X-ray Free-Electron Lasers (XFELs) provide extremely short X-ray light pulses many times brighter than synchrotrons and bring photon fluxes high enough for diffractive single particle imaging. However, to allow imaging by single laser shots before the particles are destroyed, they require ultrafast sample replenishing. In collaboration with European XFEL, which has been operating in Hamburg since 2017, MS-SPIDOC (Single Particle Imaging of Dipole Oriented Complexes) consortium is developing a sample delivery system based on native mass spectrometry (MS). MS promises key benefits over other methods for sample delivery into beam: • Very low sample consumption • Minimal background water scattering • Selection of populations/transient species from complex mixtures by mass-to-charge ratios or shape • Particles manipulations for tremendous datasets reduction by orienting molecules prior to imaging