A SERS-based 3D nanobiosensor: towards cell metabolite monitoring

The development of surface-enhanced Raman scattering (SERS) spectroscopy as an analytical technique has been mainly focused on improving detection limits, nanoparticle (NP) stability and reproducibility. However, a step further on the functionalities of these promising sensing platforms is needed to enable their integration as in situ biosensors able to continuously monitor the cellular microenvironment and cell communication. Herein, we developed a biocompatible SERS hybrid material, by embedding gold-based nanostructures into gellan gum "sponge-like" hydrogels. This novel material was used as a SERS substrate for biochemical detection of disease associated cell metabolites. The optical and morphological characterisation of these 3D plasmonic sensors demonstrated the efficient incorporation of gold nanostars and silver coated gold nanorods, as well as their homogeneous distribution within the hydrogel matrices. By using these 3D plasmonic polymeric matrices we were able to prove the detection of two cancer-cell-related extracellular metabolites, lactate and thiocyanate. The SERS detection of these two small molecules is not trivial and was only possible due to the extra SERS enhancement offered by both types of anisotropic NPs. Further, the use of the gellan gum scaffold to support the NPs enables the potential use of these novel SERS platforms for the in situ growth and metabolism monitoring of 3D cell models.