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High and ultra-high-throughput label-free sample analysis is required by many applications, extending from environ-mental monitoring to drug discovery and industrial biotechnology. HTS methods predominantly are based on a targeted workflow, which can limit their scope. Mass spectrometry readily provides chemical identity and abundance for complex mixtures and here, we use microdroplet generation microfluidics to supply picolitre aliquots for analysis at rates up to and including 33 Hz. This is demon-strated for small molecules, peptides and proteins up to 66 kDa on three commercially available mass spectrometers from salty solutions to mimic cellular environments. Designs for chip-based interfaces that permit this coupling are presented and the merits and challenges of these interfaces are discussed. On an Orbitrap platform droplet infusion rates of 6 Hz are used for the analysis of cytochrome c, on a DTIMS Q-TOF similar rates were obtained and on a TWIMS Q-TOF utilizing IM-MS software rates up to 33 Hz are demonstrated. The potential of this approach is demonstrated with proof of concept experiments on crude mixtures including egg white, unpurified recombinant protein and a biotransformation supernatant.