Assembly of Droplet Reinjection-MS Interfaces: Overcoming Droplet Coalescence for High Throughput Screening Applications.

Droplet microfluidics coupled with mass spectrometry is evolving for high throughput screening. A commercial solution that can readily interface to existing mass spectrometry instrumentation would be highly desirable and allow the technology to become accessible to those without experience in droplet microfluidics. Here, we demonstrate a droplet reinjection workflow to infuse samples into three common mass spectrometers, each with different electrospray ionisation (ESI) source configurations. The ease of chip-mass spectrometry (MS) coupling is explored and difficulties highlighted. Particular attention has been turned to ESI sources which apply the electrospray voltage directly to the incoming droplet emitter (‘push source’), as these were found to cause droplet coalescence within the microfluidic chip reinjection channel. To overcome such a difficulty, we have identified different solutions including a grounded mesh insert as a shielding approach, and minor changes to chips and ESI sources to stabilise incoming droplets. Results obtained allow the mass spectrum of individual reinjected droplets to be determined without hindrance from the electrospray voltage. The problems and solutions identified here, outline the foundations for the development of a commercial droplet reinjection-mass spectrometry interface.