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Register a new userDetection of Influenza A Virus Nucleoprotein Through the Self-Assembly of Nanoparticles in Magnetic Particle Spectroscopy-Based Bioassays: A Method for Rapid, Sensitive, and Wash-free Magnetic Immunoassays
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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 motion, thus indicating the bound states of MNPs. These harmonics can be readily collected from nanogram quantities of iron oxide nanoparticles within 10 s. 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 achieved the sensitivity of 44 nM (442 pmole) for detecting 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, 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.
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Nowadays, there is an increasing demand for more accessible routine diagnostics for patients with respect to high accuracy, ease of use, and low cost. However, the quantitative and high accuracy bioassays in large hospitals and laboratories usually require trained technicians and equipment that is both bulky and expensive. In addition, the multi-step bioassays and long turnaround time could severely affect the disease surveillance and control especially in pandemics such as influenza and COVID-19. In view of this, a portable, quantitative bioassay device will be valuable in regions with scarce medical resources and help relieve burden on local healthcare systems. Herein, we introduce the MagiCoil diagnostic device, an inexpensive, portable, quantitative and rapid bioassay platform based on magnetic particle spectrometer (MPS) technique. MPS detects the dynamic magnetic responses of magnetic nanoparticles (MNPs) and uses the harmonics from oscillating MNPs as metrics for sensitive and quantitative bioassays. This device does not require trained technicians to operate and employs a fully automatic, one-step, wash-free assay with user friendly smartphone interface. Using a streptavidin-biotin binding system as a model, we show that the detection limit of the current portable device for streptavidin is 64 nM (equal to 5.12 pmole). In addition, this MPS technique is very versatile and allows for the detection of different diseases just by changing the surface modifications on MNPs.
In recent years, magnetic particle spectroscopy (MPS) has become a highly sensitive and versatile sensing technique for quantitative bioassays. It relies on the dynamic magnetic responses of magnetic nanoparticles (MNPs) for the detection of target analytes in liquid phase. There are many research studies reporting the application of MPS for detecting a variety of analytes including viruses, toxins, and nucleic acids, etc. Herein, we report a modified version of MPS platform with the addition of a one-stage lock-in design to remove the feedthrough signals induced by external driving magnetic fields, thus capturing only MNP responses for improved system sensitivity. This one-stage lock-in MPS system is able to detect as low as 781 ng multi-core Nanomag50 iron oxide MNPs (micromod Partikeltechnologie GmbH) and 78 ng single-core SHB30 iron oxide MNPs (Ocean NanoTech). In addition, using a streptavidin-biotin binding system as a proof-of-concept, we show that these single-core SHB30 MNPs can be used for Brownian relaxation-based bioassays while the multi-core Nanomag50 cannot be used. The effects of MNP amount on the concentration dependent response profiles for detecting streptavidin was also investigated. Results show that by using lower concentration/amount of MNPs, concentration-response curves shift to lower concentration/amount of target analytes. This lower concentrationresponse indicates the possibility of improved bioassay sensitivities by using lower amounts of MNPs.
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.
The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is a threat to the global healthcare system and economic security. As of July 2020, no specific drugs or vaccines are yet available for COVID-19, fast and accurate diagnosis for SARS-CoV-2 is essential in slowing down the spread of COVID-19 and for efficient implementation of control and containment strategies. Magnetic immunoassay is a novel and emerging topic representing the frontiers of current biosensing and magnetics areas. The past decade has seen rapid growth in applying magnetic tools for biological and biomedical applications. Recent advances in magnetic materials and nanotechnologies have transformed current diagnostic methods to nanoscale and pushed the detection limit to early stage disease diagnosis. Herein, this review covers the literatures of magnetic immunoassay platforms for virus and pathogen detections, before COVID-19. We reviewed the popular magnetic immunoassay platforms including magnetoresistance (MR) sensors, magnetic particle spectroscopy (MPS), and nuclear magnetic resonance (NMR). Magnetic Point-of-Care (POC) diagnostic kits are also reviewed aiming at developing plug-and-play diagnostics to manage the SARS-CoV-2 outbreak as well as preventing future epidemics. In addition, other platforms that use magnetic materials as auxiliary tools for enhanced pathogen and virus detections are also covered. The goal of this review is to inform the researchers of diagnostic and surveillance platforms for SARS-CoV-2 and their performances.
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 detection of SARS-CoV-2 biomarkers: spike and nucleocapsid proteins.
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