Nanopores in solid-state membranes engineered for single molecule detection

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.