilm state to survive environmental stressors. These biofilms persist on man-made and natural surfaces, and examples of the rich biofilm diversity extends from the roots of bioenergy crops to electroactive biofilms in bioelectrochemical reactors. Efforts to optimize microbial systems in the bioeconomy will benefit from an improved fundamental understanding of bacterial biofilms. An understanding of these microbial systems shows promise to increase crop yields with precision agriculture (e.g. biosynthetic fertilizer, microbial pesticides, and soil remediation) and increase commodity production yields in bioreactors. Yet conventional laboratory methods investigate these micron-scale …

Automated Intelligent Cueing Device To Improve Ambient Gait Behaviors For Patients With Parkinson's Disease, Nader Naghavi

Doctoral Dissertations

Freezing of gait (FoG) is a common motor dysfunction in individuals with Parkinson’s disease (PD). FoG impairs walking and is associated with increased fall risk. Although pharmacological treatments have shown promise during ON-medication periods, FoG remains difficult to treat during medication OFF state and in advanced stages of the disease. External cueing therapy in the forms of visual, auditory, and vibrotactile, has been effective in treating gait deviations. Intelligent (or on-demand) cueing devices are novel systems that analyze gait patterns in real-time and activate cues only at moments when specific gait alterations are detected. In this study we developed methods …

Effect Of Ambient Oxidation On Chemical Composition And Structural Properties Of Iron Nanoparticles For Hyperthermia And Medical Imaging, Adam Wesley Evans

Doctoral Dissertations

With magnetization saturation roughly twice that of iron oxide nanoparticles, metallic iron nanoparticles (also termed zero-valent iron nanoparticles) have desirable properties for use as a magnetic resonance imagining (MRI) contrast agent as well as a medium for hyperthermia treatment of cancer. Metallic iron nanoparticles, however, are difficult to synthesize and maintain due to their high degree of reactivity and proclivity for oxidation. The main goal of this study was to investigate how ambient oxidation affects the chemical composition and structural properties of metallic iron nanoparticles initially synthesized through a facile reduction reaction of iron (III) chloride with sodium borohydride. A …

Phylogenetics And Association Analyses Illustrate Substantial Cryptic Diversity Of A Newly Isolated Collection Of Cenococcum Geophilum, Jessica Velez

Doctoral Dissertations

The ectomycorrhizal fungus Cenococcum geophilum is distributed worldwide across multiple climates and soil types and is known to positively associate with a multitude of plant genera, possibly contributing to plant ability to tolerate inorganic contaminants in a soil environment. New C. geophilum isolates are easily cultured from soils in a laboratory setting, making this an ideal candidate for a model species with which to study multiple plant-fungal effects across a collection of novel isolates. However, C. geophilum is also genetically complex and, at 178Mbp, features one of the largest fungal genomes, necessitating the use of the novel restriction-associated DNA sequencing …

Analysis And Enhancement Of Human Cognitive Control Using Noninvasive Brain-Computer Interfaces, Soheil Borhani

Doctoral Dissertations

Cognitive control including attention and working memory are crucial to human daily life. Whether a civilian who walks across a street or a military service member who is responsible for navigating a mission, cognitive control is involved, entirely. This ability is subject to impairment. People with attention disorder are easily disposed to distraction and lacks the ability to maintain the focus to a task. Multiple treatment strategies have been suggested which most of them has been pharmaceutical. Evidently, the medical treatment has side effects for long-term use. Moreover, it has a risk of drug misuse. Another line of treatment is …

Engineering Platforms For Advancing Plant Synthetic Biology, Tayler Marie Schimel Mcneillie

Doctoral Dissertations

This work describes research aimed at adapting advanced engineering systems for plant biotechnology. The droplet interface bilayer (DIB) is a robust and versatile platform for replicating model cell membranes, providing a bottom-up approach for synthetic cell- and tissue-like structures. In this work, a microfluidic device featuring five inlets, one for the continuous oil phase and four discrete aqueous channels for droplet generation was designed. Droplet production rates were controlled by adjusting the applied pressure of each inlet; and thus, altering the droplet sequence for capturing linear DIB networks in a downstream hydrodynamic trapping array. This microfluidic system provides a high-throughput …

Elucidating Mechanisms Of Metastasis With Implantable Biomaterial Niches, Ryan Adam Carpenter

Doctoral Dissertations

Metastasis is the leading cause of cancer related deaths, yet it remains the most poorly understood aspect of tumor biology. This can be attributed to the lack of relevant experimental models that can recapitulate the complex and lengthy progression of metastatic relapse observed in patients. Mouse models have been widely used to study cancer, however they are critically limited to study metastasis. Most models generate aggressive metastases in the lung without the use of unique cell lines or specialized injection techniques. This limits the ability to study disseminated tumor cells (DTCs) in other relevant metastasis prone tissues. Prolonged observation of …

Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin

Doctoral Dissertations

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug …

Deep Learning For Digitized Histology Image Analysis, Sudhir Sornapudi

Doctoral Dissertations

“Cervical cancer is the fourth most frequent cancer that affects women worldwide. Assessment of cervical intraepithelial neoplasia (CIN) through histopathology remains as the standard for absolute determination of cancer. The examination of tissue samples under a microscope requires considerable time and effort from expert pathologists. There is a need to design an automated tool to assist pathologists for digitized histology slide analysis. Pre-cervical cancer is generally determined by examining the CIN which is the growth of atypical cells from the basement membrane (bottom) to the top of the epithelium. It has four grades, including: Normal, CIN1, CIN2, and CIN3. In …

Design Of X-Ray Source For Real-Time Computed Tomography, Wesley William Tucker

Doctoral Dissertations

"The reduction of motion blur in computed tomography (CT) drives the current research for multisource CT. Due to their compact nature, the current multisource systems utilize stationary angled anodes. Unfortunately, these configurations neither simplify the imaging geometry, nor satisfy the need for managing the high thermal loads demanded by real-time CT (30 acquisition frames per second). To add to the current field of knowledge, two x-ray tube concepts are presented in this dissertation. First, a simulation of transient thermal analysis was performed on a compact transmission-type x-ray tube anode operating in pulse-mode. A correlation was found between deposited beam power …

Predictive Simulation Of Human Movement And Applications To Assistive Device Design And Control, Vinh Nguyen

Doctoral Dissertations

Predictive simulation based on dynamic optimization using musculoskeletal models is a powerful approach for studying biomechanics of human gait. Predictive simulation can be used for a variety of applications from designing assistive devices to testing theories of motor controls. However, one of the challenges in formulating the predictive dynamic optimization problem is that the cost function, which represents the underlying goal of the walking task (e.g., minimal energy consumption) is generally unknown and is assumed a priori. While different studies used different cost functions, the qualities of the gaits with those cost functions were often not provided. Therefore, this dissertation …

Bioinspired Complex Nanoarchitectures By Dna Supramolecular Polymerization, Laura A. Lanier

Doctoral Dissertations

Bioinspired nanoarchitectures are of great interest for applications in fields such as nanomedicine, tissue engineering, and biosensing. With this interest, understanding how the physical properties of these complex nanostructures relate to their function is increasingly important. This dissertation describes the creation of complex nanoarchitectures with controlled structure and the investigation of the effect of nanocarrier physical properties on cell uptake for applications in nanomedicine. DNA self-assembly by supramolecular polymerization was chosen to create complex nanostructures of controlled architectures. We demonstrated that the supramolecular polymerization of DNA known as hybridization chain reaction (HCR) is in fact a living polymerization. The living …

Engineering Nanomaterials For Imaging And Therapy Of Bacteria And Biofilm-Associated Infections, Akash Gupta

Doctoral Dissertations

Infections caused by multidrug-resistant (MDR) bacteria pose a serious global burden of mortality, causing thousands of deaths each year. The “superbug” risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that are highly resistant to available treatments. Synthetic macromolecules such as polymers and nanoparticles have emerged as promising antimicrobials. Moreover, ability to modulate nanomaterial interaction with bacterial cellular systems plays a pivotal role in improving the efficacy of the strategy. In the initial studies on engineering nanoparticle surface chemistry, I investigated the role played by surface ligands in determining the antimicrobial activity of the nanoparticles. In further study, …

Electrolytic Metallization Of Halloysite Nanotubes And Antimicrobial Applications, Ahmed Humayun

Doctoral Dissertations

Due to increased reports of infections and biofouling arising from the use of invasive medical devices, novel antimicrobial agents with suitable anti-biofouling properties are critically needed. Transition metals exhibit substantial antimicrobial activity; however, their use is limited because of their inherent toxicity to eukaryotic cells. In this regard, naturally occurring halloysite clay nanotubes (HNTs) show significant promise. HNTs possess a high surface area for adsorption while its hollow lumen can be used for loading different materials.

Herein, we demonstrate an electrolytic method for generating and depositing metal nanoparticles (NPs) on the HNTs outer surface and we propose an optimized method …

Application Of Halloysite Nanotubes In Bone Disease Remediation And Bone Regeneration, Yangyang Luo

Doctoral Dissertations

Customized patient therapy has been a major research focus in recent years. There are two research fields that have made a significant contribution to realizing individualized-based treatment: targeted drug delivery and three-dimensional (3D) printing technology. With benefit from the advances in nanotechnology and biomaterial science, various drug delivery systems have been established to provide precise control of therapeutic agents release in time and space. The emergence of three-dimensional (3D) printing technology enables the fabrication of complicated structures that effectively mimic native tissues and makes it possible to print patient-specific implants. My dissertation research used a clay nanoparticle, halloysite, to develop …

Development Of A Low Profile, Endoscopic Implant For Long Term Brain Imaging, Benjamin Scott Kemp

Doctoral Dissertations

The increased public awareness of concussion and traumatic brain injury has motivated continued research into the brain, its functions, and especially its response to injury, with a focus on improving the brain’s repair capabilities. However, due to the critical nature of the tissue, it is currently difficult for researchers to acquire high resolution images below the cortex without sacrificing a lab animal. Sacrificing an animal greatly reduces the amount of data that can be obtained from it, making longitudinal studies unappealing or unfeasible because a large number of animals is needed to obtain useful data over multiple time points. Additionally, …

Walking For Object Transport: An Examination Of The Coordinative Adaptations To Locomotor, Perceptual, And Manual Task Constraints, Avelino Amado

Doctoral Dissertations

The goal of this dissertation was to understand how the intrinsic dynamics of gait adapt to support the performance of an ecologically relevant object transport task. A common object transport task is walking with a cup of water. Because the water can move relatively independent of the cup, the cup and water system is classified as a complex object. To model this task participants carried a cup with a wooden lid placed on top. On the lid there was a circular region with the same circumference as the cup and a ball. The object of the task was to keep …

Two And Three-Dimensional Models For Material And Cells Interaction, Nam H. Nguyen

Doctoral Dissertations

Three-dimensional (3D) cell spheroid model has been long considered a better model to mimic in vivo physiology compared to two-dimensional (2D) cell culture model. Traditional 2D cell models provide a simple, convenient and quick technique for drug screening but fail to simulate the complexity and heterogeneity of cells in the in vivo environment. The last few decades have remarked substantial progress toward the advancement of three-dimensional (3D) cell cultures as systems which better mimic cellcell and cell-matrix interaction in the in vivo physiology. Nowadays, 3D cell models have been emerging, not only as an important approach in drug discovery and …

Direct Printing/Patterning Of Key Components For Biosensor Devices, Yiliang Zhou

Doctoral Dissertations

Recently, biosensor devices, especially wearable devices for monitoring human health, have attracted significant interests and meanwhile, they have a huge market. These wearable biosensor devices usually consist of several key components, including microfluidics, biosensing elements and power supply. Though advanced sensing platforms have been extensively explored, high manufacturing fee and lack of practical functions are the main reasons that most of devices and techniques are still out of reach for potential users. This dissertation focuses on fabricating these key components for biosensor devices via advanced printing/patterning techniques, such as inkjet-printing and nanoimprinting. These fabrication techniques can be potentially extended to …

Building The Outer Membrane Protein G (Ompg) Nanopore Library: From The Discrimination Of Biotin-Binding Proteins In Serum To Resolving Human Carbonic Anhydrase From Human Red Blood Cells, Bib Yang

Doctoral Dissertations

The use of pore-forming proteins (PFPs) in nanopore sensing has been fruitful largely due to their nanoscale size and the ease with which protein nanopores can be manipulated and consistently reproduced at a large scale. Nanopore sensing relies heavily on a steady ionic current afforded by rigid nanopores, as the change in current is indicative of analyte detection, revealing characteristics of the analyte such as its relative size, concentration, and charge, as well as the nanopore:analyte interaction. Rigid PFPs have been used in applications such as DNA sequencing, kinetic studies, analyte discrimination, and protein conformation dynamics at the single-molecule level. …

Development Of An Astrocyte/Glioma Co-Culture System For Measuring Cellular Dynamics, Urna Kansakar

Doctoral Dissertations

Gliomas are brain tumors that primarily arise from glial cells. Gliomas account for 70% of the brain tumors and they are more prevalent in older adults. About 60% of the people with gliomas experience at least one seizure. Brain tumors can grow and metastasize to neighboring areas, thereby destroying normal brain cells. In a brain tumor microenvironment, both malignant cancer cells and healthy brain cells are present. Studies have shown that astrocytes may have a role in tumor growth in the brain. Monocultures cannot evaluate interactions between two cell types and does not accurately represent in vivo conditions. Thus, a …

Development Of A Counter-Flow Thermal Gradient Microfluidic Device, Shayan Davani

Doctoral Dissertations

This work presents a novel counter-flow design for thermal stabilization of microfluidic thermal reactors. In these reactors, precise control of temperature of the liquid sample is achieved by moving the liquid sample through the thermal zones established ideally through the conduction in the solid material of the device. The goal here is to establish a linear thermal distribution when there is no flow and to minimize the temperature change at flow condition. External convection as well as internal flowinduced effects influence the prescribed thermal distribution. The counter-flow thermal gradient device developed in this study is capable of both stabilizing the …

Applications Of Machine Learning In Nuclear Imaging And Radiation Detection, Shaikat Mahmood Galib

Doctoral Dissertations

"The main focus of this work is to use machine learning and data mining techniques to address some challenging problems that arise from nuclear data. Specifically, two problem areas are discussed: nuclear imaging and radiation detection. The techniques to approach these problems are primarily based on a variant of Artificial Neural Network (ANN) called Convolutional Neural Network (CNN), which is one of the most popular forms of 'deep learning' technique.

The first problem is about interpreting and analyzing 3D medical radiation images automatically. A method is developed to identify and quantify deformable image registration (DIR) errors from lung CT scans …

Spatiotemporal Modeling And Model Restructuration Approaches In Studies Of Intracellular Signalling Pathways, Md Shahinuzzaman

Doctoral Dissertations

"The main focus of the research is to understand the complex phenomena of cell transduction pathways and cell biology in a single cell. Mathematical modeling and experimental evaluation are widely used approaches for this kind of research. Firstly, A multiscale framework for protein-protein interaction has been established using Brownian dynamics algorithm. Sit specific feature, steric collision, diffusion, co-localization and complex formation with time and space has been included in this spatial modeling framework. By implementation of the time adaptive feature in this framework, the computation time reduces in an order of magnitude compared with traditional modeling framework. This multiscale Brownian …

Biophysical Features Of The Extracellular Matrix Direct Breast Cancer Metastasis, Alyssa Schwartz

Doctoral Dissertations

Breast cancer is plagued by two key clinical challenges; drug resistance and metastasis. Most work to date probes these events on an extremely rigid plastic surface, which recapitulates few aspects of these processes in humans. A malignant cell first resides in breast tissue, then likely travels to the bone, brain, liver, or lung, each of which has a distinct mechanical and biochemical profile. Cells transmit mechanical forces into intracellular tension and biochemical signaling events, and here we hypothesize that this mechanotransduction influences drug response, growth, and migration. To probe the impact of extracellular matrix on drug resistance, we defined a …