Live Cell Electron Microscopy Is Probably Impossible

Electron microscopy of biological cells in liquid provides unique nanoscale information. A highly attractive idea is the capability to also study physiological processes of live cells with electron microscopy. However, this idea seems unrealistic because the minimal needed electron dose to obtain contrast is already many orders of magnitude above the lethal dose known to cause reproductive-cell death. We show here that claims of electron microscopy of viable cells in recent reports are based on a questionable interpretation of the used fluorescence live/dead assay. A practical alternative to study biological processes is correlative light and electron microscopy.