The atom-probe field ion microscope may be the ultimate microanalytical tool because a single atom, chosen from its neighbors at the discretion of the experimenter, can be visualized in atomic resolution and then identified by its mass-to-charge ratio. Although the analysis procedure is destructive;the lateral and depth resolution of the atom-probe is impressive, exceeding 0.5 nm under favorable conditions. Despite these attributes, atom probe analysis has been largely confined to problems in the materials sciences. The atom probe has made no impact in biology or medicine, largely because of restrictions imposed by the technique on the preparation, imaging, and analysis of biological samples. Recent developments in each of these areas has made atom probe analysis of biological samples a more viable prospect.Biological Sample PreparationThe atom-probe technique places severe restrictions on the type of sample that can be analyzed. Field ionization is used to image a surface in atomic resolution, and field desorption provides a source of ions for analysis. These processes occur with a high probability only in electric fields greaterthan 100 MV/cm. Electric fields of this magnitude (and the nature of the imaging process) require theuse of a needlelike substrate, known as a field-emitter "tip".