Cover story: Xie ZL, Meng C, Yue DH et al. Tip-enhanced Raman scattering of glucose molecules. Opto-Electron Sci 4, 240027 (2025)

Carbon (C), hydrogen (H), and oxygen (O), as the three fundamental elements constituting living organisms, serve respectively as the skeleton of organic molecules, the core of energy production, and the key component of cellular respiration. The glucose molecule, built from these C-H-O elements, stands as one of the primary energy sources for human life activities. However, the Raman scattering cross-section of glucose molecules is extremely small, coupled with their weak or non-adsorption on bare metal, making it challenging to acquire their vibrational spectral information. To address this challenge, we developed a novel tip-enhanced Raman spectroscopy (TERS) configuration by integrating scanning near-field optical microscopy with low-background tip-enhanced nanofocusing light source featuring strong electric-field enhancement. Utilizing a shear-force feedback technique, the nanofocusing light source can be precisely positioned on the surface of clustered glucose molecules, thereby enabling a highly visualized observation of all vibrational modes of glucose within the Raman spectral window. This TERS technology seamlessly combines fiber-based structured light field regulation, plasmonic fiber tip nanofocusing, and shear-force feedback, providing a powerful tool for accurately identifying weak physicochemical processes of biomolecules at the nanoscale.