Realising a Poschenrieder dual-sector electrostatic analyser for charge-detection mass spectrometry

Résumé fourni par la source

Megadalton biomolecular assemblies, including viral vectors, synthetic nanoparticles and protein aggregates, are increasingly important chemical and therapeutic entities, yet their heterogeneity often exceeds the resolving power and space charge tolerance of conventional mass spectrometry. To overcome these limitations, here we report the first realisation of a Poschenrieder dual-sector electrostatic analyser as a charge-detection mass spectrometer. The instrument traps individual ions in a continuous closed trajectory between two spherical electrostatic sectors, enabling induced-current detection over extended transients without end-cap deceleration. Coupled to a high-mass ion-transfer interface, the analyser supports both ensemble m/z measurements and single-particle charge detection of large biomolecular ions. We validate the platform using protein standards and demonstrate megadalton mass analysis of adeno-associated virus capsids, distinguishing empty and genome-containing populations in agreement with orthogonal mass photometry and Orbitrap-based measurements. Although charge-detection noise remains the principal performance constraint in this first-generation prototype, the dual-sector architecture offers a simple, high-capacity route to charge-detection mass spectrometry with substantial scope for improved resolution through miniaturisation and reduced detector capacitance.

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