The direct analysis of separated zones on thin-layer plates using mass spectrometric detection is currently undergoing a renaissance. After many years of neglect or awkward compromises,a number of new approaches have emerged in step with general advances in mass spectrometry over the last decade. Early approaches to coupling thin-layer chromatography with mass spectrometry are summarized in [8,59] and more recent developments in [58,102,103]. In terms of scanning approaches, the breakthrough was the development of atmospheric pressure ionization sources [104]. This simplified source design and facilitated the manipulation of relatively large objects, like thin-layer plates,when compared with conventional vacuum ion sources. That said,vacuum MALDI (matrix-assisted laser desorption and ionization) is still a popular method for identifying compounds such as lipids and other medium-mass compounds [105,106]. Bruker Daltonics offeran adapter for scanning thin-layer plates using their MALDI source[105]. MALDI provides high spatial resolution and reasonable tol-erance to contamination of the sample zone by layer impurities. On the other hand, for good sensitivity and signal persistence, MALDI requires application of a solid matrix (by dipping or spraying with asolution of the matrix) prior to measurement. The combination of a high vacuum and presence of matrix ions as a spectrum backgroundlimits applications in the low mass range.