Spin-Uniform Nanodiamond Quantum Sensors for Reproducible Intracellular Thermometry

Abstract

Nanodiamond quantum sensors have been regarded as promising probes for cellular thermometry, but their poor sensor-to-sensor reproducibility has hindered practical implementation. In cellular measurements, the resulting temperature-readout offsets can be mistaken for real cell-to-cell temperature differences, limiting quantitative comparison. Here, we show that spin-uniform nitrogen vacancy (NV)-rich nanodiamonds can be produced via postenrichment oxidative size reduction, which removes defective surface layers while improving crystallinity. Compared with nanodiamonds prepared by conventional mechanical milling before NV enrichment, the particle-to-particle spread in the temperature-sensitive D values was reduced by 3.7-fold. The improved NV homogeneity also enhanced spin properties: the optically detected magnetic resonance contrast─a key signal amplitude for sensitivity─increased by more than 50%. Together, these improvements reduce cell-to-cell dispersion in D-derived single-cell temperature readouts to below 0.7 K, enabling reliable temperature comparison across cells. This approach advances nanodiamond absolute thermometry toward organelle-scale intracellular temperature mapping and practical quantum sensing in biology and medicine.