Biomedical Engineering and Bioengineering Commons^™

A Non-Invasive Fluorescence-Based Oxygen Sensor And Platform For Studying Cell Responses To Metabolic Agents In Real-Time, Koutilya Reddy Buchapudi

Doctoral Dissertations

A fluorescence-based sensor in a transverse flow/stop measurement platform has been developed to determine real-time changes in oxygen consumption rates for cell metabolic studies. The oxygen sensitive fluorophore platinum octaethylporphyrin was embedded in a cellulose acetate matrix and affixed to a fiber optic bundle, which provided for transmission of the excitation and emission wavelengths of the film. The fiber optic bundle was sealed in a sensor head that can be used in standard 24-well plates common to research labs. The utility of the sensor and sensing platform were determined by measuring the changes in oxygen consumption rates of Candida albicans …

Nanoformulation For Anticancer Drug Delivery: Enhanced Pharmacokinetics And Circulation, Gaurav Parekh

Doctoral Dissertations

In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the …

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 …

Improving Practices In Nanomedicine Through Near Real-Time Pharmacokinetic Analysis, Isidro B. Magana

Doctoral Dissertations

More than a decade into the development of gold nanoparticles, with multiple clinical trials underway, ongoing pre-clinical research continues towards better understanding in vivo interactions. The goal is treatment optimization through improved best practices. In an effort to collect information for healthcare providers enabling informed decisions in a relevant time frame, instrumentation for real-time plasma concentration (multi-wavelength photoplethysmography) and protocols for rapid elemental analysis (energy dispersive X-Ray fluorescence) of biopsied tumor tissue have been developed in a murine model. An initial analysis, designed to demonstrate the robust nature and utility of the techniques, revealed that area under the bioavailability curve …

Nanotechnology And Additive Manufacturing Platforms For Clinical Medicine: An Investigation Of 3d Printing Bioactive Constructs And Halloysite Nanotubes For Drug Delivery And Biomaterials, Jeffery A. Weisman

Doctoral Dissertations

Personalized medicine requires the development of new technologies for controlled or targeted drug delivery. Three-dimensional (3D) printing and additive manufacturing techniques can be used to generate customized constructs for bioactive compound delivery. Nanotechnology in the form of nanoparticles, used as a stand-alone construct or for material enhancements, can significantly improve established biomaterials such as PMMA based bone cements or enable new technology to have enhanced capabilities. Combinations of the technologies can be used in such applications as infectious disease treatments, chemotherapeutic targeted drug delivery or targeted delivery of nearly any bioactive compound.

Chemotherapeutic or antibiotic enhanced 3D printing filaments were …

Thermoelectric Elisa For Quantification Of 8ohdg In A Microfluidic Device, Gergana Nestorova

Doctoral Dissertations

This research demonstrates the feasibility of a novel method for performing thermoelectric enzyme-linked immunosorbent assay (ELISA) in a microfluidic device. The feasibility of the thermoelectric ELISA is demonstrated by measuring the concentration of 8-hydroxy 2-deoxyguanosine (8OHdG) in urine samples from amyloid precursor protein (APP) transgenic mice. The detection method is based on formation of a complex between 8OHdG and anti-8OHdG capture antibody conjugated to biotin. The complex is immobilized over the measuring junctions of a thermopile via biotin streptavidin interaction. The concentration of the analyte is determined by using enzyme linked secondary IgG antibody specific to the primary one. The …

Modeling And Control Of Nanoparticle Bloodstream Concentration For Cancer Therapies, Scarlett S. Bracey

Doctoral Dissertations

Currently, the most commonly used treatments for cancerous tumors (chemotherapy, radiation, etc.) have almost no method of monitoring the administration of the treatment for adverse effects in real time. Without any real time feedback or control, treatment becomes a "guess and check" method with no way of predicting the effects of the drugs based on the actual bioavailability to the patient's body. One particular drug may be effective for one patient, yet provide no benefit to another. Doctors and scientists do not routinely attempt to quantifiably explain this discrepancy. In this work, mathematical modeling and analysis techniques are joined together …

Halloysite Nanotube Composites For Sustained Release Of Antimocrobial Agents (Antiseptics And Antibiotics), Wenbo Wei

Doctoral Dissertations

Encapsulation of antimicrobial agents (simple antiseptics and more specific antibiotics) within micro-scale and nano-scale containers may provide prolonged and more evenly distributed drug release. One of such containers proposed at Louisiana Tech is natural halloysite clay nanotubes. Halloysite is an aluminosilicate tube with a length of approximately 1 µm, outer diameter of approximately 50 nm, and internal lumen of 15 nm. The chemical composition of halloysite is similar to more common clay–kaolinite, and it can be described as rolled sheets of kaolinite. Halloysite, loaded with drugs inside its lumen, has shown aqueous release of the loaded chemicals over 10-20 hours …

A Computational Model Of Nanoparticle Transport And Delivery In Tumor Tissue, Vishwa Priya Podduturi

Doctoral Dissertations

Determining the factors that influence the delivery of nanoparticles to tumors and understanding the relative importance of each of these factors is fundamental to optimize the drug delivery process. In this research, a model that combines random walk with the pressure driven flow of nanoparticles in a tumor vasculature is modeled. Nanoparticle movement in a cylindrical tube with dimensions similar to the tumor's blood capillary with a single pore is simulated. Nanoparticle velocities are calculated as a pressure driven flow over imposed to Brownian motion. During the study, the effect of red blood cells (RBC) is also studied by comparing …

Low Soluble Drug Encapsulation Based On Architecture Of Layer-By-Layer Assembly For Longer Circulation Time And Targeted Therapy, Pravin Pattekari

Doctoral Dissertations

A combined effect of sonication and layer-by-layer assembly (LbL) enhances the solubility of many poorly soluble inorganic and organic materials by forming stable particles with ca. 200 nm size and up to 90 wt% of loading. The entire method is reproducible, easy-to-handle, and flexible for varying surface properties according to the application of the materials. The method develops good colloidal stability of materials in buffers and maintains architecture for future improvement. A top-down approach, with a combined effect of sonication and LbL assembly, ruptures the material and allows adsorption of oppositely charged polyelectrolytes simultaneously. Thus, the approach is applicable for …

The Effect Of Network Transitions On Spontaneous Activity And Sycnhrony In Devloping Neural Networks, Jude P. J. Savarraj

Doctoral Dissertations

Connectivity patterns of developing neural circuits and the effects of its dynamics on network behavior, particularly the emergence of spontaneous activity and synchrony, are not clear. We attempt to quantify anatomical connectivity patterns of rat cortical cultures during different stages of development. By culturing the networks on dishes embedded with micro electrode arrays, we simultaneously record electrical activity from multiple regions of the developing network and monitor its electrical behavior, particularly its tendency to fire spontaneously and to synchronize under certain conditions. We investigate possible correlations between changes in the network connectivity patterns and spontaneous electrical activity and synchrony. Cocultures …

Intrinsic Mode Function Synchronization Measures For The Anticipation Of Seizures In Epilpsy, Daniel William Moller

Doctoral Dissertations

Epileptic seizures affect as many as 50 million people and often occur without warning or apparent provocation. We explore the applicability of noise-assisted Ensemble Empirical Mode Decomposition (EEMD) for patient-specific seizure anticipation synchronization measures as applied to the EEMD intrinsic mode function (IMF) output. Intracranial EEG data were obtained from pre-surgical monitoring at the Epilepsy Center of the University Hospital of Freiburg. Data from twenty patients were analyzed. For each recorded channel, non-overlapping time windows were submitted to the EEMD algorithm, producing twelve levels of IMFs. IMF synchronization measures (mean and maximum coherence, mean and maximum cross-correlation, correlation coefficient and …

Ultrasonication Assisted Layer-By-Layer Technology For The Preparation Of Multi-Functional Anticancer Drugs Paclitaxel And Lapatinib, Xingcai Zhang

Doctoral Dissertations

In this dissertation, ultrasonication assisted Layer-by-Layer (LbL) technology for the preparation of multifunctional poorly water-soluble anticancer drug nanoparticles, paclitaxel and lapatinib, has been developed. Many FDA approved drugs are very low soluble in water; therefore, it is very difficult to load and control their release and targeting efficiently, which greatly confines their application. The development of this method will pave the way for the development and application of those low soluble anticancer drugs.

In the first part of this dissertation, the first approach for powerful ultrasonication, the top-down approach (sonicating bulk drug crystals in polyelectrolyte solution), was successfully applied for …

New Microarray Image Segmentation Using Segmentation Based Contours Method, Yuan Cheng

Doctoral Dissertations

The goal of the research developed in this dissertation is to develop a more accurate segmentation method for Affymetrix microarray images. The Affymetrix microarray biotechnologies have become increasingly important in the biomedical research field. Affymetrix microarray images are widely used in disease diagnostics and disease control. They are capable of monitoring the expression levels of thousands of genes simultaneously. Hence, scientists can get a deep understanding on genomic regulation, interaction and expression by using such tools.

We also introduce a novel Affymetrix microarray image simulation model and how the Affymetrix microarray image is simulated by using this model. This simulation …

Engineering Microenvironments To Modulate Calcium Information Processing In Neuronal Cells, Kinsey Cotton Kelly

Doctoral Dissertations

Tissue engineered microenvironments were constructed to test the effects glial cells have on calcium information processing, and to mimic conditions in vivo for tumor invasion and residual cancer after resection of tumor. Submaximal, nM, glutamate (GLU) stimuli were applied to the engineered environments, and the resulting calcium dynamic behavior of neuronal cells was measured to help predict and interpret chaotic systems in the experimental realm. Calcium is a key signaling ion which signals through the N-methyl-D-aspartate (NMDA) glutamate receptor on the neuronal membrane. GLU binding to the NMDA receptor (NMDAR) causes a large and dynamic increase in neuronal intracellular calcium. …

Nonlinear Granger Causality And Its Application In Decoding Of Human Reaching Intentions, Mengting Liu

Doctoral Dissertations

Multi-electrode recording is a key technology that allows the brain mechanisms of decision making, cognition, and their breakdown in diseases to be studied from a network perspective. As the hypotheses concerning the role of neural interactions in cognitive paradigms become increasingly more elaborate, the ability to evaluate the direction of neural interactions in neural networks holds the key to distinguishing their functional significance.

Granger Causality (GC) is used to detect the directional influence of signals between multiple locations. To extract the nonlinear directional flow, GC was completed through a nonlinear predictive approach using radial basis functions (RBF). Furthermore, to obtain …

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 …

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 …

Quantitation And Identification Of Protein S-Nitrosylation: Implication For The Progression Of Alzheimer's Disease, Siyang Wang

Doctoral Dissertations

Protein S-nitrosylation, the covalent modification of a cysteine sulfhydryl group by nitric oxide (NO), plays a critical role in post-translational modification (PTM) that regulates a large variety of cellular functions and signalling events. The nitrosylation state changes with oxidative damage and is involved in variety of cancers and neurodegeneration diseases.

Three technologies were developed for nitrosylated protein detection and identification. Capillary gel electrophoresis with laser induced fluorescence (CGE-LIF) detection was used for the detection and quantitation of nitrosylated proteins. A two-dimensional micro-electrophoresis (2D μ-CE) separations system was also built to detect nitrosylated proteins via poly (methylmethacrylate) microchips. Proteomics following nitrosylated …

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 …

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 …

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 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 …

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 …

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 …

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, …

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 …

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 …