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- All Subjects: Biomedical Engineering
- Genre: Academic theses
Description
In the search for chemical biosensors designed for patient-based physiological applications, non-invasive diagnostic approaches continue to have value. The work described in this thesis builds upon previous breath analysis studies. In particular, it seeks to assess the adsorptive mechanisms active in both acetone and ethanol biosensors designed for breath analysis. The thermoelectric biosensors under investigation were constructed using a thermopile for transduction and four different materials for biorecognition. The analytes, acetone and ethanol, were evaluated under dry-air and humidified-air conditions. The biosensor response to acetone concentration was found to be both repeatable and linear, while the sensor response to ethanol presence was also found to be repeatable. The different biorecognition materials produced discernible thermoelectric responses that were characteristic for each analyte. The sensor output data is presented in this report. Additionally, the results were evaluated against a mathematical model for further analysis. Ultimately, a thermoelectric biosensor based upon adsorption chemistry was developed and characterized. Additional work is needed to characterize the physicochemical action mechanism.
ContributorsWilson, Kimberly (Author) / Guilbeau, Eric (Thesis advisor) / Pizziconi, Vincent (Thesis advisor) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2011
Description
Statistical process control (SPC) and predictive analytics have been used in industrial manufacturing and design, but up until now have not been applied to threshold data of vital sign monitoring in remote care settings. In this study of 20 elders with COPD and/or CHF, extended months of peak flow monitoring (FEV1) using telemedicine are examined to determine when an earlier or later clinical intervention may have been advised. This study demonstrated that SPC may bring less than a 2.0% increase in clinician workload while providing more robust statistically-derived thresholds than clinician-derived thresholds. Using a random K-fold model, FEV1 output was predictably validated to .80 Generalized R-square, demonstrating the adequate learning of a threshold classifier. Disease severity also impacted the model. Forecasting future FEV1 data points is possible with a complex ARIMA (45, 0, 49), but variation and sources of error require tight control. Validation was above average and encouraging for clinician acceptance. These statistical algorithms provide for the patient's own data to drive reduction in variability and, potentially increase clinician efficiency, improve patient outcome, and cost burden to the health care ecosystem.
ContributorsFralick, Celeste (Author) / Muthuswamy, Jitendran (Thesis advisor) / O'Shea, Terrance (Thesis advisor) / LaBelle, Jeffrey (Committee member) / Pizziconi, Vincent (Committee member) / Shea, Kimberly (Committee member) / Arizona State University (Publisher)
Created2013
Description
The effects of specific histone deacetylase inhibitors (HDACi) on transgene expression in combination with a novel polymer as a delivery vehicle are investigated in this research. Polymer vectors, although safer than viruses, are notorious for low levels of gene expression. In this investigation, the use of an emerging chemotherapeutic anti-cancer drug molecule, HDACi, was used to enhance the polymer-mediated gene expression. HDACi are capable of inhibiting deacetylation activities of histones and other non-histone proteins in the cytoplasm and nucleus, as well as increase transcriptional activities necessary for gene expression. In a prior study, a parallel synthesis and screening of polymers yielded a lead cationic polymer with high DNA-binding properties, and even more attractive, high transgene expressions. Previous studies showed the use of this polymer in conjunction with cytoplasmic HDACi significantly enhanced gene expression in PC3-PSMA prostate cancer cells. This led to the basis for the investigation presented in this thesis, but to use nuclear HDACi to potentially achieve similar results. The HDACi, HDACi_A, was a previously discovered lead drug that had potential to significantly enhance luciferase expression in PC3-PSMA cells. The results of this study found that the 20:1 polymer:plasmid DNA weight ratio was effective with 1 uM and 2 uM HDACI_A concentrations, showing up to a 9-fold enhancement. This enhancement suggested that HDACi_A was effectively aiding transfection. While not an astounding enhancement, it is still interesting enough to investigate further. Cell viabilities need to be determined to supplement the results.
ContributorsLehrman, Jennifer (Author) / Rege, Kaushal (Thesis advisor) / Caplan, Michael (Committee member) / Pizziconi, Vincent (Committee member) / Arizona State University (Publisher)
Created2012
Description
Multiple Sclerosis, an autoimmune disease, is one of the most common neurological disorder in which demyelinating of the axon occurs. The main symptoms of MS disease are fatigue, vision problems, stability issue, balance problems. Unfortunately, currently available treatments for this disease do not always guarantee the improvement of the condition of the MS patient and there has not been an accurate mechanism to measure the effectiveness of the treatment due to inter-patient heterogeneity. The factors that count for varying the performance of MS patients include environmental setting, weather, psychological status, dressing style and more. Also, patients may react differently while examined at specially arranged setting and this may not be the same while he/she is at home. Hence, it becomes a major problem for MS patients that how effectively a treatment slows down the progress of the disease and gives a relief for the patient. This thesis is trying to build a reliable system to estimate how good a treatment is for MS patients. Here I study the kinematic variables such as velocity of walking, stride length, variability and so on to find and compare the variations of the patient after a treatment given by the doctor, and trace these parameters for some patients after the treatment effect subdued.
ContributorsYin, Siyang (Author) / He, Jiping (Thesis advisor) / Pizziconi, Vincent (Committee member) / Towe, Bruce (Committee member) / Arizona State University (Publisher)
Created2012
Description
The objective of this research is to investigate the relationship among key process design variables associated with the development of nanoscale electrospun polymeric scaffolds capable of tissue regeneration. To date, there has been no systematic approach toward understanding electrospinning process parameters responsible for the production of 3-D nanoscaffold architectures with desired levels quality assurance envisioned to satisfy emerging regenerative medicine market needs. , As such, this study encompassed a more systematic, rational design of experiment (DOE) approach toward the identification of electrospinning process conditions responsible for the production of dextran-polyacrylic acid (DEX-PAA) nanoscaffolds with desired architectures and tissue engineering properties. The latter includes scaffold fiber diameter, pore size, porosity, and degree of crosslinking that together can provide a range of scaffold nanomechanical properties that closely mimics the cell microenvironment. The results obtained from this preliminary DOE study indicate that there exist electrospinning operation conditions capable of producing Dex-PAA nanoarchitecture having potential utility for regenerative medicine applications.
ContributorsEspinoza, Roberta (Author) / Pizziconi, Vincent (Thesis advisor) / Massia, Stephen (Committee member) / Garcia, Antonio (Committee member) / Arizona State University (Publisher)
Created2013
Description
The overall goal of this research project was to assess the feasibility of investigating the effects of microgravity on mineralization systems in unit gravity environments. If possible to perform these studies in unit gravity earth environments, such as earth, such systems can offer markedly less costly and more concerted research efforts to study these vitally important systems. Expected outcomes from easily accessible test environments and more tractable studies include the development of more advanced and adaptive material systems, including biological systems, particularly as humans ponder human exploration in deep space. The specific focus of the research was the design and development of a prototypical experimental test system that could preliminarily meet the challenging design specifications required of such test systems. Guided by a more unified theoretical foundation and building upon concept design and development heuristics, assessment of the feasibility of two experimental test systems was explored. Test System I was a rotating wall reactor experimental system that closely followed the specifications of a similar test system, Synthecon, designed by NASA contractors and thus closely mimicked microgravity conditions of the space shuttle and station. The latter includes terminal velocity conditions experienced by both innate material systems, as well as, biological systems, including living tissue and humans but has the ability to extend to include those material test systems associated with mineralization processes. Test System II is comprised of a unique vertical column design that offered more easily controlled fluid mechanical test conditions over a much wider flow regime that was necessary to achieving terminal velocities under free convection-less conditions that are important in mineralization processes. Preliminary results indicate that Test System II offers distinct advantages in studying microgravity effects in test systems operating in unit gravity environments and particularly when investigating mineralization and related processes. Verification of the Test System II was performed on validating microgravity effects on calcite mineralization processes reported earlier others. There studies were conducted on calcite mineralization in fixed-wing, reduced gravity aircraft, known as the `vomit comet' where reduced gravity conditions are include for very short (~20second) time periods. Preliminary results indicate that test systems, such as test system II, can be devised to assess microgravity conditions in unit gravity environments, such as earth. Furthermore, the preliminary data obtained on calcite formation suggest that strictly physicochemical mechanisms may be the dominant factors that control adaptation in materials processes, a theory first proposed by Liu et al. Thus the result of this study may also help shine a light on the problem of early osteoporosis in astronauts and long term interest in deep space exploration.
ContributorsSeyedmadani, Kimia (Author) / Pizziconi, Vincent (Thesis advisor) / Towe, Bruce (Committee member) / Alford, Terry (Committee member) / Arizona State University (Publisher)
Created2013
Description
Allogeneic islet transplantation has the potential to reverse Type 1 Diabetes in patients. However, limitations such as chronic immunosuppression, islet donor numbers, and islet survival post-transplantation prevent the widespread application of allogeneic islet transplantation as the treatment of choice. Macroencapsulation devices have been widely used in allogeneic islet transplantation due to their capability to shield transplanted cells from the immune system as well as provide a supportive environment for cell viability, but macroencapsulation devices face oxygen transport challenges as their geometry increases from preclinical to clinical scales. The goal of this work is to generate complex 3D hydrogel macroencapsulation devices with sufficient oxygen transport to support encapsulated cell survival and generate these devices in a way that is accessible in the clinic as well as scaled manufacturing. A 3D-printed injection mold has been developed to generate hydrogel-based cell encapsulation devices with spiral geometries. The spiral geometry of the macroencapsulation device facilitates greater oxygen transport throughout the whole device resulting in improved islet function in vivo in a syngeneic rat model. A computational model of the oxygen concentration within macroencapsulation devices, validated by in vitro analysis, predicts that cells and islets maintain a greater viability and function in the spiral macroencapsulation device. To further validate the computational model, pO2 Reporter Composite Hydrogels (PORCH) are engineered to enable spatiotemporal measurement of oxygen tension within macroencapsulation devices using the Proton Imaging of Siloxanes to map Tissue Oxygenation Levels (PISTOL) magnetic resonance imaging approach. Overall, a macroencapsulation device geometry designed via computational modeling of device oxygen gradients and validated with magnetic resonance (MR) oximetry imaging enhances islet function and survival for islet transplantation.
ContributorsEmerson, Amy (Author) / Weaver, Jessica (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Sadleir, Rosalind (Committee member) / Stabenfeldt, Sarah (Committee member) / Wang, Kuei-Chun (Committee member) / Arizona State University (Publisher)
Created2023
Description
Tissues within the body enable proper function throughout an individual’s life. After severe injury or disease, many tissues do not fully heal without surgical intervention. The current surgical procedures aimed to repair tissues are not sufficient to fully restore functionality. To address these challenges, current research is seeking new tissue engineering approaches to promote tissue regeneration and functional recovery. Of particular interest, biomaterial scaffolds are designed to induce tissue regeneration by mimicking the biophysical and biochemical aspects of native tissue. While many scaffolds have been designed with homogenous properties, many tissues are heterogenous in nature. Thus, fabricating scaffolds that mimic these complex tissue properties is critical for inducing proper healing after injury. Within this dissertation, scaffolds were designed and fabricated to mimic the heterogenous properties of the following tissues: (1) the vocal fold, which is a complex 3D structure with spatially controlled mechanical properties; and (2) musculoskeletal tissue interfaces, which are fibrous tissues with highly organized gradients in structure and chemistry. A tri-layered hydrogel scaffold was fabricated through layer-by-layer stacking to mimic the mechanical structure of the vocal fold. Furthermore, magnetically-assisted electrospinning and thiol-norbornene photochemistry was used to fabricate fibrous scaffolds that mimic the structural and chemical organization of musculoskeletal interfacial tissues. The work presented in this dissertation further advances the tissue engineering field by using innovative techniques to design scaffolds that recapitulate the natural complexity of native tissues.
ContributorsTindell, Raymond Kevin (Author) / Holloway, Julianne (Thesis advisor) / Green, Matthew (Committee member) / Pizziconi, Vincent (Committee member) / Stephanopoulos, Nicholas (Committee member) / Acharya, Abhinav (Committee member) / Arizona State University (Publisher)
Created2021
Description
Cardiovascular diseases (CVDs), including myocardial infarction (MI), are the major cause of death globally. Considerable research has been devoted in recent years to developing in vitro cardiac tissue models utilizing human induced pluripotent stem cells (hiPSCs) for regenerative medicine, disease modeling, and drug discovery applications. Notably, electroconductive hydrogel scaffolds have shown great promise in the development of functional hiPSC-derived cardiac tissues for both in vitro and in vivo cardiac research. However, the underlying mechanism(s) by which these nanoparticles contribute to the function and fate of stem cell-derived cardiac tissues have not been fully investigated. To address these knowledge gaps, this Ph.D. dissertation focuses on the mechanistic analysis of the impact of nanoengineered electroconductive hydrogel scaffolds on 2D and 3D hiPSC-derived cardiac tissues. Specifically, within the first phase of the project, hydrogel scaffolds were nanoengineered using either electroconductive or non-conductive nanoparticles to dissect the role of electroconductivity features of gold nanorods (GNRs) in the functionality of isogenic 2D hiPSC-derived cardiac patches. Extensive biological and electrophysiological assessments revealed that, while biophysical cues from the presence of nanoparticles could potentially play a role in cardiac tissue development, electroconductivity cues played a major role in enhancing the functional maturation of hiPSC-derived cardiac tissues in 2D cell-seeded cardiac patches. This dissertation further describes the application of GNRs in developing a biomimetic 3D electroconductive Heart-on-a-chip (eHOC) model. The 3D eHOC model was then leveraged to comprehensively investigate the cellular and molecular responses of isogenic human cardiac tissues to the electroconductive microenvironment through single-cell RNA sequencing (scRNAseq), an aspect not addressed in previous studies. The enhanced functional maturation of the 3D eHOC was demonstrated through extensive tissue-level and molecular-level assays. It was revealed that the GNR-based electroconductive microenvironment contributes to cardiac tissue development through the enrichment of calcium handling and cardiac contractile pathways.Overall, these findings offer additional insights into the role of electroconductive hydrogel scaffolds in regulating the functionalities of hiPSC-derived cardiac tissues. Furthermore, the proposed 3D eHOC platform could also serve as a more physiologically representative model of the in vivo microenvironment for in vitro applications, such as drug testing and disease modeling studies.
ContributorsEsmaeili, Hamid (Author) / Nikkhah, Mehdi (Thesis advisor) / Migrino, Raymond (Committee member) / Zhu, Wuqiang (Committee member) / Vernon, Brent (Committee member) / Weaver, Jessica (Committee member) / Arizona State University (Publisher)
Created2024
Description
Cardiovascular diseases are the number one cause of death worldwide. Cardiac biomarkers can provide objective and quantitative information to facilitate early diagnosis and guide treatment of cardiovascular diseases. Even though a variety of methods have been developed for cardiac biomarker detection, a point-of-care testing (POCT) for cardiac biomarkers with high sensitivity, specificity and precision is still missing. To fulfil this unmet need, novel digital biosensing methods based on optical imaging and nanomaterials are developed in this dissertation for high-sensitivity POCT of cardiac biomarkers.First, a high-sensitivity and POC-compatible optical imaging-based digital immunoassay is developed for rapid detection of low-abundance biomarkers. This technology was established on a model analyte IL-6 and can be adapted to various other protein targets. The digital immunoassay was also utilized as the reference method for evaluating the digital nanobiosensors developed afterwards.
Second, a microfluidic digital nanobiosensor (MDNB) is developed for POC-compatible detection of heart failure biomarker NT-proBNP from 7 µL of whole blood. Using the MDNB, detection in a clinically relevant concentration range was achieved with a 10-minute assay time. With a high potential utility in outpatient and possibly even home settings, the MDNB could become a POC device for decentralized detection of NT-proBNP to assist heart failure patient management.
Lastly, the development of a digital immunogold-linked apta-sorbent assay (DILASA) for rapid high-sensitivity detection of heart attack biomarker cardiac troponin is introduced. Reliable detection of 10 ng/L cTnT in human plasma was achieved with a 15-minute assay time using DILASA. It is expected that with further optimization and development, DILASA will be a promising candidate approach for realizing a high-sensitivity POCT of cTnT.
ContributorsChen, Chao (Author) / Wang, Shaopeng (Thesis advisor) / Snozek, Christine (Committee member) / Pizziconi, Vincent (Committee member) / Vernon, Brent (Committee member) / Weaver, Jessica (Committee member) / Arizona State University (Publisher)
Created2024