Improvement of Lipid Detection in Mouse Brain and Human Uterine Tissue Sections Using In Situ Matrix Enhanced...

The potential of mass spectrometry imaging, and especially ToF-SIMS 2D and 3D imaging, for submicrometer-scale, label-free molecular localization in biological tissues is undisputable. Nevertheless, sensitivity issues remain, especially when one wants to achieve the best lateral and vertical (nanometer-scale) resolution. In this study, the interest of in situ matrix transfer for tissue analysis with cluster ion beams (Bi_n⁺, Ar_n⁺) is explored in detail, using a series of six low molecular weight acidic (MALDI) matrices. After estimating the sensitivity enhancements for phosphatidylcholine (PC), an abundant lipid type present in almost any kind of cell membrane, the most promising matrices were softly transferred in situ on mouse brain and human uterine tissue samples using a 10 keV Ar₃₀₀₀⁺ cluster beam. Signal enhancements up to 1 order of magnitude for intact lipid signals were observed in both tissues under Bi₅⁺ and Ar₃₀₀₀⁺ bombardment. The main findings of this study lie in the in-depth characterization of uterine tissue samples, the demonstration that the transferred matrices also improve signal efficiency in the negative ion polarity and that they perform as well when using Bi_n⁺ and Ar_n⁺ primary ions for analysis and imaging.