Magnetic Particle Spectroscopy for Detection of Influenza A Virus Subtype H1N1

Abstract

Magnetic nanoparticles (MNPs) with proper surface functionalization have been extensively applied as labels for magnetic immunoassays, carriers for controlled drug/gene delivery, tracers and contrasts for magnetic imaging, etc. Here, we introduce a new biosensing scheme based on magnetic particle spectroscopy (MPS) and the self-assembly of MNPs to quantitatively detect H1N1 nucleoprotein molecules. MPS monitors the harmonics of oscillating MNPs as a metric for the freedom of rotational process, thus indicating the bound states of MNPs. These harmonics can be readily collected from nanogram quantities of iron oxide nanoparticles within 10 s. The H1N1 nucleoprotein molecule hosts multiple different epitopes that forms binding sites for many IgG polyclonal antibodies. Anchoring IgG polyclonal antibodies onto MNPs triggers the cross-linking between MNPs and H1N1 nucleoprotein molecules, thereby forming MNP self-assemblies. Using MPS and the self-assembly of MNPs, we were able to detect as low as 44 nM (4.4 pmole) H1N1 nucleoprotein. In addition, the morphologies and the hydrodynamic sizes of the MNP self-assemblies are characterized to verify the MPS results. Different MNP self-assembly models such as classical cluster, open ring tetramer, and chain model as well as multimers (from dimer to pentamer) are proposed in this paper. Herein, we claim the feasibility of using MPS and the self-assembly of MNPs as a new biosensing scheme for detecting ultralow concentrations of target biomolecules, which can be employed as rapid, sensitive, and wash-free magnetic immunoassays.

Magnetic-Nanosensor-Based Virus and Pathogen Detection Strategies before and during COVID-19

“… 44 In a MPS platform, external sinusoidal magnetic fields (also called excitation fields) are applied to periodically magnetize (and magnetically saturate) the MNPs, as shown in Figure 5 A1,A3. 85 − 87 , 95 − 101 The time-varying dipolar magnetic fields generated by MNPs as a response to the applied fields ( Figure 5 A2,A4) are monitored by pick-up coils. As a result of Faraday’s law of induction, the time-varying electric voltages from pick-up coils are recorded and MPS spectra are extracted for analysis, as shown in Figure 5 A3,A6).…”

“…Wu et al reported the volume-based MPS immunoassay platform utilizing the polyclonal-antibody-induced cross-linking of MNPs for one step, the wash-free detection of H1N1 nucleoprotein molecules. 87 In their work, the MNPs are anchored with polyclonal IgG antibodies specific to H1N1 nucleoprotein. Each H1N1 nucleoprotein molecule has many epitopes serving as binding sites for IgG polyclonal antibodies.…”

“…(E and F) MPS measurements of the third and fifth harmonics from samples I–IX at varying driving field frequencies from 400 Hz to 20 kHz. Reproduced from ref ( 87 ). Copyright 2020 American Chemical Society.…”

Superparamagnetic Iron Oxide Nanoparticles and Essential Oils: A New Tool for Biological Applications

“…This principle was used for quantitatively detecting H1N1 nucleoprotein of Influenza A Virus (IAV) subtype H1N1. The authors [ 125 ] anchored IgG polyclonal antibodies onto SPIONs surfaces. The H1N1 nucleoprotein, which hosts multiple different epitopes for these IgG polyclonal antibodies, are able to cross-link between SPIONs (IgG from the particle surface) and H1N1 nucleoproteins, forming different degrees of SPIONs clusters, depending on the number/concentration of H1N1 nucleoprotein molecules in the magnetic nanoparticle ferrofluid.…”

Specific and sensitive detection of Influenza A virus using a biotin-coated nanoparticle enhanced immunomagnetic assay

“…The LoD was 4.7 μg mL −1 . Recently, Wu et al developed a wash-free assay based on magnetic particle spectroscopy (MPS) and the selfassembly of magnetic NP to quantitatively detect H1N1 NuP [23,24]. This rapid protocol reached the LoD of 0.25 μg mL −1 for NuP and 250 TCID 50 mL −1 for Influenza A virus.…”