This study reports the optimization of the first stages of a MEMS-based, microfabricated time-of-flight mass spectrometer. The authors present an acceptable match between simulations and experimental results. It validates the use of simulations as a time efficient approach as to predict optimal experimental set points. Chips with three differently meshed ionization grids have been tested and show a significant impact of the grid size on both ionization and extraction. An optimal trade-off is found for 3 mm × 3 mm grid, with about 5 × 10?6 ion/atom ionization efficiency and over 50% extraction rate. Optimized parameters for ion focussing are found faster with the help of simulations as the experimental optimal settings are found near the predicted simulated voltages. A total ionic current of hundreds of picoamperes is measured, confirming the potential of this electron-impact ion source as the first step of the full time-of-flight mass spectrometer integrated on a single MEMS chip. © 2016 Elsevier B.V.