Journal
NATURE NANOTECHNOLOGY
Volume 10, Issue 11, Pages 986-U96Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NNANO.2015.189
Keywords
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Funding
- US National Human Genome Research Institute (NHGRI) [R01 HG003709]
- ERC [StG 106913]
- Oxford Nanopore Technologies Ltd.
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Protein nanopores such as alpha-haemolysin and Mycobacterium smegmatis porin A (MspA) can be used to sequence long strands of DNA at low cost. To provide high-speed sequencing, large arrays of nanopores are required, but current nanopore sequencing methods rely on ionic current measurements from individually addressed pores and such methods are likely to prove difficult to scale up. Here we show that, by optically encoding the ionic flux through protein nanopores, the discrimination of nucleic acid sequences and the detection of sequence-specific nucleic acid hybridization events can be parallelized. We make optical recordings at a density of similar to 10(4) nanopores per mm(2) in a single droplet interface bilayer. Nanopore blockades can discriminate between DNAs with sub-picoampere equivalent resolution, and specific miRNA sequences can be identified by differences in unzipping kinetics. By creating an array of 2,500 bilayers with a micropatterned hydrogel chip, we are also able to load different samples into specific bilayers suitable for high-throughput nanopore recording.
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