Tuning the surface enhanced Raman spectroscopy performance of Au core-Ag shell nanostructure for label-free highly sensitive detection of colorectal cancer Marker

•We have prepared a series of Au@Ag NPs with size-controlled Ag shell thickness (1 nm, 3 nm, 5 nm, 7 nm and 9 nm Ag shells) as the SERS substrates.•We have developed a novel label-free and ultrasensitive SERS based detection method for native protein•Based on the concentration-dependent SERS spectra, CRC biomarker NDKA and homologous protein NDKD can be identified directly for the first time. Moreover, several label-free proteins were also detected at ultralow concentrations with good reproducibility and high sensitivity.