Nanomaterials, in addition to their small size, possess unique physicochemical properties that differ from bulk materials, making them ideal for a host of novel applications. Magnetic nanoparticles (MNPs) are one important class of nanomaterials that have been widely studied for their potential applications in nanomedicine. Due to the fact that MNPs can be detected and manipulated by remote magnetic fields, it opens a wide opportunity for them to be used in vivo. Nowadays, MNPs have been used for diverse applications including magnetic biosensing (diagnostics), magnetic imaging, magnetic separation, drug and gene delivery, and hyperthermia therapy, etc. Specifically, we reviewed some emerging techniques in magnetic diagnostics such as magnetoresistive (MR) and micro-Hall (μHall) biosensors, as well as the magnetic particle spectroscopy, magnetic relaxation switching and surface enhanced Raman spectroscopy (SERS)-based bioassays. Recent advances in applying MNPs as contrast agents in magnetic resonance imaging and as tracer materials in magnetic particle imaging are reviewed. In addition, the development of high magnetic moment MNPs with proper surface functionalization has progressed exponentially over the past decade. To this end, different MNP synthesis approaches and surface coating strategies are reviewed and the biocompatibility and toxicity of surface functionalized MNP nanocomposites are also discussed. Herein, we are aiming to provide a comprehensive assessment of the state-of-the-art biological and biomedical applications of MNPs. This review is not only to provide in-depth insights into the different synthesis, biofunctionalization, biosensing, imaging, and therapy methods but also to give an overview of limitations and possibilities of each technology.

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 process, thus indicating the bound states of MNPs. These harmonics can be readily collected from nanogram quantities of iron oxide nanoparticles within 10 s. The 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 were able to detect as low as 44 nM (4.4 pmole) 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, and 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.

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; a fast and accurate diagnosis for SARS-CoV-2 is essential in slowing the spread of COVID-19 and for efficient implementation of control and containment strategies. Magnetic nanosensing is an emerging topic representing the frontiers of current biosensing and magnetic 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 literature of magnetic nanosensors for virus and pathogen detection before COVID-19. We review popular magnetic nanosensing techniques including magnetoresistance, magnetic particle spectroscopy, and nuclear magnetic resonance. Magnetic point-of-care 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 detection 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.

Since the first system was established and reported in 2005, magnetic particle imaging (MPI) has emerged as a non-invasive tomographic technique that has proven useful in diagnostic imaging. Magnetic particle spectroscopy (MPS), alternatively called magnetization response spectroscopy, is a novel measurement method that closely relates to MPI. An MPS system can be interpreted as a 0D MPI scanner consisting of excitation field coils and pickup coils. In MPS, a sinusoidal magnetic field with sufficiently large amplitude is applied to superparamagnetic iron oxide nanoparticles (SPIONs), which periodically drives their magnetization into and out of saturation. Their magnetic responses, which contain unique harmonics, are recorded and separated into their spectral components. While prototypes of MPI systems are still in their testing stages, MPS has been actively explored as a portable, highly-sensitive, cheap, in vitro, and easy-to-use bioassay testing kit. In this review, we briefly discuss the superparamagnetism and magnetic relaxation mechanisms associated with MPS measurements. We summarize the recent progress in the various MPS detection modes and, also, MPS-based bioassays. Finally, this review concludes with an insight of the state of art and future trends of MPS-based bioassays.

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.