Immuno-gold labeling is a technique used for the identification, localization, and distribution of proteins, antigens, and other macromolecules of interest, at an ultrastructural level, with high resolution. It is a very powerful technique for identifying active sites and the presence of biomarkers in the cell, and allows for the study of various cellular processes and response to various changes in the microenvironment, gene silencing and response to chemical treatment.

In this method a primary antibody is designed to bind onto a specific antigen of interest in the cells, and is subsequently detected using a secondary antibody conjugated to a gold probe. The gold probe has excellent electron scattering properties which allows for its detection in the TEM images. For the validation of antibody specificity several approaches are recommended including knock-out tissue and reagent controls.
The sample preparation used for this method depends on the type of sample and on the protein or macromolecule of interest. The sample must be prepared in a way that would preserve immunogenity of the antigens.

Immuno-electron micrograph of a section prepared by the Tokuyasu method, showing cross-sections through elongated spermatids expressing the A-SbT-GFP transgene, displaying specific GFP labeling with gold particles (black dots) over the mitochondria.