The projected use of oligonucleotides (ODN) and their analogs as diagnostics and antisense/antigene therapeutic agents has created a need for efficient methods for their large scale synthesis. Available systems are inherently incapable of efficient operation at the preparative scale desired (100 millimole or larger). This project involves reactor design, fluidic processing, and a new, economical solid support to provide a practical means for the preparation of ODNs at the 100g to 1 KG or greater scale. The process design may allow the execution of all available chemistries at high efficiency.