Biomedical Engineering and Bioengineering Commons^™

Development Of A Rapid Bacterial Quantification Method Based On Droplet Microfluidics, Shawn Bliss

Electronic Theses and Dissertations

The capacity to identify bacteria quickly and accurately is critical for applications such as medical diagnosis, environmental monitoring, and food safety. For instance, sepsis diagnosis requires blood cultures that take as long as 1-5 days, preventing timely intervention and increasing mortality rate. Here, we propose the joint use of microfluidics and a machine learning algorithm for rapid bacterial cell capture and quantification. The combination of high-throughput droplet microfluidics and a support vector machine (SVM) enables analysis and quantification of bacterial samples within as short as 4 hours. We have performed successful encapsulation of pathogenic bacteria such as E. coli, …

Acoustofluidic Delivery Of Biomolecules To Cells: A Novel Approach For Preparing Car-T Cells., Madison C. Colebank

Electronic Theses and Dissertations

The continuous pursuit of effective methods for gene transfection in primary human T cells is crucial for advancing cell-based therapies. Viral vectors, currently used in cell-based therapies, involve a lengthy and costly process. This thesis explores the efficacy of coupling acoustofluidic and sonoporation techniques as an alternative non-viral gene transfection approach with primary T cells. Sonoporation, in conjunction with microbubbles, has been demonstrated to induce cavitation, resulting in the formation of pores in the cell membrane through which molecules can enter. Using flow cytometry, we compared the loading efficiency of primary T cells with that of Jurkat T cells to …

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 …

Rockin’ Rehab: Novel Rocking Chair For Children With Spinal Cord Injury To Enable Trunk Muscle Activation And Detect Muscle Activation Patterns., Johnathan Jay George

Electronic Theses and Dissertations

Introduction: Activity-based locomotor training improves trunk control in children with spinal cord injury (SCI), and there is need for additional activities to allow these children to activate trunk muscles. The purpose of this research was to design, fabricate, and evaluate a rocking chair for children with SCI, and to investigate the activation of muscles during use. Sensorization of the chair to confirm muscle activation is also explored. Methods: Quality Function Deployment (QFD) design methodologies identified and ranked needs and features for the rocking chair. A design was developed and evaluated via finite element analysis. The chair was fabricated and tested …

Advancing Biological Applications Through Microfluidic-Based Tool Development, K.M. Taufiqur Rahman

Electronic Theses and Dissertations

This research undertook an interdisciplinary approach, integrating bioengineering, microbiology, molecular biology, and systems biology to investigate bacterial dynamics behavior. Specifically, it delved into the development of microfluidic devices for biological applications such as bacterial cell counts, real-time observation of plant roots (here, specialized lectin-coated microbeads are used that mimic root characteristics), and soil microbe interactions. Furthermore, Next-Generation Sequencing and systems biology methodologies were employed to explore the intricate, multifaceted survival mechanisms of Escherichia coli persister population. Studying and quantifying persisters or testing for the existence of VBNC (viable but nonculturable) is challenging. These experiments require precise counts. It has been …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Large - Scale Manufacturing Of Fluorescent Perfluorocarbon Nanoemulsions For Oxygen Delivery, Anneliese Troidle

Electronic Theses and Dissertations

Over 100,000 Americans are currently waiting for a life – saving organ transplant, yet 17 patients die daily waiting for a transplant they will never receive [1]. Preservation of organs is an area that has seen innovation throughout the years and can improve rates of transplantation, yet vascularized composite allotransplantation preservation has not followed suit [2]. Current standard of care is use of electrolyte solutions such as Histidine – Tryptophan – Ketoglutarate (HTK) or University of Wisconsin (UW) Solution, yet these perfusates lack an oxygen carrying component [3]. Hemoglobin – based oxygen carriers (HBOCs) …

Digital Twins Of The Living Knee: From Measurements To Model, Thor Erik Andreassen

Electronic Theses and Dissertations

Modern medicine has dramatically improved the lives of many. In orthopaedics, robotic surgery has given clinicians superior accuracy when performing interventions over conventional methods. Nevertheless, while these and many other methods are available to ensure treatments are performed successfully, far fewer methods exist to predict the proper treatment option for a given person. Clinicians are forced to categorize individuals, choosing the best treatment on “average.” However, many individuals differ significantly from the “average” person, for which many of these treatments are designed. Going forward, a method of testing, evaluating, and predicting different treatment options' short- and long-term effects on an …

Kinematic Analysis Of Gait And Deep Knee Flexion For Pre- And Post-Operative Total Knee Arthroplasty, Samantha Collins

Electronic Theses and Dissertations

Osteoarthritis (OA) is a form of arthritis that develops in the joint due to overuse and aging causing pain, discomfort, and disability. Total Knee Arthroplasty (TKA) is a surgical procedure performed when OA symptoms are severe with an estimated 600,000 patients in the United States currently receiving TKA. Studies have reported dissatisfaction of the knee for 14-39% of patients. This study collected knee kinematics before and after surgery using stereo radiography for precise measurement of gait and deep knee flexion activities. Results showed healthy knee kinematics were not restored and no significant changes could be seen from OA kinematics in …

Computational Methodology For Generating Patient-Specific Soft Tissue Representations, Ahilan Anantha Krishnan

Electronic Theses and Dissertations

This dissertation focused on modeling specimen-specific soft tissue structures in the context of joint replacement surgery. The research addressed four key aspects. The first study involved developing a workflow for creating finite element models of the hip capsule to replicate its torque-rotational response. Experimental data from ten cadaveric hips were used to calibrate the models, resulting in improved accuracy and relevance for surgical planning and implant design. The second study tackled the challenge of expediting the calibration of mechanical properties of the hip capsule to match patient-specific laxities. A statistical shape function model was proposed to generate patient-specific finite element …

Exploration Of Motion Capture System To Investigate Human Shoulder Kinematics, Ola Alsaadi

Electronic Theses and Dissertations

The glenohumeral joint (GH) is commonly conceptualized as a ball-and-socket joint [1], and its center of rotation (COR) is presumed to coincide with the geometric center of the medial-superior region of the humeral head [2]. Recent research has endorsed improvements in COR estimation through invasive and noninvasive techniques, including cadaver studies, stereophotogrammetry, and motion capture (MOCAP) systems. Despite increased interest in wearable technology within human movement analysis, the problem of COR estimation employing MOCAP systems and its validation against bi-planar fluoroscopy remains relatively unexplored.

This study employed a marker-based MOCAP system to compare the accuracy, error, and precision of three …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Development Of Air-Jetting System For Bioprinting Of Alginate Micro-Droplets, Nathan Lingenfelter

Electronic Theses and Dissertations

Transplantation of organoids has been demonstrated to be a promising cure to many diseases including Type-1 diabetes. However, achieving consistent and robust derivations of mature organoids from human pluripotent stem cells (hPSCs) is challenging. Cellular mechano-transduction, where mechanical stimuli is sensed and converted to biochemical signaling, has been proposed to overcome this challenge. This pathway relies on encapsulating hPSCs in a small volume of a biomaterial such as alginate, which has been widely used as cell encapsulation materials due to its biocompatibility and selective permeability. In this project, we focused on developing an air-jetting based technique to generate small and …

Hemodynamic Assessment Of Y-Incision Aortic Root Enlargement Using Computational Simulations, Astitwa Ghimire

Electronic Theses and Dissertations

The Yang procedure is a new aortic root enlargement technique used to enlarge the aortic annulus by multiple valve sizes. The procedure prevents patient prosthesis mismatch and establishes a viable platform for future valve-in-valve implantation. This study used the Yang procedure to investigate the hemodynamics in the aortic root and bioprosthetic valve regions after aortic root enlargement. Results indicate the velocity magnitude at the sinus regions of a patient who underwent the Yang procedure was slower, indicating risks of flow stasis and thrombosis. Simulation results denote computational models can be created for optimization of surgical procedures.

Development And Application Of A Microfluidic Platform For Quantifying Intra-Tumoral Compressive Stress., Zachary P. Fowler

Electronic Theses and Dissertations

Cancer progression is linked to the emergence of aberrant mechanical signaling in the tumor microenvironment. Modulation of extrinsic signals, such as ECM stiffness and composition, have been thoroughly explored. However, the development of solid stresses within the tumor remains poorly understood. To address this, we have developed a microfluidic platform that generates deformable alginate microbeads that allow for the quantification of compressive stresses generated within a growing glioblastoma (GBM) tumorsphere. PDMS microfluidic devices were fabricated via SU-8 mold with channels ranging from 10µm-40µm in diameter. Fluorescently labeled sodium alginate underwent a cross-linking reaction within the device to generate monodisperse beads …

Design And Evaluation Of A Multi-Functional Surgical Device For Microgravity Surgeries., Sienna Shacklette

Electronic Theses and Dissertations

No abstract provided.

Investigation Of Possible Inflammatory Response After Ultrasound And Microbubble Procedure In The Spinal Cord., Jenna Wilkerson

Electronic Theses and Dissertations

The purpose of this experiment is to explore the inflammatory effects of focused ultrasound paired with intravenously delivered microbubbles when used in the lumbar spinal cord. There are currently very few pharmaceuticals that can successfully enter the blood spinal cord barrier (BSCB). This technique used at the lumbar enlargement might allow targeted treatment of pathologies involving the spinal cord.

To test the possible inflammatory response of this technique, an animal experiment was performed. 15 animals were given a T12 laminectomy and allowed to fully recover. Once recovered, all animals received FUS+MB at L2 and were euthanized in groups of five …

Cad System For Early Diagnosis Of Diabetic Retinopathy Based On 3d Extracted Imaging Markers., Ahmed Sleman

Electronic Theses and Dissertations

This dissertation makes significant contributions to the field of ophthalmology, addressing the segmentation of retinal layers and the diagnosis of diabetic retinopathy (DR). The first contribution is a novel 3D segmentation approach that leverages the patientspecific anatomy of retinal layers. This approach demonstrates superior accuracy in segmenting all retinal layers from a 3D retinal image compared to current state-of-the-art methods. It also offers enhanced speed, enabling potential clinical applications. The proposed segmentation approach holds great potential for supporting surgical planning and guidance in retinal procedures such as retinal detachment repair or macular hole closure. Surgeons can benefit from the accurate …

A Virtual Method For Establishing Femoral Stem Position In Total Hip Arthroplasty, Samuel Mattei

Electronic Theses and Dissertations

Total hip arthroplasty (THA) is one of the most successful orthopedic surgeries performed, in which the hip joint is reconstructed to improve functionality and decrease pain in the joint. Despite the success of these procedures, femoral stem misalignment remains an area that influences THA success. The relationship between the femoral stem geometry and implanted femoral stem size and orientation is underreported due to limitations in the collection of radiographic data used for clinical pre-operative templating. Furthermore, the influence of anatomic measurements on the direction and size of the femoral stem are not considered due to imaging technique and difficulties associated …

Finite Element Modeling Of Patient-Specific Total Shoulder Arthroplasty, Ignacio Rivero Crespo

Electronic Theses and Dissertations

Total Shoulder Arthroplasty (TSA) is a surgical procedure designed to improve joint functionality by replacing the articulation between the humeral head and the glenoid fossa. Anatomic Total Shoulder Arthroplasty (aTSA) and Reverse Total Shoulder Arthroplasty (rTSA) are two types of replacement surgery to relieve pain and restore function of the shoulder. The overall goal of this study was to evaluate the effects of variation of certain patient and implant alignment parameters that may influence long-term outcomes of these surgical procedures, including kinematics, joint loads and contact mechanics. Computational models of six TSA subjects, three aTSA and three rTSA, were created …

Fully Coupled Fluid Structure Interaction Simulation Of Bioprosthetic Heart Valves: A Numerical And Experimental Analysis, Masod Sadipour

Electronic Theses and Dissertations

Aortic stenosis impacts approximately 7% of the global population. In the past decade, the role of computational modeling has been becoming considerably important in the design of BHVs. To obtain reliable solutions in computational modeling, it is essential to consider accurate properties of bioprosthetic heart valves (BHVs), such as density and mechanical properties. Previous computational studies assumed (bovine pericardium) BP used in BHVs density was comparable to water or blood. Yet, BP is subjected to multiple treatments like fixation and anti-calcification. In Chapter 2, I measured BP density and its effect on BHV leaflet stress and strain. In the second …

Patient Movement Monitoring Based On Imu And Deep Learning, Mohsen Sharifi Renani

Electronic Theses and Dissertations

Osteoarthritis (OA) is the leading cause of disability among the aging population in the United States and is frequently treated by replacing deteriorated joints with metal and plastic components. Developing better quantitative measures of movement quality to track patients longitudinally in their own homes would enable personalized treatment plans and hasten the advancement of promising new interventions. Wearable sensors and machine learning used to quantify patient movement could revolutionize the diagnosis and treatment of movement disorders. The purpose of this dissertation was to overcome technical challenges associated with the use of wearable sensors, specifically Inertial Measurement Units (IMUs), as a …

The Future Is Now In Twisted Coil Polymer Actuators (Tcpa), Ryan Ronquillo

Electronic Theses and Dissertations

This thesis aimed to fabricate and test twisted coiled polymer actuators (TCPA) to understand the mechanical and thermal aspects of this artificial muscle fiber. The purpose of this thesis was to find a linear relationship using the LVDT sensor, fabricating TCPA fibers, and interpreting the data. The project tested whether nylon/polymer could be used as a better artificial muscle fiber.

This research accomplished three goals: (1) designing and fabricating a system capable of creating supercoiled muscle fibers consistently, (2) calibrating the Linear Variable Differential Transformer (LVDT) and Core, and (3) analyzing/interpreting the data of the Twisted Coiled Polymer Actuators (TCPA) …

Interrogating Autism From A Multidimensional Perspective: An Integrative Framework., Mohamed T. Ali

Electronic Theses and Dissertations

Autism Spectrum Disorder (ASD) is a condition characterized by social and behavioral impairments, affecting approximately 1 in every 44 children in the United States. Common symptoms include difficulties in communication, interpersonal interactions, and behavior. While symptoms can manifest as early as infancy, obtaining an accurate diagnosis may require multiple visits to a pediatric specialist due to the subjective nature of the assessment, which may yield varying scores from different specialists. Despite growing evidence of the role of differences in brain development and/or environmental and/or genetic factors in autism development, the exact pathology of this disorder has yet to be fully …

Tumor Targeting Gold Nanoparticles For Delivery Of Rna And Dna Oligonucleotide Therapies For Glioblastoma., Nicholas Allen

Electronic Theses and Dissertations

Glioblastoma (GBM) brain tumors are highly aggressive gliomas due to genetic and cellular heterogeneity. Current GBM treatment consists of surgical resection of the tumor combined with radio- or chemo-therapies. While these treatments have increased the life expectancy for GBM patients up to 20 months, they have had little effect on the 5-year survival rate. The complex cellular and genetic composition of the tumor makes current treatments less effective long term. One approach to developing more effective GBM treatments is to customize nanoparticle-based drug delivery systems that can directly target the aberrant gene expression patterns within a particular GBM tumor. Delivery …

The Study Of Corrosion On Additive-Manufactured Metals., Braydan Daniels

Electronic Theses and Dissertations

The purpose of this study was to investigate and compare the corrosion mechanisms between wrought and additive-manufactured (3D-printed) copper and stainless steel. The experimental procedure consisted of measuring the open circuit potential, electrochemical impedance spectroscopy, linear sweep voltammetry, Tafel analysis, surface topology, and scanning electron microscopy for each metal within salt water, tap water, sulfuric acid, and synthetic body fluid (excluding copper in synthetic body fluid).

Overall, printed stainless steel was more corrosion-resistant than wrought stainless steel in tap water and synthetic body fluid based on OCP, LSV, and surface topology results. Additionally, printed copper was more corrosion-resistant than wrought …

Computational Fluid Dynamics Model Of Hyperthermic Intraperitoneal Chemotherapy., Olivia Cooney

Electronic Theses and Dissertations

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a procedure that targets abdominal tumors in the intraperitoneal space. During the procedure, chemotherapy heated to 40-43^oC is cycled through the abdomen for 1 to 2 hours. Although a majority of studies have focused on clinical outcomes, the dynamics of the intra-abdominal flow remain poorly understood. Consequently, it has been difficult to gauge the tumor targeting efficacy, which depends critically on temperature and chemotherapy flow rates. This study establishes a computational framework to evaluate the dynamics of fluid flow during HIPEC, with the goal to enable optimization of tumor drug exposure. A computer …

Metabolomic Differentiation Of Tumor Core And Edge In Glioma., Mary E. Baxter

Electronic Theses and Dissertations

Glioma is one of the most aggressive forms of brain cancer. It has been shown that the microenvironments differ significantly between the core and edge regions of glioma tumors. This study obtained metabolomic profiles of glioma core and edge regions using paired glioma core and edge tissue samples from 27 human patients. Data was acquired by performing liquid-liquid metabolite extraction and 2DLC-MS/MS on the tissue samples. In addition, a boosted generalized linear machine learning model was employed to predict the metabolomic profiles associated with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation.

A panel of 66 metabolites was found to be statistically significant …

Modeling Of Transport In Anatomic Respiratory Airways: Applications In Targeted Drug Delivery And Airborne Pathogenic Transmissions, Mohammad Mehedi Hasan Akash

Electronic Theses and Dissertations

This thesis aims to explore the potential of improving the efficacy of drugs for treatment of viral infections by targeting the nasopharynx, which is commonly the first site of infection for many viral pathogens. Currently, intranasal sprays are used, but the standard protocol (“Current Use” or CU) results in suboptimal drug deposition at the nasopharynx. To address this issue, an “Improved Use” or, IU protocol has been proposed, which involves pointing the spray bottle at a shallower angle and aiming slightly towards the cheeks. The IU delivery is also robust to perturbations in spray direction, which highlights the practical utility …

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …