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Filtration for microfluidic sample-collection devices is desirable for sample selection, concentration, preprocessing, and downstream manipulation, but microfabricating the required sub-micrometer filtration structure is an elaborate process. This thesis presents a simple method to fabricate polydimethylsiloxane (PDMS) devices with an integrated membrane filter that will sample, lyse, and extract the DNA

Filtration for microfluidic sample-collection devices is desirable for sample selection, concentration, preprocessing, and downstream manipulation, but microfabricating the required sub-micrometer filtration structure is an elaborate process. This thesis presents a simple method to fabricate polydimethylsiloxane (PDMS) devices with an integrated membrane filter that will sample, lyse, and extract the DNA from microorganisms in aqueous environments. An off-the-shelf membrane filter disc was embedded in a PDMS layer and sequentially bound with other PDMS channel layers. No leakage was observed during filtration. This device was validated by concentrating a large amount of cyanobacterium Synechocystis in simulated sample water with consistent performance across devices. After accumulating sufficient biomass on the filter, a sequential electrochemical lysing process was performed by applying 5VDC across the filter. This device was further evaluated by delivering several samples of differing concentrations of cyanobacterium Synechocystis then quantifying the DNA using real-time PCR. Lastly, an environmental sample was run through the device and the amount of photosynthetic microorganisms present in the water was determined. The major breakthroughs in this design are low energy demand, cheap materials, simple design, straightforward fabrication, and robust performance, together enabling wide-utility of similar chip-based devices for field-deployable operations in environmental micro-biotechnology.
ContributorsLecluse, Aurelie (Author) / Meldrum, Deirdre (Thesis advisor) / Chao, Joseph (Thesis advisor) / Westerhoff, Paul (Committee member) / Arizona State University (Publisher)
Created2011
Description
Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study of cellular morphology, a single cell three-dimensional (3D) imaging system

Single cell phenotypic heterogeneity studies reveal more information about the pathogenesis process than conventional bulk methods. Furthermore, investigation of the individual cellular response mechanism during rapid environmental changes can only be achieved at single cell level. By enabling the study of cellular morphology, a single cell three-dimensional (3D) imaging system can be used to diagnose fatal diseases, such as cancer, at an early stage. One proven method, CellCT, accomplishes 3D imaging by rotating a single cell around a fixed axis. However, some existing cell rotating mechanisms require either intricate microfabrication, and some fail to provide a suitable environment for living cells. This thesis develops a microvorterx chamber that allows living cells to be rotated by hydrodynamic alone while facilitating imaging access. In this thesis work, 1) the new chamber design was developed through numerical simulation. Simulations revealed that in order to form a microvortex in the side chamber, the ratio of the chamber opening to the channel width must be smaller than one. After comparing different chamber designs, the trapezoidal side chamber was selected because it demonstrated controllable circulation and met the imaging requirements. Microvortex properties were not sensitive to the chambers with interface angles ranging from 0.32 to 0.64. A similar trend was observed when chamber heights were larger than chamber opening. 2) Micro-particle image velocimetry was used to characterize microvortices and validate simulation results. Agreement between experimentation and simulation confirmed that numerical simulation was an effective method for chamber design. 3) Finally, cell rotation experiments were performed in the trapezoidal side chamber. The experimental results demonstrated cell rotational rates ranging from 12 to 29 rpm for regular cells. With a volumetric flow rate of 0.5 µL/s, an irregular cell rotated at a mean rate of 97 ± 3 rpm. Rotational rates can be changed by altering inlet flow rates.
ContributorsZhang, Wenjie (Author) / Frakes, David (Thesis advisor) / Meldrum, Deirdre (Thesis advisor) / Chao, Shih-hui (Committee member) / Wang, Xiao (Committee member) / Arizona State University (Publisher)
Created2011
Description
Laboratory automation systems have seen a lot of technological advances in recent times. As a result, the software that is written for them are becoming increasingly sophisticated. Existing software architectures and standards are targeted to a wider domain of software development and need to be customized in order to use

Laboratory automation systems have seen a lot of technological advances in recent times. As a result, the software that is written for them are becoming increasingly sophisticated. Existing software architectures and standards are targeted to a wider domain of software development and need to be customized in order to use them for developing software for laboratory automation systems. This thesis proposes an architecture that is based on existing software architectural paradigms and is specifically tailored to developing software for a laboratory automation system. The architecture is based on fairly autonomous software components that can be distributed across multiple computers. The components in the architecture make use of asynchronous communication methodologies that are facilitated by passing messages between one another. The architecture can be used to develop software that is distributed, responsive and thread-safe. The thesis also proposes a framework that has been developed to implement the ideas proposed by the architecture. The framework is used to develop software that is scalable, distributed, responsive and thread-safe. The framework currently has components to control very commonly used laboratory automation devices such as mechanical stages, cameras, and also to do common laboratory automation functionalities such as imaging.
ContributorsKuppuswamy, Venkataramanan (Author) / Meldrum, Deirdre (Thesis advisor) / Collofello, James (Thesis advisor) / Sarjoughian, Hessam S. (Committee member) / Johnson, Roger (Committee member) / Arizona State University (Publisher)
Created2012
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Description
Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of

Single cell analysis has become increasingly important in understanding disease onset, progression, treatment and prognosis, especially when applied to cancer where cellular responses are highly heterogeneous. Through the advent of single cell computerized tomography (Cell-CT), researchers and clinicians now have the ability to obtain high resolution three-dimensional (3D) reconstructions of single cells. Yet to date, no live-cell compatible version of the technology exists. In this thesis, a microfluidic chip with the ability to rotate live single cells in hydrodynamic microvortices about an axis parallel to the optical focal plane has been demonstrated. The chip utilizes a novel 3D microchamber design arranged beneath a main channel creating flow detachment into the chamber, producing recirculating flow conditions. Single cells are flowed through the main channel, held in the center of the microvortex by an optical trap, and rotated by the forces induced by the recirculating fluid flow. Computational fluid dynamics (CFD) was employed to optimize the geometry of the microchamber. Two methods for the fabrication of the 3D microchamber were devised: anisotropic etching of silicon and backside diffuser photolithography (BDPL). First, the optimization of the silicon etching conditions was demonstrated through design of experiment (DOE). In addition, a non-conventional method of soft-lithography was demonstrated which incorporates the use of two positive molds, one of the main channel and the other of the microchambers, compressed together during replication to produce a single ultra-thin (<200 µm) negative used for device assembly. Second, methods for using thick negative photoresists such as SU-8 with BDPL have been developed which include a new simple and effective method for promoting the adhesion of SU-8 to glass. An assembly method that bonds two individual ultra-thin (<100 µm) replications of the channel and the microfeatures has also been demonstrated. Finally, a pressure driven pumping system with nanoliter per minute flow rate regulation, sub-second response times, and < 3% flow variability has been designed and characterized. The fabrication and assembly of this device is inexpensive and utilizes simple variants of conventional microfluidic fabrication techniques, making it easily accessible to the single cell analysis community.
ContributorsMyers, Jakrey R (Author) / Meldrum, Deirdre (Thesis advisor) / Johnson, Roger (Committee member) / Frakes, David (Committee member) / Arizona State University (Publisher)
Created2012
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Description
High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular

High throughput transcriptome data analysis like Single-cell Ribonucleic Acid sequencing (scRNA-seq) and Circular Ribonucleic Acid (circRNA) data have made significant breakthroughs, especially in cancer genomics. Analysis of transcriptome time series data is core in identifying time point(s) where drastic changes in gene transcription are associated with homeostatic to non-homeostatic cellular transition (tipping points). In Chapter 2 of this dissertation, I present a novel cell-type specific and co-expression-based tipping point detection method to identify target gene (TG) versus transcription factor (TF) pairs whose differential co-expression across time points drive biological changes in different cell types and the time point when these changes are observed. This method was applied to scRNA-seq data sets from a SARS-CoV-2 study (18 time points), a human cerebellum development study (9 time points), and a lung injury study (18 time points). Similarly, leveraging transcriptome data across treatment time points, I developed methodologies to identify treatment-induced and cell-type specific differentially co-expressed pairs (DCEPs). In part one of Chapter 3, I presented a pipeline that used a series of statistical tests to detect DCEPs. This method was applied to scRNA-seq data of patients with non-small cell lung cancer (NSCLC) sequenced across cancer treatment times. However, this pipeline does not account for correlations among multiple single cells from the same sample and correlations among multiple samples from the same patient. In Part 2 of Chapter 3, I presented a solution to this problem using a mixed-effect model. In Chapter 4, I present a summary of my work that focused on the cross-species analysis of circRNA transcriptome time series data. I compared circRNA profiles in neonatal pig and mouse hearts, identified orthologous circRNAs, and discussed regulation mechanisms of cardiomyocyte proliferation and myocardial regeneration conserved between mouse and pig at different time points.
ContributorsNyarige, Verah Mocheche (Author) / Liu, Li (Thesis advisor) / Wang, Junwen (Thesis advisor) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not

Beta-Amyloid(Aβ) plaques and tau protein tangles in the brain are now widely recognized as the defining hallmarks of Alzheimer’s disease (AD), followed by structural atrophy detectable on brain magnetic resonance imaging (MRI) scans. However, current methods to detect Aβ/tau pathology are either invasive (lumbar puncture) or quite costly and not widely available (positron emission tomography (PET)). And one of the particular neurodegenerative regions is the hippocampus to which the influence of Aβ/tau on has been one of the research projects focuses in the AD pathophysiological progress. In this dissertation, I proposed three novel machine learning and statistical models to examine subtle aspects of the hippocampal morphometry from MRI that are associated with Aβ /tau burden in the brain, measured using PET images. The first model is a novel unsupervised feature reduction model to generate a low-dimensional representation of hippocampal morphometry for each individual subject, which has superior performance in predicting Aβ/tau burden in the brain. The second one is an efficient federated group lasso model to identify the hippocampal subregions where atrophy is strongly associated with abnormal Aβ/Tau. The last one is a federated model for imaging genetics, which can identify genetic and transcriptomic influences on hippocampal morphometry. Finally, I stated the results of these three models that have been published or submitted to peer-reviewed conferences and journals.
ContributorsWu, Jianfeng (Author) / Wang, Yalin (Thesis advisor) / Li, Baoxin (Committee member) / Liang, Jianming (Committee member) / Wang, Junwen (Committee member) / Wu, Teresa (Committee member) / Arizona State University (Publisher)
Created2022
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Description
Infrastructure systems are facing non-stationary challenges that stem from climate change and the increasingly complex interactions between the social, ecological, and technological systems (SETSs). It is crucial for transportation infrastructures—which enable residents to access opportunities and foster prosperity, quality of life, and social connections—to be resilient under these non-stationary challenges.

Infrastructure systems are facing non-stationary challenges that stem from climate change and the increasingly complex interactions between the social, ecological, and technological systems (SETSs). It is crucial for transportation infrastructures—which enable residents to access opportunities and foster prosperity, quality of life, and social connections—to be resilient under these non-stationary challenges. Vulnerability assessment (VA) examines the potential consequences a system is likely to experience due to exposure to perturbation or stressors and lack of the capacity to adapt. Post-fire debris flow and heat represent particularly challenging problems for infrastructure and users in the arid U.S. West. Post-fire debris flow, which is manifested with heat and drought, produces powerful runoff threatening physical transportation infrastructures. And heat waves have devastating health effects on transportation infrastructure users, including increased mortality rates. VA anticipates the potential consequences of these perturbations and enables infrastructure stakeholders to improve the system's resilience. The current transportation climate VA—which only considers a single direct climate stressor on the infrastructure—falls short of addressing the wildfire and heat challenges. This work proposes advanced transportation climate VA methods to address the complex and multiple climate stressors and the vulnerability of infrastructure users. Two specific regions were chosen to carry out the progressive transportation climate VA: 1) the California transportation networks’ vulnerability to post-fire debris flows, and 2) the transportation infrastructure user’s vulnerability to heat exposure in Phoenix.
ContributorsLi, Rui (Author) / Chester, Mikhail V. (Thesis advisor) / Middel, Ariane (Committee member) / Hondula, David M. (Committee member) / Pendyala, Ram (Committee member) / Arizona State University (Publisher)
Created2022
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Description
This dissertation research studies long-term spatio-temporal patterns of surface urban heat island (SUHI) intensity, urban evapotranspiration (ET), and urban outdoor water use (OWU) using Phoenix metropolitan area (PMA), Arizona as the case study. This dissertation is composed of three chapters. The first chapter evaluates the SUHI intensity for PMA using

This dissertation research studies long-term spatio-temporal patterns of surface urban heat island (SUHI) intensity, urban evapotranspiration (ET), and urban outdoor water use (OWU) using Phoenix metropolitan area (PMA), Arizona as the case study. This dissertation is composed of three chapters. The first chapter evaluates the SUHI intensity for PMA using Moderate Resolution Imaging Spectroradiometer (MODIS) land surface temperature (LST) product and a time-series trend analysis to discover areas that experienced significant changes of SUHI intensity between 2000 and 2017. The heating and cooling effects of different urban land use land cover (LULC) types was also examined using classified Landsat satellite images. The second chapter is focused on urban ET and the impacts of urban LULC change on ET. An empirical model of urban ET for PMA was built using flux tower data and MODIS land products using multivariate regression analysis. A time-series trend analysis was then performed to discover areas in PMA that experienced significant changes of ET between 2001 and 2015. The impact of urban LULC change on ET was examined using classified LULC maps. The third chapter models urban OWU in PMA using a surface energy balance model named METRIC (Mapping Evapotranspiration at high spatial Resolution with Internalized Calibration) and time-series Landsat Thematic Mapper 5 imagery for 2010. The relationship between urban LULC types and OWU was examined with the use of very high-resolution land cover classification data generated from the National Agriculture Imagery Program (NAIP) imagery and regression analysis. Socio-demographic variables were selected from census data at the census track level and analyzed against OWU to study their relationship using correlation analysis. This dissertation makes significant contributions and expands the knowledge of long-term urban climate dynamics for PMA and the influence of urban expansion and LULC change on regional climate. Research findings and results can be used to provide constructive suggestions to urban planners, decision-makers, and city managers to formulate new policies and regulations when planning new constructions for the purpose of sustainable development for a desert city.
ContributorsWang, Chuyuan (Author) / Myint, Soe W. (Thesis advisor) / Brazel, Anthony J. (Committee member) / Wang, Zhihua (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2018
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Description

Many coastal cities around the world are becoming increasingly vulnerable to natural disasters, particularly flooding driven by tropical storm and hurricane storm surge – typically the most destructive feature of these storms, generating significant economic damage and loss of life. This increase in vulnerability is driven by the interactions between

Many coastal cities around the world are becoming increasingly vulnerable to natural disasters, particularly flooding driven by tropical storm and hurricane storm surge – typically the most destructive feature of these storms, generating significant economic damage and loss of life. This increase in vulnerability is driven by the interactions between a wide number of complex social and climatic factors, including population growth, irresponsible urban development, a decrease in essential service provision, sea level rise, and changing storm regimes. These issues are exacerbated by the short-term strategic planning that dominates political action and economic decision-making, resulting in many vulnerable coastal communities being particularly unprepared for large, infrequent storm surge events. This lack of preparedness manifests in several ways, but one of the most visible is the lack of comprehensive evacuation and rescue operation plans for use after major storm surge flooding occurs. Typical evacuation or rescue plans are built using a model of a region’s intact road network. While useful for pre-disaster purposes, the immediate aftermath of large floods sees enormous swaths of a given region’s road system flooded, rendering most of these plans largely useless. Post-storm evacuation and rescue requires large amounts of atypical travel through a region (i.e., across non-road surfaces). Traditional road network models (such as those that are used to generate evacuation routes) are unable to conceptualize this type of transportation, and so are of limited utility during post-disaster scenarios. To solve these problems, this dissertation introduces an alternative network conceptualization that preserves important on-network information but also accounts for the possibility of off-network travel during a disaster. Providing this in situ context is necessary to adequately model transportation through a post-storm landscape, one in which evacuees and rescuers are regularly departing from roads and one in which many roads are completely interdicted by flooding. This modeling approach is used to automatically generate routes through a flooded coastal urban area, as well as to identify potentially critical road segments in advance of an actual storm. These tools may help both emergency managers better prepare for large storms, and urban planners in their efforts to mitigate flood damage.

ContributorsHelderop, Edward (Author) / Grubesic, Tony H. (Thesis advisor) / Kuby, Mike (Committee member) / Hondula, David M. (Committee member) / Arizona State University (Publisher)
Created2019
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Description

Environmental heat is a growing concern in cities as a consequence of rapid urbanization and climate change, threatening human health and urban vitality. The transportation system is naturally embedded in the issue of urban heat and human heat exposure. Research has established how heat poses a threat to urban inhabitants

Environmental heat is a growing concern in cities as a consequence of rapid urbanization and climate change, threatening human health and urban vitality. The transportation system is naturally embedded in the issue of urban heat and human heat exposure. Research has established how heat poses a threat to urban inhabitants and how urban infrastructure design can lead to increased urban heat. Yet there are gaps in understanding how urban communities accumulate heat exposure, and how significantly the urban transportation system influences or exacerbates the many issues of urban heat. This dissertation focuses on advancing the understanding of how modern urban transportation influences urban heat and human heat exposure through three research objectives: 1) Investigate how human activity results in different outdoor heat exposure; 2) Quantify the growth and extent of urban parking infrastructure; and 3) Model and analyze how pavements and vehicles contribute to urban heat.

In the urban US, traveling outdoors (e.g. biking or walking) is the most frequent activity to cause heat exposure during hot periods. However, outdoor travel durations are often very short, and other longer activities such as outdoor housework and recreation contribute more to cumulative urban heat exposure. In Phoenix, parking and roadway pavement infrastructure contributes significantly to the urban heat balance, especially during summer afternoons, and vehicles only contribute significantly in local areas with high density rush hour vehicle travel. Future development of urban areas (especially those with concerns of extreme heat) should focus on ensuring access and mobility for its inhabitants without sacrificing thermal comfort. This may require urban redesign of transportation systems to be less auto-centric, but without clear pathways to mitigating impacts of urban heat, it may be difficult to promote transitions to travel modes that inherently necessitate heat exposure. Transportation planners and engineers need to be cognizant of the pathways to increased urban heat and human heat exposure when planning and designing urban transportation systems.

ContributorsHoehne, Christopher Glenn (Author) / Chester, Mikhail V (Thesis advisor) / Hondula, David M. (Committee member) / Sailor, David (Committee member) / Pendyala, Ram M. (Committee member) / Arizona State University (Publisher)
Created2019