Fluorinated nanobodies for targeted molecular imaging of biological samples using nanoscale secondary ion mass spectrometry

Molecular imaging of targeted large biomolecules has been restricted in SIMS due to the limited number of probes containing SIMSdetectable isotopes.We introduce here new 19F-containingmolecules that can be conjugated in a site-specificmanner to nanobodies able to recognize fluorescent proteins (FPs) or mouse immunoglobulins (Igs). In this work, we demonstrate that it is possible to use the 19F-nanobodies to reveal the location of several cellular proteins previously tagged with FPs or Igs. This enables specific bio-imaging in SIMS for a vast repertoire of biomolecules, offering new opportunities to study specific structural and functional molecular interactions in biological specimens.