Development of a Nanopore Scanner and Elucidation of Molecular Design Principles for Nanopore Conductance, Transport and Sensing Optimization

With the support of the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Jason Dwyer and his research team at the University of Rhode Island will develop new tools and approaches to better understand how to fabricate and use a powerful new class of nanopore sensors. Nanopore devices are commercially available for single-molecule DNA sensing that supports a wide range of health-related applications such as personalized medicine. They are being developed for identifying proteins to enable earlier detection of disease, alongside other medical purposes. Nanopore devices are also useful for a wide range of other functions such as desalination and high-density molecular data storage readout. Developing better understanding of how to construct and exploit nanopores will thus pay dividends across these various domains of technology and human health. The work will focus on understanding and exploiting nanopore surface coatings. It will begin with elucidating fundamental molecular-level mechanisms of how the chemical properties of the coatings affect nanopore performance. It will then extend to investigating how to more reliably and easily recognize the various chemical building blocks of proteins, as a prelude to more elaborate protein identification applications. Student training will be a vital part of this effort, with an emphasis on broadly transferable skill development spanning from fundamental research planning to technical skill development to project management. The technological implications of the work allow for workforce training opportunities that bridge academia and industry. A new apparatus and approach—a nanopore scanner—will be designed and built to streamline the in-depth assessment of the effect of nanopore surface coating on nanopore conductance—a core metric of performance, on molecular transport—a foundation of most nanopore sensing approaches, and on nanopore signal characteristics. The work will be distinguished by using a curated set of nanopore surface coatings designed to support more comprehensive, systematic, and improved mechanistic understanding of the connection between nanopore surface coatings and nanopore performance. The nanopore scanner will be central to carrying out the systematic studies designed to dissect the coating’s microscopic contributions to the nanopore-solution interface that dictate the nanopore conductance, transport, and sensing. A close examination of electroosmosis, a core mechanism to transport neutral, or locally neutral, species in nanopore sensing will be central to the proposed work because it connects molecular transport to nanopore surface coatings. Selected peptide targets will provide both molecular diversity and biological import for connecting the studies here to future applications of both broad health and technological relevance. 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.