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Cooperative electrolyte-PEG interactions drive the signal amplification in a solid-state nanopore

Chalmers C. Chau, Fabio Marcuccio, Dimitrios Soulias, Martin A. Edwards, Sheena E. Radford, Eric W. Hewitt, Paolo Actis
doi: https://doi.org/10.1101/2021.11.01.466478
Chalmers C. Chau
1School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
2School of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, UK
3Bragg Centre for Materials Research, University of Leeds, Leeds, UK
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Fabio Marcuccio
2School of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, UK
3Bragg Centre for Materials Research, University of Leeds, Leeds, UK
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Dimitrios Soulias
2School of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, UK
3Bragg Centre for Materials Research, University of Leeds, Leeds, UK
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Martin A. Edwards
4Department of Chemistry & Biochemistry, University of Arkansas, Fayetteville, AR, 72701, USA
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Sheena E. Radford
1School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
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Eric W. Hewitt
1School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds LS2 9JT, UK
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  • For correspondence: e.w.hewitt@leeds.ac.uk p.actis@leeds.ac.uk
Paolo Actis
2School of Electronic and Electrical Engineering and Pollard Institute, University of Leeds, Leeds LS2 9JT, UK
3Bragg Centre for Materials Research, University of Leeds, Leeds, UK
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  • For correspondence: e.w.hewitt@leeds.ac.uk p.actis@leeds.ac.uk
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ABSTRACT

Nanopore systems have emerged as a leading platform for the analysis of biomolecular complexes with single molecule resolution. However, the analysis of several analytes like short nucleic acids or proteins with nanopores represents a sensitivity challenge, because their translocation lead to small signals difficult to distinguish from the noise. Here, we report a simple method to enhance the signal to noise ratio in nanopore experiments by a simple modification of the solution used in nanopore sensing. The addition of poly-ethylene glycol (PEG) and the careful selection of the supporting electrolyte leads to large signal enhancement. We observed that the translocation dynamics are in good agreement with an established method that uses the lattice energy of an electrolyte to approximate the affinity of an ion to PEG. We identified CsBr as the optimal supporting electrolyte to complement PEG to enable the analysis of dsDNA at 500 kHz bandwidth, and the detection of dsDNA as short as 75 bp.

Competing Interest Statement

The authors have declared no competing interest.

  • ABBREVIATIONS
    PBS
    Phosphate Buffered Saline
    PEG
    Poly(ethylene) glycol
    dsDNA
    double stranded DNA
    SNR
    signal-to-noise ratio
    MW
    molecular weight
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    Posted November 03, 2021.
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    Cooperative electrolyte-PEG interactions drive the signal amplification in a solid-state nanopore
    Chalmers C. Chau, Fabio Marcuccio, Dimitrios Soulias, Martin A. Edwards, Sheena E. Radford, Eric W. Hewitt, Paolo Actis
    bioRxiv 2021.11.01.466478; doi: https://doi.org/10.1101/2021.11.01.466478
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    Cooperative electrolyte-PEG interactions drive the signal amplification in a solid-state nanopore
    Chalmers C. Chau, Fabio Marcuccio, Dimitrios Soulias, Martin A. Edwards, Sheena E. Radford, Eric W. Hewitt, Paolo Actis
    bioRxiv 2021.11.01.466478; doi: https://doi.org/10.1101/2021.11.01.466478

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