There is a growing realization, especially within the diagnostic and therapeutic community, that the amount of information enclosed in a single molecule can not only enable a better understanding of biophysical pathways, but also offer exceptional value for early stage biomarker detection of disease onset. To this end, numerous single molecule strategies have been proposed, and in terms of label-free routes, nanopore sensing has emerged as one of the most promising methods. However, being able to finely control molecular transport in terms of transport rate, resolution, and signal-to-noise ratio (SNR) is essential to take full advantage of the technology benefits. Here we propose a novel solution to these challenges based on a method that allows biomolecules to be individually confined into a zeptoliter nanoscale droplet bridging two adjacent nanopores (nanobridge) with a 20 nm separation. Molecules that undergo confinement in the nanobridge are slowed down by up to 3 orders of magnitude compared to conventional nanopores. This leads to a dramatic improvement in the SNR, resolution, sensitivity, and limit of detection. The strategy implemented is universal and as highlighted in this manuscript can be used for the detection of dsDNA, RNA, ssDNA, and proteins.

中文翻译：

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使用Zeptoliter纳米桥分离的双纳米孔进行单分子捕获和传感

人们日益意识到，尤其是在诊断和治疗领域，单个分子中包含的信息量不仅可以更好地理解生物物理途径，而且还为疾病发作的早期生物标志物检测提供了非凡的价值。为此，已经提出了许多单分子策略，就无标记途径而言，纳米孔感测已成为最有前途的方法之一。但是，要充分利用技术优势，必须在传输速率，分辨率和信噪比（SNR）方面精确控制分子的传输。在这里，我们基于一种方法提出了针对这些挑战的新颖解决方案，该方法允许将生物分子单独限制在以两个20 nm距离桥接两个相邻纳米孔（纳米桥）的zeptoliter纳米级液滴中。与传统的纳米孔相比，在纳米桥中受到限制的分子最多可减慢3个数量级。这将导致SNR，分辨率，灵敏度和检测极限的显着改善。所实施的策略是通用的，并且如本手稿中突出显示的那样，可用于检测dsDNA，RNA，ssDNA和蛋白质。和检测极限。所实施的策略是通用的，并且如本手稿中突出显示的那样，可用于检测dsDNA，RNA，ssDNA和蛋白质。和检测极限。所实施的策略是通用的，并且如本手稿中突出显示的那样，可用于检测dsDNA，RNA，ssDNA和蛋白质。