Abstract
Biological processes often imply dynamics in crowded or confined media. Here, we focus on the entry of molecules into nanopores relevant for applications in health, biotechnologies, or the environment. Polymers in the semi-dilute regime that are excluded from the nanopore generate osmotic pressure, allowing controlled entry of analytes and facilitating their detection and identification inside a confined media. Using solid-state nanopores, we first study the entry dynamics of neutral polymers in a semi-dilute solution at the single-molecule level. We investigate the influence of polymer concentration, chain length and nanopore size. Second, we study the detection and identification of polysaccharides of various molecular weights in the presence of large polymers. Third, we discriminate between two peptide biomarkers with an enantiomeric difference in only one amino acid (D- or L-) for different stoichiometric ratios. From these examples, we experimentally demonstrate the universal behavior that drives large polymers into a nanopore. When the mesh size of the semi-dilute solution is smaller than the nanopore size, the osmotic energy overcomes the confinement energy, allowing the chain to enter the confined media. We found that the power-law dependency of the threshold concentration for polymer entry on the ratio between nanopore and monomer size is predicted theoretically by Pierre-Gilles de Gennes. Additionally, the depletion layer thickness depends on the screening length (mesh size), revealing three regimes that rely on the ratio between the pore size and the screening length. The application of polymer scaling laws represents a universal approach to control the dynamics of biomolecules through nanopores.
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The data generated in this study have been deposited in the recherche.data.gouv.fr repository under the title “Scaling laws in confined media applied for biomarker detection” with the identifier https://doi.org/10.57745/VLNX4L. Source data are provided with this paper.
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Acknowledgements
The authors thank S.J. Greive for careful reading and for improving the English in the manuscript. We also thank W. Zebbiche for his assistance. The authors would like to thank the China Scholarship Council for funding (202108350010, Y.C.). B.C. was supported by ANR JCJC “QuaBioNHy” No. ANR-23-CE44-0013. This work was supported by DIM RESPORE funding. M.W. acknowledges the Fellows-in-Residence program of CY Cergy Paris University. The authors thank the IHU PROMETHEUS ANR-22-IHU3-00XX-02.
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Y.C. performed the experiments and data analysis. Y.C., B.C., L.B., and J.P. designed the figures. J.P. and L.B. wrote the first draft, and Y.C., S.B., L.B., M.W. and B.C. participated in editing the manuscript and answering the referees J.P. and L.B. designed the experiments.
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Cai, Y., Cressiot, B., Winterhalter, M. et al. Scaling laws in confined media applied for biomarker detection. Nat Commun (2026). https://doi.org/10.1038/s41467-026-68912-4
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DOI: https://doi.org/10.1038/s41467-026-68912-4
