Biomedical Engineering and Bioengineering Commons^™

Investigation Of Nanosecond Pulsed Electric Fields (Nspef) Induced Anti-Cancer Mechanism And Enhanced B16f10 Melanoma Cancer Treatment, Kamal Asadipour

Biomedical Engineering Theses & Dissertations

The use of nanosecond pulsed electric fields (nsPEF) has emerged as a promising area of research with vast implications across various scientific disciplines. The ability to generate ultra-short, high-voltage electric pulses has paved the way for numerous applications, ranging from fundamental investigations of biological phenomena to the development of innovative medical therapies. The aim of this thesis is to highlight the importance of nsPEF in two critical areas: 1) Understanding the impact of subtle postpulse waveforms through a comprehensive analysis of two common pulse generators and 2) using this knowledge to advance melanoma treatment by enhancing the therapeutic effect of …

Ultrasensitive Tapered Optical Fiber Refractive Index Glucose Sensor, Erem Ujah

Biomedical Engineering Theses & Dissertations

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate extremely sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5–45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due …

Nanosecond Pulsed Electric Field Modulates Electron Transport And Mitochondrial Structure And Function, Lucas Nelson Potter

Biomedical Engineering Theses & Dissertations

Pulsed power treatment has been used to induce regulated cell death (RCD) in cells or ablate tumors in animals. A subset of pulsed power as electroporation with high voltage and pulse duration of milliseconds is used for biomedical treatment to induce pores in the plasma membrane of cells. Nanosecond Pulsed Electric Fields (nsPEFs)– an extension of electroporation, uses waveforms with pulse durations on the order of 10-900 nanoseconds. nsPEF treatment has demonstrated intracellular effects for potential biomedical applications. In this work, nsPEF treatment is used to demonstrate changes that affect viability, plasma membrane permeability ROS (Reactive Oxygen Species) in the …

Validation Of Meta Motion Imu Sensors Through Measurement Of Knee Angles During Gait, Kerri Caruso

Biomedical Engineering Theses & Dissertations

The implementation of inertial measurement units (IMU) in the biomechanical field has become increasingly popular due to their robustness, simplicity, accuracy, and the ability to move research out of a lab and into the real world. In this study, the MetaMotion IMU sensors are assessed for validity against a dynamometer and the Vicon motion capture system. Both systems have proven their measuring accuracies in the biomechanics world and are used as the truth source for this validation study. In the first part of this study, the sensors are assessed for various common sensor errors. Individual sensor components of the IMU, …

Engineering Of Ideal Systems For The Study And Direction Of Stem Cell Asymmetrical Division And Fate Determination, Martina Zamponi

Biomedical Engineering Theses & Dissertations

The cellular microenvironment varies significantly across tissues, and it is constituted by both resident cells and the macromolecules they are exposed to. Cues that the cells receive from the microenvironment, as well as the signaling transmitted to it, affect their physiology and behavior. This notion is valid in the context of stem cells, which are susceptible to biochemical and biomechanical signaling exchanged with the microenvironment, and which plays a fundamental role in establishing fate determination and cell differentiation events. The definition of the molecular mechanisms that drive stem cell asymmetrical division, and how these are modulated by microenvironmental signaling, is …

Investigating Arrhythmia Potential In Cardiac Myocytes In Presence Of Long Qt Syndrome, Victoria Lin Lam

Biomedical Engineering Theses & Dissertations

Long QT Syndrome (LQTS) is an increasingly studied condition that leads to potentially fatal heart rhythm disorders, called arrhythmias, and sudden cardiac death. The alterations in the electrocardiograms (ECGs) seen in LQTS patients is caused by mutations to genes related to ion channels in cardiac cells. Computational modeling allows the mechanistic study of these ion channel mutations in LQTS by providing quantitative predictors of cardiac behavior in human and rabbit heart models. This work hypothesizes that the repolarization reserve in cardiac Purkinje cells (PC), that form the cardiac conduction system, is lower than that of ventricular myocytes (VM), resulting in …

Subtalar Joint Definition In Biomechanical Models, Julia Noginova

Biomedical Engineering Theses & Dissertations

The effect of including a subtalar joint in a dynamic musculoskeletal model has not been fully explored or validated. The subtalar joint is often modeled as a one DOF hinge with the tri-planar axis defined as a combination of inclination and deviation angles measured from the ground and midline of the foot, respectively. The overall purposes of this dissertation were to explore how the inclusion of the subtalar joint and the definition of origin location and axis orientation affect the kinematics, joint kinetics, and muscle activations of the knee, ankle, and subtalar joint during dynamic tasks of walking and running …

Generation, Analysis, And Evaluation Of Patient-Specific, Osteoligamentous, Spine Meshes, Austin R. Tapp

Biomedical Engineering Theses & Dissertations

Scoliosis, an abnormal curvature of the spine, is traditionally corrected with bracing treatments or by a highly invasive posterior spinal fusion (PSF) operation. These correction strategies are constrained by current imaging modalities, which fail to elucidate the soft tissue anatomy that is known to play a critical role in spinal stiffness and overall structure. Osteoligamentous segmentations of the spinal column offer a foundation for downstream finite element (FE) studies seeking to optimize bracing treatments or determine ideal surgical approaches.

This thesis presents methods for automatically and semi-automatically segmenting vertebrae and surrounding soft tissues of the spinal column using X-ray computed …

Molecular Dynamics Simulations Of Ion Transport Through Electrically Stressed Biological Membranes, Federica Castellani

Biomedical Engineering Theses & Dissertations

The cell membrane is a selectively permeable barrier that controls the transport of ions, molecules, and other materials into and out of a cell. The manipulation of the cell membrane permeability is the basis for several biotechnological and biomedical applications, including electroporation. Electroporation (or electropermeabilization) occurs when the application of an external electric pulse causes water intrusion into the membrane interior and the formation of conductive transmembrane electropores. These electropores allow drugs, genetic material, and other normally impermeant molecules to enter a cell. Despite years of study, the complex mechanisms underlying this process are still not well understood. Molecular dynamics …

Integrative Computational Analysis Of Muscle Near-Infrared Spectroscopy Signals: Effects Of Oxygen Delivery And Blood Volume, Bhabuk Koirala

Biomedical Engineering Theses & Dissertations

Near-infrared spectroscopy (NIRS) is a non-invasive technology to evaluate skeletal muscle oxidative metabolism in healthy and disease states. This technology allows us to measure the dynamic response of oxygenated (Δ����������₂) and deoxygenated (Δ����������) heme group concentrations during muscle contraction. These O₂ kinetics are valuable for inferring the interplay between muscle oxygen delivery and utilization. However, the semi-quantitative nature of the NIRS signal limits its clinical application. Some of the challenges in interpreting the NIRS signal are related to the difficulties in quantifying the: 1) contribution of blood volume changes to the Δ����������₂ and Δ����������; 2) contribution …

Drive Leg And Stride Leg Ground Reaction Forces Relationship To Medial Elbow Stress And Velocity In Collegiate Baseball Pitchers, Brett Smith

Biomedical Engineering Theses & Dissertations

This study examines several different kinetic variables in relation to pitch velocity and elbow varus torque in collegiate baseball pitchers using force plates, an inertial measurement unit, and a radar unit. The purpose of this study is to investigate the kinetic variables being measured and their relationship to pitch velocity and loads being placed on the medial elbow. Twelve collegiate baseball pitchers participated in this study, which was approved by the IRB. Impulse of the drive leg in the anterior-posterior direction, stride leg peak force in the anterior-posterior (AP) direction, elbow varus torque, and pitch velocity were all measured. Two …

Nanosecond Stimulation And Defibrillation Of Langendorff-Perfused Rabbit Hearts, Johanna Neuber

Biomedical Engineering Theses & Dissertations

The search for novel defibrillation methodologies focuses on minimizing deposition of energy to the heart, as this is an indicator for side effects including pain and tissue death. In this work, we investigate the effect of reducing the duration of the applied shocks from low milliseconds to the nanosecond range.

300 ns defibrillation was observed and confirmed to require lower energy than monophasic shocks by almost an order of magnitude with no tissue damage. Additionally, the safety factor, the ratio of median effective doses for electroporative damage and defibrillation, was similar for both durations. To predict how defibrillation shocks of …

Validation Of Nanosecond Pulse Cancellation Using A Quadrupole Exposure System, Hollie A. Ryan

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric fields (nsPEFs) offer a plethora of opportunities for developing integrative technologies as complements or alternatives to traditional medicine. Studies on the biological effects of nsPEFs in vitro and in vivo have revealed unique characteristics that suggest the potential for minimized risk of complications in patients, such as the ability of unipolar nsEPs to create permanent or transient pores in cell membranes that trigger localized lethal or non-lethal outcomes without consequential heating. A more recent finding was that such responses could be diminished by applying a bipolar pulse instead, a phenomenon dubbed bipolar cancellation, paving the way …

Do Different Pathologies Affect The Relationship Between The Stiffness Of The Plantar Fascia And The Function Of The Mtp Joint?, Madeline Ryan Pauley

Biomedical Engineering Theses & Dissertations

Compared to healthy individuals, individuals with plantar fasciitis and diabetes experience material and structural property changes to soft tissues in the feet. The purpose of this study was to compare the relationship between material properties, power absorption, and energy storage characteristics to metatarsal power between healthy, plantar fasciitis symptomatic and asymptomatic, and diabetic participants. Investigating material change differences as well as energy storage and transfer trends in different pathology groups can lead to a better overall understanding of power transfer at the metatarsophalangeal joint (MTP). Participants were recruited for kinematic gait analysis and lower extremity shear wave elastography analysis and …

Impedance Analysis Of Tissues In Nspef Treatment For Cancer Therapy, Edwin Ayobami Oshin

Biomedical Engineering Theses & Dissertations

Nanosecond pulsed electric field (nsPEF) for cancer therapy is characterized by applications of high voltage pulses with low pulsed energy to induce non-thermal effects on tissues such as tumor ablation. It nonthermally treats tissues via electroporation. Electroporation is the increase in permeabilization of a cell membrane due to the application of high pulsed electric field. The objective of this study was to investigate the effect of nsPEF on tissue by monitoring the tissue’s impedance in real-time. Potato slices (both untreated and electroporated), and tumors extracted from female BALBc mice were studied. 100ns, 1-10kV pulses were applied to the tissues using …

Biphasic Gene Electrotransfer Enhances Gene Delivery In Vitro, John Bui

Biomedical Engineering Theses & Dissertations

The application of short, pulsed electric fields to eukaryotic cells and tissues has been shown to permeabilize cells. This phenomenon has been used for clinical applications for irreversible electroporation of cancer cells or for molecule delivery for drug or gene therapies. Typically, a monophasic (monopolar) pulse train is used; however, recent studies have explored the possibility of using biphasic (often referred to as bipolar) pulses, primarily for irreversible electroporation (IRE), which report reduced muscle contraction during pulse train application compared to monophasic pulses. Additional studies show improved transfection efficiency using biphasic pulses, conversely, with low cell viability. The purpose of …

Flexible Electrochemical Lactate Sensor, Peyton Miesse

Biomedical Engineering Theses & Dissertations

Lactic acid is a vital indicator for shock, trauma, stress, and exercise intolerance. It is a key biomarker for increases in stress levels and is the primary metabolically produced acid responsible for tissue acidosis that can lead to muscle fatigue and weakness. During intensive exercise, the muscles go through anerobic metabolism to produce energy. This leads to decreases in the blood flow of nutrients and oxygen to the muscles and increases in lactate production, which in turn cause lactic acidosis. Currently, changes in blood lactate concentrations are monitored by sensors that can be invasive via blood or wearable based sensors …

Estimating Cognitive Workload In An Interactive Virtual Reality Environment Using Electrophysiological And Kinematic Activity, Christoph Tremmel

Biomedical Engineering Theses & Dissertations

As virtual reality (VR) technology continues to gain prominence in commercial, educational, recreational and research applications, there is increasing interest in incorporating physiological sensors in VR devices for passive user-state monitoring to eventually increase the sense of immersion. By recording physiological signals such as the electroencephalogram (EEG), electromyography (EMG) or kinematic parameters during the use of a VR device, the user’s interactions in the virtual environment could be adapted in real time based on the user’s cognitive state. This dissertation evaluates the feasibility of passively monitoring cognitive workload via electrophysiological and kinematic activity while performing a classical n-back task in …

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal …

Thermally Assisted Pulsed Electric Field Ablation For Cancer Therapy, James Michael Hornef

Biomedical Engineering Theses & Dissertations

Pulsed Electric Fields (PEF) have promised improved treatment results in a variety of cancer types including melanoma, pancreatic and lung squamous cancer. Recent studies show that PEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. Experiments were performed to design, calibrate and implement a feedback-looped infrared laser irradiation system that could maintain specified temperatures during the treatment. The exact treatment area, penetration depth and thermal distribution of a 980-nm laser fiber were quantified using several methods, including the knife-edge technique and a tissue optical property study. In vivo and in vitro experiments using …

New Engineering Approaches To Arrhythmias And Myocardial Infarction, Frency Varghese

Biomedical Engineering Theses & Dissertations

In this thesis, we present new engineering approaches to several important cardiac diseases. Chapter 1 considers the dynamics of arrhythmias. The most dangerous arrhythmias are reentrant arrhythmias, including ventricular fibrillation and ventricular tachycardia. During these arrhythmias, there are one or several rotating excitation waves present in the heart. Because of their shape, these waves are called scroll waves; their center of rotation is a one-dimensional curve called the filament. Filaments largely constrain the configuration of a scroll wave but are much simpler, so much effort has gone into describing scroll wave dynamics in terms of the dynamics of their filaments. …

Ablation Of Cardiac Tissue With Nanosecond Pulsed Electric Fields: Experiments And Numerical Simulations, Fei Xie

Biomedical Engineering Theses & Dissertations

Cardiac ablation for the treatment of cardiac arrhythmia is usually performed by heating tissue with radio-frequency (RF) electrical currents to create conduction-blocking lesions in order to stop the propagation of electrical waves. Problems associated with RF ablation are recurrence of arrhythmias after successful treatments, tissue loss beyond the targeted tissue, long duration of the ablation procedure, and thermal side effects including thrombus formation that may lead to stroke. Here, we propose a new, non-thermal ablation method using nanosecond pulsed electric fields (nsPEFs) with better-controlled ablation volume, shorter procedure time, and no thermal side effects. We demonstrate that we can create …

Development Of A Practical Visual-Evoked Potential-Based Brain-Computer Interface, Nicholas R. Waytowich

Biomedical Engineering Theses & Dissertations

There are many different neuromuscular disorders that disrupt the normal communication pathways between the brain and the rest of the body. These diseases often leave patients in a `locked-in" state, rendering them unable to communicate with their environment despite having cognitively normal brain function. Brain-computer interfaces (BCIs) are augmentative communication devices that establish a direct link between the brain and a computer. Visual evoked potential (VEP)- based BCIs, which are dependent upon the use of salient visual stimuli, are amongst the fastest BCIs available and provide the highest communication rates compared to other BCI modalities. However. the majority of research …

Multichannel Characterization Of Brain Activity In Neurological Impairments, Yalda Shahriari

Biomedical Engineering Theses & Dissertations

Hundreds of millions of people worldwide suffer from various neurological and psychiatric disorders. A better understanding of the underlying neurophysiology and mechanisms for these disorders can lead to improved diagnostic techniques and treatments. The objective of this dissertation is to create a novel characterization of multichannel EEG activity for selected neurological and psychiatric disorders based on available datasets. Specifically, this work provides spatial, spectral, and temporal characterizations of brain activity differences between patients/animal models and healthy controls, with focus on modern techniques that quantify cortical connectivity, which is widely believed to be abnormal in such disorders. Exploring the functional brain …