Tag: Bohdan Yeroshenko

Label-free mass and size characterization of few-kDa biomolecules by hierarchical vision transformer augmented nanofluidic scattering microscopy published in Nature Communications

The principle of differential imaging in NSM, in which we subtract the light scattered (yellow arrows indicate the scattered-light direction) by an empty nanochannel from the light scattered by the same channel with a molecule inside. A sequence of differential images of a nanochannel containing a diffusing single molecule obtained in this way is combined into a kymograph, which then contains the full molecular trajectory. (Image from the article.)
Label-free mass and size characterization of few-kDa biomolecules by hierarchical vision transformer augmented nanofluidic scattering microscopy
Henrik K. Moberg, Bohdan Yeroshenko, Joachim Fritzsche, David Albinsson, Barbora Spackova, Daniel Midtvedt, Giovanni Volpe, Christoph Langhammer
Nature Communications 17, 2533 (2026)
DOI: 10.1038/s41467-026-70514-z

Nanofluidic scattering microscopy characterizes single molecules in subwavelength nanofluidic channels label-free, using the interference of visible light scattered by the molecule and nanochannel. It determines a molecule’s hydrodynamic radius by tracking its diffusion trajectory and its molecular weight by analyzing its scattering intensity along that trajectory. However, using standard analysis algorithms, it is limited to characterization of proteins larger than ≈ 60 kDa. Here, we push this limit by one order of magnitude to below ≈ 6 kDa molecular weight and ≈ 1.5 nm hydrodynamic radius — as we exemplify on the peptide hormone insulin — by using ultrasmall nanofluidic channels and by analyzing the data with a hierarchical vision transformer. When we benchmark this approach against the theoretical limit set by the Cramér–Rao Lower Bound, we find that it can be approached with sufficiently long molecular trajectories. This enables quantitative label-free single-molecule microscopy for biologically relevant families of sub-10-kDa molecules, such as cytokines, chemokines and peptide hormones.

Soft Matter Lab members present at SPIE Optics+Photonics conference in San Diego, 3-7 August 2025

The Soft Matter Lab participates to the SPIE Optics+Photonics conference in San Diego, CA, USA, 3-7 August 2025, with the presentations listed below.

Giovanni Volpe, who serves as Symposium Chair for the SPIE Optics+Photonics Congress in 2025, is a coauthor of the following invited presentations:

Giovanni Volpe will also be the reference presenter of the following Poster contributions:

Invited Presentation by B. Yeroshenko at SPIE-ETAI, San Diego, 5 August 2025

Kymographs of DNA inside Channel II. (Image from 10.1038/s41592-022-01491-6. by Barbora Špačková)
Pushing the limits of label-free single-molecule characterization by nanofluidic scattering microscopy
Bohdan Yeroshenko, Henrik Klein Moberg, Leyla Beckerman, Joachim Fritzsche, David Albinsson, Barbora Špačková, Daniel Midtvedt, Giovanni Volpe, Christoph Langhammer
SPIE-ETAI, San Diego, CA, USA, 3 – 7 August 2025
Date: 5 August 2025
Time: 8:45 AM – 9:15 AM PDT
Place: Conv. Ctr. Room 4

Nanofluidic Scattering Microscopy (NSM) is a label-free characterization method that leverages the interference of light scattered by nanochannels and single molecules within them. This technique enables accurate determination of molecular weight and hydrodynamic radius based solely on scattering, without requiring prior molecular knowledge. However, standard analysis methods limit NSM’s sensitivity to 66 kDa for proteins. In this presentation, I will demonstrate how we push this detection limit an order of magnitude further by integrating ultrasmall geometry with an advanced machine learning analysis approach, all while maintaining the same input laser power intensity.