Analysing cells and culture media with surface-enhanced Raman scattering (SERS): how to overcome the serum protein problem?

Surface-enhanced Raman scattering (SERS) has become a valuable tool in the pharmaceutical and bioanalytical fields as it presents numerous advantages making it competitive towards other analytical tools. However, a current challenge faced in biological SERS is the protein corona problem. It arises from the adsorption of serum proteins onto the SERS substrates, preventing the adsorption of the analytes themselves onto the substrates. Moreover, the protein corona stabilises suspensions of nanoparticles. This competition for the substrate surface, combined with the lack of aggregation, makes SERS analyses of native biological samples difficult. In order to circumvent these problems, several strategies were considered. When working with a suspension of gold nanoparticles (AuNPs), the colloid can be pre-aggregated before adding the serum sample. Regarding solid SERS substrates, the challenge rather concerns avoiding the adsorption of proteins onto the substrate. To that end, membranes with a low molecular weight cut-off have been employed. These membranes could let small molecules diffuse through them while retaining proteins of larger sizes. In conclusion, the use of filter membranes seems extremely promising.