(250c) Taming the Complexities of DNA Hybridization On Surfaces

DNA microarrays are high throughput, parallel assays for determining which genes are present in a sample or the level of expression of the genes. They have been identified as a key technology in genomic sciences and emergent medical techniques. 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. Improved understanding of DNA hybridization at the molecular level is key to refining these devices.

Using a carefully-parameterized coarse-grain model of DNA, we previously reported simulation results that suggested that the best way to optimize microarray performance was to inhibit, rather than enhance, hybridization on surfaces. In this presentation, we outline efforts done to apply this knowledge and the resulting outcomes. To further expand understanding of microarray systems, we also show how the presence of multiple probes on the surface affects the thermodynamics and mechanisms of hybridization. Additionally, we describe the effect of target length and complimentary sequence location on the target. The results give the most complete picture to date of the biophysics involved in microarray performance and how this knowledge can be used to improve next-generation devices.