Department of Chemical and Biological Engineering, ‡Renewable and Sustainable Energy Institute (RASEI), §BioFrontiers Institute, and ∥Materials Science and Engineering, University of Colorado Boulder , Boulder, Colorado 80309, United States.
J Am Chem Soc. 2017 Nov 1;139(43):15420-15428. doi: 10.1021/jacs.7b08246. Epub 2017 Oct 20.
Electronic conduction or charge transport through single molecules depends primarily on molecular structure and anchoring groups and forms the basis for a wide range of studies from molecular electronics to DNA sequencing. Several high-throughput nanoelectronic methods such as mechanical break junctions, nanopores, conductive atomic force microscopy, scanning tunneling break junctions, and static nanoscale electrodes are often used for measuring single-molecule conductance. In these measurements, "smearing" due to conformational changes and other entropic factors leads to large variances in the observed molecular conductance, especially in individual measurements. Here, we show a method for characterizing smear in single-molecule conductance measurements and demonstrate how binning measurements according to smear can significantly enhance the use of individual conductance measurements for molecular recognition. Using quantum point contact measurements on single nucleotides within DNA macromolecules, we demonstrate that the distance over which molecular junctions are maintained is a measure of smear, and the resulting variance in unbiased single measurements depends on this smear parameter. Our ability to identify individual DNA nucleotides at 20× coverage increases from 81.3% accuracy without smear analysis to 93.9% with smear characterization and binning (SCRIB). Furthermore, merely 7 conductance measurements (7× coverage) are needed to achieve 97.8% accuracy for DNA nucleotide recognition when only low molecular smear measurements are used, which represents a significant improvement over contemporary sequencing methods. These results have important implications in a broad range of molecular electronics applications from designing robust molecular switches to nanoelectronic DNA sequencing.
电子通过单个分子的传导或电荷传输主要取决于分子结构和锚定基团，这为从分子电子学到 DNA 测序的广泛研究奠定了基础。几种高通量纳米电子方法，如机械断裂结、纳米孔、导电原子力显微镜、扫描隧道断裂结和静态纳米级电极，通常用于测量单分子电导率。在这些测量中，由于构象变化和其他熵因素导致的“弥散”会导致观察到的分子电导率出现很大的差异，尤其是在单个测量中。在这里，我们展示了一种用于表征单分子电导测量中弥散的方法，并演示了如何根据弥散对测量进行分组，可以显著提高单个电导测量在分子识别中的应用。我们使用 DNA 大分子中单核苷酸的量子点接触测量，证明了分子结保持的距离是弥散的度量，并且无偏单测量的方差取决于这个弥散参数。在没有弥散分析的情况下，我们能够以 81.3%的准确率识别单个 DNA 核苷酸，而在进行弥散特征分析和分组 (SCRIB) 后，准确率提高到了 93.9%。此外，当仅使用低分子弥散测量时，仅需 7 次电导测量（7×覆盖率）即可实现 DNA 核苷酸识别的 97.8%准确率，这与当代测序方法相比有了显著的提高。这些结果在从设计稳健的分子开关到纳米电子 DNA 测序的广泛分子电子应用中具有重要意义。
