In light-directed synthesis of high-density oligonucleotide arrays for
sequencing by hybridization, synthesis errors result from the uninten
ded illumination of chip regions that should remain dark. Most synthes
is errors occur at the borders of illuminated regions, where light dif
fraction, internal reflection, and scattering produce the most uninten
ded illumination. A combinatorial synthesis strategy based on two-dime
nsional Gray codes was devised to reduce the overall lengths of these
borders in masks for photolithographic chip design. This article descr
ibes an application of two-dimensional Gray codes and demonstrates tha
t masks based on this approach are optimal for minimizing the border l
ength in VLSIPS (very large scale immobilized polymer synthesis). (C)
1994 Academic Press, Inc.