The optimized protocol described above was applied to all matrices and samples and MALDI-TOF spectra were collected both in the positive and negative ion mode. The intensities of 1 charge peak are compared in Fig. for BSA-protected gold nanoclusters. Whatever the matrix, MALDI-TOF peaks for AuNCs in positive mode lead to a higher signal than in negative mode, in particular when CHCA is used as matrix. This strong difference in signal intensity regarding ionization modes in MALDI was already evidenced by previous studies on ion production for peptides and proteins.