Single particle cryo-EM offers the possibility of mapping proteins with atomic resolution. However, this technique is difficult and time-consuming because measurable samples require a large, homogeneous amount of the target protein. Now, structural biologists from Vrije Universiteit Brussel have presented a new microfluidic platform called MISO to Nature Methods. This reduces the necessary protein purification by up to a factor of one thousand.

Single-particle cryogenic electron microscopy (cryo-EM) is currently the preferred technique for measuring protein structures. By visualising thousands to a few million copies of a purified protein in a nanometre-thick layer of ice, the technique can image the protein in three dimensions with atomic precision.

In theory, only a few picograms of the protein are required, which can be purified from a single cell colony. In practice, however, it is not yet possible to purify proteins in such minimal, homogeneous quantities and place them directly into the sample holder. Instead, nearly a million times more biological material is required. This bottleneck means that determining the structure of certain proteins remains impossible.