High-resolution single-molecule mass measurement of megadalton assemblies in solution

Tereza Roesel; Evangelos Efraimidis; Niklas Hansen; Yulia Yancheva; Miroslav Hekrdla; Katarzyna M. Tych; Vladimira Petrakova; Barbora Spackova

High-resolution single-molecule mass measurement of megadalton assemblies in solution

Optics 2026-07-15 v1

Authors: Tereza Roesel , Evangelos Efraimidis , Niklas Hansen , Yulia Yancheva , Miroslav Hekrdla , Katarzyna M. Tych , Vladimira Petrakova , Barbora Spackova

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Abstract

Resolving heterogeneity in megadalton assemblies requires precise single-molecule mass measurements in solution. Mass photometry infers mass from individual molecular surface-landing events, and event-to-event measurement variability limits precision. Nanofluidic scattering microscopy overcomes this limitation by continuously tracking molecules in motion, enabling repeated sampling and temporal averaging of these fluctuations. Benchmarking with 4.5 MDa DNA origami demonstrates up to a fourfold improved resolution, approaching the performance of ensemble-averaged native mass spectrometry.

Keywords

single-molecule mass measurement mass photometry nanofluidic scattering microscopy megadalton assemblies DNA origami

Cite

@article{arxiv.2607.14283,
  title  = {High-resolution single-molecule mass measurement of megadalton assemblies in solution},
  author = {Tereza Roesel and Evangelos Efraimidis and Niklas Hansen and Yulia Yancheva and Miroslav Hekrdla and Katarzyna M. Tych and Vladimira Petrakova and Barbora Spackova},
  journal= {arXiv preprint arXiv:2607.14283},
  year   = {2026}
}