Gauging and Optimizing Solid-State Nanopore Sensing Performance for Polysaccharide Sensing and Glycomics

在化学测量和成像计划、大分子、超分子和纳米化学计划(化学系)以及纳米生物传感计划(化学、生物工程、环境和运输系统系)的支持下，罗德岛大学的Jason Dwyer教授和他的团队正在开发新的纳米级传感器，以更好地表征一类重要的生物分子，即多糖或多糖。葡聚糖作为一种能量来源，在重要的生物过程中发挥着重要的作用，也可以起到治疗作用--例如，抗凝血剂肝素是最有医学价值的多糖。鉴定和鉴定葡聚糖可能非常具有挑战性，部分原因是它们是由100多个不同的糖组成的，以各种不同的方式连接在一起。药物安全可能需要检测到微妙且往往低丰度的变异；2008年，未能检测到肝素中的有毒污染物导致美国约100人死亡。Dwyer小组正在开发一种快速且廉价的工具，用于选择性分析/筛选多糖样本。参与这项多学科工作的学生学习纳米制造化学测量设备，这些设备有可能在需要的地方轻松使用，而不仅仅是在配备有训练有素的科学家的专门化学实验室中使用。因此，更广泛的影响不仅来自潜在的基于纳米孔的目标分析，如肝素，还来自学生课堂和实验室对微流体、3D打印和计算机辅助设计的原理和实践的接触，以及创新和技术转让的性质。Dwyer小组采用的方法是将纳米孔用于单分子传感器和操纵器。具体地说，代表性的多糖是使用不同大小和表面化学成分(如电荷极性)的薄膜氮化硅纳米孔作为目标的。共价和非共价标记的多糖被用来调节灵敏度和选择性。多糖之间的相互作用也在研究中。更广泛地说，这项工作解决了用于糖组学、基因组学和蛋白质组学的化学功能化纳米孔的设计和重现性，理想地具有广泛采用的低障碍的可能性。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With support from the Chemical Measurement and Imaging Program and the Macromolecular, Supramolecular and Nanochemistry Program (Division of Chemistry), and the Nanobiosensing Program (Division of Chemical, Bioengineering, Environmental, and Transport Systems), Professor Jason Dwyer and his group at the University of Rhode Island are developing new nanofabricated sensors to enable better characterization of an important class of biomolecules known as polysaccharides, or glycans. Glycans play important roles as a source of energy, as markers in important biological processes, and can also serve therapeutic functions - for example, the anticoagulant heparin is the most prominent medically useful polysaccharide. Identification and characterization of glycans can be incredibly challenging, in part because they are made from more than 100 different sugar building blocks connected in a variety of different ways. Drug safety can require detection of subtle and often low-abundance variants; in 2008, failure to detect a toxic contaminant in heparin resulted in ~100 deaths in the U.S. The Dwyer group is developing a rapid and inexpensive tool for selective analysis/screening of glycan samples. Students involved in this multidisciplinary work learn about nanofabrication of chemical measurement devices that have the potential to be used easily where they are needed, not just in a specialized chemistry laboratory staffed by highly trained scientists. Thus, broader impacts derive not only from potential nanopore-based assays for targets like heparin, but also from student classroom and laboratory exposure to the principles and practice of microfluidics, 3D printing, and computer-aided design, as well as the nature of innovation and technology transfer.The approach taken by the Dwyer group utilizes nanopores for single molecule sensors and manipulators. Specifically, representative polysaccharides are being targeted using thin-film silicon nitride nanopores of varying sizes and surface chemistries (e.g. charge-polarity). Covalent and noncovalent labelling of the glycans is used to tune sensitivity and selectivity. Interactions among polysaccharides are also being studied. More broadly, the work addresses the design and reproducibility of chemically functionalized nanopores for glycomics, genomics, and proteomics, ideally with the potential for low barriers to widespread adoption.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.