Magnetic Assembly of High-Density DNA Arrays for Genomic Analyses

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Abstract
A method for rapidly assembling high-density DNA arrays with near-perfect order is described. Photolithography is used to generate a wafer-scale array of microwells in a layer of photoresist on a chemically functionalized glass coverslip. The array is enclosed within a microfluidic device, and a suspension of superparamagnetic microbeads conjugated to DNA molecules is introduced into the chamber. A permanent magnet is used to direct the rapid assembly of the beads into the wells, with each well containing a single bead. These beads are immobilized on the glass surface via affinity binding, and excess beads can be recycled or washed away. Nonspecifically bound beads are removed by dissolving the photoresist. The result is a high-density array of beads with virtually no background. This method can be used to produce protein arrays for chip-based assays and DNA arrays for genotyping or genome sequencing.