High-throughput Analysis of Pathogens using Desorption Electrospray Ionization and 2D MS/MS

The 21st century brought with it an unprecedented number of global and regional economic and political crises, giving rise to a new generation of conflicts in which novel technological, biological, and chemical weaponry are being deployed. These crises are being exacerbated by the emergence of a combination of new and old biological threats, most notably the novel COVID-19 pathogen, existing viruses once thought to be virtually extinct due to wide adoption of vaccination, and bacterial weaponry such as Bacillus anthracis (anthrax). Collectively, these events have been a catalyst for the development of analytical technologies for rapidly detecting and characterizing biological entities, and, in particular, for quickly developing countermeasures against these pathogens. In this work we leverage the automated sample handling capabilities of liquid handling robots with a custom fully integrated mass spectrometry platform utilizing high-throughput desorption electrospray ionization and two-dimensional tandem mass spectrometry (2D MS/MS) for characterization of several model biological organisms (bacteria and viruses) and for determination of medical countermeasure efficacy against each threat. The metabolomic and lipidomic results from the DESI-2D MS/MS system - operating at a sampling rate of ~300 samples/hr - are compared with those from a benchtop LC-MS/MS system operating at a more conventional sampling rate of ~4 samples/hr.

Learning Objectives: 

1. Define high-throughput screening in the context of mass spectrometry.

2. Describe at least 3 techniques for conducting high-throughput screening by mass spectrometry.

3. Compare the advantages and disadvantages of high-throughput mass spectrometry vs. liquid chromatography mass spectrometry (LC-MS).