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.

Magnetoimpedance Biosensors and Real-Time Healthcare Monitors: Progress, Opportunities, and Challenges.

A small DC magnetic field can induce an enormous response in the impedance of a soft magnetic conductor in various forms of wire, ribbon, and thin film. Also known as the giant magnetoimpedance (GMI) effect, this phenomenon forms the basis for the development of high-performance magnetic biosensors with magnetic field sensitivity down to the picoTesla regime at room temperature. Over the past decade, some state-of-the-art prototypes have become available for trial tests due to continuous efforts to improve the sensitivity of GMI biosensors for the ultrasensitive detection of biological entities and biomagnetic field detection of human activities through the use of magnetic nanoparticles as biomarkers. In this review, we highlight recent advances in the development of GMI biosensors and review medical devices for applications in biomedical diagnostics and healthcare monitoring, including real-time monitoring of respiratory motion in COVID-19 patients at various stages. We also discuss exciting research opportunities and existing challenges that will stimulate further study into ultrasensitive magnetic biosensors and healthcare monitors based on the GMI effect.

Contribution of magnetic particles in molecular diagnosis of human viruses.

Viral diseases are the primary source of death, making a worldwide influence on healthcare, social, and economic development. Thus, diagnosis is the vital approach to the main aim of virus control and elimination. On the other hand, the prompt advancement of nanotechnology in the field of medicine possesses the probability of being beneficial to diagnose infections normally in labs as well as specifically. Nanoparticles are efficiently in use to make novel strategies because of permitting analysis at cellular in addition to the molecular scale. Henceforth, they assist towards pronounced progress concerning molecular analysis at the nanoscale. In recent times, magnetic nanoparticles conjugated through covalent bonds to bioanalytes for instance peptides, antibodies, nucleic acids, plus proteins are established like nanoprobes aimed at molecular recognition. These modified magnetic nanoparticles could offer a simple fast approach for extraction, purification, enrichment/concentration, besides viruses' recognition precisely also specifically. In consideration of the above, herein insight and outlook into the limitations of conventional methods and numerous roles played by magnetic nanoparticles to extract, purify, concentrate, and additionally in developing a diagnostic regime for viral outbreaks to combat viruses especially the ongoing novel coronavirus (COVID-19).

Paper-Based Test for Rapid On-Site Screening of SARS-CoV-2 in Clinical Samples.

Detection methods for monitoring infectious pathogens has never been more important given the need to contain the spread of the COVID-19 pandemic. Herein we propose a highly sensitive magnetic-focus-enhanced lateral flow assay (mLFA) for the detection of SARS-CoV-2. The proposed mLFA is simple and requires only lateral flow strips and a reusable magnet to detect very low concentrations of the virus particles. The magnetic focus enhancement is achieved by focusing the SARS-CoV-2 conjugated magnetic probes in the sample placed in the lateral flow (LF) strips for improved capture efficiency, while horseradish peroxidase (HRP) was used to catalyze the colorimetric reaction for the amplification of the colorimetric signal. With the magnetic focus enhancement and HRP-based amplification, the mLFA could yield a highly sensitive technology for the recognition of SARS-CoV-2. The developed methods could detect as low as 400 PFU/mL of SARS-CoV-2 in PBS buffer based on the visible blue dots on the LF strips. The mLFA could recognize 1200 PFU/mL of SARS-CoV-2 in saliva samples. With clinical nasal swab samples, the proposed mLFA could achieve 66.7% sensitivity and 100% specificity.

[Applications of separation technology in novel coronavirus research, epidemic prevention and detection].

The novel coronavirus disease 2019 (COVID-19) outbreak has brought to light unprecedented challenges to global public health security. Researchers have devoted their efforts to in-depth research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bring the epidemic under control as rapidly as possible. Among the many areas of burgeoning SARS-CoV-2 related research, various analytical technologies have been applied to the advancement of virus detection, and development of vaccines and innovative therapies. Separation technologies with the merits of simple operation, high separation efficiency, and high selectivity, have become widely used and are key to progress in life science, medicine, pharmaceutical discovery and development, and other fields. Separation technologies have played an irreplaceable role in the isolation, detection, diagnosis, treatment, and prevention of this novel coronavirus. In this review, an overview of the relevant literature is presented from ISI Web of Science spanning Jan. 1st, 2020-Dec. 31, 2020, using "SARS-CoV-2" or "COVID-19" as keywords. The top 20 research directions are summarized, based on papers published in high impact international journals (e. g. Nature, Science, and Cell). Incorporating the impact of published papers, this review summarizes the primary separation technologies applied in these coronavirus studies, and discusses contributions of the following six technologies: affinity chromatography and size exclusion chromatography, liquid chromatography, magnetic bead separation technology, centrifugal technology, micro/nano-separation technology, and electrophoresis. First, affinity chromatography and size exclusion chromatography are discussed, which are the most frequently used protein purification techniques in Nature, Science, and Cell. The SARS-CoV-2 related proteins purified by affinity chromatography and size exclusion chromatography are summarized, and their applications in coronavirus transmission, infection mechanisms, and drug screening are introduced. Subsequently, high performance liquid chromatography (HPLC) is introduced, which is mainly employed for assessing the purity of candidate drugs. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) incorporates the strengths of HPLC and MS, offering both high separation efficiency and structural analysis capabilities with extended applications. LC-MS/MS has been applied to characterization of the binding of SARS-CoV-2 related proteins to potential inhibitors, and to metabolic analyses of candidate drugs. In SARS-CoV-2 nucleic acid tests, magnetic bead separation technology plays a crucial role in the separation of novel coronaviruses. In combination with other analytical techniques, magnetic bead separation technology can be applied to cytological analyses and immunological detection by functionalization of bead surfaces. Centrifugal technology is undoubtedly the most basic separation technology. It has been employed in almost all SARS-CoV-2 related researches. By controlling centrifugation speed, centrifugal technology can rapidly isolate virus particles or cultured cells from complex samples. Micro-nano separation technologies, such as microfluidics, offer advantages including small size, low sample consumption, rapid diffusion, and large surface area. In general, microfluidic technologies are often used in combination with other technologies to realize highly sensitive detection of SARS-CoV-2 related proteins. Finally, the applications of electrophoresis are introduced, which commonly engages in the analysis of polymerase chain reaction (PCR) products. In novel coronavirus studies, the application of electrophoresis has been relatively limited but has potential with further development to contribute significantly to future research. In conclusion, this review summarizes the contributions of six primary separation technologies to novel coronavirus studies, including epidemic detection and prevention, analyzes the main problems facing coronavirus detection efforts, and discusses the role of separation technologies in addressing these problems, with the aim of providing references for broader application of separation technologies.

Magnetic Nanoparticles for Biomedical Applications: From the Soul of the Earth to the Deep History of Ourselves.

Precisely engineered magnetic nanoparticles (MNPs) have been widely explored for applications including theragnostic platforms, drug delivery systems, biomaterial/device coatings, tissue engineering scaffolds, performance-enhanced therapeutic alternatives, and even in SARS-CoV-2 detection strips. Such popularity is due to their unique, challenging, and tailorable physicochemical/magnetic properties. Given the wide biomedical-related potential applications of MNPs, significant achievements have been reached and published (exponentially) in the last five years, both in synthesis and application tailoring. Within this review, and in addition to essential works in this field, we have focused on the latest representative reports regarding the biomedical use of MNPs including characteristics related to their oriented synthesis, tailored geometry, and designed multibiofunctionality. Further, actual trends, needs, and limitations of magnetic-based nanostructures for biomedical applications will also be discussed.

Simultaneous detection of the spike and nucleocapsid proteins from SARS-CoV-2 based on ultrasensitive single molecule assays.

Nucleic acid detection technology based on polymerase chain reaction (PCR) and antibody detection based on immunochromatography still have many problems such as false negatives for the diagnosis of coronavirus disease 2019 (COVID-19). Therefore, it is of great importance to develop new techniques to improve the diagnostic accuracy of COVID-19. We herein developed an ultrasensitive, rapid, and duplex digital enzyme-linked immunosorbent assay (dELISA) for simultaneous detection of spike (S-RBD) and nucleocapsid (N) proteins of SARS-CoV-2 based on a single molecule array. This assay effectively combines magnetic bead encoding technology and the ultrasensitive detection capability of a single molecule array. The detection strategies of S-RBD protein and N-protein exhibited wide response ranges of 0.34-1065 pg/mL and 0.183-338 pg/mL with detection limits of 20.6 fg/mL and 69.8 fg/mL, respectively. It is a highly specific method for the simultaneous detection of S-RBD protein and N-protein and has minimal interference from other blood proteins. Moreover, the spike assay showed a satisfactory and reproducible recovery rate for the detection of S-RBD protein and N-protein in serum samples. Overall, this work provides a highly sensitive method for the simultaneous detection of S-RBD protein and N-protein, which shows ultrasensitivity and high signal-to-noise ratio and contributes to improve the diagnosis accuracy of COVID-19.

Carrying out pseudo dual nucleic acid detection from sample to visual result in a polypropylene bag with CRISPR/Cas12a.

Amplification-based nucleic acid detection is widely employed in food safety, medical diagnosis and environment monitoring. However, conventional nucleic acid analysis has to be carried out in laboratories because of requiring expensive instruments and trained personnel. If people could do nucleic acid detection at home by themselves, the application of nucleic acid detection would be greatly accelerated. We herein reported a polypropylene (PP) bag-based method for convenient detection of nucleic acids in the oil-sealed space. The PP bag has three chambers which are responsible for lysis, washing and amplification/detection, respectively. After adding sample, nucleic acids are adsorbed on magnetic particles (MPs) and moved into these three chambers successively through immiscible oil channel by an external magnet. Combined with isothermal amplification, the PP bag can be incubated in a water bath or milk warmer and acted as a reaction tube. With highly specific CRISPR technology, Salmonella typhimurium (St) and SARS-CoV-2 can be visually detected in these PP bags within 1 h, indicating its potential household application. To further improve the reliability of nucleic acid testing at home, a logic decision method is introduced by detecting both target and endogenous reference gene. Positive/negative/invalid detection result can be obtained by chronologically adding the CRISPR reagents of target and endogenous reference gene. We anticipate that this PP bag can provide a novel toolkit for nucleic acid detection in people's daily life.

A Review of Piezoelectric and Magnetostrictive Biosensor Materials for Detection of COVID-19 and Other Viruses.

The spread of the severe acute respiratory syndrome coronavirus has changed the lives of people around the world with a huge impact on economies and societies. The development of wearable sensors that can continuously monitor the environment for viruses may become an important research area. Here, the state of the art of research on biosensor materials for virus detection is reviewed. A general description of the principles for virus detection is included, along with a critique of the experimental work dedicated to various virus sensors, and a summary of their detection limitations. The piezoelectric sensors used for the detection of human papilloma, vaccinia, dengue, Ebola, influenza A, human immunodeficiency, and hepatitis B viruses are examined in the first section; then the second part deals with magnetostrictive sensors for the detection of bacterial spores, proteins, and classical swine fever. In addition, progress related to early detection of COVID-19 (coronavirus disease 2019) is discussed in the final section, where remaining challenges in the field are also identified. It is believed that this review will guide material researchers in their future work of developing smart biosensors, which can further improve detection sensitivity in monitoring currently known and future virus threats.

Homogeneous circle-to-circle amplification for real-time optomagnetic detection of SARS-CoV-2 RdRp coding sequence.

Circle-to-circle amplification (C2CA) is a specific and precise cascade nucleic acid amplification method consisting of more than one round of padlock probe ligation and rolling circle amplification (RCA). Although C2CA provides a high amplification efficiency with a negligible increase of false-positive risk, it contains several step-by-step operation processes. We herein demonstrate a homogeneous and isothermal nucleic acid quantification strategy based on C2CA and optomagnetic analysis of magnetic nanoparticle (MNP) assembly. The proposed homogeneous circle-to-circle amplification eliminates the need for additional monomerization and ligation steps after the first round of RCA, and combines two amplification rounds in a one-pot reaction. The second round of RCA produces amplicon coils that anneal to detection probes grafted onto MNPs, resulting in MNP assembly that can be detected in real-time using an optomagnetic sensor. The proposed methodology was applied for the detection of a synthetic complementary DNA of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2, also known as 2019-nCoV) RdRp (RNA-dependent RNA polymerase) coding sequence, achieving a detection limit of 0.4 fM with a dynamic detection range of 3 orders of magnitude and a total assay time of ca. 100 min. A mathematical model was set up and validated to predict the assay performance. Moreover, the proposed method was specific to distinguish SARS-CoV and SARS-CoV-2 sequences with high similarity.