Size Matters: Mastering Size Exclusion For Oligos

As we continue our nine-part journey with Part 5 of the Oligos Made Easy series, we turn our attention to Size Exclusion Chromatography (SEC). While methods like AEX or HILIC might take the crown for pure resolution, SEC offers a distinct advantage for desalting and buffer exchange: gentleness. By treating purification as a "molecular obstacle course," SEC separates oligonucleotides strictly by size rather than chemistry.

Your target oligos take the express lane, bypassing the porous beads that trap smaller salts and aggregates. This native-condition approach ensures your sequences remain intact and unaltered. However, mastering this technique requires precise choices regarding pore size, flow rates, and sample concentration. Understanding when to deploy SEC as a reliable workhorse versus when to seek higher-resolution alternatives is key to a smarter purification strategy.