A hybrid semi-digital transimpedance amplifier for nanopore-based DNA sequencing

Over the past two decades, nanopores have been a promising technology for next generation deoxyribonucleic acid (DNA) sequencing. As single-stranded DNA translocates through a nanopore, each nucleotide induces a blockage in the ionic channel, creating a unique current signature. However, the fast translocation speed and small current changes, which are superimposed on a much larger baseline current, pose significant technical challenges on the measurement circuitry. Furthermore, the rapid change in the baseline current that occurs during translocation necessitates the step response of the measurement circuitry be minimized. Here we present a hybrid semi-digital transimpedance amplifier to sense these minute current signatures while discharging the baseline current using a semidigital feedback loop. The amplifier achieves fast settling by adaptively altering the bandwidth of the feedback loop when a step input is detected. Measurement results show the performance of the amplifier with 100 MΩ DC gain, 560 kHz flat-gain bandwidth, and 5 fA/√Hz input-referred current noise. The fast settling response is demonstrated by observing the insertion of a protein nanopore in a lipid bilayer.