4.8 Article

Single-Stranded DNA Translocation Recordings through Solid-State Nanopores on Glass Chips at 10 MHz Measurement Bandwidth

Journal

ACS NANO
Volume 13, Issue 9, Pages 10545-10554

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsnano.9b04626

Keywords

low capacitance glass chips; solid-state nanopores; low-noise amplifier; DNA; silicon nitride; DNA sequencing

Funding

  1. W.M. Keck Foundation
  2. National Institutes of Health [R01HG009189]
  3. National Science Foundation [EFRI-1542707]
  4. NSF [ECCS-1542153]
  5. NSF through the University of Pennsylvania Materials Research Science and Engineering Center [DMR-1720530]

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Accurate and low-cost analysis of biomole-cules is important for many applications. This work seeks to further improve the measurement bandwidths achievable with solid-state nanopores, which have emerged as an important platform for this analysis. We report single-stranded DNA translocation recordings at a bandwidth of 10 MHz copolymers of 80 (C(20)A(20)C(20)A(20)), 90 (C(30)A(30)C(30)), and 200 (C(50)A(50)C(50)A(50)) nucleotides through Si nanopores with effective diameters of 1.4-2.1 nm and effective membrane thicknesses 0.5-8.9 nm. By optimizing glass chips with thin nanopores and by integrating them with custom-designed amplifiers based on complementary metal-oxide-semiconductor technology, this work demonstrates detection of translocation events as brief as 100 ns with a signal-to-noise ratio exceeding seven at a measurement bandwidth of 10 MHz. We also report data robustness and variability across 13 pores of similar size and thickness, yielding a current blockade between 30 and 60% with a mean ionic current blockade (Delta I) of , similar to 3-9 nA and a characteristic dwell time of similar to 2-21 ns per nucleotide. These measurements show that characteristic translocation rates are at least 10 times faster than previously recorded. We detect transient intraevent fluctuations, multiple current levels within translocation events, and variability of DNA translocation event signatures and durations.

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