Shan X. Wang

Electric-field control of local ferromagnetism using a magnetoelectric multiferroic.

Multiferroics are of interest for memory and logic device applications, as the coupling between ferroelectric and magnetic properties enables the dynamic interaction between these order parameters. Here, we report an approach to control and switch local ferromagnetism with an electric field using multiferroics. We use two types of electromagnetic coupling phenomenon that are manifested in heterostructures consisting of a ferromagnet in intimate contact with the multiferroic BiFeO(3). The first is an internal, magnetoelectric coupling between antiferromagnetism and ferroelectricity in the BiFeO(3) film that leads to electric-field control of the antiferromagnetic order. The second is based on exchange interactions at the interface between a ferromagnet (Co(0.9)Fe(0.1)) and the antiferromagnet. We have discovered a one-to-one mapping of the ferroelectric and ferromagnetic domains, mediated by the colinear coupling between the magnetization in the ferromagnet and the projection of the antiferromagnetic order in the multiferroic. Our preliminary experiments reveal the possibility to locally control ferromagnetism with an electric field.

Matrix-insensitive protein assays push the limits of biosensors in medicine

Advances in biosensor technologies for in vitro diagnostics have the potential to transform the practice of medicine. Despite considerable work in the biosensor field, there is still no general sensing platform that can be ubiquitously applied to detect the constellation of biomolecules in diverse clinical samples (for example, serum, urine, cell lysates or saliva) with high sensitivity and large linear dynamic range. A major limitation confounding other technologies is signal distortion that occurs in various matrices due to heterogeneity in ionic strength, pH, temperature and autofluorescence. Here we present a magnetic nanosensor technology that is matrix insensitive yet still capable of rapid, multiplex protein detection with resolution down to attomolar concentrations and extensive linear dynamic range. The matrix insensitivity of our platform to various media demonstrates that our magnetic nanosensor technology can be directly applied to a variety of settings such as molecular biology, clinical diagnostics and biodefense.

Multiplex protein assays based on real-time magnetic nanotag sensing

Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly sought after in molecular diagnostics such as cancer diagnosis and treatment monitoring, has been challenging. Here, we demonstrate multiplex protein detection of potential cancer markers at subpicomolar concentration levels and with a dynamic range of more than four decades. With the addition of nanotag amplification, the analytic sensitivity extends into the low fM concentration range. The multianalyte ability, sensitivity, scalability, and ease of use of the MNT-based protein assay technology make it a strong contender for versatile and portable molecular diagnostics in both research and clinical settings.

Advances in Giant Magnetoresistance Biosensors With Magnetic Nanoparticle Tags: Review and Outlook

We present a review of giant magnetoresistance (GMR) spin valve sensors designed for detection of magnetic nanoparticles as biomolecular labels (nanotags) in magneto-nano biodetection technology. We discuss the intricacy of magneto-nano biosensor design and show that as few as approximately 14 monodisperse 16-nm superparamagnetic nanoparticles can be detected by submicron spin valve sensors at room temperature without resorting to lock-in (narrow band) detection. GMR biosensors and biochips have been successfully applied to the detection of biological events in the form of both protein and DNA assays with great speed, sensitivity, selectivity, and economy. The limit of molecular detection is well below 10 pM in concentration, and the protein or DNA assay time can be under two hours. The technology is highly scalable to deep multiplex detection of biomarkers in a complex disease, and amenable to integration of microfluidics and CMOS electronics for portable applications. On-chip CMOS circuitry makes a sensor density of 0.1-1 million sensors per square centimeter feasible and affordable. The theoretical and experimental results thus far suggest that magneto-nano biochip-based GMR sensor arrays and nanotags hold great promise in biomedicine, particularly for point-of-care molecular diagnostics of cancer, infectious diseases, radiation injury, cardiac diseases, and other diseases.

Detection of single micron-sized magnetic bead and magnetic nanoparticles using spin valve sensors for biological applications

We have fabricated a series of highly sensitive spin valve sensors on a micron scale that successfully detected the presence of a single superparamagnetic bead (Dynabeads M-280, 2.8 μm in diameter), and thus showed suitability for identifying biomolecules labeled by such magnetic beads. By polarizing the magnetic microbead on a spin valve sensor with a dc magnetic field and modulating its magnetization with an orthogonal ac magnetic field, we observed a magnetoresistance (MR) signal reduction caused by the magnetic dipole field from the bead that partially cancelled the applied fields to the spin valve. A lock-in technique was used to measure a voltage signal due to the MR reduction. A signal of 1.2 mV rms or 5.2 mΩ of resistance reduction was obtained from a 3 μm wide sensor and a signal of 3.8 mV rms or 11.9 mΩ from a 2.5 μm wide sensor. Micromagnetic simulations were also performed for the spin valve sensors with a single bead and gave results consistent with experiments. Further experiments and simula...

Sandwich films: Properties of a new soft magnetic material

The development of advanced electromagnetic devices has been constrained by a lack of soft magnetic materials with a suitably high saturation magnetization (over 20 kilogauss) and a large permeability roll-off frequency (greater than 1 gigaherz). For example, magnetic hard-disk-drive technology is rapidly approaching the perceived superparamagnetic limit at which the stored bits become thermally unstable — disks with higher anisotropy are more stable but are not usable because magnetic write heads become saturated. Here we describe a new soft magnetic material with a saturation magnetization of 24 kilogauss and a large permeability of 1,000–1,400 in a wide frequency range of up to about 1.2 gigaherz. This new material promises to have wide application in devices such as magnetic recording heads and integrated inductors.

Nanoscale Control of Exchange Bias with BiFeO3 Thin Films

We demonstrate a direct correlation between the domain structure of multiferroic BiFeO3 thin films and exchange bias of Co 0.9Fe 0.1/BiFeO3 heterostructures. Two distinct types of interactions - an enhancement of the coercive field ( exchange enhancement) and an enhancement of the coercive field combined with large shifts of the hysteresis loop ( exchange bias) - have been observed in these heterostructures, which depend directly on the type and crystallography of the nanoscale ( approximately 2 nm) domain walls in the BiFeO3 film. We show that the magnitude of the exchange bias interaction scales with the length of 109 degrees ferroelectric domain walls in the BiFeO 3 thin films which have been probed via piezoresponse force microscopy and X-ray magnetic circular dichroism.

Quantification of protein interactions and solution transport using high-density GMR sensor arrays

Monitoring the kinetics of protein interactions on a high density sensor array is vital to drug development and proteomic analysis. Label-free kinetic assays based on surface plasmon resonance are the current gold standard, but they have poor detection limits, suffer from non-specific binding, and are not amenable to high throughput analyses. Here we show that magnetically responsive nanosensors that have been scaled to over 100,000 sensors/cm2 can be used to measure the binding kinetics of various proteins with high spatial and temporal resolution. We present an analytical model that describes the binding of magnetically labeled antibodies to proteins that are immobilized on the sensor surface. This model is able to quantify the kinetics of antibody-antigen binding at sensitivities as low as 20 zeptomoles of solute.

One-pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications

One-pot reaction of iron(III) acetylacetonate, Fe(acac)3, [or Fe(acac)3 and M(acac)2 where M = Mn and Co], with 1,2-alkanediol, oleic acid, and oleylamine in high boiling organic solvent leads to monodisperse ferrite MFe2O4 nanoparticles. Depending on the concentration of the metal precursors, surfactant-to-metal precursor ratio and the solvent used in the reaction, the particle size from this one-pot reaction can be tuned from 4 to 15 nm. The as-synthesized iron oxide nanoparticles have an inverse spinel structure, and their magnetic properties are controlled by particle size and M in the MFe2O4 structure. The hydrophobic iron oxide nanoparticles are readily transformed into hydrophilic ones by functional phospholipid addition to the as-synthesized particles and as a result, the monodisperse nanoparticles are readily functionalized with biotin, -COOH, -SH, and -NH2, facilitating their link to biomolecules for biomedical applications.

Giant Magnetoresistive Biochip for DNA Detection and HPV Genotyping

A giant magnetoresistive (GMR) biochip based on spin valve sensor array and magnetic nanoparticle labels was developed for inexpensive, sensitive and reliable DNA detection. The DNA targets detected in this experiment were PCR products amplified from Human Papillomavirus (HPV) plasmids. The concentrations of the target DNA after PCR were around 10 nM in most cases, but concentrations of 10 pM were also detectable, which is demonstrated by experiments with synthetic DNA samples. A mild but highly specific surface chemistry was used for probe oligonucleotide immobilization. Double modulation technique was used for signal detection in order to reduce the 1/f noise in the sensor. Twelve assays were performed with an accuracy of approximately 90%. Magnetic signals were consistent with particle coverage data measured with Scanning Electron Microscopy (SEM). More recent research on microfluidics showed the potential of reducing the assay time below one hour. This is the first demonstration of magnetic DNA detection using plasmid-derived samples. This study provides a direct proof that GMR sensors can be used for biomedical applications.