Biomedical Engineering and Bioengineering Commons^™

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 …

Multi-Classifier Fusion Strategy For Activity And Intent Recognition Of Torso Movements, Abhijit Kadrolkar

Doctoral Dissertations

As assistive, wearable robotic devices are being developed to physically assist their users, it has become crucial to develop safe, reliable methods to coordinate the device with the intentions and motions of the wearer. This dissertation investigates the recognition of user intent during flexion and extension of the human torso in the sagittal plane to be used for control of an assistive exoskeleton for the human torso. A multi-sensor intent recognition approach is developed that combines information from surface electromyogram (sEMG) signals from the user’s muscles and inertial sensors mounted on the user’s body. Intent recognition is implemented by following …

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 …

Anxiolytic Effects Of Propranolol And Diphenoxylate On Mice And Automated Stretch-Attend Posture Analysis, Kevin Scott Holly

Doctoral Dissertations

The prevention of social anxiety, performance anxiety, and social phobia via the combination of two generic drugs, diphenoxylate HC1 (opioid) plus atropine sulfate (anticholinergic) and propranolol HCl (beta blocker) was evaluated in mice through behavioral studies. A patent published on a September 8, 2011 by Benjamin D. Holly, US 2011/0218215 Al, prompted the research. The drug combination of diphenoxylate and atropine plus propranolol could be an immediate treatment for patients suffering from acute phobic and social anxiety disorders. Demonstrating the anxiolytic effects of the treatment on mice would validate a mouse model for neuroscientist to be used to detect the …

Potential Applications For Halloysite Nanotubes Based Drug Delivery Systems, Lin Sun

Doctoral Dissertations

Drug delivery refers to approaches, formulations, technologies, and systems for transporting a drug in the body. The purpose is to enhance the drug efficacy and to reduce side reactions, which can significantly improve treatment outcomes. Halloysite is a naturally occurred alumino-silicate clay with a tubular structure. It is a biocompatible material with a big surface area which can be used for attachment of targeted molecules. Besides, loaded molecules can present a sustained release manner in solution. These properties make halloysite nanotubes (HNTs) a good option for drug delivery.

In this study, a drug delivery system was built based on halloysite …

Generalized Partial Directed Coherence And Centrality Measures In Brain Networks For Epileptogenic Focus Localization, Joshua Aaron Adkinson

Doctoral Dissertations

Accurate epileptogenic focus localization is required prior to surgical resection of brain tissue for treatment of patients with intractable temporal lobe epilepsy, a clinical need that is partially fulfilled to date through a subjective, and at times inconclusive, evaluation of the recorded electroencephalogram (EEG). Using brain connectivity analysis, patterns of causal interactions between brain regions were derived from multichannel EEG of 127 seizures in nine patients with focal, temporal lobe epilepsy (TLE). The statistically significant directed interactions in the reconstructed brain networks were estimated from three second intracranial multi-electrode EEG segments using the Generalized Partial Directed Coherence (GPDC) and validated …

Lab-On-A-Chip Nucleic-Acid Analysis Towards Point-Of-Care Applications, Varun Lingaiah Kopparthy

Doctoral Dissertations

Recent infectious disease outbreaks, such as Ebola in 2013, highlight the need for fast and accurate diagnostic tools to combat the global spread of the disease. Detection and identification of the disease-causing viruses and bacteria at the genetic level is required for accurate diagnosis of the disease. Nucleic acid analysis systems have shown promise in identifying diseases such as HIV, anthrax, and Ebola in the past. Conventional nucleic acid analysis systems are still time consuming, and are not suitable for point-ofcare applications. Miniaturized nucleic acid systems has shown great promise for rapid analysis, but they have not been commercialized due …

Next Generation In-Vivo Forward Solution Physiological Model Of The Human Lower Limb To Predict Implanted Knee Mechanics, Bradley Allen Meccia

Doctoral Dissertations

Current total knee arthroplasty (TKA) evaluation methods are both time consuming and expensive. They require fabrication of the TKA and then utilize a wear or cadaveric simulator which does not necessarily replicate in-vivo conditions. Other analysis methods involve following the long-term success of TKA in subjects for five or more years. Mathematical modeling of TKA provide an efficient method at a greatly reduced cost for evaluating TKA. Obviously, the accuracy of a mathematical model is extremely important to the validity of the results.

Mathematical modeling of the knee faces many difficulties. The number of muscles actuating the knee is much …

Development Of A Portable Cmos Time-Domain Fluorescence Lifetime Imager, Hongtao Wang

Doctoral Dissertations

Modern laboratory equipments to measure the excited-state lifetime of fluorophores usually include an expensive picosecond pulsed-laser excitation source, a fragile photomultiplier tube, and a large instrument body for optics. A portable and robust device to make fluorescence lifetime measurement in nanosecond scale is of great attraction for chemists and biologists. This dissertation reports the development of a portable LED time-domain fluorimeter from an all-solid-state discrete-component prototype to its advanced CMOS integrated circuit implementation. The motivation of the research is to develop a multiplexed fluorimeter for point-of-care diagnosis. Instruments developed by this novel method have higher fill factor, are more portable, …

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 …

Three-Dimensional Printing And Nanotechnology For Enhanced Implantable Materials, Karthik Kumar Tappa

Doctoral Dissertations

Orthopedic and oro-maxillofacial implants have revolutionized treatment of bone diseases and fractures. Currently available metallic implants have been in clinical use for more than 40 years and have proved medically efficacious. However, several drawbacks remain, such as excessive stiffness, accumulation of metal ions in surrounding tissue, growth restriction, required removal/revision surgery, inability to carry drugs, and susceptibility to infection. The need for additional revision surgery increases financial costs and prolongs recovery time for patients. These metallic implants are bulk manufactured and often do not meet patient's requirements. A surgeon must machine (cut, weld, trim or drill holes) them in order …

Nano Clay-Enhanced Calcium Phosphate Cements And Hydrogels For Biomedical Applications, Udayabhanu Jammalamadaka

Doctoral Dissertations

Biomaterials are used as templates for drug delivery, scaffolds in tissue engineering, grafts in surgeries, and support for tissue regeneration. Novel biomaterial composites are needed to meet multifaceted requirements of compatibility, ease of fabrication and controlled drug delivery. Currently used biomaterials in orthopedics surgeries suffer limitations in toxicity and preventing infections. Polymethyl methacrylate (PMMA) used as bone cement suffers from limitations of thermal necrosis and monomer toxicity calls for development of better cementing biomaterials. A biodegradable/bioresorbable cement with good mechanical properties is needed to address this short coming. Metal implants used in fixing fractures or total joint replacement needs improvements …

Adaptive Kernel Estimation For Enhanced Filtering And Pattern Classification Of Magnetic Resonance Imaging: Novel Techniques For Evaluating The Biomechanics And Pathologic Conditions Of The Lumbar Spine, Nicholas Vincent Battaglia

Doctoral Dissertations

This dissertation investigates the contribution the lumbar spine musculature has on etiological and pathogenic characteristics of low back pain and lumbar spondylosis. This endeavor necessarily required a two-step process: 1) design of an accurate post-processing method for extracting relevant information via magnetic resonance images and 2) determine pathological trends by elucidating high-dimensional datasets through multivariate pattern classification. The lumbar musculature was initially evaluated by post-processing and segmentation of magnetic resonance (MR) images of the lumbar spine, which characteristically suffer from nonlinear corruption of the signal intensity. This so called intensity inhomogeneity degrades the efficacy of traditional intensity-based segmentation algorithms. Proposed …

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 …

A Comparative Study On Calcification Of Aortic Valves, Shirin Masjedi

Doctoral Dissertations

Calcific Aortic Valve Disease (CAVD) is a major disorder in the developed countries among elderly. It is characterized by calcific deposition and stiffening of the aortic valve cusps. CAVD is a highly cell-mediated condition where valvular interstitial cells (VICs) become activated and differentiate into osteoblast-like cells. This is associated with upregulation of calcific markers like Alkaline phosphatase (ALP) and Runx2. ECM remodeling in another characteristic of stenotic aortic valves due to VIC activation. Reports show that CAVD initiates majorly on the noncoronary side of the aortic valves. Additionally, male sex is a significant risk factor of CAVD. Aortic valves are …

Improving Droplet Interface Bilayers As Models For Cell Membranes, Graham Jeffery Taylor

Doctoral Dissertations

This work describes research aimed at improving the droplet interface bilayer (DIB) platform for creating and characterizing biologically relevant model cell membranes. Improvements are made possible in part through the development of a portable, compact platform for controlling temperature with DIBs. Feedback-controlled heating allows studies to be conducted across a range of temperatures, from ambient up to at least 80°C, and also provides new understanding of methods to form DIBs using mixtures of total lipids extracted from bacterial and eukaryotic cells. The membranes formed from total lipid extracts (TLE) are introduced along with evidence that model membranes formed using lipid …

Inter-Droplet Membranes For Mechanical Sensing Applications, Nima Tamaddoni Jahromi

Doctoral Dissertations

This dissertation combines self-assembly phenomena of amphiphilic molecules with soft materials to create and characterize mechanoelectrical transducers and sensors whose sensing elements are thin-film bioinspired membranes comprised of phospholipids or amphiphilic polymers. We show that the structures of these amphiphilic molecules tune the mechanical and electrical properties of these membranes. We show that these properties affect the mechanoelectrical sensing characteristic and range of operation of these membrane transducers. In the experiments, we construct and characterize a membrane-based hair cell embodiment that enables the membrane to be responsive to mechanical perturbations of the hair. The resulting oscillations of membranes formed between …

Mutlifunctional Platforms For Gene And Drug Delivery For Cancer Therapy, Jeffery J. Ambrose Jr.

Doctoral Dissertations

The National Cancer Institute and the American Cancer Society estimate that 1.6 million new cancer incidences and over half a million cancer related deaths occur annually [1][2]. Cancer the second most common cause of death in the United States [1], [2]. Although the causes of cancer can vary depending on cell type, all or almost all instances of cancer arise from a mutation or from an abnormal activation of the cellular genes that control cell growth and mitosis [3].

Treatment of a given cancer type depends on the subtype, stage and progression of the cancer. Varieties of cancer therapy include …

Enhanced Bioactive Scaffolds For Bone Tissue Regeneration, Sonali Karnik

Doctoral Dissertations

Bone injuries are commonly termed as fractures and they vary in their severity and causes. If the fracture is severe and there is loss of bone, implant surgery is prescribed. The response to the implant depends on the patient's physiology and implant material. Sometimes, the compromised physiology and undesired implant reactions lead to post-surgical complications. [4, 5, 20, 28] Efforts have been directed towards the development of efficient implant materials to tackle the problem of post-surgical implant failure. [ 15, 19, 24, 28, 32]

The field of tissue engineering and regenerative medicine involves the use of cells to form a …

Detecting And Screening Of The Prostate Cancer By Using An Optical Nanoporous Thin-Film Sensor, Salah Eldeen Mofleh Alzghoul

Doctoral Dissertations

Prostate cancer (PC) affects elderly men more than young men. The currently used cancer biomarker, prostate-specific antigen (PSA), highly overestimates PC population. Men with high PSA levels often have to go through unnecessary, but physically painful, and expensive prosesses, such as prostate biopsies. Finding a prostate cancer marker that is produced selectively by cancer, but not by normal prostate cells will increase the reliability of PC test. In 2006, our collaborator (Dr. Girish Shah) discovered a novel protein, referred as neuroendocrine marker (NEM), secreted only by malignant prostate cells and released in blood circulation.

To examine whether the combined NEM-PSA …

Point Of Care Diagnostics And Health Monitoring Devices, Akshaya Shanmugam

Doctoral Dissertations

Existing disease screening methods mostly rely on symptom based diagnosis. This is mainly because of lack of accessibility and cost associated with the tests. Testing for the presence of the disease after the onset of symptoms has a negative impact on chances of survival and treatment costs. Miniaturized low cost diagnostic devices that can be used outside the hospital setting can provide continuous health monitoring and aid in early diagnosis. This thesis presents techniques to develop such disease screening and health monitoring devices. The techniques presented here focus on medical devices that can benefit from microfluidic devices, fluorescence imaging, and …

Improving Nano-Drug Delivery By Using Near-Real Time Sensing And Feedback, Pratik Adhikari

Doctoral Dissertations

Personalized medicine, seen as the solution to address the variability among the individuals, is the movement which proposes customization of medical procedures based on the need of the patient during the stages of prevention, diagnosis, treatment, and follow up. As the technology in medicine expands and newer methods of diagnosis and treatment are introduced in the clinic, real time data from the procedures is critical to assess the performance at point of care. Real time feedback, through collection of data at point of care would help make informed clinical decisions, potentially improving the efficacy of the treatment. In this dissertation, …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Detecting, Segmenting And Tracking Bio-Medical Objects, Mingzhong Li

Doctoral Dissertations

"Studying the behavior patterns of biomedical objects helps scientists understand the underlying mechanisms. With computer vision techniques, automated monitoring can be implemented for efficient and effective analysis in biomedical studies. Promising applications have been carried out in various research topics, including insect group monitoring, malignant cell detection and segmentation, human organ segmentation and nano-particle tracking.

In general, applications of computer vision techniques in monitoring biomedical objects include the following stages: detection, segmentation and tracking. Challenges in each stage will potentially lead to unsatisfactory results of automated monitoring. These challenges include different foreground-background contrast, fast motion blur, clutter, object overlap and …