Sapphire Nanopores for Low-Noise DNA Sensing

Solid-state nanopores have broad applications in single-molecule biosensing and diagnostics, but their high electrical noise associated with a large device capacitance has seriously limited both their sensing accuracy and recording speed. Current strategies to mitigate the noise has focused on introducing insulating materials (such as polymer or glass) to decrease the device capacitance, but the complex process integration schemes diminish the potential to reproducibly create such nanopore devices. Here, we report a scalable and reliable approach to create nanopore membranes on sapphire with triangular shape and controlled dimensions by anisotropic wet etching a crystalline sapphire wafer, thus eliminating the noise-dominating stray capacitance that is intrinsic to conventional Si based devices. We demonstrate tunable control of the membrane dimension in a wide range from ∼200 m to as small as 5 m, which corresponds to <1 pF membrane capacitance for a hypothetical 1-2 nm thick membrane. Further, we have demonstrated that a sapphire nanopore chip (∼7 nm pore diameter in a 30 nm thick and 70 m wide SiN membrane) has more than two-order-of-magnitude smaller device capacitance (10 pF) compared to a float-zone Si based nanopore chip (4 nm pore in 23 nm thick and ∼4 m wide SiN membrane, ∼1.3 nF), despite having a 100 times larger membrane area. The sapphire chip has a current noise of 18 pA over 100 kHz bandwidth at a 50 mV bias, much smaller than that from the Si chip (46 pA) and only slightly larger than the open-headstage system noise (∼11 pA). Further, we demonstrate that the sapphire nanopore chip outperforms the Si chip with a higher signal-to-noise ratio (SNR, 21 versus 11), despite of its thicker membrane and larger nanopore size. We believe the low-noise and high-speed sensing capability of sapphire nanopore chips, together with their scalable fabrication strategy, will find broad use in a number of applications in molecular sensing and beyond.