This perspective commemorates 50 years of surface-enhanced Raman scattering (SERS) by highlighting the paradigm shift toward rationally designed semiconductor substrates, enabling ultrasensitive and molecule-selective detection. Several enhancement strategies have been developed to effectively modulate the electronic band structure and charge transfer (CT) processes, such as energy level customization, amorphization, quasi-metallization, and morphology control, achieving high enhancement factors with good selectivity and stability. Moreover, semiconductor SERS substrates show broad prospects in the fields of bio-sensing and cancer diagnosis. Nevertheless, standardization gaps in substrate reproducibility and data comparability hinder its widespread adoption. Resolving these challenges through multi-stakeholder collaboration is essential to bridge the technology transfer gap and establish SERS as a core platform for next-generation inspection.

The development of efficient three-dimensional cell imaging technology is a necessary means to study cell composition and structure, especially to track and monitor the phagocytosis process of nanoparticles by cells. Herein, we prepared a MoO₂ hollow nanosphere with a strong surface plasmon resonance effect in the visible light region, which exhibited an excellent surface enhanced Raman scattering effect. When the 4-mercaptobenzoic acid (4-MBA) molecules are modified, it can be efficiently used as Raman probe molecules to perform clear three-dimensional cell imaging. No matter when the nanoparticles are located inside the cell, outside the cell or partly inside the cell, they all can be clearly presented by this enhanced Raman probe molecule. These results provide a rapid and accurate method for three-dimensional imaging of cells, especially for tracking the phagocytosis of nanoparticles.