Article

Dramatic enhancement of the detection limits of bioassays via ultrafast deposition of polydopamine

  • Nature Biomedical Engineering 1, Article number: 0082 (2017)
  • doi:10.1038/s41551-017-0082
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Abstract

The ability to detect biomarkers with ultrahigh sensitivity radically transformed biology and disease diagnosis. However, owing to incompatibilities with infrastructure in current biological and medical laboratories, recent innovations in analytical technology have not yet been adopted broadly. Here, we report a simple, universal ‘add-on’ technology (dubbed EASE) that converts the ordinary sensitivities of common bioassays to extraordinary ones, and that can be directly plugged into the routine practices of current research and clinical laboratories. The assay relies on the bioconjugation capabilities and ultrafast and localized deposition of polydopamine at the target site, which permit a large number of reporter molecules to be captured and lead to detection-sensitivity enhancements exceeding three orders of magnitude. The application of EASE in the ELISA-based detection of the HIV antigen in blood from patients leads to a sensitivity lower than 3 fg ml−1. We also show that EASE allows for the direct visualization, in tissues, of the Zika virus and of low-abundance biomarkers related to neurological diseases and cancer immunotherapy.

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Acknowledgements

This work was supported in part by the NIH (R21CA192985, R01AI100989, AI083019, AI104002, and AI060389) and the Department of Bioengineering at the University of Washington. J.L. thanks the Howard Hughes Medical Institute for a student fellowship. We are also grateful to B. Lutz and D. Leon for help with the lateral flow test, and P. Zrazhevskiy for discussions on immunostaining.

Author information

Affiliations

  1. Department of Bioengineering, University of Washington, Seattle, Washington 98195, USA.

    • Junwei Li
    • , Wanyi Tai
    •  & Xiaohu Gao
  2. Department of Pharmacology, University of Washington, Seattle, Washington 98105, USA.

    • Madison A. Baird
    •  & Larry S. Zweifel
  3. Department of Immunology, University of Washington, Seattle, Washington 98105, USA.

    • Michael A. Davis
    •  & Michael Gale Jr
  4. Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington 98105, USA.

    • Michael A. Davis
    • , Kristina M. Adams Waldorf
    • , Michael Gale Jr
    •  & Lakshmi Rajagopal
  5. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, Washington 98105, USA.

    • Larry S. Zweifel
  6. Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 98105, USA.

    • Kristina M. Adams Waldorf
  7. Department of Global Health, University of Washington, Seattle, Washington 98105, USA.

    • Kristina M. Adams Waldorf
    • , Michael Gale Jr
    •  & Lakshmi Rajagopal
  8. Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 3, Gothenburg 41390, Sweden.

    • Kristina M. Adams Waldorf
  9. Department of Pediatrics, University of Washington, Seattle, Washington 98105, USA.

    • Lakshmi Rajagopal
  10. Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, Washington 98101, USA.

    • Lakshmi Rajagopal
  11. Fred Hutchinson Cancer Research Center, Program in Immunology, 1100 Fairview Avenue N, Seattle, Washington 98109, USA.

    • Robert H. Pierce

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Contributions

J.L. and X.G. conceived the idea and designed the project. J.L. and W.T. performed the majority of the experiments, with help from M.A.B. and L.S.Z. for CRF imaging in the brain, from M.A.D., K.M.A.W., M.G. and L.R. for ZIKA imaging, and R.H.P. for PD-L1 imaging. All authors were involved in data analysis. J.L., L.S.Z., K.M.A.W., M.G., L.R., R.H.P. and X.G. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiaohu Gao.

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    Supplementary Information

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