Chemically Modified Hydrogel-Filled Nanopores: A Tunable Platform for Single-Molecule Sensing

Dana Al Sulaiman, Paolo Cadinu, Aleksandar P. Ivanov, Joshua B. Edel, Sylvain Ladame

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Label-free, single-molecule sensing is anideal candidate for biomedical applications that rely on the detection of low copy numbers in small volumes and potentially complex biofluids. Among them, solid-state nanopores can be engineered to detect single molecules of charged analytes when they are electrically driven through the nanometer-sized aperture. When successfully applied to nucleic acid sensing, fast transport in the range of 10-100 nucleotides per nanosecond often precludes the use of standard nanopores for the detection of the smallest fragments. Herein, hydrogel-filled nanopores (HFN) are reported that combine quartz nanopipettes with biocompatible chemical poly(vinyl) alcohol hydrogels engineered in-house. Hydrogels were modified physically or chemically to finely tune, in a predictable manner, the transport of specific molecules. Controlling the hydrogel mesh size and chemical composition allowed us to slow DNA transport by 4 orders of magnitude and to detect fragments as small as 100 base pairs (bp) with nanopores larger than 20 nm at an ionic strength comparable to physiological conditions. Considering the emergence of cell-free nucleic acids as blood biomarkers for cancer diagnostics or prenatal testing, the successful sensing and size profiling of DNA fragments ranging from 100 bp to >1 kbp long under physiological conditions demonstrates the potential of HFNs as a new generation of powerful and easily tunable molecular diagnostics tools.
Original languageEnglish (US)
Pages (from-to)6084-6093
Number of pages10
JournalNano Letters
Volume18
Issue number9
DOIs
StatePublished - Sep 12 2018
Externally publishedYes

ASJC Scopus subject areas

  • Bioengineering
  • General Materials Science
  • General Chemistry
  • Mechanical Engineering
  • Condensed Matter Physics

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