Biomedical Engineering and Bioengineering Commons^™

Generation Of Bipolar Nanosecond Pulses, Sambasiva Rao Rajulapati

Electrical & Computer Engineering Theses & Dissertations

Bipolar pulse generation has been studied using transmission line technology, which was mainly used for monopolar pulse generation. In this thesis, low impedance, high current, nanosecond pulse generators were designed, constructed and tested. Five transmission lines were connected in parallel, so the impedance was 10 n. The transmission lines were switched by a spark gap switch operated in air. The closing of the switch creates a matched condition on one side of the transmission lines and a short circuit on the other side of the transmission lines. When the transmission lines are precharged, one of the two waves in opposite …

Dielectric Characterization Of Coastal Cartilage Chondrocytes, Michael W. Stacey, Ahmet C. Sabuncu, Ali Beskok

Bioelectrics Publications

BACKGROUND: Chondrocytes respond to biomechanical and bioelectrochemical stimuli by secreting appropriate extracellular matrix proteins that enable the tissue to withstand the large forces it experiences. Although biomechanical aspects of cartilage are well described, little is known of the bioelectrochemical responses. The focus of this study is to identify bioelectrical characteristics of human costal cartilage cells using dielectric spectroscopy.

METHODS: Dielectric spectroscopy allows non-invasive probing of biological cells. An in house computer program is developed to extract dielectric properties of human costal cartilage cells from raw cell suspension impedance data measured by a microfluidic device. The dielectric properties of chondrocytes are …

Delivery Of Interleukin-15 To B16 Melanoma By Electroporation Leads To Tumor Regression And Long-Term Survival, Bernadette Marrero, Shawna Shirley, Richard Heller

Bioelectrics Publications

Electroporation (EP) is a method used to physically deliver therapeutic molecules such as plasmid DNA directly to tissues. It has been used safely and successfully in clinical studies and preclinical cancer models to deliver genes to a variety of tissues. In cancer research cytokine therapy is emerging as a promising tool that can be used to boost the host response to tumor antigens. The delivery of cytokines as recombinant proteins can result in toxicity and other adverse effects; however the delivery of cytokine genes using EP has been shown to be safe and effective. Interleukin 15 (IL-15) is a cytokine …

Temporal Modulation Of Plasma Species In Atmospheric Dielectric Barrier Discharges, Aijun Yang, Xiaohua Wang, Dingxin Liu, Mingzhe Rong, Michael G. Kong

Bioelectrics Publications

The atmospheric pressure dielectric barrier discharge in helium is a pulsed discharge in nature and the moment of maximum species densities is almost consistent with peak discharge current density. In this paper, a one-dimensional fluid model is used to investigate the temporal structure of plasma species in an atmospheric He-N₂ dielectric barrier discharge (DBD). It is demonstrated that there exist microsecond delays of the moments of the maximum electron and ion densities from the peak of discharge current density. These time delays are caused by a competition between the electron impact and Penning ionizations, modulated by the N_{2 …}

Design And Study Of The Efflux Function Of The Egfp Fused Mexab-Oprm Membrane Transporter In Pseudomonas Aeruginosa Using Spectroscopy, Feng Ding, Kerry J. Lee, Ardeschir Vahedi-Faridi, Hiroshi Yoneyama, Christopher J. Osgood, Xiao-Hong Nancy Xu

Biological Sciences Faculty Publications

Multidrug membrane transporters (efflux pumps) can selectively extrude a variety of structurally and functionally diverse substrates (e.g., chemotoxics, antibiotics), leading to multidrug resistance (MDR) and ineffective treatment of a wide variety of diseases. In this study, we have designed and constructed a fusion gene (egfp-mexB) of N-terminal mexB with C-terminal egfp, inserted it into a plasmid vector (pMMB67EH), and successfully expressed it in the Δ MexB (MexB deletion) strain of Pseudomonas aeruginosato create a new strain that expresses MexA-(EGFP-MexB)-OprM. We characterized the fusion gene using gel electrophoresis and DNA sequencing, and determined its expression in live …

Autologous Platelet Rich Plasma (Platelet Gel): An Appropriate Intervention For Salvaging Cardiac Myocytes Under Oxidative Stress After Myocardial Infarction, Barbara Y. Hargrave

Bioelectrics Publications

Background: The prompt restoration of blood flow (reperfusion) to the ischemic myocardium after an acute myocardial infarction is critical to the survival of non damaged heart tissue. However, reperfusion is responsible for additional myocardial damage. Our objective was to investigate the role of autologous platelet rich plasma or platelet gel prepared using nanosecond pulsed electric fields (nsPEFs) in improving left ventricular mechanical function after ischemic reperfusion.

Methods: The hearts of nine adult female New Zealand White rabbits were perfused using the Langendorff model. The hearts were exposed to global ischemia for 30 min and reperfused for 60 min. The hearts …

A Nonrigid Registration Method For Correcting Brain Deformation Induced By Tumor Resection, Yixun Liu, Chengjun Yao, Fotis Drakopoulos, Jinsong Wu, Liangfu Zhou, Nikos Chrisochoides

Computer Science Faculty Publications

Purpose: This paper presents a nonrigid registration method to align preoperative MRI with intraoperative MRI to compensate for brain deformation during tumor resection. This method extends traditional point-based nonrigid registration in two aspects: (1) allow the input data to be incomplete and (2) simulate the underlying deformation with a heterogeneous biomechanical model.

Methods: The method formulates the registration as a three-variable (point correspondence, deformation field, and resection region) functional minimization problem, in which point correspondence is represented by a fuzzy assign matrix; Deformation field is represented by a piecewise linear function regularized by the strain energy of a heterogeneous biomechanical …

Electrotransfer Of Single-Stranded Or Double-Stranded Dna Induces Complete Regression Of Palpable B16.F10 Mouse Melanomas, Loree Heller, Vesba Todorovic, Maja Cemazar

Bioelectrics Publications

Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of single-stranded or double-stranded DNA with or without CpG motifs in both …

Subtalar Joint Instability: Diagnosis And Conservative Treatment, Julie Choisne

Mechanical & Aerospace Engineering Theses & Dissertations

Subtalar instability may be caused by various ligamentous injuries. Combined instability at the ankle and subtalar joint is not adequately diagnosed. Further, isolated subtalar instability is usually misdiagnosed which may lead to long term damage to the joint. Developing a non-invasive and clinically practical tool to diagnose subtalar joint instability would be an important asset. The ability of an ankle brace, a common treatment for hindfoot instability, to promote stability for the subtalar joint was not well established. The purposes of this study were to 1) assess the kinematics of the subtalar, ankle, and hindfoot in the presence of isolated …

Protein Loop Length Estimation From Medium Resolution Cryoem Images, Andrew R. Mcknight

Computer Science Theses & Dissertations

In the post-genomic era, proteomics research presents a new frontier in life science. Proteins play roles in virtually every biological process, and understanding their atomic structures is the key to unraveling how they carry out their work. Compared to the over half million protein sequences in UniProt, only around 25,000 unique sequences have been atomically modeled and deposited to PDB (Protein Databank). Cryoelectron Microscopy (cryoEM) is an important biophysical technique that produces 3D subnanometer resolution images of molecules not amenable to past approaches like x-ray crystallography or nuclear magnetic resonance. De novo modeling is becoming a promising approach to derive …

Section Abstracts: Biomedical And General Engineering

Virginia Journal of Science

Abstracts of the Biomedical and General Engineering Section for the 91st Annual Virginia Journal of Science Meeting, May 2013

An Empirical Muscle Intracellular Action Potential Model With Multiple Erlang Probability Density Functions Based On A Modified Newton Method, Gyutae Kim, Mohammed M. Ferdjallah, Frederic D. Mckenzie

Computational Modeling & Simulation Engineering Faculty Publications

The convolution of the transmembrane current of an excitable cell and a weighting function generates a single fiber action potential (SFAP) model by using the volume conductor theory. Here, we propose an empirical muscle IAP model with multiple Erlang probability density functions (PDFs) based on a modified Newton method. In addition, we generate SFAPs based on our IAP model and referent sources, and use the peak-to-peak ratios (PPRs) of SFAPs for model verification. Through this verification, we find that the relation between an IAP profile and the PPR of its SFAP is consistent with some previous studies, and our IAP …

Cpg And Interleukin-15 Synergize To Enhance Ifn-Gamma Production By Activated Cd8(+) T Cells, Dustin Cobb, Sigi Guo, Ronald B. Smeltz

Bioelectrics Publications

Interleukin-15 (IL-15) regulates the development and maintenance of memory CD8(+) T cells. Paradoxically, we previously reported that IL-15 could enhance CD8(+) T-cell responses to IL-12, a proinflammatory cytokine required for optimal priming of effector CD8(+) T cells. To expand the physiological relevance of these findings, we tested IL-15 for its ability to enhance T-cell responses to bacterial CpG. Expectedly, CpG enhanced the production of IFN-gamma by CD8(+) T cells polyclonally activated with anti-CD3. However, addition of IL-15 to CpG-stimulated cultures led to a striking increase in IFN-gamma production. The effect of CpG and IL-15 was also evident with CD8(+) T …

Atomic Force Microscopy Characterization Of Collagen ‘Nanostraws’ In Human Costal Cartilage, Michael W. Stacey, Diganta Dutta, Anthony Asmar, H. Elsayed-Ali, R. Kelly Jr., A. Beskok

Bioelectrics Publications

Costal cartilage, a type of hyaline cartilage that bridges the bony ribs and sternum, is relatively understudied compared to the load bearing cartilages. Deformities of costal cartilage can result in deformation of the chest wall, where the sternum is largely pushed toward or away from the spine, pectus excavatum and pectus carinatum, respectively, with each condition having significant clinical impact. In the absence of extensive literature describing morphological features of costal cartilage, we characterized a sample from the costal margin immunohistologically and through atomic force microscopy. We had previously observed the presence of collagen ‘nanostraws’ running the length of costal …

Primary Pathways Of Intracellular Ca2+ Mobilization By Nanosecond Pulsed Electric Field, Iurii Semenov, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Permeabilization of cell membranous structures by nanosecond pulsed electric field (nsPEF) triggers transient rise of cytosolic Ca²⁺ concentration ([Ca²⁺]_i), which determines multifarious downstream effects. By using fast ratiometric Ca²⁺ imaging with Fura-2, we quantified the external Ca²⁺ uptake, compared it with Ca²⁺ release from the endoplasmic reticulum (ER), and analyzed the interplay of these processes. We utilized CHO cells which lack voltage-gated Ca²⁺ channels, so that the nsPEF-induced [Ca²⁺]_i changes could be attributed primarily to electroporation. We found that a single 60-ns pulse caused fast [Ca2+]_i increase …

Response To "Sodium Current Inhibition By Nanosecond Pulsed Electric Field (Nspef) - Fact Or Artifact?" By Verkerk Et Al, Andrei G. Pakhomov

Bioelectrics Publications

It was nice to learn that our studies of nanosecond pulsed electric field (nsPEF) effects on membrane currents [Nesin et al., 2012; Nesin and Pakhomov, 2012] gained the attention of scientists outside the immediate field of bioelectromagnetics.

Distal Placement Of An End-To-Side Bypass Graft Anastomosis: A 3d Computational Study, John Di Cicco, Ayodeji Demuren

Mechanical & Aerospace Engineering Faculty Publications

A three-dimensional (3D) computational fluid dynamics study of shear rates around distal end-to-side anastomoses has been conducted. Three 51% and three 75% cross-sectional area-reduced 6 mm cylinders were modeled each with a bypass cylinder attached at a 30-degree angle at different placements distal to the constriction. Steady, incompressible, Newtonian blood flow was assumed, and the full Reynolds-averaged Navier-Stokes equations, turbulent kinetic energy, and specific dissipation rate equations were solved on a locally structured multiblock mesh with hexahedral elements. Consequently, distal placement of an end-to-side bypass graft anastomosis was found to have an influence on the shear rate magnitudes. For the …

Induction Of Cell Death Mechanisms And Apoptosis By Nanosecond Pulsed Electric Fields (Nspefs), Stephen J. Beebe, Nova M. Sain, Wei Ren

Bioelectrics Publications

Pulse power technology using nanosecond pulsed electric fields (nsPEFs) offers a new stimulus to modulate cell functions or induce cell death for cancer cell ablation. New data and a literature review demonstrate fundamental and basic cellular mechanisms when nsPEFs interact with cellular targets. NsPEFs supra-electroporate cells creating large numbers of nanopores in all cell membranes. While nsPEFs have multiple cellular targets, these studies show that nsPEF-induced dissipation of DeltaPsim closely parallels deterioration in cell viability. Increases in intracellular Ca2+ alone were not sufficient for cell death; however, cell death depended of the presence of Ca2+. When both events occur, cell …

Functional Near Infrared Detection Of Real And Imagined Finger Taps Using Support Vector Machine, Linear Discriminant Analysis, And Decision Tree Classification Methods, Eugene A. Stoudenmire

Computational Modeling & Simulation Engineering Theses & Dissertations

This study investigates the thesis that given cerebral response samples of an individual's left, right, both, and imagined finger tapping, continuous wave (CW) functional Near Infrared (fNIR), unregistered with fMRI, can differentiate between any two of the four categories.

Fifty subjects were outfitted with a single source/detector attached to a single, square pad, affixed to their heads using devices such as elastic bands and caps for light shielding. Slides depicting arrows pointing left, right, both directions, or made of dashed lines were presented to each subject, with a slide of text interspersed between each. Subjects tapped with their left finger, …

Subnanosecond Exposure Systems For Biological Studies, Jongbong Nah

Electrical & Computer Engineering Theses & Dissertations

The research of bioelectrics has expanded to subnanosecond pulse region and entered a new domain of biophysics of cell interaction with ultra-short and intense electric fields. As subnanosecond pulses may be delivered by antennas to the human body and is very attractive to the medical community, the study of subnanosecond pulse effects calls for exposure systems for both cells and tissues. Two systems were designed in the scope of this thesis, used for cells and tissues respectively. The exposure system designed for cell exposure is a cuvette consisting of two parallel aluminum gaps. This cuvette is placed in a coaxial …

Evaluation Of Autonomous Robotic Milling Methodology For Natural Tooth-Shaped Implants Based On Sko Optimization, Yongki Yoon

Mechanical & Aerospace Engineering Theses & Dissertations

Robotic surgery is one of the most demanding and challenging applications in the field of automatic control. One of the conventional surgeries, the dental implantation, is the standard methodology to place the artificial tooth root composed of titanium material into the upper or lower jawbone. During the dental implant surgery, mechanical removal of the bone material is the most critical procedure because it may affect the patient's safety including damage to the mandibular canal nerve and/or piercing the maxillary sinus. With this problem, even though short term survival rates are greater than 95%, long term success rate of the surgery …

Real-Time Virtual Pathology Using Signal Analysis And Synthesis, Dennis L. Bergin

Computational Modeling & Simulation Engineering Theses & Dissertations

This dissertation discusses the modeling and simulation (M& S) research in the area of real-time virtual pathology using signal analysis and synthesis. The goal of this research is to contribute to the research in the M&S area of generating simulated outputs of medical diagnostics tools to supplement training of medical students with human patient role players.

To become clinically competent physicians, medical students must become skilled in the areas of doctor-patient communication, eliciting the patient's history, and performing the physical exam. The use of Standardized Patients (SPs), individuals trained to realistically portray patients, has become common practice. SPs provide the …

Development And Validation Methodology Of The Nuss Procedure Surgical Planner, Krzysztof J. Rechowicz

Computational Modeling & Simulation Engineering Theses & Dissertations

Pectus excavatum (PE) is a congenital chest wall deformity which is characterized, in most cases, by a deep depression of the sternum. A minimally invasive technique for the repair of PE (MIRPE), often referred to as the Nuss procedure, has been proven to be more advantageous than many other PE treatment techniques. The Nuss procedure consists of placement of a metal bar(s) underneath the sternum, thereby forcibly changing the geometry of the ribcage. Because of the prevalence of PE and the popularity of the Nuss procedure, the demand to perform this surgery is greater than ever. Therefore, a Nuss procedure …

Section Abstracts: Biomedical And General Engineering

Virginia Journal of Science

Abstracts of the Biomedical and General Engineering Section for the 90th Annual Meeting of the Virginia Academy of Science, May 23-25, 2012, Norfolk State University, Norfolk, Virginia.

Image-Guided Robotic Dental Implantation With Natural-Root-Formed Implants, Xiaoyan Sun

Electrical & Computer Engineering Theses & Dissertations

Dental implantation is now recognized as the standard of the care for tooth replacement. Although many studies show high short term survival rates greater than 95%, long term studies (> 5 years) have shown success rates as low as 41.9%. Reasons affecting the long term success rates might include surgical factors such as limited accuracy of implant placement, lack of spacing controls, and overheating during the placement.

In this dissertation, a comprehensive solution for improving the outcome of current dental implantation is presented, which includes computer-aided preoperative planning for better visualization of patient-specific information and automated robotic site-preparation for superior …

Nonosecond Pulsed Electric Field Induced Changes In Dielectric Properties Of Biological Cells, Jie Zhuang

Electrical & Computer Engineering Theses & Dissertations

Nanosecond pulsed electric field induced biological effects have been a focus of research interests since the new millennium. Promising biomedical applications, e.g. tumor treatment and wound healing, are emerging based on this principle. Although the exact mechanisms behind the nanosecond pulse-cell interactions are not completely understood yet, it is generally believed that charging along the cell membranes (including intracellular membranes) and formation of membrane pores trigger subsequent biological responses, and the number and quality of pores are responsible for the cell fate. The immediate charging response of a biological cell to a nanosecond pulsed electric field exposure relies on the …

Electrokinetic Transport Phenomena In Nanofluidic Devices, Mingkan Zhang

Mechanical & Aerospace Engineering Theses & Dissertations

Nanofluidic devices have wide potential applications in biology, chemistry and medicine, and have been proven to be very valuable in sensing biological particles (e.g., DNA and proteins) due to their efficiency, sensitivity and portability. Electrokinetic control of ion, fluid, and particle transport by using only electric field is the most popular method employed in nanofluidic devices. A comprehensive understanding of the electrokinetic ion, fluid, and particle transport in nanofluidics is essential for developing nanofluidic devices for the detection of single molecules, such as the next generation nanopore-based DNA sequencing technology. This research explored numerical simulation of electrokinetic ion and fluid …

Synergistic Effect Of Subnanosecond Pulsed Electric Fields And Temperature On The Viability Of Biological Cells, James Thomas Camp

Electrical & Computer Engineering Theses & Dissertations

Pulsed electric fields have been used to induce a biological response in cells, and at sufficient energy, can cause cell death. By reducing the pulse duration from presently used nanosecond to subnanosecond ranges, the electric field can be delivered to biological tissue non-invasively by the use of an antenna instead of electrodes, such as needles. Studies have previously been completed in which the aim was to determine the energy density (electric field strength, number of pulses) required to induce cell death with 800 ps pulses. Based on this data, it was concluded that for pulse durations of 200 ps, with …

Cell Permeabilization And Inhibition Of Voltage-Gated Ca²+ And Na+ Channel Currents By Nanosecond Pulsed Electric Fields, Vasyl Nesin, Angela M. Bowman, Shu Xiao, Andrei G. Pakhomov

Bioelectrics Publications

Previous studies have found that nanosecond pulsed electric field (nsPEF) exposure causes long-term permeabilization of the cell plasma membrane. In this study, we utilized the whole-cell patch-clamp method to study the nsPEF effect on currents of voltage-gated (VG) Ca²⁺ and Na⁺ channels (I_Ca and I_Na) in cultured GH3 and NG108 cells. We found that a single 300 or 600 ns pulse at or above 1.5-2 kV/cm caused prolonged inhibition of I_Ca and I_Na. Concurrently, nsPEF increased a non-inactivating leak current (I_leak), presumably due to the formation of nanoelectropores or larger …

Alignment And Composition Of Laminin-Polycaprolactone Nanofiber Blends Enhance Peripheral Nerve Regeneration, Rebekah A. Neal, Sunil S. Tholpady, Patricia L. Foley, Nathan Swami, Roy C. Ogle, Edward A. Botchwey

School of Medical Diagnostics & Translational Sciences Publications

Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and lamininpolycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector …