Aptamer-based novel Ag-coated magnetic recognition and SERS nanotags with interior nanogap biosensor for ultrasensitive detection of protein biomarker

The design of a rapid, simple, and ultrasensitive detection platform of protein biomarkers has become an urgent need in early diagnosis and treatment. Surface-enhanced Raman scattering (SERS) technology, with the unique advantages of ultra-sensitivity and fingerprint recognition, has attracted much attention in biomarker detection. An innovative aptamer SERS biosensor for highly sensitive protein biomarker detection was presented. This biosensor contains a SERS tag (reporter-labeled Au nano-bridged nanogaps particles, Au NNPs) and novel magnetic capture substrate (Ag-coated Fe 3 O 4 -Au NPs, Ag MNPs). C-reactive protein (CRP), a representative biomarker for diagnosing, was used to assess the SERS performance of this biosensor. Aptamers against CRP were modified on both SERS tag and magnetic capture substrate for specific recognition by Au NNPs-CRP-Ag MNPs sandwich assay. This strategy achieved sensitive detection of CRP with a limit of detection (LOD) of 10 fM (1.14 pg/mL), and is much lower than reported analytical methods. Besides, this method exhibits excellent selectivity and specificity for CRP under the interference of other proteins and displays high accuracy in the detection of actual human serum samples. This proposed detection strategy can be extended to the sensitive detection of other biomarker proteins and hold great promise in the clinical diagnosis of diseases.