DESI-MS

The first generation of the HT-DESI-MS technology was built under the DARPA Make It program. It consists of a Biomek i7 liquid handling workstation equipped with a pin tool, a PF3400 SCARA for plate transfer, and a Thermo LTQ XL ion trap mass spectrometer coupled to a Prosolia DESI 2D ion source. Additional capabilities for on-the-fly solvent switching are available through a custom solvent delivery system. The platform is controlled using a custom Python-based software termed CHRIS. This platform is routinely used for organic reaction screening and multi-stage MS (MSn) experiments.

The HT-DESI-MS platform was extended to a second mass spectrometer, a Waters™ Synapt™ G2-Si quadrupole time-of-flight equipped with Traveling Wave Ion Mobility Spectrometry (TWIMS) capabilities, and a 2D DESI stage which includes a Waters™ XS-generation DESI sprayer and a prototype heated transfer line, both of which provide increased robustness and higher ion fluxes. This system is routinely used for higher-sensitivity applications including biological sample screening and biological assays.

This new system was developed as part of the NCATS ASPIRE program in collaboration with Waters Corporation and Hamilton Robotics. It includes a Hamilton Vantage 2.0 fluid handler integrated with a Waters™ Xevo™ G2-XS mass spectrometer equipped with a prototype AutoDESI source. The system also includes an entry/exit device which extends the sample capacity to ca. 100,000 samples per run, with an overall throughput that can be flexibly customized up to 3 Hz. Hardware integration uses a custom enclosure, a track gripper, and an open landing position setup of the AutoDESI source, whereas software integration is based on a custom seamless driver that interfaces Hamilton Venus and the Waters AutoDESI prototype software through JSON messaging. The entire system follows an easy-to-trigger worklist-driven workflow that connects a VBA-backed worklist, a custom Hamilton interface, the Waters™ AutoDESI control, and a custom MATLAB app for data handling. This system is routinely utilized for drug discovery (both synthesis and analysis) projects.