Nature Communications (Nov 2023)
Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes
- Ren Ren,
- Shenglin Cai,
- Xiaona Fang,
- Xiaoyi Wang,
- Zheng Zhang,
- Micol Damiani,
- Charlotte Hudlerova,
- Annachiara Rosa,
- Joshua Hope,
- Nicola J. Cook,
- Peter Gorelkin,
- Alexander Erofeev,
- Pavel Novak,
- Anjna Badhan,
- Michael Crone,
- Paul Freemont,
- Graham P. Taylor,
- Longhua Tang,
- Christopher Edwards,
- Andrew Shevchuk,
- Peter Cherepanov,
- Zhaofeng Luo,
- Weihong Tan,
- Yuri Korchev,
- Aleksandar P. Ivanov,
- Joshua B. Edel
Affiliations
- Ren Ren
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- Shenglin Cai
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- Xiaona Fang
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Aptamer Selection Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
- Xiaoyi Wang
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- Zheng Zhang
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Aptamer Selection Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
- Micol Damiani
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- Charlotte Hudlerova
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- Annachiara Rosa
- The Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute
- Joshua Hope
- The Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute
- Nicola J. Cook
- The Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute
- Peter Gorelkin
- National University of Science and Technology “MISIS”
- Alexander Erofeev
- National University of Science and Technology “MISIS”
- Pavel Novak
- ICAPPIC Limited
- Anjna Badhan
- Molecular Diagnostic Unit, Section of Virology, Department of Infectious Disease, Faculty of Medicine, Imperial College London
- Michael Crone
- Section of Structural and Synthetic Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London
- Paul Freemont
- Section of Structural and Synthetic Biology, Department of Infectious Disease, Faculty of Medicine, Imperial College London
- Graham P. Taylor
- Molecular Diagnostic Unit, Section of Virology, Department of Infectious Disease, Faculty of Medicine, Imperial College London
- Longhua Tang
- State Key Laboratory of Modern Optical Instrumentation, College of Optical Science and Engineering, International Research Center for Advanced Photonics, Zhejiang University
- Christopher Edwards
- Department of Metabolism, Digestion and Reproduction, Imperial College London
- Andrew Shevchuk
- Department of Metabolism, Digestion and Reproduction, Imperial College London
- Peter Cherepanov
- The Chromatin Structure and Mobile DNA Laboratory, The Francis Crick Institute
- Zhaofeng Luo
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Aptamer Selection Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
- Weihong Tan
- The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Aptamer Selection Center, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences
- Yuri Korchev
- Department of Metabolism, Digestion and Reproduction, Imperial College London
- Aleksandar P. Ivanov
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- Joshua B. Edel
- Department of Chemistry, Imperial College London, Molecular Sciences Research Hub
- DOI
- https://doi.org/10.1038/s41467-023-43004-9
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 16
Abstract
Abstract We report on single-molecule nanopore sensing combined with position-encoded DNA molecular probes, with chemistry tuned to simultaneously identify various antigen proteins and multiple RNA gene fragments of SARS-CoV-2 with high sensitivity and selectivity. We show that this sensing strategy can directly detect spike (S) and nucleocapsid (N) proteins in unprocessed human saliva. Moreover, our approach enables the identification of RNA fragments from patient samples using nasal/throat swabs, enabling the identification of critical mutations such as D614G, G446S, or Y144del among viral variants. In particular, it can detect and discriminate between SARS-CoV-2 lineages of wild-type B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.539 (Omicron) within a single measurement without the need for nucleic acid sequencing. The sensing strategy of the molecular probes is easily adaptable to other viral targets and diseases and can be expanded depending on the application required.