High performance interface for boosting ion transmission in native mass spectrometry and beyond.

Electrospray ionization (ESI)-based native mass spectrometry (MS) has been extensively used to study non-covalent protein complexes and their structural aspects in the gas phase. As such it has a stable place in the portfolio of modern structural biology and biopharmaceutical analysis techniques. It is also promising as an approach to deliver pro-teins and their assemblies into the gas phase for single particle experiments at advanced light sources such as free electron lasers and synchrotrons. Here we report on a novel radiofrequency ion transfer interface enabling gas flow laminarization at low pressure for efficient capture, focusing, thermalization, trapping and gating of ions into a mass analyser, boosting up to 19-fold the observable signal intensities especially for notoriously challenging multi-megadalton assemblies such as in-tact viral capsids. The new ion transfer interface offers unique opportunities for interdisciplinary approaches intersecting native MS-guided structural biology, molecular and cluster physics as well as (bio)analytical applications. Additionally, when combined with sensitive detection of individual particles, this technology could eventually also open new avenues in clinical diagnostics, enabling for example the analysis of viruses at very low concentrations directly from dilute patient-derived samples as well as viral therapeutic vectors along the biopharmaceutical production chain, thereby helping to un-lock the full potential of native MS.