Tunable Nanofiber Mesh Coatings for Improved Nanopores Sensing

描述（由申请人提供）：虽然固态纳米孔作为生物医学应用的单分子传感器显示出前景，但为了提高其分辨率和效率，分析物分子必须更频繁地探测，并且必须在纳米孔传感体积中停留更长时间。该提案描述了一种新颖、简单、通用的方法，通过减缓易位速度和通过纳米孔外的相互作用提高捕获效率来提高纳米孔的灵敏度和时间分辨率，同时仍然使纳米孔本身可进一步功能化。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，其中其纤维（疏水，阳离子或阴离子）可能在从纳米孔外传感期间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通过它的运动。NFM由直径100- 1000nm的聚（?）-己内酯（PCL）掺杂聚甘油-co-？-己内酯)(PGC)，通过静电纺丝沉积在表面上。该聚合物的PGC组分可以被修饰为包括一系列赋予NFM疏水、阴离子或阳离子性质的侧基。通过调整静电纺丝参数，可以控制纤维的细度和网密度。因此，聚合物NFM参数的调整将完全独立于纳米孔表面本身的改变。通过简单选择合适的NFM，任何固态纳米孔应用都可以获得广泛的设计易位特性。我们将首先构建具有不同电荷和网格特性的纳米-纳米纤维网（NP-NFM）混合器件，然后对这些器件进行筛选，以确定哪些组合适合用于纳米孔传感。候选设备将使用一系列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。外部化学可调涂层的应用可以提高传感效率和分辨率，而无需对纳米孔进行内在修饰，这将直接支持开发可行的基于纳米孔的测序和诊断平台，从而实现更慢的易位速度和更高的穿线概率。

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.