A droplet-chip/mass spectrometry approach to study organic synthesis at nanoliter scale

A droplet-based microfluidic device with seamless hyphenation to electrospray mass spectrometry was developed to rapidly investigate organic reactions in segmented flow providing a versatile tool for drug development. A chip-MS interface with an integrated counterelectrode allowed for a flexible positioning of the chip-emitter in front of the MS orifice as well as an independent adjustment of the electrospray potentials. This was necessary to avoid contamination of the mass spectrometer as well as sample overloading due to the high analyte concentrations. The device was exemplarily applied to study the scope of an amino-catalyzed domino reaction with low picomole amount of catalyst in individual nanoliter sized droplets.