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

Nat Commun. 2019 May 8;10(1):2109. doi: 10.1038/s41467-019-10147-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / chemistry*
  • Antibodies / immunology
  • Biosensing Techniques / instrumentation*
  • Biosensing Techniques / methods
  • Kallikreins / analysis
  • Kallikreins / immunology
  • Limit of Detection
  • Magnetite Nanoparticles / chemistry*
  • Membranes, Artificial
  • Nanopores*
  • Prostate-Specific Antigen / analysis
  • Prostate-Specific Antigen / immunology
  • Silicon Compounds / chemistry
  • Time Factors

Substances

  • Antibodies
  • Magnetite Nanoparticles
  • Membranes, Artificial
  • Silicon Compounds
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen
  • silicon nitride