Engineering Commons^™

6d Single-Fluorogen Orientation-Localization Microscopy For Elucidating The Architecture Of Beta-Sheet Assemblies And Biomolecular Condensates, Tingting Wu, Weiyan Zhou, Jai S. Rudra, Rohit V. Pappu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We develop six-dimensional single-molecule orientation-localization microscopy (SMOLM) to measure the 3D positions and 3D orientations simultaneously of single fluorophores. We show how careful optimization of phase and polarization modulation components can encode phase, polarization, and angular spectrum information from each fluorescence photon into a microscope’s dipole-spread function. We used the transient binding and blinking of Nile red (NR) to characterize the helical structure of fibrils formed by designed amphipathic peptides, KFE8^L and KFE8^D, and the pathological amyloid-beta peptide Aβ42. We also deployed merocyanine 540 to uncover the interfacial architectures of biomolecular condensates.

Synthesis And Characterization Of Sodium Cathode Materials, He Zhou

McKelvey School of Engineering Theses & Dissertations

As sodium batteries hold great promise as a next-generation energy storage device to replace lithium batteries, the development of sodium battery materials has become increasingly urgent. The current study aims to investigate two potential sodium-ion battery cathode materials, Sodium Vanadium Phosphate, and Sodium Manganese Hexacyanoferrate, optimize the experimental procedures, conduct a systematic analysis of material properties and characterization, and ultimately determine the ideal synthesis conditions for these materials.

In the first part of the study, we focused on optimizing the synthesis of Sodium Vanadium Phosphate. By investigating various synthesis conditions, such as annealing temperature, pressure, ascorbic acid content, and material …

Synthesis, Radiolabeling And Evaluation Of A Suite Of Tracers With 44Sc For Detecting Extracellular Dna, Zhiyao Li

McKelvey School of Engineering Theses & Dissertations

Neutrophil extracellular traps involve the rapid translocation of DNA to the outside of the cell under certain stimuli. This structure forms a fibrous network that is able to limit the spread of pathogens and to kill microorganisms. It has also been shown to be present in various pathological processes such as inflammation, autoimmune diseases, and cancer metastasis. Currently, the formation process of NETs in vivo is being extensively studied. However noninvasive detection and quantitation has yet to be achieved. A class of PET tracers are described here that consists of a DNA dye as the backbone that is labeled with …

The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow

Arts & Sciences Electronic Theses and Dissertations

This dissertation covers a wide range of topics but is linked by the common theme of radiation interacting with materials and studying the result of those interactions. The introduction describes the fundamentals of how radiation interacts with material and how we are able to detect that radiation and the application of how we use those interactions in radiation oncology. The thesis starts with a chapter detailing the temperature dependence of the photophysics in two organic scintillators. This chapter is the foundation for a future study that will look the degree to which these scintillators can distinguish between gammas and neutrons …

Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi

Arts & Sciences Electronic Theses and Dissertations

Ultrasensitive detection and quantification of soluble, secreted and cell surface-bound proteins is critical for advancing our understanding of cellular systems, enabling effective drug development, novel therapies, and bio-diagnostics. However, exiting technologies are largely limited by their sensitivity, making the detection and quantification of low-abundant proteins extremely challenging. This forms a major barrier in various fields of biology and biomedical sciences. In this work, we introduce novel cellular analysis methodologies based on plasmon-enhanced fluorescence for analyzing cell structure and probing surface and secreted proteins from cells. In the first part, we introduce plasmon-enhanced expansion microscopy and demonstrate the effectiveness of employing …

Investigating Applications Of Deep Learning For Diagnosis Of Post Traumatic Elbow Disease, Hugh James

McKelvey School of Engineering Theses & Dissertations

Traumatic events such as dislocation, breaks, and arthritis of musculoskeletal joints can cause the development of post-traumatic joint contracture (PTJC). Clinically, noninvasive techniques such as Magnetic Resonance Imaging (MRI) scans are used to analyze the disease. Such procedures require a patient to sit sedentary for long periods of time and can be expensive as well. Additionally, years of practice and experience are required for clinicians to accurately recognize the diseased anterior capsule region and make an accurate diagnosis. Manual tracing of the anterior capsule is done to help with diagnosis but is subjective and timely. As a result, there is …

Six-Dimensional Single-Molecule Imaging With Isotropic Resolution Using A Multi-View Reflector Microscope, Oumeng Zhang, Zijian Guo, Yuanyuan He, Tingting Wu, Michael D. Vahey, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Imaging of both the positions and orientations of single fluorophores, termed single-molecule orientation-localization microscopy, is a powerful tool for the study of biochemical processes. However, the limited photon budget associated with single-molecule fluorescence makes high-dimensional imaging with isotropic, nanoscale spatial resolution a formidable challenge. Here we realize a radially and azimuthally polarized multi-view reflector (raMVR) microscope for the imaging of the three-dimensional (3D) positions and 3D orientations of single molecules, with precisions of 10.9 nm and 2.0° over a 1.5-μm depth range. The raMVR microscope achieves 6D super-resolution imaging of Nile red molecules transiently bound to lipid-coated spheres, accurately resolving …

Speeding Up The Quantification Of Contrast Sensitivity Functions Using Multidimensional Bayesian Active Learning, Shohaib Shaffiey

McKelvey School of Engineering Theses & Dissertations

No abstract provided.

Dynamics Of Spatiotemporal Heterogeneities In Particulate Intercalation Electrodes, Shubham Agrawal

McKelvey School of Engineering Theses & Dissertations

Electrochemical energy systems rely on particulate porous electrodes to store or convert energies. While the three-dimensional porous structures of the electrodes were introduced to maximize the interfacial area for better overall performance of the system, spatiotemporal heterogeneities arising from materials thermodynamics localize the charge transfer processes onto a limited portion of the available interfaces. These reaction heterogeneities may cause local hot and cold spots, and early battery failures. This dissertation focuses on the following three aspects of the dynamic reaction heterogeneities in the particulate cathodes and anodes in the lithium-ion batteries: (i) the real-time evolution of reaction heterogeneities in graphite …

Evaluation And Clinical Implementation Of A Dual-Energy Ct Stopping-Power Ratio Mapping Technique For Proton-Therapy Treatment Planning, Maria Jose Medrano Matamoros

McKelvey School of Engineering Theses & Dissertations

Proton radiotherapy has the potential to treat tumors with better conformal dose distribution than competing modalities when the rapid dose falloff at the end of the proton-beam range is correctly aligned to the edge of the clinical target volume (CTV). However, its clinical potential is dependent on the accurate localization of the Bragg-peak position from predicted stopping-power ratio maps. The method that is most commonly used in today’s clinical practice for predicting stopping-power ratio (SPR) consists of a stoichiometric calibrationtechnique based on single-energy CT (SECT) for direct estimation of patient-specific SPR distribution from vendor-reconstructed Hounsfield Unit (HU) images. Unfortunately, this …

Fate Of Metals In Presence Of Minerals And Mineral-Organic Assemblages, Neha Sharma

McKelvey School of Engineering Theses & Dissertations

Metals can enter aquatic systems from natural and anthropogenic processes associated with weathering, sediment re-suspension, industrial activities, and atmospheric deposition. Metals pose health and environmental risks at high concentrations due to their potential toxicity and bioaccumulation, but many trace metals also serve as essential micronutrients for biogeochemical processes in natural aquatic systems. Biogeochemical processes such as methanogenesis, denitrification, and mercury methylation require transition metals such as nickel (Ni), cobalt (Co), copper (Cu), and molybdenum (Mo) for completion. These biogeochemical processes can be substantial contributors of greenhouse gases, such as methane (CH4) and nitrous oxide (N2O), into the atmosphere. The behavior, …

Model-Based Deep Learning For Computational Imaging, Xiaojian Xu

McKelvey School of Engineering Theses & Dissertations

This dissertation addresses model-based deep learning for computational imaging. The motivation of our work is driven by the increasing interests in the combination of imaging model, which provides data-consistency guarantees to the observed measurements, and deep learning, which provides advanced prior modeling driven by data. Following this idea, we develop multiple algorithms by integrating the classical model-based optimization and modern deep learning to enable efficient and reliable imaging. We demonstrate the performance of our algorithms by validating their performance on various imaging applications and providing rigorous theoretical analysis.

The dissertation evaluates and extends three general frameworks, plug-and-play priors (PnP), regularized …

Plasmonic Nanomaterials-Based Point-Of-Care Biosensors, Rohit Gupta

McKelvey School of Engineering Theses & Dissertations

Point-of-care (POC) biosensors, although rapid and easy-to-use, are orders magnitude less sensitive than laboratory-based tests. Further they are plagued by poor stability of recognition element thus limiting its widespread applicability in resource-limited settings. Therefore, there is a critical need for realizing stable POC biosensors with sensitivity comparable to gold-standard laboratory-based tests. This challenge constitutes the fundamental basis of this dissertation work– to expand access to quality and accurate biodiagnostic tools. At the heart of these solutions lies plasmonic nanoparticles which exhibit unique optical properties which are attractive for label-free and labelled biosensors.Firstly, we improve the stability and applicability of label-free …

Modeling, Analysis, And Simulation To Reveal The Mechanisms Of Ciliary Beating, Louis Woodhams

McKelvey School of Engineering Theses & Dissertations

Cilia are microscopic cellular appendages that help us breathe by clearing our airways, maintain the health of our central nervous system by circulating cerebrospinal fluid, and allow us to reproduce by transporting eggs and propelling sperm cells. Cilia even determine the asymmetry of our internal organs during embryonic development. However, the mechanisms underlying ciliary beating are not fully understood. Questions remain as to how arrays of the motor protein dynein generate the propulsive waveforms observed in cilia and how structural elements within the cilium and its connection to the cell deform during beating. In the current work, mathematical modeling, analysis, …

Development Of The Assessment Of Clinical Prediction Model Transportability (Apt) Checklist, Sean Chonghwan Yu

McKelvey School of Engineering Theses & Dissertations

Clinical Prediction Models (CPM) have long been used for Clinical Decision Support (CDS) initially based on simple clinical scoring systems, and increasingly based on complex machine learning models relying on large-scale Electronic Health Record (EHR) data. External implementation – or the application of CPMs on sites where it was not originally developed – is valuable as it reduces the need for redundant de novo CPM development, enables CPM usage by low resource organizations, facilitates external validation studies, and encourages collaborative development of CPMs. Further, adoption of externally developed CPMs has been facilitated by ongoing interoperability efforts in standards, policy, and …

Design & Analysis Of Mixed-Mode Integrated Circuit For Pulse-Shape Discrimination, Bryan Orabutt

McKelvey School of Engineering Theses & Dissertations

In nuclear science experiments it is usually necessary to determine the type of radiation, its energy and direction with considerable accuracy. The detection of neutrons and discriminating them from gamma rays is particularly difficult. A popular method of doing so is to measure characteristics intrinsic to the pulse shape of each radiation type in order to perform pulse-shape discrimination (PSD).

Historically, PSD capable systems have been designed with two approaches in mind: specialized analog circuitry, or digital signal processing (DSP). In this work we propose a PSD capable circuit topology using techniques from both the analog and DSP domains. We …

Resolving The Three-Dimensional Rotational And Translational Dynamics Of Single Molecules Using Radially And Azimuthally Polarized Fluorescence, Oumeng Zhang, Weiyan Zhou, Jin Lu, Tingting Wu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

We report a radially and azimuthally polarized (raPol) microscope for high detection and estimation performance in single-molecule orientation-localization microscopy (SMOLM). With 5000 photons detected from Nile red (NR) transiently bound within supported lipid bilayers (SLBs), raPol SMOLM achieves 2.9 nm localization precision, 1.5° orientation precision, and 0.17 sr precision in estimating rotational wobble. Within DPPC SLBs, SMOLM imaging reveals the existence of randomly oriented binding pockets that prevent NR from freely exploring all orientations. Treating the SLBs with cholesterol-loaded methyl-β-cyclodextrin (MβCD-chol) causes NR’s orientational diffusion to be dramatically reduced, but curiously NR’s median lateral displacements drastically increase from 20.8 to …

Interfacial Engineering And Photoelectrochemistry Of Patterned Metal/Semiconductor Heterostructures, Che Tan

McKelvey School of Engineering Theses & Dissertations

Photoelectrochemical (PEC) cells enable the conversion of solar energy into storable fuels, which is critical in overcoming the intermittent nature of this largest renewable source. However, the majority of semiconductors used as photoelectrodes in these cells have low conversion efficiencies and/or stabilities. Silicon (Si) is an attractive semiconductor material for photoelectrodes, but the development of efficient Si-based photoanodes is challenging due to their instability in alkaline solutions. Thus, one focus of this dissertation is the design and fabrication of highly stable nickel (Ni)-patterned Si photoanodes through interfacial engineering of the barrier heights. Recently, hot carriers in plasmonic metal nanostructures have …

Single-Molecule Localization Microscopy Of 3d Orientation And Anisotropic Wobble Using A Polarized Vortex Point Spread Function, Tianben Ding, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Within condensed matter, single fluorophores are sensitive probes of their chemical environments, but it is difficult to use their limited photon budget to image precisely their positions, 3D orientations, and rotational diffusion simultaneously. We demonstrate the polarized vortex point spread function (PSF) for measuring these parameters, including characterizing the anisotropy of a molecule’s wobble, simultaneously from a single image. Even when imaging dim emitters (∼500 photons detected), the polarized vortex PSF can obtain 12 nm localization precision, 4°–8° orientation precision, and 26° wobble precision. We use the vortex PSF to measure the emission anisotropy of fluorescent beads, the wobble dynamics …

The Challenges Of Applying Computational Legal Analysis To Mhealth Security And Privacy Regulations, Brian Tung

McKelvey School of Engineering Theses & Dissertations

As our world has grown in complexity, so have our laws. By one measure, the United States Code has grown over 30x as long since 1935, and the 186,000-page Code of Federal Regulations has grown almost 10x in length since 1938. Our growing legal system is too complicated; it’s impossible for people to know all the laws that apply to them. However, people are still subject to the law, even if they are unfamiliar with it. Therein lies the need for computational legal analysis. Tools of computation (e.g., data visualization, algorithms, and artificial intelligence) have the potential to transform civic …

Machine Learning For Analog/Mixed-Signal Integrated Circuit Design Automation, Weidong Cao

McKelvey School of Engineering Theses & Dissertations

Analog/mixed-signal (AMS) integrated circuits (ICs) play an essential role in electronic systems by processing analog signals and performing data conversion to bridge the analog physical world and our digital information world.Their ubiquitousness powers diverse applications ranging from smart devices and autonomous cars to crucial infrastructures. Despite such critical importance, conventional design strategies of AMS circuits still follow an expensive and time-consuming manual process and are unable to meet the exponentially-growing productivity demands from industry and satisfy the rapidly-changing design specifications from many emerging applications. Design automation of AMS IC is thus the key to tackling these challenges and has been …

Continuous-Time And Complex Growth Transforms For Analog Computing And Optimization, Oindrila Chatterjee

McKelvey School of Engineering Theses & Dissertations

Analog computing is a promising and practical candidate for solving complex computational problems involving algebraic and differential equations. At the fundamental level, an analog computing framework can be viewed as a dynamical system that evolves following fundamental physical principles, like energy minimization, to solve a computing task. Additionally, conservation laws, such as conservation of charge, energy, or mass, provide a natural way to couple and constrain spatially separated variables. Taking a cue from these observations, in this dissertation, I have explored a novel dynamical system-based computing framework that exploits naturally occurring analog conservation constraints to solve a variety of optimization …

A Neuromorphic Machine Learning Framework Based On The Growth Transform Dynamical System, Ahana Gangopadhyay

McKelvey School of Engineering Theses & Dissertations

As computation increasingly moves from the cloud to the source of data collection, there is a growing demand for specialized machine learning algorithms that can perform learning and inference at the edge in energy and resource-constrained environments. In this regard, we can take inspiration from small biological systems like insect brains that exhibit high energy-efficiency within a small form-factor, and show superior cognitive performance using fewer, coarser neural operations (action potentials or spikes) than the high-precision floating-point operations used in deep learning platforms. Attempts at bridging this gap using neuromorphic hardware has produced silicon brains that are orders of magnitude …

Photoacoustic Imaging, Feature Extraction, And Machine Learning Implementation For Ovarian And Colorectal Cancer Diagnosis, Eghbal Amidi

McKelvey School of Engineering Theses & Dissertations

Among all cancers related to women’s reproductive systems, ovarian cancer has the highest mortality rate. Pelvic examination, transvaginal ultrasound (TVUS), and blood testing for cancer antigen 125 (CA-125), are the conventional screening tools for ovarian cancer, but they offer very low specificity. Other tools, such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET), also have limitations in detecting small lesions. In the USA, considering men and women separately, colorectal cancer is the third most common cause of death related to cancer; for men and women combined, it is the second leading cause of cancer deaths. …

Algebraic, Computational, And Data-Driven Methods For Control-Theoretic Analysis And Learning Of Ensemble Systems, Wei Miao

McKelvey School of Engineering Theses & Dissertations

In this thesis, we study a class of problems involving a population of dynamical systems under a common control signal, namely, ensemble systems, through both control-theoretic and data-driven perspectives. These problems are stemmed from the growing need to understand and manipulate large collections of dynamical systems in emerging scientific areas such as quantum control, neuroscience, and magnetic resonance imaging. We examine fundamental control-theoretic properties such as ensemble controllability of ensemble systems and ensemble reachability of ensemble states, and propose ensemble control design approaches to devise control signals that steer ensemble systems to desired profiles. We show that these control-theoretic properties …

Improving Additional Adversarial Robustness For Classification, Michael Guo

McKelvey School of Engineering Theses & Dissertations

Although neural networks have achieved remarkable success on classification, adversarial robustness is still a significant concern. There are now a series of approaches for designing adversarial examples and methods to defending against them. This paper consists of two projects. In our first work, we propose an approach by leveraging cognitive salience to enhance additional robustness on top of these methods. Specifically, for image classification, we split an image into the foreground (salient region) and background (the rest) and allow significantly larger adversarial perturbations in the background to produce stronger attacks. Furthermore, we show that adversarial training with dual-perturbation attacks yield …

Interaction Of Aqueous U(Vi) With Goethite, Montmorillonite, And Uo2(S), Anshuman Satpathy

McKelvey School of Engineering Theses & Dissertations

Uranium contamination in subsurface environments is a matter of great concern throughout the world. Fate and transport of uranium in the subsurface can be controlled by U(VI) adsorption and reduction onto common iron (oxy)hydroxides and clay minerals. Aqueous U(VI) can also exchange uranium atoms with solids comprised of uranium which can potentially lead to changes in the morphology of the uranium-containing solids and affect their stability. First, the performance of multiple surface complexation models (SCMs) on adsorption of U(VI) onto goethite was analyzed for a broad range of input conditions. Individual models could fit the data for which they were …

Assessment And Diagnosis Of Human Colorectal And Ovarian Cancer Using Optical Imaging And Computer-Aided Diagnosis, Yifeng Zeng

McKelvey School of Engineering Theses & Dissertations

Tissue optical scattering has recently emerged as an important diagnosis parameter associated with early tumor development and progression. To characterize the differences between benign and malignant colorectal tissues, we have created an automated optical scattering coefficient mapping algorithm using an optical coherence tomography (OCT) system. A novel feature called the angular spectrum index quantifies the scattering coefficient distribution. In addition to scattering, subsurface morphological changes are also associated with the development of colorectal cancer. We have observed a specific mucosa structure indicating normal human colorectal tissue, and have developed a real-time pattern recognition neural network to localize this specific structure …

A Collaborative Knowledge-Based Security Risk Assessments Solution Using Blockchains, Tara Thaer Salman

McKelvey School of Engineering Theses & Dissertations

Artificial intelligence and machine learning have recently gained wide adaptation in building intelligent yet simple and proactive security risk assessment solutions. Intrusion identification, malware detection, and threat intelligence are examples of security risk assessment applications that have been revolutionized with these breakthrough technologies. With the increased risk and severity of cyber-attacks and the distributed nature of modern threats and vulnerabilities, it becomes critical to pose a distributed intelligent assessment solution that evaluates security risks collaboratively. Blockchain, as a decade-old successful distributed ledger technology, has the potential to build such collaborative solutions. However, in order to be used for such solutions, …

Metal Salt Hydrolysis For Electrochemically Active Conducting Polymer Nanocomposites, Hongmin Wang

Arts & Sciences Electronic Theses and Dissertations

The diversity of nanostructures obtained from organic polymerization is limited when compared to the vast amount of inorganic nanostructures. This dissertation will focus on a synergistic mechanism between organic polymerization and in situ inorganic salt hydrolysis for developing electrochemically active organic-inorganic hybrid nanostructures. The degree of polymerization, crystallinity and doping level of the conjugated polymer backbone is controlled using oxidative radical vapor-phase polymerization resulting in organic semiconductors featuring high crystallinity and superior electrical conductivity. An aqueous metal salt solution of iron (III) chloride serves as an oxidant for initiating the polymerization and interestingly, this inorganic salt hydrolyzes in situ producing …