In the search for alternative inert surfaces replacing silicon chips in Desorption/Ionization On porous Silicon (DIOS)-like mass spectrometry analyses, nanostructured silicon-based NALDI™ chips were evaluated in Laser Desorption/Ionization (LDI) of peptides. Comparisons were made using commercially available DIOS chips (MassPREP™-DIOS-target™), amorphous carbon powder from lead pencil and porous silica gel used for chromatographic purposes as reference supports. A set of synthetic model peptides presenting variable amino acid sequences of various lengths was analyzed under all conditions. The LDI responses of the four ‘matrix-free’ techniques were compared, especially in terms of peptide detection sensitivity and overall experiment robustness. Copyright © 2009 John Wiley & Sons, Ltd.