A robust and tunable read-out integrated circuit architecture is presented for carbon nanotube-based bio-sensor with nano-amperes current measurement at 1ms to 16 minutes intervals. The circuit contains an on-chip 8-bit analog-to-digital convertor and a trans-impedance amplifier with tunable control parameters to accommodate not easily controlled single-walled nanotube sensor fabrication with a wide distribution of resistance ranges. For one of the prepared carbon nanotube devices, the current estimation accuracy is within 0.38 nA for a carbon nanotube sensor with expected effective resistance range between 5–30 MΩ This corresponds to current measurements between 5–45 nA. This CMOS instrumentation core has an approximate area of 639 μm2 and consumes 33 mW at 5 MHz sampling rate.