column-based method used to separate proteins by size/shape – either for:

  1. purification (preparative SEC), often as a “polishing step” after you’ve done other separations (e.g. affinity and/or ion exchange) or 
  2. to see if proteins interact (analytical SEC)

It works by flowing a protein-containing mixture through a column filled with little beads (resin). The beads have secret tunnels in them only small things can enter. Small proteins thus have a longer path to travel so it takes them longer to get through and they will come out the end of the column (elute) later.