Phase separation in alcohol/liquid carbon dioxide solvent systems facilitates critical point drying.

Carbon dioxide and methanol or ethanol, although miscible, form alcohol/CO2 solutions that do not easily mix with additional pure liquid CO2. If the CO2 inlet is situated at the top of a critical point drying apparatus chamber, pure CO2 will entirely displace the alcohol/CO2 phase (which is more dense) while keeping the chamber filled with liquid. This unexpected phenomenon is invaluable in critical point drying delicate biological tissues which remain continuously immersed, avoiding surface or convection currents. By providing an objective criterion for intermediate solvent displacement, the protocol also eliminates ambiguous 'flushing' steps.