Biomedical Engineering and Bioengineering Commons^™

Electrostatic Effects On Lipid Bilayer Physicochemal Properties And Vesicle Adhesion, Oscar Zabala-Ferrera

Doctoral Dissertations

Lipids are an integral part of cells, being the principal component of the cell membrane, and contributing to the function and regulation of biological processes. Lipid nanoparticles mimicking a cell’s endosomes or exosomes are of particular interest within the pharmaceutical industry for their ability to deliver cargo such as RNA into target cells. The delivery process faces a multitude of challenges, so a rational design approach for vesicles that considers a lipid’s physicochemical contribution to the membrane is desired. To that end, this thesis explores the creation of large area biomembranes along with the development of electromechanical and optical characterization …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

A Rapid And Ultra-Sensitive Biosensing Platform Based On Tunable Dielectrophoresis For Robust Poc Applications, Yu Jiang

Doctoral Dissertations

With the ongoing pandemic, there have been increasing concerns recently regarding major public health issues such as abuse of organophosphorus compounds, pathogenic bacterial infections, and biosecurity in agricultural production. Biosensors have long been considered a kernel technology for next-generation diagnostic solutions to improve food safety and public health. Significant amounts of effort have been devoted to inventing novel sensing mechanisms, modifying their designs, improving their performance, and extending their application scopes. However, the reliability and selectivity of most biosensors still have much to be desired, which holds back the development and commercialization of biosensors, especially for on-site and point-of-care (POC) …

Interactions Between Soft Nanoparticles And Mammalian Cells, Mitchell Raith

Doctoral Dissertations

Nanoparticles have been of interest to the pharmaceutical industry since the 1980s. The first FDA approved nanoparticle-based therapies included liposomal anesthesia agents. Since then, the amount of FDA-approved nanoparticle therapies remains low. This is because nanoparticle-patient interactions can be very complex and are not well understood. Complicating factors also include increasing obesity rates among the patient population and many small animal pre-clinical trials are completed with healthy, lean animals. The biochemical differences between lean and obese patients prevents early studies from accurately predicting nanoparticle clinical behaviors. Many nanoparticles fail in trails. In this thesis, I aimed to uncover how nanoparticles …

Studies On Protein Solubility, Ke Li

Doctoral Dissertations

"Solubility is a critical factor of protein-based drugs during processing and patient administration. This study focused on two aspects of solubility: one was the poly (ethylene) glycol (PEG) precipitation of monoclonal antibodies (mAbs) and another was crystallins aggregation that is associated with cataracts. Protein precipitation by PEG is a common technique for downstream processing. The effects of pH, ionic strength and the exclude volume effect on the protein precipitation by PEG were extensively studied, but the effects of glycosylation on protein precipitation by PEG has not been examined. Protein aggregation is not only a problem in downstream processing, but it …

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 …

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 …

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 …

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, …

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 …

Structure-Property Relationships Of Polymer Films And Hydrogels To Control Bacterial Adhesion, Kristopher W. Kolewe

Doctoral Dissertations

The emergence and spread of antibiotic resistance across microbial species necessitates the need for alternative approaches to mitigate the risk of infection without relying on commercial antibiotics. Biofilm-related infections are a class of notoriously difficult to treat healthcare-associated infections that frequently develop on the surface of implanted medical devices. As biofilm formation is a surface-associated phenomenon, understanding how the intrinsic properties of materials affect bacterial adhesion enables the development of structure-property relationships that can guide the future design of infection-resistant materials. Despite lacking visual, auditory, and olfactory perception, bacteria still manage to sense and attach to surfaces. Previously, it has …

Analyses Of Densely Crosslinked Phenolic Systems Using Low Field Nmr, Jigneshkumar Patel

Doctoral Dissertations

A uniform dispersion of reactants is necessary to achieve a complete reaction involving multi-components, especially for the crosslinking of rigid high-performance materials. In these reactions, miscibility is crucial for curing efficiency. This miscibility is typically enhanced by adding a third component, a plasticizer. For the reaction of the highly crystalline crosslinking agent hexamethylenetetramine (HMTA) with a strongly hydrogen-bonded phenol formaldehyde resin, furfural has been traditionally used as the plasticizer. However, the reason for its effectiveness is not clear. In this doctoral thesis work, miscibility and crosslinking efficiency of plasticizers in phenolic curing reactions are studied by thermal analysis and spectroscopic …

Biopolymer Electrospun Nanofiber Mats To Inactivate And Remove Bacteria, Katrina Ann Rieger

Doctoral Dissertations

The persistence of antibiotic resistance in bacterial pathogens remains a primary concern for immunocompromised and critically-ill hospital patients. Hospital associated infections can be deadly and reduce the successes of medical advancements, such as, cancer therapies and medical implants. Thus, it is imperative to develop materials that can (i) deliver new antibiotics with accuracy, as well as (ii) uptake pathogenic microbes. In this work, we will demonstrate that electrospun nanofiber mats offer a promising platform for both of these objectives because of their high surface-to-volume ratio, interconnected high porosity, gas permeability, and ability to contour to virtually any surface. To provide …

Extracellular Matrix Control Of Breast Cancer Metastasis And Dormancy, Lauren Barney

Doctoral Dissertations

To metastasize, a cell must travel through circulation to a secondary tissue, and this process causes 90% of all cancer deaths. Although inefficient, metastasis is not random, and only capable seeds in hospitable soils are capable of outgrowing into detectable metastases. The overall hypothesis in this work is that the secondary tissue microenvironment, particularly the extracellular matrix (ECM), mediates metastasis. We posit that the ability of metastatic cells to survive dormancy, exit quiescence, and colonize a tissue depends upon the ability of the soil to sustain survival, and subsequently trigger outgrowth. We created a simple biomaterial platform with systematic control …

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment. A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has a mechanical …

Structure And Dynamics Of Charged Colloidal Disks In Colloid-Polymer Mixtures, Suhasini Kishore

Doctoral Dissertations

Complex fluid mixtures of colloids and polymers are extensively used in several conventional and emerging technological applications. Particles self-assemble under different conditions to form colloidal glasses and gels and it often leads to the development of unusual viscoelastic features. In the case of aspherical particles, shape anisotropy and physical aging effects add to the existing complexities so the implementation of a strategic formulation method to improve performance and stability remains a critical challenge. This thesis presents a comprehensive analysis of particle interactions in mixtures of charged disk-shaped colloids and weakly-adsorbing polymers like poly(ethylene oxide) (PEO). Here, we discuss the behavior …

In Silico Driven Metabolic Engineering Towards Enhancing Biofuel And Biochemical Production, Richard Adam Thompson

Doctoral Dissertations

The development of a secure and sustainable energy economy is likely to require the production of fuels and commodity chemicals in a renewable manner. There has been renewed interest in biological commodity chemical production recently, in particular focusing on non-edible feedstocks. The fields of metabolic engineering and synthetic biology have arisen in the past 20 years to address the challenge of chemical production from biological feedstocks. Metabolic modeling is a powerful tool for studying the metabolism of an organism and predicting the effects of metabolic engineering strategies. Various techniques have been developed for modeling cellular metabolism, with the underlying principle …

Mimicking The Arterial Microenvironment With Peg-Pc To Investigate The Roles Of Physicochemical Stimuli In Smc Phenotype And Behavior, William G. Herrick

Doctoral Dissertations

The goal of this dissertation was to parse the roles of physical, mechanical and chemical cues in the phenotype plasticity of smooth muscle cells (SMCs) in atherosclerosis. We first developed and characterized a novel synthetic hydrogel with desirable traits for studying mechanotransduction in vitro. This hydrogel, PEG-PC, is a co-polymer of poly(ethylene glycol) and phosphorylcholine with an incredible range of Young’s moduli (~1 kPa - 9 MPa) that enables reproduction of nearly any tissue stiffness, exceptional optical and anti-fouling properties, and support for covalent attachment of extracellular matrix (ECM) proteins. To our knowledge, this combination of mechanical range, low …

Diamond Mems Biosensors: Development And Applications, Wenli Zhang

Doctoral Dissertations

This research focuses on the development a dielectrophoresis-enhanced microfluidic impedance biosensor (DEP-e-MIB) to enable fast response, real-time, label-free, and highly sensitive sensor for bacterial detection in clinical sample. The proposed design consists of application of dielectrophoresis (DEP) across a microfluidic channel to one of the impedance spectroscopy electrodes in order to improve the existent bacterial detection limits with impedance spectroscopy. In order to realize such a design, choice of electrode material with a wide electrochemical potential window for water is very important. Conventional electrode material, such as gold, are typically insulated for the application of DEP, and they fail when …

Gold Nanoparticle Enhancements In Electroporation Mediated Dna And Rna Therapeutics, Shuyan Huang

Doctoral Dissertations

Nonviral gene delivery methods have been explored as the replacement of viral systems for their low toxicity and immunogenicity. However, they have yet to reach levels competitive to their viral counterparts. Electroporation figured prominently as an effective nonviral gene delivery approach for its balance on the transfection efficiency and cell viability, no restrictions of probe or cell type, and operation simplicity. The commercial electroporation systems have been widely adopted in the past two decades but still carry drawbacks associated with the high applied electric voltage, unsatisfied delivery efficiency, and/or low cell viability. What we did was to improve electroporation performance …

Cell Adhesion Biophysics On Dynamic Polymer Constructs, Andreas Kourouklis

Doctoral Dissertations

The biophysical characteristics of cell adhesion from single protein to cell length scales have primarily been studied using purely elastic substrates. However, natural extracellular matrix (ECM) is viscoelastic and contains mobile components. In this work, we combined chemistry and cell biology tools to design and characterize laterally mobile viscoelastic polymer films that promote receptor-specific cell adhesion. Moreover, we used amphiphilic block copolymers that are end-labeled with RGD peptide ligands to allow for integrin-mediated cell adhesion. The addition of a trace hydrophobic homopolymer in the supported bilayer block-copolymer films is used to tune the lateral mobility of the films. NIH 3T3 …

Strategies For Improving Oxygen Transport And Mechanical Strength In Alginate-Based Hydrogels, Joseph C. White

Doctoral Dissertations

Hydrogels have attracted significant interest over the past several decades due to their outstanding versatility as biomaterials. Alginate-based hydrogels are among the most popular studied due to their low cost, biocompatibility, and tunable physical properties. However, as with all hydrogels, persistent oxygen solubility and poor mechanical strength limits their utility for creating macroscopic devices for biomedical use. This thesis presents two strategies for improving oxygen transport and mechanical properties of alginate-based hydrogel. The former involves incorporating perfluorocarbons, hydrophobic compounds with very high oxygen solubility, into the formulation. The perfluorocarbons are stabilized by nonionic surfactants, Pluronics®, and the emulsion is entrapped …

Microfluidic Devices Applied On Enriching Post –Translational Modified Proteins For Proteomics, Hui Xia

Doctoral Dissertations

In this work, microfluidic devices were developed for enriching post-translational modified proteins. Post-translational modifications (PTM) of proteins play essential roles in cellular physiology and disease. The identification of protein substrates and detection of modification site helps understand PTM-mediated regulation in essential biological pathways and functions in various diseases. However, PTM proteins are typically present only at trace levels, making them difficult to identify in mass spectrometry based proteomics. This work study is about the design, fabrication and testing of the microfluidic device for the enrichment of abundant amount of PTMs. Carbonylated protein is used as a representative PTM to illustrate …

Modulation Of Bone And Nerve Cell Behavior Using Biodegradable Polymer Networks, Lei Cai

Doctoral Dissertations

This dissertation presents novel biodegradable and photo-crosslinkable building blocks to achieve polymer networks with controlled surface chemistry, stiffness, and topographical features for investigating cell-material interactions and targeting hard and soft tissue engineering applications. Chapter I reviews the recent progress in polymeric gel systems and how their physical properties can be tailored to regulate cell functions and satisfy the clinical needs. Chapter II presents a facile method to synthesize photo-crosslinkable poly(epsilon-caprolactone) acrylates (PCLAs) and reveal tunable cell responses to photo-crosslinked PCLAs. Chapter III investigates the mechanism of colorization in preparing crosslinkable polymers by reacting hydroxyl-containing polymers with unsaturated anhydrides or acyl …

Role Of Ammonia In The Activiation Of Methanol Dehydrogenase/Cytochrome C(L) Enzyme, Ancy Kunjumon

Doctoral Dissertations

Recent advancement in enzyme catalysis has opened ways to design efficient biocatalysts, bio-sensors and bio-fuel cells. An in-depth knowledge about the mechanism of the reaction taking place within the enzymes is of great importance to achieve these goals. In this dissertation, various computation methods are applied to investigate the mechanism behind enzyme catalysis in the presence of compounds called activators.

Methanol dehydrogenase (MDH) is a well-known bio-catalyst that can oxidize excess of methanol from the environment to formaldehyde. The enzyme works well within the bacterial environment, but under in vitro, it loses activity. Ammonia is used as an activator …

Investigation Of Microbubble/Droplet Formation In Cross-Flow And Co-Flow Micro Devices, Tom J. John

Doctoral Dissertations

The primary goal of the work presented in this dissertation is to generate microbubbles of a diameter of less than 15μm inside micro channels. In order to achieve this detailed understanding, the facts and limitations behind the generation of microbubbles inside a micro channel are determined from existing literature. The major limitations of the current bubble/droplet generators are found to be the bubble confinement effect, the merging of bubbles, the difficulty in determining bubble diameter and the need for smaller channels to generate smaller bubbles. A device eliminating these drawbacks is conceptualized, and its feasibility is studied using COMSOL® and …

A Simulation Of The Neural Action Potential Under The Influence Of Acetylcholinesterase Inhibitors Modeled In The Neuromuscular Junction, Frank Jenkins

Doctoral Dissertations

The rise of terrorism has created an interest in better ways to detect when humans are exposed to neurotoxins, especially nerve gases developed for military use, most of which are acetylcholinesterase inhibitors. Many current methods of detection are based on mass spectrometry, a method that is cumbersome and not particularly robust when used as an early warning method. The detection of acetylcholinesterase inhibitors would benefit from a combined model of the processes occurring in the neuromuscular junction between the presynaptic action potential and the motor end-plate action potential that includes the kinetics of acetylcholine and acetylcholinesterase in the synaptic cleft. …