Fundamentals and applications of surface-enhanced Raman spectroscopy–based biosensors

Surface-enhanced Raman scattering (SERS) has become a mature spectroscopic technique with the fast development in the past four decades, and its detection applications in the fields of chemistry, materials science, biochemistry and life sciences are rapidly expanding. In particular, advances in the design and construction of SERS-based biosensors have delivered tremendous development in the biological and biomedical sensing applications. Electromagnetic enhancement contributes dominantly to SERS enhancement, and the hotspot structures are crucial to sensitive and reproducible detection performance. SERS-based biosensors can be produced by direct and indirect techniques according to the sensing needs. In this mini-review, the enhancing mechanism and SERS structures are briefly described and the various common fabrication techniques are discussed. Recent state-of-the-art applications of SERS-based biosensors such as detection of ex vivo biofluids and biomolecules such as proteins, DNAs and microRNAs, as well as monitoring of cellular properties including pH, temperature and ion concentrations, are reviewed.