Emerging trends in paper spray mass spectrometry: Microsampling, storage, direct analysis, and applications

: Recent advancements in the sensitivity of chemical instrumentation have led to increased interest in the use of microsamples for translational and biomedical research. Paper substrates are by far the most widely used media for biofluid collection, and mass spectrometry is the preferred method of analysis of the resultant dried blood spot (DBS) samples. Although there have been a variety of review papers published on DBS, there has been no attempt to unify the century old DBS methodology with modern applications utilizing modified paper and paper-based microfluidics for sampling, storage, processing, and analysis. This critical review will discuss how mass spectrometry has expanded the utility of paper substrates from sample collection and storage, to direct complex mixture analysis to on-surface reaction monitoring.