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- Creators: Arizona State University
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Description
Locomotion of microorganisms is commonly observed in nature. Although microorganism locomotion is commonly attributed to mechanical deformation of solid appendages, in 1956 Nobel Laureate Peter Mitchell proposed that an asymmetric ion flux on a bacterium's surface could generate electric fields that drive locomotion via self-electrophoresis. Recent advances in nanofabrication have enabled the engineering of synthetic analogues, bimetallic colloidal particles, that swim due to asymmetric ion flux originally proposed by Mitchell. Bimetallic colloidal particles swim through aqueous solutions by converting chemical fuel to fluid motion through asymmetric electrochemical reactions. This dissertation presents novel bimetallic motor fabrication strategies, motor functionality, and a study of the motor collective behavior in chemical concentration gradients. Brownian dynamics simulations and experiments show that the motors exhibit chemokinesis, a motile response to chemical gradients that results in net migration and concentration of particles. Chemokinesis is typically observed in living organisms and distinct from chemotaxis in that there is no particle directional sensing. The synthetic motor chemokinesis observed in this work is due to variation in the motor's velocity and effective diffusivity as a function of the fuel and salt concentration. Static concentration fields are generated in microfluidic devices fabricated with porous walls. The development of nanoscale particles that swim autonomously and collectively in chemical concentration gradients can be leveraged for a wide range of applications such as directed drug delivery, self-healing materials, and environmental remediation.
ContributorsWheat, Philip Matthew (Author) / Posner, Jonathan D (Thesis advisor) / Phelan, Patrick (Committee member) / Chen, Kangping (Committee member) / Buttry, Daniel (Committee member) / Calhoun, Ronald (Committee member) / Arizona State University (Publisher)
Created2011
Description
Mesoporous materials that possess large surface area, tunable pore size, and ordered structures are attractive features for many applications such as adsorption, protein separation, enzyme encapsulation and drug delivery as these materials can be tailored to host different guest molecules. Films provide a model system to understand how the pore orientation impacts the potential for loading and release of selectively sized molecules. This research work aims to develop structure-property relationships to understand how pore size, geometry, and surface hydrophobicity influence the loading and release of drug molecules. In this study, the pore size is systematically varied by incorporating pore-swelling agent of polystyrene oligomers (hPS) to soft templated mesoporous carbon films fabricated by cooperative assembly of poly(styrene-block-ethylene oxide) (SEO) with phenolic resin. To examine the impact of morphology, different compositions of amphiphilic triblock copolymer templates, poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-PPO-PEO), are used to form two-dimensional hexagonal and cubic mesostructures. Lastly, the carbonization temperature provides a handle to tune the hydrophobicity of the film. These mesoporous films are then utilized to understand the uptake and release of a model drug Mitoxantrone dihydrochloride from nanostructured materials. The largest pore size (6nm) mesoporous carbon based on SEO exhibits the largest uptake (3.5μg/cm2); this is attributed to presence of larger internal volume compared to the other two films. In terms of release, a controlled response is observed for all films with the highest release for the 2nm cubic film (1.45 μg/cm2) after 15 days, but this is only 56 % of the drug loaded. Additionally, the surface hydrophobicity impacts the fraction of drug release with a decrease from 78% to 43%, as the films become more hydrophobic when carbonized at higher temperatures. This work provides a model system to understand how pore morphology, size and chemistry influence the drug loading and release for potential implant applications.
ContributorsLabiano, Alpha (Author) / Vogt, Bryan (Thesis advisor) / Rege, Kaushal (Committee member) / Dai, Lenore (Committee member) / Potta, Thrimoorthy (Committee member) / Arizona State University (Publisher)
Created2011
Description
Controlled release formulations for local, in vivo drug delivery are of growing interest to device manufacturers, research scientists, and clinicians; however, most research characterizing controlled release formulations occurs in vitro because the spatial and temporal distribution of drug delivery is difficult to measure in vivo. In this work, in vivo magnetic resonance imaging (MRI) of local drug delivery is performed to visualize and quantify the time resolved distribution of MRI contrast agents. I find it is possible to visualize contrast agent distributions in near real time from local delivery vehicles using MRI. Three dimensional T1 maps are processed to produce in vivo concentration maps of contrast agent for individual animal models. The method for obtaining concentration maps is analyzed to estimate errors introduced at various steps in the process. The method is used to evaluate different controlled release vehicles, vehicle placement, and type of surgical wound in rabbits as a model for antimicrobial delivery to orthopaedic infection sites. I are able to see differences between all these factors; however, all images show that contrast agent remains fairly local to the wound site and do not distribute to tissues far from the implant in therapeutic concentrations. I also produce a mathematical model that investigates important mechanisms in the transport of antimicrobials in a wound environment. It is determined from both the images and the mathematical model that antimicrobial distribution in an orthopaedic wounds is dependent on both diffusive and convective mechanisms. Furthermore, I began development of MRI visible therapeutic agents to examine active drug distributions. I hypothesize that this work can be developed into a non-invasive, patient specific, clinical tool to evaluate the success of interventional procedures using local drug delivery vehicles.
ContributorsGiers, Morgan (Author) / Caplan, Michael R (Thesis advisor) / Massia, Stephen P (Committee member) / Frakes, David (Committee member) / McLaren, Alex C. (Committee member) / Vernon, Brent L (Committee member) / Arizona State University (Publisher)
Created2013
Description
The primary objective of this research project is to develop dual layered polymeric microparticles with a tunable delayed release profile. Poly(L-lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) phase separate in a double emulsion process due to differences in hydrophobicity, which allows for the synthesis of double-walled microparticles with a PLA shell surrounding the PLGA core. The microparticles were loaded with bovine serum albumin (BSA) and different volumes of ethanol were added to the PLA shell phase to alter the porosity and release characteristics of the BSA. Different amounts of ethanol varied the total loading percentage of the BSA, the release profile, surface morphology, size distribution, and the localization of the protein within the particles. Scanning electron microscopy images detailed the surface morphology of the different particles. Loading the particles with fluorescently tagged insulin and imaging the particles through confocal microscopy supported the localization of the protein inside the particle. The study suggest that ethanol alters the release characteristics of the loaded BSA encapsulated in the microparticles supporting the use of a polar, protic solvent as a tool for tuning the delayed release profile of biological proteins.
ContributorsFauer, Chase Alexander (Author) / Stabenfeldt, Sarah (Thesis director) / Ankeny, Casey (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
The goal of this research study was to empirically study a poster-based messaging campaign in comparison to that of a project-based learning approach in assessing the effectiveness of these methods in conveying the scope of biomedical engineering to upper elementary school students. For the purpose of this honors thesis, this research paper specifically reflects and analyzes the first stage of this study, the poster-based messaging campaign. 6th grade students received socially relevant messaging of juniors and seniors at ASU achieving their biomedical aspirations, and received information regarding four crucial themes of biomedical engineering via daily presentations and a website. Their learning was tracked over the course of the weeklong immersion program through a pre/post assessment. This data was then analyzed through the Wilcoxon matched pairs test to determine whether the change in biomedical engineering awareness was statistically significant. It was determined that a poster-based messaging campaign indeed increased awareness of socially relevant themes within biomedical engineering, and provided researchers with tangible ways to revise the study before a second round of implementation. The next stage of the study aims to explain biomedical engineering through engaging activities that stimulate making while emphasizing design-aesthetic appeal and engineering habits of mind such as creativity, teamwork, and communication.
ContributorsSwaminathan, Swetha Anu (Author) / Ganesh, Tirupalavanam (Thesis director) / Shrake, Scott (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
One of the most prominent biological challenges for the field of drug delivery is the blood-brain barrier. This physiological system blocks the entry of or actively removes almost all small molecules into the central nervous system (CNS), including many drugs that could be used to treat diseases in the CNS. Previous studies have shown that activation of the adenosine receptor signaling pathway through the use of agonists has been demonstrated to increase BBB permeability. For example, regadenoson is an adenosine A2A receptor agonist that has been shown to disrupt the BBB and allow for increased drug uptake in the CNS. The goal of this study was to verify this property of regadenoson. We hypothesized that co-administration of regadenoson with a non-brain penetrant macromolecule would facilitate its entry into the central nervous system. To test this hypothesis, healthy mice were administered regadenoson or saline concomitantly with a fluorescent dextran solution. The brain tissue was either homogenized to measure quantity of fluorescent molecule, or cryosectioned for imaging with confocal fluorescence microscopy. These experiments did not identify any significant difference in the amount of fluorescence detected in the brain after regadenoson treatment. These results contradict those of previous studies and highlight potential differences in injection methodology, time windows, and properties of brain impermeant molecules.
ContributorsWohlleb, Gregory Michael (Author) / Sirianni, Rachael (Thesis director) / Stabenfeldt, Sarah (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2015-05
Description
The aim of the present study was to review the symptoms and current treatment options of the most common skin infections seen in outpatient settings and develop a preliminary alternative treatment solution. The specific skin infections evaluated were those caused by Staphylococcus and Streptococcus bacterial species, and are frequently treated with a wide variety of systemic antibiotics or topical ointments. Systemic antibiotics have shown increased occurrence of adverse side effects as well as the development of antibiotic-resistant bacteria. Additionally, these medications are usually overprescribed, which may further exacerbate negative side effects. Another issue that is addressed is the development of infections following treatment of a new laceration or other trauma to the skin. A patient may be treated for their wound with stitches or another alternative, but there is still the possibility of developing an infection later.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.
This study synthesizes information found from extensive research and provides a review of the most optimal techniques for developing an alternative to systemic antibiotics. The final deliverable is a report detailing the significant findings and discussing the ways that this solution may be developed further and implemented in a clinical setting. The solution is a hydrogel bandage designed to deliver antibiotics directly to the wound site, while also offering protection and enhanced wound healing. The target population is patients suffering from skin conditions in an outpatient setting. The antibiotics of interest for this solution are clindamycin, doxycycline, and trimethoprim-sulfamethoxazole (co-trimoxazole), as they offer excellent treatment against gram-positive bacteria and methicillin-resistant Staphylococcus aureus. However, other broad-spectrum antibiotics could potentially be incorporated to protect against gram-negative bacteria. The design features a polyvinyl alcohol (PVA) hydrogel that has shown many properties that are beneficial to biomedical applications, including biocompatibility, flexibility, high drug-loading capacity, high absorption of wound exudate, increased promotion of wound healing, and more. Preliminary mathematical models of the hydrogel’s drug delivery behaviors are also included. Due to the scope and timeframe of this project, the majority of findings herein are based on research of prior literature instead of development of the novel device. Future directions would include further research and development of the mechanisms behind the device, creation of a physical prototype, experimental testing, and statistical analyses to verify device specifications and capabilities.
ContributorsTanner, Emily Christine (Author) / Pizziconi, Vincent (Thesis director) / Nguyen, Eric (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / School of Mathematical and Statistical Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Advancements in healthcare and the emergence of an aging population has led to an increase in the number of prosthetic joint procedures in the United States. According to Healthcare Cost and Utilization Project, 660,876 and 348,970 total hip and knee arthroplasties were performed in 2014[1].The percentage of total hip or knee procedures that are revised due to an infection is 1.23% and 1.21% respectively[3], [4]. Although the percent of infections may be small, an infection can have a tremendous burden on the patient and healthcare system. It is expected that prosthetic joint infections (PJIs) will cost the healthcare system an estimated $1.62 billion by 2020[5]. PJIs are often difficult to treat due to the formation of biofilm at the site of the infection. A large majority of PJIs are the result of a bacterial biofilm, but around 1% of PJIs are due to fungal infections[3]. The current method of treatment is to surgically remove all infected tissue at the site of infection through a process called debridement and then insert a medicated bone cement spacer[7], [10]–[12]. One such medication that is loaded into the bone cement is caspofungin, a member of the echinocandin class of compounds that inhibit the synthesis of 1,3-β-D-glucan which is a crucial element of the cell wall of the target fungi[13]–[15]. For the studies reported herein, the caspofungin-loaded bone cement samples were made at 5 dosage strengths according to standard operating room practices. The elution of the drug was analyzed using ultraviolet spectrophotometry. The elution profiles were analyzed for 19 days consecutively, during which the 70 mg, 1 g, and 5 g dosage groups showed a prolonged, sustained release of the caspofungin. The 70 mg and 1 g dosage cumulative mass release profiles were not statistically significant, but it is unlikely that the difference would not have a clinical significance especially in the treatment of a fungal biofilm infection. The determination of the elution profile for caspofungin from loaded-bone cement can provide clinicians with a basis for how the drug will release into the infected joint.
ContributorsMoore, Rex C. (Author) / Vernon, Brent (Thesis director) / Overstreet, Derek (Committee member) / Industrial, Systems & Operations Engineering Prgm (Contributor) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
With microspheres growing in popularity as viable systems for targeted drug therapeutics, there exist a host of diseases and pathology induced side effects which could be treated with poly(lactic-co-glycolic acid) [PLGA] microparticle systems [6,10,12]. While PLGA systems are already applied in a wide variety the clinical setting [11], microparticles still have some way to go before they are viable systems for drug delivery. One of the main reasons for this is a lack of fabrication processes and systems which produce monodisperse particles while also being feasible for industrialization [10]. This honors thesis investigates various microparticle fabrication techniques \u2014 two using mechanical agitation and one using fluid dynamics \u2014 with the long term goal of incorporating norepinephrine and adenosine into the particles for metabolic stimulatory purposes. It was found that mechanical agitation processes lead to large values for dispersity and the polydispersity index while fluid dynamics methods have the potential to create more uniform and predictable outcomes. The research concludes by needing further investigation into methods and prototype systems involving fluid dynamics methods; however, these systems yield promising results for fabricating monodisperse particles which have the potential to encapsulate a wide variety of therapeutic drugs.
ContributorsRiley, Levi Louis (Author) / Vernon, Brent (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Originally conceived as a way to scaffold molecules of interest into three-dimensional (3D) crystalline lattices for X ray crystallography, the field of deoxyribonucleic acid (DNA) nanotechnology has dramatically evolved since its inception. The unique properties of DNA nanostructures have promoted their use not only for X ray crystallography, but for a suite of biomedical applications as well. The work presented in this dissertation focuses on both of these exciting applications in the field: 1) Nucleic acid nanostructures as multifunctional drug and vaccine delivery platforms, and 2) 3D DNA crystals for structure elucidation of scaffolded guest molecules.Chapter 1 illustrates how a wide variety of DNA nanostructures have been developed for the delivery of drugs and vaccine components. However, their applications are limited under physiological conditions due to their lack of stability in low salt environments, susceptibility to enzymatic degradation, and tendency for endosomal entrapment. To address these issues, Chapter 2 describes a PEGylated peptide coating molecule was designed to electrostatically adhere to and protect DNA origami nanostructures and to facilitate their cytosolic delivery by peptide-mediated endosomal escape. The development of this molecule will aid in the use of nucleic acid nanostructures for biomedical purposes, such as the delivery of messenger ribonucleic acid (mRNA) vaccine constructs. To this end, Chapter 3 discusses the fabrication of a structured mRNA nanoparticle for more cost-efficient mRNA vaccine manufacture and proposes a multi-epitope mRNA nanostructure vaccine design for targeting human papillomavirus (HPV) type 16-induced head and neck cancers.
DNA nanotechnology was originally envisioned to serve as three-dimensional scaffolds capable of positioning proteins in a rigid array for their structure elucidation by X ray crystallography. Accordingly, Chapter 4 explores design parameters, such as sequence and Holliday junction isomeric forms, for efficient crystallization of 3D DNA lattices. Furthermore, previously published DNA crystal motifs are used to site-specifically position and structurally evaluate minor groove binding molecules with defined occupancies. The results of this study provide significant advancement towards the ultimate goal of the field.
ContributorsHenry, Skylar J.W. (Author) / Stephanopoulos, Nicholas (Thesis advisor) / Anderson, Karen (Thesis advisor) / Blattman, Joseph (Committee member) / Yan, Hao (Committee member) / Arizona State University (Publisher)
Created2023