In the past, oligonucleotide synthesis was carried out manually in solution or on solid phase. The solid-phase synthesis was implemented using, as containers for the solid phase, miniature glass columns similar in their shape to low-pressure chromatography columns or syringes equipped with porous filters. Currently, solid phase oligonucleotide synthesis is carried out automatically using oligonucleotide synthesizers (oligonucleotide synthesis instruments) and is technically implemented in column, multi-well plate, and array formats. The column format is best suited for research and large scale applications where a high-throughput is not required. Multi-well plate format is designed specifically for high-throughput synthesis on small scale to satisfy the growing demand of industry and academia for synthetic oligonucleotides.

Millions of oligonucleotides are synthesized every year for use in laboratories around the world. For most applications, very small quantities of DNA or RNA are required, and oligonucleotide synthesis is performed mainly on the 40 nmol scale or lower. This provides ample quantities for most biochemical and biological experiments. Much larger amounts (10 µmol or more) of DNA can be prepared for use in biophysical studies (e.g. NMR, X-ray crystallography) and in the extreme, multi-kilogram quantities of oligonucleotides for use as drug molecules (e.g. antisense oligonucleotides). For all these purposes, oligonucleotides are manufactured almost exclusively using automated solid-phase methods.