Abstract: | We recently showed that electrowetting‐enhanced sample preparation for MALDI‐MS (eMALDI) can increase the intensity of the MALDI signal by 2–25 times compared with conventional drop drying by concentrating all the dried sample in a single spot rather than leaving behind a heterogeneous coffee‐stain pattern. Here, we demonstrate that the eMALDI signal enhancement can be further increased to more than 100 times by systematically optimizing the electrowetting actuation frequency and amplitude. This enables 30 times signal increase for a peptide standard. Simultaneously, drop drying times can be reduced approximately five times by increasing the actuation voltage and/or decreasing the initial drop volume. Copyright © 2017 John Wiley & Sons, Ltd. |