CAREER: Amplification-Coupled Solid-State Nanopore Digital Counting based a Versatile Platform for Point-of-Care Nucleic Acid Testing

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This CAREER project supports an integrated research and education approach to address the fundamental and applied challenges in solid-state nanopore-based single molecule counting platform towards the fully integrated point-of-care nucleic acid testing. This project is motivated by a growing demand for decentralized nucleic acid testing for applications ranging from infectious disease, food safety to homeland security. In recognition of using nanopore as simple as a single molecule counter and the fact that target nucleic acids can be sensitively and specifically replicated in numbers during the amplification reaction, this project seeks to develop a solid-state nanopore-based point of care nucleic acid testing device in which sample preparation is fully integrated. The proposed research activities will be synergistically integrated with educational activities to provide hands-on based education to inspire and train future STEM leaders and to increase public awareness of biosensing devices and their societal impacts.The overall research objective of this proposal is to explore a highly sensitive nanopore digital counting paradigm for point-of-care nucleic acid testing. Due to its potential for minimization and integration, solid-state nanopore sensing is a rapidly evolving field. Considerable effort has been made for developing various applications. However, translating solid-state nanopore sensors to practical settings has seen limited progress as compared to their biological counterparts adopted in the DNA sequencing, mainly due to the challenges in reproducible size control, introducing specificity, prolonged sensing time at low analyte concentrations, and the lack of integrated sample preparation. The proposed work aims to address these issues and explore a fully integrated solid-state nanopore digital counting paradigm towards nucleic acid testing at the point of need. The research activity will address four research aims regarding the sensing kinetics, nanopore fabrication, cartridge and system integration, and validation. This research is multidisciplinary in nature and spans the range from fundamental to applied research, with low- and high-risk components. Together, they constitute a complete research program to advance and translating the solid-state nanopore sensors.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.