Sub-femtomolar drug monitoring via co-calibration mechanism with nanoconfined DNA probes

Yonghuan Chen, Xiuying Li, Xinru Yue, Weihua Yu, Yuesen Shi, Zilong He, Yuanfeng Wang, Yu Huang (), Fan Xia and Fengyu Li ()
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Yonghuan Chen: Jinan University
Xiuying Li: Jinan University
Xinru Yue: Jinan University
Weihua Yu: Jinan University
Yuesen Shi: Guangdong Province Key Laboratory of Psychoactive Substances Monitoring and Safety
Zilong He: Jinan University
Yuanfeng Wang: China University of Political Science and Law
Yu Huang: China University of Geosciences
Fan Xia: China University of Geosciences
Fengyu Li: Jinan University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Synthetic drugs fundamentally reshape the illicit drug market due to their low cost, ease of production, and rapid manufacturing processes. However, current drug detection methods, which rely on complex instruments, have limited applicability and often neglect the influence of pH fluctuations, leading to potential bias and unreliable results. Herein, we propose co-calibration DNA probes on a nanoconfined biosensor (NCBS), covering the range of sweat pH 3–8 to achieve significantly enhanced target signal recognition. The NCBS exhibits a linear response range of 103-108 fM with a low limit of detection (LOD) of 3.58 fM in artificial sweat. Compared to the single-aptamer NCBS, the dual-aptamer NCBS offers a broader linear response range, primarily due to the synergistic effects of changes in surface wettability and the capture of hydrion, which together reduce signal interference in proton transport. The linear response range doubles, and its detection sensitivity improves by 4–5 orders of magnitude compared to existing drug detection methods. This sensing strategy expands the application scope of aptamer-based composite probes, offering an approach for ultra-sensitive drug detection and demonstrating significant potential in sweat sensing and drug monitoring fields.

Date: 2025
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DOI: 10.1038/s41467-025-57112-1

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