Biomedical Engineering and Bioengineering Commons^™

The Contribution Of Oxidative Stress In The Protein Damage And Dna Lesion In Alzheimer's Disease Neuropathology, Cheng Zhang

Doctoral Dissertations

Glutathione (GSH) plays an essential role in the intracellular antioxidant defense against the oxidant radicals, especially the ·OH radical. To understand the early and progressive cellular changes in Alzheimer's disease (AD) development, we investigated reduced glutathione/oxidized glutathione (GSH/GSSG) status in a double mutated AD transgenic mouse model (B6.Cg-Tg), which carries Swedish amyloid precursor protein mutation (APPswe) and exon 9 deletion of the PSEN1 gene. Likewise, S-glutathionylation (Pr-SSG) is a specific post-translational modification (PTM) of cysteine residues by the addition of glutathione. S-glutathionylated proteins induced by oxidative stress play an essential role in understanding the pathogenesis of the aging …

A Novel Microfluidic Enrichment Technique For Carbonylated Proteins, Bryant C. Hollins

Doctoral Dissertations

Proteins are the building blocks of cells in living organisms, and are composed of amino acids. The expression of proteins is regulated by the processes of transcription and translation. Proteins undergo post-translational modifications in order to dictate their role physiologically within a cell.

Not all post-translational modifications are beneficial for the protein or the cell. One type of post-translational modification, called carbonylation, irreversibly places a carbonyl group onto an amino acid residue, most commonly proline, lysine, arginine, and threonine. This modification can have severe consequences physiologically, including loss of solubility, loss of function, and protein aggregation.

Carbonylated proteins have commonly …

Oscillator-Based Neuronal Modeling For Seizure Progression Investigation And Seizure Control Strategy, Wu Chen

Doctoral Dissertations

The coupled oscillator model has previously been used for the simulation of neuronal activities in in vitro rat hippocampal slice seizure data and the evaluation of seizure suppression algorithms. Each model unit can be described as either an oscillator which can generate action potential spike trains without inputs, or a threshold-based unit. With the change of only one parameter, each unit can either be an oscillator or a threshold-based spiking unit. This would eliminate the need for a new set of equations for each type of unit. Previous analysis has suggested that long kernel duration and imbalance of inhibitory feedback …

A Hybrid Brain-Computer Interface Based On Motor Intention And Visual Working Memory, Ching-Chang Kuo

Doctoral Dissertations

Non-invasive electroencephalography (EEG) based brain-computer interface (BCI) is able to provide alternative means for people with disabilities to communicate with and control over external assistive devices. A hybrid BCI is designed and developed for following two types of system (control and monitor).

Our first goal is to create a signal decoding strategy that allows people with limited motor control to have more command over potential prosthetic devices. Eight healthy subjects were recruited to perform visual cues directed reaching tasks. Eye and motion artifacts were identified and removed to ensure that the subjects' visual fixation to the target locations would have …

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …

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 …

Passive Micromixers And Organic Electrochemical Transistors For Biosensor Applications, Senaka Krishna Kanakamedala

Doctoral Dissertations

Fluid handling at the microscale has greatly affected different fields such as biomedical, pharmaceutical, biochemical engineering and environmental monitoring due to its reduced reagent consumption, portability, high throughput, lower hardware cost and shorter analysis time compared to large devices. The challenges associated with mixing of fluids in microscale enabled us in designing, simulating, fabricating and characterizing various micromixers on silicon and flexible polyester substrates. The mixing efficiency was evaluated by injecting the fluids through the two inlets and collecting the sample at outlet. The images collected from the microscope were analyzed, and the absorbance of the color product at the …

Nanofabrication Of Halloysite-Pcl Composite Scaffolds And Functionalization Of Titanium For Tissue Regeneration, Shraddha Parshottambhai Patel

Doctoral Dissertations

Major medical needs may be achieved through regenerative medicine. Nanotechnology has triggered a research revolution in many important areas such as the biomedical sciences and bioengineering at the molecular level which has grown significantly due to the availability of new analytical applications and tools based on nanotechnology. Clinical conditions and diseases being targeted by nanotechnology research include burns, Alzheimer's and Parkinson's disease, implant failure, improved wound healing, birth defects, osteoporosis and congestive heart defects. Therapeutic use of growth factors and drugs to stimulate the production and/or function of endogenous cells represents a key area of regenerative medicine. The development of …

Manipulating Cellular Growth Responses To Patterning, Apoptotic, And Environmental Cues, James N. Mcnamara

Doctoral Dissertations

In this work, various methods of controlling cell growth are examined. Cell-cell interaction, apoptotic cues, three dimensional scaffolds, and non-adherent environments are evaluated for their ability to affect the differentiation, morphology, and growth rate of different cell types. Previous work has shown that cell growth and cell morphology can be influenced by patterns of polymers coated on surfaces in two dimensions, designated here as the x and y dimensions of a standard Cartesian coordinate system. Tissue engineering and regenerative medicine studies have shown limited success in modifying growth in the third, z dimension. This work considers not only the x, …

Ultrasonic Assisted Layer-By-Layer Assembly For Stable Nanocolloids Of Curcumin And Paclitaxel, Zhiguo Zheng

Doctoral Dissertations

Researchers have been trying to fight cancer with synthesis of new bioactive compounds but many of these novel drugs have low solubility in water and it is difficult to deliver them into a patient's body. One way of solving this particular problem is to use nanoscale drug delivery systems. In this dissertation, we describe using an ultrasonic assisted layer-by-layer encapsulation process to prepare anti-cancer drugs with 50∼200 nm particle size with designed coating to achieve sustained release and target delivery.

Two methods for systematic manufacture of low solubility anti-cancer drug nanoparticles were proposed: I) Top-down approach to breakdown larger drug …

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 …

Surface Morphology Of Platelet Adhesion Influenced By Activators, Inhibitors And Shear Stress, Melanie Groan Watson

Doctoral Dissertations

Platelet activation involves multiple events, one of which is the generation and release of nitric oxide (NO), a platelet aggregation inhibitor. Platelets simultaneously send and receive various agents that promote a positive and negative feedback control system during hemostasis. Although the purpose of platelet-derived NO is not fully understood, NO is known to inhibit platelet recruitment. NO's relatively large diffusion coefficient allows it to diffuse more rapidly than platelet agonists. It may thus be able to inhibit recruitment of platelets near the periphery of a growing thrombus before agonists have substantially accumulated in those regions.

Results from two studies in …

Classification Of Emg Signals To Control A Prosthetic Hand Using Time-Frequesncy Representations And Support Vector Machines, Juan Manuel Fontana

Doctoral Dissertations

Myoelectric signals (MES) are viable control signals for externally-powered prosthetic devices. They may improve both the functionality and the cosmetic appearance of these devices. Conventional controllers, based on the signal's amplitude features in the control strategy, lack a large number of controllable states because signals from independent muscles are required for each degree of freedom (DoF) of the device. Myoelectric pattern recognition systems can overcome this problem by discriminating different residual muscle movements instead of contraction levels of individual muscles. However, the lack of long-term robustness in these systems and the design of counter-intuitive control/command interfaces have resulted in low …

Nonlinear Control Strategy For A Cost Effective Myoelectric Prosthetic Hand, Cristian Federico Pasluosta

Doctoral Dissertations

The loss of a limb tremendously impacts the life of the affected individual. In the past decades, researchers have been developing artificial limbs that may return some of the missing functions and cosmetics. However, the development of dexterous mechanisms capable of mimicking the function of the human hand is a complex venture. Even though myoelectric prostheses have advanced, several issues remain to be solved before an artificial limb may be comparable to its human counterpart. Moreover, the high cost of advanced limbs prevents their widespread use among the low-income population.

This dissertation presents a strategy for the low-level of control …

Modeling And Its Numerical Method For Micro-Scaled Diffusion -Reaction Systems In The Neuromuscular Junction, Abdul Khaliq

Doctoral Dissertations

The main subject of this research is the neuromuscular junction (NMJ). The NMJ is a biological structure composed of the interface between a neuron and a muscle cell. Currently, there is not a fully three dimensional model of diffusion-reaction processes occurring in the NMJ. Developing a useful predictive model of this structure will assist in the therapeutic efforts to restore and rehabilitate NMJ function to humans and in developing strategies to prevent damage to the NMJ. This research work developed 1D mass transport and full 3D reaction diffusion models. A new finite difference scheme is presented for solving 1D mass …

In Vivo Non-Invasive Monitoring Of Optically Resonant Metal Nanoparticles Using Multi-Wavelength Photoplethysmography, Gregory J. Michalak

Doctoral Dissertations

Nanotechnology has recently emerged as a powerful modality in many biomedical applications. In particular, several classes of nanoparticles have been employed as cancer therapy and imaging contrast agents. These particles can have architecture of varying complexity, depending on their specific application. These complex architectures are achieved by various chemical techniques usually performed in specific sequences to add complexity and functionality. One such class of nanoparticle, used in tumor treatment and as contrast agents in several optical imaging techniques, is the plasmon resonant metal nanoparticle. The most common metal used for these particles is gold because of its biocompatibility, lack of …

Dna Microarray Image Segmentation Using Active Contours Without Edges Method, Shenghua Ni

Doctoral Dissertations

The goal of this dissertation is to build a better segmentation method for DNA microarray image processing. Segmentation is a partitioning process used to separate a spot area from a non-spot area in DNA microarrays. It directly affects the accuracy of gene expression analysis in the data mining process that follows. A number of DNA microarray segmentation methods have been proposed in the area, but even modern segmentation methods seem to have accuracy problems. In this dissertation, I will present a segmentation method based on the Active Contours Without Edges (ACWE) algorithm and apply it to two types of DNA …

Improvement Of Eeg Based Brain Computer Interface By Application Of Tripolar Electrodes And Independent Component Analysis, Hongbao Cao

Doctoral Dissertations

For persons with severe disabilities, a brain computer interface (BCI) may be a viable means of communication, with scalp-recorded electroencephalogram (EEG) being the most common signal employed in the operation of a BCI. Various electrode configurations can be used for EEG recording, one of which was a set of concentric rings that was referred to as a Laplacian electrode. It has been shown that Lapalacian EEG could improve classification in EEG recognition, but the complete advantages of this configuration have not been established.

This project included two parts. First, a modeling study was performed using Independent Component Analysis (ICA) to …

Micro, Nano Encapsulation Methods For Sustained Release Drug Formulations And Biomimetic Applications, Shantanu Balkundi

Doctoral Dissertations

The Layer-by-Layer (LbL) assembly technique was used to obtain a new type of protein/polyphenol microcapsule based on naturally occurring polyphenol (-)-epigallocatechin gallate (EGCG) and gelatin, type A. The dependence of permeability on the molecular weight of permeating substances was studied and compared with commonly used polyallylamine/polystyrene sulfonate capsules. A quartz crystal microbalance was used to monitor the regularities of EGCG adsorption in alternation with type A and B Gelatins and electrophoretic mobility measurements were used that indicated that the nature of assembly was dependent on Gelatin properties. It was shown that EGCG retains its antioxidant activity in the LbL assemblies. …

Applied Electrokinetics For Tissue Engineering Applications, Stephanie R. Tully-Dartez

Doctoral Dissertations

Tissue engineering could provide an alternative source of transplant tissue regardless of donor supply and with reduced risk of immune rejection. Engineered tissue requires three critical components for successful development: the cells, growth factors, and the scaffold on which they will initially grow. The scaffold acts as a temporary extracellular matrix (ECM) allowing cell attachment and acclimation to the environment prior to synthesis and construction of the cell's native ECM. Prior to cell seeding, the scaffold must be characterized to determine whether or not the pore geometry is conducive to cell implantation. Electrochemical impedance spectroscopy (EIS) provides a unique and …

Nano-Formulation And Controlled Delivery Of Low Solubility Anticancer Drugs, Anshul Agarwal

Doctoral Dissertations

Optimal drug delivery and reduction of systemic adverse effects have been age old problems in chemotherapeutics in all types of human cancer. During chemotherapy, using water insoluble drugs like paclitaxel and tamoxifen, it has been realized that better formulations are needed for more specific and controlled drug delivery of these agents. In a novel approach to form high content stable nanocolloids of these drugs with controllable release rate, a sonicated layer-by-layer (LbL) polyelectrolyte coating technology is suggested. The desired features of pharmaceutical carriers for intravenous administration include their small size and biodegradability, good loading capacity for a given drug, high …

Infrared Light Activated Floating Micro Stimulators For Neuro-Prosthetic Applications, Kimberlyn M. Gray

Doctoral Dissertations

The most common failures in neural stimulation implants are due to interconnect complications such as tissue response, lead migration, and lead breakages. The challenge in eliminating interconnects lies in minimizing device size to maintain spatial selectivity required in the CNS. One approach to this problem is a current generating device that can be stimulated by an external signal, such as light or sound. Here, we report the design, construction and testing of rnicrophotodiode devices that can be stimulated remotely with near-infrared (NIR) light to generate current that can be injected locally into the peripheral nervous system. The use of near-infrared …

Nanoengineered Templates For Controlled Delivery Of Bioactive Compounds, Nalinkanth Ghone Veerabadran

Doctoral Dissertations

The significance of any drugs, therapeutic proteins, or any bioactive compounds, is based not only on their effects on diseases but also on how specifically, how readily, how controllable and how prolonged their effects on the disease without having any side effects. Thus the techniques involved in the drug encapsulation and its controlled release for a longer duration of time form one of the important processes of drug reformulation. In recent years nanoparticles have created overwhelming attention for delivering drugs by nanoencapsulation. The smaller size of nanoparticles has longer circulation time and higher cellular uptake when compared with larger size …

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. …

Poly(Ethylenedioxythiophene) Based Electronic Devices For Sensor Applications, Jie Liu

Doctoral Dissertations

Organic electronic devices, based on Poly (3,4-ethylenedioxythiophene)-Poly (styrene sulfonic acid) (PEDOT-PSS) as the active layer for sensor applications, have been studied. Two sets of sensors have been developed. In one case, sensors consisting of PEDOT-PSS resistors have been realized and demonstrated for soil moisture monitoring. The resistor model for the soil moisture sensor enables the sensor device to be fabricated at low cost and easily tested with a simple structure. Unlike the large dimension device used in Time Domain Reflectometry (TDR), the sensors are small and are capable of capturing microscale behavior of moisture in soil which is useful for …

Fabrication Of Bioactive Osteogenic Controlled-Release Systems, Cellular Platforms, And Cellular Capsules Using Layer -By -Layer Nanoassembly, Skylar Stewart-Clark

Doctoral Dissertations

There is an ever-increasing awareness that the field of tissue engineering offers many potential solutions to clinical problems. While advances along these lines have been made, the design and implementation of an "off the shelf" tissue is yet to be realized. Thus, the objectives of this work were largely aimed at the design and fabrication of biocompatible, bioactive structures which could be integrated into existing biomaterial products.

The electrostatic layer-by-layer (LbL) self-assembly technique was used to incorporate biologically relevant molecules within controlled release systems, cell culture platforms, and 3-D cellular capsules. Two delivery systems were investigated to determine the release …

Acquisition Of Cardiac Control Parameters From Whole Vagus Nerve Recordings, Marcia A. Pool

Doctoral Dissertations

Heart rate varies continuously depending on the amount of activity being performed or the emotional state of an individual. Both branches of the autonomic nervous system work to alter heart rate depending on the needs of the body. While healthy individuals are capable of altering their heart rate, individuals with certain types of heart disease do not have this ability. For these individuals, cardiac pacemakers are used to alter heart rate. Cardiac pacemakers use sensors to determine the pacing frequency for the heart; however, there is no current optimum sensor. In order to discover a better sensor, this study investigated …

Gene Synthesis, Cloning, Expression, Purification And Biophysical Characterization Of The C2 Domain Of Human Tensin, Kiran Sukumar Gajula

Doctoral Dissertations

Tensin is a large "docking" protein found in the adhesive junctions of animal cells and recruited early in the development of cell-substrate contacts. There it binds to the cytoplasmic domain of integrin β1 and caps the barbed ends of filamentous actin. This forms a rational basis for its implication in a direct role in the mechanics of membrane-cytoskeleton interactions. Tensin provides a physical link between the actin cytoskeleton, integrins, and other proteins at the cell-substrate contacts. Its overall biochemical properties are a function of its domain composition and architecture, i.e., the domains that are present and their relative positions in …

Computer Simulation And Human Experiment On The Laplacian Electrocardiogram (Ecg), Ting Chen

Doctoral Dissertations

The electrocardiogram (ECG) provides useful global temporal assessment of cardiac activity, but has limited spatial capabilities. Laplacian electrocardiogram (LECG) and body surface Laplacian mapping (BSLM), improvements over ECG provides high spatiotemporal distributed information about cardiac electrical activation.

This project was divided into two parts: computer simulation and human experiment. In the computer simulation, a comparison of the performance of the tripolar and bipolar as well as spline LECG and BSLMs for localizing and imaging the cardiac electrical activation has been investigated. A simple planar surface model and a simplified eccentric heart-torso sphere-cylinder homogeneous volume conductor model were developed. Multiple dipoles …

Development And Analysis Of An Internet Browsing Utilizing The Overscan Technique For Persons With Physical Disabilities, Patrick Paul Clerkin

Doctoral Dissertations

Persons with a severe disability often use scanning as an indirect selection technique for operating augmentative and alternative communication aids and computer access. For information that can be organized in advance, including lists of communication elements such as words and phrases, users often employ rate enhancing scanning methods like the row-column scanning technique. However, row-column scanning requires selection elements to be grouped into defined rows and columns, and therefore does not work well with Internet browsing due to the non-grouped layout of HTML pages.

This work attempts to develop an improved scanning technique for Internet browsing by designing interfaces to …