Engineering Commons^™

Engineering Cell-Free Protein Synthesis Biosensors For Point Of Care Use, Tyler Jordan Free

Theses and Dissertations

Diagnostic tests can dramatically improve and save lives. Survival rates and patient outcomes related to cancer and other diseases can be improved when routine testing guides personalized treatment. Highly accurate laboratory tests exist for thousands of biomarkers, including those of interest in this dissertation, but cost and complexity limit access to life-saving lab tests in many cases throughout the world. To fill this need and increase accessibility of diagnostics, in this report we report our engineering advancements towards portable biosensors for colorimetric detection of glutamine, endocrine disrupting compounds (EDC), and pathogenic RNA which are key biomarkers in cancer treatment monitoring, …

Shape Memory Alloy Capsule Micropump For Drug Delivery Applications, Youssef Mohamed Kotb

Theses and Dissertations

Implantable drug delivery devices have many benefits over traditional drug administration techniques and have attracted a lot of attention in recent years. By delivering the medication directly to the tissue, they enable the use of larger localized concentrations, enhancing the efficacy of the treatment. Passive-release drug delivery systems, one of the various ways to provide medication, are great inventions. However, they cannot dispense the medication on demand since they are nonprogrammable. Therefore, active actuators are more advantageous in delivery applications. Smart material actuators, however, have greatly increased in popularity for manufacturing wearable and implantable micropumps due to their high energy …

Bcl2 Mediated Targeted Drug Delivery For The Treatment Of Kidney Fibrosis And Stomach Cancer, Humayra Afrin

Open Access Theses & Dissertations

Apoptosis, the programmed death of cells, is primarily regulated by a delicate balance between pro-apoptotic and anti-apoptotic signals. The Bcl-2 (B-cell lymphoma 2) family of proteins acts as anti-apoptotic agents, promoting cell survival. Dysregulation of these proteins is a common occurrence in conditions such as cancer and fibrosis, where overexpression of anti-apoptotic members can foster tumor cell survival and fibroblast activation. In this study, our aim was to explore the therapeutic potential of Bcl-2 inhibitors, both as a small molecule (specifically Navitoclax (Navi)), inhibitor and as Bcl-2 siRNA, for targeted treatment. Intravenous administration of Navi often leads to thrombocytopenia, necessitating …

Development And Evaluation Of A Modeling Platform For Evaluating Immunotherapeutic Efficacy In The Tumor Microenvironment., Dylan Andrew Goodin

Electronic Theses and Dissertations

The tumor microenvironment (TME) represents the complex outcome of numerous tumor, stromal, and immune interactions, and whose composition can significantly affect treatment response. Particularly, immunotherapeutic efficacy is subject to multiple tumor-specific TME interactions that may be difficult to evaluate/predict clinically. Mathematical modelling has been formulated to evaluate specific aspects of the TME, including vasculature, ECM deposition, and immune-tumor interactions. However, the computational challenge of simulating multiple TME interactions has led to sacrificing varying degrees of model generalizability and clinical relevance. This work describes increased computational performance of a 3D continuum model that simulates tumor tissue, ECM, and vasculature using a …

Microwave Imaging Technique For Breast Cancer Detection, Nure Alam Chowdhury

Theses and Dissertations

Breast cancer is a global problem, and it is inevitable to detect cancerous cells at early stages. In recent years, microwave imaging technology has been widely applied in biomedical applications for its non-ionizing radiation. In this study, we design a micro-strip patch antenna with an inverted T-type notch in the partial ground to detect tumor cells inside the human breast. The size of the current antenna is small enough (18 mm × 21 mm × 1.6 mm) to distribute around the breast phantom. The operating frequency has been observed from 6–14 GHz with a minimum return loss of −61.18 dB …

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 …

Cancer Treatment By Targeting Hdac4 Translocation Induced By Microsecond Pulsed Electric Field Exposure: Mechanistic Insights Through Kinases And Phosphatases, Zahra Safaei

Theses and Dissertations

Epigenetic modifications, arising from sub-cellular shifts in histone deacetylase (HDAC) activity and localization, present promising strategies for diverse cancer treatments. HDACs, enzymes responsible for post-translational histone modifications, induce these epigenetic changes by removing acetyl groups from ε-N-acetyl-lysine residues on histones, thereby suppressing gene transcription. Within the HDAC group, class IIa HDACs are notable for their responsiveness to extracellular signals, bridging the gap between external stimuli, plasma membrane, and genome through nuclear-cytoplasmic translocation. This localization offers two significant mechanisms for cancer treatment: nuclear accumulation of HDACs represses oncogenic transcription factors, such as myocyte-specific enhancer factor 2C (MEF2C), triggering various cell death …

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 …

Engineered Exosomes For The Multimodal Imaging Directed Photo-Immunotherapy Of Colorectal Cancer, Deepak S. Chauhan, Meena Jaggi, Subhash C. Chauhan, Murali M. Yallapu

Research Symposium

Background: Rio Grande Valley experience severe cancer health disparity. A novel therapeutic modality may serve as better therapeutic option. Nanohybrids endowed with multifunctionality, longer circulation time, large surface area have emerged as an active preference for cancer research. However, rising concern of nanomaterials toxicity and scalability issues has slowed their translation to clinics. Exosomes (Exo) are endogenous endocytic origin 40-100 nm vesicles found in various body fluids, which in comparison to synthetic nanoparticles, are biodegradable, highly biocompatible as well as immunocompatible in nature. Although bulk isolation of exosomes from human body fluids is still a problem and engineering of exosomes …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Magnetic Softness Tuned Superparamagnetic Nanoparticles For Highly Efficient Cancer Theranostics, Jie Wang

Theses and Dissertations

Magnetic resonance imaging (MRI)-guided magnetic nanofluid hyperthermia (MNFH) using iron oxide based superparamagnetic nanoparticles (SPNPs) has recently attracted considerable attention as a treatment modality for cancer theranostics, because MRI-guided MNFH can allow for diagnosis, therapeutics, and prognosis simultaneously using the same administrated magnetic nanofluid agent. However, several primary limiting factors: (1) insufficient AC magnetic heating induction (specific loss power/intrinsic loss power, SLP/ILP) at the biologically safe and physically tolerable range of AC magnetic field (H_AC,safe: f_appl × H_appl < 3.0 ~ 5.0×10⁹ A·m^-1·s^-1), (2) low _r2- relaxivity directly related to the low resolution of …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

An In Vivo Biocompatibility Analysis Of A Novel Tissue Regeneration Matrix Using A Pig Model, Shamar Thomas

All Theses

The goal of this project is to develop an injectable bead scaffold to promote tissue regeneration in the void created by lumpectomy and to alleviate post lumpectomy problems by preventing local recurrence and minimizing surgical-related infections. Microbeads were synthesized from collagen type I and crosslinked with tannic acid to form the basis for this injectable therapeutic. Tannic acid acts as a therapeutic anticancer agent. The action mechanisms of tannins in breast cancer cells have been studied with studies showing tannins to be cytotoxic to cancer cells in a dose-dependent manner. Tannic acid induces apoptosis in breast cancer cells via caspase …

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 …

Cost-Benefit Analysis Of Increased Water Treatment Plant Service Goals On Reducing Water Quality Risk, Briton Polen, Kendra Sanner

Williams Honors College, Honors Research Projects

To treat water to make it safe to drink, disinfection processes are used in water treatment plants. These disinfection processes produce disinfection byproducts (DBPs) through the reaction of organic matter and the disinfectant, such as chlorine. DBPs have been shown to pose a cancer risk to consumers. In this report, the focus is on two types of DBPs, trihalomethanes (THMs) and haloacetic acids (HAAs). The cancer risks associated with DBPs are analyzed through ingestion and inhalation pathways. Ingestion and inhalation consist of common water uses like drinking, cooking, or bathing. In addition to this, DBPs have been shown to increase …

Investigation Of Mechanical Regulation On Stat3 Activity And Mmp Production, Jaxson R. Libby

Honors Theses and Capstones

Transcription factor, STAT3, is inappropriately expressed in cancer cells, and has contrasting activation in 2D versus 3D microenvironments. 2D plates are often used for drug screening and do not always recapitulate in vivo responses. To combat inaccurate 2D drug studies, a 3D hydrogel was created to support the growth of cancer cells into a tumor-like environment. The hydrogel consists of a biocompatible dextran homopolysaccharide, cell adhesion RGD sequences, and crosslinker MMP labile peptides. A pH dependent reaction couples the RGD sequences to dextran then the polymers are crosslinked into a gel. Crosslinking is accomplished using terminal cysteine peptide sequences, allowing …

Development Of Nucleic Acid Diagnostics For Targeted And Non-Targeted Biosensing, Christopher William Smith

Legacy Theses & Dissertations (2009 - 2024)

The field of nucleic acid technology is rapidly expanding with new impactful discoveriesbeing made each year. Starting from the discovery of the double-helix structure, cloning, gene editing, polymerase chain reaction (PCR), CRISPR technology, and even the late mRNA vaccines; nucleic acid technology is at the forefront of improving medicine. Nucleic acid technology is extremely versatile due to its easy programmability, automated cheap synthesis, and even its catalog for numerous chemical modifications that can be used to alter structure stability. For example, the number of permutations that can be made with DNA just by altering the code for adenine (A), cytosine …

Multiscale Anisotropy Analysis Of Second-Harmonic Generation Imaging Of Pancreatic Cancer, Joshua D. Hamilton

Electronic Theses and Dissertations

Despite recent advancements in biomedicine, cancer is still the second leading cause of death in the United States. Early detection of cancer is critical to improving patient care, but there are risks of over screening caused by the need for surgical biopsies in many cancers for final diagnostics. Recent advancements in computer aided diagnostics for breast cancer screening has reduced the need for biopsies and resulted in earlier diagnoses which has lowered the mortality rate from breast cancer within the past two decades. Developing new computer aided diagnostic tools that can be applied to a vast majority of cancers would …

Long Non-Coding Rna Pvt1 – An Exploratory Study In Ovarian And Endometrial Cancer, Kevin Tabury

Theses and Dissertations

Gynecological cancers, ovarian and endometrial cancer, are still leading causes of cancer-related death in women worldwide. Early detection methods as well as treatment resistance remain a challenge. Long non-coding RNAs (lncRNAs) are emerging as therapeutic targets with diagnostic and prognostic potential with lncRNA PVT1 being one of them.

Here I test and demonstrate the role of PVT1 in ovarian cancer growth and metastasis. PVT1 is amplified and overexpressed in ovarian cancer and has predictive value for survival and response to targeted therapeutics. We find that expression of PVT1 is regulated by tumor cells in response to cellular stress, particularly loss …

Sequential Illumination In A Tomographic Microendoscopic Probe For Imaging Tumor Microvasculature, Zachariah Neumeier

Biomedical Engineering Undergraduate Honors Theses

Knowledge of colorectal cancer biology is improving how we approach cancer treatment. Specifically, the tumor microenvironment and abnormal angiogenesis are of particular interest. Optical methods are a prime candidate for research of the tumor microenvironment due to their ability to quantitively assess tissue structure and perfusion in real time. Particularly, the “transport scattering regime” has been identified as a method of obtaining high-resolution images and reflectance spectroscopy data; this light scattering regime has been demonstrated compatible with endoscopic imaging systems. In this study, a proof-of-concept optical imaging system is presented, capable of resolving absorbers within scattering turbid media using a …

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 Modeling Platform To Predict Cancer Survival And Therapy Outcomes Using Tumor Tissue Derived Metabolomics Data., Hunter Allan Miller

Electronic Theses and Dissertations

Cancer is a complex and broad disease that is challenging to treat, partially due to the vast molecular heterogeneity among patients even within the same subtype. Currently, no reliable method exists to determine which potential first-line therapy would be most effective for a specific patient, as randomized clinical trials have concluded that no single regimen may be significantly more effective than others. One ongoing challenge in the field of oncology is the search for personalization of cancer treatment based on patient data. With an interdisciplinary approach, we show that tumor-tissue derived metabolomics data is capable of predicting clinical response to …

Interrogating The Role Of Ing4 In Hematopoietic Stem Cells And Cancer, Zanshé Thompson

Theses and Dissertations

We recently identified the tumor suppressor, Ing4, as a critical regulator of hematopoietic stem cell (HSC) homeostasis. The mis-regulation of Ing4 in human cancers has also been shown to lend malignant cells specific advantages that support carcinogenesis and tumor progression. This activity is, in part, due to Ing4 mediated regulation of overlapping signaling pathways that regulate stem cell activity and cancer cells, including NF-B and c-Myc. In a two-part study, we have investigated the role of Ing4 in murine hematopoiesis and human malignancies. While the specific mechanisms of stem cell self-renewal, maintenance, and differentiation are poorly characterized, we have determined …

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 …

Novel Microfabricated Systems To Elucidate The Role Of Anisotropic Stiffness In The Tumor Microenvironment, Jiten Narang

Theses and Dissertations

Cancer is the second leading cause of death in women and late stage (metastatic) cancers have abysmal survival rates compared to early stage regional cases (27% vs 86%). As a tumor grows, the surrounding extracellular matrix (ECM) is reorganized into a dense, collagen rich matrix. The new matrix of aligned collagen fibers provides unique mechanical cues such as anisotropic stiffness and contact guidance. Matrix turnover also constricts local vasculature and restricts delivery of key nutrients and signaling molecules to malignant cells to outside the tumor creating a chemotactic gradient from outside to inside. In this work, we developed a novel …

Phase-Changing Nanodroplets As Nanotheranostic Platform For Combination Cancer Therapy, Catalina-Paula Spatarelu

Dartmouth College Ph.D Dissertations

Cancer is a cluster of diseases, and 1.8 million Americans are newly diagnosed each year. Treatment issues such as drug instability, the occurrence of severe side effects, as well as resistance make the need for solutions to improve conventional methods, like chemotherapy, apparent. Nano-sized drug-delivery platforms, particles loaded with therapeutic molecules that escape the immune system clearance and accumulate at the tumor site, were proposed as one of these solutions. Despite the expansion of the field, several aspects still need to be addressed: inconsistent delivery of the drugs, inability of measuring the effective dose being delivered to the tumor, lack …

Laser Stimulated Dynamic Thermal Imaging System For Tumor Detection, Hongyu Meng

McKelvey School of Engineering Theses & Dissertations

Laser stimulated dynamic thermal imaging system for tumor detectionby Hongyu Meng Doctor of Philosophy in Biomedical Engineering Washington University in St. Louis, 2021 Professor Samuel Achilefu, Chair Recent advances in infrared sensor technology have enabled the rapid application of thermal imaging in materials science, security and medicine. Relying on the infrared characteristics of living systems, thermal imaging has been used to generate individual heat maps, detect inflammation and tumor. As an imaging system, thermal imaging has the advantages of portability, real-time, non-invasive, and non-contact. But the low specificity of thermal imaging hinders its wide clinical application.

Unfortunately, label-free DTI is …