Recent advances in surface-enhanced Raman spectroscopy for the detection of tumor markers

Abstract

Sensitive and accurate detection of tumor markers is critically essential for the early clinical diagnosis, treatment and prognosis of cancers. Surface-enhanced Raman spectroscopy (SERS) utilizes plasmonic nanomaterials to generate a strong surface plasmon resonance (SPR) effect in the visible to near-infrared region, such as silver and gold nanostructures. The SPR effect can significantly enhance the Raman signals of adsorbed molecules on the surface of nanostructures, allowing to gain the sensitive fingerprint information for the analyte itself or the Raman reporter. Benefitted from the superior properties of high sensitivity, good selectivity, fast and noninvasive analysis, SERS has attracted increasing interest and become a very promising technique for biological analysis. In comparison with other bioanalytical techniques, such as enzyme-linked immunosorbent assay, fluorescence and electrochemical methods, SERS possesses the following advantages: (1) SERS has an ultrahigh sensitivity, even down to single molecule level; (2) SERS can provide the intrinsic molecular fingerprint information, and the bandwidths of SERS peaks are usually very narrow; (3) SERS is suitable for long-term monitoring, because of the resistance of photobleaching and photodegradation; (4) non-invasive detection can be achieved with a low amount of sample and no preparation; (5) the interference of water is very weak, so biological samples can conveniently be detected in aqueous solutions; (6) various SERS-active nanostructures can be designed for multiplex detection. In this review, we provide an overview of recent advances in SERS technology for the detection of different tumor markers, including proteins, enzymes, nucleic acids, cells, tissues, gases and others. Great successes have been achieved by utilizing SERS, which can facilitate the fabrication of assays for tumor biomarkers. However, SERS has not been widely applied in clinical bioanalysis and biodiagnosis in the past over 40 years. SERS-based bioassay involves complex interactions between light, surface plasmon nanomaterials, and bioassay systems. It is difficult to obtain reproducible and reliable Raman spectroscopy data, which is one of the main bottlenecks in SERS bioassay, resulting in the deficiency of clinical and standardized applications. Therefore, there are still many efforts to be done to control the potential factors: (1) It is necessary to prepare a SERS substrate with high uniformity, high enhancement, clean, or/and to properly modify its surface; (2) the suitable Raman reporters and tags are selected to improve the biocompatibility and avoid unspecific adsorption, which can trap analytes in the “hot spots”; (3) biological samples are retained in their native state during the storage and pretreatment procedure to avoid irreversible degradation; (4) appropriate SERS detection conditions are performed, such as excitation wavelength, exposure time, and laser power, to obtain real detection information; (5) accurate biomolecule database are established for spectral assignments. By further improving these challenges, we anticipate the more widespread application of SERS-based assay in biomedicine and bioanalysis fields.