Magnetic particle spectroscopy (MPS), also called magnetization response spectroscopy, is a novel measurement tool derived from magnetic particle imaging (MPI). It can be interpreted as a zero-dimensional version of MPI scanner. MPS was primarily designed for characterizing superparamagnetic iron oxide nanoparticles (SPIONs) regarding their applicability for MPI. In recent years, it has evolved into an independent, versatile, highly sensitive, inexpensive platform for biological and biomedical assays, cell labeling and tracking, and blood analysis. MPS has also developed into an auxiliary tool for magnetic imaging and hyperthermia by providing high spatial and temporal mappings of temperature and viscosity. Furthermore, other MPS-based applications are being explored such as magnetic fingerprints for product tracking and identification in supply chains. There are a variety of novel MPS-based applications being reported and demonstrated by many groups. In this short review, we highlighted some of the representative applications based on MPS platform, thereby providing a roadmap of this technology and our insights for researchers in this area.

The giant magnetoresistance (GMR) effect has seen flourishing development from theory to application in the last three decades since its discovery in 1988. Nowadays, commercial devices based on the GMR effect, such as hard-disk drives, biosensors, magnetic field sensors, microelectromechanical systems (MEMS), etc., are available in the market, by virtue of the advances in state-of-the-art thin-film deposition and micro- and nanofabrication techniques. Different types of GMR biosensor arrays with superior sensitivity and robustness are available at a lower cost for a wide variety of biomedical applications. In this paper, we review the recent advances in GMR-based biomedical applications including disease diagnosis, genotyping, food and drug regulation, brain and cardiac mapping, etc. The GMR magnetic multilayer structure, spin valve, and magnetic granular structure, as well as fundamental theories of the GMR effect, are introduced at first. The emerging topic of flexible GMR for wearable biosensing is also included. Different GMR pattern designs, sensor surface functionalization, bioassay strategies, and on-chip accessories for improved GMR performances are reviewed. It is foreseen that combined with the state-of-the-art complementary metal-oxide-semiconductor (CMOS) electronics, GMR biosensors hold great promise in biomedicine, particularly for point-of-care (POC) disease diagnosis and wearable devices for real-time health monitoring.

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.

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. It's foreseen that this kind of portable device can transform the multi-step, laboratory-based bioassays to one-step field testing in non-clinical settings such as schools, homes, offices, etc.

Magnetic nanoparticles (MNPs) have unique physical and chemical properties, such as high surface area to volume ratio and size-related magnetism, which are completely different from their bulk materials. Benefiting from the facile synthesis and chemical modification strategies, MNPs have been widely studied for applications in nanomedicine. Herein, we firstly summarized the designs of MNPs from the perspectives of materials and physicochemical properties tailored for biomedical applications. Magnetic particle spectroscopy (MPS), first reported in 2006, has flourished as an independent platform for many biological and biomedical applications. It has been extensively reported as a versatile platform for a variety of bioassays along with the artificially designed MNPs, where the MNPs serve as magnetic nanoprobes to specifically probe target analytes from fluid samples. In this review, the mechanisms and theories of different MPS platforms realizing volumetric- and surface-based bioassays are discussed. Some representative works of MPS platforms for applications such as disease diagnosis, food safety and plant pathology monitoring, drug screening, thrombus maturity assessments are reviewed. At the end of this review, we commented on the rapid growth and booming of MPS-based bioassays in its first 15 years. We also prospected opportunities and challenges that portable MPS devices face in the rapidly growing demand for fast, inexpensive, and easy-to-use biometric techniques.