Probing Cellular Activity Via Charge‐Sensitive Quantum Nanoprobes

Nitrogen-vacancy (NV) based quantum sensors hold great potential for real-time single-cell sensing with far-reaching applications in fundamental biology and medical diagnostics. Although highly sensitive, the mapping of quantum measurements onto cellular physiological states has remained an exceptional challenge. Here, we introduce a novel quantum sensing modality capable of detecting changes in cellular activity. Our approach is based on the detection of environment-induced charge depletion within an individual particle that, owing to a previously unaccounted transverse dipole term, induces systematic shifts in the zero-field splitting (ZFS). Importantly, these charge-induced shifts serve as a reliable indicator for lipopolysaccharide (LPS)-mediated inflammatory response in macrophages. Furthermore, we demonstrate that surface modification of our diamond nanoprobes effectively suppresses these environment-induced ZFS shifts, providing an important tool for differentiating electrostatic shifts caused by the environment from other unrelated effects, such as temperature variations. Notably, this surface modification also leads to significant reductions in particle-induced toxicity and inflammation. Our findings shed light on systematic drifts and sensitivity limits of NV spectroscopy in a biological environment with ramifications for the critical discussion surrounding single-cell thermogenesis. Notably, this work establishes the foundation for a novel sensing modality capable of probing complex cellular processes through straightforward physical measurements.