Surface-Enhanced Raman Spectroscopy Biosensing: In Vivo Diagnostics and Multimodal Imaging

Abstract

This perspective presents recent developments in the application of surface-enhanced Raman spectroscopy (SERS) to biosensing, with a focus on in vivo diagnostics. We describe the concepts and methodologies developed to date and the target analytes that can be detected. We also discuss how SERS has evolved from a "point-and-shoot" stand-alone technique in an analytical chemistry laboratory to an integrated quantitative analytical tool for multimodal imaging diagnostics. Finally, we offer a guide to the future of SERS in the context of clinical diagnostics.

Cancer characterization and diagnosis with SERS-encoded particles

“…Nanostars and nanorods accumulate the electromagnetic field at their tips, giving rise to very strong single particle SERS intensities (Alvarez-Puebla et al 2010). Similar approaches as for spherical colloids were applied for the preparation of SEPs using Au nanostars functionalized with thiolated PEG (Morla-Folch et al 2014;Yuan et al 2012), or coated with silica shells (Andreou et al 2016;Henry et al 2016;Huang et al 2016;Mir-Simon et al 2015;Oseledchyk et al 2017). Figure 2d, h shows Au nanostars coated with Ag and silica, respectively.…”

“…To increase the SERS efficiency of SEPs, similar constructs were produced by using aggregates instead of individual nanoparticles. These structures are also usually encapsulated in silica, PEG or mixed BSA-glutaraldehyde for stability and protection of the SERS codes (Henry et al 2016). This approach creates a collection of hot spots within the SEPs, leading to a considerable intensity increase.…”

“…As conceptual and instrumentational advancements in the standalone application of SERS imaging of cancers are progressively expanding this technique beyond the academic level to clinical settings, parallel efforts have been dedicated to the integration of SEPs into novel multifunctional hybrid materials with improved performance for multimodal applications (Conde et al 2014;Gao et al 2015;Henry et al 2016;Qian et al 2011;Von Maltzahn et al 2009). With such complementary approaches, multimodal imaging technologies have been developed implementing SERS with other imaging techniques based on different physical effects such as fluorescence (Cui et al 2011;Qian et al 2011;Wang et al 2014b), magnetic resonance (Gao et al 2015;Ju et al 2015) and photoacoustics (Bao et al 2013;Chen et al 2016;Dinish et al 2015;Jokerst et al 2012a;Kircher et al 2012).…”

Advances in the clinical translation of nanotechnology

“…In these sensors, surface plasmons in metals such as silver or gold enhance the Raman scattering signal of an adsorbed material. Metal nanoparticles functionalized with molecular recognition elements such as antibodies or aptamers, enable measurements of analyses such as neurotoxins, glucose, and cancer biomarkers with the potential for detection down to zeptomolar levels (42). …”

Spatial Analysis of Metal–PLGA Hybrid Microstructures Using 3D SERS Imaging

“…[24] Gold nanoparticles, in contrast to PLGA, are optically active and show interesting behavior upon laser irradiation, including local heating that can be exploited for thermoresponsive delivery methods, as well as the above-mentioned SERS activity, which can be used for imaging. [25] These biological applications are favored for gold nanoparticles with shape anisotropy, such as gold nanostars (AuNSs), which absorb ≈800 nm, where tissue displays reduced absorption and, in turn, increased penetration depth. [26] However, anisotropic nanoparticles are often grown in water or other solvents with high dielectric constants, which may hinder their encapsulation in polymers.…”