Challenges of Single-Molecule DNA Sequencing with Solid-State Nanopores
A powerful DNA sequencing tool with high accuracy, long read length and high-throughput would be required more and more for decoding the complicated genetic code. Solid-state nanopore has attracted many researchers for its promising future as a next-generation DNA sequencing platform due to the processability, the robustness and the large-scale integratability. While the diverse materials have been widely explored for a solid-state nanopore, silicon nitride (Si3N4) is especially preferable from the viewpoint of mass production based on semiconductor fabrication process. Here, as a nanopore sensing mechanism, we focused on the ionic blockade current method which is the most developed technique. We also highlight the main challenges of Si3N4 nanopore-based DNA sequencer that should be addressed: the fabrication of ultra-small nanopore and ultra-thin membrane, the modulation of DNA translocation speed and the detection of base-specific signals. In this chapter, we discuss the recent progress relating to solid-state nanopore DNA sequencing, which helps to provide a comprehensive information about the current technical situation.
The authors would like to express the utmost thanks to all co-workers for their dedication to Hitachi’s solid-state nanopore DNA sequencer project.
- Edel JB, Albrecht T. Engineered nanopores for bioanalytical applications. Amsterdam: Elsevier Science; 2013.Google Scholar
- Goto Y, Akahori R, Matsui K, Yanagawa Y, Aoki M, Yanagi I, Nara Y, Yoshida M, Yokoi T, Takeda K. Solid-state nanopore DNA sequencing: single-nucleotide discrimination and bidirectional DNA translocation. In: Advances in genome biology and technology (AGBT) The General Meeting. Hollywood: The Diplomat Beach Resort; 13–16 February, 2017.Google Scholar
- Yanagi I, Ishida T, Fujisaki K, Takeda K. Fabrication of 3-nm-thick Si3N4 membranes for solid-state nanopores using the poly-Si sacrificial layer process. Sci Rep. 2015;5:14656.Google Scholar