We are developing new methods for the loss-less (no blotting steps) sample preparation of nanoliter volumes for negative stain and cryo-EM. Our work includes hardware and software development. These methods are then used to look at the proteome of single mammalian cells by electron microscopy.
In recent years there has been a renaissance of electron microscopy (EM) in biological research. While image acquisition and processing have largely benefited from new direct electron detection (DED) cameras, sample preparation is still in the pre-DED era. Current methods suffer from two major drawbacks: i) high sample consumption (around 3 µl/grid) and ii) massive blotting steps that remove more than 99% of the sample. In addition, these blotting steps are known to generate unrepresentative sample populations on the EM grid.
We are developing methods to reproducibly deposit a nanolitre volume of sample onto an EM grid at room and at cryo-temperatures.