Larkin, JosephHenley, Robert Y.Jadhav, VivekKorlach, JonasWanunu, Meni2020-04-292020-04-292017-12Joseph Larkin, Robert Y Henley, Vivek Jadhav, Jonas Korlach, Meni Wanunu. 2017. "Length-independent DNA packing into nanopore zero-mode waveguides for low-input DNA sequencing.." Nat Nanotechnol, Volume 12, Issue 12, pp. 1169 - 1175. https://doi.org/10.1038/nnano.2017.1761748-3395https://hdl.handle.net/2144/40453Compared with conventional methods, single-molecule real-time (SMRT) DNA sequencing exhibits longer read lengths than conventional methods, less GC bias, and the ability to read DNA base modifications. However, reading DNA sequence from sub-nanogram quantities is impractical owing to inefficient delivery of DNA molecules into the confines of zero-mode waveguides-zeptolitre optical cavities in which DNA sequencing proceeds. Here, we show that the efficiency of voltage-induced DNA loading into waveguides equipped with nanopores at their floors is five orders of magnitude greater than existing methods. In addition, we find that DNA loading is nearly length-independent, unlike diffusive loading, which is biased towards shorter fragments. We demonstrate here loading and proof-of-principle four-colour sequence readout of a polymerase-bound 20,000-base-pair-long DNA template within seconds from a sub-nanogram input quantity, a step towards low-input DNA sequencing and mammalian epigenomic mapping of native DNA samples.p. 1169 - 1175en-USDNAEpigenomicsHumansOptogeneticsSequence analysis, DNANanoscience & nanotechnologyArticle10.1038/nnano.2017.176504793