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Abstract

The rapid-freeze technique is currently touted as a revolutionary new tool for the analysis of nerve structure and function69. However, supercooling for instantaneous vitrification of water has been known for over 100 years. For example, in the popular literature of 1877, Jules Verne described just such instantaneous freezing of the oceans of an entire planetoid32. While rapid freezing on such a scale has not proven possible, freeze preservation of cell structure has met with increasing success since the early days of light2,21,70 and electron microscopies71,72,77. Likewise, the ‘new’ concept of contact freezing of nerve cells against a liquid-nitrogen- or liquid-helium-cooled metal block12,13,27,29,36 was first described over 40 years ago70 and adapted for electron microscopy nearly 20 years ago83–86. However, the rapid-freeze technique could not be utilized fully in neurobiology until the techniques of freeze substitution, freeze fracture and freeze etch were developed17,44,77 and the kinetics of rapid freezing were analysed19,27,88,89. This report summarizes the unique opportunities and limitations now afforded by the rapid-freezing technique in neurobiology.