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Zhu, X.* ; Bennett, T.J.D.* ; Zouboulis, K.C.* ; Soulias, D.* ; Grzybek, M.* ; Benesch, J.L.P.* ; El-Sagheer, A.H.* ; Coskun, Ü. ; Krishnan, M.*

Measurements of molecular size and shape on a chip.

Science 388:eadt5827 (2025)
DOI PMC
Closed: Publ. Version/Full Text online available 05/2026
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Hydrodynamic Properties; Dna; Insulin; Protein; Rna; Binding; Macromolecules; Diffusion; Radii; Mass
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 388, Issue: 6747, Pages: , Article Number: eadt5827 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-002
Grants German Center for Diabetes Research (DZD e.V.)
Federal Ministry of Education and Research (BMBF)
Royal Society of Chemistry Research grant
Royal Society Research Grant
Wellcome LEAP Delta Tissue Program
Biotechnology and Biological Sciences Research Council
European Research Council
DOI 10.1126/science.adt5827
WOS ID 001485181400010
Scopus ID 105008906198
PubMed ID 40339025
Erfassungsdatum 2025-05-11
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