Sensing with (One or Many) Upconverting Nanoparticles

) have positioned UCNPs as a practical platform for intracellular thermometry despite their moderate sensitivity. Their response can be measured with standard microscopes using inexpensive NIR excitation sources, enabling experiments that are not easily achieved with other types of nanoscale thermometers. However, using UCNPs inside living cells also reveals important limitations because the intracellular medium is chemically complex and may alter the emission properties that form the basis of the thermal readout. Variations in local pH, ion concentration, viscosity, or molecular crowding can shift energy levels or modify nonradiative relaxation pathways. As a result, establishing the reliability of UCNP thermometry inside cells requires dedicated studies on particle stability, surface chemistry, and the influence of the cytoplasmic environment. Understanding these effects is essential for determining whether ratiometric UCNP thermometry can serve as a quantitative intracellular tool rather than only a qualitative indicator of heating. UCNPs have also enabled new single-particle experiments through optical trapping. A tightly focused NIR beam can immobilize an individual nanoparticle while simultaneously exciting its upconversion emission, allowing continuous monitoring of spectral changes, rotational dynamics, and local mechanical properties. These studies provide access to information that is hidden in ensemble measurements, such as particle-particle radiative interactions or the coupling between particle rotation/movement and local viscosity. Yet optical trapping also brings its own challenges: the forces acting on sub-100 nm UCNPs are modest, and trapping stability is strongly affected by laser-induced heating. Increasing dopant concentration improves confinement but raises thermal load, leading to a trade-off that must be carefully balanced. Approaches based on plasmonic enhancement are not suitable due to their additional heating, motivating interest in alternative photonic structures such as dielectric metasurfaces that could strengthen confinement while keeping temperatures low. Together, intracellular thermometry and single-particle trapping illustrate both the strengths and the current limitations of UCNPs. Their optical properties make them accessible probes for measuring local temperature and mechanical responses, but their performance heavily depends on the surrounding environment. In this Account, we summarize our efforts to understand UCNP behavior under realistic biological and trapping conditions. We discuss the stability of the thermometric response inside cells, the confinement-heating balance in optical traps, and the opportunities offered by single-particle measurements for studying light-matter interactions at the nanoscale. These considerations outline a path toward more reliable sensing and manipulation strategies based on UCNPs.