Tunable Nanofiber Mesh Coatings for Improved Nanopores Sensing

描述(申请人提供)：虽然固态纳米孔在生物医学应用中显示出作为单分子传感器的前景，但为了提高其分辨率和效率，分析物分子必须更频繁地被探测，并且必须在纳米孔传感体积中停留更长时间。这项建议描述了一种新颖、简单和通用的方法，通过减缓纳米孔的移位速度和通过纳米孔外的相互作用提高捕获效率，同时仍使纳米孔本身可用于进一步的功能化，从而提高纳米孔的灵敏度和时间分辨率。这将通过将化学可调的纳米纤维聚合物网(NFM)直接应用于固态纳米孔芯片来实现，在固态纳米孔芯片中，其纤维(疏水、阳离子或阴离子)在从纳米孔外感应期间可能与分析物分子相互作用，引导它们进入传感体积并减缓它们在其中的移动。NFM是由聚己内酯(PCL)和聚甘油-己内酯(PGC)掺杂形成的直径100-1000 nm的纤维网络组成的，通过静电纺丝沉积在表面上。该聚合物的PGC组分可以被修饰以包括赋予NFM疏水性、阴离子或阳离子性质的一系列侧基。通过调整电纺工艺参数，可以控制纤维尺寸和网眼密度。因此，聚合物NFM参数的调整将完全独立于对纳米孔表面本身的改变。通过简单地选择适当的NFM，任何固态纳米孔应用都可以获得广泛的设计者易位特性。我们将首先构建具有不同电荷和网格特性的纳米孔-纳米纤维网(NP-NFM)杂化器件，然后对这些器件进行筛选，以确定哪些组合适合于纳米孔传感。候选设备将使用一系列的ssDNA和dsDNA长度进行测试，以确定每种类型的NFM如何影响易位和捕获。应用化学可调的外部涂层可以提高传感效率和分辨率，而不需要对纳米孔进行内在修改，这将直接支持开发基于纳米孔的可行测序和诊断平台的努力，因为它能够实现较慢的移位速度和增加的穿线概率。

DESCRIPTION (provided by applicant): While solid-state nanopores show promise as single-molecule sensors for biomedical applications, in order to improve their resolution and efficiency, analyte molecules must be probed more frequently and must remain longer in the nanopore sensing volume. This proposal describes a novel, simple, and versatile method to improve nanopore sensitivity and temporal resolution by slowing translocation speed and increasing capture efficiency via interactions outside the nanopore, while still leaving the nanopore itself available for further functionalization. This will be achieved by applying a chemically tunable nanofiber polymeric mesh (NFM) directly to a solid-state nanopore chip, where its fibers (hydrophobic, cationic, or anionic) may interact with analyte molecules during sensing from outside the nanopore, guiding them into the sensing volume and slowing their movement through it. The NFM is composed of a network of fibers (100-1000 nm diameter) formed from poly(?-caprolactone) (PCL) doped with poly(glycerol-co-?-caprolactone) (PGC), deposited onto a surface by electrospinning. The PGC component of this polymer may be modified to include a range of side groups which confer hydrophobic, anionic, or cationic properties to the NFM. The fiber size and mesh density may be controlled by adjusting the electrospinning parameters. Thus, adjustment of the polymer NFM parameters will be completely independent of alterations to the nanopore surface itself. A broad range of designer translocation properties will be accessible for any solid-state nanopore application through simple selection of an appropriate NFM. We will first construct nanopore-nanofiber mesh (NP-NFM) hybrid devices with different charge and mesh characteristics, then screen these devices to determine which combinations are suitable for nanopore sensing. Candidate devices will be tested using a range of ssDNA and dsDNA lengths to determine how each type of NFM affects translocation and capture. The application of an external, chemically tunable coating that can improve sensing efficiency and resolution without requiring intrinsic modification of the nanopore will directly support efforts t develop viable nanopore-based sequencing and diagnostic platforms by enabling slower translocation speeds and increased threading probability.