Roy Somenath, Chen Xiaojun, Li Mo-Huang, Peng Yanfen, Anariba Franklin, Gao Zhiqiang
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669.
J Am Chem Soc. 2009 Sep 2;131(34):12211-7. doi: 10.1021/ja901704t.
In this report, an electrical detection scheme for the quantification of DNA using a nanogap sensor array is detailed. The prime objective is to develop a novel sensing procedure, based on the electronic transduction mechanism, which would mitigate the problems intrinsic to nanostructure-based biosensing devices. Design considerations of the sensor array take into account the feasibility of mass production in a cost-effective way by using standard silicon microfabrication technologies. The sensing mechanism relies on bridging the nanogap upon hybridization of the two termini of a target DNA with two different surface-bound capture probes, followed by a simple metallization step. About 2 orders of magnitude enhancement in conductance, as referred to a clean background (<1.0 pS) observed at a control sensor, was obtained in the presence of as little as 1.0 fM target DNA. This sensitivity is comparable to the best of electrochemical/electrical biosensors. A linear relationship between the conductance and the DNA concentration was obtained from 1.0 fM to 1.0 pM with an exceptional signal intensity of 2.1 x 10(4)% change per unit concentration. This change in conductivity is so large that it can unambiguously detect the concentration of DNA quantitatively and may obviate the need for target amplification used in current DNA tests. Moreover, the sensor array exhibited excellent single-base mismatch discrimination due to its unique vertically aligned nanostructure and the two-probe configuration.
在本报告中,详细介绍了一种使用纳米间隙传感器阵列对DNA进行定量的电学检测方案。主要目标是基于电子转导机制开发一种新颖的传感程序,以减轻基于纳米结构的生物传感装置固有的问题。传感器阵列的设计考虑了通过使用标准硅微加工技术以具有成本效益的方式进行大规模生产的可行性。传感机制依赖于目标DNA的两个末端与两个不同的表面结合捕获探针杂交时桥接纳米间隙,随后进行简单的金属化步骤。在存在低至1.0 fM目标DNA的情况下,相对于在对照传感器上观察到的干净背景(<1.0 pS),电导提高了约2个数量级。这种灵敏度与最佳的电化学/电学生物传感器相当。在1.0 fM至1.0 pM范围内获得了电导与DNA浓度之间的线性关系,每单位浓度的信号强度变化异常,为2.1×10⁴%。这种电导率变化非常大,以至于可以明确地定量检测DNA浓度,并且可能无需当前DNA测试中使用的目标扩增。此外,由于其独特的垂直排列纳米结构和双探针配置,该传感器阵列表现出出色的单碱基错配区分能力。