Ultraphotostable Mesoporous Silica-Coated Gap-Enhanced Raman Tags (GERTs) for High-Speed Bioimaging

Surface-enhanced Raman scattering (SERS) tags can be utilized as optical labeling nanoprobes similar to fluorescent dyes and quantum dots for bioimaging with additional advantages of fingerprint vibrational signals as unique optical codes and ultranarrow line widths for multiplexing. However, the development of the SERS imaging technique is much less well-established compared to the devlopment of fluorescence imaging mainly because of speed limitations. An effective strategy for improving the SERS imaging speed and simultaneously maintaining the photostability of SERS tags has not, to the best of our knowledge, been reported. In this work, mesoporous silica- (MS-) coated gap-enhanced Raman tags (GERTs) were designed with built-in Raman reporters for off-resonance near-infrared laser excitation and reduced photothermal effects, leading to ultraphotostability during laser irradiation. Additionally, they achieve large amplification of Raman signals by combining the chemical (CHEM) and electromagnetic (EM) enhancement effects due to the subnanometer core-shell junction, so SERS imaging can be performed in a dramatically reduced duration. With these unique structural and optical advantages, MS GERTs exhibit high storage, pH, serum, and photostabilities; strong Raman enhancements; and favorable biocompatibility. Therefore, MS GERTs achieve long-term cell imaging that can last for 30 min without being photobleached and also maintain decent imaging effects. Furthermore, MS GERTs enable continuous and stable imaging in living tissues for more than 30 min. With these advantages, MS GERTs might potentially have more biomedical applications.