Detecting single-abasic residues within a DNA strand immobilized in a biological nanopore using an integrated CMOS sensor.
Detecting single-abasic residues within a DNA strand immobilized in a biological nanopore using an integrated CMOS sensor.
复制标题
使用集成 CMOS 传感器检测固定在生物纳米孔中的 DNA 链内的单碱基残基。
DOI：
10.1016/j.snb.2012.11.027
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Dunbar,WilliamB
中科院分区：
文献类型：
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作者：
Kim,Jungsuk;Maitra,RajD;Pedrotti,Ken;Dunbar,WilliamB
在这篇文章中，我们展示了一种为纳米孔应用定制的新型电流测量传感器(CMS)的应用。低噪声CMS是在0.35μm的CMOS工艺下制造的，并在α-溶血素(α-HL)纳米孔中捕获DNA的实验中实现。具体地说，CMS用于建立电流幅度图，作为捕获并保持在孔中的均聚胞嘧啶单链DNA(SsDNA)中单碱基残基的不同位置的函数。每个单链DNA通过生物素-链霉亲和素连接固定。对五种不同的DNA模板进行了测量和比较：一个是全胞嘧啶单链DNA，另四个是当链被固定时，位于∼-HL通道的1.5 nm孔径内或附近的单一碱性残基取代的α-HL通道。结果表明，CMOSCMS能够解决不同模板中基本残基的∼5Å位移。该演示代表了应用特定电路的进步，该电路针对包括基因组测序在内的小足迹纳米孔应用进行了优化。
In this paper, we demonstrate the application of a novel current-measuring sensor (CMS) customized for nanopore applications. The low-noise CMS is fabricated in a 0.35μm CMOS process and is implemented in experiments involving DNA captured in an α-hemolysin (α-HL) nanopore. Specifically, the CMS is used to build a current amplitude map as a function of varying positions of a single-abasic residue within a homopolymer cytosine single-stranded DNA (ssDNA) that is captured and held in the pore. Each ssDNA is immobilized using a biotin–streptavidin linkage. Five different DNA templates are measured and compared: one all-cytosine ssDNA, and four with a single-abasic residue substitution that resides in or near the ∼1.5nm aperture of the α-HL channel when the strand is immobilized. The CMOS CMS is shown to resolves the ∼5Å displacements of the abasic residue within the varying templates. The demonstration represents an advance in application-specific circuitry that is optimized for small-footprint nanopore applications, including genomic sequencing.