Design and characterization of a current sensing platform for silicon-based nanopores with integrated tunneling nanoelectrodes

Solid-state nanopores have been gaining popularity in nano-biotechnology for single molecule detection, in particular for label-free high-throughput DNA sequencing. In order to address the improvement of the resolution/speed trade-off critical in this application, here we present a new two-channel current amplifier tailored for solid-state nanopore devices with integrated tunneling electrodes. The simultaneous detection of ion and tunneling currents provides enhanced molecule tracking capability. We describe the system design starting from a detailed noise analysis and device modeling, highlighting the detrimental role of the conductive silicon substrate and of all the stray capacitive couplings between the electrodes. Given the high input capacitance (0.1–1 nF), the input voltage noise has been carefully minimized choosing a discrete couple of matched low-noise JFETs as input stage, thus achieving an equivalent input noise of 1.5 nV/√Hz (corresponding to a current noise floor of 15 fA/√Hz at 10 kHz). Low-noise performance (11 pA rms noise integrated over a 75 kHz bandwidth) is preserved at a wide bandwidth (300 kHz) and high gain (100 MΩ) thanks to the adoption of an improved integrator/differentiator cascade topology. Furthermore, along with biasing networks and selectable low-pass filters, an AC-coupled channel providing additional gain has been introduced in order to “zoom” in the current signature during pore blockade events. Together with an experimental characterization of the system (and comparison with the noise performance of other instruments), the platform is validated by demonstrating the detection of λ-DNA with 20 nm pores.