Means and methods for time-resolved sampling

The present invention relates to the field of time-resolved protein sampling, more specifically for use in structural biology, even more specifically for structural analysis of proteins by Cryogenic-electron microscopy (Cryo-EM). The invention provides for methods and devices for preparing vitrified samples for transmission electron microscopy at millisecond time-resolution using a microfluidics-based integrated device. More specifically, the sampling means and methods combine fast mixing with a tunable droplet-on-demand generation to control droplet formation, spraying and sampling velocity, resulting in a sampling method requiring very limited protein amounts.