Coupling droplet microfluidics with mass spectrometry

Emily Kempa: With the number of variants in a combinatorial library regularly exceeding 105 entities, SYNBIOCHEM Manchester are looking for new high throughput technologies for screening these variations for useful mutations to take forward into the next round of development. Although the Sphere Fluidics droplet platform and the FACS system are regularly utilised in the department for this use, their inherent downfall is the reliance upon the target compound to be fluorescent. To overcome this, a label-free approach in which the Sphere Fluidics droplet platform will be modified and coupled to a mass spectrometer has been devised.

This project has begun by coupling a droplet microfluidic chip with mass spectrometry through the insertion of a stainless steel emitter into a chip, and integrating this chip with the Agilent 6560 IM Q-TOF Mass Spectrometer. Droplets (~2 nL in size) are generated in the chip at a rate of 5 Hz and are introduced into the MS almost immediately with each droplet being detected as a distinct peak in the total ion chromatogram. Each peak in this chromatogram allows us to obtain a mass spectrum for each droplet, something that will be come of up-most importance when filling droplets with individual variants from the library or even monitoring reaction progress.