Guanxiong Li

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...

Model and experiment of detecting multiple magnetic nanoparticles as biomolecular labels by spin valve sensors

We present an analytical model for detection of multiple magnetic nanoparticles (NP) as biomolecular labels by spin valve (SV) sensors, aiming to establish the relationship between the SV sensor signal and the number of magnetic labels. The model is based on the assumptions of equivalent average field of magnetic NPs and the coherent magnetization rotation of SVs free layer. Using the model, we have calculated the sensor signals of multiple NPs uniformly or randomly distributed over a SV sensor at various aspect ratios of the NP array. Satisfactory signal linearity at low particle number or high aspect ratio has been found. The model also reveals that the SV sensors could be made insensitive to the random configuration of NPs and only sensitive to the number of NPs. This feature is desired for quantitative bio-detection. To check the validity of the model, we performed experiments on a monolayer of 16-nm Fe/sub 3/O/sub 4/ NPs coated on 0.3-/spl mu/m-wide SV sensors. We found that the measured signals could be well described by the analytical model.

Analytical and micromagnetic modeling for detection of a single magnetic microbead or nanobead by spin valve sensors

In this paper, we present an analytical analysis based on the Stoner-Wolhfarth model for the detection of a single magnetic microbead or nanobead by spin valve sensors. The analytical model is compared with micromagnetic simulations and experiments.

Spin valve biosensors: Signal dependence on nanoparticle position

Experimental and theoretical studies have been carried out on the spin valve sensor signal dependence on the spatial locations of magnetic nanoparticles as potential biomolecular labels in the magnetic biodetection technology. Superparamagnetic 16 nm magnetite (Fe3O4) nanoparticles were site specifically deposited at different positions relative to a submicron-wide spin valve sensor. The spin valve sensor signal showed both polarity and magnitude differences with the particles at different positions. A theoretical model including magnetic sensor-particle interaction confirms the experimental results and provides a design guide to the sensing area. Moreover, the theoretical calculations reveal a nonmonotonic signal dependence on the vertical particle-to-sensor distance due to the sensor-particle interaction, and show that an optimum distance exists for signal strength and quantification.

Biochemical stability of components for use in a DNA detection system

We have proposed a DNA detection system that relies on superparamagnetic nanoparticles (Co and Fe/sub 3/O/sub 4/) as biological labels and submicrometer spin valves as sensors. In sensor operation, the magnetic labels are subjected to annealing at 95/spl deg/C-98/spl deg/C, at which DNA denatures, and the spin valve sensor surface is exposed to various DNA containing buffer solutions. We have performed stability studies to validate that the components of our system will survive normal sensor operation. We demonstrate that our proposed biological labels are magnetically stable after five thermal cycles of 5 min (with T/sub max/=98/spl deg/C). By tracking the magnetic diameter (D/sub m/) of the nanoparticles, obtained from a Langevin function fitting method, we observe that D/sub m/ decreases by about 20% after the fifth temperature cycle. Compliance of the submicrometer spin valve sensor with a width of 300 nm and an magnetoresistance (MR) ratio of /spl sim/7 % is studied by immersion cycling in buffer solutions (pH=7.5-7.9) with a high DNA concentration. The spin valve sensor maintains its characteristic MR ratio after four 30 min exposures to DNA solution and continues to perform with a /spl sim/ 7 % MR after 24 h in solution. Notably, the spin valve sensor demonstrates this survivability with an ultra thin passivation layer (/spl sim/ 4 nm). Thus, the biochemical stability of these components suggests that our DNA detection system is compliant with standard biological sensor operation.

Design and fabrication of bio-magnetic sensors and magnetic nanobead labels for DNA detection and identification

In this paper, the main challenges in developing a magnetic DNA microarray include: 1) The spin valve sensors must be sensitive to as few as 1-10 nanobeads to be useful for applications such as biological pathogen detection; to achieve this, the distance between the sensor and magnetic labels must be minimized. 2) The nanobeads must be monodisperse, water soluble, chemically and magnetically stable, and functionalized to attach to a DNA fragment; the nanobeads should also be superparamagnetic so that they will not agglomerate in the absence of applied fields. 3) The bio-magnetic DNA microarrays need to be designed to maximise the active sensing surface area.