Polystyrene Encapsulated SERS Tags as Promising Standard Tools: Simple and Universal in Synthesis; Highly Sensitive and Ultrastable for Bioimaging.

Surface coating determined the sensitivity and stability of surface-enhanced Raman scattering (SERS) tags in bioanalysis. The reported various coatings suffered from the drawbacks of a lack of rigidity, stability, or synthesis versatility. Herein, we demonstrated robust polystyrene (PS) coated SERS tags that could be prepared by an easy and universal approach. Taking advantages of biocompatible, transparent, compact properties of PS shell, the coated tags showed satisfactory sensitivity, biocompatibility, and superior structural stability in cell and in vivo imaging applications. More importantly, the PS coating strategy allowed for the encapsulation of SERS tags encoded with not only thiolated but also nonthiolated Raman reporters without loss of sensitivity, as exemplified in the synthesis of 9 different resonant dye-encoded tags. Moreover, the coating of SERS tags with various kinds of substrates was achieved via the same standard protocol. Comparing with widespread silica coated tags, the PS coated ones were more stable in harsh conditions and had an easily expanded ultrasensitive (resonant) tags library with much lower cost (no need of expensive sulfhydryl/isothiocyano reporters with limited types), illustrating great promise as standard analytical tools of commercialized value for bioanalysis, medical diagnostics, and environmental science studies.