High Uniformity and Enhancement Au@AgNS 3D Substrates for the Diagnosis of Breast Cancer

[Image: see text] Breast cancer appears to be one of the leading causes of cancer-related morbidity and mortality for women worldwide. The accurate and rapid diagnosis of breast cancer is hence critical for the treatment and prognosis of patients. With the vibrational fingerprint information and high detection sensitivity, surface-enhanced Raman spectroscopy (SERS) has been extensively applied in biomedicine. Here, an optimized bimetallic nanosphere (Au@Ag NS) 3D substrate was fabricated for the aim of the diagnosis of breast cancer based on the SERS analysis of the extracellular metabolites. The unique stacking mode of 3D Au@Ag NSs provided multiple plasmonic hot spots according to the theoretical calculations of the electromagnetic field distribution. The low relative standard deviation (RSD = 2.7%) and high enhancement factor (EF = 1.42 × 10(5)) proved the uniformity and high sensitivity. More importantly, the normal breast cells and breast cancer cells could be readily distinguished from the corresponding SERS spectra based on the extracellular metabolites. Furthermore, the clear clusters of SERS spectra from MCF-7 and MDA-MB-231 extracellular metabolites in the orthogonal partial least-squares discriminant analysis plot indicate the distinct metabolic fingerprint between breast cancer cells, which imply their potential clinical application in the diagnosis of breast cancer.