A critical step in MALDI MS is sample preparation. Unfortunately, the optimal way to obtain decent ion signal is highly dependent on the matrix and on the nature of the sample. We investigated different sample preparation strategies to optimize the response of the present protein-protected NCs in the negative mode using three matrices: SA, DHB, and CHCA. Table summarizes the different conditions investigated based on BSA and BSA-AuNCs. Reproducibility of MALDI-MS results are summarized in Table .