Label-free nanofluidic scattering microscopy of size and mass of single diffusing molecules and nanoparticles
Artikel i vetenskaplig tidskrift, 2022

Nanofluidic scattering microscopy enables label-free, quantitative measurements of the molecular weight and hydrodynamic radius of biological molecules and nanoparticles freely diffusing inside a nanofluidic channel. Label-free characterization of single biomolecules aims to complement fluorescence microscopy in situations where labeling compromises data interpretation, is technically challenging or even impossible. However, existing methods require the investigated species to bind to a surface to be visible, thereby leaving a large fraction of analytes undetected. Here, we present nanofluidic scattering microscopy (NSM), which overcomes these limitations by enabling label-free, real-time imaging of single biomolecules diffusing inside a nanofluidic channel. NSM facilitates accurate determination of molecular weight from the measured optical contrast and of the hydrodynamic radius from the measured diffusivity, from which information about the conformational state can be inferred. Furthermore, we demonstrate its applicability to the analysis of a complex biofluid, using conditioned cell culture medium containing extracellular vesicles as an example. We foresee the application of NSM to monitor conformational changes, aggregation and interactions of single biomolecules, and to analyze single-cell secretomes.


Barbora Spackova

Chalmers, Fysik, Kemisk fysik

Henrik Klein Moberg

Chalmers, Fysik, Kemisk fysik

Joachim Fritzsche

Chalmers, Fysik, Kemisk fysik

Johan Tenghamn

Chalmers, Fysik, Kemisk fysik

Gustaf Sjosten

Göteborgs universitet

Hana Jungová

Chalmers, Fysik, Nano- och biofysik

David Albinsson

Chalmers, Fysik, Kemisk fysik

Quentin Lubart

Chalmers, Biologi och bioteknik, Kemisk biologi

Daniel van Leeuwen

Chalmers, Biologi och bioteknik, Kemisk biologi

Fredrik Westerlund

Chalmers, Biologi och bioteknik, Kemisk biologi

Daniel Midtvedt

Göteborgs universitet

Elin Esbjörner Winters

Chalmers, Biologi och bioteknik, Kemisk biologi

Mikael Käll

Chalmers, Fysik, Nano- och biofysik

Giovanni Volpe

Göteborgs universitet

Christoph Langhammer

Chalmers, Fysik, Kemisk fysik

Nature Methods

1548-7091 (ISSN) 1548-7105 (eISSN)

Vol. 19 6 751-758


Nanovetenskap och nanoteknik

Hälsa och teknik


Fysikalisk kemi

Analytisk kemi






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