DNA microarrays are chip-based, analysis tools which can perform hundreds of thousands of parallel assays to determine the identity of genes or gene expression levels present in a sample. They have been identified as a key technology in genomic sciences and emergent medical techniques; however, despite their abundant use in research laboratories, microarrays have not been used in the clinical setting to the fullest potential due to the difficulty of obtaining reproducible results. Microarrays work on the principle of DNA hybridization, and can only be as accurate as this process is robust. Fundamental, molecular-level understanding of hybridization on surfaces is needed to further refine these devices.This work shows how orientation of DNA probes with respect to the surface affects the thermodynamics and stability of hybridization. Ideal surface hybridization (a DNA duplex bound to the surface on one end) is compared to more realistic conditions such as interaction between DNA and the surface in multiple locations. This research also describes the effect of mismatch location and number of mismatches on a single target strand. The results clarify key details of the biophysics involved in microarray performance and this knowledge can be used to improve next-generation devices. The disparity between surface and bulk hybridization behavior is examined here in molecular level detail that is not currently possible with experimental techniques.
College and Department
Ira A. Fulton College of Engineering and Technology; Chemical Engineering
BYU ScholarsArchive Citation
Pratt, Kyle Evan, "The Effects of Mismatches and Probe Tethering Configurations on the Stability of DNA Duplexes on Surfaces" (2013). Theses and Dissertations. 4056.
DNA, molecular modeling, microarray, simulation, hybridization