Purpose Surface-enhanced Raman scattering (SERS) spectroscopy on serum and other biofluids for cancer diagnosis represents an emerging field, which has shown promising preliminary results in several types of malignancies. The purpose of this study was to demonstrate that SERS spectroscopy on serum can be employed for the differential diagnosis between five of the leading malignancies, ie, breast, colorectal, lung, ovarian and oral cancer. Patients and methods Serum samples were acquired from healthy volunteers (n=39) and from patients diagnosed with breast (n=42), colorectal (n=109), lung (n=33), oral (n=17), and ovarian cancer (n=13), comprising n=253 samples in total. SERS spectra were acquired using a 532 nm laser line as excitation source, while the SERS substrates were represented by Ag nanoparticles synthesized by reduction with hydroxylamine. The classification accuracy yielded by SERS was assessed by principal component analysis–linear discriminant analysis (PCA-LDA). Results The sensitivity and specificity in discriminating between cancer patients and controls was 98% and 91%, respectively. Cancer samples were correctly assigned to their corresponding cancer types with an accuracy of 88% for oral cancer, 86% for colorectal cancer, 80% for ovarian cancer, 76% for breast cancer and 59% for lung cancer. Conclusion SERS on serum represents a promising strategy of diagnosing cancer which can discriminate between cancer patients and controls, as well as between cancer types such as breast, colorectal, lung ovarian and oral cancer.

Chloride-capped silver nanoparticles (Cl-AgNPs) allow for high-intensity surface-enhanced Raman scattering (SERS) spectra of cationic molecules to be obtained (even at nanomolar concentration) and may also play a key role in understanding some fundamental principles behind SERS. In this study, we describe a fast (<10 min) and simple protocol for obtaining highly SERS-active colloidal silver nanoparticles (AgNPs) with a mean diameter of 36 nm by photoconversion from AgCl precursor microparticles in the absence of any organic reducing or capping agent. The resulting AgNPs are already SERS-activated by the Cl− ions chemisorbed onto the metal surface where the chloride concentration in the colloidal solution is 10−2 M. Consequently, the enhanced SERS spectra of cationic dyes (e.g., crystal violet or 9-aminoacridine) demonstrate the advantages of Cl-AgNPs compared to the as-synthesized AgNPs obtained by standard Ag+ reduction with hydroxylamine (hya-AgNPS) or citrate (cit-AgNPs). The results of SERS experiments on anionic and cationic test molecules comparing Cl-AgNPs, hya-AgNPs and cit-AgNPs colloids activated with different amounts of Cl− and/or cations such as Ag+, Mg2+ or Ca2+ can be explained within the understanding of the adatom model – the chemisorption of cationic analytes onto the metal surface is mediated by the Cl− ions, whereas ions like Ag+, Mg2+ or Ca2+ mediate the electronic coupling of anionic species to the silver metal surface. Moreover, the SERS effect is switched on only after the electronic coupling of the adsorbate to the silver surface at SERS-active sites. The experiments presented in this study highlight the SERS-activating role played by ions such as Cl−, Ag+, Mg2+ or Ca2+, which is a process that seems to prevail over the Raman enhancement due to nanoparticle aggregation.

We highlight a new metal−molecule charge transfer process by tuning the Fermi energy of plasmonic silver nanoparticles (AgNPs) in situ. The strong adsorption of halide ions upshifts the Fermi level of AgNPs by up to ∼0.3 eV in the order Cl − < Br − < I − , favoring the spontaneous charge transfer to aligned molecular acceptor orbitals until charge neutrality across the interface is achieved. By carefully quantifying, experimentally and theoretically, the Fermi level upshift, we show for the first time that this effect is comparable in energy to different plasmonic effects such as the plasmoelectric effect or hot-carriers production. Moreover, by monitoring in situ the adsorption dynamic of halide ions in different AgNP−molecule systems, we show for the first time that the catalytic role of halide ions in plasmonic nanostructures depends on the surface affinity of halide ions compared to that of the target molecule.

Background: There is an ongoing research for breast cancer diagnostic tools that are cheaper, more accurate and more convenient than mammography. Methods: In this study, we employed surface-enhanced Raman scattering (SERS) for analysing urine from n = 53 breast cancer patients and n = 22 controls, with the aim of discriminating between the two groups using multivariate data analysis techniques such as principal component analysis—linear discriminant analysis (PCA-LDA). The SERS spectra were acquired using silver nanoparticles synthesized by reduction with hydroxylamine hydrochloride, which were additionally activated with Ca2+ 10−4 M. Results: The addition of Ca(NO3)2 10−4 M promoted the specific adsorption to the metal surface of the anionic purine metabolites such as uric acid, xanthine and hypoxanthine. Moreover, the SERS spectra of urine were acquired without any filtering or processing step for removing protein traces and other contaminants. Using PCA-LDA, the SERS spectra of urine from breast cancer patients were classified with a sensitivity of 81%, a specificity of 95% and an overall accuracy of 88%. Conclusion: The results of this preliminary study contribute to the translation of SERS in the clinical setting and highlight the potential of SERS as a novel screening strategy for breast cancer.