Probing chemical structures and physical processes with nanopores

This thesis develops and applies the nanopore tool to probe chemical structures and physical processes at the single-molecule level: from single ions to DNA molecules. Nanopore experiments electrically measure the ionic transport through the pore and its modulation from the local environment which can be caused by translocations of an analyte such as objects like DNA molecules or change of the physical conditions such as surface charge. Its precision relies on the physical dimension of the nanopore probe. In this thesis, the atom by atom engineering of single-layer molybdenum disulfide (MoS2) nanopores was achieved using transmission electron microscopy (TEM) or controlled electrochemical reaction (ECR), which further enabled the following investigations. On the translational side, the key driver of the application of nanopores is single molecule DNA sequencing. The sequence of DNA can be extracted based on the modulation of ionic current through the pore by individual nucleotides. To this end, we realized for the first time with solid-state nanopores, identification of all four types of nucleotides by introducing an ionic liquid based viscosity gradient system to control the translocation dynamics. This method provides a potential route for sequencing with solid-state nanopores. On the fundamental side, nanopore experiments could probe physics of single ion transport and with subnanometer pores, we discovered Coulomb blockade for the first time in ionic transport, as the counterpart of quantum dots, and proposed a new mesoscopic understanding for biological ion channel transport. From an engineering perspective, measurement with a single nanopore can avoid averaging over many pores and allow accurately identifying individual parameters for membrane-based processes. With single-layer MoS2 nanopores, we realized the first exploration of a two-dimensional (2D) membrane for osmotic power generation. This thesis demonstrates that nanoscopic, atomically thin pores allow for the exploration of applications in DNA sequencing and investigations of fundamental ion transport for biological ion channels and membrane-based processes.

Electrochemical Reaction in Single Layer MoS2: nanopores opened atom by atom

Duncan Alexander, Roman Bulushev, Dumitru Dumcenco, Jiandong Feng, Michael Graf, Andras Kis, Daria Krasnozhon, Martina Lihter, Ke Liu, Aleksandra Radenovic

Ultrathin nanopore membranes based on 2D materials have demonstrated ultimate resolution toward DNA sequencing. Among them, molybdenum disulfide (MoS2) shows long-term stability as well as superior sensitivity enabling high throughput performance. The traditional method of fabricating nanopores with nanometer precision is based on the use of focused electron beams in transmission electron microscope (TEM). This nanopore fabrication process is time-consuming, expensive, not scalable, and hard to control below 1 nm. Here, we exploited the electrochemical activity of MoS2 and developed a convenient and scalable method to controllably make nanopores in single-layer MoS2 with subnanometer precision using electrochemical reaction (ECR). The electrochemical reaction on the surface of single-layer MoS2 is initiated at the location of defects or single atom vacancy, followed by the successive removals of individual atoms or unit cells from single-layer MoS2 lattice and finally formation of a nanopore. Step-like features in the ionic current through the growing nanopore provide direct feedback on the nanopore size inferred from a widely used conductance vs pore size model. Furthermore, DNA translocations can be detected in situ when as-fabricated MoS2 nanopores are used. The atomic resolution and accessibility of this approach paves the way for mass production of nanopores in 2D membranes for potential solid-state nanopore sequencing.

Amer Chemical Soc2015

Atomically Thin Molybdenum Disulfide Nanopores with High Sensitivity for DNA Translocation

Jiandong Feng, Andras Kis, Ke Liu, Aleksandra Radenovic

Atomically thin nanopore membranes are considered to be a promising approach to achieve single base resolution with the ultimate aim of rapid and cheap DNA sequencing. Molybdenum disulfide (MoS2) is newly emerging as a material complementary to graphene due to its semiconductive nature and other interesting physical properties that can enable a wide range of potential sensing and nanoelectronics applications. Here, we demonstrate that monolayer or few-layer thick exfoliated MoS2 with subnanometer thickness can be transferred and suspended on a predesigned location on the 20 nm thick SiNx. membranes. Nanopores in MoS2 are further sculpted with variable sizes using a transmission electron microscope (TEM) to drill through suspended portions of the MoS2 membrane. Various types of double-stranded (ds) DNA with different lengths and conformations are translocated through such a novel architecture, showing improved sensitivity (signal-to-noise ratio >10) compared to the conventional silicon nitride (SiNx) nanopores with tens of nanometers thickness. Unlike graphene nanopores, no special surface treatment is needed to avoid hydrophobic interaction between DNA and the surface. Our results imply that MoS2 membranes with nanopore can complement graphene nanopore membranes and offer potentially better performance in transverse detection.

Amer Chemical Soc2014

Identification of single nucleotides in MoS2 nanopores

Roman Bulushev, Dumitru Dumcenco, Jiandong Feng, Sergey Khlybov, Andras Kis, Ke Liu, Aleksandra Radenovic

The size of the sensing region in solid-state nanopores is determined by the size of the pore and the thickness of the pore membrane, so ultrathin membranes such as graphene and single-layer molybdenum disulphide could potentially offer the necessary spatial resolution for nanopore DNA sequencing. However, the fast translocation speeds ( 3,000-50,000 nt ms(-1)) of DNA molecules moving across such membranes limit their usability. Here, we show that a viscosity gradient system based on room-temperature ionic liquids can be used to control the dynamics of DNA translocation through MoS2 nanopores. The approach can be used to statistically detect all four types of nucleotide, which are identified according to current signatures recorded during their transient residence in the narrow orifice of the atomically thin MoS2 nanopore. Our technique, which exploits the high viscosity of room-temperature ionic liquids, provides optimal single nucleotide translocation speeds for DNA sequencing, while maintaining a signal-to-noise ratio higher than 10.

Nature Publishing Group2015