One-Step, Wash-free, Nanoparticle Clustering-Based Magnetic Particle Spectroscopy Bioassay Method for Detection of SARS-CoV-2 Spike and Nucleocapsid Proteins in the Liquid Phase

Kai Wu, Vinit Kumar Chugh, Venkatramana D. Krishna, Arturo Di Girolamo, Yongqiang Andrew Wang, Renata Saha, Shuang Liang, Maxim C.J. Cheeran, Jian Ping Wang

Research output: Contribution to journalArticlepeer-review


With the ongoing global pandemic of coronavirus disease 2019 (COVID-19), there is an increasing quest for more accessible, easy-to-use, rapid, inexpensive, and high-accuracy diagnostic tools. Traditional disease diagnostic methods such as qRT-PCR (quantitative reverse transcription-PCR) and ELISA (enzyme-linked immunosorbent assay) require multiple steps, trained technicians, and long turnaround time that may worsen the disease surveillance and pandemic control. In sight of this situation, a rapid, one-step, easy-to-use, and high-accuracy diagnostic platform will be valuable for future epidemic control, especially for regions with scarce medical resources. Herein, we report a magnetic particle spectroscopy (MPS) platform for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) biomarkers: spike and nucleocapsid proteins. This technique monitors the dynamic magnetic responses of magnetic nanoparticles (MNPs) and uses their higher harmonics as a measure of the nanoparticles' binding states. By anchoring polyclonal antibodies (pAbs) onto MNP surfaces, these nanoparticles function as nanoprobes to specifically bind to target analytes (SARS-CoV-2 spike and nucleocapsid proteins in this work) and form nanoparticle clusters. This binding event causes detectable changes in higher harmonics and allows for quantitative and qualitative detection of target analytes in the liquid phase. We have achieved detection limits of 1.56 nM (equivalent to 125 fmole) and 12.5 nM (equivalent to 1 pmole) for detecting SARS-CoV-2 spike and nucleocapsid proteins, respectively. This MPS platform combined with the one-step, wash-free, nanoparticle clustering-based assay method is intrinsically versatile and allows for the detection of a variety of other disease biomarkers by simply changing the surface functional groups on MNPs.

Original languageEnglish (US)
JournalACS Applied Materials and Interfaces
StatePublished - Sep 22 2021

Bibliographical note

Funding Information:
This study was financially supported by the Institute of Engineering in Medicine, the Robert F. Hartmann Endowed Chair professorship, the University of Minnesota Medical School, and the University of Minnesota Physicians and Fairview Health Services through COVID-19 Rapid Response Grant. This study was also financially supported by the U.S. Department of Agriculture—National Institute of Food and Agriculture (NIFA) under award number 2020-67021-31956. Research reported in this publication was supported by the National Institute Of Dental & Craniofacial Research of the National Institutes of Health under award number R42DE030832. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) under award number ECCS-1542202.

Publisher Copyright:
© 2021 American Chemical Society.


  • COVID-19
  • SARS-CoV-2
  • disease diagnostics
  • magnetic nanoparticle
  • magnetic particle spectroscopy
  • nucleocapsid protein
  • spike protein


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