Rapid and Sensitive\nChemical Analysis of Individual\nPicolitre Droplets by Mass Spectrometry

Aerosol droplets\nare unique microcompartments containing\nmicroscopic\namounts of material and exhibiting surprising chemical reactivity.\nAlthough a diverse set of tools exists to characterize the chemical\ncomposition of individual submicron particles in air, comparatively\nfewer approaches can chemically analyze individual, airborne picolitre\ndroplets. We describe a novel approach for mass spectrometric analysis\nof individual aqueous picolitre droplets (∼2–180 pL\nvolume) containing down to ∼1 pg analyte mass per droplet.\nIndividual droplets are generated using a microdroplet dispenser,\nimparted a small amount of net charge, and guided to the inlet of\na high-resolution mass spectrometer using a linear quadrupole-electrodynamic\nbalance. Analyte molecules within the aqueous droplet are ionized\nusing droplet assisted ionization, where droplet breakup within the\nmass spectrometer inlet leads to generation of molecular ions. This\nsingle droplet mass spectrometry approach is demonstrated for small\nmolecules and proteins. The approach generates clean mass spectra,\npermits timing of droplet delivery for chemical analysis, and, by\navoiding a separate ionization stage, avoids potential artifacts arising\nfrom current electrospray-based approaches for picolitre droplet analysis.\nIt is anticipated this approach will permit exploration of the factors\ngoverning accelerated chemical reactions in aerosol droplets and will\nbe suitable for sensitive analysis of particularly precious samples\nin different application domains.