Biomedical Engineering and Bioengineering Commons^™

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 …

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 …

A Novel Non-Enzymatic Glucose Biofuel Cell With Mobile Glucose Sensing, Ankit Baingane

Electrical & Computer Engineering Theses & Dissertations

Herein, we report a novel non-enzymatic glucose biofuel cell with mobile glucose sensing. We characterized the power generation and biosensing capabilities in presence of glucose analyte. This system was developed using a non-enzymatic glucose biofuel cell consisting of colloidal platinum coated gold microwire (Au-co-Pt) employed as an anode and the cathode which was constructed using a Gas diffusion electrode (GDE) with a platinum catalyst. The non-enzymatic glucose biofuel cell produced a maximum open circuit voltage of 0.54 V and delivered and a maximum short circuit current density of 1.6 mA/cm2 with a peak power density of 0.226 mW/cm2 at a …

Secretion Of Proteins And Antibody Fragments From Transiently Transfected Endothelial Progenitor Cells, Loree Heller, Reynald Thinard, Melanie Chevalier, Sezgi Arpag, Yu Jing, Ruth Greferath, Richard Heller, Claude Nicolau

Bioelectrics Publications

In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis and amyotrophic lateral sclerosis, neuroinflammation can lead to blood-brain barrier (BBB) breakdown. After intravenous or intra-arterial injection into mice, endothelial progenitor cells (EPCs) home to the damaged BBB to promote neurovascular repair. Autologous EPCs transfected to express specific therapeutic proteins offer an innovative therapeutic option. Here, we demonstrate that EPC transfection by electroporation with plasmids encoding the reporter protein GFP or an anti-beta-amyloid antibody fragment (Fab) leads to secretion of each protein. We also demonstrate the secreted anti-beta-amyloid Fab protein functions in beta-amyloid aggregate solubilization.

Probing Nanoelectroporation And Resealing Of The Cell Membrane By The Entry Of Ca2+ And Ba2+ Ions, Wenfei Bo, Mantas Silkunas, Uma Mangalanathan, Vitalij Novickij, Maura Casciola, Iurii Semenov, Shu Xiao, Olga N. Pakhomova, Andrei G. Pakhomov

Bioelectrics Publications

The principal bioeffect of the nanosecond pulsed electric field (nsPEF) is a lasting cell membrane permeabilization, which is often attributed to the formation of nanometer-sized pores. Such pores may be too small for detection by the uptake of fluorescent dyes. We tested if Ca²⁺, Cd²⁺, Zn²⁺, and Ba²⁺ ions can be used as nanoporation markers. Time-lapse imaging was performed in CHO, BPAE, and HEK cells loaded with Fluo-4, Calbryte, or Fluo-8 dyes. Ca²⁺ and Ba²⁺ did not change fluorescence in intact cells, whereas their entry after nsPEF increased fluorescence within <1 ms. The threshold for one 300-ns pulse was at 1.5–2 kV/cm, much lower than >7 …

Deep Cellular Recurrent Neural Architecture For Efficient Multidimensional Time-Series Data Processing, Lasitha S. Vidyaratne

Electrical & Computer Engineering Theses & Dissertations

Efficient processing of time series data is a fundamental yet challenging problem in pattern recognition. Though recent developments in machine learning and deep learning have enabled remarkable improvements in processing large scale datasets in many application domains, most are designed and regulated to handle inputs that are static in time. Many real-world data, such as in biomedical, surveillance and security, financial, manufacturing and engineering applications, are rarely static in time, and demand models able to recognize patterns in both space and time. Current machine learning (ML) and deep learning (DL) models adapted for time series processing tend to grow in …

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 …

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 …

The Hsp90 Inhibitor, Auy-922, Ameliorates The Development Of Nitrogen Mustard-Induced Pulmonary Fibrosis And Lung Dysfunction In Mice, Pavel Solopov, Ruben M.L. Colunga Biancatelli, Margarita Marinova, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

Increased levels of heat shock protein 90 (HSP90) have been recently implicated in the pathogenesis of pulmonary fibrosis and the use of HSP90 inhibitors constitutes a potential therapeutic approach. Similarly, acute exposure to nitrogen mustard (NM) is related to the development of chronic lung injury driven by TNF-α, TGF-β, ERK and HSP90. Thus, we developed a murine model of NM-induced pulmonary fibrosis by instilling C57BI/6J mice with 0.625 mg/kg mechlorethamine hydrochloride. After 24 h, mice began receiving AUY-922, a second generation HSP90 inhibitor, at 1 mg/kg 2 times per week or 2 mg/kg 3 times per week, for either 10 …

Thermal Analysis Of Infrared Irradiation-Assisted Nanosecond-Pulsed Tumor Ablation, James Hornef, Chelsea M. Edelblute, Karl H. Schoenbach, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond Pulsed Electric Fields (nsPEF) have the potential to treat a variety of cancer types including melanoma, pancreatic and lung squamous cancers. Recent studies show that nsPEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. A feedbacklooped heating system, utilizing a 980-nm fiber optic laser, was integrated into nsPEF electrodes for tumor ablation. The laser beam profile was determined to be Gaussian using a knife-edge technique. Thermal properties of the biological target were evaluated based on the treatment area, penetration depth and thermal distribution due to laser irradiation with or without nsPEF. Synergistic …

Electrochemical Detection Of Neurotransmitters, Saikat Banerjee, Stephanie Mccracken, Md Faruk Hossain, Gymama Slaughter

Bioelectrics Publications

Neurotransmitters are important chemical messengers in the nervous system that play a crucial role in physiological and physical health. Abnormal levels of neurotransmitters have been correlated with physical, psychotic, and neurodegenerative diseases such as Alzheimer's, Parkinson's, dementia, addiction, depression, and schizophrenia. Although multiple neurotechnological approaches have been reported in the literature, the detection and monitoring of neurotransmitters in the brain remains a challenge and continues to garner significant attention. Neurotechnology that provides high-throughput, as well as fast and specific quantification of target analytes in the brain, without negatively impacting the implanted region is highly desired for the monitoring of the …

Hsp90 Inhibition And Modulation Of The Proteome: Therapeutical Implications For Idiopathic Pulmonary Fibrosis (Ipf), Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Idiopathic Pulmonary fibrosis (IPF) is a catastrophic disease with poor outcomes and limited pharmacological approaches. Heat shock protein 90 (HSP90) has been recently involved in the wound-healing pathological response that leads to collagen deposition in patients with IPF and its inhibition represents an exciting drug target against the development of pulmonary fibrosis. Under physiological conditions, HSP90 guarantees proteostasis through the refolding of damaged proteins and the degradation of irreversibly damaged ones. Additionally, its inhibition, by specific HSP90 inhibitors (e.g., 17 AAG, 17 DAG, and AUY-922) has proven beneficial in different preclinical models of human disease. HSP90 inhibition modulates a complex …

Electrotransfer Of Il-15/Il-15rα Complex For The Treatment Of Established Melanoma, Shawna A. Shirley, Cathryn G. Lundberg, Richard Heller

Bioelectrics Publications

Gene electrotransfer (GET) is a safe, reliable, and effective method of delivering plasmid DNA (pDNA) to solid tumors. GET has been previously used to deliver interleukin-15 (IL-15) to mouse melanoma, resulting in long-term tumor regression and the survival of a percentage of treated animals after challenge. To enhance this effect, we evaluated modulating the expression levels of IL-15 and co-expressing its receptor, IL-15Rα. GET was used to deliver plasmids encoding IL-15 and IL-15Rα to established B16.F10 tumors on days 0, 4, and 7. Two delivery protocols that yielded different expression profiles were utilized. Mice that were tumor-free for 50 days …

Electropermeabilization Does Not Correlate With Plasma Membrane Lipid Oxidation, Olga Michel, Andrei G. Pakhomov, Maura Casciola, Jolanta Saczko, Julita Kulbacka, Olga N. Pakhomova

Bioelectrics Publications

The permeabilized condition of the cell membrane after electroporation can last minutes but the underlying mechanisms remain elusive. Previous studies suggest that lipid peroxidation could be responsible for the lasting leaky state of the membrane. The present study aims to link oxidation within the plasma membrane of live cells to permeabilization by electric pulses. We have introduced a method for the detection of oxidation by ratiometric fluorescence measurements of BODIPY-C11 dye using total internal reflection fluorescence (TIRF) microscopy, limiting the signal to the cell membrane. CHO-K1 cells were cultured on glass coverslips coated with an electroconductive indium tin oxide (ITO) …

Label-Free Microrna Optical Biosensors, Meimei Lai, Gymama Slaughter

Bioelectrics Publications

MicroRNAs (miRNAs) play crucial roles in regulating gene expression. Many studies show that miRNAs have been linked to almost all kinds of disease. In addition, miRNAs are well preserved in a variety of specimens, thereby making them ideal biomarkers for biosensing applications when compared to traditional protein biomarkers. Conventional biosensors for miRNA require fluorescent labeling, which is complicated, time-consuming, laborious, costly, and exhibits low sensitivity. The detection of miRNA remains a big challenge due to their intrinsic properties such as small sizes, low abundance, and high sequence similarity. A label-free biosensor can simplify the assay and enable the direct detection …

Estimating Cognitive Workload In An Interactive Virtual Reality Environment Using Eeg, Christoph Tremmel, Christain Herff, Tetsuya Sato, Krzysztof Rechowicz, Yusuke Yamani, Dean J. Krusienski

Electrical & Computer Engineering Faculty Publications

With the recent surge of affordable, high-performance virtual reality (VR) headsets, there is unlimited potential for applications ranging from education, to training, to entertainment, to fitness and beyond. As these interfaces continue to evolve, passive user-state monitoring can play a key role in expanding the immersive VR experience, and tracking activity for user well-being. By recording physiological signals such as the electroencephalogram (EEG) during 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. Current VR headsets provide a logical, convenient, and unobtrusive framework for mounting EEG …

Paper-Based Flexible Electrode Using Chemically-Modified Graphene And Functionalized Multiwalled Carbon Nanotube Composites For Electrophysiological Signal Sensing, Md Faruk Hossain, Jae Sang Heo, John Nelson, Insoo Kim

Bioelectrics Publications

Flexible paper-based physiological sensor electrodes were developed using chemically-modified graphene (CG) and carboxylic-functionalized multiwalled carbon nanotube composites (f@MWCNTs). A solvothermal process with additional treatment was conducted to synthesize CG and f@MWCNTs to make CG-f@MWCNT composites. The composite was sonicated in an appropriate solvent to make a uniform suspension, and then it was drop cast on a nylon membrane in a vacuum filter. A number of batches (0%~35% f@MWCNTs) were prepared to investigate the performance of the physical characteristics. The 25% f@MWCNT-loaded composite showed the best adhesion on the paper substrate. The surface topography and chemical bonding of the proposed CG-f@MWCNT …

Computational Analysis And Design Optimization Of Convective Pcr Devices, Jung Il Shu

Mechanical & Aerospace Engineering Theses & Dissertations

Polymerase Chain Reaction (PCR) is a relatively novel technique to amplify a few copies of DNA to a detectable level. PCR has already become common in biomedical research, criminal forensics, molecular archaeology, and so on. Many have attempted to develop PCR devices in numerous types for the purpose of the lab-on-chip (LOC) or point-of-care (POC). To use PCR devices for POC lab testing, the price must be lower, and the performance should be comparable to the lab devices. For current practices with the existing methods, the price is pushed up higher partially due to too much dependence on numerous developmental …

Using Feature Extraction From Deep Convolutional Neural Networks For Pathological Image Analysis And Its Visual Interpretability, Wei-Wen Hsu

Electrical & Computer Engineering Theses & Dissertations

This dissertation presents a computer-aided diagnosis (CAD) system using deep learning approaches for lesion detection and classification on whole-slide images (WSIs) with breast cancer. The deep features being distinguishing in classification from the convolutional neural networks (CNN) are demonstrated in this study to provide comprehensive interpretability for the proposed CAD system using the domain knowledge in pathology. In the experiment, a total of 186 slides of WSIs were collected and classified into three categories: Non-Carcinoma, Ductal Carcinoma in Situ (DCIS), and Invasive Ductal Carcinoma (IDC). Instead of conducting pixel-wise classification (segmentation) into three classes directly, a hierarchical framework with the …

Modulation Of Biological Responses To 2 Ns Electrical Stimuli By Field Reversal, Esin B. Sözer, P. Thomas Vernier

Bioelectrics Publications

Nanosecond bipolar pulse cancellation, a recently discovered Phenomenon, is modulation of the effects of a unipolar electric pulse exposure by a second pulse of opposite polarity. This attenuation of biological response by reversal of the electric field direction has been reported with pulse durations from 60 ns to 900 ns for a wide range of endpoints, and it is not observed with conventional electroporation pulses of much longer duration (> 100 mu s) where pulses are additive regardless of polarity. The most plausible proposed mechanisms involve the field-driven migration of ions to and from the membrane interface (accelerated membrane discharge). …

Estimation Of Arterial Wall Parameters Via Model-Based Analysis Of Noninvasively Measured Arterial Pulse Signals, Dan Wang

Mechanical & Aerospace Engineering Theses & Dissertations

This dissertation presents a model-based method for estimating arterial wall parameters from noninvasively measured arterial pulse signals via a microfluidic-based tactile sensor. The sensor entails a polydimethylsiloxane (PDMS) microstructure embedded with 5×1 transducer array built on Pyrex/Polyethylene terephthalate (PET) substrate. The arterial pulse causes a time-varying deflection on the top of the PDMS microstructure, which registers as a resistance change by the transducer at the site of the artery.

Owing to the time-harmonic nature of its radial motion, the arterial wall is modeled as a second-order dynamic system. By combining this dynamic model with a hemodynamic model of blood flow, …

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 …

Walking Biomechanics And Energetics Of Individuals With A Visual Impairment: A Preliminary Report, Hunter J. Bennett, Kevin A. Valenzuela, Kristina Fleenor, Steven Morrison, Justin A. Haegele

Human Movement Studies & Special Education Faculty Publications

Purpose.

Although walking gait in sighted populations is well researched, few studies have investigated persons with visual impairments (VIs). Given the lack of physical activity in people with VIs, it is possible that reduced efficiency in walking could adversely affect activity. The purposes of this preliminary study were to (1) examine the biomechanics and energetics utilized during independent and guided walking in subjects with VIs, and (2) compare gait biomechanics between people with VIs and sighted controls.

Methods.

Three-dimensional motion capture and force platforms were used during independent and guided walking at self-selected speeds. Joint angles, moments, external work, and …

Initiation Of Action Potential In Murine Ventricular Myocytes By Bursts Of Nanosecond Pulses, Iurii Semenov

Bioelectrics Publications

[First slide] Current situation

I. Among 300,000 persons die from sudden cardiac arrest every year over 40% are victims of fibrillation

II. Defibrillation by an electric shock is the effective therapy against sudden cardiac death

III. Current approach to stop fibrillation may involve disruption of plasma membrane (PM) by an electroporation

IV. Electroporation is damaging, it can: I. Induce post shock arrhythmias II. Complicate patient's recovery III. Lead to death after initially successful resuscitation

Nanosecond Pulsed Electric Signals Can Affect Electrostatic Environment Of Protiens Below The Threshold Of Conformational Effects: The Case Study Of Sod1 With A Molecular Simulation Study, Elena Della Valle, Paolo Marracino, Olga Pakhomova, Micaela Liberti, Francesca Apollonio

Bioelectrics Publications

Electric fields can be a powerful tool to interact with enzymes or proteins, with an intriguing perspective to allow protein manipulation. Recently, researchers have focused the interest on intracellular enzyme modifications triggered by the application of nanosecond pulsed electric fields. These findings were also supported by theoretical predictions from molecular dynamics simulations focussing on significant variations in protein secondary structures. In this work, a theoretical study utilizing molecular dynamics simulations is proposed to explore effects of electric fields of high intensity and very short nanosecond duration applied to the superoxide dismutase (Cu/Zn-SOD or SOD-1), an important enzyme involved in the …

Selective Distant Electrostimulation By Synchronized Bipolar Nanosecond Pulses, Elena C. Gianulis, Maura Casciola, Carol Zhou, Enbo Yang, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

A unique aspect of electrostimulation (ES) with nanosecond electric pulses (nsEP) is the inhibition of effects when the polarity is reversed. This bipolar cancellation feature makes bipolar nsEP less efficient at biostimulation than unipolar nsEP. We propose to minimize stimulation near pulse-delivering electrodes by applying bipolar nsEP, whereas the superposition of two phase-shifted bipolar nsEP from two independent sources yields a biologically-effective unipolar pulse remotely. This is accomplished by electrical compensation of all nsEP phases except the first one, resulting in the restoration of stimulation efficiency due to cancellation of bipolar cancellation (CANCAN-ES). We experimentally proved the CANCAN-ES paradigm by …

Intratumoral Delivery Of Plasmid Il12 Via Electroporation Leads To Regression Of Injected And Noninjected Tumors In Merkel Cell Carcinoma, Shailender Bhatia, Natalie V. Longino, Natalie J. Miller, Rima Kulikauskas, Jayasri G. Iyer, Dafina Ibrani, Astrid Blom, David R. Byrd, Upendra Parvathaneni, Christopher Twitty, Jean S. Campbell, Mai H. Le, Sharron Gargosky, Robert H. Pierce, Richard Heller, Adil Daud, Paul Nghiem

Bioelectrics Publications

Purpose: Interleukin-12 (IL12) promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.

Experimental Design: Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. …

Special Collection On Electroporation-Based Therapies: A Selection Of Papers From The Second World Congress On Electroporation, Richard Heller, Rafael V. Davalos

Bioelectrics Publications

No abstract provided.

A Fully-Flexible Solution-Processed Autonomous Glucose Indicator, Jonathan D. Yuen, Ankit Baingane, Qumrul Hasan, Lisa C. Shriver-Lake, Scott A. Walper, Daniel Zabetakis, Joyce C. Breger, David A. Stenger, Gymama Slaughter

Bioelectrics Publications

We present the first demonstration of a fully-flexible, self-powered glucose indicator system that synergizes two flexible electronic technologies: a flexible self-powering unit in the form of a biofuel cell, with a flexible electronic device - a circuit-board decal fabricated with biocompatible microbial nanocellulose. Our proof-of-concept device, comprising an enzymatic glucose fuel cell, glucose sensor and a LED indicator, does not require additional electronic equipment for detection or verification; and the entire structure collapses into a microns-thin, self-adhering, single-centimeter-square decal, weighing less than 40 mg. The flexible glucose indicator system continuously operates a light emitting diode (LED) through a capacitive charge/discharge …