Towards Tunneling Electrodes for Nanopore-based DNA Sequencing

نویسنده

  • Axel FANGET
چکیده

The advent of DNA sequencing has revolutionized fundamental research and brought incredible hope for personalized medicine. However, the race still continues for cheaper and faster techniques that can surpass conventional methods and ultimately reach the $1000 genome goal. This thesis describes the fabrication and first characterizations of nanopores-based devices with embedded tunneling electrodes for single-molecule DNA sensing. This constitutes a unique and very promising approach for label-free detection and structural analysis of individual molecules. Nanopores are nanometer-sized holes in thin biological or solid-state membranes, which charged molecules or particles, including DNA molecules, can be threaded through under the driving force of an external electric field. When performed in an electrolyte, the translocation of individual molecules results in ionic current blockades that provide useful information about the molecule’s properties such as length, conformation and eventually local structure. After more than a decade of extensive investigations, it is widely admitted that pure ionic analysis suffers from limited temporal and structural resolutions for DNA sequencing. Since it has been demonstrated that single-base resolution can be achieved through transverse tunneling current, coupling nanopores to tunneling junctions might be the solution to nanopore-based sequencing. The fabrication of such devices is extremely challenging, as the electrodes need to be aligned with the nanopore and spaced only few nanometers apart for tunneling to be possible. We have investigated two strategies for such an achievement with solid-state nanopores drilled with an electron beam. First, we present a method for embedding single-wall carbon nanotubes (SWCNTs) nanoelectrodes across the diameter of a nanopore. A reproducible fabrication process for the synthesis with location control and circuit integration of individual SWCNTs is established and combined to the fabrication of nanopores. By cutting the nanotubes and drilling a pore in a single step using a focused electron beam, we show a proof of principle device but damaging of the SWCNT electrode tips is difficult to avoid. To overcome the relative low-throughput of the first method, we present a process for nanopores with metallic tunneling junctions using advanced electron beam lithography (EBL) and electrodeposition techniques. It is possible to fabricate electrodes that are separated by 7nm and aligned with the nanopore with an exceptional reproducibility and process yield. By electrodeposition, a large number of nanogap electrodes can be reduced down to few nanometers with spacing control.

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تاریخ انتشار 2013