Portable paper-in-tip spray ionization for the direct mass spectrometric analysis of target analytes in biofluid samples

Portable sampling of target analytes in complex biofluid samples makes mass spectrometric analysis more efficient. This study reports the development of paper-in-tip spray ionization for solid-phase microextraction and in situ electrospray of therapeutic drugs and proteins in complex biological matrices using a piece of hydrophobic paper substrate. This technique possesses a long (more than 8 min) and stable spray duration with only 20 μL of spray solvent. The entire analytical process for a complex sample can be completed in less than 1.5 min and enables high sensitivity (picogram-per-milliliter level) and high quantitation precision.