Matching Items (8)
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- All Subjects: Particle Image Velocimetry
- All Subjects: Tissue Engineering
- Creators: Vernon, Brent
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 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
Description
Myocardial infarction (MI) remains the leading cause of mortality and morbidity in the U.S., accounting for nearly 140,000 deaths per year. Heart transplantation and implantation of mechanical assist devices are the options of last resort for intractable heart failure, but these are limited by lack of organ donors and potential surgical complications. In this regard, there is an urgent need for developing new effective therapeutic strategies to induce regeneration and restore the loss contractility of infarcted myocardium. Over the past decades, regenerative medicine has emerged as a promising strategy to develop scaffold-free cell therapies and scaffold-based cardiac patches as potential approaches for MI treatment. Despite the progress, there are still critical shortcomings associated with these approaches regarding low cell retention, lack of global cardiomyocytes (CMs) synchronicity, as well as poor maturation and engraftment of the transplanted cells within the native myocardium. The overarching objective of this dissertation was to develop two classes of nanoengineered cardiac patches and scaffold-free microtissues with superior electrical, structural, and biological characteristics to address the limitations of previously developed tissue models. An integrated strategy, based on micro- and nanoscale technologies, was utilized to fabricate the proposed tissue models using functionalized gold nanomaterials (GNMs). Furthermore, comprehensive mechanistic studies were carried out to assess the influence of conductive GNMs on the electrophysiology and maturity of the engineered cardiac tissues. Specifically, the role of mechanical stiffness and nano-scale topographies of the scaffold, due to the incorporation of GNMs, on cardiac cells phenotype, contractility, and excitability were dissected from the scaffold’s electrical conductivity. In addition, the influence of GNMs on conduction velocity of CMs was investigated in both coupled and uncoupled gap junctions using microelectrode array technology. Overall, the key contributions of this work were to generate new classes of electrically conductive cardiac patches and scaffold-free microtissues and to mechanistically investigate the influence of conductive GNMs on maturation and electrophysiology of the engineered tissues.
ContributorsNavaei, Ali (Author) / Nikkhah, Mehdi (Thesis advisor) / Brafman, David (Committee member) / Migrino, Raymond Q. (Committee member) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2018
Description
Cardiac tissue engineering has major applications in regenerative medicine, disease modeling and fundamental biological studies. Despite the significance, numerous questions still need to be explored to enhance the functionalities of the engineered tissue substitutes. In this study, three dimensional (3D) cardiac micro-tissues were developed through encapsulating co-culture of cardiomyocytes and cardiac fibroblasts, as the main cellular components of native myocardium, within photocrosslinkable gelatin-based hydrogels. Different co-culture ratios were assessed to optimize the functional properties of constructs. The geometry of the micro-tissues was precisely controlled using micro-patterning techniques in order to evaluate their role on synchronous contraction of the cells. Cardiomyocytes exhibited a native-like phenotype when co-cultured with cardiac fibroblasts as compared to the mono-culture condition. Particularly, elongated F-actin fibers with abundance of sarcomeric α-actinin and troponin-I were observed within all layers of the hydrogel constructs. Higher expressions of connexin-43 and integrin β1 indicated improved cell-cell and cell-matrix interactions. Amongst co-culture conditions, 2:1 (cardiomyocytes: cardiac fibroblasts) ratio exhibited enhanced functionalities, whereas decreasing the construct size adversely affected the synchronous contraction of the cells. Therefore, this study indicated that cell-cell ratio as well as the geometrical features of the micropatterned constructs are among crucial parameters, which need to be optimized in order to enhance the functionalities of engineered tissue substitutes and cardiac patches.
ContributorsSaini, Harpinder (Author) / Nikkhah, Mehdi (Thesis advisor) / Vernon, Brent (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2015
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 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.
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
Description
Stromal cell-derived factor-1α (SDF-1α) and its key receptor, CXCR4 are ubiquitously expressed in systems across the body (e.g. liver, skin, lung, etc.). This signaling axis regulates a myriad of physiological processes that range from maintaining of organ homeostasis in adults to, chemotaxis of stem/progenitor and immune cell types after injury. Given its potential role as a therapeutic target for diverse applications, surprisingly little is known about how SDF-1α mediated signaling propagates through native tissues. This limitation ultimately constrains rational design of interventional biomaterials that aim to target the SDF-1α/CXCR4 signaling axis. One application of particular interest is traumatic brain injury (TBI) for which, there are currently no means of targeting the underlying biochemical pathology to improve prognosis.
Growing evidence suggests a relationship between SDF-1α/CXCR4 signaling and endogenous neural progenitor/stem cells (NPSC)-mediated regeneration after neural injury. Long-term modulation of the SDF-1α/CXCR4 signaling axis is thus hypothesized as a possible avenue for harnessing and amplifying endogenous regenerative mechanisms after TBI. In order to understand how the SDF-1α/CXCR4 signaling can be modulated in vivo, we first developed and characterized a sustained protein delivery platform in vitro. We were the first, to our knowledge, to demonstrate that protein release profiles from poly(D,L,-lactic-co-glycolic) acid (PLGA) particles can be tuned independent of particle fabrication parameters via centrifugal fractioning. This process of physically separating the particles altered the average diameter of a particle population, which is in turn was correlated to critical release characteristics. Secondly, we demonstrated sustained release of SDF-1α from PLGA/fibrin composites (particles embedded in fibrin) with tunable burst release as a function of fibrin concentration. Finally, we contrasted the spatiotemporal localization of endogenous SDF-1α and CXCR4 expression in response to either bolus or sustained release of exogenous SDF-1α. Sustained release of exogenous SDF-1α induced spatially diffuse endogenous SDF-1/CXCR4 expression relative to bolus SDF-1 administration; however, the observed effects were transient in both cases, persisting only to a maximum of 3 days post injection. These studies will inform future systematic evaluations of strategies that exploit SDF-1α/CXCR4 signaling for diverse applications.
Growing evidence suggests a relationship between SDF-1α/CXCR4 signaling and endogenous neural progenitor/stem cells (NPSC)-mediated regeneration after neural injury. Long-term modulation of the SDF-1α/CXCR4 signaling axis is thus hypothesized as a possible avenue for harnessing and amplifying endogenous regenerative mechanisms after TBI. In order to understand how the SDF-1α/CXCR4 signaling can be modulated in vivo, we first developed and characterized a sustained protein delivery platform in vitro. We were the first, to our knowledge, to demonstrate that protein release profiles from poly(D,L,-lactic-co-glycolic) acid (PLGA) particles can be tuned independent of particle fabrication parameters via centrifugal fractioning. This process of physically separating the particles altered the average diameter of a particle population, which is in turn was correlated to critical release characteristics. Secondly, we demonstrated sustained release of SDF-1α from PLGA/fibrin composites (particles embedded in fibrin) with tunable burst release as a function of fibrin concentration. Finally, we contrasted the spatiotemporal localization of endogenous SDF-1α and CXCR4 expression in response to either bolus or sustained release of exogenous SDF-1α. Sustained release of exogenous SDF-1α induced spatially diffuse endogenous SDF-1/CXCR4 expression relative to bolus SDF-1 administration; however, the observed effects were transient in both cases, persisting only to a maximum of 3 days post injection. These studies will inform future systematic evaluations of strategies that exploit SDF-1α/CXCR4 signaling for diverse applications.
ContributorsDutta, Dipankar (Author) / Stabenfeldt, Sarah E (Thesis advisor) / Kleim, Jeffrey (Committee member) / Nikkhah, Mehdi (Committee member) / Sirianni, Rachael (Committee member) / Vernon, Brent (Committee member) / Arizona State University (Publisher)
Created2016
Description
Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, causing nearly 25% of deaths in the United States. Despite the efforts to create in vitro models for the study and treatment of CVDs, these are still limited in their recapitulation of the heart tissue. Thus, the engineering of accurate cardiac models is imperative to gain more understanding and improve the outcome of CVDs. This Ph.D. dissertation focuses on the development and characterization of isogenic cardiac organoids derived from human induced pluripotent stem cells (hiPSCs). Additionally, the integration of chemical and biological cues for enriching their microenvironment and promoting their maturation state and function were studied. First, hiPSC-derived cardiac cells were utilized for the fabrication of multicellular spherical microtissues, namely isogenic cardiac organoids. The cellular composition and culture time of the engineered tissues were optimized to induce cellular aggregation and the formation of cell-cell interactions. Also, ribbon-like gold nanoparticles, namely gold nanoribbons (AuNRs), were synthesized, characterized, and biofunctionalized for their integration into the isogenic cardiac organoids. In-depth biological evaluation of the organoids showed enhanced cardiac maturation markers. Furthermore, a supplement-free cell culture regime was designed and evaluated for fabricating isogenic cardiac organoids. Mechanistic, cellular, and molecular-level studies demonstrated that the presence of hiPSC-derived cardiac fibroblasts (hiPSC-CFs) significantly improves the morphology and gene expression profile of the organoids. Electrophysiological-relevant features of the organoids, such as conduction velocity (CV), were further investigated utilizing a microelectrode array (MEA) platform. It was shown that MEA offers a simple, yet powerful approach to assessing electrophysiological responses of the tissues, where a trend in decreased CV was found due to the presence of hiPSC-CFs. Overall, this dissertation has a broad impact casting light on the development strategy and biological mechanisms that govern the formation and function of isogenic cardiac organoids. Moreover, this study presents two unique approaches to promote maturation of stem cell-derived cardiac organoids: 1) through the integration of novel biofunctionalized nanomaterials, and 2) through a cell culture regime, leading to enhanced function of the organoids. The proposed micro-engineered organoids have broad applications as physiologically relevant tissues for drug discovery, CVDs modeling, and regenerative medicine.
ContributorsPatino, Alejandra (Author) / Nikkhah, Medhi (Thesis advisor) / Blain-Christen, Jennifer (Committee member) / Kodibagkar, Vikram (Committee member) / Vernon, Brent (Committee member) / Zhu, Wuqiang (Committee member) / Arizona State University (Publisher)
Created2023
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 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.
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
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 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.
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