A Low-Noise CMOS Front-End with 534 MΩ Transimpedance Gain for Single-Molecule Signal Acquisition

We designed and characterized a low-noise RTIA (transimpedance amplifier) with $534 \mathrm{M}\Omega$ transimpedance gain fabricated in a $0.18- \mu \mathrm{m}$ CMOS process for pA signal acquisition, which lay the foundation for nanopore sequencing. A feedback resistance with $268 \mathrm{M}\Omega$ and source degeneration were firstly demonstrated to suppress the input referred noise. Next, dual-end output configuration was adapted for doubling the actual signal gain. Finally, we show an output buffer with the gain of 17 dB leading to $7 \times$ equivalent feedback capacitance can be utilized for boosting the bandwidth. Our experimental results confirm that this amplifier design can detect the interaction between DNA molecules and the nanopore sensor. The noise level of our system exhibits 5.5 pA
RMS
(<1 kHz) and 14.1 pA
RMS
(<5 kHz), which is in a reasonable agreement with our control tests on the “gold standard” Axo-patch 200B amplifier.