Retractable ion guide, grid holder, and technology for removal of cryogenic sample from vacuum

A method for preparing a sample for cryo-electron microscopy (cryo-EM) comprising the steps of:

• a) generating charged or uncharged analyte particles and collecting said analyte particles in an ion guide, wherein the ion guide comprises a vacuum valve separating the ion guide into a first region and a second region, wherein the first region has a first internal pressure;
• b) positioning a sample holder having a receiving surface in a sample vacuum chamber having a second pressure when the vacuum valve is closed, wherein the sample vacuum chamber is connected to the second region of the ion guide;
• c) cooling the receiving surface in the sample vacuum chamber to a temperature of −100° C. or less;
• d) producing a controllable vapor stream, wherein the vapor stream is able to generate an amorphous solid;
• e) opening the vacuum valve and transmitting the analyte particles from the first region of the ion guide, through the second region, and into the sample vacuum chamber;
• f) transmitting the vapor stream into the sample vacuum chamber;
• and
• g) contacting the cooled receiving surface with the analyte particles and vapor stream, thereby forming a layer of analyte particles on the receiving surface, wherein the analyte particles are coated with the amorphous solid.