The discovery in 1974 of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is considered a landmark in the history of spectroscopic and analytical techniques. Much experimental and theoretical effort has been spent toward understanding the surface enhanced Raman scattering (SERS) effect, and demonstrating its potential toward various types of ultrasensitive sensing applications in a wide variety of fields. Forty five years later, SERS has blossomed as an extremely rich area of research and technology, but additional efforts are still needed before it can be routinely used as a commercial product. In this Review, prominent authors from all over the world joined efforts to summarize the current state-of-the-art in understanding and using SERS, as well as to propose what can be expected in the near future, in terms of research, applications, and technological development.

Surface enhanced Raman spectroscopy (SERS) is meeting the requirements in biomedical science being a highly sensitive and specific analytical tool. By employing portable Raman systems in combination with customized sample pre-treatment, point-of-care-testing (POCT) becomes feasible. Powerful SERS-active sensing surfaces with high stability and modification layers if required are available for testing and application in complex biological matrices such as body fluids, cells or tissues. This review summarizes the current state in sample collection and pretreatment in SERS detection protocols, SERS detection schemes, i.e. direct and indirect SERS as well as targeted and non-targeted SERS, and SERS-active sensing surfaces. Moreover, the recent developments and advances of SERS in biomedical application scenarios, such as infectious diseases, cancer diagnostics and therapeutic drug monitoring is given, which enables the readers to identify the sample collection and preparation protocols, SERS substrates and detection strategies that are best-suited for their specific applications in biomedicine.

A comprehensive review of theoretical approaches to simulate plasmonic-active metallic nano-arrangements is given. Further, various fabrication methods based on bottom-up, self-organization and top-down techniques are introduced. Here, analytical approaches are discussed to investigate the optical properties of isotropic and non-magnetic spherical or spheroidal particles. Furthermore, numerical methods are introduced to research complex shaped structures. A huge variety of fabrication methods are reviewed, e.g. bottom-up preparation strategies for plasmonic nanostructures to generate metal colloids and core–shell particles as well as complex-shaped structures, self-organization as well as template-based methods and finally, top-down processes, e.g. electron beam lithography and its variants as well as nanoimprinting. The review article is aimed at beginners in the field of surface enhanced spectroscopy (SES) techniques and readers who have a general interest in theoretical modelling of plasmonic substrates for SES applications as well as in the fabrication of the desired structures based on methods of the current state of the art.