Biomedical Engineering and Bioengineering Commons^™

Deciphering The Rules Of Odor-Driven Learning In The Fruit Fly Olfactory System, Cole B. Hanan

McKelvey School of Engineering Graduate Student Theses & Dissertations

Odorant identity is encoded by patterns of activity across olfactory receptor neurons (ORNs) and their corresponding glomeruli in the antennal lobe (AL). An odorant's valence can be modified by experience, allowing animals to associate previously neutral odors with appetitive or aversive outcomes. However, some odors appear resistant to such reassignment, and the factors determining whether an odor can acquire learned valence and whether that association generalizes to chemically related odors remain poorly understood. This thesis uses Drosophila melanogaster to address this question using a fully automated proboscis extension reflex (PER) conditioning assay. Odorants are presented via a computer-controlled olfactometer, reward …

A Functional Ultrasound Imaging (Fusi) Pipeline For Investigating Brain-Wide Hemodynamics During Torpor-Like Hypothermia, Owen J. Culver

McKelvey School of Engineering Graduate Student Theses & Dissertations

Torpor is a regulated state of reduced metabolic demand that enables animals to conserve energy under unfavorable environmental conditions. The controlled induction of a similar state, termed synthetic torpor, has potential applications in ischemic protection, organ preservation, cancer treatment, radiation protection, and long-term spaceflight. Although neuronal populations within the preoptic hypothalamus have been shown to initiate hypothermic and hypometabolic states, the distributed cerebral hemodynamic dynamics accompanying their induction and maintenance remain poorly understood. In this thesis, we developed an accessible functional ultrasound imaging (fUSI) acquisition and analysis pipeline and applied it to investigate cerebral hemodynamics during chemogenetic activation of the …

Single Fluorogens And Orientation-Localization Microscopy For Quantifying Chemical And Biomolecular Dynamics At The Nanoscale, Yiyang Chen, Yuanxin Qiu, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Many chemical systems look uniform only because ensemble measurements average over their most interesting molecules. Electron-transfer rates vary across electrode surfaces; lipid membranes contain nanodomains with distinct packing and fluidity; peptide aggregates exhibit local polymorphism; and biomolecular condensates contain transient networks of interactions that are blurred in ensemble images. A central challenge in chemical imaging is not simply to see smaller structures, but to measure chemical variables such as polarity, redox potential, and molecular confinement at the single-molecule level. In this Account, we describe how fluorogens, molecules whose brightness, blinking, spectral shifts, orientation, rotational mobility, and motion are directly shaped …

Laponite Nanosilicate As A Platform For Antigen–Adjuvant Co-Delivery In Vaccination, Haoyu Qi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Nanosilicates are two-dimensional, charged nanomaterials with tunable surface chemistry that enable electrostatic interactions with proteins and nucleic acids. These properties make Laponite nanosilicate a promising platform for vaccine delivery, where coordinated antigen–adjuvant presentation and lymph node delivery are important for shaping immune responses. This thesis investigated nanosilicates as scaffolds for lysozyme-based antigen delivery and co-delivery with CpG.

The preparation method reduced the apparent size of the NS–Lys–CpG complex at pH 10, although neutralization to pH 7 promoted larger aggregate formation. In vivo IVIS imaging after footpad injection showed persistent Cy7-associated fluorescence at the injection site for up to three weeks …

Cloud-Deployed Rna-Seq Analytics For Identifying Imaging And Therapeutic Targets In Chemotherapy-Induced Toxicities, Zhimu Wang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapy has significantly improved cancer survival rates; however, many anticancer agents induce severe acute and chronic side effects that substantially reduce patient quality of life and limit therapeutic efficacy. Despite their clinical importance, the molecular mechanisms underlying chemotherapy-induced toxicities across different organs remain incompletely understood, in part due to the lack of integrated, scalable, and accessible analytical platforms capable of synthesizing large transcriptomic datasets across tissues and experimental models.

This thesis describes the development of a cloud-deployed RNA-seq analytics platform designed to identify candidate imaging biomarkers and therapeutic targets associated with chemotherapy induced toxicities. The platform integrates large-scale transcriptomic datasets …

Optimization Of Refolding, Purification, And Analytical Characterization Of Proinsulin(F25d) Soluble Antigen Array Immunotherapy, Abigail Richardson

McKelvey School of Engineering Graduate Student Theses & Dissertations

Type 1 Diabetes (T1D) is characterized by autoreactive immune responses to insulin and its precursor, proinsulin. Soluble antigen arrays (SAgAs) displaying the metabolically inactive proinsulin variant, proinsulin(F25D), represent a promising antigen‑specific immunotherapy candidate for T1D. However, the production of these platforms is hindered by substantial practical challenges, including protein aggregation, inefficient refolding, and the lack of sensitive analytical tools to verify quality and dosage. This work establishes an integrated, scalable pipeline for the purification, conjugation, and quantification of a proinsulin(F25D) SAgA. First, we optimized the refolding of recombinant methionine-proinsulin(F25D) (M-PI(F25D)) from inclusion bodies using controlled buffer systems and created a …

Voltage-Sensor–Targeting Modulators Of Iks: Identifying Critical Functional Groups Of C28 Via Electrophysiology And Sar Modeling, Jiacheng Huang

McKelvey School of Engineering Graduate Student Theses & Dissertations

I_Ks (KCNQ1/KCNE1) channels are essential for cardiac repolarization, and their dysfunction contributes to arrhythmogenic disorders such as Long QT Syndrome type 1 (LQT1). Pharmacological activation of I_Ks has therefore emerged as a promising therapeutic strategy. C28, a recently identified voltage-sensor–targeting activator, has been shown to markedly shift KCNQ1/KCNE1 voltage dependence and enhance current amplitude, validating the voltage-sensing domain (VSD) as a druggable site. However, the structural determinants that underlie C28’s activity remain incompletely understood. In this study, we aimed to identify critical functional groups of C28 by screening a structurally diverse set of C28-like analogs and evaluating their …

Automated Segmentation And Structural Remodeling Analysis Of Ipsc-Derived Cardiomyocyte, Bahareh Bahmani

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cardiomyopathy is a disease of the heart muscle that can change cell structure, protein organization, and overall heart function. Some forms of cardiomyopathy are genetically inherited, including Hypertrophic Cardiomyopathy (HCM), the most common inherited cardiomyopathy affecting nearly 1 in 200 individuals1,2, and Desmin-Related Cardiomyopathy (DRM), a rarer disease that affects approximately 1 in 2000 individuals3. Changes in cardiomyocytes’ cellular structure define cardiomyopathies, and these changes are typically studied with fluorescence microscopy. However, manual image analysis is slow, labor-intensive, and often gives inconsistent results, especially when images are analyzed by non-experts. This thesis presents an automated computational framework for analyzing cardiomyocyte …

Multiscale Architecture Governs Stability In Suction-Actuated Variable Stiffness Catheters, Sheridan Lee

McKelvey School of Engineering Graduate Student Theses & Dissertations

Endovascular procedures require devices with widely varying mechanical properties: flexibility for navigating tortuous vessels and rigidity for stable therapeutic delivery. Suction-actuated variable stiffness sheaths address this challenge by incorporating axial wire string arrays that mechanically couple under suction to increase flexural rigidity. However, prototype devices achieve stiffening ratios below theoretical predictions, suggesting that interlayer mechanics and string positioning play a critical role. This study investigates whether interweaving polytetrafluoroethylene (PTFE) tape within the string array enhances flexural rigidity modulation and curvature stability. Prototype devices with varying wrap configurations were fabricated and evaluated using flexural testing, curvature stability testing, and mathematical modeling. …

Opportunistic Breast Cancer Detection With Photon-Counting Ct: A Quantitative Pilot Study Of Reconstruction-Dependent Image Quality, Graham Hannon

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photon-counting computed tomography (PCCT) has emerged as a promising imaging modality with improved spatial resolution and contrast capabilities compared to conventional energy-integrating detector systems. These advantages present an opportunity for opportunistic detection of breast cancer in routine thoracic CT scans that include breast tissue. In this pilot study, we evaluated the feasibility of opportunistic breast cancer detection using clinical PCCT data through quantitative image analysis. Two patients with confirmed breast malignancies and corresponding thoracic PCCT scans were retrospectively analyzed. Dedicated reconstructions were performed with varying convolution kernels, field-of-view sizes, and virtual monoenergetic spectra. Image quality was assessed using signal-to-noise ratio …

Sensing Negative-Cone Rotational Diffusion Of Dipole-Like Emitters, Yuanxin Qiu, Kaizhi A. Nie, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Fluorescence anisotropy and single-molecule orientation-localization microscopy (SMOLM) are powerful techniques that quantify the rotational diffusion of dipole-like emitters, which is important for sensing molecular interactions and chemical environments at the nanoscale. Numerous theoretical and experimental studies have thoroughly characterized single-molecule rotations even when those rotations are much faster than the detector integration time. Here, we extend the theory of measuring rotational diffusion to situations where a single dipole rotates uniformly everywhere outside of an isotropic cone of a certain size, termed a negative cone. This scenario corresponds to negative fluorescence anisotropy 𝑟 and has been observed in emitters exhibiting strong …

Optimization Of Research Pipeline To Characterize The Effects Of Atp-Sensitive Potassium Channels Mutations On Native Skeletal Muscle Fibers And Evaluate Potential Drug Therapy, Yuezhou Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

The ATP-sensitive potassium (KATP) channel is a critical metabolic sensor in skeletal muscle, yet its definitive molecular composition and functional roles remain contested. In this study, I conclusively demonstrate that the Kir6.2/SUR2 complex forms sarcolemmal KATP channel in mouse fast-twitch muscle. Genetic knock-out (KO) of Kir6.2 (Kcnj11−/−) or SUR2 (Abcc9−/−) resulted in a similar phenotype with increased fatigue resistance and a pathological rise in unstimulated resting tension at high-frequency stimulation. In contrast, SUR1 (Abcc8−/−) KO was ineffective. Furthermore, a CRISPR/Cas9 knock-in mouse model of a human SUR2A truncation variant (KCGV/KCGV) recapitulated the abnormal force accumulation, demonstrating that even loss-of-function of …

Functional Characterization Of Abcc8 Mutations Potentially Linked To The Transition From Hyperinsulinemic Hypoglycemia To Diabetes, Hao Zhang

McKelvey School of Engineering Graduate Student Theses & Dissertations

ATP-sensitive potassium (KATP) channels, composed of the SUR1 and Kir6.2 subunits encoded by the ABCC8 and KCNJ11 genes, are critical regulators of membrane excitability and insulin secretion in pancreatic β-cells. Gain-of-function (GOF) mutations in these genes cause neonatal diabetes mellitus through impaired insulin secretion and persistent hyperglycemia, whereas loss-of-function (LOF) mutations lead to congenital hyperinsulinism (CHI) with hypoglycemia due to β-cell hyperexcitability. I have addressed a paradoxical form of maturity-onset diabetes of the young (MODY) arising from KATP mutations, in which patients transition from CHI to glucose intolerance later in life. My experiments indicate that many KATP mutations associated with …

Expansion Limits Of Meshed Split-Thickness Skin Grafts, Haomin Yu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Split-thickness skin grafts are widely used to treat chronic wounds. Procedure design requires surgeons to predict how much a patch of the patient's own skin expands when it is meshed with rows of slits and stretched over a larger wound area. Accurate prediction of graft expansion remains a challenge, with current models overestimating the actual expansion, leading to suboptimal outcomes. Inspired by the principles of mechanical metamaterials, we developed a model that distinguishes between the kinematic rearrangement of structural elements and their stretching, providing a more accurate prediction of skin graft expansion. Our model was validated against extensive data …

2d-Nanosilicate Carriers For Sustained Delivery Of Vaccine Components, Chih Yun Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Laponite® 2D Nanosilicates (NS) are disc-shaped platelets (~30 nm diameter, ~1 nm thick) with positively charged edges and negatively charged faces, capable of loading proteins, drugs, and nucleic acids via electrostatic interactions to form a house-of-cards gel that sequesters cargo. Here, we evaluated NS for sustained delivery of antigens and Toll-like receptor (TLR) agonists to extend germinal center duration and enhance antibody quality. The model antigen ovalbumin (OVA) was adsorbed onto NS at acidic pH in a ~1:1 ratio, with partial unfolding that remained stable at physiological pH. NS-OVA complexes were efficiently internalized by dendritic cells, with uptake driven primarily …

Single-Molecule Orientation And Localization Microscopy, Sophie Brasselet, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Single-molecule localization microscopy (SMLM) offers enhanced spatial resolution in optical microscopy, providing detailed insights into the spatial organization of proteins in cells at the nanoscale. Over the past decade, SMLM has progressively incorporated the capability to retrieve the orientations of single molecules using their polarized dipolar emission pattern. Here we explore recent advancements in single-molecule orientation and localization microscopy (SMOLM), which yields super-resolved images of molecular three-dimensional (3D) orientations, wobble and 3D positions. This advancement opens possibilities to explore the nanoscale organization and conformation of biological molecules as well as to monitor and design local 3D optical fields in nanophotonics. …

Development Of A Light-Based Platform To Assess Cervical Mucus Barrier Function And Physical Mucus Properties, Elizabeth J. Buzbee

McKelvey School of Engineering Graduate Student Theses & Dissertations

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide, yet current clinical tools for predicting its risk lack specificity and reliability. Cervical mucus plays a crucial role in maintaining pregnancy by forming a barrier that protects the uterus against infection. This study investigates the use of laser speckle rheology as a noninvasive technique to assess cervical mucus biomechanics. Synthetic cervical mucus was fabricated at varying hydration levels and tested using a conventional rheometer that confirmed that the mechanical properties of the synthetic mucus samples were representative of physiological cervical mucus. These results were compared to the complex …

Direct Computations Of Spatially Resolved Viscoelastic Moduli Of Biomolecular Condensates, Liwen Gu

McKelvey School of Engineering Graduate Student Theses & Dissertations

Biomolecular condensates are viscoelastic materials formed by liquid-liquid phase separations (LLPS) of biopolymers. In this study, we develop a modified graph Laplacian-based collective model to characterize viscoelastic heterogeneity within condensates based on results of lattice-based Metropolis Monte Carlo (MMC) simulations. By integrating random graph models and simulations of A1-LCD, a type of intrinsically disordered protein, we examine how network topology influences storage modulus, loss modulus, crossover frequency, and relaxation time spectra. Our results reveal a strong correlation between topological features and mechanical response, with the condensate interior exhibiting higher stiffness and faster relaxation than the interface. The relaxation spectra provide …

The Role Of Piezo1 In Mediating Chondrocyte Cell Signaling And Senescence, Sophie Gretler Paradi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Osteoarthritis (OA), the leading cause of disability, is driven by articular cartilage degeneration and inflammation. Mechanosensitive ion channels PIEZO1 and PIEZO2 have been implicated in OA progression via calcium signaling in chondrocytes. This study investigates the role of conditional Piezo channel knockout (cKO) in modulating calcium signaling and senescence in OA, particularly under the supra-physiologic inflammatory condition of a high-fat diet (HFD). Using calcium imaging, we found that Piezo1 cKO and dual Piezo1/2 cKO significantly reduced Yoda1-induced calcium signaling, while Piezo2 cKO alone had no effect. Under HFD conditions, Piezo1 cKO showed a non-significant trend toward reduced calcium influx, potentially …

Automated Beam Stitching And Segmentation Procedure For Space Division Multiplexing Optical Coherence Tomography Angiography, Andrew J. Song

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical Coherence Tomography Angiography (OCTA) has revolutionized ophthalmic imaging and its capability to produce high-resolution 3D maps of the retinal microvasculature is instrumental in diagnosing retinovascular diseases such as diabetic retinopathy and age-related macular degeneration; However, the existing OCTA devices often suffer from slow acquisition speed limiting the field-of-view (FOV) in the clinic. Space Division Multiplexing OCTA (SDM-OCTA) address these limitations by acquiring multiple beams simultaneously, achieving manyfold faster acquisition speeds than single beam OCTA systems. But as each beam contains only part of the image, SDM-OCTA requires additional processing steps to produce coherent wide-field images. Though manual stitching and …

A Neuroimmune Circuit Mediates Chemo Brain Pathology, Daniel Ahmadi

McKelvey School of Engineering Graduate Student Theses & Dissertations

Chemotherapeutic agents, while effective in targeting malignant tumors, often reduce the patients’ quality of life by inducing fatigue, pain, and motivational deficits. These symptoms are collectively referred to as “chemo brain.” The mechanisms underlying these adverse effects, and specifically whether fatigue and motivational impairments share a common etiology, remain poorly understood. The neural–immune substrates of these symptoms remain obscure, in part because standard preclinical regimens either bypass key systemic signals or introduce local toxicity confounds. Here, I establish and validate a three‑day, low‑dose intravenous cisplatin protocol that avoids peritoneal inflammation and severe renal injury yet produces robust, reversible fatigue and …

Painting Rich Six-Dimensional Pictures Using Polarized Fluorescence Microscopy, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

No abstract provided.

Characterizing Locust Anemotaxis: The Impact Of Sensory Perturbations On Flight Behavior, Yi-Xiao Huang

McKelvey School of Engineering Graduate Student Theses & Dissertations

This thesis investigates the effects of sensory perturbations on locust flight behavior, with the goal of better understanding how locusts integrate multiple sensory inputs to maintain flight control. Through a series of experiments, locusts were subjected to visual impairment, turbulent wind conditions, mechanical impairments of their wings and antennae, and pheromonal interference. These perturbations allowed for the exploration of the contributions each sensory pathway makes to flight stability and navigation in a controlled environment.

Results show that while visual impairment does not significantly impact average flight speed, it increases variability in flight stability, suggesting that visual cues are important for …

Single-Molecule Orientation Imaging Reveals The Nano-Architecture Of Amyloid Fibrils Undergoing Growth And Decay, Brian Sun, Tianben Ding, Weiyan Zhou, Tara S. Porter, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid-beta (Aβ42) aggregates are characteristic Alzheimer’s disease signatures, but probing how their nanoscale architectures influence their growth and decay remains challenging using current technologies. Here, we apply time-lapse single-molecule orientation-localization microscopy (SMOLM) to measure the orientations and rotational “wobble” of Nile blue (NB) molecules transiently binding to Aβ42 fibrils. We correlate fibril architectures measured by SMOLM with their growth and decay over the course of 5 to 20 min visualized by single-molecule localization microscopy (SMLM). We discover that stable Aβ42 fibrils tend to be well-ordered and signified by well-aligned NB orientations and small wobble. SMOLM also shows that increasing order …

Data-Driven Insights Into Spatial Patterns And Disease Etiologies Of White Matter Hyperintensities, Sugandha Roy

McKelvey School of Engineering Graduate Student Theses & Dissertations

In this thesis, we have applied Orthogonal Projective Non-Negative Matrix Factorization (opNMF) to identify spatial patterns of white matter hyperintensities (WMH) within UK Biobank's imaging data. Our selection criteria excluded subjects with a history of neurological, mental, and specific cerebrovascular conditions, allowing us to focus on WMH patterns in a healthy aging population. We have interrogated the association of location-specific WMHs with a variety of demographic, clinical, and genetic factors. Our multivariable regression analysis evaluates the strength and nature of the associations between these factors and WMH distribution. The analysis integrates variables such as age, sex, smoking habits, medication usage …

An Attention Lstm U-Net Model For Drosophila Melanogaster Heart Tube Segmentation, Xiangping Ouyang

McKelvey School of Engineering Graduate Student Theses & Dissertations

Machine learning is commonly used in biomedical image analysis, as it allows automated image segmentation and identification that minimizes the need for tedious human involvement. Drosophila melanogaster is often used as a cardiac disease model, where optical coherence microscopy (OCM) is used to image and analyze its beating dynamics. As OCM often generates a large volume of images, automated image segmentation is necessary to quantify the heart beating efficiently. Our most recent heart segmentation model, FlyNet 2.0+, is a fully convolutional LSTM U-Net model. However, the performance of the model diminishes in the presence of artifacts, such as image reflection …

Calcium Analysis Of Intercellular Communications Between Alpha Cells And Delta Cells Across The Pancreatic Islet, Shichao Gao

McKelvey School of Engineering Graduate Student Theses & Dissertations

The intricate communication between different cell types within pancreatic islets plays a crucial role in regulating glucose homeostasis. Among these cellular interactions, the interplay between α cells (responsible for glucagon secretion) and δ cells (secreting somatostatin) is particularly intriguing due to the inhibitory effects of somatostatin on glucagon release. Understanding the intercellular interactions between α and δ cells may provide insights into the mechanisms underlying the coordinated regulation of blood glucose levels. In this study, we employed a multi-modal approach combining confocal imaging, image analysis, and correlation network analysis to investigate the spatial relationships and potential functional connections between α …

Structured Light Radial-View Endoscope Imaging Development For Evaluation Of Human Tissue, Xiyan Li

McKelvey School of Engineering Graduate Student Theses & Dissertations

In this thesis, we improved an existing structured light methodology to more accurately estimate tissue optical properties imaged in a single snapshot. The developed approach is a major enhancement of the traditional three-phase spatial frequency domain imaging system: It greatly simplifies the operational procedure while also maintaining high accuracy in optical property measurements .

Leveraging this improved approach, we have developed a low-cost, compact, and radial-view endoscope prototype. This prototype combines affordability with high functionality and a user-friendly design. To assess the performance and reliability of our endoscope, we conducted comprehensive evaluations involving tissue-mimicking phantoms, as well as ex vivo …

Evaluating Neuroimaging Modalities In The A/T/N Framework: Single And Combined Fdg-Pet And T1-Weighted Mri For Alzheimer’S Diagnosis, Peiwang Liu

McKelvey School of Engineering Graduate Student Theses & Dissertations

With the escalating prevalence of dementia, particularly Alzheimer's Disease (AD), the need for early and precise diagnostic techniques is rising. This study delves into the comparative efficacy of Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and T1-weighted Magnetic Resonance Imaging (MRI) in diagnosing AD, where the integration of multimodal models is becoming a trend. Leveraging data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we employed linear Support Vector Machines (SVM) to assess the diagnostic potential of these modalities, both individually and in combination, within the AD continuum. Our analysis, under the A/T/N framework's 'N' category, reveals that FDG-PET consistently outperforms T1w-MRI across …

Integrating Implantable Bci Devices Within Bci2000 Using A Unified Framework And Toolchain For In-Vivo Research, Dhruva Mehta

McKelvey School of Engineering Graduate Student Theses & Dissertations

The field of neurotechnology research has a bright and promising future as more devices are created. However, there are still many gaps in the field as the potential for neuromodulation grows. Devices such as the Micro-Leads StimZ system and the Ripple Grapevine/Summit system help bridge that gap by allowing for a broader variety of closed-loop neuromodulation experiments to be implemented thanks to their portability and versatility. Despite these devices being on the market, however, there needs to be a method to collaborate and interact with them across multiple research institutions. BCI2000 helps to address that by creating a standardized working …