Ultra-low-noise ASIC-based electronics for nanopore sensing applications within the DYNAMO project

Before the start of the DYNAMO project, nanopore sensing had already emerged as a powerful technology for single-molecule analysis and DNA characterization[cite: 2]. Both biological nanopores and solid-state nanopores were widely investigated for biosensing applications due to their capability to detect ionic current modulations produced by molecular translocation events through nanoscale pores[cite: 2]. Despite significant progress in nanopore fabrication and fluidic integration, the electronic readout systems remained one of the main limitations for high-performance sensing[cite: 2]. Nanopore measurements require extremely low-noise current sensing circuits capable of detecting picoampere and sub-picoampere current variations while maintaining sufficient bandwidth to resolve fast transient events[cite: 2].

At that time, most nanopore readout platforms relied on discrete laboratory instrumentation or commercial patch-clamp amplifiers[cite: 2]. Although these systems provided good sensitivity, they were generally bulky, expensive, power-consuming, and difficult to scale toward large multi-channel arrays[cite: 2]. In addition, many existing CMOS integrated solutions suffered from limitations related to input-referred noise, bandwidth, stability, and dynamic range[cite: 2].

A major challenge in CMOS current sensing was the implementation of ultra-high-value feedback elements in transimpedance amplifiers (TIAs)[cite: 2]. Conventional pseudo-resistors operating in the subthreshold region were commonly used to emulate very large resistances, but these structures often exhibited process variability, nonlinearity, thermal noise contribution, and bias sensitivity[cite: 2].

Furthermore, the simultaneous handling of large DC baseline currents together with small transient nanopore events represented another critical limitation[cite: 2]. In many reported systems, the DC baseline current reduced the available dynamic range and degraded the sensitivity of the analog front-end[cite: 2]. Consequently, there was a strong need for compact, low-noise, high-bandwidth, and scalable ASIC-based nanopore readout systems capable of supporting future multi-channel sensing platforms and integrated biosensing technologies[cite: 2].