High-Voltage Biomolecular Sensing Using a Bacteriophage Portal Protein Covalently Immobilized within a Solid-State Nanopore

Mehrnaz Mojtabavi, Sandra J Greive, Alfred A Antson, Meni Wanunu

Research output: Contribution to journalArticlepeer-review


The application of nanopores as label-free, single-molecule biosensors for electrical or optical probing of structural features in biomolecules has been widely explored. While biological nanopores (membrane proteins and bacteriophage portal proteins) and solid-state nanopores (thin films and two-dimensional materials) have been extensively employed, the third class of nanopores known as hybrid nanopores, where an artificial membrane substitutes the organic support membrane of proteins, has been only sparsely studied due to challenges in implementation. G20c portal protein contains a natural DNA pore that is used by viruses for filling their capsid with viral genomic DNA. We have previously developed a lipid-free hybrid nanopore by "corking" the G20c portal protein into a SiN x nanopore. Herein, we demonstrate that through chemical functionalization of the synthetic nanopore, covalent linkage between the solid-state pore and the G20c portal protein considerably improves the hybrid pore stability, lifetime, and voltage resilience. Moreover, we demonstrate electric-field-driven and motor protein-mediated transport of DNA molecules through this hybrid nanopore. Our integrated protein/solid-state device can serve as a robust and durable framework for sensing and sequencing at high voltages, potentially providing higher resolution, higher signal-to-noise ratio, and higher throughput compared to the more conventional membrane-embedded protein platforms.

Original languageEnglish
Pages (from-to)22540–22548
Number of pages9
JournalJournal of the American Chemical Society
Issue number49
Early online date1 Dec 2022
Publication statusPublished - 14 Dec 2022

Bibliographical note

© 2022 American Chemical Society. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

Cite this