The Aksimentiev Group

Voltage-driven transport of double-stranded DNA through nanoscale pores holds much potential for applications in quantitative molecular biology and biotechnology, yet the microscopic details of translocation have proven to be challenging to decipher. Earlier experiments showed strong dependence of transport kinetics on pore size: fast regular transport in large pores (> 5 nm diameter), and slower yet heterogeneous transport time distributions in sub-5 nm pores, which imply a large positional uncertainty of the DNA in the pore as a function of the translocation time. In this work, we show that this anomalous transport is a result of DNA self-interaction, a phenomenon that is strictly pore-diameter dependent. We identify a regime in which DNA transport is regular, producing narrow and well-behaved dwell-time distributions that fit a simple drift-diffusion theory. Furthermore, a systematic study of the dependence of dwell time on DNA length reveals a single power-law scaling of 1.37 in the range of 35–20,000 bp. We highlight the resolution of our nanopore device by discriminating via single pulses 100 and 500 bp fragments in a mixture with >98% accuracy. When coupled to an appropriate sequence labeling method, our observation of smooth DNA translocation can pave the way for high-resolution DNA mapping and sizing applications in genomics.