Development of DNA Sequencing Technologies Using Gating Nanopores

选通纳米孔是第三代DNA测序技术的关键设备。这些纳米设备将以低成本和闻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，或者只使用电流而不使用荧光标记来识别单个小分子。我们已经开发了垂直和平行的栅极纳米孔，在固态纳米孔中嵌入了纳米间隙电极。垂直型由单个纳米间隙电极组成，纳米孔垂直于硅衬底表面。平行型由单个纳米间隙电极组成，纳米孔平行于衬底表面。我们采用11步纳米加工工艺合成了直径为30 nm的垂直栅极纳米孔。垂直门控纳米孔可以通过改变纳米电极之间的电流来识别通过它们的单个Au纳米颗粒(~=28 nm)。DNA的单个碱基分子可以通过使用平行的门控纳米孔在纳米电极之间的隧道电流的变化来识别，在纳米制造的机械可控的断口连接中结合了微流体通道。我们发现，单分子电导顺序胸腺嘧啶&lt；胞嘧啶&lt；腺嘌呤&lt；鸟嘌呤对应于最高占据分子轨道(HOMO)能级。

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.