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

在化学测量和成像项目、大分子、超分子和纳米化学项目（化学系）以及纳米生物传感项目（化学、生物工程、环境和运输系统系）的支持下，罗德岛大学的杰森·德怀尔教授和他的团队正在开发新的纳米传感器，以更好地表征一类重要的生物分子，即多糖或聚糖。聚糖作为能量来源、重要生物过程中的标志物发挥着重要作用，还具有治疗功能——例如，抗凝血肝素是最突出的医学上有用的多糖。聚糖的鉴定和表征是非常具有挑战性的，部分原因是它们由100多种不同的糖构建块以各种不同的方式连接而成。药物安全可能需要检测细微的、通常是低丰度的变异；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而廉价的工具，用于选择性分析/筛选聚糖样品。参与这项多学科工作的学生了解化学测量设备的纳米制造，这些设备有可能在需要的地方轻松使用，而不仅仅是在由训练有素的科学家组成的专业化学实验室中使用。因此，更广泛的影响不仅来自潜在的基于纳米孔的肝素等目标检测，还来自学生在课堂和实验室中接触到的微流体、3D打印和计算机辅助设计的原理和实践，以及创新和技术转移的本质。Dwyer团队采用的方法是利用纳米孔制造单分子传感器和操纵器。具体来说，有代表性的多糖是用不同尺寸和表面化学性质（如电荷极性）的薄膜氮化硅纳米孔靶向的。共价和非共价标记的聚糖是用来调整灵敏度和选择性。多糖之间的相互作用也在研究中。更广泛地说，这项工作解决了糖组学、基因组学和蛋白质组学中化学功能化纳米孔的设计和可重复性，理想情况下具有广泛采用的低障碍潜力。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.