Development of bioorthogonal SERS imaging probe in biological and biomedical applications

Living-cell imaging demands high specificity, sensitivity, and minimal background interference to the targets of interest. However, developing a desirable imaging probe that can possess all the above features is still challenging. The bioorthogonal surface-enhanced Raman scattering (SERS) imaging has been recently emerged through utilizing Raman reporters with characteristic peaks in Raman-silent region of cells (1800−2800 cm−1), which opens a revolutionary avenue for living-cell imaging with multiplexing capability. In this review, we focus on the recent advances in the technology development and the biological and biomedical applications of the living-cell bioorthogonal SERS imaging technique. After introduction of fundamental principles for bioorthogonal tag or label, we present applications for visualization of various intracellular components and environment including proteins, nucleic acids, lipids, pH and hypoxia, even for cancer diagnosis in tissue samples. Then, various bioorthogonal SERS imaging-guided therapy strategies have been discussed such as phototherapy and surgery. In conclusion, this strategy has great potential to be a flexible and robust tool for visualization detection and diseases diagnosis.