Magnetic Particle Spectroscopy for Point-of-Care: A Review on Recent Advances.

Since its first report in 2006, magnetic particle spectroscopy (MPS)-based biosensors have flourished over the past decade. Currently, MPS are used for a wide range of applications, such as disease diagnosis, foodborne pathogen detection, etc. In this work, different MPS platforms, such as dual-frequency and mono-frequency driving field designs, were reviewed. MPS combined with multi-functional magnetic nanoparticles (MNPs) have been extensively reported as a versatile platform for the detection of a long list of biomarkers. The surface-functionalized MNPs serve as nanoprobes that specifically bind and label target analytes from liquid samples. Herein, an analysis of the theories and mechanisms that underlie different MPS platforms, which enable the implementation of bioassays based on either volume or surface, was carried out. Furthermore, this review draws attention to some significant MPS platform applications in the biomedical and biological fields. In recent years, different kinds of MPS point-of-care (POC) devices have been reported independently by several groups in the world. Due to the high detection sensitivity, simple assay procedures and low cost per run, the MPS POC devices are expected to become more widespread in the future. In addition, the growth of telemedicine and remote monitoring has created a greater demand for POC devices, as patients are able to receive health assessments and obtain results from the comfort of their own homes. At the end of this review, we comment on the opportunities and challenges for POC devices as well as MPS devices regarding the intensely growing demand for rapid, affordable, high-sensitivity and user-friendly devices.

Five-Minute Magnetic Nanoparticle Spectroscopy-Based Bioassay for Ultrafast Detection of SARS-CoV-2 Spike Protein.

In this work, we report a 5-min magnetic particle spectroscopy (MPS)-based bioassay strategy. In our approach, surface-functionalized magnetic nanoparticles are incubated with target analytes at 37 °C with agitation for 3 min, and the MPS reading is then taken at the fifth minute. We prove the feasibility of 5 min ultrafast detection of SARS-CoV-2 spike protein with a detection limit below 5 nM (0.2 pmol). Our proposed 5-min bioassay strategy may be applied to reduce the assay time for other liquid-phase, volumetric biosensors such as NMR, quantum dots, fluorescent biosensors, etc.

Clinical value of laboratory indicators for predicting disease progression and death in patients with COVID-19: a retrospective cohort study.

OBJECTIVES: As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: Hospital-based study in China. PARTICIPANTS: Adult patients with COVID-19 from December 15, 2019 to March 15, 2020. END POINT: Disease severity and mortality. METHODS: Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis. RESULTS: 29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05). CONCLUSIONS: The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.

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.

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.

Magnetic Particle Spectroscopy with One-Stage Lock-In Implementation for Magnetic Bioassays with Improved Sensitivities.

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 the liquid phase. There are many research studies reporting the application of MPS for detecting a variety of analytes including viruses, toxins, nucleic acids, and so forth. Herein, we report a modified version of the 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). We first demonstrated the performance of this MPS system for bioassay-related applications. Using the SARS-CoV-2 spike protein as a model, we have achieved a detection limit of 125 nM (equal to 5 pmole) for detecting spike protein molecules in the liquid phase. 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 were also investigated. Results show that by using a lower concentration/ amount of MNPs, concentration-response curves shift to a lower concentration/amount of target analytes. This lower concentration-response indicates the possibility of improved bioassay sensitivities by using lower amounts of MNPs.

A Portable Magnetic Particle Spectrometer for Future Rapid and Wash-Free Bioassays.

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 multistep 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 the 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, and wash-free assay with a 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. Although MPS-based bioassays show high sensitivities as reported in many literatures, at the current stage, this portable device faces insufficient sensitivity and needs further improvements. It is foreseen that this kind of portable device can transform the multistep, laboratory-based bioassays to one-step field testing in nonclinical settings such as schools, homes, offices, etc.

Computed tomography in coronavirus disease 2019: diagnosis and clinical significance

Objective To investigate the computed tomography (CT) features of the coronavirus disease 2019 (COVID-19) and the clinical significance, so as to improve our understanding of CT imaging of this disease. Methods The chest CT features of seven COVID-19 patients, who were diagnosed by virus nucleic acid test from Jan. 25 to Feb. 15, 2020 in Changhai Hospital of Naval Medical University (Second Military Medical University), were analyzed retrospectively. There were six males and one female, aged (51.1±18.8) years (range 29-75 years). All the seven patients received chest CT plain scan examimation. The CT images were interpreted by two experienced senior radiologists, and the distribution, location and density of lesions, number of involved lobes, air bronchogram, mediastinal lymphadenopathy and pleural effusion were analyzed. Results The average time from onset of symptoms to CT examination was 3.6 d (range 1-9 d) in the seven COVID-19 patients. The lesions were distributed in single lung in one case and bilateral lungs in six cases. The lesions involved middle and lateral fields of lungs in five cases and the whole field of lungs in two cases. The lesions showed ground-glass opacity in four cases and mixed shadow in three cases. The lesions involved two or less lobes in four cases and five lobes in three cases. One case had air bronchogram. No mediastinal lymphadenopathy or pleural effusion were found. Conclusion COVID-19 patients have characteristic CT findings, which has important clinical significance for the diagnosis and treatment of COVID-19. However, the diagnosis should be confirmed based on the patient's epidemic history, clinical symptoms and laboratory indicators.

Magnetic Nanosensor-Based Virus and Pathogen Detection Strategies Before and During COVID-19

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 nanosensor 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 nanomaterials 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 nanosensors for virus and pathogen detections, before COVID-19. We reviewed the popular magnetic nanosensors 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 nanomaterials 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.