The chemistry of photolithographic nucleic acid synthesis is a modified form of the phosphoramidite chemistry used in standard solid phase synthesis. The primary modification is the replacement of the acid labile dimethoxytrityl (DMTr) protecting group on the 5′ hydroxyl group of the sugar (3′ hydroxyl in the case of 5′ to 3′ synthesis) with 2-(2-nitrophenyl) propoxycarbonyl (NPPOC) or a derivative thereof, either benzoyl-2-(2-nitrophenyl)propoxycarbonyl (Bz-NPPOC) or thiophenyl-2-(2-nitrophenyl) propoxycarbonyl (SPh-NPPOC) . This change allows high-resolution spatial control of deprotection through the use of patterned exposures with UV light, and therefore the parallel synthesis of very large numbers of sequencedefined oligonucleotides on a surface. Photodeprotection has some additional distinct advantages over acid-based deblocking: it can be much faster, it eliminates the risk of depurination, and can reduce the need for regular oxidation reactions. The chemical cycle for light-directed phosphoramidite chemistry is illustrated in Figure .