Keynote title: Complementarity and versatility of mass photometry and native mass spectrometry for the characterization of biomolecular assemblies, from immune-complexes to gene-delivery vehicles.   

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Abstract: Most methods for mass analysis typically measure ensembles of thousand to millions of molecules. While this approach enables analysis of monodisperse recombinant proteins, some heterogeneous protein assemblies pose a significant challenge, whereby co-occurring stoichiometries, sub-complexes, and modifications hamper analysis. To tackle the challenges posed by mass heterogeneity, single-particle methods may come to the rescue. Recently, two such approaches have been introduced, namely mass photometry (MP) and Orbitrap-based charge detection mass spectrometry (CDMS). Both methods assess masses of individual molecules, albeit adhering to distinct physical principles. In this talk I will describe and compare these methods side-by-side, with a prime focus on mass photometry. I will discuss pros and cons of these single-molecule techniques, also in the context of other techniques used for mass analysis. Several applications will be highlighted including analysis of antibody binding to the SARS-Cov2 spike-trimer, the buildup of the initial classical complement activation cascade, ribosomal particles, mRNA and AAV-based gene delivery vehicles.