Life Sciences Commons^™

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, …

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) …

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 …

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 …

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

McKelvey School of Engineering 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 …

Identification Of Proteins Involved In Cell Membrane Permeabilization By Nanosecond Electric Pulses (Nsep), Giedre Silkuniene, Uma Mangalanathan, Alessandra Rossi, Peter A. Mollica, Andrei G. Pakhomov, Olga N. Pakhomova

Bioelectrics Publications

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Closed-Loop Brain-Computer Interfaces For Memory Restoration Using Deep Brain Stimulation, David Xiaoliang Wang

Electrical Engineering Theses and Dissertations

The past two decades have witnessed the rapid growth of therapeutic brain-computer interfaces (BCI) targeting a diversity of brain dysfunctions. Among many neurosurgical procedures, deep brain stimulation (DBS) with neuromodulation technique has emerged as a fruitful treatment for neurodegenerative disorders such as epilepsy, Parkinson's disease, post-traumatic amnesia, and Alzheimer's disease, as well as neuropsychiatric disorders such as depression, obsessive-compulsive disorder, and schizophrenia. In parallel to the open-loop neuromodulation strategies for neuromotor disorders, recent investigations have demonstrated the superior performance of closed-loop neuromodulation systems for memory-relevant disorders due to the more sophisticated underlying brain circuitry during cognitive processes. Our efforts are …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

Electroporation And Cell Killing By Milli- To Nanosecond Pulses And Avoiding Neuromuscular Stimulation In Cancer Ablation, Emily Gudvangen, Vitalii Kim, Vitalij Novickij, Federico Battista, Andrei G. Pakhomov

Bioelectrics Publications

Ablation therapies aim at eradication of tumors with minimal impact on surrounding healthy tissues. Conventional pulsed electric field (PEF) treatments cause pain and muscle contractions far beyond the ablation area. The ongoing quest is to identify PEF parameters efficient at ablation but not at stimulation. We measured electroporation and cell killing thresholds for 150 ns–1 ms PEF, uni- and bipolar, delivered in 10- to 300-pulse trains at up to 1 MHz rates. Monolayers of murine colon carcinoma cells exposed to PEF were stained with YO-PRO-1 dye to detect electroporation. In 2–4 h, dead cells were labeled with propidium. Electroporation and …

In Vivo Metabolic Analysis Of The Anticancer Effects Of Plasma-Activated Saline In Three Tumor Animal Models, Miao Qi, Dehui Xu, Shuai Wang, Bing Li, Sansan Peng, Qiaosong Li, Hao Zhang, Runze Fan, Hai-Lan Chen, Michael G. Kong

Bioelectrics Publications

In recent years, the emerging technology of cold atmospheric pressure plasma (CAP) has grown rapidly along with the many medical applications of cold plasma (e.g., cancer, skin disease, tissue repair, etc.). Plasma-activated liquids (e.g., culture media, water, or normal saline, previously exposed to plasma) are being studied as cancer treatments, and due to their advantages, many researchers prefer plasma-activated liquids as an alternative to CAP in the treatment of cancer. In this study, we showed that plasma-activated-saline (PAS) treatment significantly inhibited tumor growth, as compared with saline, in melanoma, and a low-pH environment had little effect on tumor growth in …

Gradient Generating Microfluidic Coculture System For Disease Modeling And Neural Development, Phaneendra Chennampally

Electronic Theses and Dissertations

Cellular microenvironment or cell niche plays an important role in developmental biology and disease pathophysiology. Physical or chemical signals in microenvironment drive the cellular activity. These signaling molecules are generated from the surrounding cells/tissues as part of intercellular communication; a fundamental property of a cell. Dynamic profile of these signaling molecules in the microenvironment plays a pivotal role in transfer of molecular information from cell to cell in disease proliferation or fate determination. Recapitulating these signaling cues in an in vitro study is difficult to achieve using standard cell culture techniques. However microfluidic systems are capable of addressing these issues, …

Acute Effect Of High‑Definition And Conventional Tdcs On Exercise Performance And Psychophysiological Responses In Endurance Athletes: A Randomized Controlled Trial, Daniel Gomes Da Silva Machado, Marom Bikson, Abhishek Datta, Egas Caparelli‑Dáquer, Gozde Unal, Abrahão F. Baptista, Edilson Serpeloni Cyrino, Li Min Li, Edgard Morya, Alexandre Moreira, Alexandre Hideki Okano

Publications and Research

Transcranial direct current stimulation (tDCS) has been used aiming to boost exercise performance and inconsistent findings have been reported. One possible explanation is related to the limitations of the so-called “conventional” tDCS, which uses large rectangular electrodes, resulting in a diffuse electric field. A new tDCS technique called high-definition tDCS (HD-tDCS) has been recently developed. HD-tDCS uses small ring electrodes and produces improved focality and greater magnitude of its aftereffects. This study tested whether HD-tDCS would improve exercise performance to a greater extent than conventional tDCS. Twelve endurance athletes (29.4 ± 7.3 years; 60.15 ± 5.09 ml kg− 1 min− …

The Impact Of Nanopulse Treatment On The Tumor Microenvironment In Breast Cancer: Overturning The Treg Immunosuppressive Dominance, Anthony Nanajian

Biomedical Sciences Theses & Dissertations

Nanopulse treatment (NPT) is a high-power electric engineering modality that has been shown to be an effective local tumor treatment approach in multiple cancer models. Our previous studies on the orthotopic 4T1-luc breast cancer model demonstrated that NPT ablated local tumors. The treatment consequently conferred protection against a second live tumor challenge and minimized spontaneous metastasis. This study aims to understand how NPT mounts a potent immune response in a predominantly immunosuppressive tumor.

NPT changed the local and systemic dynamics of immunosuppressive cells by significantly reducing the numbers of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages …

Somatic Inhibition By Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Electric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the …

When The Brain Plays A Game: Neural Responses To Visual Dynamics During Naturalistic Visual Tasks, Jason Ki

Dissertations and Theses

Many day-to-day tasks involve processing of complex visual information in a continuous stream. While much of our knowledge on visual processing has been established from reductionist approaches in lab-controlled settings, very little is known about the processing of complex dynamic stimuli experienced in everyday scenarios. Traditional investigations employ event-related paradigms that involve presentation of simple stimuli at select locations in visual space and discrete moments in time. In contrast, visual stimuli in real-life are highly dynamic, spatially-heterogeneous, and semantically rich. Moreover, traditional experiments impose unnatural task constraints (e.g., inhibited saccades), thus, it is unclear whether theories developed under the reductionist …

Connexin Hemichannel Activation By S-Nitrosoglutathione Synergizes Strongly With Photodynamic Therapy Potentiating Anti-Tumor Bystander Killing, Chiara Nardin, Chiara Peres, Sabrina Putti, Tiziana Orsini, Claudia Colussi, Flavia Mazzarda, Marcello Raspa, Ferdinando Scavizzi, Anna Maria Salvatore, Francesco Chiani, Abraham Tettey-Matey, Yuanyuan Kuang, Guang Yang, Mauricio A. Retamal, Fabio Mammano

Bioelectrics Publications

In this study, we used B16-F10 cells grown in the dorsal skinfold chamber (DSC) preparation that allowed us to gain optical access to the processes triggered by photodynamic therapy (PDT). Partial irradiation of a photosensitized melanoma triggered cell death in non-irradiated tumor cells. Multiphoton intravital microscopy with genetically encoded fluorescence indicators revealed that bystander cell death was mediated by paracrine signaling due to adenosine triphosphate (ATP) release from connexin (Cx) hemichannels (HCs). Intercellular calcium (Ca²⁺) waves propagated from irradiated to bystander cells promoting intracellular Ca²⁺ transfer from the endoplasmic reticulum (ER) to mitochondria and rapid activation of …

The Role Of Reactive Oxygen Species In The Immunity Induced By Nano-Pulse Stimulation, Siqi Guo, Niculina I. Burcus, Megan Scott, Yu Jing, Iurii Semenov

Bioelectrics Publications

Reactive oxygen species (ROS) are byproducts of tumor cells treated with Nano-Pulse Stimulation (NPS). Recently, ROS have been suggested as a contributing factor in immunogenic cell death and T cell-mediated immunity. This research further investigated the role of NPS induced ROS in antitumor immunity. ROS production in 4T1-luc breast cancer cells was characterized using three detection reagents, namely, Amplex Red, MitoSox Red, and Dihydroethidium. The efficiency of ROS quenching was evaluated in the presence or absence of ROS scavengers and/or antioxidants. The immunogenicity of NPS treated tumor cells was assessed by ex vivo dendritic cell activation, in vivo vaccination assay …

Bio-Inspired Materials For Electrochemical Sensors, Matthew Joseph Hummel

Electronic Theses and Dissertations

Electrochemical biosensors are a rapidly growing research area that has greatly improved its specificity, accuracy, and precision in the detection of biomolecules in contemporary literature and industry alike. Typically, these systems exist in a three-electrode conformation with a working electrode functioning as the anode, a counter electrode functioning as the cathode, and a reference electrode allowing for the control of potential in the system. The method by which these sensors work is through the sharing of electrons via redox reactions with the target molecule and the working electrode or modifications on its surface. By exploiting the function of biomaterials that …

Photodynamic Therapy Of Inorganic Complexes For The Treatment Of Cancer, Chloe B. Smith, Lindsay C. Days, Duaa R. Alajroush, Khadija Faye, Yara Khodour, Stephen J. Beebe, Alvin Holder

Chemistry & Biochemistry Faculty Publications

Photodynamic therapy (PDT) is a medicinal tool that uses a photosensitiser and a light source to treat several conditions, including cancer. PDT uses reactive oxygen species (ROS) such as cytotoxic singlet oxygen ¹O₂ to induce cell death in cancer cells. Chemotherapy has historically utilized the cytotoxic effects of many metals, especially transition-metal complexes. However, chemotherapy is a systemic treatment so all cells in a patient's body are exposed to the same cytotoxic effects. Transition metal complexes have also shown high cytotoxicity as PDT agents. PDT is a potential localized method for treating several cancer types by using inorganic …

Development Of Light Actuated Chemical Delivery Platform On A 2-D Array Of Micropore Structure, Hojjat Rostami Azmand, Hojjat Rostami Azmand

Dissertations and Theses

Localized chemical delivery plays an essential role in the fundamental information transfers within biological systems. Thus, the ability to mimic the natural chemical signal modulation would provide significant contributions to understand the functional signaling pathway of biological cells and develop new prosthetic devices for neurological disorders. In this paper, we demonstrate a light-controlled hydrogel platform that can be used for localized chemical delivery in a high spatial resolution. By utilizing the photothermal behavior of graphene-hydrogel composites confined within micron-sized fluidic channels, patterned light illumination creates the parallel and independent actuation of chemical release in a group of fluidic ports. The …

Stobe Photography Mapping Of Cell Membrane Potential With Nanosecond Resolution, Allen S. Kiester, Bennett L. Ibey, Zachary N. Coker, Andrei G. Pakhomov, Joel N. Bixler

Bioelectrics Publications

The ability to directly observe membrane potential charging dynamics across a full microscopic field of view is vital for understanding interactions between a biological system and a given electrical stimulus. Accurate empirical knowledge of cell membrane electrodynamics will enable validation of fundamental hypotheses posited by the single shell model, which includes the degree of voltage change across a membrane and cellular sensitivity to external electric field non-uniformity and directionality. To this end, we have developed a high-speed strobe microscopy system with a time resolution of ~ 6 ns that allows us to acquire time-sequential data for temporally repeatable events (non-injurious …

Evaluating Neuromuscular Function Of The Biceps Brachii After Spinal Cord Injury: Assessment Of Voluntary Activation And Motor Evoked Potential Input-Output Curves Using Transcranial Magnetic Stimulation, Thibault Roumengous

Theses and Dissertations

Activation of upper limb muscles is important for independent living after cervical spinal cord injury (SCI) that results in tetraplegia. An emerging, non-invasive approach to address post-SCI muscle weakness is modulation of the nervous system. A long-term goal is to develop neuromodulation techniques to reinnervate (i.e. resupply nerve to) muscle fiber and thereby increase muscle function in individuals with tetraplegia. Towards this goal, developing monitoring techniques to quantify neuromuscular function is needed to better direct neurorehabilitation. Assessment of voluntary activation (VA) is a promising approach because the location of the stimulus can be applied cortically using transcranial magnetic stimulation (TMS) …

Network-Level Mechanisms Underlying Effects Of Transcranial Direct Current Stimulation (Tdcs) On Visuomotor Learning, Pejman Sehatpour, Clément Dondé, Matthew J. Hoptman, Johanna Kreither, Devin Adair, Elisa Dias, Blair Vail, Stephanie Rohrig, Gail Silipo, Javier Lopez-Calderon, Antigona Martinez, Daniel C. Javitt

Publications and Research

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant (p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence (p <.0001) and fMRI connectivity (p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

A Note From The Editor, Daphne Fauber

Ideas: Exhibit Catalog for the Honors College Visiting Scholars Series

This piece is a letter from Daphne Fauber, the editor of this issue of Ideas. In the letter, the editor introduces the work of Dr. Paschalis Gkoupidenis as well as the moment in time in which his Visiting Scholars talk occurs.

Update On The Use Of Transcranial Electrical Brain Stimulation To Manage Acute And Chronic Covid-19 Symptoms, Giuseppina Pilloni, Marom Bikson, Bashar W. Badran, Mark S. George, Steven A. Kautz, Alexandre Hideki Okano, Abrahão Fontes Baptista, Leigh E. Charvet

Publications and Research

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, …

Characterization Of Neuronal Differentiation And Activity In Human-Induced Pluripotent Neural Stem Cells, Allison Biddinger

The Journal of Purdue Undergraduate Research

No abstract provided.

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 …