A dilution series of the Ultimate SPLASH ONE mix of 69 deuterated lipid standards was used as a benchmark to investigate ionization and adduction behaviors of the new setup. The µF/mnESI in both the 5-and 8-nozzle configuration was compared to the AF/ESI platform first using the same injection volume (i.e. 0.2 µL). A 16-fold median increase in ion abundances in the 5-nozzle configuration was observed compared to AF/ESI, with a particular gain for CEs of up to 3 orders of magnitude (Fig. /S1, Table ). The 8-nozzle configuration presented a 24-fold median increase without further notable rise for the CE class. As AF workflows work with higher mass loads compared to capillary setups, the effective gain was estimated by comparing the μF/mnESI setup (0.2 μL injection) with our AF/ESI protocol based on a 3 μL volume injection. We obtained a 1.2-fold effective improvement across all the standards. Notably, CEs displayed a gain of 2-4 orders of magnitude. Linearity across the dilution range was comparable between methods. The ISF behavior of the mnESI exhibited significant differences compared to the high-flow ESI by offering much milder conditions for lipid classes such as PI, PGs and Cer (Table ). The adduction patterns of the injected standards also showed marked differences between the two flows regimens (Table ). In the AF/ESI method, the protonated/ammoniated ion abundances were moderately higher than the sodium adducts or water losses (up to 10x higher peak areas). PGs, Cer, DGs and CEs displayed nearly similar intensities of the main ion compared to their sodiated or water-loss counterparts. In contrast, the µF/mnESI method clearly favored the protonated/ammoniated species. This phenomenon was particularly striking for TGs and CEs, whose abundances as ammoniated adducts were increased 20-80x compared to sodium species. The 8-nozzle emitter, which provided almost half of the flow rate at nebulization (375 vs. 600 nL/min), produced a further decrease in sodium adduct signals.