An electrochemical biosensor exploiting binding-induced changes in electron transfer of electrode-attached DNA origami to detect hundred nanometer-scale targets
An electrochemical biosensor exploiting binding-induced changes in electron transfer of electrode-attached DNA origami to detect hundred nanometer-scale targets
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DOI：
10.1039/d0nr00952k
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发表时间：
2020-07-14
期刊：
影响因子：
6.7
通讯作者：
Lukeman, Philip S.
中科院分区：
文献类型：
--
作者：
Arroyo-Curras, Netzahualcoyotl;Sadeia, Muaz;Lukeman, Philip S.
对临床样品中尺寸为数十至数百纳米的分析物（例如病毒和大蛋白）进行特异性检测将改善疾病诊断。然而，这些“介观尺度”分析物（相对于其纳米尺度成分）的检测具有挑战性，因为它需要同时结合多个间隔通常超过数十纳米的识别位点。为此，我们采用了 DNA 折纸技术，以其无与伦比的可定制性，在相关长度范围内精确显示多个靶标结合位点，并将其应用于电化学生物传感器平台。我们的概念验证采用了共价连接到金电极上的三角形折纸，并通过氧化还原报告基因进行功能化。该平台的电化学询问以与粗粒度分子动力学模拟一致的方式成功地监测了电子转移中尺度、目标结合引起的变化。我们的方法能够对显示识别位点的分析物进行特异性检测，这些识别位点的间距约为 40 nm，该间距明显大于使用抗体或适体的类似传感器架构中实现的间距。
The specific detection in clinical samples of analytes with dimensions in the tens to hundreds of nanometers, such as viruses and large proteins, would improve disease diagnosis. Detection of these "mesoscale" analytes (as opposed to their nanoscale components), however, is challenging as it requires the simultaneous binding of multiple recognition sites often spaced over tens of nanometers. In response, we have adapted DNA origami, with its unparalleled customizability to precisely display multiple target-binding sites over the relevant length scale, to an electrochemical biosensor platform. Our proof-of-concept employs triangular origami covalently attached to a gold electrode and functionalized with redox reporters. Electrochemical interrogation of this platform successfully monitors mesoscale, target-binding-induced changes in electron transfer in a manner consistent with coarse-grained molecular dynamics simulations. Our approach enables the specific detection of analytes displaying recognition sites that are separated by similar to 40 nm, a spacing significantly greater than that achieved in similar sensor architectures employing either antibodies or aptamers.