Surface-enhanced Raman scattering (SERS) nanoparticles for biodiagnostics, bioimaging, and spectroscopy-guided cancer surgery

Surface-enhanced Raman scattering (SERS) continues to attract great excitement because it is one of the very few techniques that provide both ultrahigh sensitivity and molecular specificity. For biomedical applications, there are two emerging trends. One is to exploit the intrinsically label-free capabilities of SERS to detect and differentiate complete biomolecular signatures, often aided by artificial intelligence or deep learning algorithms. The second trend is to develop SERS nanoparticles as ultrabright detection tags (called nanotags). In this article, we focus on the development of SERS nanoparticles as encoded spectroscopic tags and will discuss their applications in diagnostics, biomolecular imaging, and spectroscopy-guided cancer surgery. In contrast to fluorescence, SERS signals are much more stable against photobleaching, and their peak widths are often less than a few nanometers. Also, SERS probes with different spectral signatures can all be excited at a single wavelength and detected with simple instrumentation for multiplexing. To put these concepts in perspective, we will start this article by briefly discussing the principles of SERS, follow by recent progress in developing in-vitro and in-vivo SERS tags. The article will then provide highlights of current and emerging applications in biology and medicine. The article will conclude with a discussion of the challenges and opportunities in translating SERS nanotags for clinical use.