Engineering Commons^™

Physio-Chemical Modifications To Re-Engineer Small Extracellular Vesicles For Targeted Anticancer Therapeutics Delivery And Imaging, Rahmat Asfiya, Lei Xu, Anjugam Paramanantham, Kuanysh Kabytaev, Anna Chernatynskaya, Grace Mccully, Hu Yang, Akhil Srivastava

Chemical and Biochemical Engineering Faculty Research & Creative Works

Cancer theranostics developed through nanoengineering applications are essential for targeted oncologic interventions in the new era of personalized and precision medicine. Recently, small extracellular vesicles (sEVs) have emerged as an attractive nanoengineering platform for tumor-directed anticancer therapeutic delivery and imaging of malignant tumors. These natural nanoparticles have multiple advantages over synthetic nanoparticle-based delivery systems, such as intrinsic targeting ability, less immunogenicity, and a prolonged circulation time. Since the inception of sEVs as a viable replacement for liposomes (synthetic nanoparticles) as a drug delivery vehicle, many studies have attempted to further the therapeutic efficacy of sEVs. This article discusses engineering strategies …

Identifying Sick Cells From High-Resolution Solid-State Micropore Data, Abdul Hafeez, Azhar Ilyas, Ali R. Butt, Samir M. Iqbal

Mechanical Engineering Faculty Publications and Presentations

Early detection of diseases such as cancer can drastically improve prognosis and treatment. To this end, solid-state micropores can measure distinct mechanical properties of diseased cells from their translocation behavior — detected as pulses in the temporal data stream of ionic current — and help diagnose diseases at early stages. However, the obstacle in such approaches is that the accuracy of the sensor is affected by noise, making the pulse detection task too subjective. This is inefficient especially when the disease-relevant data is only a fraction of the total acquired data. Thus, it is important to intelligently automate the detection …

Effect Of Resin Bleed Out On Compaction Behavior Of The Fiber Tow Gap Region During Automated Fiber Placement Manufacturing, Von Clyde Jamora, Virginia Rauch, Sergii G. Kravchenko, Oleksandr G. Kravchenko

Mechanical & Aerospace Engineering Faculty Publications

Automated fiber placement is a state-of-the-art manufacturing method which allows for precise control over layup design. However, AFP results in irregular morphology due to fiber tow deposition induced features such as tow gaps and overlaps. Factors such as the squeeze flow and resin bleed out, combined with large non-linear deformation, lead to morphological variability. To understand these complex interacting phenomena, a coupled multiphysics finite element framework was developed to simulate the compaction behavior around fiber tow gap regions, which consists of coupled chemo-rheological and flow-compaction analysis. The compaction analysis incorporated a visco-hyperelastic constitutive model with anisotropic tensorial prepreg viscosity, which …

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …

Simulating The Effect Of Gut Microbiome On Cancer Cell Growth Using A Microfluidic Device, Ekansh Mittal, Grace Cupp, Youngbok (Abraham) Kang

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

The imbalance in the gut microbiome plays a vital role in the progression of many diseases, including cancer, due to increased inflammation in the body. Since gut microbiome-induced inflammation can serve as a novel therapeutic strategy, there is an increasing need to identify novel approaches to investigate the effect of inflammation instigated by gut microbiome on cancer cells. However, there are limited biomimetic co-culture systems that allow testing of the causal relationship of the microbiome on cancer cells. Here we developed a microfluidic chip that can simulate the interaction of the gut microbiome and cancer cells to investigate the effects …

Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi

Electrical & Computer Engineering Faculty Publications

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids …

A Machine Learning Framework For Identifying Molecular Biomarkers From Transcriptomic Cancer Data, Md Abdullah Al Mamun

FIU Electronic Theses and Dissertations

Cancer is a complex molecular process due to abnormal changes in the genome, such as mutation and copy number variation, and epigenetic aberrations such as dysregulations of long non-coding RNA (lncRNA). These abnormal changes are reflected in transcriptome by turning oncogenes on and tumor suppressor genes off, which are considered cancer biomarkers.

However, transcriptomic data is high dimensional, and finding the best subset of genes (features) related to causing cancer is computationally challenging and expensive. Thus, developing a feature selection framework to discover molecular biomarkers for cancer is critical.

Traditional approaches for biomarker discovery calculate the fold change for each …

Synergic Antitumor Effect Of Photodynamic Therapy And Chemotherapy Mediated By Nano Drug Delivery Systems, Mozhgan Aghajanzadeh, Mostafa Zamani, Fereshteh Rajabi Kouchi, Josh Eixenberger, Dorsa Shirini, David Estrada, Farhad Shirini

Materials Science and Engineering Faculty Publications and Presentations

This review provides a summary of recent progress in the development of different nano-platforms for the efficient synergistic effect between photodynamic therapy and chemotherapy. In particular, this review focuses on various methods in which photosensitizers and chemotherapeutic agents are co-delivered to the targeted tumor site. In many cases, the photosensitizers act as drug carriers, but this review, also covers different types of appropriate nanocarriers that aid in the delivery of photosensitizers to the tumor site. These nanocarriers include transition metal, silica and graphene-based materials, liposomes, dendrimers, polymers, metal–organic frameworks, nano emulsions, and biologically derived nanocarriers. Many studies have demonstrated various …

Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian

Articles

Glioblastoma multiforme (GBM) is the most aggressive and commonly diag- 11 nosed brain cancer and presents a strong resistance to routine chemotherapeutic drugs. 12 The present study involves the synthesis of Lignin-g- p (NIPAM-co-DMAEMA) gold 13 nanogel, loaded with curcumin and piperine to treat GBM. The application has three 14 functions: (1) overcome the limitations of biodistribution, (2) enhance the toxicity of an- 15 ticancer drugs against GBM, (3) identify the uptake pathway. Atom transfer radical 16 polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with 17 the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and …

Enhanced Anticancer Response Of Curcumin- And Piperine-Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against U-251 Mg Glioblastoma Multiforme, Bilal Javed, Xinyi Zhao, Daxiang Cui, James Curtin, Furong Tian

Articles

Glioblastoma multiforme (GBM) is the most aggressive and commonly diagnosed brain cancer and is highly resistant to routine chemotherapeutic drugs. The present study involves the synthesis of Lignin-g-p (NIPAM-co-DMAEMA) gold nanogel, loaded with curcumin and piperine, to treat GBM. The ongoing study has the application potential to (1) overcome the limitations of drugs biodistribution, (2) enhance the toxicity of anticancer drugs against GBM, and (3) identify the drugs uptake pathway. Atom transfer radical polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and morphological analysis confirmed that the …

Investigation Of Carbon-Based Label-Free Electrochemical Aptasensors For Point-Of-Care Cancer Biomarker Detection, Shahrzad Forouzanfar

FIU Electronic Theses and Dissertations

Cancer is the second cause of death, with millions of fatalities every year. The early detection of cancer can tremendously increase the survival chances of the patients. An effective approach for early detection of cancer is developing reliable and relatively cheap biosensors that can quantify the cancer biomarkers from blood samples. These classes of the biosensor are commonly referred to as point-of-care (POC) cancer biomarker biosensors. The label-free electrochemical biosensors based on carbon dravite materials can be feasible for POC cancer biomarker biosensors. The present dissertation aims to design, develop, and optimize carbon-based biosensors for label-free detection of lactic acid …

Bibliometric Analysis Of Named Entity Recognition For Chemoinformatics And Biomedical Information Extraction Of Ovarian Cancer, Vijayshri Khedkar, Charlotte Fernandes, Devshi Desai, Mansi R, Gurunath Chavan Dr, Sonali Tidke Dr., M. Karthikeyan Dr.

Library Philosophy and Practice (e-journal)

With the massive amount of data that has been generated in the form of unstructured text documents, Biomedical Named Entity Recognition (BioNER) is becoming increasingly important in the field of biomedical research. Since currently there does not exist any automatic archiving of the obtained results, a lot of this information remains hidden in the textual details and is not easily accessible for further analysis. Hence, text mining methods and natural language processing techniques are used for the extraction of information from such publications.Named entity recognition, is a subtask that comes under information extraction that focuses on finding and categorizing specific …

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 …

The Resistive Barrier Discharge: A Brief Review Of The Device And Its Biomedical Applications, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

This paper reviews the principles behind the design and operation of the resistive barrier discharge, a low temperature plasma source that operates at atmospheric pressure. One of the advantages of this plasma source is that it can be operated using either DC or AC high voltages. Plasma generated by the resistive barrier discharge has been used to efficiently inactivate pathogenic microorganisms and to destroy cancer cells. These biomedical applications of low temperature plasma are of great interest because in recent times bacteria developed increased resistance to antibiotics and because present cancer therapies often are accompanied by serious side effects. Low …

Position-Scanning Peptide Libraries As Particle Immunogens For Improving Cd8+ T-Cell Responses, Michael C. Vega

Faculty Peer-Reviewed Publications

Short peptides reflecting major histocompatibility complex (MHC) class I (MHC-I) epitopes frequently lack sufficient immunogenicity to induce robust antigen (Ag)-specific CD8⁺ T cell responses. In the current work, it is demonstrated that position-scanning peptide libraries themselves can serve as improved immunogens, inducing Ag-specific CD8⁺ T cells with greater frequency and function than the wild-type epitope. The approach involves displaying the entire position-scanning library onto immunogenic nanoliposomes. Each library contains the MHC-I epitope with a single randomized position. When a recently identified MHC-I epitope in the glycoprotein gp70 envelope protein of murine leukemia virus (MuLV) is assessed, only one …

Modulation Of Ros In Nanosecond-Pulsed Plasma-Activated Media For Dosage-Dependent Cancer Cell Inactivation In Vitro, Chunqi Jiang, Esin Bengisu Sozer, Shutong Song, Nicola Lai, P. Thomas Vernier, Sigi Guo

Bioelectrics Publications

Dosage control of reactive oxygen and nitrogen species (RONS) is critical to low-temperature plasma applications in cancer therapy. Production of RONS by atmospheric pressure, nonequilibrium plasmas in contact with liquid may be modulated via plasma conditions including plasma treatment time and pulse voltage and repetition frequency. In this study, a terephthalic acid-based probe was used to measure hydroxyl radicals [OH_aq] in water exposed to plasma and to demonstrate that the OH_ag concentration increases linearly with treatment time. Fluorometric measurements of hydrogen peroxide concentration in plasma-activated water show a linear relationship between the H₂O₂ production …

Using Case-Level Context To Classify Cancer Pathology Reports, Shang Gao, Mohammed Alawad, Noah Schaefferkoetter, Lynne Penberthy, Xiao-Cheng Wu, Eric B. Durbin, Linda Coyle, Arvind Ramanathan, Georgia Tourassi

Kentucky Cancer Registry Faculty Publications

Individual electronic health records (EHRs) and clinical reports are often part of a larger sequence-for example, a single patient may generate multiple reports over the trajectory of a disease. In applications such as cancer pathology reports, it is necessary not only to extract information from individual reports, but also to capture aggregate information regarding the entire cancer case based off case-level context from all reports in the sequence. In this paper, we introduce a simple modular add-on for capturing case-level context that is designed to be compatible with most existing deep learning architectures for text classification on individual reports. We …

A Dual Approach For Positive T–S Fuzzy Controller Design And Its Application To Cancer Treatment Under Immunotherapy And Chemotherapy, Elham Ahmadi, Jafar Zarei, Roozbeh Razavi-Far, Mehrdad Saif

Electrical and Computer Engineering Publications

This study proposes an effective positive control design strategy for cancer treatment by resorting to the combination of immunotherapy and chemotherapy. The treatment objective is to transfer the initial number of tumor cells and immune–competent cells from the malignant region into the region of benign growth where the immune system can inhibit tumor growth. In order to achieve this goal, a new modeling strategy is used that is based on Takagi–Sugeno. A Takagi-Sugeno fuzzy model is derived based on the Stepanova nonlinear model that enables a systematic design of the controller. Then, a positive Parallel Distributed Compensation controller is proposed …

A Compendium Of Single Cell Analysis In Aging And Disease, Uday Chintapula, Samir M. Iqbal, Young-Tae Kim

Electrical and Computer Engineering Faculty Publications and Presentations

Cell is the fundamental structural and functional unit of complex multicellular organisms. Conventional methods which involve average analysis of cells in bulk populations can undermine physiologically significant cell populations, whereas analysis of cells at a single cell level may reveal unique biomarkers and other mechanisms that govern the genotype and phenotype in various physiological processes in presumed homogenous cell populations. Cellular abnormalities such as irregularities in cellular mechanisms have been linked to human aging and other major diseases including neurodegenerative, vascular, autoimmune, and cancer. Aging is a functional decline associated with various diseases in an organism, majorly arising from cellular …

Engineered Fn3 Protein Has Targeted Therapeutic Effect On Mesothelin-Expressing Cancer Cells And Increases Tumor Cell Sensitivity To Chemotherapy, Allison R. Sirois, Daniela A. Deny, Yanxuan Li, Yacine D. Fall, Sarah J. Moore

Engineering: Faculty Publications

Mesothelin is a protein expressed at high levels on the cell surface in a variety of cancers, with limited expression in healthy tissues. The presence of mesothelin on tumor tissue correlates with increased invasion and metastasis, and resistance to traditional chemotherapies, through mechanisms that remain poorly understood. Molecules that specifically recognize mesothelin and interrupt its contribution to tumor progression have significant potential for targeted therapy and targeted drug delivery applications. A number of mesothelin-targeting therapies are in preclinical and clinical development, although none are currently approved for routine clinical use. In this work, we report the development of a mesothelin-targeting …

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 …

Biomedical Engineering Or Biomedical Optics: Will The Real Discipline Please Stand Up?, Brian W. Pogue

Dartmouth Scholarship

This editorial reflects on the shape of biomedical engineering as a discipline, and its relation to biomedical optics.

A Layman's Guide To Malignancies: Cancer And Cancer Research In Everyday Terms, Bailee Bartash

Honors College

In the 200,000 years that humans have existed in our current homo sapien sapien form, we built our civilizations based in part on our desire to understand the world around us. The difficult part about this is the fact that our world has grown so vast and so quickly (think Moore’s Law, the observation that the speed and capability of computers is projected to double each year with an increasing number of transistors that can fit into a microchip), especially within the past century, that many people have been left behind due to their capability to understand. This gap in …

The Effect Of Proteome And Lipidome On The Behavior Of Membrane Bound Systems In Thermally-Assisted Acoustophoresis, Elnaz Mirtaheri

FIU Electronic Theses and Dissertations

Changes in the biomechanical properties of cells accompanying the development of various pathological conditions have been increasingly reported as biomarkers for various diseases, including cancers. In cancer cells, the membrane properties have been altered compared to their healthy counterparts primarily due to proteomic and lipidomic dysregulations conferred by the underlying pathology. The separation and selective recovery of these cells or extracellular vesicles secreted from such cells is of high diagnostic and prognostic value.

In this dissertation, the research builds on thermally-assisted acoustophoresis technique which was developed in our laboratory for the separation of vesicles of the same size, charge and …

Diagnostic Performance Of Receptor-Specific Surgical Specimen Staining Correlates With Receptor Expression Level, Jasmin M. Schaefer, Connor W. Barth, Scott C. Davis, Summer L. Gibbs

Dartmouth Scholarship

Intraoperative margin assessment is imperative to cancer cure but is a continued challenge to successful surgery. Breast conserving surgery is a relevant example, where a cosmetically improved outcome is gained over mastectomy, but re-excision is required in >25  %   of cases due to positive or closely involved margins. Clinical translation of margin assessment modalities that must directly contact the patient or required administered contrast agents are time consuming and costly to move from bench to bedside. Tumor resections provide a unique surgical opportunity to deploy margin assessment technologies including contrast agents on the resected tissues, substantially shortening the path to …

Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley

Bioelectrics Publications

Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell's compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical roles …

Review Of Methods For Intraoperative Margin Detection For Breast Conserving Surgery, Benjamin W. Maloney, David M. Mcclatchy, Brian W. Pogue, Keith D. Paulsen, Wendy A. Wells, Richard J. Barth

Dartmouth Scholarship

Breast conserving surgery (BCS) is an effective treatment for early-stage cancers as long as the margins of the resected tissue are free of disease according to consensus guidelines for patient management. However, 15% to 35% of patients undergo a second surgery since malignant cells are found close to or at the margins of the original resection specimen. This review highlights imaging approaches being investigated to reduce the rate of positive margins, and they are reviewed with the assumption that a new system would need high sensitivity near 95% and specificity near 85%. The problem appears to be twofold. The first …

Cip2a Immunosensor Comprised Of Vertically-Aligned Carbon Nanotube Interdigitated Electrodes Towards Point-Of-Care Oral Cancer Screening, Shaowei Ding, Suprem R. Das, Benjamin J. Brownlee, Kshama Parate, Taylor Davis, Loreen R. Stromberg, Edward K.L. Chan, Joseph Katz, Brian D. Iverson, Jonathan C. Claussen

Faculty Publications

Vertically aligned carbon nanotube array (VANTA) coatings have recently garnered much attention due in part to their unique material properties including light absorption, chemical inertness, and electrical conductivity. Herein we report the first use of VANTAs grown via chemical vapor deposition in a 2D interdigitated electrode (IDE) footprint with a high height-to-width aspect ratio (3:1 or 75:25 µm). The VANTA-IDE is functionalized with an antibody (Ab) specific to the human cancerous inhibitor PP2A (CIP2A)—a alivary oncoprotein that is associated with a variety of malignancies such as oral, breast, and multiple myeloma cancers. The resultant immunosensor is capable of detecting CIP2A …

Perspective Review Of What Is Needed For Molecular-Specific Fluorescence-Guided Surgery, Brian W. Pogue, Eben L. Rosenthal, Samuel Achilefu, Gooitzen M. Van Dam

Dartmouth Scholarship

Molecular image-guided surgery has the potential for translating the tools of molecular pathology to real-time guidance in surgery. As a whole, there are incredibly positive indicators of growth, including the first United States Food and Drug Administration clearance of an enzyme-biosynthetic-activated probe for surgery guidance, and a growing number of companies producing agents and imaging systems. The strengths and opportunities must be continued but are hampered by important weaknesses and threats within the field. A key issue to solve is the inability of macroscopic imaging tools to resolve microscopic biological disease heterogeneity and the limitations in microscopic systems matching surgery …

Ion-Sensitive Field-Effect Transistors With Micropillared Gates For Measuring Cell Ion Exchange At Molecular Levels, Mohammad G. Abdallah, Rayan Khan, Christian Garcia, Young-Tae Kim, Samir M. Iqbal

Electrical and Computer Engineering Faculty Publications and Presentations

The detection of small concentrations of cancer cells before cancer takes over the primary organ completely, or metastasizes to other areas of the body is important for early screening of cancer. One approach to address cancer early screening is through cell ion exchange bioelectricity, which characterizes voltage potential in non-neuronal cells to regulate shape changing, proliferation, differentiation, migration, and cancer formation. Herein, novel ion-sensitive field-effective transistor (ISFET) modality is shown to measure cell behavior during the change of cell properties at molecular levels. ISFETs produce low resistance signals and consume low power. The small size of ISFETs enables miniature diagnosis …