AUTHOR=Shan Yaqi , Wu Jihao , Cui Kai , Yang Juan TITLE=Label-free detection of single cell by ZnO/Graphene/AgNPs hybrid microcavity enhanced Raman scattering JOURNAL=Frontiers in Chemistry VOLUME=Volume 13 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2025.1636525 DOI=10.3389/fchem.2025.1636525 ISSN=2296-2646 ABSTRACT=Ultrasensitive detection of Escherichia coli (E. coli) is important for early diagnosis of foodborne diseases. Current analytical techniques face limitations in performing label-free quantification of viable bacterial cells at single-cell resolution. Herein, a hybrid enhanced Raman scattering probe was constructed by assembling a layer of graphene and silver nanoparticles on a hexagonal ZnO microrod (ZnO/Graphene/AgNPs) for ultrasensitive analysis of pathogens directly. Ultimately, quantitative detection of E. coli was successfully carried out with excellent detectability from 1 cell mL−1 to 1 × 108 cells mL−1. It provided a detection limit as low as 4.57 × 10−2 cell mL−1 for E. coli. This can be attributed to the synergistic effect of different components, i.e., the ZnO microrod provides natural whispering gallery mode (WGM) microcavity which enhances light-matter interaction through multiple total internal reflections, graphene assists charge transfer, and AgNPs produce surface plasmons. These three enhancement factors are integrated to achieve label-free ultrasensitive detection. This work highlights a label-free approach for a variety of clinically relevant biomolecules to achieve early diagnosis of the disease.