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- Genre: Masters Thesis
- Resource Type: Text
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 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
Continuous advancements in biomedical research have resulted in the production of vast amounts of scientific data and literature discussing them. The ultimate goal of computational biology is to translate these large amounts of data into actual knowledge of the complex biological processes and accurate life science models. The ability to rapidly and effectively survey the literature is necessary for the creation of large scale models of the relationships among biomedical entities as well as hypothesis generation to guide biomedical research. To reduce the effort and time spent in performing these activities, an intelligent search system is required. Even though many systems aid in navigating through this wide collection of documents, the vastness and depth of this information overload can be overwhelming. An automated extraction system coupled with a cognitive search and navigation service over these document collections would not only save time and effort, but also facilitate discovery of the unknown information implicitly conveyed in the texts. This thesis presents the different approaches used for large scale biomedical named entity recognition, and the challenges faced in each. It also proposes BioEve: an integrative framework to fuse a faceted search with information extraction to provide a search service that addresses the user's desire for "completeness" of the query results, not just the top-ranked ones. This information extraction system enables discovery of important semantic relationships between entities such as genes, diseases, drugs, and cell lines and events from biomedical text on MEDLINE, which is the largest publicly available database of the world's biomedical journal literature. It is an innovative search and discovery service that makes it easier to search
avigate and discover knowledge hidden in life sciences literature. To demonstrate the utility of this system, this thesis also details a prototype enterprise quality search and discovery service that helps researchers with a guided step-by-step query refinement, by suggesting concepts enriched in intermediate results, and thereby facilitating the "discover more as you search" paradigm.
avigate and discover knowledge hidden in life sciences literature. To demonstrate the utility of this system, this thesis also details a prototype enterprise quality search and discovery service that helps researchers with a guided step-by-step query refinement, by suggesting concepts enriched in intermediate results, and thereby facilitating the "discover more as you search" paradigm.
ContributorsKanwar, Pradeep (Author) / Davulcu, Hasan (Thesis advisor) / Dinu, Valentin (Committee member) / Li, Baoxin (Committee member) / Arizona State University (Publisher)
Created2010
Description
Vitamin D is a nutrient that is obtained through the diet and vitamin D supplementation and created from exposure to Ultraviolet B (UVB) radiation. While there are many factors that determine how much serum 25-hydroxyvitamin D (25(OH)D) concentration is in the body, little is known about how genetic variation in vitamin D-related genes influences serum 25(OH)D concentrations resulting from daily vitamin D intake and exposure to direct sunlight. Previous studies show that common genetic variants rs10741657 (CYP2R1), rs4588 (GC), rs228678 (GC), and rs4516035 (VDR) act as moderators and alter the effect of outdoor time and vitamin D intake on serum 25(OH)D concentrations. The objective of this study is to analyze the associations between serum 25(OH)D concentrations resulting from outdoor time and vitamin D intake, and genetic risk scores (GRS) established from previous studies involving single nucleotide polymorphisms (SNP) located on or near genes involving vitamin D synthesis, transport, activation, and degradation in 102 Hispanic and Non-Hispanic adults in the San Diego County, California. This study is a secondary analysis of data from the Community of Mine study. Global Positioning System (GPS) data collected by the Qstarz GPS device worn by each participant was used to measure outdoor time, a proxy measurement for sun exposure time. Vitamin D intake was assessed using two 24-hour dietary recalls. Blood samples were measured for serum 25(OH)D concentrations. DNA was provided to assess each participant for the various genetic variants. Adjusted analyses of the GRS and serum 25(OH)D concentrations showed that individuals with high GRS (3-4) had lower serum 25(OH)D concentrations than individuals with low GRS (0-2) for both Nissen GRS and Rivera-Paredez GRS.
ContributorsAnderson, Heather Ray (Author) / Sears, Dorothy (Thesis advisor) / Alexon, Christy (Committee member) / Dinu, Valentin (Committee member) / Jankowska, Marta (Committee member) / Arizona State University (Publisher)
Created2022