Numerical Characterization and Experimental Optimization of Microfluidic DNA Microarray Hybridization

Abstract

Background/Objectives: Mathematical modeling and computational simulation are important tools in the analysis of fluid transport phenomena and surface reactions. These include surface hybridization that takes place in a microfluidic channel, creating a DNA microarray. Methods: In this work, the surface hybridization of target samples with multiple DNA probe spots immobilized on the bottom of a microfluidic channel was investigated using computational modeling. The model incorporates the 2D transport process, coupled with convective/diffusive mass transport (infinite dilution) and surface binding models for both non-specific adsorption and specific hybridization in a 1 × 3 array. Results: Hybridization signals obtained at different reaction times, various flow rates, and two different channel depths were analyzed, aiming at enhanced surface hybridization while minimizing assay time and sample usage. It was found that a high aspect ratio (width/height) channel geometry would enable significantly improved reagent utilization and reduced inter-diffusional mixing time. Conclusions: The numerical characterization of the surface hybridization was verified by experimental results of a 4 × 7 DNA array. The numerical study also suggested the implementation of a tapered channel design that accommodates the growth of the co-laminar mixing zone in the downstream direction.