Lee, J.K. et al. Proc. Natl. Acad. Sci. USA 112, 3898–3903 (2015).

A variety of approaches have been developed to study very fast chemical reaction kinetics in solution, including fast mixing in microfluidics devices, phototriggered reaction initiation and temperature-jump methods. Mass spectrometry can be used as the readout for characterizing the kinetics of rapid reactions, but it has been limited to millisecond time resolution. Lee et al. report an approach that improves the temporal resolution to as low as 3 microseconds, as applied to the study of the acid-induced unfolding of cytochrome c and the hydrogen-deuterium exchange reaction of the short peptide bradykinin. They achieved this excellent time resolution by colliding two streams of microscopic liquid droplets using pressurized nitrogen gas, thereby allowing rapid droplet fusion. The droplets are then directed to a mass spectrometer to determine the masses of the reaction intermediates and their products.