Highly sensitive mass spectrometric detection in droplet microfluidics to monitor single cell catalysis and metabolite secretion

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Droplet-based microfluidics has become a powerful platform technology for numerous (bio)chemical applications from pharmaceutical assays over microchemical conversions to single cell analysis. On the other hand, mass spectrometry (MS) is the most powerful tool to characterize the processes on the molecular level. The main limitation encountered in the droplet microfluidics-MS technology is the achievable detection sensitivity with the commercial coaxial sheath flow sprayer for electrospray ionization (ESI) used so far. For this reason, MS analysis of low abundant chemical compounds is barely possible. In order to overcome these limitations this project aims at developing advanced, highly sensitive and robust nanoESI droplet microfluidics-MS couplings. A nanoflow sheath liquid approach will enable a robust, flexible and sensitive approach due to low amount of optimized sheath liquid with the idea to electrospray only the aqueous phase due to movable capillaries. In the sheathless approach a monolithic 3D-microstructured chip interface generated by laser induced etching will be investigated by a dilution free electrical contacting of the integrated ESI emitter tip. The developed coupling techniques will be experimentally benchmarked, compared with the current state of the art, and applied to monitor single cell catalysis, metabolite secretion, and forced degradation studies of pharmaceutical proteins in order to explore the possibilities and limitations of the newly developed droplet microfluidics-MS technology.