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We report an observation of a peculiar effect in which the vibrational frequencies of antibody-conjugated SERS-active reporter molecules are shifted in quantitative correlation with the concentration of the targeted antigen. We attribute the frequency shifts to mechanical perturbations in the antibody-reporter complex, as a result of antibody-antigen interaction forces. Our observation thus demonstrates the potentiality of an antibody-conjugated SERS-active reporter complex as a SERS-active nanomechanical sensor for biodetection. Remarkably, our sensing scheme, despite employing only one antibody, was found to be able to achieve detection sensitivity comparable to that of a conventional sandwich immunoassay. Additionally, we have carried out a proof-of-concept study into using multiple "stress-sensitive" SERS reporters for multiplexed detection of antigen-antibody bindings at the subdiffraction limit. The current work could therefore pave the way to realizing a label-free high-density protein nanoarray.
Kho et al. (Tue,) studied this question.