Improving the Temporal Resolution of Nanopore Recordings

Abstract

Solid-state nanopores are being pursued for a number of applications including, most notably, DNA sequencing. One of the challenges that nanopores present is the fast rate at which molecules translocate. Significant improvements in the measurement bandwidth can be obtained through the optimization of detection electronics and reduction in nanopore membrane capacitance. We present a low-noise, custom-designed complementary metal-oxide-semiconductor (CMOS) amplifier chip capable of recording translocation dynamics in nanopores at bandwidths up to 10 MHz. We integrate state-of-the-art silicon nitride nanopores with this amplifier to achieve signal to noise ratios (SNRs) of better than 10 at 5 MHz bandwidth in ssDNA translocation experiments. We observe transient features with durations as short as 200 ns in some translocation events, features that would have been hidden at lower recording bandwidths. We also use our platform to record ssDNA translocation through glass-passivated silicon-nitride nanopores with membrane capacitances of less than 1 pF, further extending the achievable recording bandwidth. At these speeds, the potential exists to realize free-running DNA sequencing using solid-state nanopores.