The Vengeance Formulation - S3-E9
Factual error: Sheldon's voice becomes squeaky when helium is pumped into his office. But if the room contained enough helium to make his voice squeaky just by breathing, Sheldon would actually be suffocating due to lack of oxygen, the lighter helium having displaced the heavier oxygen. You can do it with a balloon because you can breathe normal air between huffs, but if you're in a room full of helium, you won't last long before passing out and asphyxiating.