Development of DNA Sequencing Technologies Using Gating Nanopores

门控纳米孔是第三代DNA测序技术的关键器件。这些纳米装置将以低成本和前所未闻的速度，对千碱基长度的单链基因组DNA或RNA进行测序，或仅使用电流而不使用荧光标记来识别单个小分子。我们开发了垂直和平行的门控纳米孔，在固态纳米孔中嵌入纳米间隙电极。垂直型包括具有垂直于硅衬底表面的纳米孔的单个纳米隙电极。平行型包括一个纳米间隙电极，其纳米孔平行于衬底表面。我们采用11步纳米工艺合成了直径为30 nm的垂直门控纳米孔。垂直门控纳米孔可以通过纳米电极之间电流的变化来识别穿过它们的单个金纳米粒子（~ = 28 nm）。利用平行门控纳米孔，在纳米制造的机械可控断结中加入微流控通道，通过纳米电极之间隧道电流的变化来识别DNA的单碱基分子。我们发现，胸腺嘧啶<胞嘧啶<腺嘌呤<鸟嘌呤的单分子电导顺序与最高占据分子轨道（HOMO）能量顺序一致。

Gating nanopores are the key devices for third generation DNA sequencing technologies. These nanodevices will make sequencing kilobase length single-stranded genomic DNA or RNA or identifying individual small molecules using only electric currents and without fluorescent labels at low cost and unheard speeds. We have developed vertical and parallel gating nanopores with embedded nanogap-electrodes in a solid-state nanopore. The vertical type consists of a single nanogap electrode with the nanopore perpendicular to the surface of the silicon substrate. The parallel type consists of a single nanogap electrode with the nanopore parallel to the surface of the substrate. We synthesized vertical gating nanopores with a diameter of 30 nm using an 11-step nanofabrication process. Vertical gating nanopores can indetify a single Au nanoparticle (~ = 28 nm) passing through them by changes in the electric current flowing between the nano-electrodes. Single base molecules of DNA can be identified by changes in tunneling current between nano-electrodes using parallel gating nanopores, incorporating a microfluidic channel in to nano-fabricated mechanically controllable break junction. We found that single-molecule electrical conductance order thymine < cytosine < adenine < guanine corresponds to the highest occupied molecular orbital (HOMO) energy order.