Plasmonic Nanoparticle Monolayer‐Decorated Nanopipette Enabling in Situ Monitoring of Single‐Cell Redox Metabolism

Abstract

Abstract The in‐depth study of how single cells respond to redox perturbations is pivotal for predicting cell fate decisions. Surface‐enhanced Raman spectroscopy (SERS)‐active nanopipettes hold promise for single‐cell analysis, yet challenges remain in achieving both signal sensitivity and reproducibility. Here, a plasmonic nanoparticle monolayer‐decorated nanopipette has been developed, which serves as a biomimetic endoscope to monitor single‐cell redox metabolism. This is accomplished by the conformal transferring of gold nanoparticle monolayer onto the nanopipette followed by the functionalization of redox‐responsive probes. The strong near‐field coupling within monolayer forms uniform hotspots, enabling highly sensitive and reproducible tracking of SERS signals changes triggered by redox species. Modulated by the nanopipette technology, the endoscope allows for in situ monitoring of global redox states with low invasiveness and high spatial resolution. Further, study of ferroptosis events via simultaneous optical and electrical recording elucidates the correlation between redox imbalance and membrane damage during various ferroptosis‐inducers stimulation, which has not been observed at the single‐cell level. This work provides profound insights into the cellular redox dynamics, contributing to a deeper understanding of related physiopathological pathways.