The Role of Nanoparticle Design in Determining Analytical Performance of Lateral Flow Immunoassays

Li Zhan, Shuang Zhuang Guo, Fayi Song, Yan Gong, Feng Xu, David R. Boulware, Michael C. McAlpine, Warren C.W. Chan, John C. Bischof

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Rapid, simple, and cost-effective diagnostics are needed to improve healthcare at the point of care (POC). However, the most widely used POC diagnostic, the lateral flow immunoassay (LFA), is ∼1000-times less sensitive and has a smaller analytical range than laboratory tests, requiring a confirmatory test to establish truly negative results. Here, a rational and systematic strategy is used to design the LFA contrast label (i.e., gold nanoparticles) to improve the analytical sensitivity, analytical detection range, and antigen quantification of LFAs. Specifically, we discovered that the size (30, 60, or 100 nm) of the gold nanoparticles is a main contributor to the LFA analytical performance through both the degree of receptor interaction and the ultimate visual or thermal contrast signals. Using the optimal LFA design, we demonstrated the ability to improve the analytical sensitivity by 256-fold and expand the analytical detection range from 3 log10 to 6 log10 for diagnosing patients with inflammatory conditions by measuring C-reactive protein. This work demonstrates that, with appropriate design of the contrast label, a simple and commonly used diagnostic technology can compete with more expensive state-of-the-art laboratory tests.

Original languageEnglish (US)
Pages (from-to)7207-7212
Number of pages6
JournalNano letters
Issue number12
StatePublished - Dec 13 2017

Bibliographical note

Funding Information:
This work is supported by Minnesota-Mayo Partnership Grant (J.C.B., D.R.B.), IEM Seed Grant (UM) and Kuhrmeyer Chair to J.C.B. The authors thank Dr. Zhenpeng Qin who helped train Mr. Zhan on thermal contrast, Dr. Zhe Gao for help with SEM imaging, and Kai Wang and Cathylin Wang for help with the experiments. W.C.W.C. acknowledges the Canadian Institutes of Health Research and Natural Sciences and Engineering Research Council of Canada. F.X. and G.Y. were financially supported by the National Instrumentation Program of China (2013YQ190467). D.R.B. acknowledges the National Institute of Health (R01NS086312). M.C.M. acknowledges the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award No. 1DP2EB020537). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2017 American Chemical Society.


  • C-reactive protein
  • Gold nanoparticles
  • immunoassay
  • size dependent
  • thermal contrast


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