Gray code masks for sequencing by hybridization.
In light-directed synthesis of high-density oligonucleotide arrays for sequencing by hybridization, synthesis errors result from the unintended illumination of chip regions that should remain dark. Most synthesis errors occur at the borders of illuminated regions, where light diffraction, internal reflection, and scattering produce the most unintended illumination. A combinatorial synthesis strategy based on two-dimensional Gray codes was devised to reduce the overall lengths of these borders in masks for photolithographic chip design. This article describes an application of two-dimensional Gray codes and demonstrates that masks based on this approach are optimal for minimizing the border length in VLSIPS (very large scale immobilized polymer synthesis).