Rapid and Sensitive Chemical Analysis of Individual Picolitre Droplets by Mass Spectrometry

JIM WALKER, Bryan R. Bzdek, University of Bristol

     Abstract Number: 285
     Working Group: Instrumentation and Methods

Abstract
Routine and sensitive chemical analysis is extremely challenging if the analyte of interest is rare or expensive to produce. We introduce a Single Picodroplet Mass Spectrometry approach allowing mass spectrometric analysis of picogram quantities of analyte contained within individual aerosol droplets, without the need for intermediary ionization devices. In the approach, individual picolitre droplets of known composition and size are reproducibly generated using a droplet-on-demand dispenser and guided to the mass spectrometer inlet using a linear quadrupole electrodynamic balance (LQ-EDB). The LQ-EDB is housed within an environmentally controlled sheath and a high-resolution imaging assembly allows droplets to be imaged during transit (i.e. to calculate the diameter). Ionization is accomplished using droplet assisted ionization, where rapid evaporation of an aqueous droplet within the mass spectrometer inlet leads to the formation of molecular ions. The technique permits discrete and rapid (10 Hz) sampling from a continuous stream of droplets, with no carry-over in the observed signal between individual droplets. Benchmarking studies of droplets containing aqueous solutions of peptides and other biological molecules demonstrate the approach is capable of routine analysis of samples containing as little as 2 pg of analyte, with the potential to go much lower. Picodroplet mass spectra show a significant reduction in spectral noise compared to electrospray ionization of the same solution. The effect of droplet size and analyte concentration on ion yield is explored, providing insight into the ionization mechanism. This Picodroplet Mass Spectrometry approach could have widespread applications for chemical analysis of scarce samples.