Atomically Flat Au Nanoplate Platforms Enable Ultraspecific Attomolar Detection of Protein Biomarkers

Atomically flat surfaces of single-crystalline Au nanoplates can maximize the functionality of biomolecules, thus realizing extremely high-performance biosensors. Here, we report both highly specific and supersensitive detection of C-reactive protein (CRP) by employing atomically flat Au nanoplates. CRP is a protein biomarker for inflammation and infection and can be used as a predictive or prognostic marker for various cardiovascular diseases. To maximize the binding capacity for CRP, we carefully optimized the Au nanoplate-Cys3-protein G-anti-CRP structure by observing atomic force microscopy (AFM) images. The optimally anti-CRP-immobilized Au nanoplates allowed extremely specific detection of CRP at the attomolar level. To confirm the binding of CRP onto the Au nanoplate, we assembled Au nanoparticles (NPs) onto the CRP-captured Au nanoplate by sandwich immunoreaction and obtained surface-enhanced Raman scattering (SERS) spectra and scanning electron microscopy (SEM) images. Both the SERS and SEM results showed that we completely eliminated the nonspecific binding of Au NPs onto the optimally anti-CRP-immobilized Au nanoplate. Compared with the anti-CRP-immobilized rough Au film and the randomly anti-CRP-attached Au nanoplate, the optimally anti-CRP-immobilized Au nanoplate provided a highly improved detection limit of 10–17 M. In this study, it was validated that ultraclean and ultraflat Au nanoplates can maximize the sensing capability of CRP. We expect that these Au nanoplates will enable the feasible detection of many important biomarkers with high specificity and high sensitivity.