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A nanogap-enhanced SERS nanotag–based lateral flow assay for ultrasensitive and simultaneous monitoring of SARS-CoV-2 S and NP antigens

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Abstract

A lateral flow assay (LFA) strip based on dual 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB)–encoded satellite Fe3O4@Au (Mag@Au) SERS tags with nanogap is reported for  ultrasensitive and simultaneous diagnosis of two SARS-CoV-2 functional proteins. Composed of Fe3O4 core, satellite gold shell with nanogaps, and double-layer DTNB, the Mag@Au nanoparticles with an average size of 238 nm were designed as multifunctional tags to efficiently enrich the target SARS-CoV-2 protein from complex samples, significantly enhancing the SERS signal of the LFA strip and provide quantitative SERS detection of analyte on test lines. The developed dual DTNB-encoded satellite Mag@Au-based LFA allowed simultaneous quantification of spike (S) protein and nucleocapsid (NP) protein with detection limits of 23 pg mL−1 and 2 pg mL−1, respectively, lower than commercial ELISA kits and reported SERS-LFA detection system–based Au NPs and Fe3O4@3 nm Au MNPs. This magnetic SERS-LFA also showed high performance of multi-variant strain detection and further distinguished clinical samples of Omicron variant infection, demonstrating the potential of in situ detection of respiratory virus diseases.

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Funding

This study was supported by the National Key Research and Development Program of China (Grant nos. 2021YFC2301102).

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Author notes

  1. Xiaoxian Liu and Xingsheng Yang contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People’s Republic of China

    Xiaoxian Liu, Xingsheng Yang & Rui Xiao

  2. College of Engineering and Applied Sciences, Nanjing University, Jiangsu, 210093, People’s Republic of China

    Xiaoxian Liu & Guanghui Wang

  3. Bioinformatics Center of AMMS, Beijing, 100850, People’s Republic of China

    Xingsheng Yang, Qiqi Liu & Yanlei Ding

  4. Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510000, People’s Republic of China

    Chongwen Wang

  5. GI Department, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China

    Shiping Xu

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  1. Xiaoxian Liu
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Contributions

RX, GHW, and CWW designed and managed the project. XXL and XSY performed all the experiments. QQL and YLD did the analysis of PCR. SPX provided clinical samples. XXL and XSY wrote the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Shiping Xu, Guanghui Wang or Rui Xiao.

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Liu, X., Yang, X., Wang, C. et al. A nanogap-enhanced SERS nanotag–based lateral flow assay for ultrasensitive and simultaneous monitoring of SARS-CoV-2 S and NP antigens. Microchim Acta 191, 104 (2024). https://doi.org/10.1007/s00604-023-06126-x

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