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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
Description
Esophageal adenocarcinoma (EAC) is one of the most lethal and fastest growing cancers in the United States. Its onset is commonly triggered by metaplastic transformation of normal squamous esophageal epithelial cells to Barrett's esophagus (BE) cells in response to acid reflux. BE patients are believed to progress through non-dysplastic metaplasia and increasing grades of dysplasia prior to EAC. Conventional cancer diagnostic tools rely on bulk-cell analyses that are incapable of identifying intratumoral heterogeneity or rare driver cells that play important roles in cancer progression. An improved single-cell method of cancer diagnosis would overcome this challenge by detecting cancer initiating cells before they progress into untreatable stages. In this study, using EAC as a model, we attempted to identify a more effective method of cancer diagnosis. We quantified the single- and bulk-cell mRNA expression of genes that have been proposed to be instrumental in the progression of EAC through BE. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis was performed on human primary cells to measure the mRNA expression levels of BE- and EAC-associated genes. Our results showed high levels of heterogeneity of CDX2 and TFF3 at the single-cell resolution in human BE and EAC samples. Additionally, while expression of VEGF is generally low at the bulk-cell level, our results showed that a few, rare cells had significantly higher VEGF expression levels than the majority of cells in the EAC sample. In conclusion, we have affirmed that EAC cancer cells, as well as BE cells, show high levels of heterogeneity. Based on the VEGF gene expression pattern, single-cell analysis could potentially be more effective for identifying rare, but essential cells for cancer progression, which could then be targeted for treatment. Future studies will focus on analyzing human samples from thousands of normal and cancer subjects to validate the use of single-cell profiling in cancer.
ContributorsHaeuser, Kelsey Lynn (Author) / Tran, Thai (Thesis director) / Kelbauskas, Laimonas (Committee member) / Gao, Weimin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-12
Description
Background
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.
Grading schemes for breast cancer diagnosis are predominantly based on pathologists' qualitative assessment of altered nuclear structure from 2D brightfield microscopy images. However, cells are three-dimensional (3D) objects with features that are inherently 3D and thus poorly characterized in 2D. Our goal is to quantitatively characterize nuclear structure in 3D, assess its variation with malignancy, and investigate whether such variation correlates with standard nuclear grading criteria.
Methodology
We applied micro-optical computed tomographic imaging and automated 3D nuclear morphometry to quantify and compare morphological variations between human cell lines derived from normal, benign fibrocystic or malignant breast epithelium. To reproduce the appearance and contrast in clinical cytopathology images, we stained cells with hematoxylin and eosin and obtained 3D images of 150 individual stained cells of each cell type at sub-micron, isotropic resolution. Applying volumetric image analyses, we computed 42 3D morphological and textural descriptors of cellular and nuclear structure.
Principal Findings
We observed four distinct nuclear shape categories, the predominant being a mushroom cap shape. Cell and nuclear volumes increased from normal to fibrocystic to metastatic type, but there was little difference in the volume ratio of nucleus to cytoplasm (N/C ratio) between the lines. Abnormal cell nuclei had more nucleoli, markedly higher density and clumpier chromatin organization compared to normal. Nuclei of non-tumorigenic, fibrocystic cells exhibited larger textural variations than metastatic cell nuclei. At p<0.0025 by ANOVA and Kruskal-Wallis tests, 90% of our computed descriptors statistically differentiated control from abnormal cell populations, but only 69% of these features statistically differentiated the fibrocystic from the metastatic cell populations.
Conclusions
Our results provide a new perspective on nuclear structure variations associated with malignancy and point to the value of automated quantitative 3D nuclear morphometry as an objective tool to enable development of sensitive and specific nuclear grade classification in breast cancer diagnosis.
ContributorsNandakumar, Vivek (Author) / Kelbauskas, Laimonas (Author) / Hernandez, Kathryn (Author) / Lintecum, Kelly (Author) / Senechal, Patti (Author) / Bussey, Kimberly (Author) / Davies, Paul (Author) / Johnson, Roger (Author) / Meldrum, Deirdre (Author) / Ira A. Fulton Schools of Engineering (Contributor) / School of Electrical, Computer and Energy Engineering (Contributor) / Biodesign Institute (Contributor) / Center for Biosignatures Discovery Automation (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Life Sciences (Contributor) / Department of Physics (Contributor)
Created2012-01-05
Description
Productivity in the construction industry is an essential measure of production efficiency and economic progress, quantified by craft laborers' time spent directly adding value to a project. In order to better understand craft labor productivity as an aspect of lean construction, an activity analysis was conducted at the Arizona State University Palo Verde Main engineering dormitory construction site in December of 2016. The objective of this analysis on craft labor productivity in construction projects was to gather data regarding the efficiency of craft labor workers, make conclusions about the effects of time of day and other site-specific factors on labor productivity, as well as suggest improvements to implement in the construction process. Analysis suggests that supporting tasks, such as traveling or materials handling, constitute the majority of craft labors' efforts on the job site with the highest percentages occurring at the beginning and end of the work day. Direct work and delays were approximately equal at about 20% each hour with the highest peak occurring at lunchtime between 10:00 am and 11:00 am. The top suggestion to improve construction productivity would be to perform an extensive site utilization analysis due to the confined nature of this job site. Despite the limitations of an activity analysis to provide a complete prospective of all the factors that can affect craft labor productivity as well as the small number of days of data acquisition, this analysis provides a basic overview of the productivity at the Palo Verde Main construction site. Through this research, construction managers can more effectively generate site plans and schedules to increase labor productivity.
ContributorsFord, Emily Lucile (Author) / Grau, David (Thesis director) / Chong, Oswald (Committee member) / Civil, Environmental and Sustainable Engineering Programs (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
The overall energy consumption around the United States has not been reduced even with the advancement of technology over the past decades. Deficiencies exist between design and actual energy performances. Energy Infrastructure Systems (EIS) are impacted when the amount of energy production cannot be accurately and efficiently forecasted. Inaccurate engineering assumptions can result when there is a lack of understanding on how energy systems can operate in real-world applications. Energy systems are complex, which results in unknown system behaviors, due to an unknown structural system model. Currently, there exists a lack of data mining techniques in reverse engineering, which are needed to develop efficient structural system models. In this project, a new type of reverse engineering algorithm has been applied to a year's worth of energy data collected from an ASU research building called MacroTechnology Works, to identify the structural system model. Developing and understanding structural system models is the first step in creating accurate predictive analytics for energy production. The associative network of the building's data will be highlighted to accurately depict the structural model. This structural model will enhance energy infrastructure systems' energy efficiency, reduce energy waste, and narrow the gaps between energy infrastructure design, planning, operation and management (DPOM).
ContributorsCamarena, Raquel Jimenez (Author) / Chong, Oswald (Thesis director) / Ye, Nong (Committee member) / Industrial, Systems (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Building construction, design and maintenance is a sector of engineering where improved efficiency will have immense impacts on resource consumption and environmental health. This research closely examines the Leadership in Environment and Energy Design (LEED) rating system and the International Green Construction Code (IgCC). The IgCC is a model code, written with the same structure as many building codes. It is a standard that can be enforced if a city's government decides to adopt it. When IgCC is enforced, the buildings either meet all of the requirements set forth in the document or it fails to meet the code standards. The LEED Rating System, on the other hand, is not a building code. LEED certified buildings are built according to the standards of their local jurisdiction and in addition to that, building owners can chose to pursue a LEED certification. This is a rating system that awards points based on the sustainable measures achieved by a building. A comparison of these green building systems highlights their accomplishments in terms of reduced electricity usage, usage of low-impact materials, indoor environmental quality and other innovative features. It was determined that in general IgCC is more holistic, stringent approach to green building. At the same time the LEED rating system a wider variety of green building options. In addition, building data from LEED certified buildings was complied and analyzed to understand important trends. Both of these methods are progressing towards low-impact, efficient infrastructure and a side-by-side comparison, as done in this research, shed light on the strengths and weaknesses of each method, allowing for future improvements.
ContributorsCampbell, Kaleigh Ruth (Author) / Chong, Oswald (Thesis director) / Parrish, Kristen (Committee member) / Civil, Environmental and Sustainable Engineering Programs (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
This paper describes the research done to quantify the relationship between external air temperature and energy consumption and internal air temperature and energy consumption. The study was conducted on a LEED Gold certified building, College Avenue Commons, located on Arizona State University's Tempe campus. It includes information on the background of previous studies in the area, some that agree with the research hypotheses and some that take a different path. Real-time data was collected hourly for energy consumption and external air temperature. Intermittent internal air temperature was collected by undergraduate researcher, Charles Banke. Regression analysis was used to prove two research hypotheses. The authors found no correlation between external air temperature and energy consumption, nor did they find a relationship between internal air temperature and energy consumption. This paper also includes recommendations for future work to improve the study.
ContributorsBanke, Charles Michael (Author) / Chong, Oswald (Thesis director) / Parrish, Kristen (Committee member) / Mechanical and Aerospace Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The Chinese Construction Industry has grown to be one of the largest construction markets in the world within the last 10 years. The size of the Chinese Construction Industry is on par with many developed nations, despite it being a developing country. Despite its rapid growth, the productivity and profitability of the Chinese Construction Industry is low compared to similar sized construction industries (United States, United Kingdom, etc.). In addition to the low efficiency of the Chinese Construction Industry, there is minimal documentation available showing the performance of the Chinese Construction Industry (projects completed on time, on budget, and customer satisfaction ratings).
The purpose of this research is to investigate potential solutions that could address the poor efficiency and performance of the Chinese Construction Industry. This research is divided into three phases; first, a literature review to identify countries that have similar construction industries to the Chinese Construction Industry. The second phase is to compare the risks and identify solutions that are proposed to increase the performance of similar construction industries and the Chinese Construction Industry. The third phase is to create a survey from the literature-based information to validate the concepts with the Chinese Construction Industry professionals and stakeholders.
The purpose of this research is to investigate potential solutions that could address the poor efficiency and performance of the Chinese Construction Industry. This research is divided into three phases; first, a literature review to identify countries that have similar construction industries to the Chinese Construction Industry. The second phase is to compare the risks and identify solutions that are proposed to increase the performance of similar construction industries and the Chinese Construction Industry. The third phase is to create a survey from the literature-based information to validate the concepts with the Chinese Construction Industry professionals and stakeholders.
ContributorsChen, Yutian (Author) / Chong, Oswald (Thesis advisor) / Kashiwagi, Dean T. (Committee member) / Badger, Willliam (Committee member) / Arizona State University (Publisher)
Created2020
Description
Traditional Reinforcement Learning (RL) assumes to learn policies with respect to reward available from the environment but sometimes learning in a complex domain requires wisdom which comes from a wide range of experience. In behavior based robotics, it is observed that a complex behavior can be described by a combination of simpler behaviors. It is tempting to apply similar idea such that simpler behaviors can be combined in a meaningful way to tailor the complex combination. Such an approach would enable faster learning and modular design of behaviors. Complex behaviors can be combined with other behaviors to create even more advanced behaviors resulting in a rich set of possibilities. Similar to RL, combined behavior can keep evolving by interacting with the environment. The requirement of this method is to specify a reasonable set of simple behaviors. In this research, I present an algorithm that aims at combining behavior such that the resulting behavior has characteristics of each individual behavior. This approach has been inspired by behavior based robotics, such as the subsumption architecture and motor schema-based design. The combination algorithm outputs n weights to combine behaviors linearly. The weights are state dependent and change dynamically at every step in an episode. This idea is tested on discrete and continuous environments like OpenAI’s “Lunar Lander” and “Biped Walker”. Results are compared with related domains like Multi-objective RL, Hierarchical RL, Transfer learning, and basic RL. It is observed that the combination of behaviors is a novel way of learning which helps the agent achieve required characteristics. A combination is learned for a given state and so the agent is able to learn faster in an efficient manner compared to other similar approaches. Agent beautifully demonstrates characteristics of multiple behaviors which helps the agent to learn and adapt to the environment. Future directions are also suggested as possible extensions to this research.
ContributorsVora, Kevin Jatin (Author) / Zhang, Yu (Thesis advisor) / Yang, Yezhou (Committee member) / Praharaj, Sarbeswar (Committee member) / Arizona State University (Publisher)
Created2021
Description
Although Saudi Arabia is moving towards a sustainable future, Existing residential buildings in the country are extremely unsustainable. Therefore, there is a necessity for greening the existing residential building. Mostadam green rating systems was developed by the Saudi ministry of housing in 2019 to address the long-term sustainability vision in residential buildings in the country. By setting Mostadam requirements as an objective of the retrofit process, it will ensure that the building achieve sustainability. However, Mostadam is new and there is a lack of knowledge of implementing its requirements on existing buildings. The aim of this research is to develop a framework to green existing residential buildings in Saudi Arabia to achieve Mostadam energy and water minimum requirements. The framework was developed based on an extensive keyword-based search and an analysis of 92 relevant research. The process starts with assessing the building against the minimum requirements of energy and water of Mostadam. After that, optimization phase is conducted. Building information modelling is used in the optimization phase. Energy and water efficiency optimization measures are identified from the analysed literature. Revit is used in the base model authoring and Green building studio cloud is used to simulate the energy and water efficiency measures. Then, payback period is calculated for all the efficiency measured to assess the decision making. A case study of a villa in Riyadh, Saudi Arabia is provided. result shows that the implemented efficiency measures led to an increment of 37.5% in annual energy savings and 26.1% in the annual water savings. Results shows that the application of the proposed framework supports evaluating energy and water efficiency measures to implement it on the buildings to achieve Mostadam minimum energy and water requirements. Recommendations were made for future work to bridge the knowledge gap.
ContributorsMohamed, Sara Murad (Author) / Sullivan, Kenneth (Thesis advisor) / Chong, Oswald (Committee member) / Hurtado, Kristen (Committee member) / Arizona State University (Publisher)
Created2022