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This paper introduces a high-speed mixed-signal readout array in 130-nm CMOS for the amplification and digitization of picoampere-range signals. Its design is inspired by the needs of emerging DNA sequencing technologies based on biological nanopore sensors. To overcome switching and substrate noise this system adopts an in-pixel analog-to-digital converter (ADC) architecture and a novel readout technique while consuming 10x less power than similar designs described in the literature. The in-pixel ADC architecture is inherently scalable and immune to electrical interference which can be extended to 100s of channels. With a 5 pF input capacitance, the amplifiers achieve a maximum bandwidth of 100 kHz and demonstrate a noise floor as low as 4 fA/<inline-formula> <tex-math notation="LaTeX">$\sqrt {\text{Hz}}$ </tex-math></inline-formula> and a gain in the range of <inline-formula> <tex-math notation="LaTeX">$\text{G}\Omega $ </tex-math></inline-formula> at 10 kHz. Circuit noise behaviour and theoretical maximum performance estimates using behavioural models are also discussed.