Vishva Ray

DNA Translocation through Graphene Nanopores

We report on DNA translocations through nanopores created in graphene membranes. Devices consist of 1-5 nm thick graphene membranes with electron-beam sculpted nanopores from 5 to 10 nm in diameter. Due to the thin nature of the graphene membranes, we observe larger blocked currents than for traditional solid-state nanopores. However, ionic current noise levels are several orders of magnitude larger than those for silicon nitride nanopores. These fluctuations are reduced with the atomic-layer deposition of 5 nm of titanium dioxide over the device. Unlike traditional solid-state nanopore materials that are insulating, graphene is an excellent electrical conductor. Use of graphene as a membrane material opens the door to a new class of nanopore devices in which electronic sensing and control are performed directly at the pore.

Rapid electronic detection of probe-specific microRNAs using thin nanopore sensors

Small RNA molecules have an important role in gene regulation and RNA silencing therapy, but it is challenging to detect these molecules without the use of time-consuming radioactive labelling assays or error-prone amplification methods. Here, we present a platform for the rapid electronic detection of probe-hybridized microRNAs from cellular RNA. In this platform, a target microRNA is first hybridized to a probe. This probe:microRNA duplex is then enriched through binding to the viral protein p19. Finally, the abundance of the duplex is quantified using a nanopore. Reducing the thickness of the membrane containing the nanopore to 6 nm leads to increased signal amplitudes from biomolecules, and reducing the diameter of the nanopore to 3 nm allows the detection and discrimination of small nucleic acids based on differences in their physical dimensions. We demonstrate the potential of this approach by detecting picogram levels of a liver-specific miRNA from rat liver RNA.

CMOS-compatible fabrication of room-temperature single-electron devices

Devices in which the transport and storage of single electrons are systematically controlled could lead to a new generation of nanoscale devices and sensors. The attractive features of these devices include operation at extremely low power, scalability to the sub-nanometre regime and extremely high charge sensitivity. However, the fabrication of single-electron devices requires nanoscale geometrical control, which has limited their fabrication to small numbers of devices at a time, significantly restricting their implementation in practical devices. Here we report the parallel fabrication of single-electron devices, which results in multiple, individually addressable, single-electron devices that operate at room temperature. This was made possible using CMOS fabrication technology and implementing self-alignment of the source and drain electrodes, which are vertically separated by thin dielectric films. We demonstrate clear Coulomb staircase/blockade and Coulomb oscillations at room temperature and also at low temperatures.

Fabrication and characterization of nanopores with insulated transverse nanoelectrodes for DNA sensing in salt solution

We report on the fabrication, simulation, and characterization of insulated nanoelectrodes aligned with nanopores in low‐capacitance silicon nitride membrane chips. We are exploring these devices for the transverse sensing of DNA molecules as they are electrophoretically driven through the nanopore in a linear fashion. While we are currently working with relatively large nanopores (6–12 nm in diameter) to demonstrate the transverse detection of DNA, our ultimate goal is to reduce the size sufficiently to resolve individual nucleotide bases, thus sequencing DNA as it passes through the pore. We present simulations and experiments that study the impact of insulating these electrodes, which is important to localize the sensing region. We test whether the presence of nanoelectrodes or insulation affects the stability of the ionic current flowing through the nanopore, or the characteristics of DNA translocation. Finally, we summarize the common device failures and challenges encountered during fabrication and experiments, explore the causes of these failures, and make suggestions on how to overcome them in the future.

Single-particle placement via self-limiting electrostatic gating

This letter reports single-particle placement in which exactly one nanoparticle is electrostatically guided and placed onto a target location. Using an ∼20 nm Au nanoparticle colloid as a model system, we demonstrate that self-limiting interactions between a charged nanoparticle and a charged substrate surface are extremely effective in positioning a single Au nanoparticle on each target location. Detailed theoretical calculations revealed that the self-limiting capability in the nanoparticle positioning is due to an increase in the free energy barrier after the first nanoparticle lands on a target position, effectively blocking the approach of other nanoparticles.

Nanopore DNA sensors in CMOS with on-chip low-noise preamplifiers

We present an integrated platform for single-molecule electrochemical analysis in which solid-state nanopore sensors are post-fabricated into a custom CMOS preamplifier die. The usable bandwidth of solid-state nanopore sensors is typically constrained by noise caused by parasitic impedances from the sensors support substrate and external measurement electronics. By integrating the sensor with a dedicated amplifier we provide a path to significantly reduce these parasitics. The new system includes a low-noise 8-channel preamplifier in a 0.13µm CMOS process. The chip is post-processed to fabricate Ag/AgCl microelectrodes and silicon nitride nanopores.

Solid-state nanopores integrated with low-noise preamplifiers for high-bandwidth DNA analysis

Nanopore sensing platforms have been limited in bandwidth and noise performance by the use of external measurement electronics with significant parasitic impedances. In this work, we describe progress toward integrating detection electronics with solid-state nanopore sensors. This new platform for high-bandwidth single-molecule electrochemical DNA analysis includes a low-noise 8-channel 0.13µm CMOS preamplifier with integrated Ag/AgCl microelectrodes. We also demonstrate monolithic integration of solid-state nanopores in the amplifier chip. This arrangement provides an opportunity to extend the useful bandwidth of nanopore sensors by a factor of ten or more.