Biomedical Engineering and Bioengineering Commons^™

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

Reactive Chemistries For Protein Labeling, Degradation, And Stimuli Responsive Delivery, Myrat Kurbanov

Doctoral Dissertations

Reactive chemistries for protein chemical modification play an instrumental role in chemical biology, proteomics, and therapeutics. Depending on the application, the selectivity of these modifications can range from precise modification of an amino acid sequence by genetic manipulation of protein expression machinery to a stochastic modification of lysine residues on the protein surface. Ligand-Directed (LD) chemistry is one of the few methods for targeted modification of endogenous proteins without genetic engineering. However, current LD strategies are limited by stringent amino acid selectivity. To bridge this gap, this thesis focuses on the development of highly reactive LD Triggerable Michael Acceptors (LD-TMAcs) …

Unobtrusive Assessment Of Upper-Limb Motor Impairment Using Wearable Inertial Sensors, Brandon R. Oubre

Doctoral Dissertations

Many neurological diseases cause motor impairments that limit autonomy and reduce health-related quality of life. Upper-limb motor impairments, in particular, significantly hamper the performance of essential activities of daily living, such as eating, bathing, and changing clothing. Assessment of impairment is necessary for tracking disease progression, measuring the efficacy of interventions, and informing clinical decision making. Impairment is currently assessed by trained clinicians using semi-quantitative rating scales that are limited by their reliance on subjective, visual assessments. Furthermore, existing scales are often burdensome to administer and do not capture patients' motor performance in home and community settings, resulting in a …

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 …

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 …

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, …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

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 …

Application Of Polyelectrolyte Layer-By-Layer Nano-Assembly For Surface Modification, Encapsulation And Controlled Release, Nikhil Anil Pargaonkar

Doctoral Dissertations

In this study, we applied the traditional Electrostatic layer-by-layer (ELBL) assembly procedure to fabricate nanothin films over flat surfaces, and modify particle surfaces to influence the drug particle size, and drug release. The ELBL assembly has previously been applied to fabricate multilayer nano-scale thin films, but its ability to instantaneously influencing particle size is unique. Other unique observations such as influence on drug release as a result of polymer complexation, and thermal changes occurring during layer fabrication are recorded.

The ELBL self-assembly process was applied to produce dexamethasone particles layered with various polyelectrolyte layer combinations. These combinations were further applied …

Organization And Signal Processing Of The Descending Tracts In The Cervical Spinal Cord, Yanmei Tie

Doctoral Dissertations

This dissertation addresses the research for the development of spinal cord-computer interface (SCCI). The main objective of SCCI is to generate voluntary motor control signals for individuals with spinal cord injury (SCI).

In the neuroscience aspect, organization of the fibers in the descending tracts of the dorsolateral funiculus of the cervical spinal cord was investigated in cats. The spinal cord was penetrated with silicon substrate microelectrodes at 400 μm intervals in the medio-lateral direction at the C5/C6 and C6/C7 segmental borders. The stimulus consisted of a 20 ms train of charge-balanced biphasic pulses at 330 Hz. The evoked activities from …

Effects Of Diabetes And Aging On Posture And Acceleration Thresholds During Lateral Translations, Samantha Jean Richerson

Doctoral Dissertations

Research objectives. One source of falls in the elderly may be an inability to sufficiently adjust to transient postural perturbations or slips. Identifying useful predictors of fall potential, as well as factors that affect the ability of an individual to detect a movement of the standing support surface may provide insight into postural stability and methods to increase stability in elders. To do this, acceleration thresholds to short, precise, lateral platform translations and the resultant psychophysical responses of adults with early Type 2 diabetes to age-matched controls and young adults were measured.

Methods. Using an innovative SLIP-FALLS platform, …

Modular Machine Learning Methods For Computer-Aided Diagnosis Of Breast Cancer, Mia Kathleen Markey '94

Doctoral Dissertations

The purpose of this study was to improve breast cancer diagnosis by reducing the number of benign biopsies performed. To this end, we investigated modular and ensemble systems of machine learning methods for computer-aided diagnosis (CAD) of breast cancer. A modular system partitions the input space into smaller domains, each of which is handled by a local model. An ensemble system uses multiple models for the same cases and combines the models' predictions.

Five supervised machine learning techniques (LDA, SVM, BP-ANN, CBR, CART) were trained to predict the biopsy outcome from mammographic findings (BIRADS™) and patient age based on a …

X-Ray-Induced Specific-Locus Mutation Rates In Newborn And Young Mice, Paul Bruce Selby

Doctoral Dissertations

The specific-locus mutation frequency resulting from 300 R of acute X irradiation has been determined for the germ cells present in male mice at 0, 2, 4, 6, 8, 10, 14, 21, 28, and 35 days of age and also for female mice at 0 days of age, Sample size was much larger for the males irradiated on day 0 than for other age groups but in all groups it was large enough to insure that an extremely high rate would be noticed. At 35 days of age the testis is histologically similar to that of the adult. It was …