Inductively coupled plasma with time-of-flight mass spectrometry (ICP-ToF-MS) is currently setting new benchmarks for the analysis of single particles (SP) and elemental mapping using laser ablation (LA). The rapid collection of full elemental mass spectra promotes non-target approaches, fast imaging as well as inquiries of particle composition. However, one shortcoming often associated with ICP-ToF-MS is a lack of detection power due to lower duty cycles relative to sequentially operating mass analysers targeting only a limited number of elements. The sensitivity of ICP-ToF-MS can be increased using two strategies, which are detailed in this study. First, instead of analysing full mass spectra, elements in the low and high mass ranges were excluded from analysis using a Bradbury–Nielsen gate. The resulting restricted mass range was acquired up to 5 times faster increasing duty cycles and sensitivity accordingly. Second, isotopes of polyisotopic elements recorded simultaneously were accumulated to increase signal to noise ratios. In a proof of concept, we applied SP ICP-ToF-MS for the first time to characterise upconversion nanoparticles (UCNPs) that contained Gd and Yb. Both signal amplification strategies were combined and the consequences for detection limits and signal to noise ratios were considered and compared to a standard method. Sensitivities were increased up to factor 27 when accumulating all Gd and Yb isotopes at 177 kHz, and size detection limits decreased by a factor of approximately 3. Improved figures of merit promoted more accurate investigations of UCNPs, which were characterised regarding size distributions and composition. As a second application, we demonstrated the utility of the described strategies in LA-ICP-ToF-MS. Mo and Se were targeted as relatively rare elements in rat brain tissue. Increased acquisition frequencies of 180 kHz and isotope accumulation resulted in drastically improved signal to noise ratios and enabled the mapping of both elements while still considering relevant neuroanatomical elements such as Fe and Zn.