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Register a new userPortable Magnetic Particle Spectrometer (MPS) for Future Rapid and Wash-free Bioassays
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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.
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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.
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.
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.
We demonstrate a portable all-optical intrinsic scalar magnetic gradiometer composed of miniaturized cesium vapor cells and vertical-cavity surface-emitting lasers (VCSELs). Two cells, with an inner dimension of 5 mm x 5 mm x 5 mm and separated by a baseline of 5 cm, are driven by one VCSEL and the resulting Larmor precessions are probed by a second VCSEL through optical rotation. The off-resonant linearly polarized probe light interrogates two cells at the same time and the output of the intrinsic gradiometer is proportional to the magnetic field gradient measured over the given baseline. This intrinsic gradiometer scheme has the advantage of avoiding added noise from combining two scalar magnetometers. We achieve better than 18 fT/cm/rt-Hz sensitivity in the gradient measurement. Ultra-sensitive short-baseline magnetic gradiometers can potentially play an important role in many practical applications, such as nondestructive evaluation and unexploded ordnance (UXO) detection. Another application of the gradiometer is for magnetocardiography (MCG) in an unshielded environment. Real-time MCG signals can be extracted from the raw gradiometer readings. The demonstrated gradiometer greatly simplifies the MCG setup and may lead to ubiquitous MCG measurement in the future.
An extensive comparison of the path uncertainty in single particle tracking systems for ion imaging was carried out based on Monte Carlo simulations. The spatial resolution as function of system parameters such as geometry, detector properties and the energy of proton and helium beams was investigated to serve as a guideline for hardware developments. Primary particle paths were sampled within a water volume and compared to the most likely path estimate obtained from detector measurements, yielding a depth-dependent uncertainty envelope. The maximum uncertainty along this curve was converted to a conservative estimate of the minimal radiographic pixel spacing for a single set of parameter values. Simulations with various parameter settings were analysed to obtain an overview of the reachable pixel spacing as function of system parameters. The results were used to determine intervals of detector material budget and position resolution that yield a pixel spacing small enough for clinical dose calculation. To ensure a pixel spacing below 2 mm, the material budget of a detector should remain below 0.25 % for a position resolution of 200 $mathrm{mu m}$ or below 0.75 % for a resolution of 10 $mathrm{mu m}$. Using protons, a sub-millimetre pixel size could not be achieved for a phantom size of 300 mm or at a large clearance. With helium ions, a sub-millimetre pixel spacing could be achieved even for a large phantom size and clearance, provided the position resolution was less than 100 $mathrm{mu m}$ and material budget was below 0.75 %.
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