Direct conjugation of antibodies to the ZnS shell of quantum dots for FRET immunoassays with low picomolar detection limits

Compact and functional nanoparticle-antibody conjugates are of paramount importance for the development of quantum dot (QD)-based immunoassays. Here, we present a simple strategy to directly conjugate IgG, F(ab')₂, and Fab antibodies via their endogenous disulfide groups directly to the inorganic ZnS shell of compact penicillamine-coated QDs. The functionality of the conjugates was demonstrated by terbium (Tb)-to-QD FRET immunoassays against prostate specific antigen in serum samples. Detection limits of 2.5 pM (0.080 ng mL^-1) were 10 and 25 times lower compared to conjugation via maleimide-terminated ligands and polymer chains, respectively. These more compact, simple, and sensitive QD-antibody conjugates will be highly advantageous for nanocrystal-based biosensing applications.