Impact of anesthesia on micromagnetic stimulation (µMS) of the vagus nerve.

To treat diseases associated with vagal nerve control of peripheral organs, it is necessary to selectively activate efferent and afferent fibers in the vagus. As a result of the nerve's complex anatomy, fiber-specific activation proves challenging. Spatially selective neuromodulation using micromagnetic stimulation(µMS) is showing incredible promise. This neuromodulation technique uses microcoils(µcoils) to generate magnetic fields by powering them with a time-varying current. Following the principles of Faraday's law of induction, a highly directional electric field is induced in the nerve from the magnetic field. In this study on rodent cervical vagus, a solenoidalµcoil was oriented at an angle to left and right branches of the nerve. The aim of this study was to measure changes in the mean arterial pressure (MAP) and heart rate (HR) followingµMS of the vagus. Theµcoils were powered by a single-cycle sinusoidal current varying in pulse widths(PW = 100, 500, and 1000µsec) at a frequency of 20 Hz. Under the influence of isoflurane,µMS of the left vagus at 1000µsec PW led to an average drop in MAP of 16.75 mmHg(n = 7). In contrast,µMS of the right vagus under isoflurane resulted in an average drop of 11.93 mmHg in the MAP(n = 7). Surprisingly, there were no changes in HR to either right or left vagalµMS suggesting the drop in MAP associated with vagusµMS was the result of stimulation of afferent, but not efferent fibers. In urethane anesthetized rats, no changes in either MAP or HR were observed uponµMS of the right or left vagus(n = 3). These findings suggest the choice of anesthesia plays a key role in determining the efficacy ofµMS on the vagal nerve. Absence of HR modulation uponµMS could offer alternative treatment options using VNS with fewer heart-related side-effects.

Micromagnetic Stimulation (µMS) Controls Dopamine Release: An in vivo Study Using WINCS Harmoni.

Objective: Research into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of the in vivo changes in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCS Harmoni tool to study the real time in vivo changes in dopamine release in rodent brains for the micromagnetic neuromodulation therapy. Approach: Although still in its infancy, micromagnetic stimulation (µMS) using micro-meter sized coils or microcoils (µcoils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These µcoils are powered by a time-varying current which generates a magnetic field. As per Faraday's Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped µcoil to stimulate the medial forebrain bundle (MFB) of the rodent brain in vivo. The evoked in vivo dopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV). Results: Our experiments report that µcoils can successfully activate the MFB in rodent brains, triggering dopamine release in vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the µcoil. Furthermore, varied intensities of µMS can control the concentration of dopamine releases in the striatum. Significance: This work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like µMS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for µMS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.

Micromagnetic stimulation (µMS) dose-response of the rat sciatic nerve.

Objective.The objective of this study was to investigate the effects of micromagnetic stimuli strength and frequency from theMagneticPen(MagPen) on the rat right sciatic nerve. The nerve's response was measured by recording muscle activity and movement of the right hind limb.Approach.The MagPen was custom-built to be stably held over the sciatic nerve. Rat leg muscle twitches were captured on video, and movements were extracted using image processing algorithms. EMG recordings were also used to measure muscle activity.Main results.The MagPen prototype, when driven by an alternating current, generates a time-varying magnetic field, which, according to Faraday's law of electromagnetic induction, induces an electric field for neuromodulation. The orientation-dependent spatial contour maps of the induced electric field from the MagPen prototype have been numerically simulated. Furthermore, in thisin vivowork onµMS, a dose-response relationship has been reported by experimentally studying how varying the amplitude (Range: 25 mVp-pthrough 6Vp-p) and frequency (range: 100 Hz through 5 kHz) of the MagPen stimuli alters hind limb movement. The primary highlight of this dose-response relationship (repeated overnrats, wheren= 7) is that for aµMS stimuli of higher frequency, significantly smaller amplitudes can trigger hind limb muscle twitch. This frequency-dependent activation can be justified by Faraday's Law, which states that the magnitude of the induced electric field is directly proportional to the frequency.Significance.This work reports thatµMS can successfully activate the sciatic nerve in a dose-dependent manner. The impact of this dose-response curve addresses the controversy in this research community about whether the stimulation from theseµcoils arise from a thermal effect or micromagnetic stimulation. MagPen probes do not have a direct electrochemical interface with tissue and therefore do not experience electrode degradation, biofouling, and irreversible redox reactions like traditional direct contact electrodes. Magnetic fields from theµcoils create more precise activation than electrodes because they apply more focused and localized stimulation. Finally, unique features ofµMS, such as the orientation dependence, directionality, and spatial specificity, have been discussed.

Magnetic nanoparticles and magnetic particle spectroscopy-based bioassays: a 15 year recap.

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.

Giant Magnetoresistance Biosensors in Biomedical Applications.

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.

Strength-frequency curve for micromagnetic neurostimulation through excitatory postsynaptic potentials (EPSPs) on rat hippocampal neurons and numerical modeling of magnetic microcoil (µcoil).

Objective.The objective of this study was to measure the effect of micromagnetic stimulation (µMS) on hippocampal neurons, by using single microcoil (µcoil) prototype, magnetic pen (MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving theµcoil will be demonstrated. Finally, the optimal stimulation frequency of the current driving theµcoil to minimize power will be estimated.Approach.A biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of theµcoil and its distance over the hippocampal tissue in anin vitrorecording setting. Finite element modeling of theµcoil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V m-1). The induced electric field profiles generated at different values of current applied to theµcoil can elicit a neuronal response, which was validated by numerical modeling. The modeling settings for theµcoil were replicated in experiments on rat hippocampal neurons.Main results.The preferred orientation of MagPen over the Schaffer Collateral fibers was demonstrated such that they elicit a neuron response. The recorded EPSPs from CA1 region due toµMS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs fromµMS while after prolonged TTX washout, a partial recovery of the EPSP fromµMS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving theµcoil, led to a decrease in the current amplitude threshold for micromagnetic neurostimulation.Significance.This work reports that micromagnetic neurostimulation can be used to evoke population EPSP responses in the CA1 region of the hippocampus. It demonstrates the strength-frequency curve forµMS and its unique features related to orientation dependence of theµcoils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related toµMS experiments were studied including ways to overcome them.

A review on magnetic and spintronic neurostimulation: challenges and prospects.

In the treatment of neurodegenerative, sensory and cardiovascular diseases, electrical probes and arrays have shown quite a promising success rate. However, despite the outstanding clinical outcomes, their operation is significantly hindered by non-selective control of electric fields. A promising alternative is micromagnetic stimulation (µMS) due to the high permeability of magnetic field through biological tissues. The induced electric field from the time-varying magnetic field generated by magnetic neurostimulators is used to remotely stimulate neighboring neurons. Due to the spatial asymmetry of the induced electric field, high spatial selectivity of neurostimulation has been realized. Herein, some popular choices of magnetic neurostimulators such as microcoils (µcoils) and spintronic nanodevices are reviewed. The neurostimulator features such as power consumption and resolution (aiming at cellular level) are discussed. In addition, the chronic stability and biocompatibility of these implantable neurostimulator are commented in favor of further translation to clinical settings. Furthermore, magnetic nanoparticles (MNPs), as another invaluable neurostimulation material, has emerged in recent years. Thus, in this review we have also included MNPs as a remote neurostimulation solution that overcomes physical limitations of invasive implants. Overall, this review provides peers with the recent development of ultra-low power, cellular-level, spatially selective magnetic neurostimulators of dimensions within micro- to nano-range for treating chronic neurological disorders. At the end of this review, some potential applications of next generation neuro-devices have also been discussed.

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.

Investigation of Commercial Iron Oxide Nanoparticles: Structural and Magnetic Property Characterization.

Magnetic nanoparticles (MNPs) have been extensively used as tiny heating sources in magnetic hyperthermia therapy, contrast agents in magnetic resonance imaging, tracers in magnetic particle imaging, carriers for drug/gene delivery, etc. There have emerged many MNP/microbead suppliers since the past decade, such as Ocean NanoTech, Nanoprobes, US Research Nanomaterials, Miltenyi Biotec, micromod Partikeltechnologie GmbH, nanoComposix, and so forth. In this paper, we report the physical and magnetic characterizations on iron oxide nanoparticle products from Ocean NanoTech. Standard characterization tools such as vibrating-sample magnetometry, X-ray diffraction, dynamic light scattering, transmission electron microscopy, and zeta potential analysis are used to provide MNP customers and researchers with an overview of these iron oxide nanoparticle products. In addition, the dynamic magnetic responses of these iron oxide nanoparticles in aqueous solutions are investigated under low- and high-frequency alternating magnetic fields, giving a standardized operating procedure for characterizing the MNPs from Ocean NanoTech, thereby yielding the best of MNPs for different applications.

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.

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.

Irregularly Shaped Iron Nitride Nanoparticles as a Potential Candidate for Biomedical Applications: From Synthesis to Characterization.

Magnetic nanoparticles (MNPs) have been extensively used in drug/gene delivery, hyperthermia therapy, magnetic particle imaging (MPI), magnetic resonance imaging (MRI), magnetic bioassays, and so forth. With proper surface chemical modifications, physicochemically stable and nontoxic MNPs are emerging contrast agents and tracers for in vivo MRI and MPI applications. Herein, we report the high magnetic moment, irregularly shaped γ'-Fe4N nanoparticles for enhanced hyperthermia therapy and T2 contrast agent for MRI application. The static and dynamic magnetic properties of γ'-Fe4N nanoparticles are characterized by a vibrating sample magnetometer (VSM) and a magnetic particle spectroscopy (MPS) system, respectively. Compared to the γ-Fe2O3 nanoparticles, γ'-Fe4N nanoparticles show at least three times higher saturation magnetization, which, as a result, gives rise to the stronger dynamic magnetic responses as proved in the MPS measurement results. In addition, γ'-Fe4N nanoparticles are functionalized with an oleic acid layer by a wet mechanical milling process. The morphologies of as-milled nanoparticles are characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), and nanoparticle tracking analyzer (NTA). We report that with proper surface chemical modification and tuning on morphologies, γ'-Fe4N nanoparticles could be used as tiny heating sources for hyperthermia and contrast agents for MRI applications with minimum dose.

Spin current nano-oscillator (SCNO) as a potential frequency-based, ultra-sensitive magnetic biosensor: a simulation study.

This work is a micromagnetic simulation-based study on the GHz-frequency ferromagnetic resonances (FMR) for the detection of magnetic nanoparticles (MNPs) using spin current nano-oscillator (SCNO) operating in precession mode. Capture antibody-antigen-detection antibody-MNP complex on the SCNO surface generates magnetic fields that modify the FMR peaks and generate measurable resonance peak shifts. Moreover, our results strongly indicate the position-sensitive behavior of the SCNO biosensor and demonstrate ways to eradicate this effect to facilitate improved bio-sensing. Additionally, a study has been made on how MNPs with different sizes can alter the SCNO device performance. This simulation-based study on the SCNO device shows the feasibility of a frequency-based nano-biosensor with the sensitivity of detecting a single MNP, even in presence of background noise.

Magnetic Particle Spectroscopy for Detection of Influenza A Virus Subtype H1N1.

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.

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; 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.

Magnetic nanoparticles in nanomedicine: a review of recent advances.

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 Nanoparticle Relaxation Dynamics-Based Magnetic Particle Spectroscopy for Rapid and Wash-Free Molecular Sensing.

Magnetic nanoparticles (MNPs) have been extensively used as contrasts and tracers for bioimaging, heating sources for tumor therapy, carriers for controlled drug delivery, and labels for magnetic immunoassays. Here, we describe a MNP Brownian relaxation dynamics-based magnetic particle spectroscopy (MPS) method for the quantitative detection of molecular biomarkers. In MPS measurements, the harmonics of oscillating MNPs are recorded and used as a metric for the freedom of rotational motion, which indicates the bound states of the MNPs. These harmonics can be collected from microgram quantities of iron oxide nanoparticles within 10 s. As the harmonics are largely dependent on the quantity of the MNPs in the sample, the MPS bioassay results could be biased by the deviations of MNP quantities in each sample, especially for the very low-concentration biomarker detection scenarios. Herein, we report three MNP concentration/quantity-independent metrics for characterizing the bound states of MNPs in MPS. Using a streptavidin-biotin binding system as a model, we demonstrate the feasibility of using MPS and MNP concentration/quantity-independent metrics to sense these molecular interactions, showing that this method can achieve rapid, wash-free bioassays, and is suitable for future point-of-care, sensitive, and versatile diagnosis.

Advances in Magnetoresistive Biosensors.

Magnetoresistance (MR) based biosensors are considered promising candidates for the detection of magnetic nanoparticles (MNPs) as biomarkers and the biomagnetic fields. MR biosensors have been widely used in the detection of proteins, DNAs, as well as the mapping of cardiovascular and brain signals. In this review, we firstly introduce three different MR devices from the fundamental perspectives, followed by the fabrication and surface modification of the MR sensors. The sensitivity of the MR sensors can be improved by optimizing the sensing geometry, engineering the magnetic bioassays on the sensor surface, and integrating the sensors with magnetic flux concentrators and microfluidic channels. Different kinds of MR-based bioassays are also introduced. Subsequently, the research on MR biosensors for the detection of protein biomarkers and genotyping is reviewed. As a more recent application, brain mapping based on MR sensors is summarized in a separate section with the discussion of both the potential benefits and challenges in this new field. Finally, the integration of MR biosensors with flexible substrates is reviewed, with the emphasis on the fabrication techniques to obtain highly shapeable devices while maintaining comparable performance to their rigid counterparts.