ABSTRACT
High-bandwidth and low-noise nanopore sensor and detection electronics are crucial in achieving single-DNA-base resolution. A potential way to accomplish this goal is to integrate solid-state nanopores within a CMOS platform, in close proximity to the biasing electrodes and custom-designed amplifier electronics. Here we report the integration of solid-state nanopore devices in a commercial complementary metal-oxide-semiconductor (CMOS) potentiostat chip implemented in On-Semiconductor's 0.5 µm technology. Nanopore membranes incorporating electrodes are fabricated by post-CMOS micromachining utilizing the n+ polysilicon/SiO2/n+ polysilicon capacitor structure available in the aforementioned process. Nanopores are created in the CMOS process by drilling in a transmission electron microscope and shrinking by atomic layer deposition. We also describe a batch fabrication method to process a large of number of electrode-embedded nanopores with sub-10 nm diameter across CMOS-compatible wafers by electron beam lithography and atomic layer deposition. The CMOS-compatibility of our fabrication process is verified by testing the electrical functionality of on-chip circuitry. We observe high current leakage with the CMOS nanopore devices due to the ionic diffusion through the SiO2 membrane. To prevent this leakage, we coat the membrane with Al2O3, which acts as an efficient diffusion barrier against alkali ions. The resulting nanopore devices also exhibit higher robustness and lower 1/f noise as compared to SiO2 and SiNx. Furthermore, we propose a theoretical model for our low-capacitance CMOS nanopore devices, showing good agreement with the experimental value. In addition, experiments and theoretical models of translocation studies are presented using 48.5 kbp λ-DNA in order to prove the functionality of on-chip pores coated with Al2O3.
Subject(s)
Nanopores/ultrastructure , Nanotechnology/instrumentation , Nanotechnology/methods , DNA/chemistry , DNA/isolation & purification , Electric Conductivity , Microscopy, Electron, Transmission , Particle Size , Reproducibility of Results , Semiconductors , Silicon Dioxide/chemistryABSTRACT
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.
ABSTRACT
We have explored the electromechanical properties of DNA by using an electric field to force single hairpin molecules to translocate through a synthetic pore in a silicon nitride membrane. We observe a threshold voltage for translocation of the hairpin through the pore that depends sensitively on the diameter and the secondary structure of the DNA. The threshold for a diameter 1.5 < d < 2.3 nm is V > 1.5 V, which corresponds to the force required to stretch the stem of the hairpin, according to molecular dynamics simulations. On the other hand, for 1.0 < d < 1.5 nm, the threshold voltage collapses to V < 0.5 V because the stem unzips with a lower force than required for stretching. The data indicate that a synthetic nanopore can be used like a molecular gate to discriminate between the secondary structures in DNA.