Liang Tu

Magnetoresistive performance and comparison of supermagnetic nanoparticles on giant magnetoresistive sensor-based detection system

Giant magnetoresistive (GMR) biosensors have emerged as powerful tools for ultrasensitive, multiplexed, real-time electrical readout, and rapid biological/chemical detection while combining with magnetic particles. Finding appropriate magnetic nanoparticles (MNPs) and its influences on the detection signal is a vital aspect to the GMR bio-sensing technology. Here, we report a GMR sensor based detection system capable of stable and convenient connection, and real-time measurement. Five different types of MNPs with sizes ranging from 10 to 100 nm were investigated for GMR biosensing. The experiments were accomplished with the aid of DNA hybridization and detection architecture on GMR sensor surface. We found that different MNPs markedly affected the final detection signal, depending on their characteristics of magnetic moment, size, and surface-based binding ability, etc. This work may provide a useful guidance in selecting or preparing MNPs to enhance the sensitivity of GMR biosensors, and eventually lead to a versatile and portable device for molecular diagnostics.

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.

Magnetic Detection of Mercuric Ion Using Giant Magnetoresistance-Based Biosensing System

We have demonstrated a novel sensing strategy employing a giant magnetoresistance (GMR) biosensor and DNA chemistry for the detection of mercuric ion (Hg(2+)). This assay takes advantages of high sensitivity and real-time signal readout of GMR biosensor and high selectivity of thymine-thymine (T-T) pair for Hg(2+). The assay has a detection limit of 10 nM in both buffer and natural water, which is the maximum mercury level in drinking water regulated by U.S. Environmental Protection Agency (EPA). The magnitude of the dynamic range for Hg(2+) detection is up to three orders (10 nM to 10 μM). Herein, GMR sensing technology is first introduced into a pollutant monitoring area. It can be foreseen that the GMR biosensor could become a robust contender in the areas of environmental monitoring and food safety testing.

Giant magnetoresistive-based biosensing probe station system for multiplex protein assays

In this study, a sensitive immune-biosensing system capable of multiplexed, real-time electrical readout was developed based on giant magnetoresistive (GMR) sensor array to detect a panel of protein biomarkers simultaneously. PAPP-A, PCSK9, and ST2 have been regarded as promising candidate biomarkers for cardiovascular diseases. Early detection of multiple biomarkers for a disease could enable accurate prediction of a disease risk. 64 nano-size GMR sensors were assembled onto one 16 mm × 16 mm chip with a reaction well, and they could work independently and be monitored simultaneously. A detect limit of 40 pg/mL for ST2 antigen had been achieved, and the dynamic ranges for the three proteins detection were up to four orders of magnitude. The GMR sensing platform was also selective enough to be directly used in serum samples. In addition, a lab-based probe station has been designed to implement quick lab-on-a-chip experiments instead of wire bonding. It has a potential application in clinical biomarkers identification and screening, and can be extended to fit other biosensing schemes.

Surface Modification for Protein and DNA Immobilization onto GMR Biosensor

Giant magnetoresistance (GMR) biosensor with 20 nm SiO 2 on surface was successfully modified by 3-aminopropyltriethoxy silane (APTES) and glutaraldehyde (Glu). The resultant functionalized surface with terminal aldehyde groups was able to efficiently capture Interleukin-6 (IL-6) antibody and amine modified DNA (deoxyribonucleic acid) oligonucleotide. The immobilized IL-6 antibody could bind to IL-6 antigen, and fluorescence sandwich assay was demonstrated. The immobilized DNA could also hybridize with complementary DNA oligonucleotide. Streptavidin labeled magnetic nanoparticles with a diameter of 30 nm were both successfully bound to IL-6 antibody and DNA immobilized GMR biosensors after their respective sandwich binding and complementary hybridization. This APTES-Glu modification method could be also applicable to other surface for protein and DNA microarrays.

Magnetic nanoparticles colourization by a mixing-frequency method

Brownian and Neel relaxation of magnetic nanoparticles (MNPs) can be characterized by a highly sensitive mixing-frequency method using a search-coil based detection system. The unique magnetic properties of MNPs have been used for biomarkers detection. In this paper, we present a theory and implement an experimental detection scheme using the mixing-frequency method to identify different MNPs simultaneously. A low-frequency sinusoidal magnetic field is applied to saturate the MNPs periodically. A high-frequency sinusoidal magnetic field is then applied to generate mixing-frequency signals that are highly specific to the magnetization of MNPs. The spectra of each MNP can be defined as the complex magnetization of the MNPs over the field frequency. The magnetic spectra of various MNPs and magnetic beads have been characterized and compared. The differences between the MNPs spectra enable us to identify the individual MNPs at the same time. A test has been done to verify the ratio of two different MNPs in mixed samples based on the proposed theory. The experimental results show that the mixing-frequency method is a promising method for MNPs colourization.

Viscosity effect on the brownian relaxation based detection for immunoassay applications

Magnetic nanoparticles (MNPs) coated with Protein-G have been a model system to be used in different antibodies binding study. It is highly desirable to use a substrate-free biosensing system to detect antibodies binding in real-time. In this paper, we developed and applied a MNPs and search-coils integrated detection system, which is not only sensitive to the hydrodynamic volume of MNPs but also sensitive to the environment of MNPs, such as viscosity and temperature of the solution. We demonstrated that the viscosity effect influenced the amplitudes and phases of the 3rd (fH±2fL) and 5th (fH±4fL) harmonics for the mixed frequency testing scheme. The binding between antibodies and Protein-G on MNPs increased hydrodynamic volume of particles, as a result, it also changed the amplitudes and phases of harmonics, which are the object signals we need to analyze. We demonstrated that the viscosity of antibody solution is lower than that of MNP solution, and the antibody binding effect could be shielded by the viscosity effect to certain extent.