Biomedical Engineering and Bioengineering Commons^™

Design And Synthesis Of Analogs Of Myo-Inositol, Serine, And Cysteine To Enable Chemical Biology Studies, Tanei J. Ricks

Doctoral Dissertations

Phosphorylated myo-inositol compounds including inositol phosphates (InsPs) as well as the phosphatidylinositol polyphosphate lipids (PIP_ns) are critical biomolecules that regulate many of the most important biological processes and pathways. They are aberrant in many disease states due to their regulatory function. The same is true of the phospholipid phosphatidylserine (PS) which can serve as a marker to begin apoptosis. However, the full scope of activities of these structures is not clear, particularly since techniques that enable global detection and analysis of the production of these compounds spatially and temporally are lacking. With all of these obstacles in …

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 …

Protein-Nanoparticle Co-Engineering: Self-Assembly, Intracellular Protein Delivery, And Crispr/Cas9-Based Gene Editing, Rubul Mout

Doctoral Dissertations

Direct cytoplasmic delivery of gene editing nucleases such CRISPR/Cas9 systems and therapeutic proteins provides enormous opportunities in curing human genetic diseases, and assist research in basic cell biology. One approach to attain such a goal is through engineering nanotechnological tools to mimic naturally existing intra- and extracellular protein delivery/transport systems. Nature builds transport systems for proteins and other biomolecules through evolution-derived sophisticated molecular engineering. Inspired by such natural assemblies, I employed molecular engineering approaches to fabricate self-assembled nanostructures to use as intracellular protein delivery tools. Briefly, proteins and gold nanoparticles were co-engineered to carry complementary electrostatic recognition elements. When these …

Tissue-Guided Engineering Of Polyethylene Glycol Hydrogels, Lauren Jansen

Doctoral Dissertations

Polyethylene glycol (PEG) hydrogels are tunable cell culture platforms that recapitulate tissue geometry, water content, and bulk modulus. Despite these benefits, PEG hydrogels elicit an acute immune response, limiting their use in regenerative medicine, and they critically underrepresent the cell-instructive proteins found in the extracellular matrix (ECM). Here, I developed a new class of tissue-specific PEG-based materials and provided biocompatible strategies to improve the user handling and cell viability post-encapsulation when using these hydrogels. I also demonstrated that decreasing the protein fouling to PEG does not decrease the foreign body response to implanted hydrogels, a common misconception in the field. …

Crafting Nanostructured Neural Interfaces With Hydrogel Particles, Emily Ann Morin

Doctoral Dissertations

Central nervous system neural device functionality hinges on effective communication with surrounding neurons. This depends on both the permissiveness of the device material to promote neuron integration and the ability of the device to avoid a chronic inflammatory response. Here, a facile approach has been developed exploring the multiple functionalities of hydrogel particles to provide cues to impart neural integration for such materials. Three distinct, yet interconnected tasks were undertaken: investigating hydrogel particle-modified substrate neuron integration and central nervous system inflammatory response, investigating guided hydrogel particle adsorption, and investigating hydrogel particles as local reservoirs for counteracting adverse effects from oxidative …

Development And Implementation Of A Forward Solution Hip Mathematical Model To Determine In Vivo Mechanics And Predict Hip Separation, Michael Thomas Lacour

Doctoral Dissertations

Osteoarthritis, signified by excessive wear of joint cartilage, is most common in hip, knee, and spinal joints [1]. Current treatment for extreme osteoarthritis is total joint arthroplasty, where the damaged bone and cartilage are removed and replaced by artificial bone representations separated by artificial cartilage representations. While this treatment does generally improve patient quality of life, current joint replacement systems unfortunately still yield atypically high forces, premature component wear, and abnormal kinematics compared to native joints [2] [3] [4] [5].

For total hip arthroplasty, one common complication is in vivo separation and dislocation of the femoral head within the acetabular …

Managing Exoelectrogenic Microbial Community Development Through Bioprocess Control For Conversion Of Biomass-Derived Streams, Alex James Lewis

Doctoral Dissertations

Bioelectrochemical systems are an emerging technology capable of utilizing aqueous waste streams generated during biomass conversion of lignocellulosic feedstocks to produce valuable co-products and thus, have potential to be integrated into biorefineries. In a microbial electrolysis cell, organic compounds are converted to electrons, protons, and CO₂ by fermentative and exoelectrogenic bacteria in the anode compartment. By having the ability to extract electrons from waste streams, these systems can treat water while also producing hydrogen, and thus can improve the efficiency of biomass to fuel production by minimizing external hydrogen requirement and enabling water recycle. The overall goal of this …

Understanding The Surface Fouling Mechanism Of Ultrananocrystalline Diamond Microelectrodes Using Microfluidics For Neurochemical Detection, An-Yi Chang

Doctoral Dissertations

Electrochemical methods are widely used for chronic neurochemical sensing, but thus far, the organic solution redox reactions fouled the electrodes' surface. It caused the reduction of sensitivity and the electrodes' lifetime.

Here, we present the boron-doped nanocrystalline diamond microelectrodes (BDUNCD) as the next generation electrode material for neurochemical sensor development. To aid in long-term chronic monitoring of neurochemicals, they have a wide window of electrochemical potential, extremely low background current, and excellent chemical inertness. The main research goal is to reduce the rate of electrode fouling due to the reaction by-products, and significantly extend their useful lifetime.

We systematically characterize …

Dynamic Simulation And Analysis Of Gait Modification For Treating Knee Osteoarthritis, Taylor Elyse Schlotman

Doctoral Dissertations

Roughly 47.5 million people in the US have a disability, with 8.6 million reporting arthritis as their main cause of disability, making arthritis the leading cause of physical disability. With decreased mortality rates and a large, aging baby boomer generation, there will be more adults living with chronic musculoskeletal conditions causing disabilities that limit walking. Since walking ability is directly related to an individual’s independence at home and in the community, losing this ability is a major setback for patients with arthritis. Knee osteoarthritis (OA) is the most prevalent form of arthritis affecting approximately 27 million adults and accounts for …

Musculoskeletal Loads During Stationary Cycling And The Effects Of Pedal Modifications For Knee Osteoarthritis, Rachel Lynn Thompson

Doctoral Dissertations

Knee OA is a deteriorating joint disease affecting 27 million people in the US and current exercise prescriptions may be improved with new knowledge of their effects on muscle forces and joint contact loads. Cycling rather than other exercise modalities is generally considered an alternative for people with knee OA. If these research objectives were achieved, clinicians would have additional tools related to joint contact loads for treating people with OA with an cycling exercise while controlling progression of OA. The long-term goal of this research is to provide a scientific basis for planning, evaluation and improvement of subject-specific rehabilitation …

High-Throughput Functional System For Encapsulated Networks Of Model Cell Membranes, Mary-Anne Kim Anh Nguyen

Doctoral Dissertations

Synthetic lipid bilayers provide models of cell membranes to study biomolecular interactions and signal transduction. The droplet interface bilayer (DIB) is a highly versatile technique for assembling planar lipid membranes between water droplets in oil. The DIB method thus provides a unique capability for developing digital, droplet-based membrane platforms for rapid membrane characterization, drug screening and ion channel recordings. In this work, a new microfluidic system is presented that automates droplet generation, sorting, and sequential trapping in designated locations to enable rapid assembly of arrays of DIBs along with in situ electrical measurements. This platform provides repeatable processes for forming …

Characterization And Manipulation Of Lipid Self-Assembly To Construct Stable, Portable Synthetic Lipid Bilayers, Guru Anand Venkatesan

Doctoral Dissertations

The overarching goal of this research work is to further our understanding of lipid self-assembly and its organization at an oil-water interface to support the development of synthetic lipid bilayer systems that can be used in biologically relevant fields such as membrane biophysics, protein electrophysiology, development of synthetic biomolecules, drugs, nanoparticles and other applications. Self-assembly kinetics and interfacial properties of lipid monolayers formed at a liquid-air and liquid-liquid interface are characterized using Langmuir-Blodgett trough and pendant drop tensiometer. Insights gained from these studies not only allow us to answer questions related to droplet interface bilayer (DIB; a promising technique to …

Modeling, Analysis, Force Sensing And Control Of Continuum Robots For Minimally Invasive Surgery, Caroline Bryson Black

Doctoral Dissertations

This dissertation describes design, modeling and application of continuum robotics for surgical applications, specifically parallel continuum robots (PCRs) and concentric tube manipulators (CTMs). The introduction of robotics into surgical applications has allowed for a greater degree of precision, less invasive access to more remote surgical sites, and user-intuitive interfaces with enhanced vision systems. The most recent developments have been in the space of continuum robots, whose exible structure create an inherent safety factor when in contact with fragile tissues. The design challenges that exist involve balancing size and strength of the manipulators, controlling the manipulators over long transmission pathways, and …

Improvement Of Fluorescence-Based Microfluidic Dna Analyzers, Collin Tranter

Doctoral Dissertations

A tremendous effort continues in the development of micro-total-analysis-systems; in support of this, many chemical passivation methods have been developed to enhance the biocompatibility of such microfluidic systems. However, the suitability of these passivation techniques to many fluorescence-based assays still remains inconsistent. This part of this work is focused on the performance of a third generation intercalating DNA dye when used within microfluidic devices treated with a select variety of passivating coatings. The results of these tests indicate that passivation coatings which are intended to shed DNA based on electrostatic repulsion will in fact imbibe the fluorescent DNA intercalating dye …

Development Of A Nonlinear Model For The Prediction Of Response Times Of Glucose Affinity Sensors Using Concanavalin A And Dextran And The Development Of A Differential Osmotic Glucose Affinity Sensor, Louis G. Reis

Doctoral Dissertations

With the increasing prevalence of diabetes in the United States and worldwide, blood glucose monitoring must be accurate and reliable. Current enzymatic sensors have numerous disadvantages that make them unreliable and unfavorable among patients. Recent research in glucose affinity sensors correct some of the problems that enzymatic sensors experience. Dextran and concanavalin A are two of the more common components used in glucose affinity sensors. When these sensors were first explored, a model was derived to predict the response time of a glucose affinity sensor using concanavalin A and dextran. However, the model assumed the system was linear and fell …

Expanding The Applications Of Poly(Dimethylsiloxane) In Biomicrofluidics, Sawyer D. Stone

Doctoral Dissertations

This work aims to create novel applications for poly(dimethylsiloxane) (PDMS) in the field of biomicrofluidics through oxidative stress detection, doping of the polymer for intentional leaching into microdevices, and the development of low-cost implements for fabricating PDMS microfluidic devices. PDMS has become the polymer of choice for research in microfluidics due to its optical clarity, ease of fabrication, flexibility in design, good mechanical properties, and the ability to chemically modify the surface.

Biomicrofluidics enables the rapid throughput and analysis of small biological samples requiring less time investment and reagent use than traditional macroscale laboratory techniques. Polymer devices are inexpensive, easily …