Reactive Gas Cluster Ion Beams for Enhanced Drug Analysis by Secondary Ion Mass Spectrometry

In this study, we investigate the formation and composition of Gas Cluster Ion Beams (GCIBs) and their application in Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis. We focus on altering the carrier gas composition, leading to the formation of (Ar/CO₂)_n or (H₂O)_n GCIBs. Our results demonstrate that the addition of a reactive species (CO₂) to water GCIBs significantly enhances the secondary ion yield of small pharmaceutical compounds in the positive ion mode. In negative ion mode, the addition of CO₂ resulted in either a positive enhancement or no effect, depending on the sample. However, an excess of CO₂ in the carrier gas leads to the formation of carbon dioxide clusters, resulting in reduced yields compared to that of water cluster beams. Cluster size also plays a crucial role in overall yields. In a simple two-drug system, CO₂-doped water clusters prove effective in mitigating matrix effects in positive ion mode compared to pure water cluster, while in negative ion mode, this effect is limited. These clusters are also applied to the analysis of drugs in a biological matrix, leading to more quantitative measurements as shown by a better fitting calibration curve. Overall, the doping of water clusters with small amounts of a reactive gas demonstrates promising benefits for higher sensitivity, higher resolution molecular analysis, and imaging using ToF-SIMS. The effectiveness of these reactive cluster beams varies depending on the experimental parameters and sample type.