Preparation of ssDNA-coated cryo-EM grids. (1) Before application onto the cryo-EM holey carbon grid, dsDNA is heated to 98°C for 10 min to obtain ssDNA. The ssDNA solution is then immediately placed on ice to prevent the formation of double-stranded DNA. (2) 5 µl of the ssDNA is applied onto a holey grid. (3) After 30 s, the ssDNA is blotted from the opposite side of the grid. (4) The ssDNA-coated grid is ready to be used for a regular sample-vitrification procedure.