Enhanced MALDI Ionization Efficiency at the Metal-Matrix Interface: Practical and Mechanistic Consequences of Sample Thickness and Preparation Method

Electrosprayed spots of varying thickness were evaluated for use as reproducible, homogenous, high efficiency MALDI samples. Thin samples on stainless steel plates were found to give exceptionally strong signals, as did the last layers of thick samples, when ablated down to the steel substrate. A small enhancement was also observed for thin samples on a gold substrate, and with a few-nanometer gold coating on top of a thick sample. Ion yields and intensity ratios can be understood in the context of the previously described quantitative MALDI model including the matrix-metal interfacial ionization potential reduction effect (Knochenmuss, R.; Anal. Chem. 2004, 76, 3179–3184). The absolute and relative stabilities of ion signals were found to be at least a factor of two better for the thin electrosprayed spots, compared to spots prepared by dried droplet methods.