Tuning the Surface Enhanced Raman Spectroscopy Performance of Au Core-Ag Shell Nanostructure for Label-Free Highly Sensitive Detection of Colorectal Cancer Marker

Abstract Early detection is vital for the prevention and treatment of patients with colorectal cancer (CRC). However, existent methods (such as enzyme immunoassay, chemiluminescent immunoassay and radioimmunoassay) for early detection of CRC are time consuming, costly and complicated multistage processes, limiting their further applications. Here, a novel label-free and ultrasensitive detection method is developed for CRC protein marker NDKA by Cr3+ ions aggregating Au@Ag NPs (ICNPs) via surface-enhanced Raman spectroscopy (SERS) spectra for the first time. The Au@Ag NPs with size-controlled Ag shell thickness (1 nm, 3 nm, 5 nm, 7 nm and 9 nm Ag shells) are prepared as the SERS substrates and its Raman signals are Ag shells thickness-dependent sensitivity to proteins. By using Cr3+ ions as aggregating agents, the aggregating effect between the SERS substrates of Au@Ag ICNPs and protein analyte results in significantly enhanced and reproducible Raman signals owing to formation of lots of hotspots. Using this novel method, several label-free proteins, myoglobin (3 fg/mL), human serum albumin (30 fg/mL), lysozyme (30 ng/mL) and cytochrome C (30 ng/mL) were also detected at ultralow concentrations with good reproducibility and high sensitivity, demonstrating the potential applications in the fields of medical therapy and clinical diagnosis.