The Influence of Primary Ion Species and Cluster Size on the Time-of-Flight Secondary Ion Mass Spectrum of Ciprofloxacin in Water Ice

Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) can provide label-free 2D and 3D images of pharmaceuticals, lipids, and metabolites in biological studies. Because the measurements are made in high vacuum, analysis of frozen hydrated biological samples is required in order to maintain the native sample structure and prevent migration of the analytes. However, water cluster ion peaks can interfere with the detection of analytes. In this study, the influence of bismuth and argon cluster primary ions on the spectrum of a cryogenic frozen hydrated cell-free model biofilm sample has been investigated with the aim of reducing interference from the water cluster background to the analyte ciprofloxacin. The data show that Bi₁⁺ primary ions are by far the most effective of the primary ions studied in minimizing the water ice cluster background at temperatures from 103 to 153 K. Other bismuth cluster ions, including Bi₃⁺ and Bi₅⁺, increased the ion yield of ciprofloxacin but increased the yield of water cluster ions yet more. Argon cluster primary ions, which typically improve the ion yield for organic molecules, resulted in high water cluster background signals in the mass range above 200 <i>m</i>/<i>z</i> and a low ion yield for ciprofloxacin. Analysis of frozen hydrated samples with Bi₁⁺ primary ions at a temperature of 153 K provided the highest signal-to-background ratio and is recommended.