Bioelectrical and Neuroengineering Commons^™

Toward Electrical Impedance Sensing Surgical Drill For Tissue Boundary Detection, Harshavardhan Devaraj

Dartmouth College Ph.D Dissertations

Dental implantation is an increasingly common procedure used to treat missing teeth. However, surgical drilling to place the implant poses a high risk of injury to critical anatomy, such as inferior alveolar nerve injury or maxillary sinus perforation. A real-time surgical feedback system sensing proximity of these critical anatomy could reduce injury risks. This dissertation investigates the development of such a system that incorporates an electrical impedance sensor into the tip of a surgical drill.

A simulation framework based on finite element method (FEM) was developed to optimize the sensor as it approached a high impedance boundary. The accuracy of …

Interpatient Differences In Neural Recruitment Patterns During Pudendal Nerve Stimulation – A Computational Investigation, Amolak S. Jhand, Luis C. Ruiz, Nystha Baishya, Ehsan Mirzakhalili, Gaurang Shah, Priyanka Gupta, Tim M. Bruns, Scott F. Lempka

Medical Student Research Symposium

Bladder dysfunction impairs the quality of life for millions of individuals around the world. Common causes of bladder dysfunction include aging, trauma, and neurological disorders. Due to inadequacies in conventional treatments, neuromodulation therapies to address bladder dysfunction, such as sacral nerve stimulation, have emerged. However, patient needs still remain unmet. Pudendal nerve stimulation (PNS) has recently gained clinical interest as a promising treatment for bladder dysfunction. While PNS has been extensively investigated in preclinical settings, there is a gap in our understanding of the mechanisms of action and efficacy of PNS as limited studies of PNS have been performed on …

Nanosecond Pulsed Electric Fields Increase Antibiotic Susceptibility In Methicillin-Resistant Staphylococcus Aureus, Alexandra E. Chittams-Miles, Areej Malik, Erin B. Purcell, Claudia Muratori

Bioelectrics Publications

Staphylococcus aureus is the leading cause of skin and soft-tissue infections (SSTIs). SSTIs caused by bacteria resistant to antimicrobials, such as methicillin-resistant S. aureus (MRSA), are increasing in incidence and have led to higher rates of hospitalization. In this study, we measured MRSA inactivation by nanosecond pulsed electric fields (nsPEF), a promising new cell ablation technology. Our results show that treatment with 120 pulses of 600 ns duration (28 kV/cm, 1 Hz), caused modest inactivation, indicating cellular damage. We anticipated that the perturbation created by nsPEF could increase antibiotic efficacy if nsPEF were applied as a co-treatment. To test this …

Dihydroethidium-Derived Fluorescence In Electrically Stressed Cells Indicates Intracellular Microenvironment Modifications Independent Of Ros, Esin B. Sözer, Iurii Semenov, P. Thomas Vernier

Bioelectrics Publications

Intracellular reactive oxygen species (ROS) generation is widely suggested as a trigger for biological consequences of electric field exposures, such as those in electroporation applications. ROS are linked with membrane barrier function degradation, genetic damage, and complex events like immunological cell death. Dihydroethidium (DHE) is commonly used to monitor ROS in cells. DHE is linked to intracellular ROS by a primary oxidation product, Ethidium (Eth⁺), that shows increased fluorescence upon binding to polynucleotides. We observed changes in DHE-derived fluorescence in Chinese hamster ovary (CHO) cells post 300-ns electric pulse exposures, comparing them to tert-butyl-hydroperoxide (t-BHP) induced oxidative stress. …

Synergistic Effects Of Nanosecond Pulsed Plasma And Electric Field On Inactivation Of Pancreatic Cancer Cells In Vitro, Edwin A. Oshin, Zobia Minhas, Ruben M. L. Colunga Biancatelli, John D. Catravas, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond pulsed atmospheric pressure plasma jets (ns-APPJs) produce reactive plasma species, including charged particles and reactive oxygen and nitrogen species (RONS), which can induce oxidative stress in biological cells. Nanosecond pulsed electric field (nsPEF) has also been found to cause permeabilization of cell membranes and induce apoptosis or cell death. Combining the treatment of ns-APPJ and nsPEF may enhance the effectiveness of cancer cell inactivation with only moderate doses of both treatments. Employing ns-APPJ powered by 9 kV, 200 ns pulses at 2 kHz and 60-nsPEF of 50 kV/cm at 1 Hz, the synergistic effects on pancreatic cancer cells (Pan02) …

Dynamics Of Cell Membrane Lesions And Adaptive Conductance Under The Electrical Stress, Mantas Silkunas, Olga N. Pakhomova, Giedre Silkuniene, Andrei G. Pakhomov

Bioelectrics Publications

Exceeding physiological limits of the cell membrane potential compromises structural integrity, enabling the passage of normally impermeant solutes and disrupting cell function. Electropermeabilization has been studied extensively at the cellular scale, but not at the individual membrane lesion level. We employed fast total internal reflection fluorescence (TIRF) imaging of Ca(2+) entry transients to discern individual lesions in a hyperpolarized cell membrane and characterize their focality, thresholds, electrical conductance, and the lifecycle. A diffuse and momentary membrane permeabilization without a distinct pore formation was observed already at a -100 mV threshold. Polarizing down to -200 mV created focal pores with a …

Relating Temperature, Sleep, And Pathology In Mouse Models Of Alzheimer's Disease, Jun Wang

Theses and Dissertations--Biomedical Engineering

It is well established that sleep plays an important role in Alzheimer’s disease (AD) pathology. There is growing evidence that sleep issues may accelerate AD pathology by interrupting the physiological clearance of amyloid‐β (Aβ) from the brain, which mainly occurs in normal sleep. As the over-accumulation of amyloid‐β (Aβ) is believed to lead the cascade effect that eventually causes neurodegeneration in AD patients, development of therapeutic strategies for improving sleep quality may help slow disease progression. It is well documented that the composition and dynamics of sleep are sensitive to changes in ambient temperature. We therefore developed a sleep enhancement …

Nano-Pulse Treatment Overcomes The Immunosuppressive Tumor Microenvironment To Elicit In Situ Vaccination Protection Against Breast Cancer, Anthony Nanajian, Megan Scott, Niculina I. Burcus, Brittney L. Ruedlinger, Edwin A. Oshin, Stephen J. Beebe, Siqi Guo

Bioelectrics Publications

We previously reported that nano-pulse treatment (NPT), a pulsed power technology, resulted in 4T1-luc mammary tumor elimination and a strong in situ vaccination, thereby completely protecting tumor-free animals against a second live tumor challenge. The mechanism whereby NPT mounts effective antitumor immune responses in the 4T1 breast cancer predominantly immunosuppressive tumor microenvironment (TME) remains unanswered. In this study, orthotopic 4T1 mouse breast tumors were treated with NPT (100 ns, 50 kV/cm, 1000 pulses, 3 Hz). Blood, spleen, draining lymph nodes, and tumors were harvested at 4-h, 8-h, 1-day, 3-day, 7-day, and 3-month post-treatment intervals for the analysis of frequencies, death, …

Optimizing Transcranial Focused Ultrasound: Calibration, Neuro Navigation, And Bold Fmri Evidence Of Neuromodulation, Amilcar J. Malave

Dissertations and Theses

This thesis presents the development, calibration, and initial implementation of transcranial focused ultrasound (tFUS) for neuromodulation in a human study. The primary objectives were to design a system capable of delivering precise and safe ultrasound stimulation to targeted brain regions and to conduct preliminary trials to assess its effects on brain activity. A custom calibration device was developed to ensure accurate measurement of acoustic pressure, addressing challenges such as voltage alterations caused by changes in system impedance. Additionally, a neuro-navigation tool was created to facilitate precise targeting of the right subgenual anterior cingulate cortex (right sgACC), enabling accurate placement of …

Modulation Of Motor Learning With High-Intensity Transcranial Electric Stimulation, Gavin Hsu

Dissertations and Theses

Research thus far on noninvasive, transcranial electric stimulation have produced mixed results from in vivo human experiments. This work tests the hypothesis that applying higher stimulation intensities would induce intracranial electric fields that more closely match the higher magnitudes used in animal and in vitro studies and subsequently yield more robust effects. As done commonly in the literature, we targeted the motor cortex (M1), specifically in the context of neuroplastic changes taking place during motor learning in healthy adult humans. This work also seeks a better understanding of the neural correlates underlying motor skill learning.

Through multiple large-sample studies, this …

On The Modes Of Nanosecond Pulsed Plasmas For Combustion Ignition Of Quiescent Ch₄-Air Mixtures, Chunqi Jiang, Akash C. Dhotre, Meimei Lai, Sayan Biswas, James R. Macdonald, Isaac W. Ekoto

Bioelectrics Publications

The effect of transient plasma modes on ignition kernel development are discussed here for a quiescent CH₄-air combustion model system. A 10 ns high-voltage pulse was applied to a pin-to-pin electrode in lean fuel-air mixtures at room temperature and atmospheric pressure. High-impedance streamer, transient spark and low-impedance spark discharges were identified based on pulse waveforms of voltage and current. A sustained ignition kernel expansion was observed when the plasma discharge transitioned into a transient spark or spark discharge. The minimum ignition energy was obtained at the transient spark mode, which has less than a third of the energy …

Multi-Magnetic Material Transcranial Magnetic Stimulation Coils Development And Electric Field Measurement & Modeling Using Machine Learning, Mohannad Tashli

Theses and Dissertations

Transcranial Magnetic Stimulation (TMS) is a safe, effective, and non-invasive therapy for treating several psychiatric and neurological disorders. TMS is Food and Drug Administration (FDA) approved treatment and is commonly applied to patients who do not respond to medications for the treatment of clinical depression, smoking cessation, obsessive-compulsive disorder and migraine. Recently, there has been an increase in the development of electromagnetic neuromodulation techniques targeted at enhancing the effectiveness of TMS devices for the treatment of mental diseases. In TMS stimulation, focality is an important factor which determines the specificity of the pulses induced in different brain tissues. The electromagnetic …

Development Of An Automated Delivery System To Apply Copper Sulfate Crystals Using Precision Dry Fertilizer Application Technology, Kevin Charles Wise

Theses and Dissertations

The digenetic trematode, Bolbophorus damnificus, poses a substantial threat to catfish aquaculture, causing significant economic losses. Infestations lead to suppressed feed consumption, secondary bacterial infections and poor production performance. Survey data reveals widespread infestation in the in the southeastern United States. Current control strategies involve the application of a concentrated copper sulfate solution to reduce snail populations which serve as the first intermediate host of the trematode life cycle. This study aimed to improve treatment efficacy by developing a granular copper sulfate application system. A modified Gandy fertilizer applicator, equipped with a programmable control system, demonstrated accurate distribution of copper …

Tissue-Engineered Models For Investigating Nerve Infiltration In Fibrotic Microenvironments, Nikolas Ala-Kokko

Graduate Theses and Dissertations

Neuron infiltration is involved in a multitude of diseased states and is critical in the regeneration of physiologic conditions. Modeling of innervation in three-dimensional, heterogenous, environments would allow early investigation in the crosstalk of neurons and native cells in normal and pathophysiologic microenvironments to gain an understanding of mechanistic functions. This would allow for greater insight into the role of metabolism, cell adhesion, microenvironmental alternations, cellular crosstalk, and signaling pathways that play a role in the promotion and prevention of neurite growth. In this thesis, with the construction of collagen-based hydrogels as the foundation for cell culture, we investigate cell …

1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (Mptp)-Treated Adult Zebrafish As A Model For Parkinson’S Disease, Emmeline Bagwell

All Theses

The use of adult zebrafish, Danio rerio, as a model for human neurodegenerative diseases has proven valuable in pharmaceutical development and genetic disease research due to their high genetic homology to humans, cost-effective husbandry, and quick life cycle breeding times. Despite their promise, most zebrafish research has focused on embryonic stage organisms, primarily due to the ease of direct handling protocols and rapid progression through developmental stages. Recognizing the limitations of early-stage organisms in modeling adult diseases, recent efforts have shifted the applicability of zebrafish models, particularly for Parkinson's Disease, due to the nature of the disease impacting patients 55 …

Controlled Radiation Capsule For Precision And Rapid Cancer Treatment, Hoseon Lee, Zsolt Kollar, Bailey R. White, Junia Nguyen, David Roque, Sowjanya Palagani

Symposium of Student Scholars

This research aims to transform cancer treatment through the optimization of brachytherapy, with a focus on reducing treatment duration, setup complexities, and financial burdens, all while emphasizing patient safety. Patients living at a distance from radiation clinics, particularly those undergoing extended Low Dose Radiation brachytherapy, often struggle with the formidable financial challenges associated with securing nearby accommodations. In response to these issues, the research introduces a radiation capsule designed to condense the conventional six-month treatment period to approximately just one week, thereby significantly reducing the duration of required accommodations. This capsule is especially relevant considering the construction cost of $40 …

Improving Peripheral Nerve Regeneration Through Rehabilitation And Biomaterial-Based Drug Delivery Strategies, Yunfan Kong

Theses & Dissertations

Peripheral nerve injury (PNI) is a common problem worldwide, with trauma being a common cause. PNI can lead to loss of sensory and motor functions, chronic neuropathic pain, and mental health issues, significantly impacting patients' family life, work, and social situation. Recent studies revealed that beyond the topical injury site at peripheral nerves, PNIs can also induce dysfunctions in the central nervous system (CNS) by causing maladaptive plasticity, which will result in exaggeration and exacerbation of the pathological condition caused by primary injuries. The common therapy strategies for PNI treatment are using sutures, nerve autografts or conduits in cases requiring …

A Novel Brain Computer Interface Design, Steven Vogan

Senior Honors Theses

A brain computer interface (BCI) is a system which connects neural signals to a computer system. They have been used for controlling systems including robotics, on-screen computer control such as mouse movement, typing, and synthesizing audio signals. Invasive, or implanted, systems are often long-term medical solutions, or used for research where very clear signal is required. Non-invasive systems usually rely on exterior signals gathered through a headset using one or more electrode sensors. These signals are composed of sums of neuron activation potentials from brain activity and can be used to determine particular aspects of brain function. All BCIs rely …

Characterization And Estimation Of Musculoskeletal Pain Using Machine Learning, Boluwatife Faremi

Master's Theses

Traditional scales utilized for recording pain are known to be highly subjective and biased due to inaccuracies in recollecting actual pain intensities. As a result, machine learning (ML) models that are trained using these scores as ground truth are reported to have low performance for objective pain classification because of the huge disparity between what was felt in moments of pain and the scores recorded afterward.

In the present study, two devices were designed for gathering real-time, continuous in-session subjective pain scores and the recording of the autonomic nervous system (ANS) altered endodermal (EDA) activity. 24 participants were recruited to …

Analytical Pipeline To Facilitate Electroencephalography Pain State Identification In Patients With Chronic Low Back Pain, Emma Katharina Jacobs

Master's Theses

Chronic low back pain (cLBP) affects the quality of life of over 23% of American adults and places an immense burden on the economy.^1–3 To more effectively diagnose and treat cLBP, quantitative biomarkers are needed to objectively measure pain and better identify the underlying mechanisms of cLBP. The overarching goal of this work is to create an analytical pipeline to investigate brain activity patterns measured with electroencephalogram (EEG) data of cLBP patients treated with transcutaneous spinal cord stimulation (tSCS). The specific aims of this project are to 1) investigate whether there is a difference between baseline EEG measurements and …

Control Of The Electroporation Efficiency Of Nanosecond Pulses By Swinging The Electric Field Vector Direction, Vitalii Kim, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Ruben M. L. Colunga Biancatelli, Andrei G. Pakhomov

Bioelectrics Publications

Reversing the pulse polarity, i.e., changing the electric field direction by 180°, inhibits electroporation and electrostimulation by nanosecond electric pulses (nsEPs). This feature, known as “bipolar cancellation,” enables selective remote targeting with nsEPs and reduces the neuromuscular side effects of ablation therapies. We analyzed the biophysical mechanisms and measured how cancellation weakens and is replaced by facilitation when nsEPs are applied from different directions at angles from 0 to 180°. Monolayers of endothelial cells were electroporated by a train of five pulses (600 ns) or five paired pulses (600 + 600 ns) applied at 1 Hz or 833 kHz. Reversing …

The Effect Of Spinal Cord Stimulation And Video Games Training On Body-Machine Interface Control, Jie Fei

McKelvey School of Engineering Graduate Student Theses & Dissertations

Damage to the spinal cord causes long-lasting loss of motor and sensory function, and currently, there is no ‘cure’ for paralysis. However, even people with severe spinal cord injuries (SCI) have some residual mobility. Studies have shown that transcutaneous electrical spinal cord stimulation (tSCS) combined with functional training targeting residual mobility can further improve the motor function of individuals with SCI. In this study, we present a technical framework that aims to enhance rehabilitation outcomes by targeting residual mobility through a motor training-based approach. Our technical framework centers around a non-invasive body-machine interface (BoMI) that relies on the use of …

Cerebral Blood Flow Measured By Diffuse Correlation Spectroscopy For Monitoring Depth Of Anesthesia In Piglets, Mert Deniz Polat, Kurtulus Izzetoglu, Randolph Sinahon, Meltem Izzetoglu, Shadi Malaeb

St. Chris Research Day

No abstract provided.

Preparing Non-Human Primates To Study Hand-Eye Coordination In Frontal Eye Fields (Fef) During Delayed Movement Task, Juliusz Cydzik

McKelvey School of Engineering Graduate Student Theses & Dissertations

ABSTRACT OF THE THESIS Preparing Non-Human Primates to Study Hand-Eye Coordination in Frontal Eye Fields (FEF) During Delayed Movement Task by Juliusz Cydzik Master of Science in Biomedical Engineering Washington University in St. Louis, 2023 Professor Lawrence Snyder, Chair Hand-eye coordination enables humans and non-human primates to use their hands and eyes to perform various tasks. We are interested in coordination at the systems level, where saccades and reaches are encoded. The parietal reach region (PRR), situated at the posterior end of the intraparietal sulcus (IPS) and overlapping portions of the medial intraparietal area (MIP) and V6a, is commonly attributed …

A Proof Of Concept For Detection Of Palato-Lingual Contact Without Intraoral Electrodes In A Human Participant, Amitava Biswas

Master's Theses

The author of this thesis conceived and investigated an unexpected electrical signal that may not be noticed during regular electroglottography (EGG) when electrodes are conventionally placed on the anterior surface of the throat. It appears that there is a measurable electrical signal from the EGG equipment when electrodes are placed over the frontal cheek (belly of zygomatic muscle), and the tongue is elevated to contact the hard palate, or the tongue is lowered to break the contact. Therefore, this phenomenon is designated as unconventional electroglottography (UEGG, Dr. Steven Cloud, private communication, July 17, 2022).

Two distinctive patterns of waveforms were …

Metabolomic Differentiation Of Tumor Core And Edge In Glioma., Mary E. Baxter

Electronic Theses and Dissertations

Glioma is one of the most aggressive forms of brain cancer. It has been shown that the microenvironments differ significantly between the core and edge regions of glioma tumors. This study obtained metabolomic profiles of glioma core and edge regions using paired glioma core and edge tissue samples from 27 human patients. Data was acquired by performing liquid-liquid metabolite extraction and 2DLC-MS/MS on the tissue samples. In addition, a boosted generalized linear machine learning model was employed to predict the metabolomic profiles associated with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation.

A panel of 66 metabolites was found to be statistically significant …

On The Chronological Understanding Of The Homogeneous Dielectric Barrier Discharge, Xinpei Lu, Zhi Fang, Dong Dai, Tao Shao, Feng Liu, Cheng Zhang, Dawei Liu, Lanlan Nie, Chunqi Jiang

Bioelectrics Publications

Dielectric barrier discharges (DBD) are widely utilised non-equilibrium atmospheric pressure plasmas with a diverse range of applications, such as material processing, surface treatment, light sources, pollution control, and medicine. Over the course of several decades, extensive research has been dedicated to the generation of homogeneous DBD (H-DBD), focussing on understanding the transition from H-DBD to filamentary DBD and exploring strategies to create and sustain H-DBD. This paper first discusses the influence of various parameters on DBD, including gas flow, dielectric material, surface conductivity, and mesh electrode. Secondly, a chronological literature review is presented, highlighting the development of H-DBD and the …

Extracellular Vesticles In Acute Respiratory Distress Syndrome: Understanding Protective And Harmful Signaling For The Development Of New Therapeutics, Matthew Bavuso, Noel Miller, Joshua M. Sill, Anca Dobrian, Ruben M. L. Colunga Biancatelli

Bioelectrics Publications

Acute respiratory distress syndrome (ARDS) is a severe respiratory condition characterized by increased lung permeability, hyper-inflammatory state, and fluid leak into the alveolar spaces. ARDS is a heterogeneous disease, with multiple direct and indirect causes that result in a mortality of up to 40%. Due to the ongoing Covid-19 pandemic, its incidence has increased up to ten-fold. Extracellular vesicles (EVs) are small liposome-like particles that mediate intercellular communication and play a major role in ARDS pathophysiology. Indeed, they participate in endothelial barrier dysfunction and permeability, neutrophil, and macrophage activation, and also in the development of a hypercoagulable state. A more …

Evaluation Of Cold Atmospheric Plasma For The Decontamination Of Flexible Endoscopes, R. C. Hervé, Michael G. Kong, Sudhir Bhatt, Hai-Lan Chen, E. E. Comoy, J-P. Deslys, T. J. Secker, C. W. Keevil

Bioelectrics Publications

Background: Despite adherence to standard protocols, residues including live microorganisms may remain on the various surfaces of reprocessed flexible endoscopes. Prions are infectious proteins notoriously difficult to eliminate.

Aim: We tested the potential of cold atmospheric plasma (CAP) for the decontamination of flexible endoscope various surfaces, measuring total proteins and prion-residual infectivity as an indicator of efficacy.

Methods: New PTFE endoscope channels and metal test surfaces spiked with test soil or prion-infected tissues were treated using different CAP-generating prototypes. Surfaces were then examined for the presence of residues using very sensitive fluorescence epi-microscopy. Prion residual infectivity was determined using the …

Pulsed Electric Field Ablation Of Esophageal Malignancies And Mitigating Damage To Smooth Muscle: An In Vitro Study, Emily Gudvangen, Uma Mangalanathan, Iurii Semenov, Allen S. Kiester, Mark A. Keppler, Bennett L. Ibey, Joel N. Bixler, Andrei G. Pakhomov

Bioelectrics Publications

Cancer ablation therapies aim to be efficient while minimizing damage to healthy tissues. Nanosecond pulsed electric field (nsPEF) is a promising ablation modality because of its selectivity against certain cell types and reduced neuromuscular effects. We compared cell killing efficiency by PEF (100 pulses, 200 ns–10 µs duration, 10 Hz) in a panel of human esophageal cells (normal and pre-malignant epithelial and smooth muscle). Normal epithelial cells were less sensitive than the pre-malignant ones to unipolar PEF (15–20% higher LD50, p < 0.05). Smooth muscle cells (SMC) oriented randomly in the electric field were more sensitive, with 30–40% lower LD50 (p < 0.01). Trains of ten, 300-ns pulses at 10 kV/cm caused twofold weaker electroporative uptake of YO-PRO-1 dye in normal epithelial cells than in either pre-malignant cells or in SMC oriented perpendicularly to the field. Aligning SMC with the field reduced the dye uptake fourfold, along with a twofold reduction in Ca²⁺ transients. A 300-ns pulse induced a twofold smaller transmembrane potential in cells aligned with the field, making them …