Nanopores in solid-state membranes engineered for single molecule detection

Abstract

A nanopore is an analytical tool with single molecule sensitivity. For detection, a nanopore relies on the electrical signal that develops when a molecule translocates through it. However, the detection sensitivity can be adversely affected by noise and the frequency response. Here, we report measurements of the frequency and noise performance of nanopores </=8 nm in diameter in membranes compatible with semiconductor processing. We find that both the high frequency and noise performance are compromised by parasitic capacitances. From the frequency response we extract the parameters of lumped element models motivated by the physical structure that elucidates the parasitics, and then we explore four strategies for improving the electrical performance. We reduce the parasitic membrane capacitances using: (1) thick Si(3)N(4) membranes; (2) miniaturized composite membranes consisting of Si(3)N(4) and polyimide; (3) miniaturized membranes formed from metal-oxide-semiconductor (MOS) capacitors; and (4) capacitance compensation through external circuitry, which has been used successfully for patch clamping. While capacitance compensation provides a vast improvement in the high frequency performance, mitigation of the parasitic capacitance through miniaturization offers the most promising route to high fidelity electrical discrimination of single molecules.

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The role of fluid-wall interactions on confined liquid diffusion using Mori theory

“…(6) and (7) and hyperbolic secant memory function, given by Eq. (10). The results are shown in Figs.…”

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“…The exact reason for this discrepancy has not been addressed before. Dimitrov et al [20] performed comprehensive analysis by considering all parasitic capacitors associated with the nanopore devices, but all associated time constants are still orders of magnitude smaller than a millisecond. We suspect that dielectric absorption or soakage in the membrane capacitor plays a significant role here.…”

“…As a result, the continuous ping-pong control of a single DNA molecule will fail [19] since the translocation of another molecule will trigger the electronics servo. To diminish membrane capacitance effects, Dimitrov et al [20] designed a complex nanopore structure and modified the electronic system to minimize the transient current spike.…”