The use of dried matrix spots (DMSs) has recently re-emerged as a useful sample storage technique and analytical platform along with the increased adoption of and general preference for ambient ionization mass-spectrometric methods. However, challenges associated with precise liquid confinement and sample targeting persist. In this paper, we present a laser micromachining-based approach to prepare DMSs on hydrophobic paper substrates that include visual recognition elements, or reticles, around surface energy traps (SETs). This targeted DMS substrate is combined with direct mass spectrometric analyses, namely liquid microjunction–surface sampling probe–mass spectrometry (LMJ-SSP-MS) and flowing atmospheric-pressure afterglow–mass spectrometry (FAPA-MS). With the laser-based micromachining approach, DMSs flanked by crosshairs for enhanced visualization are prepared on SETs as small as 0.55 mm in diameter, which offers an approximately 12-fold reduction in size compared to traditional DMS preparations. The DMSs prepared on these targeting SETs are demonstrated with the detection of caffeine in model aqueous and artificial urine solutions using LMJ-SSP-MS and FAPA-MS, respectively. With further refinement, this approach could be automated using computer vision and robotics to broaden the scope of DMSs and improve the analytical workflow.
Reddy et al. (Thu,) studied this question.