Plasmon-enhanced spectroscopy at nanopores

Before the start of the DYNAMO project, nanopore sensing had already emerged as a powerful technology for single-molecule analysis and DNA characterization[cite: 12]. 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: 12].

Despite significant progress in nanopore fabrication and fluidic integration, the electronic readout systems remained one of the main limitations for high-performance sensing[cite: 12]. 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: 12].

At that time, most nanopore readout platforms relied on discrete laboratory instrumentation or commercial patch-clamp amplifiers[cite: 12]. Although these systems provided good sensitivity, they were generally bulky, expensive, power-consuming, and difficult to scale toward large multi-channel arrays[cite: 12]. In addition, many existing CMOS integrated solutions suffered from limitations related to input-referred noise, bandwidth, stability, and dynamic range[cite: 12].

A major challenge in CMOS current sensing was the implementation of ultra-high-value feedback elements in transimpedance amplifiers (TIAs)[cite: 12]. 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: 12].

Furthermore, the simultaneous handling of large DC baseline currents together with small transient nanopore events represented another critical limitation[cite: 12]. In many reported systems, the DC baseline current reduced the available dynamic range and degraded the sensitivity of the analog front-end[cite: 12].

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: 12].

Plasmon-enhanced spectroscopy at nanopores

Recent years have seen major advances in integrated nanopore sensing electronics, particularly in the development of CMOS ASICs dedicated to low-current biosensing applications[cite: 11]. Modern nanopore readout systems increasingly focus on improving noise performance, scalability, integration density, and compatibility with large sensor arrays[cite: 11].

Within this context, the work developed in the DYNAMO project contributed to the realization of a complete ASIC-based nanopore sensing platform centered around the custom dual-channel ASIC QC01a[cite: 11]. The platform integrates low-noise analog front-end circuitry, DC current handling, data acquisition electronics, PCB implementation, and real-time digital processing[cite: 11].

One of the main innovations of the developed system is the implementation of a PN-junction diode feedback technique in the transimpedance amplifier architecture[cite: 11]. Unlike conventional pseudo-resistors relying on subthreshold channel conduction, the proposed approach uses MOSFET PN-junction conduction to realize ultra-high equivalent resistance with reduced thermal and flicker noise contribution[cite: 11]. The developed system experimentally demonstrated minimum input-referred current noise levels of approximately 1.5 fA/√Hz together with readout bandwidths up to 1 MHz[cite: 11].

The platform was experimentally validated using solid-state nanopore measurements with Lambda DNA translocation experiments performed in 1 M KCl electrolyte solution[cite: 11]. Stable baseline operation and clear transient current blockade events were successfully detected, demonstrating the capability of the system for high-sensitivity nanopore sensing applications[cite: 11].

The developed work also resulted in scientific dissemination and intellectual property generation, including an accepted IEEE Solid-State Circuits Letters (SSC-L) publication and two patent applications related to the developed readout technology[cite: 11]. Additional journal publications are currently under preparation[cite: 11].