Biomedical Engineering and Bioengineering Commons^™

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 A Programmable, Open-Source, And Cost-Effective Fluidic System For Cell Culture Applications, Charles Montoya

Biomedical Engineering ETDs

Open-source laboratory equipment has become an increasingly popular alternative to commercially available options due to its simple implementation, capability of user-customized modifications, and cost-effectiveness. Presented here is the development of a programmable and open-source fluidic system comprised of three custom-built syringe pumps for cell culture applications. The fluidic system was directly integrated with a multiwell plate on an environmentally controlled microscope platform for live-cell imaging and time-lapse analyses of cellular responses as culture conditions are adjusted using the programmable fluidic system. Proof-of-concept of this system is obtained by controlling autophagic activity in A549 cells by adjustment of nutrient supply. The …

Fumarate-Based Polymers: Oligo(Poly(Ethylene Glycol) Fumarate) And Poly(Butylene Fumarate) For Tissue Engineering Heart Valve And Bone Tissue, Christian T. Denny

Biomedical Engineering ETDs

Tissue engineering is an emerging field that came from the fields of medicine, materials science, and engineering. The foundation of tissue engineering uses a paradigm that incorporates cells, biomaterials, and exogenous factors to create living tissues for medical, pharmaceutical, and research purposes. Within the last 100 years, biomaterials have been developed to solve many medical and research problems. As biomaterials have developed throughout the years new materials have been developed to have specific properties appropriate for medical applications. Fumarate is a naturally derived molecule in the body and has been found useful for developing polyesters that can be crosslinked into …

Characterization Of Phase Behavior In Idp Solutions By Uv-Vis Spectrophotometry And Phase Volume Fraction Measurements In Capillaries, Qing Sun

Biomedical Engineering ETDs

Intrinsically disordered proteins (IDPs) play vital roles in cell signaling and regulation by changing conformation dynamically under various stimulus. Thus, it is crucial to understand their physical properties in vitro especially liquid-liquid phase separation (LLPS). Here, we first used UV-vis spectrophotometry to investigate two of IDPs' physical properties – transition temperature (Tt) and coacervate size. This deeper insight allows us to further understand the dynamics of phase growth. We then constructed a binodal curve in the phase diagram by measurement of volume ratios in phase separated IDP solution in glass capillaries.

The Development Of An Instrument To Measure Transdermal Hydrogen Sulfide As A Way To Evaluate Microvascular Health In Humans, Benjamin Thomas Matheson

Biomedical Engineering ETDs

Hydrogen sulfide (H₂S) is a gasotransmitter critical in maintaining microcirculation homeostasis. Impaired microcirculation occurs in multiple disease states such as peripheral vascular disease, diabetes mellitus (DM), and hypertension. Early detection and identification of patients with DM who are at risk for heart attack, stroke and amputation due to microvascular disease is crucial. Human skin is an accessible vascular bed that provides an opportunity to non-invasively measure H₂S, which could be used as a biomarker to evaluate microvascular health.

In this work, a novel H₂S gas sensor, called the transdermal arterial gasotransmitter sensor (TAGS^{TM …}

Correlating Diffusional Dynamics And Receptor Tyrosine Kinase Function Using Single Quantum Dot Tracking, Irais Ortiz Caraveo

Biomedical Engineering ETDs

Epidermal growth factor receptor (EGFR) signal transduction is initiated via ligand (EGF) binding, followed by dimerization, autophosphorylation of the C-terminal tails, and recruitment of proteins that form a larger signaling complex to propagate the signal. We explored the relationship between receptor mobility and signaling using single-particle tracking (SPT) by examining the diffusional dynamics of EGFR and two truncation mutants to understand whether mobility changes are correlated with signaling. Results revealed that phosphorylation of the C-terminal tail of EGFR is required for maximal reduction in mobility that occurs with EGF stimulation, indicating that receptor mobility is a read-out for receptor signaling. …

Dectin-1 Mediated Mechanical Force Generation In Candida Albicans Fungal Pathogen Recognition, Rohan Choraghe

Biomedical Engineering ETDs

Candida spp. pathogens continue to be a major health care burden with high mortality and exceeding a billion dollars in terms of healthcare cost. Candidainfection ranges from superficial dermatological infection to more serious blood stream infection in debilitated patients. One of the major lines of innate immune defense against Candidais phagocytosis. Dectin-1 is the antifungal receptor in myeloid cells responsible for most immune responses against fungi including phagocytosis. We looked into the signaling pathway coordinating this mechanical process downstream of Dectin-1. We found that Dectin-1 activation gives rise to a significant mechanical force generation mediated through RHOA-ROCK-MyosinII pathway. …

The Investigation Of Surface Structures On Various Pathogens And Their Interactions With The Human Immune System, Carmen M. Villalobos

Biomedical Engineering ETDs

The cell surface is the first interface the host immune system encounters and

its investigation has led to a better understanding of cellular biology and types of

pathways that pathogens target in a host cell. The cell surface has evolved to include

many functions such as manipulation of the cytoskeleton, cell signaling, membrane

trafficking, adhesion, and integration into host tissue. The pathogens of interest are

the pathogenic fungus, Candida albicans, and the parasite, Giardia lamblia and we

investigate the consequences of drug treatments on the cell surface, leading to

promising new targets.

Photo-Characterization Of Selective Luminescent Protein Aggregate Sensors - Oligo-P-Phenylene Ethynylene (Opes), Florencia A. Monge

Biomedical Engineering ETDs

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease,

and related tauopathies, are a global health care challenge due to the lack of early

treatment and diagnostic options. These diseases take an emotional and physical

toll on patients, caretakers, and a rather large economic toll on taxpayer-based

health care systems. The pathologies of these diseases are characterized by the

aggregation of misfolded proteins, amyloid-β (Aβ) and tau, into β-sheet rich

structures called amyloids. Research has found that the presence of protein

aggregates predates cognitive symptoms by years. Current diagnostic tools are

based on the detection of these amyloid aggregates, historically by …

Screening And Characterization Of A Pan-Gtpase Inhibitor, Leyla Akhadov

Biomedical Engineering ETDs

Abnormal functioning of small GTPases is implicated in a variety of diseases, ranging from neurological and developmental diseases to cancer. In fact, mutant GTPases are found in up to 30% of cancers. Thus, small GTPases are a highly relevant target in drug discovery and development. High-throughput targeted screening of small molecules is the most productive method of discovering compounds that can give insights into drug development. This thesis describes improvements made to a high-throughput GTPase-targeted screening method to minimize confounding systematic error. It also describes the follow-up characterization of a compound that was identified in a high-throughput screen. The compound …

Assessment Of The Biocompatibilty, Stability, And Suitability Of Natural And Synthetic Polymers And Drugs In The Fda Approval Process, Phuong Anh Hoang Nguyen

Biomedical Engineering ETDs

Regulation of the development, production, marketing, and sales of medical pharmaceuticals and devices in the United States fall under the regulatory functions of the Food and Drug Administration (FDA). The current FDA approval process takes an average of 10 years from start to completion, and costs over $100 million. As a result, companies use many different methods to find additional use of their drugs through marketing directly to the physician, or recycling of previously approved drug moieties. In this work, an evaluation of the in vitro and ex vivo biocompatibility of polymers and drugs in different phases of FDA approval …

Detection And Remodeling Of Toxic Amyloid Aggregates By Novel Conjugated Polyelectrolytes, Adeline Marianne Fanni

Biomedical Engineering ETDs

The abnormal misfolding and aggregation of intrinsically disordered proteins into ordered fibrillar amyloid aggregates is recognized as a common pathological event in neurodegenerative disorders (ND) such as Alzheimer’s and Parkinson’s diseases. The key role of fibrillar and pre-fibrillar aggregates in ND makes them ideal biomarkers to better understand disease progression but also for early disease detection and therapeutic intervention. The work described herein was conducted to gain a better understanding of amyloid interaction to lipid membrane and its role in peptide toxicity. This research was also focused on evaluating the fluorescent probe, oligomeric p-phenylene ethynylene (OPE), as an amyloid …

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Biomedical Engineering ETDs

Small, biologically active molecules with unique properties and applications are potential solutions to a wide range of threats to global health including infectious agents and neurodegenerative disease. Experimental studies on a class of oligomeric p-phenylene ethynylenes (OPEs) have shown potential both as bioactive antimicrobials and fluorescent sensing agents for tracking amyloid-β (Aβ) aggregates found in Alzheimer’s Disease (AD). A second type of small molecule with potential applications in AD therapy, curcumin, has been found to interfere with Aβ fibril growth. Curcumin also attenuates Aβ-membrane interactions and Aβ toxicity. Our goal has been to use computational techniques to better understand the …

A Microfluidics-Based Cross-Flow Filtration Platform For Rapid Processing Of Amphiphilic Biomarkers From Blood, Kiersten D. Lenz

Biomedical Engineering ETDs

Early and accurate detection of bacterial infections can help save lives, prevent the spread of disease, and decrease the overuse of antibiotics. Our team at the Los Alamos National Laboratory has developed novel assays to detect bacterial biomarkers from patient blood at the point-of-care in order to facilitate a universal diagnostic platform. However, these biomarkers are amphiphilic in nature, and this biochemical property causes them to be sequestered by high-density and low-density lipoproteins (HDL and LDL) in the host’s blood. Extraction of the bacterial biomarkers from the lipoprotein complexes is thereby required for the development and deployment of a diagnostic …

Developing A Synthetic Model Of The Candida Albicans Cell Wall Using Self-Assembled Monolayers To Host Beta-Glucan As Ligands, Ushnik Ghosh

Biomedical Engineering ETDs

The goal of this investigation is to study mechanisms the immune cell receptor, Dectin-1, uses to identify the fungal cell species, Candida albicans. Dectin-1 identifies extracellular matrix polysaccharides that Candida albicans express known as β-glucan. To study the interaction of β-glucan – Dectin-1 at the nanoscopic scale, the investigators of this project have endeavored to model the Candida albicans cell wall with engineered Self-Assembled Monolayers presenting β-glucan as a ligand for immobilized Dectin-1 receptors. By engineering a simplified ex-vivo model of the Candida albicans cell wall, the investigators of this study aim to gain precise control of the composition …

Incorporation Of Egfr And Ron Receptors Into Nanodiscs, Cristina Flores-Cadengo

Biomedical Engineering ETDs

Understanding the structure-function relationship of membrane receptors is essential to comprehend the crosstalk between key signaling pathways. Aberrant trans-activation between receptors can lead to tumorigenesis. Two of these receptors known to be involved in cancer development are receptor tyrosine kinases (RTKs), RON (Recepteur d'Origine Nantais) and EGFR (Epidermal Growth Factor Receptor). There has been evidence of heterodimerization and crosstalk between these two receptors based on co-immunoprecipitation, however the structural requirements behind these interactions remain unknown. Structural studies could provide insights into these RTKs’ modes of dimerization and structure-function relationship. However, structural studies of full-length membrane proteins are often difficult due …

Effect Of Strong Electrolyte Containing Gelling Aids On The Sol-Gel Transition Temperature Of Hypromellose 2910, Elnaz Sadeghi

Biomedical Engineering ETDs

Hypromellose, or hydroxypropyl methylcellulose (HPMC) - has been widely used for biomedical and pharmaceutical applications due to its advantages, including that it is modifiable in terms of viscosity, and it has the ability to form thermally reversible hydrogels. The thermal gelation temperature (T_Gel) of a given HPMC solution strongly depends on its characteristic grade and the solution concentration. Applying certain additives can modify the T_Gel even further; depending on their nature and concentration. With the addition of said additives, a lower or higher T_Gel can be obtained. For example, the addition of sodium chloride (NaCl) reduces …

Acoustofluidics And Soft Materials Interfaces For Biomedical Applications, Frank A. Fencl

Biomedical Engineering ETDs

This dissertation describes fabrication of devices and other tools for biomedical applications through the integration of acoustofluidic systems with bio separation assays, instrumentation components, and soft materials interfaces. For example, we engineer a new class of transparent acoustic flow chambers ideal for optical interrogation. We demonstrate efficacy of these devices by enhancing the signal for high throughput acoustic flow cytometry, capable of robust particle focusing across multiple parallel flowing streams. We also investigate an automated sampling system to determine the parameters of transient particle stream focusing in between sample boluses and air bubbles to model a high throughput, multi-sampling acoustic …

Compartmentalization Of Dna-Based Molecular Computing Elements Using Lipid Bilayers, Aurora Fabry-Wood

Biomedical Engineering ETDs

This dissertation will present a progression from the detection of double-stranded DNA using a combination of toehold-mediated strand displacement and DNAzyme reactions in dilute saline solutions, to the generation of separate compartments to allow standardization of DNA computing elements, by protecting from complementary strands. In well-mixed solutions complementary regions cause spurious interactions. Importantly, these compartments also provide protection from nucleases. Along the way we will also explore the use of silica microsphere supported lipid bilayers to run compartmentalized DNA reactions on a fluid surface and the design of a molecule capable of DNA-based transmembrane signal transduction.

Next Generation Sequencing Technologies For Real-Time Genotyping And Targeted Sequencing For Precision Medicine, Priyanka Rawat

Biomedical Engineering ETDs

Astounding success of Human genome project and accelerating success of sequencing technologies have enabled $ 1000 genome goals possible. But, this is still far-fetched from the reach of many resource refrained populations with high genetic variations causing lethal genetic diseases. Based on present technology principles, I have developed prototypes for affordable, scalable and customizable point-of-care genotyping and targeted sequencing. Ion-sensitive field effect transistors with novel read-out and signal amplification techniques are used for laying foundation of possible ISFET based allele-arrays. Sequencing-by-synthesis based full-fledge sequencer is made with novel immobilization, flow-cell and data acquisition methods for massive sequenciing.

Development Of Biomimetic Membrane Assemblies On Microspheres For High-Throughput And Multiplexable Studies, Nadiezda P. Fernandez Oropeza

Biomedical Engineering ETDs

Membranes and membrane-associated components are the target of approximately 60% of the current drugs, of synthetic materials, such as polymers, which are used for drug delivery purposes and of other biomolecules, such as endotoxins, which gain entry into the cell by disrupting the membrane. Therefore, the development of biomimetic membrane assemblies allows the study of different biological processes in which cell membranes play an important role, and the characterization and screening of drug delivery tools and other membrane-bound components.

Since its development, membrane assemblies on planar silica surfaces have been the method of choice to study membrane-associated and membrane-bound components. …

A Multiscale Modeling Study Of The Mammary Gland, Joseph D. Butner

Biomedical Engineering ETDs

Multiscale, hybrid computer modeling has emerged as a valuable tool in the fields of computational systems biology and mathematical oncology. In this work, we present an overview of the motivations for, and development and implementation of, three hybrid multiscale models of the mammary gland system and early stage ductal carcinoma in situ (DCIS) in the gland. Pubertal mammary gland development was described first using a two-dimensional, lattice-based hybrid agent-based model description of the mammary terminal end bud (TEB), and then with a three-dimensional lattice-free TEB model. Both models implement a discrete, agent-based description of the cell scale, and a continuum, …

Synthesis, Characterization, And Application Of Monosized Mesoporous Silica Nanoparticle-Supported Lipid Bilayers For Targeted Therapeutic Delivery To Individual Cells, Paul Durfee

Biomedical Engineering ETDs

Mesoporous silica nanoparticle (MSNP) supported-lipid bilayers, termed ‘protocells,’ represent a potentially transformative class of therapeutic and theranostic delivery vehicles. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single ‘magic bullet’. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core can have variable size and shape to direct biodistribution and controlled pore size and surface chemistry to accommodate diverse cargos. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal …