Time-Resolved and Label-Free Evanescent Light-Scattering Microscopy for Mass Quantification of Protein Binding to Single Lipid Vesicles
Journal article, 2021

In-depth understanding of the intricate interactions between biomolecules and nanoparticles is hampered by a lack of analytical methods providing quantitative information about binding kinetics. Herein, we demonstrate how label-free evanescent light-scattering microscopy can be used to temporally resolve specific protein binding to individual surface-bound (∼100 nm) lipid vesicles. A theoretical model is proposed that translates protein-induced changes in light-scattering intensity into bound mass. Since the analysis is centered on individual lipid vesicles, the signal from nonspecific protein binding to the surrounding surface is completely avoided, offering a key advantage over conventional surface-based techniques. Further, by averaging the intensities from less than 2000 lipid vesicles, the sensitivity is shown to increase by orders of magnitude. Taken together, these features provide a new avenue in studies of protein-nanoparticle interaction, in general, and specifically in the context of nanoparticles in medical diagnostics and drug delivery.

surface plasmon resonance

surface-sensitive scattering microscopy

protein adsorption kinetics

single nanoparticle analytics


Mattias Sjöberg

Chalmers, Physics, Nano and Biophysics

Mokhtar Mapar

Chalmers, Physics, Nano and Biophysics

Antonius Armanious

Chalmers, Physics, Nano and Biophysics

Vladimir Zhdanov

Russian Academy of Sciences

Chalmers, Physics

Björn Agnarsson

Chalmers, Physics, Nano and Biophysics

Fredrik Höök

Chalmers, Physics, Nano and Biophysics

Nano Letters

1530-6984 (ISSN) 1530-6992 (eISSN)

Vol. 21 11 4622-4628

Two-dimensional flow nanometry for single nanoparticle analytics

Swedish Research Council (VR) (2018-04900), 2018-12-01 -- 2021-12-31.

Subject Categories

Physical Chemistry

Biochemistry and Molecular Biology



Chalmers Materials Analysis Laboratory





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