A Charge Detection Mass Spectrometer for the Analysis of Megadalton-sized Molecules

Advances in Electrostatic Linear Ion Trap (ELIT) Charge Detection Mass Spectrometry (CDMS) over the past 10 years have revolutionized its use for analyzing very high–molecular-weight species such as protein complexes, viral vectors, vaccines, viruses, and amyloid fibrils. Nonetheless, ELIT-based CDMS has remained confined to a small number of specialized instrumentation groups, predominantly in academia, where large and complex home-built instruments are operated by highly skilled scientists in dedicated facilities. In this report, we discuss the primary challenges addressed in the design of a benchtop ELIT-based CDMS instrument. We highlight key design aspects of the hardware, acquisition modes, and control software, and we present important performance metrics (mass range, resolution, and sensitivity) demonstrated using samples representative of the technology’s key application areas.