Host–Guest Interaction of Adamantine with a β-Cyclodextrin-Functionalized AuPd Bimetallic Nanoprobe for Ultrasensitive Electrochemical Immunoassay of Small Molecules

A modular labeling strategy was presented for electrochemical immunoassay via supramolecular host–guest interaction between β-cyclodextrin (β-CD) and adamantine (ADA). An ADA-labeled antibody (ADA–Ab) was synthesized via amidation, and the number of ADA moieties loaded on a single antibody was calculated to be ∼7. The β-CD-functionalized gold–palladium bimetallic nanoparticles (AuPd–CD) were synthesized in aqueous solution via metal-S chemistry and characterized with transmission electron microscopy and X-ray photoelectron spectra. After the ADA–Ab was bound to the antigen-modified electrode surface with a competitive immunoreaction, AuPd–CD as a signal tag was immobilized onto the immunosensor by a host–guest interaction, leading to a large loading of AuPd nanoparticles. The highly efficient electrocatalysis by AuPd nanoparticles for NaBH4 oxidation produced an ultrasensitive response to chloramphenicol as a model of a small molecule antigen. The immunoassay method showed a wide linear range from 50 pg/mL to 50 μg/mL and a detection limit of 4.6 pg/mL. The specific recognition of antigen by antibody resulted in good selectivity for the proposed method. The host–guest interaction strategy provided a universal labeling approach for the ultrasensitive detection of small molecule targets.