An area-efficient low-noise CMOS DNA detection sensor for multichannel nanopore applications

In this paper, an area-efficient low-noise DNA detection sensor is presented for multichannel nanopore applications. A resistive-feedback transimpedance amplifier (rf-TIA) is typically employed as a DNA detection sensor to amplify ionic current variations through a nanopore channel and convert it to a useful voltage range. However, big feedback resistors occupy large areas and limit the number of the DNA detection sensors that can be integrated on a given chip area for multichannel nanopore sensing. In this work, we propose a novel pseudo-resistor technique to drastically reduce the feedback resistor size. We will first review conventional pseudo resistors and then describe the new technique using a deep N-well NMOS transistor that is free from body effect. A DNA detection sensor, adopting the novel pseudo resistor, is fabricated in a 0.35 μm CMOS process and is tested using an α-hemolysin (α-HL) protein nanopore for detection individual molecules of single-stranded DNA (ssDNA) that pass through the 1.5 nm-diameter aperture. The active die area is reduced by almost 90% allowing a near 10-fold increase in the number of channels on a silicon chip. In future work, the refined CMOS DNA detection sensor arrays will functionalize multichannel nanopores formed in integrated microfluidic devices for high-throughput DNA analysis.