Triple-bond Raman probes: Expanding molecular imaging in the cell-silent region

Molecular imaging has advanced dramatically over the past few decades, providing valuable insights into cellular processes and disease progression. Raman scattering-based imaging techniques have emerged as promising approaches, surpassing the limitations of fluorescence imaging by providing unique molecular fingerprints. However, Raman imaging faces challenges due to interference from cellular background signals. Researchers have developed novel Raman tags with triple-bond moieties to overcome this obstacle, featuring strong and distinct spectral signatures in the cell-silent region. By incorporating these triple-bond Raman tags into molecular imaging probes, signal intensity and specificity are greatly enhanced, enabling the simultaneous detection of multiple biomolecules. This concise review presents a comprehensive overview of recent developments in triple-bond Raman probes for molecular imaging. It covers design principles and strategies, including conjugation effects, isotope editing, end-capping variation, electronic pre-resonance stimulated Raman scattering, and azo-enhanced Raman probes. Next, we discuss the applications of triple-bond Raman probes in various fields, such as biomolecule imaging, organelle imaging, tissue imaging, and drug tracing. Finally, we highlight current challenges and future opportunities in triple-bond Raman probes for molecular imaging.