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Description
The combination of immunohistochemical (IHC) stainings and optical microscopy has allowed for the visualization of specific microscopic structures within tissue; however, limitations in light and antibody penetration mitigate the scale on which these images can be taken (Alshammari et al, 2016; Marx, 2014). Tissue clearing, specifically the removal of lipids to improve sample transparency, solves the former weakness well, but does not improve antibody penetration significantly (Chung et al, 2013; Treweek et al, 2015). Therefore, there is a need to equalize the maximum depth that light can pass through a section with the depth at which there is recognizable fluorescence. This is particularly important when staining blood vessels as traditional size limitations exclusively allows for cross sectional visualization. Passive CLARITY Technique (PACT) has been at the forefront of tissue clearing protocols, utilizing an acrylamide hydrogel solution to maintain structure and sodium dodecyl sulfate to wash out lipids (Tomer et al, 2014). PACT is limited in its ability to clear larger sections and is not conducive to IHC antibody diffusion (Treweek et al, 2015). In order to circumvent these drawbacks, CUBIC was developed as an alternative passive protocol, aimed at being scalable to any tissue size (Richardson, 2015; Susaki et al, 2015). This study compared the effectiveness of both protocols in high and low lipid tissues in the context of blood vessel staining efficacy. Upon initial comparison, it became apparent that there was a statistically significant difference in mean DAPI intensity at all depths, up to 200 micrometers, between CUBIC and PACT \u2014 the former showcasing brighter stainings. Moreover, it was found that PACT does not remove erythrocytes from the tissue meaning that their auto-fluorescence is seen during imaging. Therefore, for blood vessel stainings, only CUBIC was optimized and quantitatively analyzed. In both tissue conditions as well as for two stainings, DAPI and fibronectin (FNCT), optimized CUBIC demonstrated a statistically significant difference from standard CUBIC with regards to mean fluorescent intensity.
ContributorsSidhu, Gurpaul Singh (Author) / VanAuker, Michael (Thesis director) / Kodibagkar, Vikram (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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
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
This study aimed to quantify glare induced into the NICU through phototherapy devices commonly used to treat neonatal jaundice. The blue light associated with the devices can cause a number of physiological affects including melatonin suppression, disturbances of one's circadian rhythm, and has the potential to lead to risk factors of age-related macular degeneration (AMD) in the long term. The study found that the phototherapy device tested emitted a sufficient amount of light to be considered 'disturbing' using the DeBoer scale. Due to this, phototherapy devices in the future should take into consideration the minimization of light emitted which is not directly treating the infant on the device to prevent potential physiological effects that nurses may experience.
ContributorsSnelling, Timothy Michael (Author) / Muthuswamy, Jitendran (Thesis director) / VanAuker, Michael (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
This study investigates the application of Computational Fluid Dynamics (CFD) to the medical field. An overview of recent advances in computational simulation and modeling in medical applications is provided, with a particular emphasis on CFD. This study attempts to validate CFD and demonstrate the possibility for applying CFD to the clinical treatment and evaluation of atherosclerotic disease. Three different geometric configurations are investigated: one idealized bifurcation with a primary diameter of 8 mm, and two different patient-specific models of the bifurcation from the common femoral artery to the superficial and deep femoral arteries. CFD is compared against experimental measurements of steady state and pulsatile flow acquired with Particle Image Velocimetry (PIV). Steady state and pulsatile flow rates that are consistent with those observed in the femoral artery are used. In addition, pulsatile CFD simulations are analyzed in order to demonstrate meaningful clinical applications for studying and evaluating the treatment of atherosclerotic disease. CFD was successfully validated for steady state flow, with an average percent error of 6.991%. Potential for validation was also demonstrated for pulsatile flow, but methodological errors warrant further investigation to reformulate methods and analyze results. Quantities frequently associated with atherosclerotic disease and arterial bifurcations, such as large variations in wall shear stress and the presence of recirculation zones are demonstrated from the pulsatile CFD simulations. Further study is required in order to evaluate whether or not such phenomena are represented by CFD accurately. Further study must also be performed in order to evaluate the practicality and utility of CFD for the evaluation of atherosclerotic disease treatment.
ContributorsMortensen, Matthew James (Author) / VanAuker, Michael (Thesis director) / Frakes, David (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
A fetus physiologically relies on blood for nutrients given by the mother. Blood supply is provided to a fetus through an umbilical cord having the structure of two pulsatile arteries with smooth muscle surrounding a thin walled vein. The two arteries transport deoxygenated blood from the fetus in the direction of the placenta while the one vein transports oxygenated blood in the direction of the fetus. This process of the movement of blood is continuous throughout the gestation cycle. Conventionally, there are two arterial coils for every one coil of the vein. Undercoiling and overcoiling of the arteries leads to fetal distress, resulting in researchers to speculate that there is a relationship between these geometries with altered blood flow patterns that may be deleterious to the fetus. The fluid dynamics of an umbilical cord artery blood flow has not been extensively modeled on a computer, meaning there is an absence of knowledge on the ideal pitch of the coiling of the umbilical cord arteries. In this study, I developed computer models with ANSYS Fluent containing fluid dynamic variables and boundary conditions including: density of blood, viscosity of blood, diameter of each artery, pitch of artery coil, flow rate in each artery, and inlet velocity. Care was taken to investigate the effect of fluid finite element size, through mesh refinement, to improve accuracy of the models. The finalized models illustrate velocity and stress distribution in a coiled artery, showing different patterns in a model representing normal as compared to abnormal pitch. Further study of the fluid mechanics in the coil of the umbilical cord arteries, may elucidate the correlation between ideal pitch and fetal distress.
ContributorsSeaney, Amanda Marie (Author) / VanAuker, Michael (Thesis director) / Lilien, Lawrence (Committee member) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Polymer drug delivery system offers a key to a glaring issue in modern administration routes of drugs and biologics. Poly(lactic-co-glycolic acid) (PLGA) can be used to encapsulate drugs and biologics and deliver them into the patient, which allows high local concentration (compared to current treatment methods), protection of the cargo from the bodily environment, and reduction in systemic side effects. This experiment used a single emulsion technique to encapsulate L-tyrosine in PLGA microparticles and UV spectrophotometry to analyze the drug release over a period of one week. The release assay found that for the tested samples, the released amount is distinct initially, but is about the same after 4 days, and they generally follow the same normalized percent released pattern. The experiment could continue with testing more samples, test the same samples for a longer duration, and look into higher w/w concentrations such as 20% or 50%.
ContributorsSeo, Jinpyo (Author) / Vernon, Brent (Thesis director) / Pal, Amrita (Committee member) / Dean, W.P. Carey School of Business (Contributor) / Harrington Bioengineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
The goal of this research project is to create a Mathcad template file capable of statistically modelling the effects of mean and standard deviation on a microparticle batch characterized by the log normal distribution model. Such a file can be applied during manufacturing to explore tolerances and increase cost and time effectiveness. Theoretical data for the time to 60% drug release and the slope and intercept of the log-log plot were collected and subjected to statistical analysis in JMP. Since the scope of this project focuses on microparticle surface degradation drug release with no drug diffusion, the characteristic variables relating to the slope (n = diffusional release exponent) and the intercept (k = kinetic constant) do not directly apply to the distribution model within the scope of the research. However, these variables are useful for analysis when the Mathcad template is applied to other types of drug release models.
ContributorsHan, Priscilla (Author) / Vernon, Brent (Thesis director) / Nickle, Jacob (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Intellectual property law and the controversy surrounding its nuances, loopholes, and obscure definitions have existed and grown since the inception of the original U.S. Constitution. The original idea was to legislate a way so that innovators and inventors of every generation could be incentivised to create new products which could increase the efficiency and productivity in all aspects of American life. However, the generalizations placed in the law, perhaps for the purpose of giving inventors more leeway, has become, over time, a double-edged sword. Because lawsuits and the lucrative settlements that follow were attached to violating intellectual property law, other individuals have mischievously used this to their advantage, namely creating as many random ideas as possible and patenting them so that when someone ingeniously creates an actual product or physical manifestation, those individuals can sue that inventor for supposedly “stealing” their “idea”. These individuals are basically unable to bring their idea to life so they set traps for those who can. So the law, which originally was supposed to motivate Americans to create has now become a weapon that can be used against those true innovators. Our topic then is to look more in-depth at a specific aspect under the broad umbrella of intellectual property law: can intellectual property law apply to biotechnology? We want to look into different forms of biotechnology, medical devices, and pharmaceuticals, observe where patent law has deviated from its original path and where it is going.
ContributorsLai, Edward (Co-author) / Goudamanis, Christy (Co-author) / Takahashi, Timothy (Thesis director) / VanAuker, Michael (Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05