Biomedical Engineering and Bioengineering Commons^™

Where Do We Go Now: An Examination Of The Role Of 3d Modeling In Cancer Research, Ella Claire Gregory, Hannah Noelle Cochran

ABE 4523/6523 Biomedical Materials

The development of three-dimensional tumor models has become an important area of cancer research. By incorporating biomaterials that can mimic the physical, chemical, and biological characteristics of the tumor environment. 3D models can provide a more physiologically relevant environment for studying tumor growth, cell interaction, metastasis, and drug response.

Evaluation Of Antibiotic Testing Protocols For Biofilm-Forming Escherichia Coli In A Microfluidic Platform, Caleb R. Telander

Master's Theses

Catheter-associated urinary tract infections remain an ongoing clinical problem due to biofilm persistence and antibiotic resistance. Standard antibiotic susceptibility testing cannot accurately reproduce flow conditions and the spatial complexity of the in vivoenvironment and is thus questionable in relevance to device-related infections. This study examines a microfluidic device designed to simulate physiologically relevant wall shear stress and antibiotic gradients in Escherichia coli biofilms. The polydimethylsiloxane-based system integrates a 16-well culture chamber with a gradient generator. Biofilm growth was observed using fluorescence microscopy of green fluorescent protein-labeled bacteria. Simulations performed using COMSOL Multiphysics software estimated the appropriate range of wall …

Optimizing Microfluidic Murine Fibroblast And Human Epidermal Keratinocyte Cell Culture In 70Μm Microwells, Christian Navarro

Master's Theses

Cell culture is an essential technique utilized in biotechnology and medicine to remove systemic influences to study cellular behavior and morphological development of individual cell lines. However, conventional cell culture is two-dimensional and static meaning it can’t easily mimic in vivo conditions such as multicellular cell to cell interactions, fluid perfusion, or 3D structures which might alter cellular behavior and morphology. Microfluidic cell culture allows for the incorporation of in vivo conditions such as perfusion and chemical gradients allowing for more physiologically accurate models. The goal of this study is to develop a protocol for testing a microfluidic chip designed …

Development Of Translational Microscale Systems To Interrogate How Biophysical And Biochemical Cues Alter The Phenotype Of Hormone Positive Breast Cancer, Braulio Ortega Quesada

All Dissertations

Cancer is a complicated disease and one in every three diagnoses are women with breast cancer. Recent research shows that the progression of cancer depends strongly on interactions with other non-cancerous cells and non-cellular components. Metastasis, the spread of cancer to other parts of the body, is a key step in cancer progression and makes treatment harder, leading to poor response to treatments culminating in death in ~90% of patients. This dissertation focused on creating a series of microdevices as novel pre-clinical models of breast cancer. Two different devices were fabricated to (1) study how exposing cancer cells to the …

In Vitro Microfluidics System For Mechanobiologic Investigations, Michael A. Daanen

Honors Theses

Mechanobiology is an emerging field that aims to study the relationships between mechanical forces and cellular behavior. Such mechanobiological relationships are especially critical in the cardiovascular system, where endothelial cells lining the vasculature align in response to fluid shear stresses from blood flow (Sinha, 2016). Implanted flow devices, diabetes, chronic hypertension, and various other diseases and pathophysiologies alter vessel geometries and flow dynamics. Such alterations impact fluid shear stress and endothelial cell behavior, leading to microcirculatory dysfunction, vessel leakage, and organ failure (Poredos, 2021; Papadaki, 1999; Leitschuh, 1987). To simulate dysfunctional endothelial cell behavior in vitro and evaluate novel therapeutic …

The Pre-Polarization And Concentration Of Cells Near Micro-Electrodes Using Ac Electric Fields Enhances The Electrical Cell Lysis In A Sessile Drop, Kishor Kaphle, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Cell lysis is the starting step of many biomedical assays. Electric field-based cell lysis is widely used in many applications, including point-of-care (POC) applications, because it provides an easy one-step solution. Many electric field-based lysis methods utilize micro-electrodes to apply short electric pulses across cells. Unfortunately, these cell lysis devices produce relatively low cell lysis efficiency as electric fields do not reach a significant portion of cells in the sample. Additionally, the utility of syringe pumps for flow cells in and out of the microfluidics channel causes cell loss and low throughput cell lysis. To address these critical issues, we …

Water Permeation Through Single Sub-Micron Pores In Single Layer Graphene Measured By A Micro-Particle Image Velocimetry Technique, Samuel F. D. J. Gomez, Michael S. H. Boutilier

Chemical and Biochemical Engineering Publications

Graphene holds potential as a high permeance membrane material for separation applications owing to its single atom thickness. Transport rates through graphene pores ultimately determine membrane performance and are an area of focus of design efforts. In this regard, single pore flow rate measurements are desirable because they are not influenced by material defects present in large-area samples and are unaffected by modeling assumptions used in simulations. However, measuring liquid flow rates through single graphene pores is challenging. In this paper, we establish a micro-particle image velocimetry technique to measure flow rates through single pores or small permeable areas by …

A Sophisticated Model Of Human Atherosclerosis On A Chip, Brandon J. Tefft

Biomedical Engineering Faculty Research and Publications

No abstract provided.

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 …

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, …

Patterned Magnetic And Plasmonic Nanostructures In Microfluidics For Extracellular Vesicle Screening And Drug Loading, John H. Molinski

Dartmouth College Ph.D Dissertations

Extracellular vesicles (EVs), once dismissed as shuttles for cellular waste, have emerged as vital nanoscale biomolecules, facilitating intercellular communication through transfer of host-cell specific molecular cargo. Tumor-derived EVs, released by cancer cells, hold potential as diagnostic biomolecules due to their links to cancer cells, abundance within biofluids, and potential for direct extraction and detection. More broadly, EVs from a wide array of cellular origins have been explored as therapeutic carriers, stemming from their innate function as cargo carriers, high biocompatibility, and their ability to evade immune detection. However, harnessing EVs for diagnostic or therapeutic applications necessitates efficient isolation, purification, and …

Investigating The Role Of Fluid Shear Stress During Metastasis On Enhanced Breast Cancer Extravasation, Alejandra M. Ham

LSU Master's Theses

In 2022, ~288,000 American women were diagnosed with metastatic breast cancer which was the leading cause of patient mortality with ~43,000 American women succumbing to the disease. Women can be diagnosed with four different molecular subtypes of breast cancer: luminal A, luminal B, human epithelial growth receptor type 2 enriched (HER2+), and triple-negative breast cancer (TNBC). TNBC accounts for ~12% of all breast cancers, yet it has the worst outcomes. TNBC is highly invasive, with ~46% of TNBC patients developing metastatic disease. A further understanding of metastatic TNBC is needed to provide a greater understanding of how to treat this …

Single And Dual Cell Encapsulation Via Liquid Core Hydrogels Using Pico Injection, Jade Houston

USF Tampa Graduate Theses and Dissertations

In this project, a comprehensive microfluidic device, along with several interdependent subsystems, was designed and developed in SolidWorks, leveraging a combination of 3D resin printing with biocompatible resin and micromachining with polymethylmethacrylate (PMMA). The microfluidics chip integrated both passive and active components to facilitate its primary function: dual cell encapsulation via liquid core sodium alginate hydrogel droplets.

Integral to the microfluidics chip design were key features including a 5-convolution Archimedes spiral for particle sorting, a flow focusing junction for droplet generation, and a pico injector for injecting additional cells into passing droplets via the manipulation of an electric field.

An …

4d Epr Oximetry Imaging For 4d Bioprinting And Tissue Engineering, Sajad Sarvari

Graduate Theses, Dissertations, and Problem Reports (ETD)

Bioprinting, akin to 3D printing, employs cell-laden hydrogels such as GelMA (Gelatine Methacrylate) and Alginate instead of plastic or resin to create biological structures. The printing process followed by subsequent tissue maturation is known as 4D bioprinting, where the fourth dimension is time. Ensuring adequate and consistent oxygen, O2, supply within 3D bioprint volume over the entire maturation period process is crucial, as even transient hypoxia can impact cellular behavior and phenotypes. However, printing of fully developed vasculature remains an unresolved technical challenge. Several approaches to chemically (peroxides) or biologically (photosynthesis) generate oxygen during bioprint maturation have been proposed. However, …

Colloid Fabrication For Biomedical Engineering Applications Through Droplet Microfluidics, Lewis I. Larsen

Biomedical Engineering ETDs

The goal of this work was to leverage soft colloid fabrication through droplet microfluidics to improve the biomedical fields of radiotracer microspheres for selective internal radiation therapy (SIRT) and 3D hydrogel tissue constructs for cell culture with future potential as a platform to study liver diseases and drug response. The importance of positron emission tomography (PET) imaging microspheres infused with positron-emitting radioisotopes such as Ga-68, Cu-64, and F-18 is that they accurately map tumor-to-liver uptake (TLR) ratio and lung shunting factor of hepatocellular carcinoma. These pretreatment radiotracers model the intravascular accumulation behavior of radioactive therapeutic Y-90 SIRT microspheres. Qualifying patients, …

Development Of Novel Biosensors For Direct Measurement Of Proteasome Activity In Intact Single Cells, Alireza Rahnama

LSU Doctoral Dissertations

Enzymes regulate nearly all cellular and biochemical processes governing cellular proliferation, metabolism, and migration. One example is the ubiquitin-proteasome system (UPS), a highly complex, tightly regulated pathway responsible for the recognition and degradation of misfolded or damaged proteins inside the cell. Protein degradation requires posttranslational addition of a polyubiquitin chain to target the protein to the proteasome for degradation which can be reversed by deubiquitinating enzymes (DUBs) which remove the chain. Dysregulation of the UPS is associated with many diseases including cancer which has resulted in the development of inhibitors, like Bortezomib and Carfilzomib, driving higher median patient survival rates …

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 …

Novel Microfluidic Devices To Model The Interactions Between Lymphatics And Breast Cancer, Jade Weber

McKelvey School of Engineering Graduate Student Theses & Dissertations

The lymphatic system is responsible for immune circulation and fluid balance in the body. It accomplishes this by draining interstitial fluid from local tissue and transferring it to lymph nodes and back into blood circulation. However, this process is implicated in many pathologies, one of the most dangerous being breast cancer metastasis to the lymph nodes. The largest factor in breast cancer patient mortality is metastasis. Lymphangiogenesis, the growth of new lymphatic vessels, has been thought to play a dynamic role in aiding breast cancer metastasis. Breast cancer tumor cells have been shown to remodel the functionality of local lymph …

The Development Of A Primer Payload With Microparticles For Uti Pathogen Identification Using Polythymidine- Modified Lamp Primers In Droplet Lamp, Jonas Otoo

KGI Theses and Dissertations

Nucleic acid amplification tests (NAATs) are among the diagnostic tests with the highest sensitivity and specificity. However, they are more complex to develop than other diagnostic tests such as biochemical tests and lateral flow immunoassay tests. Polymerase chain reaction (PCR) is the gold standard for NAATs. PCR requires thermal cycling to achieve clonal amplification of the target pathogen DNA for diagnosis. Thermal cycling poses a challenge in the development of PCR diagnostics for point-of-care (POC) settings. Loop-mediated isothermal amplification (LAMP) offers an isothermal method for NAATs diagnostics. The advancement of the microfluidics field significantly enhances the development of LAMP diagnostics …

A 3d Bioprinted Hydrogel Microfluidic Device For Screening Applications, Anant Bhusal

Theses and Dissertations

The microfluidic enabled the integration of engineered miniaturized tissue models for drug screening. Conventional polydimethylsiloxane or plastic-based devices require multiple fabrication steps, which are challenging. We developed a 3D bioprinting approach to create prototypes of hydrogel-based multi-material microfluidic devices integrated with microtissue models. The approach utilizes poly(ethylene glycol) diacrylate and gelatin-methacryloyl to create microfluidic chips using multi-material bioprinting capacity with a high resolution of 15µm on x-y and 50µm on the z-axis and post-printing viability of >90%. We demonstrated easy regulation of stiffness from 24±5 kPa to 1,180±9 kPa and burst pressure from 16±1kPa to 256±19 kPa in the chip …

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 …

Long-Range Aceo Phenomena In Microfluidic Channel, Diganta Dutta, Keifer Smith, Xavier Palmer

Electrical & Computer Engineering Faculty Publications

Microfluidic devices are increasingly utilized in numerous industries, including that of medicine, for their abilities to pump and mix fluid at a microscale. Within these devices, microchannels paired with microelectrodes enable the mixing and transportation of ionized fluid. The ionization process charges the microchannel and manipulates the fluid with an electric field. Although complex in operation at the microscale, microchannels within microfluidic devices are easy to produce and economical. This paper uses simulations to convey helpful insights into the analysis of electrokinetic microfluidic device phenomena. The simulations in this paper use the Navier–Stokes and Poisson Nernst–Planck equations solved using COMSOL …

Designing A Self-Regulating And Portable Heating Device For A Microfluidic Based Biosensor, Riya Mahajan

Discovery Undergraduate Interdisciplinary Research Internship

Paper-based biosensors are powerful microfluidic analytical devices that are potentially useful for a wide range of applications, ranging from medical diagnostics to agricultural and environmental monitoring. Molecular diagnostics have limitations because they need to send samples back to a centralized laboratory, which increases the cost and turnaround time of the test. This project aims to create a simple-to-use, low-cost, and portable heating system that would facilitate the creation of a field-deployable paper-based analytical device that can incubate the sample at elevated temperatures for conducting isothermal molecular assays. Our design aims to miniaturize a commercial water bath and will be fabricated …

Synthesis Of Thiol-Acrylate Hydrogels For 3d Cell Culture And Microfluidic Applications, Anowar Hossain Khan

LSU Doctoral Dissertations

Globally cell culture is an $18.98 billion industry as of 2020, with an 11.6 percent annual growth rate. Drug discovery has an estimated worth of $69.8 billion in 2020 and is predicted to grow to $110.4 billion by 2025. Three-dimensional (3D) cell culture of cancer cells is one of the rapidly growing felids since it better recapitulates in vivo conditions compared to two-dimensional (2D) models. However, it is challenging to grow 3D tumor spheroids outside the body, and some of the existing technology can generate these spheroids outside the human body but poorly mimic in vivo tumor models. Therefore, there …

An Electrochemical, Fluidic, Chip-Based Biosensor For Biomarker Detection, Lauren Bell

Theses and Dissertations--Biomedical Engineering

Biosensors and their use in both the research and clinical field for the detection and monitoring of critical biomarkers are prevalent and constantly improving. However, continued research needs to be done to address shortcomings, such as low sensitivity, poor specificity, and poor readiness for integration into research use and patient care. The objective of this research was to create a combined fluidic, chip-based biosensor that could detect different biomarkers with high sensitivity and ease of use. For assessing the developed sensor, three separate biomarkers were tested: glucose, cholesterol, and oxygen. Both the glucose biosensor and cholesterol biosensor were combined with …

Nano-, Encapsulated Manganese Oxide (Nemo) Particles For Mri Enhancement In Microfluidic Tumor Models, Kasey Alexis Freshwater

Graduate Theses, Dissertations, and Problem Reports (ETD)

Breast cancer is among the deadliest cancers in women, with approximately 2.3 million new cases and 685,000 deaths reported globally in 2020 alone. Magnetic Resonance Imaging (MRI) is commonly used to diagnose, stage, and develop treatment plans for patients predisposed to breast cancer. However, current MRI-based screening of breast cancer has high false-positive rates up to 25%, leading to unnecessary invasive follow-up screening and testing. The gold-standard intravenous gadolinium (Gd)-based contrast agents (GBCAs) account for false-positive rates because they are always “ON”, providing a constant MRI signal that highlights both benign and malignant tumors. The work detailed in this thesis …

Rapid Ac Electrokinetic Micromixer With Electrically Conductive Sidewalls, Fang Yang, Wei Zhao, Cuifang Kuang, Guiren Wang

Faculty Publications

We report a quasi T-channel electrokinetics-based micromixer with electrically conductive sidewalls, where the electric field is in the transverse direction of the flow and parallel to the conductivity gradient at the interface between two fluids to be mixed. Mixing results are first compared with another widely studied micromixer configuration, where electrodes are located at the inlet and outlet of the channel with electric field parallel to bulk flow direction but orthogonal to the conductivity gradient at the interface between the two fluids to be mixed. Faster mixing is achieved in the micromixer with conductive sidewalls. Effects of Re numbers, applied …

Development Of A Microfluidic Viscoelastic Hemostatic Assay For Real-Timeviscosity Measurements Of Blood, Shay Kent

Electronic Theses and Dissertations

Blood coagulation disorders are malfunctions in the body’s ability to control blood clotting. It can result in either insufficient clotting causing an increased risk of bleeding or excessive clotting obstructing blood flow. The rapid and accurate diagnosis of coagulopathies is an important, unmet need in the clinical setting. Rapidly identifying the source of bleeding, either acquired or inherited, is critical to reduce the risk of major blood loss and deliver personalized hemostatic therapies. Viscoelastic hemostatic assays, or VHAs, deliver an effective solution to the diagnosis of coagulopathies by evaluating global hemostatic function using whole blood rather than plasma. VHAs are …

Microfluidic Electrical Impedance Spectroscopy System Automation And Characterization, Keaton Frahmann

Master's Theses

In this work, a novel microfluidic cell culture platform capable of automated electrical impedance measurements and immunofluorescence and brightfield microscopy was developed for further in-vitro cellular research intended to optimize cell culture conditions. The microfluidic system design, fabrication, automation, and design verification testing are described. Electrical and optical measurements of the 16 parallel cell culture chambers were automated via a custom LabView interface. A proposed design change will enable gas diffusion, removing the need for an environmental enclosure and allow long-term cell culture experiments. This "lab on a chip" system miniaturizes and automates experiments improving testing throughput and accuracy while …

Isomotive Dielectrophoresis For Enhanced Analyses Of Cell Subpopulations., Mohamed Zakarya Rashed

Electronic Theses and Dissertations

As the relentless dream of creating a true lab-on-a-chip device is closer to realization than ever before, which will be enabled through efficient and reliable sample characterization systems. Dielectrophoresis (DEP) is a term used to describe the motion of dielectric particles/ cells, by means of a non-uniform electric field (AC or DC). Cells of different dielectric properties (i.e., size, interior properties, and membrane properties) will act differently under the influence of dielectrophoretic force. Therefore, DEP can be used as a powerful, robust, and flexible tool for cellular manipulation, separation, characterization, and patterning. However, most recent DEP applications focus on …