Nanopore blockade sensors for ultrasensitive detection of proteins in complex biological samples

Kyloon Chuah, Yanfang Wu, S. R. C. Vivekchand, Katharina Gaus, Peter J. Reece, Adam P. Micolich and J. Justin Gooding ()
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Kyloon Chuah: The University of New South Wales
Yanfang Wu: The University of New South Wales
S. R. C. Vivekchand: The University of New South Wales
Katharina Gaus: The University of New South Wales
Peter J. Reece: The University of New South Wales
Adam P. Micolich: The University of New South Wales
J. Justin Gooding: The University of New South Wales

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract Nanopore sensors detect individual species passing through a nanoscale pore. This experimental paradigm suffers from long analysis times at low analyte concentration and non-specific signals in complex media. These limit effectiveness of nanopore sensors for quantitative analysis. Here, we address these challenges using antibody-modified magnetic nanoparticles ((anti-PSA)-MNPs) that diffuse at zero magnetic field to capture the analyte, prostate-specific antigen (PSA). The (anti-PSA)-MNPs are magnetically driven to block an array of nanopores rather than translocate through the nanopore. Specificity is obtained by modifying nanopores with anti-PSA antibodies such that PSA molecules captured by (anti-PSA)-MNPs form an immunosandwich in the nanopore. Reversing the magnetic field removes (anti-PSA)-MNPs that have not captured PSA, limiting non-specific effects. The combined features allow detecting PSA in whole blood with a 0.8 fM detection limit. Our ‘magnetic nanoparticle, nanopore blockade’ concept points towards a strategy to improving nanopore biosensors for quantitative analysis of various protein and nucleic acid species.

Date: 2019
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DOI: 10.1038/s41467-019-10147-7

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