Membrane Electrospray Ionization for Direct Ultrasensitive Biomarker Quantitation in Biofluids Using Mass Spectrometry

The ability of rapid biomarker quantitation in raw biological samples would expand the application of mass spectrometry in clinical diagnosis. Up until now, the conventional chromatography–mass spectrometry method is time-consuming in both sample preparation and chromatography separation processes, while ambient ionization methods normally suffer from sensitivity. The membrane electrospray ionization (MESI) introduced in this study could not only achieve sensitive biomolecule quantitation, but also minimize the sample handling process. As a unique feature of MESI, both vertical and horizontal chemical separations could be achieved in real-time. With the capability of mass-selectively minimizing matrix effects from salts, small molecules, and macromolecules, ultrasensitive detection of cytochrome C (>500-fold sensitivity improvement) in raw urine samples was demonstrated in less than 20 min