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Main Authors: Zhu, Xin, Bennett, Timothy JD, Zouboulis, Konstantin C, Soulias, Dimitrios, Grzybek, Michal, Benesch, Justin LP, El-Sagheer, Afaf H, Coskun, Ünal, Krishnan, Madhavi
Format: Preprint
Published: 2025
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Online Access:https://arxiv.org/abs/2505.08452
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author Zhu, Xin
Bennett, Timothy JD
Zouboulis, Konstantin C
Soulias, Dimitrios
Grzybek, Michal
Benesch, Justin LP
El-Sagheer, Afaf H
Coskun, Ünal
Krishnan, Madhavi
author_facet Zhu, Xin
Bennett, Timothy JD
Zouboulis, Konstantin C
Soulias, Dimitrios
Grzybek, Michal
Benesch, Justin LP
El-Sagheer, Afaf H
Coskun, Ünal
Krishnan, Madhavi
contents Size and shape are critical discriminators between molecular species and states. We describe a micro-chip 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 over 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 sub-nanoliter and sub-zeptomole scale.
format Preprint
id arxiv_https___arxiv_org_abs_2505_08452
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Measurements of molecular size and shape on a chip
Zhu, Xin
Bennett, Timothy JD
Zouboulis, Konstantin C
Soulias, Dimitrios
Grzybek, Michal
Benesch, Justin LP
El-Sagheer, Afaf H
Coskun, Ünal
Krishnan, Madhavi
Biological Physics
Soft Condensed Matter
Size and shape are critical discriminators between molecular species and states. We describe a micro-chip 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 over 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 sub-nanoliter and sub-zeptomole scale.
title Measurements of molecular size and shape on a chip
topic Biological Physics
Soft Condensed Matter
url https://arxiv.org/abs/2505.08452