Principal Investigator/Program Director (Last, First, Middle): Bashir, Rashid Summary: Sequencing the human genome has helped to improve our understanding of disease, inheritance and individuality. The growing need for cheaper and faster genome sequencing has prompted the development of new technologies that surpass conventional Sanger chain-termination methods in terms of speed and cost. These next-generation sequencing technologies ? inspired by the $1,000 genome challenge proposed by the National Institutes of Health in 2004 ? are beginning to revolutionize personalized medicine. Nanopore sensors are one of a number of DNA sequencing technologies that are currently poised to meet this challenge. Biological nanopores such as a-hemolysin and MspA, which consist of molecular motors anchored at the pore, have shown very promising results for ionic current based sequencing of ssDNA molecules, and systems using these pores are now being commercialized by Oxford Nanopores Technologies. However, biological nanopores do not provide the potential of direct single nucleotide read since the pore length spans 5-6 bases long. Solid-state nanopores using two-dimensional materials such as graphene, MoS2, and others could address this challenge regarding spatial resolution of sensing and controlling the DNA motion are addressed. As well as robustness and durability, the solid-state approach offers the ability to potentially fabricate high- density arrays of nanopores, attractive mechanical and chemical characteristics, and the possibility of integrating with novel electronic detection mechanisms. Despite the potential promise, to-date solid state nanopores have yet to demonstrate DNA sequencing, and resolving the challenges require discovering new mechanisms of sensing and translocation control. In this proposal, we introduce a completely new type of sensor which has the desired spatial resolution of sub nanometer and can potentially control the translocation of the DNA molecule. This high risk, high reward approach consists of engineering a nanometer scale out of plane diode using a 2D heterostructure consisting of crossed junction of monolayer MoS2 on monolayer WSe2. Unlike the nanopores in single monolayers, the new sensor allows multi-terminal measurements to probe different physical phenomena within the heterostructure simultaneously, enabling correlated measurements and control of the DNA translocation through the nanopore. The out of plane electric fields at the reverse bias junction will allow for sub nanometer spatial probing of the DNA molecule, and can also reduce the stringent requirement of measuring the change in in-plane conductivity of nanoribbons in which nanopores are formed. The applied biases and local electric field can also be used to control the translocation speed of the molecule. Understanding the relative contributions, interaction, and crosstalk of these different signals is the key scientific goal of this proposal. The key technological goal is to use the new readout schema to achieve single base pair resolution in sensing within a solid state nanopore.
Bashir, Rashid Narrative: Solid-state nanopores are fast becoming an inexpensive and highly versatile alternative to biological nanopores. Here, we propose a novel nanopore sensor concept utilizing an electrically contacted two dimensional material heterostructure to build a nanometer scale diode through which a nanopore is drilled to enable both dynamic control of DNA translocation on the nanoscale as well as multiterminal electrical sensing. The scientific goal is to understand the contributions of different physical mechanisms in this new device concept while the technological goal is to achieve single base pair resolution sensing in a solid state nanopore.
