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

ACS nano(2019)

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摘要
Accurate and low-cost analysis of biomolecules 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 (CACA), 90 (CAC), and 200 (CACA) nucleotides through Si nanopores with effective diameters of 1.4 - 2.1 nm and effective membrane thickness 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 (CMOS) 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 (ΔI) of ~ 3 to 9 nA and a characteristic dwell time of ~ 2 to 21 ns per nucleotide. These measurements show that characteristic translocation rates are at least ten times faster than previously recorded. We detect transient intra-event fluctuations, multiple current levels within translocation events, and variability of DNA-translocation-event signatures and durations.
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关键词
low capacitance glass chips,solid-state nanopores,low-noise amplifier,DNA,silicon nitride,DNA sequencing
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