The second strategy relies on the fact that the sensitivity of immunogold electron microscopy is strongly influenced by the size of the gold particle used. Therefore, smaller gold grains with diameters in the range of 1 nm (referred to as ultrasmall gold particles) are used to enhance sensitivity. The obvious reason is that the interfering effects of the gold particles for antigen binding are reduced if the grain size becomes smaller. Two different kinds of gold particles are used: colloidal gold grains of 1 nm diameter and Nanogold grains (Nanoprobes, Yaphank, NY, USA) of 1.4 nm diameters.