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oai:figshare.com:article/34045531 2026-10-01T12:04:02Z category_4 category_146 category_8 category_14 category_734 category_132 portal_63 item_type_6 month_year_10_2026

Programmable Multisite Recognition Enables Amplification-Free Nanopore Detection of Mycobacterium tuberculosis in Sputum and Plasma Zhan Wang (283758) Yexiang Liu (1570966) Yanrong Chen (2611009) Ke Jiao (24241258) Lin Sun (105539) Wenjuan Nie (25156423) Siwei Wang (441466) Jing Wei (127335) Kaikai Chen (1385565) Weiwei Jiao (503411) Rui Hu (505795) Qing Zhao (170569) Biochemistry Space Science Microbiology Molecular Biology Biological Sciences not elsewhere classified Infectious Diseases single genomic locus nanopore readout provides multisite recognition strategy difficult clinical specimens demonstrated accurate identification flexible tuberculosis diagnostics mycobacterium tuberculosis (< low target abundance free nanopore detection mycobacterium tuberculosis work presents strain diversity results show reliable testing reduces dependence mtb </ direct detection binding events >) dna 5 copies Tuberculosis diagnostics remain challenged by low target abundance, strain diversity, and the need for reliable testing in difficult clinical specimens. Here, we develop an amplification-free nanopore sensing platform based on programmable linear DNA nanohook arrays for direct detection of Mycobacterium tuberculosis (<i>Mtb</i>) DNA. This work presents a dual-target, multisite recognition strategy that simultaneously captures two conserved insertion sequences, IS6110 and IS1081, and converts their binding events into resolvable nanopore electrical signatures. This design improves target recovery and reduces dependence on any single genomic locus, enabling robust detection across diverse <i>Mtb</i> strains. Using this approach, we achieved a limit of detection of 9.5 copies/μL and demonstrated accurate identification of <i>Mtb</i> in both sputum and plasma samples without nucleic acid amplification. Our results show that programmable multisite recognition combined with nanopore readout provides a powerful route toward sensitive, sample-flexible tuberculosis diagnostics. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acs.nanolett.6c03484.s001 https://figshare.com/articles/journal_contribution/Programmable_Multisite_Recognition_Enables_Amplification-Free_Nanopore_Detection_of_Mycobacterium_tuberculosis_in_Sputum_and_Plasma/34045531 CC BY-NC 4.0