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Regional and functional division of functional elements of solid-state nanochannels for enhanced sensitivity and specificity of biosensing in complex matrices

Nature Protocols volume 16, pages 4201–4226 (2021)Cite this article

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Abstract

Solid-state nanochannels (SSNs) provide a promising approach for biosensing due to the confinement of molecules inside, their great mechanical strength and diversified surface chemical properties; however, until now, their sensitivity and specificity have not satisfied the practical requirements of sensing applications, especially in complex matrices, i.e., media of diverse constitutions. Here, we report a protocol to achieve explicit regional and functional division of functional elements at the outer surface (FEOS) and inner wall (FEIW) of SSNs, which offers a nanochannel-based sensing platform with enhanced specificity and sensitivity. The protocol starts with the fabrication and characterization of the distribution of FEOS and FEIW. Then, the evaluation of the contributions of FEOS and FEIW to ionic gating is described; the FEIW mainly regulate ionic gating, and the FEOS can produce a synergistic effect. Finally, hydrophobic or highly charged FEOS are applied to ward off interference molecules, non-target molecules that may affect the ionic signal of nanochannels, which decreases false signals and helps to achieve the highly specific ionic output in complex matrices. Compared with other methods currently available, this method will contribute to the fundamental understanding of substance transport in SSNs and provide high specificity and sensitivity in SSN-based analyses. The procedure takes 3–6 d to complete.

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Fig. 1: FEOS and FEIW functionalized SSNs can be created and characterized for biosensing applications in complex matrices.
Fig. 2: Explicit spatial partitioning of FEs at the OS of nanochannels (FEOS) and at the IW of nanochannels (FEIW).
Fig. 3: Depth of IW and OS metal coating of nanochannels characterized by ToF-SIMS.
Fig. 4: Ionic and electrolytic output system.
Fig. 5: Highly efficient ion-gating systems using DNA supersandwich as FEs.
Fig. 6: Molecular formulae of glucose-sensing probes.
Fig. 7: Sensing performance of the ion-gating systems in complex matrices.

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The authors declare that the main data supporting the findings of this study are available within the article and its Supplementary Information files.

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Acknowledgements

This work is supported by the National Natural Science Foundation of China (22090050, 21974126, 21874121 and 51803194). This research is supported by the Hubei Provincial Natural Science Foundation of China (2020CFA037), Zhejiang Provincial Natural Science Foundation of China under grant nos. LY19B030001 and LD21B050001. The project is supported by the Open-end Funds from the Engineering Research Center of Nano-Geomaterials of thMinistry of Education (NGM2019KF013) and the Fundamental Research Funds for National Universities, China University of Geosciences (Wuhan). This research work was supported by the Open Funds of the State Key Laboratory of Electroanalytical Chemistry (SKLEAC202003) and the National Key Research and Development Program of China (2018YFE0206900).

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Authors and Affiliations

  1. State Key Laboratory of Biogeology and Environmental Geology, Engineering Research Center of Nano-Geomaterials of Ministry of Education, Faculty of Materials Science and Chemistry, China University of Geosciences (CUG), Wuhan, P. R. China

    Pengcheng Gao, Dagui Wang, Cheng Che, Qun Ma, Xiaoqing Wu, Yajie Chen, Hongquan Xu, Yu Lin, Defang Ding, Xiaoding Lou & Fan Xia

  2. Pharmaceutical Analysis Division, School of Pharmacy, Guangxi Medical University, Nanning, P. R. China

    Xinchun Li

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Contributions

F.X. directed the project. P.G. designed the research. D.W. and Q.M. organized the text about the preparation and modification of nanochannels. X.W and Y.C. organized the tables and the figures. X.L. organized the text about the electrochemical and fluorescent tests. P.G., C.C., X.W., D.D., Y.L. and Y.C. wrote the manuscript. All authors contributed to discussions.

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Correspondence to Fan Xia.

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Peer review information Nature Protocols thanks Hai-Chen Wu and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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Key references using this protocol

Gao, P. et al. Nat. Commun. 9, 4557 (2018): https://doi.org/10.1038/s41467-018-06873-z

Li, X. et al. Nat. Commun. 9, 40 (2018): https://doi.org/10.1038/s41467-018-03030-4

Xu, X. et al. NPG Asia Mater. 8, e234 (2016): https://doi.org/10.1038/am.2015.138

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Gao, P., Wang, D., Che, C. et al. Regional and functional division of functional elements of solid-state nanochannels for enhanced sensitivity and specificity of biosensing in complex matrices. Nat Protoc 16, 4201–4226 (2021). https://doi.org/10.1038/s41596-021-00574-6

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