Metal–Organic Cage as Single‐Molecule Carrier for Solid‐State Nanopore Analysis
Metal–Organic Cage as Single‐Molecule Carrier for Solid‐State Nanopore Analysis
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DOI：
10.1002/smtd.202200743
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发表时间：
2022-10
期刊：
影响因子：
12.4
通讯作者：
Zhan Wang;Ruisheng Hu;Rui Zhu;Wenlong Lu;Guanghao Wei;Jing Zhao;Zhi‐Yuan Gu;Qing Zhao
中科院分区：
文献类型：
--
作者：
Zhan Wang;Ruisheng Hu;Rui Zhu;Wenlong Lu;Guanghao Wei;Jing Zhao;Zhi‐Yuan Gu;Qing Zhao
在单分子水平上检测生物分子的能力处于生物研究、精准医学和早期诊断的最前沿。最近，固态纳米孔传感器已经成为一种有前途的无标记和精确诊断测定技术。然而，对小分析物的灵敏度和选择性不足是通过固态纳米孔进行临床诊断应用的巨大挑战。在这里，首次采用金属有机笼PCC-57作为载体，以基于纳米笼与生物分子的内在相互作用来提高固态纳米孔的灵敏度和选择性。首先，发现载体本身是不可检测的，除非与靶分析物结合并使用寡核苷酸作为连接物来连接PCC-57和靶分析物。其次，使用分子载体成功区分了两种小的分析物，寡核苷酸缀合的血管肽-2和多磷酸。最后，通过将PCC-57连接到寡核苷酸加尾的适配体来实现纳米孔检测的选择性，并且成功地检测了人α凝血酶样品。据信，高度可设计的金属有机笼可以作为各种生物分子的丰富载体库，促进未来基于固态纳米孔的临床相关生物分子的单分子筛选。
The ability to detect biomolecules at the single‐molecule level is at the forefront of biological research, precision medicine, and early diagnosis. Recently, solid‐state nanopore sensors have emerged as a promising technique for label‐free and precise diagnosis assay. However, insufficient sensitivity and selectivity for small analytes are a great challenge for clinical diagnosis applications via solid‐state nanopores. Here, for the first time, a metal–organic cage, PCC‐57, is employed as a carrier to increase the sensitivity and selectivity of solid‐state nanopores based on the intrinsic interaction of the nanocage with biomolecules. Firstly, it is found that the carrier itself is undetectable unless bound with the target analytes and used oligonucleotides as linkers to attach PCC‐57 and target analytes. Secondly, two small analytes, oligonucleotide conjugated angiopep‐2 and polyphosphoric acid, are successfully distinguished using the molecular carrier. Finally, selectivity of nanopore detection is achieved by attaching PCC‐57 to oligonucleotide‐tailed aptamers, and the human alpha‐thrombin sample is successfully detected. It is believed that the highly designable metal–organic cage could serve as a rich carrier repository for a variety of biomolecules, facilitating single‐molecule screening of clinically relevant biomolecules based on solid‐state nanopores in the future.