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Description
Modern day gas turbine designers face the problem of hot mainstream gas ingestion into rotor-stator disk cavities. To counter this ingestion, seals are installed on the rotor and stator disk rims and purge air, bled off from the compressor, is injected into the cavities. It is desirable to reduce the

Modern day gas turbine designers face the problem of hot mainstream gas ingestion into rotor-stator disk cavities. To counter this ingestion, seals are installed on the rotor and stator disk rims and purge air, bled off from the compressor, is injected into the cavities. It is desirable to reduce the supply of purge air as this decreases the net power output as well as efficiency of the gas turbine. Since the purge air influences the disk cavity flow field and effectively the amount of ingestion, the aim of this work was to study the cavity velocity field experimentally using Particle Image Velocimetry (PIV). Experiments were carried out in a model single-stage axial flow turbine set-up that featured blades as well as vanes, with purge air supplied at the hub of the rotor-stator disk cavity. Along with the rotor and stator rim seals, an inner labyrinth seal was provided which split the disk cavity into a rim cavity and an inner cavity. First, static gage pressure distribution was measured to ensure that nominally steady flow conditions had been achieved. The PIV experiments were then performed to map the velocity field on the radial-tangential plane within the rim cavity at four axial locations. Instantaneous velocity maps obtained by PIV were analyzed sector-by-sector to understand the rim cavity flow field. It was observed that the tangential velocity dominated the cavity flow at low purge air flow rate, its dominance decreasing with increase in the purge air flow rate. Radially inboard of the rim cavity, negative radial velocity near the stator surface and positive radial velocity near the rotor surface indicated the presence of a recirculation region in the cavity whose radial extent increased with increase in the purge air flow rate. Qualitative flow streamline patterns are plotted within the rim cavity for different experimental conditions by combining the PIV map information with ingestion measurements within the cavity as reported in Thiagarajan (2013).
ContributorsPathak, Parag (Author) / Roy, Ramendra P (Thesis advisor) / Calhoun, Ronald (Committee member) / Lee, Taewoo (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Gold nanoparticles have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs

Gold nanoparticles have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. Additionally, sub-toxic concentrations of 1,4C-1,4Bis-GNR nanoassemblies were employed to deliver expression vectors that express shRNA ('shRNA plasmid') against firefly luciferase gene in order to knock down expression of the protein constitutively expressed in prostate cancer cells. The roles of poly(amino ether) chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. The theranostic potential of 1,4C-1,4Bis-GNR nanoassemblies was demonstrated using live cell two-photon induced luminescence bioimaging. The PAE class of polymers was also investigated for the one pot synthesis of both gold and silver nanoparticles using a small library poly(amino ethers) derived from linear-like polyamines. Efficient nanoparticle synthesis dependent on concentration of polymers as well as polymer chemical composition is demonstrated. Additionally, the application of poly(amino ether)-gold nanoparticles for transgene delivery is demonstrated in 22Rv1 and MB49 cancer cell lines. Base polymer, 1,4C-1,4Bis and 1,4C-1,4Bis templated and modified gold nanoparticles were compared for transgene delivery efficacies. Differences in morphology and physiochemical properties were investigated as they relate to differences in transgene delivery efficacy. There were found to be minimal differences suggestion that 1,4C-1,4Bis efficacy is not lost following use for nanoparticle modification. These results indicate that poly(amino ether)-gold nanoassemblies are a promising theranostic platform for delivery of therapeutic payloads capable of simultaneous gene silencing and bioimaging.
ContributorsRamos, James (Author) / Rege, Kaushal (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Caplan, Michael (Committee member) / Vernon, Brent (Committee member) / Garcia, Antonio (Committee member) / Arizona State University (Publisher)
Created2014
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Description
Achieving effective drug concentrations within the central nervous system (CNS) remains one of the greatest challenges for the treatment of brain tumors. The presence of the blood-brain barrier and blood-spinal cord barrier severely restricts the blood-to-CNS entry of nearly all systemically administered therapeutics, often leading to the development of peripheral

Achieving effective drug concentrations within the central nervous system (CNS) remains one of the greatest challenges for the treatment of brain tumors. The presence of the blood-brain barrier and blood-spinal cord barrier severely restricts the blood-to-CNS entry of nearly all systemically administered therapeutics, often leading to the development of peripheral toxicities before a treatment benefit is observed. To circumvent systemic barriers, intrathecal (IT) injection of therapeutics directly into the cerebrospinal fluid (CSF) surrounding the brain and spinal cord has been used as an alternative administration route; however, its widespread translation to the clinic has been hindered by poor drug pharmacokinetics (PK), including rapid clearance, inadequate distribution, as well as toxicity. One strategy to overcome the limitations of free drug PK and improve drug efficacy is to encapsulate drug within nanoparticles (NP), which solubilize hydrophobic molecules for sustained release in physiological environments. In this thesis, we will develop NP delivery strategies for brain tumor therapy in two model systems: glioblastoma (GBM), the most common and deadly malignant primary brain tumor, and medulloblastoma, the most common pediatric brain tumor. In the first research chapter, we developed 120 nm poly(lactic acid-co-glycolic acid) NPs encapsulating the chemotherapy, camptothecin, for intravenous delivery to GBM. NP encapsulation of camptothecin was shown to reduce the drug’s toxicity and enable effective delivery to orthotopic GBM. To build off the success of intravenous NP, the second research chapter explored the utility of 100 nm PEGylated NPs for use with IT administration. Using in vivo imaging and ex vivo tissue slices, we found the NPs were rapidly transported by the convective forces of the CSF along the entire neuraxis and were retained for over 3 weeks. Based on their wide spread delivery and prolonged circulation, we examine the ability of the NPs to localize with tumor lesions in a leptomeningeal metastasis (LM) model of medulloblastoma. NPs administered to LM bearing mice were shown to penetrate into LM mets seeded within the meninges around the brain. These data show the potential to translate our success with intravenous NPs for GBM to improve IT chemotherapy delivery to LM.
ContributorsHouseholder, Kyle Thomas (Author) / Sirianni, Rachael W. (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Caplan, Michael (Committee member) / Wechsler-Reya, Robert (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Cerebral aneurysms are pathological balloonings of blood vessels in the brain, commonly found in the arterial network at the base of the brain. Cerebral aneurysm rupture can lead to a dangerous medical condition, subarachnoid hemorrhage, that is associated with high rates of morbidity and mortality. Effective evaluation and management of

Cerebral aneurysms are pathological balloonings of blood vessels in the brain, commonly found in the arterial network at the base of the brain. Cerebral aneurysm rupture can lead to a dangerous medical condition, subarachnoid hemorrhage, that is associated with high rates of morbidity and mortality. Effective evaluation and management of cerebral aneurysms is therefore essential to public health. The goal of treating an aneurysm is to isolate the aneurysm from its surrounding circulation, thereby preventing further growth and rupture. Endovascular treatment for cerebral aneurysms has gained popularity over traditional surgical techniques due to its minimally invasive nature and shorter associated recovery time. The hemodynamic modifications that the treatment effects can promote thrombus formation within the aneurysm leading to eventual isolation. However, different treatment devices can effect very different hemodynamic outcomes in aneurysms with different geometries.

Currently, cerebral aneurysm risk evaluation and treatment planning in clinical practice is largely based on geometric features of the aneurysm including the dome size, dome-to-neck ratio, and parent vessel geometry. Hemodynamics, on the other hand, although known to be deeply involved in cerebral aneurysm initiation and progression, are considered to a lesser degree. Previous work in the field of biofluid mechanics has demonstrated that geometry is a driving factor behind aneurysmal hemodynamics.

The goal of this research is to develop a more combined geometric/hemodynamic basis for informing clinical decisions. Geometric main effects were analyzed to quantify contributions made by geometric factors that describe cerebral aneurysms (i.e., dome size, dome-to-neck ratio, and inflow angle) to clinically relevant hemodynamic responses (i.e., wall shear stress, root mean square velocity magnitude and cross-neck flow). Computational templates of idealized bifurcation and sidewall aneurysms were created to satisfy a two-level full factorial design, and examined using computational fluid dynamics. A subset of the computational bifurcation templates was also translated into physical models for experimental validation using particle image velocimetry. The effects of geometry on treatment were analyzed by virtually treating the aneurysm templates with endovascular devices. The statistical relationships between geometry, treatment, and flow that emerged have the potential to play a valuable role in clinical practice.
ContributorsNair, Priya (Author) / Frakes, David (Thesis advisor) / Vernon, Brent (Committee member) / Chong, Brian (Committee member) / Pizziconi, Vincent (Committee member) / Adrian, Ronald (Committee member) / Arizona State University (Publisher)
Created2016
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Description
The application of novel visualization and modeling methods to the study of cardiovascular disease is vital to the development of innovative diagnostic techniques, including those that may aid in the early detection and prevention of cardiovascular disorders. This dissertation focuses on the application of particle image velocimetry (PIV) to the

The application of novel visualization and modeling methods to the study of cardiovascular disease is vital to the development of innovative diagnostic techniques, including those that may aid in the early detection and prevention of cardiovascular disorders. This dissertation focuses on the application of particle image velocimetry (PIV) to the study of intracardiac hemodynamics. This is accomplished primarily though the use of ultrasound based PIV, which allows for in vivo visualization of intracardiac flow without the requirement for optical access, as is required with traditional camera-based PIV methods.

The fundamentals of ultrasound PIV are introduced, including experimental methods for its implementation as well as a discussion on estimating and mitigating measurement error. Ultrasound PIV is then compared to optical PIV; this is a highly developed technique with proven accuracy; through rigorous examination it has become the “gold standard” of two-dimensional flow visualization. Results show good agreement between the two methods.

Using a mechanical left heart model, a multi-plane ultrasound PIV technique is introduced and applied to quantify a complex, three-dimensional flow that is analogous to the left intraventricular flow. Changes in ventricular flow dynamics due to the rotational orientation of mechanical heart valves are studied; the results demonstrate the importance of multi-plane imaging techniques when trying to assess the strongly three-dimensional intraventricular flow.

The potential use of ultrasound PIV as an early diagnosis technique is demonstrated through the development of a novel elasticity estimation technique. A finite element analysis routine is couple with an ensemble Kalman filter to allow for the estimation of material elasticity using forcing and displacement data derived from PIV. Results demonstrate that it is possible to estimate elasticity using forcing data derived from a PIV vector field, provided vector density is sufficient.
ContributorsWesterdale, John Curtis (Author) / Adrian, Ronald (Thesis advisor) / Belohlavek, Marek (Committee member) / Squires, Kyle (Committee member) / Trimble, Steve (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2015
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Description
Aortic pathologies such as coarctation, dissection, and aneurysm represent a

particularly emergent class of cardiovascular diseases and account for significant cardiovascular morbidity and mortality worldwide. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies and for planning their surgical repair. In vitro experiments

Aortic pathologies such as coarctation, dissection, and aneurysm represent a

particularly emergent class of cardiovascular diseases and account for significant cardiovascular morbidity and mortality worldwide. Computational simulations of aortic flows are growing increasingly important as tools for gaining understanding of these pathologies and for planning their surgical repair. In vitro experiments are required to validate these simulations against real world data, and a pulsatile flow pump system can provide physiologic flow conditions characteristic of the aorta.

This dissertation presents improved experimental techniques for in vitro aortic blood flow and the increasingly larger parts of the human cardiovascular system. Specifically, this work develops new flow management and measurement techniques for cardiovascular flow experiments with the aim to improve clinical evaluation and treatment planning of aortic diseases.

The hypothesis of this research is that transient flow driven by a step change in volume flux in a piston-based pulsatile flow pump system behaves differently from transient flow driven by a step change in pressure gradient, the development time being substantially reduced in the former. Due to this difference in behavior, the response to a piston-driven pump can be predicted in order to establish inlet velocity and flow waveforms at a downstream phantom model.

The main objectives of this dissertation were: 1) to design, construct, and validate a piston-based flow pump system for aortic flow experiments, 2) to characterize temporal and spatial development of start-up flows driven by a piston pump that produces a step change from zero flow to a constant volume flux in realistic (finite) tube geometries for physiologic Reynolds numbers, and 3) to develop a method to predict downstream velocity and flow waveforms at the inlet of an aortic phantom model and determine the input waveform needed to achieve the intended waveform at the test section. Application of these newly improved flow management tools and measurement techniques were then demonstrated through in vitro experiments in patient-specific coarctation of aorta flow phantom models manufactured in-house and compared to computational simulations to inform and execute future experiments and simulations.
ContributorsChaudhury, Rafeed Ahmed (Author) / Frakes, David (Thesis advisor) / Adrian, Ronald J (Thesis advisor) / Vernon, Brent (Committee member) / Pizziconi, Vincent (Committee member) / Caplan, Michael (Committee member) / Arizona State University (Publisher)
Created2015