Rapid and sensitive detection of SARS-CoV-2 with functionalized magnetic nanoparticles.

The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global medical systems and economies, and rules our daily living life. Controlling the outbreak of SARS-CoV-2 has become one of the most important and urgent strategies throughout the whole world. As of October, 2020, there have not yet been any medicines or therapies to be effective against SARS-CoV-2. Thus, rapid and sensitive diagnostics is the most important measures to control the outbreak of SARS-CoV-2. Homogeneous biosensing based on magnetic nanoparticles (MNPs) is one of the most promising approaches for rapid and highly sensitive detection of biomolecules. This paper proposes an approach for rapid and sensitive detection of SARS-CoV-2 with functionalized MNPs via the measurement of their magnetic response in an ac magnetic field. Experimental results demonstrate that the proposed approach allows the rapid detection of mimic SARS-CoV-2 with a limit of detection of 0.084 nM (5.9 fmole). The proposed approach has great potential for designing a low-cost and point-of-care device for rapid and sensitive diagnostics of SARS-CoV-2.

[1]  B Gleich,et al.  First experimental evidence of the feasibility of multi-color magnetic particle imaging , 2015, Physics in medicine and biology.

[2]  Thilo Viereck,et al.  Dual-frequency magnetic particle imaging of the Brownian particle contribution , 2017 .

[3]  Linqi Zhang,et al.  Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor , 2020, Nature.

[4]  B. Graham,et al.  Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation , 2020, Science.

[5]  Rob Phillips,et al.  SARS-CoV-2 (COVID-19) by the numbers , 2020, eLife.

[6]  Chin-Yih Hong,et al.  Wash-free, antibody-assisted magnetoreduction assays of orchid viruses. , 2008, Journal of virological methods.

[7]  Frank Ludwig,et al.  Fluxgate based detection of magnetic nanoparticle dynamics in a rotating magnetic field , 2011 .

[8]  Bernhard Gleich,et al.  Tomographic imaging using the nonlinear response of magnetic particles , 2005, Nature.

[9]  Michael Thompson,et al.  Harmonized guidelines for single-laboratory validation of methods of analysis (IUPAC Technical Report) , 2002 .

[10]  F. Ludwig,et al.  Magnetic nanoparticle temperature imaging with a scanning magnetic particle spectrometer , 2018, Measurement Science and Technology.

[11]  K. Yuen,et al.  Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2 , 2020, Cell.

[12]  Alankar Shrivastava,et al.  Methods for the determination of limit of detection and limit of quantitation of the analytical methods , 2011 .

[13]  M. F. Hansen,et al.  Homogeneous circle-to-circle amplification for real-time optomagnetic detection of SARS-CoV-2 RdRp coding sequence. , 2020, Biosensors & bioelectronics.

[14]  Victor M Corman,et al.  Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR , 2020, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin.

[15]  C. Y. Yang,et al.  Magnetically enhanced high-specificity virus detection using bio-activated magnetic nanoparticles with antibodies as labeling markers. , 2010, Journal of virological methods.

[16]  P. Woo,et al.  Phylogenetic and recombination analysis of coronavirus HKU1, a novel coronavirus from patients with pneumonia , 2005, Archives of Virology.

[17]  Shieh-Yueh Yang,et al.  Magnetic susceptibility reduction method for magnetically labeled immunoassay , 2006 .

[18]  Jian-Ping Wang,et al.  Real-time measurement of Brownian relaxation of magnetic nanoparticles by a mixing-frequency method , 2011 .

[19]  F. Ludwig,et al.  Dependence of biomolecule detection on magnetic nanoparticle concentration , 2021 .

[20]  Wolfgang J. Parak,et al.  Homogeneous Biosensing Based on Magnetic Particle Labels , 2016, Sensors.

[21]  Renata Saha,et al.  Magnetic Nanoparticle Relaxation Dynamics-Based Magnetic Particle Spectroscopy for Rapid and Wash-Free Molecular Sensing. , 2019, ACS applied materials & interfaces.

[22]  Ping Chen,et al.  Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission , 2020, Science China Life Sciences.

[23]  Barjor Gimi,et al.  Molecular sensing with magnetic nanoparticles using magnetic spectroscopy of nanoparticle Brownian motion. , 2013, Biosensors & bioelectronics.

[24]  Frank Ludwig,et al.  Binding assays with streptavidin-functionalized superparamagnetic nanoparticles and biotinylated analytes using fluxgate magnetorelaxometry , 2009 .

[25]  R. Peeling,et al.  Rapid tests for sexually transmitted infections (STIs): the way forward , 2006, Sexually Transmitted Infections.

[26]  H. Mao,et al.  Detecting the Coronavirus (COVID-19) , 2020, ACS sensors.

[27]  C. Hong,et al.  Ultra-highly sensitive and wash-free bio-detection of H5N1 virus by immunomagnetic reduction assays. , 2008, Journal of virological methods.

[28]  F. Ludwig,et al.  Magnetic nanoparticle-based biomolecule imaging with a scanning magnetic particle spectrometer , 2020, Nanotechnology.

[29]  E. Holmes,et al.  A new coronavirus associated with human respiratory disease in China , 2020, Nature.

[30]  A. M. Leontovich,et al.  The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 , 2020, Nature Microbiology.

[31]  Bingliang Zeng,et al.  Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT? , 2020, European Journal of Radiology.

[32]  Yan Liu,et al.  Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV , 2020, Nature Communications.

[33]  G. Gao,et al.  A Novel Coronavirus from Patients with Pneumonia in China, 2019 , 2020, The New England journal of medicine.

[34]  Hongzhou Lu,et al.  Outbreak of pneumonia of unknown etiology in Wuhan, China: The mystery and the miracle , 2020, Journal of medical virology.