Development of a Ultra High Throughput Screening Platform for Synthetic Biology - From Cells to Validated Target

This project will develop an ultra-high throughput screening platform based on microfluidic delivery of single cells1 coupled to mass spectrometry analysis2. You will apply this to rapidly screen synthetic biology libraries to identify and quantify small molecule targets. Droplets will be directed to the electrospray ionisation source of a given mass spectrometer, for subsequent rapid mass analysis enabling identification, and to determine the 'success' of a given cell type in a given library. Ultimately, this project will aim to use the picodroplet driven mass spectrometry analysis to target hit compounds and develop the fluidics control to learn from this to then trigger the sorting of identical picodroplets to a dispenser for subsequent downstream processing.
Working in the Manchester Institute of Biotechnology in our SYNBIOCHEM centre you will develop and optimise the interface of this novel microfluidic platform to a mass spectrometer. The picodroplet device has already been shown to be capable of screening 200,000 picodroplets in 5.4 hours, which potentially would allow 2-4 entire libraries to be assayed in a day.
This screening platform will be applied to the analysis of SYNBIOCHEM libraries. We will focus initial analysis on libraries designed to generate terpenes and flavonoids, although we anticipate that this technology will have wide use on a number of systems. Using our expertise in protein mass spectrometry3 we will also develop the necessary ionisation and droplet dispension protocols to also analyse directly from cells the proteins that have been engineered to make the small molecule targets. In this way this platform will be used to optimise library design and build and form an integral part of our synthetic biology centre.