Glass Chip for Nanopore Based Low Noise Resistive Pulse Sensing

Abstract

Resistive-pulse sensing provides structural insights on individual proteins when translocated through nanopores. The substrate capacitance, however, induces noise in the ionic current signal, which increases strongly with increasing bandwidth of the recording. For this reason, minimizing substrate capacitance is critical for characterizing single molecules through resistive-pulse sensing. Inspired by recent reports on low-noise nanopore substrates, we engineered a glass chip for low noise nanopore resistive-pulse measurements using microfabrication. Replacing silicon substrate material with fused silica gives an approximately 5-fold reduction of noise at a bandwidth of ∼57 kHz. For fabrication, we deposited a 30 nm thick silicon nitride (SiNx) layer on glass by low-pressure chemical vapor deposition. After etching the glass a SiNx membrane with a diameter of ∼20 µm remained and prepared a ∼20 nm diameter nanopore in the membrane by controlled dielectric breakdown. For a glass chip, the standard deviation of the ionic current during resistive-pulse measurements was 8 pA at 15 kHz recording bandwidth and 19 pA at 57 kHz and for a silicon chip, the standard deviation of the ionic current was 29 pA at 15 kHz and 95 pA at 57 kHz. We demonstrate improved sensitivity for resistive-pulse sensing by using IgG protein as test particle translocating through the glass-based nanopore. The low noise from the glass chip at high bandwidth improves the shape characterization of the protein and potentially allows the detection of subtle changes in protein dynamics within the nanopore. Additionally, we have shown low laser-induced noise from glass chips during ionic current measurements, in contrast to silicon-based chips, which respond to laser by significantly increased noise. The absence of light-induced noise from electrically insulating and optically transparent chips for nanopore recordings makes them compelling for synchronized electrical and optical measurements.