Peptide analysis: Solid phase extraction-elution on diamond combined with atmospheric pressure matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry

Electrospray ionization (ESI) has been an indispensable ion generation technique for mass spectrometric analysis of biopolymers such as intact proteins and protein digests operated at atmospheric pressure. Since its advent in 1998, atmospheric pressure matrix-assisted laser desorption/ionization (AP-MALDI) quickly became a popular alternative for the analysis of peptides. Although AP-MALDI sources typically share the same vacuum interface and ion transmission hardware with ESI, it is generally found that ESI is superior in detection sensitivity. Here we present a method based on solid phase extraction and elution with surface-functionalized diamond nanocrystals (which we previously referred to as “SPEED”) that not only streamlines AP-MALDI mass spectrometric analyses of peptides and other small biomolecules under typical operational conditions but also outruns ESI in ultimate detectable concentration by at least one order of magnitude.