Photolithographic synthesis of high-density DNA probe arrays: Challenges and opportunities

The continual need for increased manufacturing capacity in the production of GeneChip™ DNA probe arrays, and the expanding use of these arrays into new areas of application such as molecular medicine, has stimulated the development of new chemistries and production methods with higher efficiency and resolution. For current production methods based on contact photolithography, modifications in substrate materials and photoactivated synthesis reagents have provided significant improvements in array performance and information content ( ≥ 4 × 10 6 sequences ∕ cm 2 ) . An alternative next-generation manufacturing process is also in development, which utilizes photoacid generating polymer films, and automated projection lithography systems. This process has the ability to fabricate arrays with 1 micron feature pitch and smaller, providing an unprecedented sequence density of 10 8 ∕ cm 2 and greater.