Shu-Jen Han

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.

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.

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.

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.

GMR Biosensor Arrays: A System Perspective

Giant magnetoresistive biosensors are becoming more prevalent for sensitive, quantifiable biomolecular detection. However, in order for magnetic biosensing to become competitive with current optical protein microarray technology, there is a need to increase the number of sensors while maintaining the high sensitivity and fast readout time characteristic of smaller arrays (1-8 sensors). In this paper, we present a circuit architecture scalable for larger sensor arrays (64 individually addressable sensors) while maintaining a high readout rate (scanning the entire array in less than 4s). The system utilizes both time domain multiplexing and frequency domain multiplexing in order to achieve this scan rate. For the implementation, we propose a new circuit architecture that does not use a classical Wheatstone bridge to measure the small change in resistance of the sensor. Instead, an architecture designed around a transimpedance amplifier is employed. A detailed analysis of this architecture including the noise, distortion, and potential sources of errors is presented, followed by a global optimization strategy for the entire system comprising the magnetic tags, sensors, and interface electronics. To demonstrate the sensitivity, quantifiable detection of two blindly spiked samples of unknown concentrations has been performed at concentrations below the limit of detection for the enzyme-linked immunosorbent assay. Lastly, the multiplexing capability and reproducibility of the system was demonstrated by simultaneously monitoring sensors functionalized with three unique proteins at different concentrations in real-time.

Room temperature exchange bias and spin valves based on BiFeO3∕SrRuO3∕SrTiO3∕Si (001) heterostructures

We report the growth and characterization of exchange bias and spin valve heterostructures based on the multiferroic antiferromagnet BiFeO3 on Si (001) substrates. Using Co0.9Fe0.1 as the ferromagnet, we demonstrate heterostructures with large negative exchange bias and negligible training (or a decrease in exchange bias field as a function of repeated magnetic cycling) at room temperature. We additionally report the manufacture of spin valve structures that have been found to have current in-plane magnetoresistance of over 2.25% at room temperature.

A High-Density Magnetoresistive Biosensor Array with Drift-Compensation Mechanism

A DNA microarray of 1008 magnetoresistive sensors employing multidivided array structures for detecting either tow concentration or large-scale gene information is integrated with a 0.25mum BiCMOS chip. The input-referred noise is below 55nV/radicHz. Ionic solution interferences and drifts during biological reaction are removed by applying an in-plane AC magnetic field with two DC field states. Parallel readout is realized by combining FDM with TDM.

CMOS Integrated DNA Microarray Based on GMR Sensors

A high density GMR sensor array was integrated with a standard CMOS chip for DNA hybridization detection. Absorption of magnetic nanoparticles by the hybridized DNA alters the sensor resistance, and generated electrical signals are directly measured with the on-die circuitry. The proposed biochip can be applied to other bio-reaction detection, e.g. protein assay, through different surface modifications

Giant Magnetoresistive Sensors for DNA Microarray

Giant magnetoresistive (GMR) sensors are developed for a DNA microarray. Compared with the conventional fluorescent sensors, GMR sensors are cheaper, more sensitive, can generate fully electronic signals, and can be easily integrated with electronics and microfluidics. The GMR sensor used in this work has a bottom spin valve structure with an MR ratio of 12%. The single-strand target DNA detected has a length of 20 bases. Assays with DNA concentrations down to 10 pM were performed, with a dynamic range of three logs. A double modulation technique was used in signal detection to reduce the 1/f noise in the sensor while circumventing electromagnetic interference. The logarithmic relationship between the magnetic signal and the target DNA concentration can be described by the Temkin isotherm. Furthermore, GMR sensors integrated with microfluidics has great potential of improving the sensitivity to 1 pM or below, and the total assay time can be reduced to less than 1 h .