Unique Vibrational Features as a Direct Probe of Specific Antigen–Antibody Recognition at the Surface of a Solid‐Supported Hybrid Lipid Bilayer

Here, we demonstrate how sum frequency generation (SFG), a vibrational spectroscopy based on a nonlinear three‐photon mixing process, may provide a direct and unique fingerprint of bio‐recognition; This latter can be detected with an intrinsically discriminating unspecific adsorption, thanks to the high sensitivity of the second‐order nonlinear optical (NLO) response to preferential molecular orientation and symmetry properties. As a proof of concept, we have detected the biological event at the solid/liquid interface of a model bio‐active antigen platform, based on a solid‐supported hybrid lipid bilayer (ss‐HLB) of a 2,4‐dinitrophenyl (DNP) lipid, towards a monoclonal mouse anti‐DNP complementary antibody.