Measurements of molecular size and shape on a chip
Size and shape are critical discriminators between molecular species and states. We describe a microchip-based high-throughput imaging approach offering rapid and precise determination of molecular properties under native solution conditions. Our method detects differences in molecular weight across at least three orders of magnitude and down to two carbon atoms in small molecules. We quantify the strength of molecular interactions across more than six orders of magnitude in affinity constant and track reactions in real time. Highly parallel measurements on individual molecules serve to characterize sample-state heterogeneity at the highest resolution, offering predictive input to model three-dimensional structure. We further leverage the method's structural sensitivity for diagnostics, exploiting ligand-induced conformational changes in the insulin receptor to sense insulin concentration in serum at the subnanoliter and subzeptomole scale.
Authors
- Michał Grzybek (ORCID: https://orcid.org/0000-0003-2083-0506)
- Timothy J. D. Bennett (ORCID: https://orcid.org/0000-0001-7419-7756)
- Ünal Coskun (ORCID: https://orcid.org/0000-0003-4375-3144)
- Madhavi Krishnan (ORCID: https://orcid.org/0000-0003-1274-7155)
- Konstantin Zouboulis (ORCID: https://orcid.org/0000-0003-3246-219X)
- Afaf H. El‐Sagheer (ORCID: https://orcid.org/0000-0001-8706-1292)
- Xin Zhu (ORCID: https://orcid.org/0000-0002-9413-7125)
- Dimitrios Soulias (ORCID: https://orcid.org/0000-0003-4700-6744)
- Justin L. P. Benesch (ORCID: https://orcid.org/0000-0002-1507-3742)
Institutions
- Center for NanoScience (DE)
- University of Oxford (GB)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- German Center for Diabetes Research (DE)
- University Hospital Carl Gustav Carus (DE)
- Paul Langerhans Institute Dresden (DE)
- University of Southampton (GB)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Science
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1126/science.adt5827
- Citations
- 5
- Primary Topic
- Microfluidic and Capillary Electrophoresis Applications
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- Royal Society of Chemistry
- Bundesministerium für Bildung und Forschung
- National Institutes of Health
- Directorate for Biological Sciences