Yuanpeng Li

A Detection System Based on Giant Magnetoresistive Sensors and High-Moment Magnetic Nanoparticles Demonstrates Zeptomole Sensitivity: Potential for Personalized Medicine†

Zeptomole detector: A highly sensitive giant-magnetoresistive chip and FeCo nanoparticles can be used to linearly detect 600-4500 copies of streptavidin. Under unoptimized conditions, this system also detects human IL-6 with a sensitivity 13-times higher than that of standard ELISA techniques.

Nanomagnetic competition assay for low-abundance protein biomarker quantification in unprocessed human sera

A novel giant magnetoresistive sensor and uniform high-magnetic-moment FeCo nanoparticles (12.8 nm)-based detecting platform with minimized detecting distance was developed for rapid biomolecule quantification from body fluids. Such a system demonstrates specific, accurate, and quick detection and quantification of interleukin-6, a low-abundance protein and a potential cancer biomarker, directly in 4 muL of unprocessed human sera. This platform is expected to facilitate the identification and validation of disease biomarkers. It may eventually lead to a low-cost personal medical device for chronic disease early detection, diagnosis, and prognosis.

A Three-Layer Competition-Based Giant Magnetoresistive Assay for Direct Quantification of Endoglin from Human Urine

This study presents a three-layer competition-based assay for ultrasensitive detection and quantification of endoglin from unprocessed human urine samples using a giant magnetoresistive (GMR) sensor and high-moment magnetic nanoparticle-based biosensing technology. This biosensing platform detects as few as 1000 copies of endoglin at concentrations as low as 83 fM with high detection specificity and has a three-order dynamic range. The results reveal that endoglin levels in urine have the potential to predict for the presence of prostate cancer and to distinguish between prostate cancers of different grades.

Real-time measurement of Brownian relaxation of magnetic nanoparticles by a mixing-frequency method

A detection scheme for real-time Brownian relaxation of magnetic nanoparticles (MNPs) is demonstrated by a mixing-frequency method in this paper. MNPs are driven into the saturation region by a low frequency sinusoidal magnetic field. A high frequency sinusoidal magnetic field is then applied to generate mixing-frequency signals that are highly specific to the magnetization of MNPs. These highly sensitive mixing-frequency signals from MNPs are picked up by a pair of balanced built-in detection coils. The phase delays of the mixing-frequency signals behind the applied field are derived, and are experimentally verified. Commercial iron oxide MNPs with the core diameter of 35 nm are used for the measurement of Brownian relaxation. The results are fitted well with Debye model. Then a real-time measurement of the binding process between protein G and its antibody is demonstrated using MNPs as labels. This study provides a volume-based magnetic sensing scheme for the detection of binding kinetics and interaction affinities between biomolecules in real time.

ATOMIC LAYER ETCHING OF GAAS(110) WITH BR2 STUDIED BY SCANNING TUNNELING MICROSCOPY

Scanning tunneling microscopy studies of GaAs(110) exposed to Br2 at 720 K show preferential etching at single‐height [112] and [001] steps with little etching at double‐height steps. Etching in the [110] direction is at least ∼4.5 times faster than in the [001] direction, producing rectangular etch pits. For higher Br2 exposures, etching is dominated by single‐height step flow but triangular double‐layer etch pits also form on extended terraces.

Quantitative analysis of interaction between domain walls and magnetic nanoparticles

We have studied the potential energy and effective field induced by the presence of a single superparamagnetic particle above a magnetic domain wall in a 5 nm ferromagnetic film (Ms = 800 emu/cm3) with uniaxial crystalline anisotropy (Ku < 107 erg/cm3). The wall width, wall type (head-to-head, Neel, and perpendicular Bloch), film dimensions, particle height, and external applied field are found to affect the performance of particle sensing systems. Results and optimization strategies derived from this model are presented. The calculated change in depinning field (ΔHdp) is compared against experimental data and micromagnetic simulation. This comparison provides justification for further development in terms of integration with micromagnetic simulations.

A new and facile method for measurement of apparent density of monodisperse polymer beads

The apparent density, an intrinsic physical property of polymer beads, plays an important role in the application of beads in micro-total analysis systems and separation. Here we have developed a new, facile and milligram-scale method to describe the motion of beads in aqueous solution and further detect the apparent density of beads. The motion of beads in solutions is determined by the viscosity of solutions and the density difference between beads and solutions. In this study, using various glycerol aqueous solutions with certain viscosities and densities, the motion time (i.e. floating or sedimentation time) of hybrid polymer beads was experimentally measured and theoretically deduced, and consequently, the apparent density of monodisperse beads can be quickly and easily calculated. The results indicated that the present method provided a more precise way to predict the movement of hybrid beads in aqueous solution compared with the approach for commercial use. This new method can be potentially employed in flow cytometry, suspension stability, and particle analysis systems.

Biomarker quantification in unprocessed human sera by using a new nanomagnetic protein assay

Early recognition and prevention of chronic disease, such as lung cancer, require a fast, accurate detection and longitudinal monitoring on potential biomarkers, which could identify the molecule change in the initial stage of the chronic disease. Here we report the realization of specific and accurate quantification of a low‐abundance serum protein in unprocessed human sera, using our novel giant magnetoresistive (GMR) biosensing system with uniform high‐magnetic‐moment nanoparticles and a competition based detection scheme. Only one antibody is needed for such detection scheme. The quantification of interleukin‐6 (IL‐6, a low‐abundance protein and a potential cancer biomarker), as low as 125 fM IL‐6 proteins, directly in 4 μL of unprocessed human sera was demonstrated within 5 minutes by such system. The results nicely differentiate normal individuals and lung cancer patients. This platform has great potential to facilitate the identification and validation of disease biomarkers.

Construction of a Magnetic Biosensor for Pathogen Detection

Current methods for pathogen detection require days before a result is available, while biosensors offer the advantage of quick, on the spot results. In this project we present the proof of concept of a biosensor that uses giant magnetoresistance (GMR) sensors and a microfluidic system. The bioprobe consists of a 30 bp oligonucleotide, 5′ functionalized with a thiol group (T-DNA30) immobilized on a gold surface. Hybridization was tested with a 5′-biotinylated oligonucleotide complementary to T-DNA30 to which Streptavidin-R-Phycoerythrin was attached later. The difference in fluorescence between the target sample and control samples was observed using a scanning laser confocal fluorescence microscope. The GMR device consists of an Ir0.8Mn0.2∕Co0.9Fe0.1∕Cu∕Co0.9Fe0.1∕Ni0.82Fe0.12 multilayer structure. Magnetic nanoparticles were deposited directly on the surface of the GMR sensors. An external magnetic field was employed to polarize the nanoparticles, which can then be detected by comparing the resistance change loops of the GMR sensors before and after their deposition. A transparent elastomer, polydimethylsiloxane (PDMS), was used for the microfluidic system. The system comprises two microfluidic channels separated by a 200μm PDMS wall. The channel width is 200μm and its height 100μm. The PDMS channel was permanently bonded to the SiO2 surface of the GMR sensor. The integrated biosensor will immobilize thiolated DNA on the gold surface below which the GMR device is located. For hybridization, biotinylated DNA will be used. Finally, magnetic nanoparticles, coated with streptavidin will be attached to the hybridized DNA and detected by the GMR device.

851 EARLY DEVELOPMENT OF A MULTIPLEX GIANT MAGNETORESISTIVE NANOSENSOR TO DETECT URINARY MARKERS TO DISCRIMINATE BETWEEN HIGH AND LOW GRADE PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: Transperineal mapping template prostate biopsy (TMTPB) has emerged as a diagnostic option for men with a history of negative transrectal guided prostate biopsies. Reported advantages include more precise sampling of the entire prostate gland including the anterior and apical regions. We sought to determine the detection rate and distribution of prostate cancer (PCa) in a group of men with previous negative TRUS biopsy. METHODS: Forty one patients with a history of 1 or more previous negative biopsies underwent TMTPB for primary indication of elevated PSA, elevated PSA velocity, and/or abnormal DRE. Using a transperineal approach, the prostate was systematically biopsied in 26 unique regions guided by a brachytherapy template. Prostate size determined total number of cores. Clinical and biopsy parameters were evaluated as predictors for presence and location of PCa. RESULTS: The overall PCa detection rate was 53.7% (22 of 41). Significant PCa (Gleason score 7) was noted in 14 of 41 (34.1%) patients including 4/41 (9.8%) with high grade PCa (Gleason score 8). There was an average of 4.32 cores positive (S.D. 3.54). 79.8% of positive cores were in the anterior zones vs. only 22.2% were in the posterior zones (p 0.0001). However, the 13 positive cores for Gleason 8 or 9 cancers were evenly distributed: anterior in 7 cores, posterior in 5 cores and periurethral in 1 core. Men had a mean of 2.78 (S.D. 1.46) prior biopsies prior to TMTPB and the number of prior biopsies was not associated with detection. On multivariate analysis for predictors of presence of cancer, only prostate volume was significant (p 0.03). Complications were limited in 8 patients (19.5%): urinary retention (3), hematuria (4) and atrial fibrillation with rapid ventricular rate (1) requiring admission. CONCLUSIONS: TMTPB has a high rate of cancer detection, especially in the anterior zones, even in the setting of multiple previous negative biopsies. A majority of the detected cancers were clinically significant based on Gleason score. Therefore, TMTPB should be considered in any high risk patient with previous negative biopsies.