Indexed on: 15 Aug '18Published on: 15 Aug '18Published in: Nano Letters
Label-free, single-molecule sensing nanotechnologies represent ideal candidates for biomedical applications that rely on the detection of low copy number of biomolecules in small volumes of potentially complex biofluids. Among them, solid-state nanopores can be engineered that detect single molecules of charged analytes when they are electrically driven through the nanometer-sized aperture. Successfully applied to nucleic acid sensing, a 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, next generation 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-down DNA transport by four orders of magnitude and to detect fragments as small as 100bp with nanopores larger than 20 nm, at ionic strength comparable to physiological conditions. Considering the emergence of cell-free nucleic acids as blood biomarkers for cancer diagnostics or prenatal testing, successful sensing and size profiling of DNA fragments ranging from 100bp to >1kbp long under physiological conditions demonstrates the potential of HFNs as a new generation of powerful, easily tunable, molecular diagnostics tools.