Chapter 9: Low Noise Nanopore Platforms Optimised for the Synchronised Optical and Electrical Detection of Biomolecules

Nanopores are valuable tools for single-molecule sensing and biomolecular analysis. This can not only be seen from their prevalence in academic and industrial research, but in the growing capabilities at the cutting edge of the field. Recently the demand for improved structural resolution and accelerated analytical throughput has led to the incorporation of additional detection methods, such as fluorescence spectroscopy. The most frequently used solid-state nanopore platforms consist of a bulk silicon substrate and silicon nitride membrane. Although these platforms have many potential uses, they exhibit high photo-induced ionic current noise when probed with light. Due to the high translocation velocity of molecules, high bandwidth electrical measurements are essential for structural information to be investigated via resistive pulse sensing. Consequently, the applicability of Si substrate based nanopore sensors to synchronized optical and electrical measurements is limited at high-bandwidth and high-laser-power. This chapter describes the development and application of a unique low-noise nanopore platform, composed of a predominately Pyrex substrate and silicon nitride membrane. Proof-of-principle experiments are presented that show a Pyrex substrate greatly reduces ionic current noise arising from both platform capacitance and laser illumination. Furthermore, using confocal microscopy and a partially metallic nanopore as a zero mode waveguide, high signal-to-noise synchronized optical and electrical detection of dsDNA is demonstrated.