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Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on

Cellular heterogeneity is a key factor in various cellular processes as well as in disease development, especially associated with immune response and cancer progression. Cell-to-cell variability is considered to be one of the major obstacles in early detection and successful treatment of cancer. Most present technologies are based on bulk cell analysis, which results in averaging out the results acquired from a group of cells and hence missing important information about individual cells and their behavior. Understanding the cellular behavior at the single-cell level can help in obtaining a complete profile of the cell and to get a more in-depth knowledge of cellular processes. For example, measuring transmembrane fluxes oxygen can provide a direct readout of the cell metabolism.

The goal of this thesis is to design, optimize and implement a device that can measure the oxygen consumption rate (OCR) of live single cells. A microfluidic device has been designed with the ability to rapidly seal and unseal microchambers containing individual cells and an extracellular optical oxygen sensor for measuring the OCR of live single cells. The device consists of two parts, one with the sensor in microwells (top half) and the other with channels and cells trapped in Pachinko-type micro-traps (bottom half). When the two parts of the device are placed together the wells enclose each cell. Oil is flown in through the channels of the device to produce isolated and sealed microchamber around each cell. Different fluids can be flowed in and out of the device, alternating with oil, to rapidly switch between sealed and unsealed microenvironment around each cell. A fluorescent ratiometric dual pH and oxygen sensor is placed in each well. The thesis focuses on measuring changes in the oxygen consumption rate of each cell within a well. Live and dead cells are identified using a fluorescent live/dead cell assay. Finally, the technology is designed to be scalable for high-throughput applications by controlling the flow rate of the system and increasing the cell array density.
ContributorsRodrigues, Meryl (Author) / Meldrum, Deirdre (Thesis advisor) / Kelbauskas, Laimonas (Committee member) / LaBelle, Jeffrey (Committee member) / Arizona State University (Publisher)
Created2014
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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
An urgent need for developing new chemical separations that address the capture of dilute impurities from fluid streams are needed. These separations include the capture of carbon dioxide from the atmosphere, impurities from drinking water, and toxins from blood streams. A challenge is presented when capturing these impurities because the

An urgent need for developing new chemical separations that address the capture of dilute impurities from fluid streams are needed. These separations include the capture of carbon dioxide from the atmosphere, impurities from drinking water, and toxins from blood streams. A challenge is presented when capturing these impurities because the energy cost for processing the bulk fluid stream to capture trace contaminants is too great using traditional thermal separations. The development of sorbents that may capture these contaminants passively has been emphasized in academic research for some time, producing many designer materials including metal-organic frameworks (MOFs) and polymeric resins. Scaffolds must be developed to effectively anchor these materials in a passing fluid stream. In this work, two design techniques are presented for anchoring these sorbents in electrospun fiber scaffolds.

The first technique involves imbedding sorbent particles inside the fibers: forming particle-embedded fibers. It is demonstrated that particles will spontaneously coat themselves in the fibers at dilute loadings, but at higher loadings some get trapped on the fiber surface. A mathematical model is used to show that when these particles are embedded, the polymeric coating provided by the fibers may be designed to increase the kinetic selectivity and/or stability of the embedded sorbents. Two proof-of-concept studies are performed to validate this model including the increased selectivity of carbon dioxide over nitrogen when the MOF ZIF-8 is embedded in a poly(ethylene oxide) and Matrimid polymer blend; and that increased hydrothermal stability is realized when the water-sensitive MOF HKUST-1 is embedded in polystyrene fibers relative to pure HKUST-1 powder.

The second technique involves the creation of a pore network throughout the fiber to increase accessibility of embedded sorbent particles. It is demonstrated that the removal of a blended highly soluble polymer additive from the spun particle-containing fibers leaves a pore network behind without removing the embedded sorbent. The increased accessibility of embedded sorbents is validated by embedding a known direct air capture sorbent in porous electrospun fibers, and demonstrating that they have the fastest kinetic uptake of any direct air capture sorbent reported in literature to date, along with over 90% sorbent accessibility.
ContributorsArmstrong, Mitchell (Author) / Mu, Bin (Thesis advisor) / Green, Matthew (Committee member) / Seo, Dong (Committee member) / Lackner, Klaus (Committee member) / Holloway, Julianne (Committee member) / Arizona State University (Publisher)
Created2018
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Description
Iodide (I-) in surface and groundwaters is a potential precursor for the formation of iodinated disinfection by-products (I-DBPs) during drinking water treatment. The aim of this thesis is to provide a perspective on the sources and occurrence of I- in United States (US) source waters based on ~9200 surface water

Iodide (I-) in surface and groundwaters is a potential precursor for the formation of iodinated disinfection by-products (I-DBPs) during drinking water treatment. The aim of this thesis is to provide a perspective on the sources and occurrence of I- in United States (US) source waters based on ~9200 surface water (SW) and groundwater (GW) sampling locations. The median I- concentrations observed was 16 μg/l and 14 μg/l, respectively in SW and GW. However, these samples were rarely collected at water treatment plant (WTP) intakes, where such iodide occurrence data is needed to understand impacts on DBPs. Most samples were collected in association with geochemical studies. We conclude that I- occurrence appears to be influenced by geological features, including halite rock/river basin formations, saline aquifers and organic rich shale/oil formations. Halide ratios (Cl-/I-, Br-/I- and Cl-/Br-) were analyzed to determine the I- origin in source waters. SW and GW had median Cl-/I- ratios of ~3600 μg/μg and median Br-/I- ratios of ~15 μg/μg. For states with I- concentration >50 μg/l (e.g., Montana and North Dakota), a single source (i.e., organic rich formations) can be identified. However, for states like California and Texas that have wide-ranging I- concentration of below detection limit to >250 μg/l, I- occurrence can be attributed to a mixture of marine and organic signatures. The lack of information of organic iodine, inorganic I- and IO3- in source waters limits our ability to predict I-DBPs formed during drinking water treatment, and new occurrence studies are needed to fill these data gaps. This is first of its kind study to understand the I- occurrence through historical data, however we also identify the shortcomings of existing databases used to carry out this study.
ContributorsSharma, Naushita (Author) / Westerhoff, Paul (Thesis advisor) / Lackner, Klaus (Committee member) / Herckes, Pierre (Committee member) / Arizona State University (Publisher)
Created2018
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Description
This is a report of a study that investigated the thinking of a high-achieving precalculus student when responding to tasks that required him to define linear formulas to relate covarying quantities. Two interviews were conducted for analysis. A team of us in the mathematics education department at Arizona State University

This is a report of a study that investigated the thinking of a high-achieving precalculus student when responding to tasks that required him to define linear formulas to relate covarying quantities. Two interviews were conducted for analysis. A team of us in the mathematics education department at Arizona State University initially identified mental actions that we conjectured were needed for constructing meaningful linear formulas. This guided the development of tasks for the sequence of clinical interviews with one high-performing precalculus student. Analysis of the interview data revealed that in instances when the subject engaged in meaning making that led to him imagining and identifying the relevant quantities and how they change together, he was able to give accurate definitions of variables and was usually able to define a formula to relate the two quantities of interest. However, we found that the student sometimes had difficulty imagining how the two quantities of interest were changing together. At other times he exhibited a weak understanding of the operation of subtraction and the idea of constant rate of change. He did not appear to conceptualize subtraction as a quantitative comparison. His inability to conceptualize a constant rate of change as a proportional relationship between the changes in two quantities also presented an obstacle in his developing a meaningful formula that relied on this understanding. The results further stress the need to develop a student's ability to engage in mental operations that involve covarying quantities and a more robust understanding of constant rate of change since these abilities and understanding are critical for student success in future courses in mathematics.
ContributorsKlinger, Tana Paige (Author) / Carlson, Marilyn (Thesis director) / Thompson, Pat (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Statistical Sciences (Contributor)
Created2014-05
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Description
This thesis examines the use of the moisture swing resin materials employed at the Center for Negative Carbon Emissions (CNCE) in order to provide carbon dioxide from ambient air to photobioreactors containing extremophile cyanobacteria cultured at the Arizona Center for Algae Technology and Innovation (AzCATI). For this purpose, a

This thesis examines the use of the moisture swing resin materials employed at the Center for Negative Carbon Emissions (CNCE) in order to provide carbon dioxide from ambient air to photobioreactors containing extremophile cyanobacteria cultured at the Arizona Center for Algae Technology and Innovation (AzCATI). For this purpose, a carbon dioxide feeding device was designed, built, and tested. The results indicate how much resin should be used with a given volume of algae medium: approximately 500 grams of resin can feed 1% CO2 at about three liters per minute to a ten liter medium of the Galdieria sulphuraria 5587.1 strain for one hour (equivalent to about 0.1 grams of carbon dioxide per hour per seven grams of algae). Using the resin device, the algae grew within their normal growth range: 0.096 grams of ash-free dry weight per liter over a six hour period. Future applications in which the resin-to-algae process can be utilized are discussed.
ContributorsBeaubien, Courtney (Author) / Lackner, Klaus (Thesis advisor) / Lammers, Peter (Committee member) / Atkins, Steve (Committee member) / Arizona State University (Publisher)
Created2016
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Description

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural

The emerging field of neuroprosthetics is focused on the development of new therapeutic interventions that will be able to restore some lost neural function by selective electrical stimulation or by harnessing activity recorded from populations of neurons. As more and more patients benefit from these approaches, the interest in neural interfaces has grown significantly and a new generation of penetrating microelectrode arrays are providing unprecedented access to the neurons of the central nervous system (CNS). These microelectrodes have active tip dimensions that are similar in size to neurons and because they penetrate the nervous system, they provide selective access to these cells (within a few microns). However, the very long-term viability of chronically implanted microelectrodes and the capability of recording the same spiking activity over long time periods still remain to be established and confirmed in human studies. Here we review the main responses to acute implantation of microelectrode arrays, and emphasize that it will become essential to control the neural tissue damage induced by these intracortical microelectrodes in order to achieve the high clinical potentials accompanying this technology.

ContributorsFernandez, Eduardo (Author) / Greger, Bradley (Author) / House, Paul A. (Author) / Aranda, Ignacio (Author) / Botella, Carlos (Author) / Albisua, Julio (Author) / Soto-Sanchez, Cristina (Author) / Alfaro, Arantxa (Author) / Normann, Richard A. (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-07-21
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Description

In this study, a low-cycle fatigue experiment was conducted on printed wiring boards (PWB). The Weibull regression model and computational Bayesian analysis method were applied to analyze failure time data and to identify important factors that influence the PWB lifetime. The analysis shows that both shape parameter and scale parameter

In this study, a low-cycle fatigue experiment was conducted on printed wiring boards (PWB). The Weibull regression model and computational Bayesian analysis method were applied to analyze failure time data and to identify important factors that influence the PWB lifetime. The analysis shows that both shape parameter and scale parameter of Weibull distribution are affected by the supplier factor and preconditioning methods Based on the energy equivalence approach, a 6-cycle reflow precondition can be replaced by a 5-cycle IST precondition, thus the total testing time can be greatly reduced. This conclusion was validated by the likelihood ratio test of two datasets collected under two different preconditioning methods Therefore, the Weibull regression modeling approach is an effective approach for accounting for the variation of experimental setting in the PWB lifetime prediction.

ContributorsPan, Rong (Author) / Xu, Xinyue (Author) / Juarez, Joseph (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-11-12
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Studies about the data quality of National Bridge Inventory (NBI) reveal missing, erroneous, and logically conflicting data. Existing data quality programs lack a focus on detecting the logical inconsistencies within NBI and between NBI and external data sources. For example, within NBI, the structural condition ratings of some bridges improve

Studies about the data quality of National Bridge Inventory (NBI) reveal missing, erroneous, and logically conflicting data. Existing data quality programs lack a focus on detecting the logical inconsistencies within NBI and between NBI and external data sources. For example, within NBI, the structural condition ratings of some bridges improve over a period while having no improvement activity or maintenance funds recorded in relevant attributes documented in NBI. An example of logical inconsistencies between NBI and external data sources is that some bridges are not located within 100 meters of any roads extracted from Google Map. Manual detection of such logical errors is tedious and error-prone. This paper proposes a systematical “hypothesis testing” approach for automatically detecting logical inconsistencies within NBI and between NBI and external data sources. Using this framework, the authors detected logical inconsistencies in the NBI data of two sample states for revealing suspicious data items in NBI. The results showed that about 1% of bridges were not located within 100 meters of any actual roads, and few bridges showed improvements in the structural evaluation without any reported maintenance records.

ContributorsDin, Zia Ud (Author) / Tang, Pingbo (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-05-20
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Description

Background: Robotic devices have been utilized in gait rehabilitation but have only produced moderate results when compared to conventional physiotherapy. Because bipedal walking requires neural coupling and dynamic interactions between the legs, a fundamental understanding of the sensorimotor mechanisms of inter-leg coordination during walking, which are not well understood but are

Background: Robotic devices have been utilized in gait rehabilitation but have only produced moderate results when compared to conventional physiotherapy. Because bipedal walking requires neural coupling and dynamic interactions between the legs, a fundamental understanding of the sensorimotor mechanisms of inter-leg coordination during walking, which are not well understood but are systematically explored in this study, is needed to inform robotic interventions in gait therapy.

Methods: In this study we investigate mechanisms of inter-leg coordination by utilizing novel sensory perturbations created by real-time control of floor stiffness on a split-belt treadmill. We systematically alter the unilateral magnitude of the walking surface stiffness and the timing of these perturbations within the stance phase of the gait cycle, along with the level of body-weight support, while recording the kinematic and muscular response of the unperturbed leg. This provides new insight into the role of walking surface stiffness in inter-leg coordination during human walking. Both paired and unpaired unadjusted t-tests at the 95 % confidence level are used in the appropriate scenario to determine statistical significance of the results.

Results: We present results of increased hip, knee, and ankle flexion, as well as increased tibialis anterior and soleus activation, in the unperturbed leg of healthy subjects that is repeatable and scalable with walking surface stiffness. The observed response was not impacted by the level of body-weight support provided, which suggests that walking surface stiffness is a unique stimulus in gait. In addition, we show that the activation of the tibialis anterior and soleus muscles is altered by the timing of the perturbations within the gait cycle.

Conclusions: This paper characterizes the contralateral leg’s response to ipsilateral manipulations of the walking surface and establishes the importance of walking surface stiffness in inter-leg coordination during human walking.

ContributorsSkidmore, Jeffrey (Author) / Artemiadis, Panagiotis (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-03-22